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-[{"mag_id": 2469651880, "corpus_id": 7571069, "title": "[Extended hepatic pedicle occlusion in major hepatectomy for primary liver cancer].", "abstract": "OBJECTIVE\nTo evaluate the influence of extended hepatic pedicle occlusion (HPO) on hepatic ischemic/reperfusion (I/R) injury and intraoperative blood loss in major hepatectomy for primary liver cancer (PLC).\n\n\nMETHODS\nBetween June 2001 and December 2005, a total number of 843 patients with PLC had been operated on. Those whose hepatic pedicle were occluded continuously for or longer than 30 min during hepatectomy were retrospectively reviewed (continuous HPO group) and compared to the patients whose hepatic pedicle were occluded for the same length of time but intermittently (intermittent HPO group). The amount of intraoperative blood loss, the percentage of the patients who needed blood transfusion and postoperative liver biochemical tests were compared between the two groups.\n\n\nRESULTS\nThere were 35 cases in continuous HPO group and 38 cases in intermittent HPO group with occlusion time between 30 min and 45 min. The two groups were matched for underlying liver disease ,preoperative liver function, tumor size and location, major intrahepatic vessel involvements and the types and extensions of the hepatectomies. The mean intraoperative blood loss in continuous HPO group was significantly less than that in intermittent HPO group (660 ml vs. 1054 ml, P < 0.05); accordingly, the percentage of patients who need blood transfusion in continuous HPO group was significantly lower than that in intermittent HPO group (48.6% vs. 78.9%, P < 0.01). Patients in both of the groups were recovered smoothly after operation, with no occurrence of liver failure.\n\n\nCONCLUSIONS\nThe hepatic pedicle can be continuously occluded for 3045 min in cirrhotic patients with well compensated liver function, and when compared to routine intermittent HPO, continuous HPO significantly decreases the intraoperative blood loss and reduces the need for transfusion. Meanwhile it does not increase the hepatic I/R injury.", "descriptor": "Liver Neoplasms", "qualifier": "surgery"}, {"mag_id": 2128734851, "corpus_id": 22715986, "title": "Accuracy of MRI for treatment response assessment after taxane- and anthracycline-based neoadjuvant chemotherapy in HER2-negative breast cancer.", "abstract": "BACKGROUND\nStudies suggest that MRI is an accurate means for assessing tumor size after neoadjuvant chemotherapy (NAC). However, accuracy might be dependent on the receptor status of tumors. MRI accuracy for response assessment after homogenous NAC in a relative large group of patients with stage II/III HER2-negative breast cancer has not been reported before.\n\n\nMETHODS\n250 patients from 26 hospitals received NAC (docetaxel, adriamycin and cyclophosphamide) in the context of the NEOZOTAC trial. MRI was done after 3 cycles and post-NAC. Imaging (RECIST 1.1) and pathological (Miller and Payne) responses were recorded. Accuracy measures were calculated and MRI and pathologically assessed tumor sizes were correlated. Tumor size over- and underestimation were quantified.\n\n\nRESULTS\nAccuracy of MRI for determining pathological complete response (pCR) was 76%. The ROC-curve of MRI response and pCR had an area under the curve value of 0.63 (95% C.I. 0.52-0.74). The correlation coefficient of MRI and histopathological tumor measurements was 0.46 (p < 0.001). Correlations were different for ER-positive (r = 0.40, p < 0.001) and ER-negative (r = 0.76, p < 0.001) breast tumors. MRI under- and overestimated the tumor size in 47% and 40% of all patients. In cases of substantial tumor size underestimation (>2 cm), surgical margins were more often tumor positive compared to the rest of the patients (33% vs.12%, p = 0.005).\n\n\nCONCLUSION\nMRI measurements correlated moderately with tumor size on the surgical specimen. Only in ER-negative breast tumors, MRI tumor sizes correlated sufficiently with residual tumor size on the pathological specimen. Therefore, post-NAC MRI should be interpreted with caution.", "descriptor": "Breast Neoplasms", "qualifier": "pathology"}, {"mag_id": 2065216512, "corpus_id": 18299466, "title": "Quantitative Study of Liver Magnetic Resonance Spectroscopy Quality at 3T Using Body and Phased Array Coils with Physical Analysis and Clinical Evaluation", "abstract": "This study aims to investigate the quality difference of short echo time (TE) breathhold 1H magnetic resonance spectroscopy (MRS) of the liver at 3.0T using the body and phased array coils, respectively. In total, 20 pairs of single-voxel proton spectra of the liver were acquired at 3.0T using the phased array and body coils as receivers. Consecutive stacks of breathhold spectra were acquired using the point resolved spectroscopy (PRESS) technique at a short TE of 30 ms and a repetition time (TR) of 1500 ms. The first spectroscopy sequence was \u201ccopied\u201d for the second acquisition to ensure identical voxel positioning. The MRS prescan adjustments of shimming and water suppression, signal-to noise ratio (SNR), and major liver quantitative information were compared between paired spectra. Theoretical calculation of the SNR and homogeneity of the region of interest (ROI, 2 cm\u00d72 cm\u00d72 cm) using different coils loaded with 3D liver electromagnetic model of real human body was implemented in the theoretical analysis. The theoretical analysis showed that, inside the ROI, the SNR of the phase array coil was 2.8387 times larger than that of body coil and the homogeneity of the phase array coil and body coil was 80.10% and 93.86%, respectively. The experimental results showed excellent correlations between the paired data (all r > 0.86). Compared with the body coil group, the phased array group had slightly worse shimming effect and better SNR (all P values < .01). The discrepancy of the line width because of the different coils was approximately 0.8 Hz (0.00625 ppm). No significant differences of the major liver quantitative information of Cho/Lip2 height, Cho/Lip2 area, and lipid content were observed (all P values >0.05). The theoretical analysis and clinical experiment showed that the phased array coil was superior to the body coil with respect to 3.0T breathhold hepatic proton MRS.", "descriptor": "Liver", "qualifier": "anatomy & histology"}, {"mag_id": 2808109470, "corpus_id": 49301382, "title": "Circulating Tumor Cells Undergoing EMT Provide a Metric for Diagnosis and Prognosis of Patients with Hepatocellular Carcinoma.", "abstract": "To clarify the significance of circulating tumor cells (CTC) undergoing epithelial-mesenchymal transition (EMT) in patients with hepatocellular carcinoma (HCC), we used an advanced CanPatrol CTC-enrichment technique and in situ hybridization to enrich and classify CTC from blood samples. One hundred and one of 112 (90.18%) patients with HCC were CTC positive, even with early-stage disease. CTCs were also detected in 2 of 12 patients with hepatitis B virus (HBV), both of whom had small HCC tumors detected within 5 months. CTC count \u226516 and mesenchymal-CTC (M-CTC) percentage \u22652% prior to resection were significantly associated with early recurrence, multi-intrahepatic recurrence, and lung metastasis. Postoperative CTC monitoring in 10 patients found that most had an increased CTC count and M-CTC percentage before clinically detectable recurrence nodules appeared. Analysis of HCC with high CTC count and high M-CTC percentage identified 67 differentially expressed cancer-related genes involved in cancer-related biological pathways (e.g., cell adhesion and migration, tumor angiogenesis, and apoptosis). One of the identified genes, BCAT1, was significantly upregulated, and knockdown in Hepg2, Hep3B, and Huh7 cells reduced cell proliferation, migration, and invasion while promoting apoptosis. A concomitant increase in epithelial marker expression (EpCAM and E-cadherin) and reduced mesenchymal marker expression (vimentin and Twist) suggest that BCAT1 may trigger the EMT process. Overall, CTCs were highly correlated with HCC characteristics, representing a novel marker for early diagnosis and a prognostic factor for early recurrence. BCAT1 overexpression may induce CTC release by triggering EMT and may be an important biomarker of HCC metastasis.Significance: In liver cancer, CTC examination may represent an important \"liquid biopsy\" tool to detect both early disease and recurrent or metastatic disease, providing cues for early intervention or adjuvant therapy. Cancer Res; 78(16); 4731-44. \u00a92018 AACR.", "descriptor": "Liver Neoplasms", "qualifier": "blood"}, {"mag_id": 2052590949, "corpus_id": 12951093, "title": "Interactions between ionic liquid surfactant [C12mim]Br and DNA in dilute brine.", "abstract": "Interactions between ionic liquid surfactant [C(12)mim]Br and DNA in dilute brine were investigated in terms of various experimental methods and molecular dynamics (MD) simulation. It was shown that the aggregation of [C(12)mim]Br on DNA chains is motivated not only by electrostatic attractions between DNA phosphate groups and [C(12)mim]Br headgroups but also by hydrophobic interactions among [C(12)mim]Br alkyl chains. Isothermal titration calorimetry analysis indicated that the [C(12)mim]Br aggregation in the presence and absence of DNA are both thermodynamically favored driven by enthalpy and entropy. DNA undergoes size transition and conformational change induced by [C(12)mim]Br, and the charges of DNA are neutralized by the added [C(12)mim]Br. Various microstructures were observed such as DNA with loose coil conformation in nature state, necklace-like structures, and compact spherical aggregates. MD simulation showed that the polyelectrolyte collapses upon the addition of oppositely charged surfactants and the aggregation of surfactants around the polyelectrolyte was reaffirmed. The simulation predicted the gradual neutralization of the negatively charged polyelectrolyte by the surfactant, consistent with the experimental results.", "descriptor": "DNA", "qualifier": "chemistry"}, {"mag_id": 1981798983, "corpus_id": 36428819, "title": "Exclusion in liver by polymerase chain reaction of hepatitis B and C viruses in acute liver failure attributed to sporadic non-A, non-B hepatitis.", "abstract": "Hepatitis B and C viruses have been implicated in a few cases of acute liver failure attributed to sporadic (community acquired) non-A, non-B hepatitis, but reports are conflicting. We determined whether hepatitis B virus and hepatitis C virus were detectable in prospectively stored hepatectomies from seven British patients grafted for acute liver failure attributed to sporadic non-A, non-B hepatitis. For hepatitis B virus, we used nested polymerase chain reaction with primers to the core and surface regions. For hepatitis C virus, we used one round of reverse transcription polymerase chain reaction with primers to the 5' untranslated region and Southern hybridization using an internal oligonucleotide probe as well as nested PCR for the E1 region. Positive controls were native livers from two patients with unequivocal fulminant hepatitis B and from four patients with cirrhosis attributed to hepatitis C virus. Our negative findings suggest that, in the UK, acute liver failure attributed to sporadic non-A, non-B hepatitis most likely is caused by agent/s other than hepatitis B and C viruses.", "descriptor": "Liver", "qualifier": "virology"}, {"mag_id": 2745937803, "corpus_id": 13704746, "title": "End-of-Life Intensity for Adolescents and Young Adults With Cancer: A Californian Population-Based Study That Shows Disparities.", "abstract": "PURPOSE\nCancer is the leading cause of nonaccidental death among adolescents and young adults (AYAs). High-intensity end-of-life care is expensive and may not be consistent with patient goals. However, the intensity of end-of-life care for AYA decedents with cancer-especially the effect of care received at specialty versus nonspecialty centers-remains understudied.\n\n\nMETHODS\nWe conducted a retrospective, population-based analysis with the California administrative discharge database that is linked to death certificates. The cohort included Californians age 15 to 39 years who died between 2000 and 2011 with cancer. Intense end-of-life interventions included readmission, admission to an intensive care unit, intubation in the last month of life, and in-hospital death. Specialty centers were defined as Children's Oncology Group centers and National Cancer Institute-designated comprehensive cancer centers.\n\n\nRESULTS\nOf the 12,938 AYA cancer decedents, 59% received at least one intense end-of-life care intervention, and 30% received two or more. Patients treated at nonspecialty centers were more likely than those at specialty-care centers to receive two or more intense interventions (odds ratio [OR], 1.46; 95% CI, 1.32 to 1.62). Sociodemographic and clinical factors associated with two or more intense interventions included minority race/ethnicity (Black [OR, 1.35, 95% CI, 1.17 to 1.56]; Hispanic [OR, 1.24; 95% CI, 1.12 to 1.36]; non-Hispanic white: reference), younger age (15 to 21 years [OR, 1.36; 95% CI, 1.19 to 1.56; 22 to 29 years [OR,1.26; 95% CI,1.14 to 1.39]; \u2265 30 years: reference), and hematologic malignancies (OR, 1.53; 95% CI, 1.41 to 1.66; solid tumors: reference).\n\n\nCONCLUSION\nThirty percent of AYA cancer decedents received two or more high-intensity end-of-life interventions. In addition to sociodemographic and clinical characteristics, hospitalization in a nonspecialty center was associated with high-intensity end-of-life care. Additional research is needed to determine if these disparities are consistent with patient preference.", "descriptor": "Neoplasms", "qualifier": "mortality"}, {"mag_id": 2001660913, "corpus_id": 25774071, "title": "Beyond internalised stigma: daily moralities and subjectivity among self-identified kothis in Karnataka, South India", "abstract": "The Bill and Melinda Gates Foundation has poured a tremendous amount of resources into epidemic prevention in India's high HIV prevalence zones, through their Avahan initiative. These community-centred programmes operate under the assumption that fostering community-based organisational development and empowering the community to take charge of HIV prevention and education will help to transform the wider social inequalities that inhibit access to health services. Focusing on the South Indian state of Karnataka, this paper explores a troubling set of local narratives that, we contend, hold broader implications for future programme planning and implementation. Although confronting stigma and discrimination has become a hallmark in community mobilisation discourse, communities of self-identified kothis (feminine men) who were involved in Avahan programme activities continued to articulate highly negative attitudes about their own sexualities in relation to various spheres of social life. Rather than framing an understanding of these narratives in psychological terms of \u2018internalized stigma\u2019, we draw upon medical anthropological approaches to the study of stigma that emphasise how social, cultural and moral processes create stigmatising conditions in the everyday lives of people. The way stigma continues to manifest itself in the self-perceptions of participants points to an area that warrants critical public health attention.", "descriptor": "HIV Infections", "qualifier": "prevention & control"}, {"mag_id": 2018722125, "corpus_id": 2067264, "title": "Complications, functional outcome and quality of life after intensive preoperative chemoradiotherapy for rectal cancer.", "abstract": "AIMS\nTo investigate early and late complications in 44 patients with locally advanced mid-low rectal cancer enrolled in a phase I-II study, who had received an aggressive chemoradiation treatment (50.4Gy/28F; 5-FU continuous infusion and weekly Oxaliplatin) followed by total mesorectal excision and 5-FU based postoperative chemotherapy. The aim of the present study is also to evaluate functional outcome and quality of life (QoL) in a sub-group of 22 patients.\n\n\nMETHODS\nStandardized forms for early and late surgical complications were completed for all patients. Anorectal function and QoL were also investigated in 22 patients who underwent surgery in the same surgical unit, using the fecal incontinence scoring system (FIS) and EORTC-QLQ-CR38 questionnaires, compiled before and after radiotherapy and at least 8 months after surgery. The differences over time in scores were analyzed using repeated measure ANOVA.\n\n\nRESULTS\nThe median age of patients (25 males and 19 females) was 58 (range: 34-73) years. A low anterior resection was performed in 39 cases, radical resection in 41, and 12 patients had a pathological complete response. There were no operative deaths; 4 and 9 patients required re-operation for early and late complications, respectively. FIS score did not present a significant worsening over time. According to data in the EORTC-QLQ-CR38 questionnaire, a significant improvement over time was found only for \"future perspective\".\n\n\nCONCLUSION\nOur findings seem to indicate that this aggressive 5-FU-Oxalipaltin-based treatment implies no impairment of QoL and anorectal function, even if a high rate of late major complications was observed. Studies on larger series are required to confirm these results.", "descriptor": "Adenocarcinoma", "qualifier": "surgery"}, {"mag_id": 2125939309, "corpus_id": 33392241, "title": "Generalized connective tissue nevi and ichthyosis in Down's syndrome.", "abstract": "The first description of a localized connective tissue nevus with a decreased amount of elastic tissue is credited to Lewandowsky in 1921. Various authors designated these localized hamartomas as nevus anelasticus according to the histologic presentation of the nevus. Sachs1reported a generalized process that developed after furunculosis and Loewenthal2described a case in which the lesions became generalized over a ten-year period. We report a case of generalized connective tissue nevi with a decrease in elastic tissue in a patient with Down's syndrome. Report of a Case A 47-year-old man who had Down's syndrome was admitted to Bronx Municipal Medical Center, New York, for treatment of sepsis. His family related a history of crops of boils that appeared approximately ten years ago. After draining a whitish material, there were residual nodules. Simultaneously, a \"mossy appearance\" of the skin occurred at the periphery of the nodules. There was no", "descriptor": "Skin Neoplasms", "qualifier": "complications"}, {"mag_id": 1987380889, "corpus_id": 25945941, "title": "Mechanisms of [2,3-butanedione bis(N4-dimethylthiosemicarbazone)]zinc (Zn-ATSM2)-induced protection of cultured hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.", "abstract": "Hyperexcitation of glutamatergic neurons may play a key role in ischemia-related neurodegeneration. Recent studies have suggested that the zinc ion (Zn2+), which is present in the central nervous system, has a modulatory role in glutamatergic neuron activity. Zinc ions block glutamate-induced depolarizing currents and neuronal damage by binding with zinc sites on the NMDA subtypes. Therefore, we examined the usefulness of zinc as a therapeutic agent for the prevention of ischemic neuronal damage in the brain. In our previous study, 2,3-butanedione bis(N4-dimethylthiosemicarbazonato) zinc complex (Zn-ATSM2), with high brain uptake, showed significant neuroprotective effects against cerebral ischemia in rats when administered systemically. In this study, to elucidate the mechanism of the neuroprotective effect of Zn-ATSM2, we first examined its in vitro protective effects against glutamate-, NMDA- and kainite-induced neurotoxicity in primary cultures of hippocampal neurons. Zn-ATSM2 elicited protective effects against this glutamate- and NMDA-induced neurotoxicity, but did not affect kainite-induced cytotoxicity. In addition, we studied the effects of Zn-ATSM2 on influx of Ca2+, which undergoes modification subsequent to NMDA activation. Zn-ATSM2 significantly decreased glutamate-induced 45Ca2+ uptake. Thus, Zn-ATSM2 protected against glutamate-induced neurotoxicity and its protective effect was, at least in part, due to the blockage of NMDA receptor-mediated Ca2+ influx.", "descriptor": "Neurons", "qualifier": "drug effects"}, {"mag_id": 2029365371, "corpus_id": 1578952, "title": "Biotransformation of nicotine by microorganism: the case of Pseudomonas spp.", "abstract": "Several bacterial species are capable of using nicotine, the main alkaloid in tobacco plants, as a substrate for growth. The dominant species include members of two genera, Pseudomonas and Arthrobacter. The degradation pathway and genetic structure of nicotine catabolism in Arthrobacter nicotinovorans were recently reviewed (Brandsch Appl Microbiol Biotechnol 69:493\u2013498, 2006). Here, we present up-to-date information on biodegradation of nicotine by Pseudomonas spp. Species in this genus capable of degrading nicotine are summarized and analyzed phylogenetically. Their metabolic intermediates and nicotine degradation-related genes were summarized, and the nicotine-biotransformation pathways were compared and discussed.", "descriptor": "Bacterial Proteins", "qualifier": "genetics"}, {"mag_id": 2984463798, "corpus_id": 58654765, "title": "Upregulation of long noncoding RNA ANRIL correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma.", "abstract": "PURPOSE\nEsophageal cancer (EC) is the 9th most common carcinoma worldwide with poor prognosis. Specific biomarkers can help predicting the development of esophageal squamous cell carcinoma (ESCC), which can improve the assessment of prognosis. This study aimed to explore long noncoding RNA (lncRNA) ANRIL expression and its potential value in ESCC prognosis.\n\n\nMETHODS\nQuantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was utilized to detect lncRNA ANRIL expression in 50 pairs of ESCC and matched normal samples in order to explore the role of lncRNA ANRIL in ESCC. Moreover, the association was investigated between clinical characteristics of ESCC and the expression level of ANRIL.\n\n\nRESULTS\nDisease-free survival (DFS) and overall survival (OS) were significantly shorter in ESCC patients with higher expression level of lncRNA ANRIL. ESCC tissues examined showed an obvious increment in ANRIL expression when compared to normal tissues. Furthermore, ANRIL was positively related to lymph nodes metastasis, TNM stage and tumor clinical stage. Moreover, upregulated ANRIL expression was remarkably associated with shorter survival in ESCC patients,which was also an independent prognostic factor for both OS and DFS.\n\n\nCONCLUSIONS\nThis study suggested that lncRNA ANRIL could be a potential oncogene of ESCC. ANRIL expression might be served as another potential therapeutic target and prognostic biomarker for ESCC.", "descriptor": "Carcinoma, Squamous Cell", "qualifier": "secondary"}, {"mag_id": 2040608333, "corpus_id": 1951469, "title": "Solubilization and reconstitution of chick renal mitochondrial 25-hydroxyvitamin D3 24-hydroxylase.", "abstract": "Chick kidney mitochondrial 25-hydroxyvitamin D3 24-hydroxylase has been solubilized with sodium cholate and reconstituted with NADPH, beef adrenal ferredoxin, and beef adrenal ferredoxin reductase, each component being essential for maximal 24-hydroxylase activity. The product 24(R),25-dihydroxyvitamin D3 was identified by cochromatography with synthetic compound on straight-phase and reversed-phase high-performance liquid chromatography and by periodate oxidation. The enzyme has an apparent Km for 25-hydroxyvitamin D3 of 0.67 microM. At 1 microM 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3 production is linear with time for up to 15 min and with protein concentrations of up to 2 mg/mL. The antioxidant diphenyl-p-phenylenediamine (1.3 X 10(-4) M) has no effect on this reaction. Reconstituted 24-hydroxylase activity is enhanced by the addition of NaCl and KCl up to 100 mM, with higher concentrations having an inhibitory effect. 1 alpha-Hydroxylase is not present in this preparation from vitamin D replete chicks. The similarities of this reconstituted system to the 25-hydroxyvitamin D3 1 alpha-hydroxylase and the adrenal systems suggest that the 25-hydroxyvitamin D3 24-hydroxylase is also a cytochrome P-450 type mixed-function oxidase.", "descriptor": "Kidney", "qualifier": "enzymology"}, {"mag_id": 2411382587, "corpus_id": 41176992, "title": "Effect of serum on cell membrane Na-K transport of vascular smooth muscle in culture--a comparative study between normotensive and hypertensive rats.", "abstract": "In order to elucidate the effect of serum and its differential characteristics in primary hypertension, we investigated the influence of serum from spontaneously hypertensive rats (SHR) on the cell membrane Na-K pump, Na-H antiport and passive K permeability of cultured vascular smooth muscle cells (VSMC) from SHR and Wistar-Kyoto rats (WKY). In the absence of serum, the Na-K pump activity, described as ouabain-sensitive 86Rb uptake (OS), was greater in the VSMC of the SHR than that of the WKY. Addition of serum to the quiescent VSMC stimulated the OS, of which activation was significantly greater with the SHR serum than with the WKY serum. Determination of intracellular Na concentrations in the presence of 1 mM ouabain showed that Na uptake in the absence of serum of the SHR VSMC was greater than that of the WKY VSMC. Subjecting the VSMC to rat serum stimulated Na uptake, which effect was more profound with SHR serum than with WKY serum. A greater stimulation of 5-(N,N-hexamethylene) amiloride(HMA)-sensitive Na uptake by SHR serum accounted for this difference. When the Na-K pump was active, intracellular Na concentrations were unchanged in the presence of serum. Furthermore, serum from either of the two strains produced a substantial increase in the washout rate constant of 86Rb washout (Ke), which effect was also larger in SHR serum than in WKY serum. In the absence of serum, basal Ke of the SHR VSMC was greater than that of the WKY VSMC. It is concluded that serum from SHR produced a more pronounced activation of the Na-K pump, Na-H antiport and passive K permeability in cultured VSMC. The study suggests that in addition to an innate augmented activity of Na-K transporters in the VSMC of SHR, there are humoral factors in SHR serum which elicit the stimulation of the Na-H antiport, leading to either the activation of the Na-K pump or secondary stimulation of passive K permeability across the cell membrane.", "descriptor": "Hypertension", "qualifier": "metabolism"}, {"mag_id": 1536796647, "corpus_id": 729808, "title": "Hypocretin/orexin\u2010containing neurons are produced in one sharp peak in the developing ventral diencephalon", "abstract": "The birth date of hypocretin\u2010containing neurons was analysed using the bromodeoxyuridine method in the rat. The results indicate that these neurons are generated between embryonic days 11 (E11) and E14, with a sharp peak on E12. This spatiotemporal pattern of genesis contrasts with that of the co\u2010distributed neurons producing the melanin\u2010concentrating hormone in the lateral hypothalamic area, which have been described as generated in one large peak from E10 to E16. These observations may be linked to the relative distribution area of both populations.", "descriptor": "Neurons", "qualifier": "metabolism"}, {"mag_id": 1972179043, "corpus_id": 205889946, "title": "Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice", "abstract": "Hepatocytes possess a remarkable capacity to regenerate and reconstitute the parenchyma after liver damage. However, in the case of chronic injury, their proliferative potential is impaired and hepatic progenitor cells (HPCs) are activated, resulting in a ductular reaction known as oval cell response. Proapoptotic and survival signals maintain a precise balance to spare hepatocytes and progenitors from hyperplasia and cell death during regeneration. Survivin, a member of the family of inhibitor of apoptosis proteins (IAPs), plays key roles in the proliferation and apoptosis of various cell types. Here, we characterized the in vivo function of Survivin in regulating postnatal liver development and homeostasis using mice carrying conditional Survivin alleles. Hepatic perinatal loss of Survivin causes impaired mitosis, increased genome ploidy, and enlarged cell size in postnatal livers, which eventually leads to hepatocyte apoptosis and triggers tissue damage and inflammation. Subsequently, HPCs that retain genomic Survivin alleles are activated, which finally differentiate into hepatocytes and reconstitute the whole liver. By contrast, inducible ablation of Survivin in adult hepatocytes does not affect HPC activation and liver homeostasis during a long\u2010life period. Conclusion: Perinatal Survivin deletion impairs hepatic mitosis in postnatal liver development, which induces HPC activation and reconstitution in the liver, therefore providing a novel HPC induction model. (Hepatology 2013; 58:2109\u20132121)", "descriptor": "Liver", "qualifier": "growth & development"}, {"mag_id": 1974971881, "corpus_id": 37298950, "title": "Serum lipids and lipoproteins are less powerful predictors of extracranial carotid artery atherosclerosis than are cigarette smoking and hypertension.", "abstract": "The effect of serum lipids and lipoproteins on extracranial carotid artery atherosclerosis (CAS) was studied in patients who underwent carotid arteriography. Serum lipid and lipoprotein values along with data on other potential predictors of extracranial CAS were determined in 240 patients who had at least one extracranial carotid artery visualized. In a multiple logistic regression analysis, the independently significant predictors of the presence of extracranial CAS were, in decreasing order of significance, duration of smoking of cigarettes, hypertension, age, and low-density lipoprotein cholesterol. Serum cholesterol, triglycerides, high-density lipoprotein cholesterol, and apolipoprotein A-I did not show an independent effect. Although low-density lipoprotein cholesterol was an independent predictor of the presence of extracranial CAS, its effect as a predictor was far outweighed by the effects of the duration of smoking of cigarettes and a history of hypertension.", "descriptor": "Hypertension", "qualifier": "complications"}, {"mag_id": 2591954093, "corpus_id": 35444181, "title": "dUTPase inhibition augments replication defects of 5-Fluorouracil", "abstract": "The antimetabolite 5-Fluorouracil (5-FU) is used in the treatment of various forms of cancer and has a complex mode of action. Despite 6 decades in clinical application the contribution of 5-FdUTP and dUTP [(5-F)dUTP] and 5-FUTP misincorporation into DNA and RNA respectively, for 5-FU-induced toxicity is still under debate. This study investigates DNA replication defects induced by 5-FU treatment and how (5-F)dUTP accumulation contributes to this effect. We reveal that 5-FU treatment leads to extensive problems in DNA replication fork progression, causing accumulation of cells in S-phase, DNA damage and ultimately cell death. Interestingly, these effects can be reinforced by either depletion or inhibition of the deoxyuridine triphosphatase (dUTPase, also known as DUT), highlighting the importance of (5-F)dUTP accumulation for cytotoxicity. With this study, we not only extend the current understanding of the mechanism of action of 5-FU, but also contribute to the characterization of dUTPase inhibitors. We demonstrate that pharmacological inhibition of dUTPase is a promising approach that may improve the efficacy of 5-FU treatment in the clinic.", "descriptor": "Neoplasms", "qualifier": "drug therapy"}, {"mag_id": 2107133784, "corpus_id": 23051933, "title": "Inhibition of hepatic lipase by m-aminophenylboronate. Application of phenylboronate affinity chromatography for purification of human postheparin plasma lipases.", "abstract": "Phenylboronates are competitive inhibitors of serine. hydrolases including lipases. We studied the effect of m-aminophenylboronate on triglyceride-hydrolyzing activity of hepatic lipase (EC 3.1,1.3). m-Aminophenylboronate inhibited hepatic lipase activity with a Ki value of 55 microM. Furthermore, m-aminophenylboronate protected hepatic lipase activity from inhibition by di-isopropyl fluorophosphate, an irreversible active site inhibitor of serine hydrolases. Inhibition of hepatic lipase activity by m-aminophenylboronate was pH-dependent. The inhibition was maximal at pH 7.5, while at pH 10 it was almost non-existent. These data were used to develop a purification procedure for postheparin plasma hepatic lipase and lipoprotein lipase. The method is a combination of m-aminophenylboronate and heparin-Sepharose affinity chromatographies. Hepatic lipase was purified to homogeneity as analyzed on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The specific activity of purified hepatic lipase was 5.46 mmol free fatty acids h-1 mg-1 protein with a total purification factor of 14,400 and a final recovery of approximately 20%. The recovery of hepatic lipase activity in m-aminophenylboronate affinity chromatography step was 95%. The purified lipoprotein lipase was a homogeneous protein with a specific activity of 8.27 mmol free fatty acids h-1 mg-1. The purification factor was 23,400 and the final recovery approximately 20%. The recovery of lipoprotein lipase activity in the m-aminophenylboronate affinity chromatography step was 87%. The phenylboronate affinity chromatography step can be used for purification of serine hydrolases which interact with boronates.", "descriptor": "Liver", "qualifier": "enzymology"}, {"mag_id": 2012525905, "corpus_id": 5767513, "title": "Non-alcoholic fatty liver disease in HIV-positive patients predisposes for acute-on-chronic liver failure: two cases.", "abstract": "Non-alcoholic fatty liver disease is a prominent feature in HIV-positive patients. We present two patients with long-lasting HIV-infection who suffered from this disease, as induced by highly active anti-retroviral therapy (HAART). The patients developed acute-on-chronic (AOC) liver failure after either (case 1) acute infection with hepatitis A virus (HAV) or (case 2) methamphetamine abuse ('Ecstasy'). Approximately 1 week after visiting an area endemic for HAV, case 1, a male patient, presented with icterus, elevated liver transaminases and HAV IgM. Previous examinations had demonstrated normal liver transaminase activities while hepatic steatosis had been suspected. He developed complications associated with liver failure including renal failure as well as pleural and pericardial effusions. Case 2, a second male patient, developed both liver failure and lactic acidosis 24 h after methamphetamine abuse. Both patients suffered from fatty liver in the pre-acute stage as indicated by ultrasound examination. After developing symptoms of liver failure, HAART was discontinued in both patients. Follow-up visits demonstrated that the patients recovered clinically with almost normalized laboratory parameters. In HIV infection, HAART-induced hepatopathological alterations may exist despite the absence of relevant laboratory parameters. These patients are likely to develop AOC liver failure when subjected to acute risk factors such as hepatitis viruses and narcotics or other drugs. In patients treated with HAART, we thus highly recommend hepatitis A and B virus vaccinations, and close monitoring of liver parameters.", "descriptor": "HIV Infections", "qualifier": "complications"}, {"mag_id": 2554941292, "corpus_id": 5777824, "title": "Cortical Arousal With Deep Brain Stimulation After General Anesthesia for Laparoscopic Cholecystectomy.", "abstract": "To JNA Readers: Deep brain stimulation (DBS) is a well-established treatment for Parkinson disease (PD) and other movement disorders.1 There are approximately over 100,000 patients with such devices in North America, and it is likely that these patients will require anesthesia care for non-neurological procedures.2 In this report, we present a patient with DBS in situ who showed a clinical and electro-encephalogram evidence of cortical arousal upon turning \u201con\u201d the DBS device after general anesthesia for laparoscopic cholecystectomy. A 62-year-old man (height 182 cm, weight 92kg) was scheduled for an elective laparoscopic cholecystectomy. He was diagnosed PD 18 years ago, and underwent bilateral subthalamic nucleus DBS insertion 4 years ago for refractory bradykinesia and tremors. Patient was recently seen in the movement disorder clinic and his DBS was checked to be functioning well. General anesthesia was induced using standard doses of propofol, fentanyl and rocuronium, and maintained with oxygen nitrous oxide and desflurane mixture. Depth of surgical anesthesia was monitored using entropy (Datex-Ohmeda, GE Healthcare, Helsinki, Finland), titrated to values between 40 and 50. The DBS was switched off following induction of anesthesia, and remained off during the whole procedure. To minimize electrical interference, the surgeons used harmonic scalpel exclusively. Intraoperative course was unremarkable. At the end of the surgery, the neuromuscular blockade was reversed. The inhaled anesthetics were stopped, and the end-tidal desflurane concentration was 0.4 volume% (minimum alveolar concentration 0.1). However, entropy values were (response entropy/state entropy) 14/13 and the patient was not awakening. The DBS was switched on at this time. We noticed an instantaneous increase in entropy values from 14/13 to 98/85 (Fig. 1) along with spontaneous eye opening. The patient was extubated within the next few minutes and his postoperative course was uneventful. To our knowledge this is the first report of cortical arousal with subthalamic nucleus stimulation. A previous case report has described a similar phenomenon of cortical arousal during globus pallidus internus stimulation during DBS insertion for dystonia.3 In addition to the transthalamic arousal system, cortical arousal is regulated by an interplay of different subcortical arousal-promoting and sleep-promoting systems involving cholinergic and/or orexinergic neurotransmission. Emergence from anesthesia in patients with PD can be variable depending upon the disease progression, interaction between PD and anesthetic medications. It is recommend that the DBS device be switched off following induction of general anesthesia to prevent electrical injury to the pulse generator as well neural structures in the brain.1,5 Patients with DBS device in situ are a special subset of population where delayed recovery from anesthesia may result if the DBS device is inadvertently left in the \u201coff\u201d position after surgery. We found that there were no clinical or electrical signs of emergence despite using short acting anesthetic agents (propofol and fentanyl), and ensuring adequate elimination of inhaled anesthetics and reversal of neuromuscular blockade. It is important to be aware of this cortical arousal phenomenon with DBS activation to ensure a timely and complete recovery from general anesthesia.", "descriptor": "Postoperative Complications", "qualifier": "therapy"}, {"mag_id": 1984455211, "corpus_id": 37329360, "title": "Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion", "abstract": "Human papillomavirus (HPV) infections account for more than 50% of infection\u2010linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV\u2010infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK\u2010cell infiltration in HPV\u2010associated preneoplastic cervical lesions. Since HPVs cannot grow in vitro, virus\u2010like particles (VLPs) were used as a model for studying the NK\u2010cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF\u2010\u03b1 and IFN\u2010\u03b3) in the presence of HPV\u2010VLPs. Using flow cytometry and microscopy, we observed that NK\u2010cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16+ and CD16\u2212 NK\u2010cell lines and a CD16\u2010blocking antibody, we demonstrated that CD16 is necessary for HPV\u2013VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV\u2010induced lesions.", "descriptor": "Carcinoma, Squamous Cell", "qualifier": "virology"}, {"mag_id": 1565711667, "corpus_id": 2738288, "title": "Escherichia coli SspA is a transcription activator for bacteriophage P1 late genes", "abstract": "The stringent starvation protein A (SspA), an Escherichia coli RNA polymerase (RNAP)\u2010associated protein, has been reported to be essential for lytic growth of bacteriophage P1. Unlike P1 early promoters, P1 late promoters are not recognized by RNAP alone. A phage\u2010encoded early protein, Lpa (late promoter activator protein, formerly called gp10), has been shown to be required for P1 late transcription in vivo. Here, we demonstrate that SspA is a transcription activator for P1 late genes. Our results indicated that Lpa is not limiting in an sspA mutant. However, the transcription of P1 late genes was deficient in an sspA mutant in vivo. We demonstrated that SspA/Lpa are required for transcription activation of the P1 late promoter Ps in vitro. In addition, SspA and Lpa were shown to facilitate the binding of RNAP to Ps late promoter DNA. Activation of late transcription by SspA/Lpa was dependent on holoenzyme containing \u03c370 but not \u03c3S, indicating that the two activators discriminate between the two forms of the holoenzyme. Furthermore, P1 early gene expression was downregulated in the wild\u2010type background, whereas it persisted in the sspA mutant background, indicating that SspA/Lpa mediate the transcriptional switch from the early to the late genes during P1 lytic growth. Thus, this work provides the first evidence for a function of the E. coli RNAP\u2010associated protein SspA.", "descriptor": "Escherichia coli", "qualifier": "virology"}, {"mag_id": 2564097348, "corpus_id": 31171055, "title": "Dietary polychlorinated biphenyls, long-chain n-3 polyunsaturated fatty acids and incidence of malignant melanoma.", "abstract": "BACKGROUND\nFor malignant melanoma, other risk factors aside from sun exposure have been hardly explored. Polychlorinated biphenyls (PCBs)-mainly from fatty fish- may affect melanogenesis and promote melanoma progression, while long-chain n-3 polyunsaturated fatty acids seem to exert antineoplastic actions in melanoma cells.\n\n\nOBJECTIVES\nWe aimed to assess the association of validated estimates of dietary PCB exposure as well as the intake of eicosapentaenoic acid and docosahexaenoic acid\u00a0(EPA-DHA), accounting for sun habits and skin type, with the risk of malignant melanoma in middle-aged and elderly women.\n\n\nMETHODS\nWe included 20,785 women at baseline in 2009 from the prospective population-based Swedish Mammography Cohort. Validated estimates of dietary PCB exposure and EPA-DHA intake were obtained via a food frequency questionnaire. Incident melanoma cases were ascertained through register-linkage.\n\n\nRESULTS\nDuring 4.5 years of follow-up, we ascertained 67 incident cases of melanoma. After multivariable adjustments, exposure to dietary PCBs was associated with four-fold increased risk of malignant melanoma (hazard ratio [HR], 4.0 [95% confidence interval {CI}, 1.2-13; P for trend\u00a0=\u00a00.02]), while EPA-DHA intake was associated with 80% lower risk (HR, 0.2 [95% CI, 0.1-0.8; P for trend\u00a0=\u00a00.03]), comparing the highest exposure tertiles with the lowest.\n\n\nCONCLUSION\nWhile we found a direct association between dietary PCB exposure and risk of melanoma, EPA-DHA intake showed to have a substantial protective association. Question of benefits and risk from fish consumption is very relevant and further prospective studies in the general population verifying these findings are warranted.", "descriptor": "Skin Neoplasms", "qualifier": "epidemiology"}, {"mag_id": 2334237725, "corpus_id": 13587988, "title": "Acute otitis media in pediatrics: are there rational issues for empiric therapy?", "abstract": "BACKGROUND\nAcute otitis media in children is a significant clinical problem that requires a rational approach to treatment. The condition is extremely common and has important economic implications. At present there is considerable controversy over the most appropriate strategy and over the use and choice of antibiotics.\n\n\nOBJECTIVES\nTo analyze the various factors that influence therapeutic decisions and consider how these may assist in the formulation of a rational approach to therapy.\n\n\nDISCUSSION\nOtitis media has a multifactorial etiology but it is extremely difficult to differentiate between bacterial and viral causes on clinical grounds. Culture of the middle ear fluid is rarely practicable; however, nasal swabs are relatively noninvasive and can provide useful microbiologic information, especially in excluding a bacterial cause. Published information provides little guidance on the most appropriate therapy; a rational approach to treatment is based on many considerations including the local epidemiology. The minimum criteria for the empiric choice of an antibiotic for acute otitis media are that it should be rapidly bactericidal and reach adequate concentrations in the middle ear fluid. In areas where beta-lactamase-producing strains are prevalent, a beta-lactamase-stable antibiotic should be chosen; good absorption from the gastrointestinal tract and high and consistent penetration into the middle ear are important characteristics. Compliance-enhancing factors such as fewer doses per day and good palatability are also important.", "descriptor": "Anti-Bacterial Agents", "qualifier": "therapeutic use"}, {"mag_id": 2468486553, "corpus_id": 3158690, "title": "[Experiences of liver retransplantation for postoperative diffuse biliary strictures].", "abstract": "OBJECTIVE\nTo investigate the feasibility and management of retransplantation for diffuse biliary strictures occurring after initial liver transplantation.\n\n\nMETHODS\nThe clinical data of 53 consecutive liver retransplantation patients at our hospital from January 2001 to December 2009 were collected and analyzed retrospectively. Among them, 20 (37.7%) were due to diffuse biliary strictures.\n\n\nRESULTS\nDiffuse biliary strictures appeared at 3 - 16 months after initial transplantation. The mean time was 6.3 months. The specific types included intra-hepatic diffuse biliary strictures (n = 16) and multi-strictures involving both intra- & extra-hepatic biliary ducts (n = 4). Retransplantation was performed after a failure of intervention or/and other comprehensive treatments. Among them, 14 were cured and 6 died from peri-operative complications including serious abdominal infection & MODS (multiple organ dysfunction syndrome) (n = 3, 50%), biliary fistula (n = 2, 33.3%) and hepatic artery embolism (n = 1, 16.7%). These patients were followed up for a mean time of 1.8 years (range: 1 - 5 years). The accumulative survival rates at 1, 3 and 6 months were 80.0%, 75.0% and 70.0% respectively.\n\n\nCONCLUSIONS\nLiver retransplantation is the ultimate treatment for diffuse biliary strictures after liver transplantation. The survival rate is associated with operative timing, surgical techniques and peri-operative management.", "descriptor": "Postoperative Complications", "qualifier": "surgery"}, {"mag_id": 2008876371, "corpus_id": 38902968, "title": "Role of manidipine in the management of patients with hypertension", "abstract": "Manidipine is a third-generation dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. In clinical studies, manidipine has been shown to significantly lower office and 24-h blood pressure compared with placebo in patients with essential hypertension. The resulting reduction in blood pressure is maintained over 24 h, with preservation of the circadian blood pressure pattern; its blood pressure-lowering capacity appears to be similar to that of other calcium antagonists. In elderly patients with mild-to-moderate essential hypertension, manidipine is able to significantly decrease blood pressure compared with placebo for up to 3 years of treatment. The drug also significantly lowers blood pressure in patients with hypertension and concomitant Type 2 diabetes mellitus or renal impairment, and is devoid of adverse metabolic effects. It is well-tolerated with few untoward adverse effects related to vasodilation. In particular, manidipine appears to have less potential for pedal edema than other calcium channel blockers.", "descriptor": "Hypertension", "qualifier": "drug therapy"}, {"mag_id": 2130371350, "corpus_id": 34623102, "title": "Age-Dependent Postdiapause Development in the Gypsy Moth (Lepidoptera: Lymantriidae) Life Stage Model", "abstract": "ABSTRACT \n For the last \u224810 yr, the Gypsy Moth Life Stage (GLS) model has been used by pest managers to predict when important events in the gypsy moth, Lymantria dispar L., life cycle will occur (e.g., peak second larval instar population and male moth flight). Although the GLS model has been shown to outperform other gypsy moth phenology models, its predictions have not always been as accurate as desired. Differences between predicted and observed egg hatch phenology prompted a re-examination of the original experimental data that were used in the construction of the egg hatch submodels of the original GLS model, and a data processing error was discovered to have truncated the postdiapause experimental data. Analysis of the complete data set confirmed that developmental rates in the postdiapause phase were age and temperature dependent but that the developmental response to temperature is distinctly nonlinear at postdiapause initiation, in contrast to the indeterminate response previously reported. By incorporating the new estimates of developmental rate patterns and parameters into the GLS model, errors in the GLS-simulated egg hatch period were reduced by 33\u201371% and error in date of 50% cumulative egg hatch by 25\u2013100%.", "descriptor": "Aging", "qualifier": "physiology"}, {"mag_id": 2410663629, "corpus_id": 40716988, "title": "Endocervical involvement by endometrial carcinoma on fractional curettage: a clinicopathological study of 37 cases.", "abstract": "This is a retrospective study of 37 patients with endometrial carcinoma and presence of tumor on endocervical curettage (clinical Stage II). We intended to correlate the presence or absence of endocervical stromal invasion with the clinical behavior and other prognostic factors. Based on the endocervical curettage, three categories (CAT) were defined: CAT I: tumor fragments only (seven cases); CAT II: endocervical tissue and free-floating tumor fragments (13 cases); and CAT III: endocervical tissue and tumor with evidence of stromal invasion (17 cases). Five tumors were partly of clear cell and/or papillary serous types and three of them belonged to CAT I. Six of seven tumors with a nuclear Grade 3 were in CAT III (p less than 0.05). Nine patients had local recurrence, metastases, or died of their disease (median follow-up: 56 mo) and seven of them were in the CAT III (p less than 0.05). We conclude that despite the presence of tumor on the endocervical curettage, the lack of endocervical tissue invasion is associated with a lower nuclear grade and a less aggressive behavior. These tumors should be regarded and treated as Stage I disease. Special attention must be paid to staging of clear cell and papillary serous adenocarcinomas because of the tendency for these tumors to contaminate the endocervical curettage.", "descriptor": "Adenocarcinoma", "qualifier": "pathology"}, {"mag_id": 2617982897, "corpus_id": 3629378, "title": "FOLFOXIRI Plus Bevacizumab as Conversion Therapy for Patients With Initially Unresectable Metastatic Colorectal Cancer: A Systematic Review and Pooled Analysis", "abstract": "Importance The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial. Objective To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions. Data Sources A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer). Study Selection Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded. Data Extraction and Synthesis Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial. Main Outcomes and Measures Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions. Results Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2\u2009=\u200925%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30.2 months (95% CI, 26.5-33.7 months) in 6 trials with data available, and progression-free survival was 12.4 months (95% CI, 10.0-14.3 months) in 9 trials with data available. In meta-regression analysis, variables significantly associated with conversion surgery were disease limited to the liver and a higher median number of cycles (close to 12). Conclusions and Relevance For patients with surgically unresectable metastatic colorectal cancer, FOLFOXIRI-Bev is associated with a significant overall response rate. Such an effective regimen leads to a probability of surgical conversion of distant metastases approaching 40%, with more than one-fourth of patients having an R0 resection.", "descriptor": "Liver Neoplasms", "qualifier": "secondary"}, {"mag_id": 2473469715, "corpus_id": 2348872, "title": "Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment", "abstract": "BackgroundCombination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have considered combination treatments. The current study modeled bacterial growth in the intestine of pigs after intramuscular combination treatment (i.e. using two antibiotics simultaneously) and sequential treatments (i.e. alternating between two antibiotics) in order to identify the factors that favor the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.ResultsSimulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.ConclusionSequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.", "descriptor": "Anti-Bacterial Agents", "qualifier": "pharmacology"}, {"mag_id": 160165132, "corpus_id": 7443004, "title": "[A sudden redness and swelling of the face].", "abstract": "Two patients were referred to a department of oral and maxillofacial surgery with a redness and swelling of the face which had suddenly developed together with a mild illness. The diagnosis of erysipelas was made clinically. This skin infection is generally caused by betahaemolytic streptococci group-A. Treatment is generally in the first instance medicinal. The drugs of choice for treating erysipelas in the vast majority of cases are narrow-spectrum penicillins.", "descriptor": "Anti-Bacterial Agents", "qualifier": "therapeutic use"}, {"mag_id": 1991417725, "corpus_id": 3386859, "title": "Canine superficial bacterial pyoderma: evaluation of skin surface sampling methods and antimicrobial susceptibility of causal Staphylococcus isolates.", "abstract": "OBJECTIVE\nTo evaluate three easily performed methods of skin surface sampling for bacterial culture of Staphylococcus isolates obtained from dogs with superficial bacterial pyoderma (SBP) presenting to two veterinary teaching hospitals in Sydney, Australia, and to determine the antimicrobial susceptibility of isolates.\n\n\nDESIGN\nProspective study of 27 dogs with SBP. Cytologically confirmed SBP lesions were sampled for bacterial culture using a dry cotton swab, a saline-moistened cotton swab and a skin surface scraping. Isolates were identified by standard discriminatory phenotypic and biochemical analyses, and confirmed using matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF MS). Susceptibilities to 14 antimicrobials were determined by disk diffusion and by detection of the mecA gene using PCR. Sampling methods were compared according to bacterial yield, antibiograms and bacterial phenotypic analysis. Location of causative bacteria was evaluated via 8-mm punch skin biopsies using haematoxylin and eosin, Gram-Twort and Giemsa staining, and fluorescence in situ hybridisation (FISH).\n\n\nRESULTS\nStaphylococcus sp. were isolated from lesions in all dogs, either S. pseudintermedius (24 dogs) or S. schleiferi (3 dogs). Susceptibility was highest to cephalexin (96%) and amoxycillin clavulanate (96%). Methicillin resistance assessed by mecA real-time PCR and phenotypic oxacillin resistance was found in one dog (4.3%). Routine histology and FISH revealed bacteria within superficial stratum corneum.\n\n\nCONCLUSION\nStaphylococcal isolates from canine SBP demonstrated high susceptibility to common empirical antimicrobials. Histological techniques confirmed presence of bacteria at superficial sites, likely to be accessed by the sampling techniques. The three techniques afforded similar results and may be equally suitable for obtaining samples for culture.", "descriptor": "Anti-Bacterial Agents", "qualifier": "pharmacology"}, {"mag_id": 1995197542, "corpus_id": 13014668, "title": "In vitro study of cysteine oxidase in rat brain", "abstract": "Effects of some cysteine analogs and other compounds on in vitro cysteine oxidase were studied in rat brain microsomes. Among the tested compounds, maximum inhibition of microsomal cysteine oxidase was by \u03b1,\u03b1\u2032-dipyridyl and the least inhibition by dithiothreitol. Kinetic and dialysis studies foundl-homocysteine to be a competitive and reversible inhibitor of cysteine oxidase. Epinephrine was shown to inhibit cysteine oxidase, whereas pyridoxal HCl activated cysteine oxidase at the same concentration. Except for the Mg2+ ion, other metallic ions inhibited cysteine oxidase activity in the following order: Zn2+>Cu2+>Li+ >Ca2+>Co2+>K+>Mn2+. A 12 mM concentration of Mg2+ ion was required to obtain maximum cysteine oxidase activity.", "descriptor": "Brain", "qualifier": "enzymology"}, {"mag_id": 2014098233, "corpus_id": 20656466, "title": "Surgical Management of Normocalcemic Primary Hyperparathyroidism", "abstract": "BackgroundPrimary hyperparathyroidism (pHPT), typically defined as elevated serum calcium levels associated with inappropriately elevated parathyroid hormone (PTH) levels, can occur also in patients with normal serum calcium levels. This study investigated the characteristics, workup, and surgical management of patients with normocalcemic pHPT.MethodsA retrospective chart review of a prospectively collected, single-institution parathyroid database was performed on patients with sporadic pHPT who underwent parathyroidectomy between 12/99 and 12/08.ResultsIn all, 93 of 771 (12%) pHPT patients had normal serum calcium levels 3\u00a0months prior to surgery. Ionized calcium (iCa) levels were available for 58 patients and were elevated in 50 (86%). Among those with elevated iCa levels 90% had single-gland disease (SGD), whereas 63% with normal iCa levels had SGD (p\u00a0=\u00a00.07). Preoperative imaging identified SGD in 60% of patients with normal iCa and in 66% with elevated iCa levels. Intraoperative PTH (IOPTH) monitoring identified cure in 51 of 58 (88%) patients including 6 (75%) with normal iCa. At a median follow-up of 358\u00a0days, postoperative calcium and PTH levels were similar in the groups. One (1%) patient had recurrent disease.ConclusionsMost patients with apparent normocalcemic pHPT have elevated ionized calcium levels. For patients with normocalcemic pHPT, we recommend measuring iCa levels preoperatively, performing localization studies, and utilizing IOPTH monitoring to guide a successful operation.", "descriptor": "Calcium", "qualifier": "blood"}, {"mag_id": 2904808248, "corpus_id": 54470774, "title": "Lung cancer screening: assessment of health literacy and readability of online educational resources", "abstract": "BackgroundLung cancer screening can reduce mortality but can be a complex, multi-step process. Poor health literacy is associated with unfavorable outcomes and decreased use of preventative services, so it is important to address barriers to care through efficient and practical education. The readability of lung cancer screening materials for patients is unknown and may not be at the recommended 6th grade reading level set by the American Medical Association. Our goals were to: (1) measure the health literacy of a lung cancer screening population from an urban academic medical center, and (2) examine the readability of online educational materials for lung cancer screening.MethodsWe performed a retrospective cross sectional study at a single urban academic center. Health literacy was assessed using three validated screening questions. To assess the readability of educational materials, we performed a Google search using the phrase, \u201cWhat is lung cancer screening?\u201d and the Flesch-Kincaid Grade Level (FKGL) formula was used to estimate the grade level required to understand the text.ResultsThere were 404 patients who underwent lung cancer screening during the study period. The prevalence of inadequate/marginal health literacy was 26.7\u201338.0%. Fifty websites were reviewed and four were excluded from analysis because they were intended for medical providers. The mean FKGL for the 46 websites combined was 10.6\u2009\u00b1\u20092.2.ConclusionsLow health literacy was common and is likely a barrier to appropriate education for lung cancer screening. The current online educational materials regarding lung cancer screening are written above the recommended reading level set by the American Medical Association.", "descriptor": "Lung Neoplasms", "qualifier": "diagnosis"}, {"mag_id": 2020334067, "corpus_id": 21915555, "title": "A sporulation-induced sigma-like regulatory protein from b. subtilis", "abstract": "We have isolated a sigma-like regulatory protein termed sigma 29 whose synthesis or association with Bacillus subtilis RNA polymerase was induced during spore formation. sigma 29 is a sporulation-specific component of RNA polymerase as it was absent in enzyme from an early-blocked sporulation mutant (SpoOA). We have demonstrated specific RNA synthesis by sigma 29-RNA polymerase using as a DNA template a cloned cluster of vegetative and sporulation genes from the purA-cysA region of the B. subtilis chromosome. The pattern of gene recognition by sigma 29-RNA polymerase was distinct from that observed for RNA polymerases containing sigma 55 or sigma 37, species of sigma factor that are present in vegetative cells of B. subtilis. A reconstitution experiment in which purified sigma 29 was added to core RNA polymerase demonstrates that sigma 29 was directly responsible for the altered transcriptional specificity of sporulation RNA polymerase. We propose that sigma 29 is a regulatory protein that controls developmental gene transcription at an early stage of spore formation.", "descriptor": "Bacterial Proteins", "qualifier": "physiology"}, {"mag_id": 2019812803, "corpus_id": 2867533, "title": "Basic Symptoms, Temperament and Character in Adolescent Psychiatric Disorders", "abstract": "Objective: Basic symptoms are early subtle changes in thinking, feeling and perception that are subjectively experienced and precede the onset of a psychotic illness. In adult samples, high basic symptom scores are regarded as specific risk factors for the development of schizophrenia. The aim of this study was to explore the relevance of basic symptoms of psychiatric disorders in adolescent patients with special focus on early detection of psychosis. Furthermore, the association between basic symptoms and personality traits has been investigated. Method: From89 adolescents, who were consecutive inpatients with different psychiatric disorders in 1995 and 1997, 54 were followed up 4.7 years later. Patients were examined with the Bonn Scale for the Assessment of Basic Symptoms at the time of the first presentation and follow-up. Additionally, personality traits were assessed at follow-up using the Junior Temperament and Character Inventory. Results: Noneof the subjects made the transition to schizophrenia, despite high baseline scores of basic symptoms at the initial assessment. Indirect minus symptoms were found to be the most valid predictor of a persisting psychiatric diagnosis. In addition, this specific category was strongly associated with the personality traits harm avoidance and self-directedness. Conclusion: Inadolescents, basic symptomsin association with personality traitspresent as a nonspecificindicator of psychopathology rather than as an indicator of vulnerability to schizophrenia.", "descriptor": "Mental Disorders", "qualifier": "diagnosis"}, {"mag_id": 2048878567, "corpus_id": 34528760, "title": "Prostate cancer: The growing evidence supporting mid-life PSA testing", "abstract": "Serum PSA testing remains controversial as the data regarding its utility are conflicting. However, a recent study adds to the growing body of evidence supporting its usefulness in middle-aged men, especially in the determination of the long-term risk of metastasis and death from prostate cancer.", "descriptor": "Prostatic Neoplasms", "qualifier": "mortality"}, {"mag_id": 3038248843, "corpus_id": 220253194, "title": "Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults", "abstract": "APOE-\u03b54 is a major genetic risk factor for late-onset Alzheimer's disease that interacts with other risk factors, but the nature of such combined effects remains poorly understood. We quantified the impact of\u00a0APOE-\u03b54, family history (FH) of dementia, and obesity on white matter (WM) microstructure in 165 asymptomatic adults (38-71 years old) using quantitative magnetization transfer and neurite orientation dispersion and density imaging. Microstructural properties of the fornix, parahippocampal cingulum, and uncinate fasciculus were compared with those in motor and whole-brain WM regions. Widespread interaction effects between APOE, FH, and waist-hip ratio were found in the myelin-sensitive macromolecular proton fraction from quantitative magnetization transfer. Among individuals with the highest genetic risk (FH+ and\u00a0APOE-\u03b54), obesity was associated with reduced macromolecular proton fraction in the right parahippocampal cingulum, whereas no effects were present for those without FH. Risk effects on apparent myelin were moderated by hypertension and inflammation-related markers. These findings suggest that genetic risk modifies the impact of obesity on WM myelin consistent with neuroglia models of aging and late-onset Alzheimer's disease.", "descriptor": "Obesity", "qualifier": "genetics"}, {"mag_id": 2053872736, "corpus_id": 72743254, "title": "Progression of a Pedunculated Polyp", "abstract": "A 56-year-old man underwent a colonoscopy after a positive fecal occult-blood test. Colonoscopy revealed two pedunculated polyps, one in the ascending colon and one in the transverse colon. One polyp was removed with a polypectomy snare (Panel A), but removal of the other was deferred owing to procedural difficulties. Unfortunately, the patient did not return for follow-up, for personal reasons. Five years later, he returned to our hospital after another positive fecal occult-blood test. Colonoscopy revealed a lesion, 15 mm in diameter, at the site of the previously detected pedunculated polyp (Panel B); no additional polyps were found. Complete surgical .\u00a0.\u00a0.", "descriptor": "Adenocarcinoma", "qualifier": "pathology"}, {"mag_id": 2411292440, "corpus_id": 8367700, "title": "Diagnostic techniques in head and neck cancer.", "abstract": "The evaluation of a patient with a cancer in the head and neck should begin with a complete history. A thorough physical examination will aid in determining the tumor extent. Finally, diagnostic techniques have been outlined that can help in determining the extent of the primary tumor and metastases.", "descriptor": "Carcinoma, Squamous Cell", "qualifier": "diagnosis"}, {"mag_id": 2399108376, "corpus_id": 38142885, "title": "Effect of DL-ethionine and S-ethyl-L-cysteine on rat liver regeneration.", "abstract": "The administration of diets containing 0.05\u20130.40% dl-ethionine to partially hepatectomized rats decreases the extent of liver regeneration over a period of 10.5 days. Body weight losses and definite liver pathology are noted for animals of either sex fed the rations with 0.30% or 0.40% ethionine. The effect is neutralized by the simultaneous feeding of methionine but not by choline, thereby reflecting definite amino acid antagonism. S-ethyl-l-cysteine, a homolog of ethionine, at a dietary level of 0.40% is without effect on the rate of liver regeneration.", "descriptor": "Liver", "qualifier": "drug effects"}, {"mag_id": 2008256611, "corpus_id": 1999423, "title": "Asbestos exposure among Finnish lung cancer patients: occupational history and fiber concentration in lung tissue.", "abstract": "In a series of 65 surgically treated lung cancer patients, past exposure to asbestos was evaluated by personal interviews, and by scanning electron microscopy analyses of the mineral fibers in lung tissue. Lung tissue samples of 17 autopsied male office workers were analyzed as referents. According to occupational history, 37% of the lung cancer patients had definite or probable, 31% possible, and 32% unlikely exposure to asbestos. The fiber concentration in the lung tissue ranged from < 0.1 to 65 million fibers per gram dry tissue in the lung cancer group, and from < 0.1 to 0.8 million fibers per gram dry tissue in the reference group. In 26% of the lung cancer patients, but in none of the referents, the fiber concentration exceeded 1 million fibers per gram dry tissue. Most of the exposed patients had been employed in various construction jobs, and valuable information about the exposure levels could be obtained by the mineral fiber analyses. In general, there was a good accord between the exposure categorization and the fiber burden measured in the lung.", "descriptor": "Lung", "qualifier": "pathology"}, {"mag_id": 2043537498, "corpus_id": 40542361, "title": "Partial degradation of transfer RNAs by sheep kidney nuclease.", "abstract": "Abstract Sheep kidney nuclease attacks, in the presence of Mg2+, several tRNAs exclusively or primarily at the 3\u2032-side of the double-stranded acceptor stem. Accordding to oligonucleotide analysis the products formed from yeast tRNAPhe were a mixture of 80 % Phe 1\u201369 with 20 % Phe 1\u201370 and small oligonucleotides from the 3\u2032-terminal sequence. The degradations of wheat germ tRNAPhe, yeast tRNAVal, tRNATyr and tRNASer were studied by disc electrophoretic methods. In the absence of Mg2+ the tRNAs were degraded rather fast to several fragments and oligonucleotides. Mixtures of Phe 1\u201369/70 with Phe 21\u201376 possessed significant acceptor activity for phenylalanine. Poly(A), poly(U) and poly(C) could be degraded by sheep kidney nuclease to homologous series of oligo- and polynucleotides. Oligo- and polyadenylic acids up to a chain length of about 40 nucleotides were separated by disc electrophoresis.", "descriptor": "Kidney", "qualifier": "enzymology"}, {"mag_id": 2091826796, "corpus_id": 29978311, "title": "S-100 in the central nervous system of rat, rabbit and guinea pig during postnatal development", "abstract": "The accumulation of the brain-specific S-100 protein has been studied during postnatal development of rat, rabbit and guinea pig quantitatively, using immunoelectrophoresis, and qualitatively, by immunoelectron microscopy. Newborn guinea pigs show high levels of S-100. The distribution was similar to that of adult animals with an enrichment of S-100 to the postsynaptic membranes and to the astrocytic filaments. The neuronal plasma membranes as well as the neuronal nuclear membranes, astrocytic and oligodendroglial plasma membranes, also showed a specific activity for S-100. The amount of S-100 increased linearly from birth until the 3rd and 4th postnatal week of rabbit and rat, respectively. During the 2nd and 3rd week rabbit and rat nervous systems showed an accumulation of S-100, especially in the postsynaptic membranes and in the astrocytic filaments. In this study we present evidence that the S-100 protein quantitatively and ultrastructurally appears according to a pattern which parallels the muturation of brain, showing adult characteristics already at birth in early developing brains (guinea pig) and a change towards adult pattern after birth in late developing brains (rat and rabbit). In the latter two species change towards an adult S-100 distribution pattern proceeds during the postnatal period concomitant with the enzymatic and electrophysiogical maturation of the brain.", "descriptor": "Brain", "qualifier": "growth & development"}, {"mag_id": 68672169, "corpus_id": 5737324, "title": "Status of the \u201cProtein Kinase CK2\u2013HMG14\u201d System in Age-Related Amnesia in Rats", "abstract": "The experiments described here demonstrate that disruption of the phosphorylation of transcription factors of the HMG cAMP/Ca-independent protein kinase CK2 class may be the cause of decreased gene expression in age-related cognitive deficits. Amnesia for a conditioned passive avoidance reaction (CPAR) in aged rats (24 months old) was accompanied by decreases in the synthesis of synaptosomal proteins and transcription in nuclei isolated from cortical, hippocampal, and striatal neurons. There was a decrease in chromatin protein kinase CK2 activity and a significant decrease in the phosphorylation of HMG14 by protein kinase CK2. Selective activators of protein kinase CK2 (1-ethyl-4-carbamoyl-5-methylcarbamoylimidazole and 1-ethyl-4,5-dicarbamoylimidazole) increased HMG14 phosphorylation by protein kinase CK2, increased transcription, increased the synthesis of synaptosomal proteins, and decreased amnesia for the CPAR in aged rats. Thus, activation of the \u201cprotein kinase CK2\u2013HMG14\u201d system is accompanied by optimization of synaptic plasticity in aged animals. The results provide evidence for the high therapeutic potential of protein kinase CK2 activators.", "descriptor": "Aging", "qualifier": "physiology"}, {"mag_id": 1993622445, "corpus_id": 26850348, "title": "The treatment of shock complicating acute myocardial infarction.", "abstract": "FTER ACUTE MYOCARDIAL INFARCTION, the clinical course of approximately 12 per cent of patients is complicated by manifestations of circulatory shock. 1-4 With supportive treatment, including oxygen breathing and analgesic drugs, fewer than 1 of 5 patients survive. ~ The initial enthusiasm for \"vasopressor\" drugs, introduced 15 years ago, has been sustained by reports that the survival rate was doubled after introduction of these drugs2 Yet, others find no definitive evidence that these drugs have improved survival. 2,7's Since our understanding of both mechanisms and treatment of acute myocardial infarction and its complications is still very meager, convention rather than proved efficacy guides much of current practice in this field. After greater understanding of mechanisms is achieved, the rational basis for treatment will undoubtedly be greatly improved. Even modest improvement would profoundly alter the dismal outlook. A decrease in mortality of but 15 per cent would essentially double the number of survivors. The conscientious clinician, however, is alerted not only to the potential benefits of newer drugs and other innovations of management but he is properly suspicious that innovations are likely to entail greater risks before their ultimate value is established. With these considerations in mind, we reviewed experimental and clinical data on the treatment of shock complicating myocardial infarction, aided by the results of our own investigations in the University of Southern California Shock Research Unit at the Los Angeles County General Hospital. 9 This contribution is intended as a guide or, preferably, a resource to aid in the planning of bedside treatment.", "descriptor": "Myocardial Infarction", "qualifier": "complications"}, {"mag_id": 2052765198, "corpus_id": 9417052, "title": "WAVE2\u2010 and microtubule\u2010dependent formation of long protrusions and invasion of cancer cells cultured on three\u2010dimensional extracellular matrices", "abstract": "Invadopodia, small protrusions formed at ventral membranes of several types of invasive cancer cells upon contact with the extracellular matrix (ECM), are implicated in cell invasion; however, the relationship between invadopodia formation and cell invasion through the ECM is still unknown. To correlate the formation of membrane protrusions and cell invasion, a three\u2010dimensional (3\u2010D) gel culture system with native collagen type\u2010I matrix overlaid with a thin basement membrane equivalent (Matrigel) was made. Human breast cancer cell line MDA\u2010MB\u2010231 formed long protrusions in addition to small protrusions reminiscent of invadopodia and migrated into the collagen layer. Comparative analyses with other cancer cell lines indicate that cellular ability to form long protrusions, but not small protrusions or invadopodia, correlates with cellular invasiveness in the 3\u2010D culture. Some of the long protrusions in MDA\u2010MB\u2010231 cells appeared to extend from the adherence membrane, implying that they are derived from small protrusions. The formation of long protrusions and invasion, as well as the formation of invadopodia, required WAVE2 in MDA\u2010MB\u2010231 cells. Accumulation of tubulin was observed in long protrusions but not in invadopodia. Correspondingly, a microtubule\u2010stabilizing agent, paclitaxel, suppressed the formation of long protrusions and invasion, but not the formation of invadopodia, in MDA\u2010MB\u2010231 cells. These results suggest that long protrusions formed in a WAVE2\u2010 and microtubule\u2010dependent manner may identify the cells at the later stage of invasion, possibly after the formation of invadopodia in the 3\u2010D cultures. (Cancer Sci 2008; 99: 2252\u20132259)", "descriptor": "Neoplasms", "qualifier": "metabolism"}, {"mag_id": 2991667416, "corpus_id": 45732404, "title": "[Severe right-ventricular heart failure due to malignant pericardial mesothelioma].", "abstract": "A case of a 63-year old female with symptomatic advanced right-ventricular (RV) heart failure due to malignant pericardial mesothelioma is presented. Echocardiography revealed that RV failure was due to the tumour-induced compression of the right atrium and not due to metastatic mesothelioma involving pericardial sac.", "descriptor": "Myocardial Infarction", "qualifier": "etiology"}, {"mag_id": 2159327390, "corpus_id": 9847609, "title": "A geometry-based generic predictor for catalytic and allosteric sites.", "abstract": "An important aspect of understanding protein allostery, and of artificial effector design, is the characterization and prediction of substrate- and effector-binding sites. To find binding sites in allosteric enzymes, many of which are oligomeric with allosteric sites at domain interfaces, we devise a local centrality measure for residue interaction graphs, which behaves well for both small/monomeric and large/multimeric proteins. The measure is purely structure based and has a clear geometrical interpretation and no free parameters. It is not biased towards typically catalytic residues, a property that is crucial when looking for non-catalytic effector sites, which are potent drug targets.", "descriptor": "Proteins", "qualifier": "chemistry"}, {"mag_id": 2128331836, "corpus_id": 35946043, "title": "The identification and localization of a human gene with sequence similarity to Polycomblike of Drosophila melanogaster.", "abstract": "The Drosophila Polycomb group (PcG) of genes is required for the epigenetic regulation of a number of important developmental genes, including the homeotic (Hox) genes. The members of this gene family encode proteins that do not share sequence similarity, implying that each plays a unique role in this epigenetic repression mechanism. Polycomblike (Pcl) was the second PcG gene to be identified. We report here the isolation and characterization of a human cDNA, termed PHF1, which encodes a protein with significant sequence similarity to Drosophila Polycomblike (PCL). The region of similarity between PHF1 and PCL includes the two PHD fingers (C4-H-C3 motif), the region between them, and sequences C-terminal to the PHD fingers. PHF1 and PCL are 34% identical over this 258-residue region. PHF1 was mapped to 6p21.3 by fluorescence in situ hybridization. While several genetic diseases that are likely to result from developmental abnormalities map to this region, PHF1 is not a clear candidate gene for any of them.", "descriptor": "Proteins", "qualifier": "genetics"}, {"mag_id": 2143467551, "corpus_id": 2131888, "title": "Views on primary prevention of cardiovascular disease - an interview study with Swedish GPs", "abstract": "BackgroundGeneral practitioners (GPs) have gradually become more involved in the prevention of cardiovascular disease (CVD), both through more frequent prescribing of pharmaceuticals and by giving advice regarding lifestyle factors. Most general practitioners are now faced with decisions about pharmaceutical or non-pharmaceutical treatment for primary prevention every day. The aim of this study was to explore, structure and describe the views on primary prevention of cardiovascular disease in clinical practice among Swedish GPs.MethodsIndividual interviews were conducted with 21 GPs in southern Sweden. The interview transcripts were analysed using a qualitative approach, inspired by phenomenography.ResultsTwo main categories of description emerged during the analysis. One was the degree of reliance on research data regarding the predictability of real risk and the opportunities for primary prevention of CVD. The other was the allocation of responsibility between the patient and the doctor. The GPs showed different views, from being convinced of an actual and predictable risk for the individual to strongly doubting it; from relying firmly on protection from disease by pharmaceutical treatment to strongly questioning its effectiveness in individual cases; and from reliance on prevention of disease by non-pharmaceutical interventions to a total lack of reliance on such measures.ConclusionsThe GPs' different views, regarding the rationale for and practical management of primary prevention of CVD, can be interpreted as a reflection of the complexity of patient counselling in primary prevention in clinical practice. The findings have implications for development and implementation of standard treatment guidelines, regarding long-time primary preventive treatment.", "descriptor": "Cardiovascular Diseases", "qualifier": "prevention & control"}, {"mag_id": 2049488766, "corpus_id": 46597595, "title": "Skin disorders in organ transplant recipients. External anogenital lesions.", "abstract": "SINCE THE early 1960s, more than 400 000 transplantations of various organs have been performed worldwide. Dermatologists play an increasingly important role in the diagnosis and management of the common skin problems experienced by these patients. Some kind of dermatologic lesion has been found in 45% to 100% of patients examined. 1-3 Four major categories of skin lesions can be identified. The first category includes side effects of the immunosuppressive agents, mainly cushingoid effects of prednisone therapy (buffalo hump, moon face, acne, striae, facial erythema, increased hair growth, dry skin, atrophic and friable skin, purpura, and telangiectasia), and hypertrichosis, sebaceous hyperplasia, epidermal cysts, pilar keratosis, and gum hypertrophy caused by cyclosporine administration. 1-6 The second category includes various types of bacterial infection that, at times, may be life-threatening; fungal infections (pityriasis versicolor, candidiasis, tinea, and onychomycosis); and viral infections (herpes simplex, herpes zoster, varicella, and warts). 1,3-6 Warts are", "descriptor": "Skin Neoplasms", "qualifier": "etiology"}, {"mag_id": 2231014272, "corpus_id": 8596433, "title": "High Prevalence of Diabetic Retinopathy in Diabetic Patients Concomitant with Metabolic Syndrome", "abstract": "Objective To evaluate the relationship between metabolic syndrome (MetS) and the prevalence of diabetic retinopathy (DR). Research Design and Methods We conducted a case-controlled study, with data obtained from 2,551 Chinese participants between 18\u201379 years of age (representing a population of 1,660,500 in a district of Beijing). 74 cases of DR were found following data assessment by two 45\u00b0 digital retinal images. Subjects without DR (NDR group) selected from the remaining 2,477 subjects were matched 1:1 to the DR group by HbA1c. MetS was defined by incorporating diagnostic criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). Results There were no statistical differences between the DR group and NDR group in a number of biological or laboratory tests. However, the percentage of patients with DR increased vs. patients without DR with the number of MetS components from 1 to 5 (14.3% vs. 85.7%, 38.9% vs. 61.1%, 49.1% vs. 50.9%, 61.4% vs. 38.6% and 83.3% vs. 16.7%, respectively) (Pearson \u03c72 = 9.938, P = 0.037). The trend to develop DR with MetS was significantly higher than that without MetS (NMetS) (\u03c72 = 5.540, P = 0.019). MetS was an independent statistical indicator of the presence of DR after adjusting for age and sex [odds ratio (95% CI): 2.701(1.248\u20135.849), P = 0.012], which is still the case with an additional adjustment for WC, SBP, TC, HbA1c and duration of diabetes [odds ratio (95% CI): 2.948(1.134\u20137.664), P = 0.027]. Conclusion DR is one of the diabetic microvascular complications. Apart from poor glycemic control, the concomitance of other metabolic factors can also influence DR. MetS, defined as a cluster of metabolic risk factors, is a strong and independent indicator of DR, even to the same extent as glycemic control.", "descriptor": "Diabetes Mellitus, Type 2", "qualifier": "pathology"}, {"mag_id": 1953266920, "corpus_id": 205819169, "title": "Knowledge and attitudes towards HIV/AIDS amongst Kuwait University dental students.", "abstract": "The HIV and AIDS have emerged as complex health threats to the world population. As future dentists, it is pertinent that the dental students have sufficient knowledge and a positive approach towards the disease. Accordingly, the aim of this study was to assess the HIV/AIDS related knowledge and attitudes amongst clinical dental students at Kuwait University. A cross-sectional survey was conducted amongst the clinical dental students using a structured questionnaire with 60 questions to examine their knowledge under various categories and 13 questions to examine their attitudes towards the disease. The survey revealed that almost 58% of the respondents demonstrated a high level of knowledge (mean score: 45.23 \u00b1 4.35 SD). Majority of the students (63.6%) expressed negative attitude (mean score: 5.36 \u00b1 2.56 SD). The mean knowledge score of the fifth year dental students was significantly higher (P = 0.022) than that of the final year dental students regarding the knowledge of virus and disease process. However, no significant difference was observed with respect to other knowledge categories. Despite their high level of knowledge, the majority displayed a negative attitude towards HIV/AIDS. Hence, the findings imply that there is a need to address, more clearly, the students' misconceptions and attitudes towards the disease.", "descriptor": "HIV Infections", "qualifier": "psychology"}, {"mag_id": 2040148020, "corpus_id": 21303641, "title": "Detecting Functional Connectivity During Audiovisual Integration with MEG: A Comparison of Connectivity Metrics", "abstract": "In typical magnetoencephalography and/or electroencephalography functional connectivity analysis, researchers select one of several methods that measure a relationship between regions to determine connectivity, such as coherence, power correlations, and others. However, it is largely unknown if some are more suited than others for various types of investigations. In this study, the authors investigate seven connectivity metrics to evaluate which, if any, are sensitive to audiovisual integration by contrasting connectivity when tracking an audiovisual object versus connectivity when tracking a visual object uncorrelated with the auditory stimulus. The authors are able to assess the metrics' performances at detecting audiovisual integration by investigating connectivity between auditory and visual areas. Critically, the authors perform their investigation on a whole-cortex all-to-all mapping, avoiding confounds introduced in seed selection. The authors find that amplitude-based connectivity measures in the beta band detect strong connections between visual and auditory areas during audiovisual integration, specifically between V4/V5 and auditory cortices in the right hemisphere. Conversely, phase-based connectivity measures in the beta band as well as phase and power measures in alpha, gamma, and theta do not show connectivity between audiovisual areas. The authors postulate that while beta power correlations detect audiovisual integration in the current experimental context, it may not always be the best measure to detect connectivity. Instead, it is likely that the brain utilizes a variety of mechanisms in neuronal communication that may produce differential types of temporal relationships.", "descriptor": "Brain", "qualifier": "physiology"}, {"mag_id": 2416292494, "corpus_id": 21316564, "title": "[Possibilities of hemosorption in the compensation of cardiac dysfunction in patients with ischemic heart disease associated with diabetes mellitus].", "abstract": "A total of 36 patients with unstable angina and type II diabetes mellitus were studied in the dynamic. All the patients underwent extracorporeal hemocarboperfusion. Marked improvement in the inotropic function of the myocardium was noted with the increase in the rate of relaxation and contraction of the posterior wall of the myocardium. A decrease in the pressure in the lesser circulation and specific peripheral resistance were registered. Using radiometry technique a corresponding decrease in the volume of extravascular fluid in the lungs was observed.", "descriptor": "Diabetes Mellitus, Type 2", "qualifier": "complications"}, {"mag_id": 2365395319, "corpus_id": 24634382, "title": "[Study on early change features of microRNA in the peripheral blood of Sophorae tonkinensis radix et rhizoma induced liver injury rats].", "abstract": "OBJECTIVE\nTo study early change features of microRNA (miRNA) in the peripheral blood of Sophorae Tonkinensis Radix et Rhizoma induced liver injury rats, and to look for the miRNA biomarkers in the peripheral blood of early liver injury.\n\n\nMETHODS\nSixty Wistar rats were randomly divided into the control group and the Sophorae Tonkinensis Radix et Rhizoma (abbreviated as STRR) group, 30 in each group. Rats in the STRR group was administered with STRR decoction at 12 g/kg (2 mL/100 g), while equal volume of the distilled water was given to those in the control group. Rats were anesthetized on day 3, 7, 14, and 28, and 28 days after withdrawal. The serum samples were withdrawn. The alanine aminotransferase (ALT), aspartate transaminase (AST), total bile (TBIL), alkaline phosphatase (ALP), total protein (TP), and albumin (ALB) were detected. The globulin (GLO) level was calculated. HE staining was performed on the liver tissue to observe the pathomorphological changes. The whole blood was collected on day 7, 14, and 28 to perform the microarray test. The differentially expressed miRNAs were screened and verified by RT-PCR.\n\n\nRESULTS\nThe ALT activity obviously increased on day 7 - 28 in the STRR group (P <0.05). The histopathological results showed the degeneration and swelling of the liver cells on day 28. In the microarray test, there were 11, 22, and 13 up regulated expressed miRNAs on day 7, 14, and 28, respectively. There were 1, 13, 2 down regulated expressed miRNAs on day 7, 14, and 28, respectively. By target gene prediction and pathway analysis of differentially expressed miRNA on day 7, 14, and 28, they involved in regulating and controlling signal transduction, cellular interaction, cytoskeleton. Differentially expressed miRNA might possibly participate in the process of liver injury. The RT-PCR result of the expression of miR-291a-5p with the peak time efficiency on day 7 showed that the expressions of miR-291a-5p in the peripheral blood and the liver tissue were basically identical.\n\n\nCONCLUSION\nmiR-291a-5p could early indicate the liver injury, which could be taken as one of an early marker in STRR induced liver injury.", "descriptor": "Liver", "qualifier": "pathology"}, {"mag_id": 2014260912, "corpus_id": 189884646, "title": "A non-local gap-penalty for profile alignment", "abstract": "The length of an alignment of biological sequences is typically longer than the mean length of its component sequences. (This arises from the insertion of gaps in the alignment.) When such an alignment is used as a profile for the alignment of further sequences (or profiles), it will have a bias toward additional sequences that match the length of the profile, rather than the mean length of sequences in the profile, as the alignment of these well entail fewer (or smaller) insertions) so avoiding gap-penalties). An algorithm is described to correct this bias that entails monitoring the correspondence, for every pair of positions, of the mean separations in both profiles as they are aligned. The correction was incorporated into a standard dynamic programming algorithm through a modification of the gap-penalty, but, unlike other approaches, this modification is not local and takes into consideration the overall alignment of the sequences. This implies that the algorithm cannot guarantee to find the optimal alignment, but tests suggest that close approximations are obtained. The method was tested on protein families by measuring the area in the parameter space of the phase containing the correct multiple alignment. No improvement (increase in phase area) was found with a family that required few gaps to be aligned correctly. However, for highly gapped alignments, a 50% increase in area was obtained with one family and the correct alignment was found for another that could not be aligned with the unbiased method.", "descriptor": "Proteins", "qualifier": "chemistry"}, {"mag_id": 2908632726, "corpus_id": 58611751, "title": "Systems-based approaches for investigation of inter-tissue communication[S]", "abstract": "Secreted proteins serve as crucial mediators of many physiology processes, and beginning with the discovery of insulin, studies have revealed numerous context-specific regulatory networks across various cell types. Here, we review \u201comics\u201d approaches to deconvolute the complex milieu of proteins that are released from the cell. We emphasize a novel \u201csystems genetics\u201d approach our laboratory has developed to investigate mechanisms of tissue-tissue communication using population-based datasets. Finally, we highlight potential future directions for these studies, discuss several caveats, and propose new ways to investigate modes of endocrine communication. Graphical Abstract", "descriptor": "Proteins", "qualifier": "metabolism"}, {"mag_id": 2570677492, "corpus_id": 42608121, "title": "Outcomes Bronchoscopic Evaluation in A University Hospital.", "abstract": "INTRODUCTION\nStudy of clinical profile of the patients and diagnostic yield of the selected bronchoscopic procedures gives us important information in clinical decision making and better patient care. There are hardly very few studies regarding these entities. Therefore, we decided to study clinical characteristics and outcomes of the patients who underwent bronchoscopic evaluation in our setting.\n\n\nMETHODS\nThis was a cross-sectional study the consecutive patients who underwent bronchoscopy from 1st May 2013- 30th April 2015 in division of pulmonary, critical care and sleep medicine. The main procedure performed was bronchoalveolar lavage.\n\n\nRESULTS\nThe mean age was 54.71 years with 76 (76%) males. Recurrent hemoptysis in 58 (58%) patients were the commonest indication. Total 95 (95%) patients have chest X-ray abnormalities. The commonest bronchoscopic finding was bronchiectasis 23 (23%) of patients followed by chronic bronchitis in 18 (18%) and endobronchial tuberculosis in 16 (16%). Total 10 (71%) of the 14 bronchoscopically suspected lung cancer patients have intraluminal lesions. Bronchoalveolar lavage culture for tuberculosis showed growth in 46 (46%), positive for malignancy in 7 (7%) positive Ziehl Neelson stain for tuberculosis in 6 (6%).\n\n\nCONCLUSIONS\nBronchoscopic evaluation of patients with pulmonary diseases gives us a lot of information that may help us in better patient care and bronchoalveolar lavage has high diagnostic yield in diagnosing pulmonary tuberculosis.", "descriptor": "Lung Neoplasms", "qualifier": "diagnosis"}, {"mag_id": 2946230544, "corpus_id": 152283182, "title": "Exosomal PD-L1 Retains Immunosuppressive Activity and is Associated with Gastric Cancer Prognosis", "abstract": "BackgroundA recent study showed that circulating exosomal PD-L1 is an effective predictor for anti-PD-1 therapy in melanomas. Exosomal PD-L1 induced immunosuppression microenvironments in cancer patients. However, its prognostic value and immunosuppressive effect in gastric cancer (GC) were poorly understood.MethodsWe retrospectively evaluated the prognostic value of exosomal PD-L1 and soluble PD-L1 in preoperative plasma of 69 GC patients. The correlation between exosomal PD-L1 and the T cell counts or cytokine in the plasma was evaluated in 31 metastatic GC patients before chemotherapy.ResultsOverall survival (OS) was significantly lower in the high exosomal PD-L1 group compared with the low exosomal PD-L1 group (P\u2009=\u20090.004). Exosomal PD-L1 was an independent prognostic factor in GC (n\u2009=\u200969, 95% confidence interval\u2009=\u20091.142\u20137.669, P\u2009=\u20090.026). However, soluble PD-L1 showed no correlation with OS (P\u2009=\u20090.139). Additionally, exosomal PD-L1 in the plasma samples of 31 metastatic GC patients was negatively associated with CD4+ T cell count (P\u2009=\u20090.001, R\u2009=\u2009\u2212\u20090.549), CD8+ T-cell count (P\u2009=\u20090.054, R\u2009=\u2009\u2212\u20090.349), and granzyme B (P\u2009=\u20090.002, R\u2009=\u2009\u2212\u20090.537), indicating that exosomal PD-L1 was associated with immunosuppressive status of GC patients. GC cells also secreted exosomal PD-L1 and were positively associated with the amount of PD-L1 in corresponding GC cell lines. Besides, exosomal PD-L1 significantly decreased T-cell surface CD69 and PD-1 expressions compared with soluble PD-L1 due to its stable and MHC-I expression.ConclusionsOverall, exosomal PD-L1 predicts the worse survival and reflects the immune status in GC patients, resulting from a stronger T-cell dysfunction due to its stable and MHC-I expression.", "descriptor": "Adenocarcinoma", "qualifier": "secondary"}, {"mag_id": 2469200161, "corpus_id": 22869324, "title": "Weight reduction interventions for persons with a chronic illness: findings and factors for consideration.", "abstract": "Obesity in persons with a concomitant chronic illness poses complex issues relating to the choice of appropriate interventions. More recent emphasis on modification of risk factors has resulted in the need to prescribe complex therapeutic regimens with multiple treatment goals. The traditional approach to weight reduction in such persons has been nutrition education. Studies have shown, however, that knowledge alone does not translate into self-care behaviors that in turn result in weight loss and weight maintenance. Although the latter outcomes continue to be primary goals of therapy in obese individuals with a chronic illness, improvement in the physiologic parameters associated with the illness is also a desired outcome. Behavior therapy and group support appear to be enabling factors that go beyond knowledge to facilitate behavior change and subsequent changes in health-related indexes. This article describes various approaches to the problem of combined interventions for patients education and weight reduction. Findings and factors are discussed about whether the primary goal of weight reduction interventions for persons with a chronic illness should focus on pounds lost or improvement in metabolic or physiologic status.", "descriptor": "Obesity", "qualifier": "therapy"}, {"mag_id": 2982874394, "corpus_id": 207891798, "title": "Prevalence and correlates of early-onset menopause among women living with HIV in Canada.", "abstract": "OBJECTIVE\nMenopause is a pivotal transition for women. Previous studies have suggested increased risk of early menopause (40-45 years) and premature menopause (<40 years) for women with HIV. We aimed to determine age of menopause, prevalence of early menopause and premature menopause, and risk factors for menopause <45 years in Canadian women with HIV.\n\n\nMETHODS\nThis was a cross-sectional analysis from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study. Analyses were restricted to biologically female participants reporting being postmenopausal (regardless of etiology). Primary outcome was median age at menopause. Predetermined variables, and those with P\u200a<\u200a0.10 in univariable analyses were considered for inclusion into multivariable logistic regression model, to determine independent correlates of menopause <45 years.\n\n\nRESULTS\n229 women were included. Median age of menopause was 48 years (interquartile range 43, 51); 29.7% of women experienced menopause <45 years: 16.6% with early menopause and 13.1% with premature menopause. In univariable analyses, menopause <45 years was more likely (P\u200a<\u200a0.05) with birth in Canada, white ethnicity, less than high-school education, smoking, recreational drug use, and hepatitis C co-infection. In multivariable modeling, less than high-school education (adjusted odds ratio [aOR] 2.45, 95% confidence interval [CI] 1.22-4.93) and hepatitis C co-infection (aOR 1.90, 95% CI 1.04-3.50) were independently associated with menopause <45 years.\n\n\nCONCLUSIONS\nIn Canadian women with HIV, median age of menopause was 48 years; 3 years younger than the general population. Only lower education and hepatitis C co-infection were independently associated with menopause <45 years, highlighting importance of socioeconomic factors and comorbidities. These findings have implications for counseling and management of women with HIV.", "descriptor": "HIV Infections", "qualifier": "epidemiology"}, {"mag_id": 1978268820, "corpus_id": 22392969, "title": "Short latency activation of local circuit neurons in the cat somatosensory cortex", "abstract": "Intracellular horseradish peroxidase (HRP) study was performed in the cat primary somatosensory cortex (SI) under Nembutal anesthesia. Response properties of neurons were analysed with stimulation of the peripheral nerve (superficial radial nerve; SR) and thalamic ventrobasal nucleus (VB). A total number of 23 cells (15 in layers III and IV, 6 in layer V and 2 in layer VI) were identified morphologically as local circuit neurons with intracellular HRP staining. The latencies of SR-induced (7.7-8.5 ms) as well as VB-induced excitatory postsynaptic potentials (EPSPs) (1.3-1.5 ms) were significantly shorter than those of pyramidal neurons (9.1-10.6 ms for SR and 1.6-2.8 ms VB EPSPs). Morphological features of identified local circuit neurons are all, except one in layer VI, aspiny and presumed to be inhibitory in nature. The present study indicates that presumed inhibitory interneurons in the cat SI could be activated first by thalamic inputs among cortical neurons and set to inhibit the output cells for the sharp contrast in the sensory processing.", "descriptor": "Neurons", "qualifier": "physiology"}, {"mag_id": 2085229244, "corpus_id": 45636293, "title": "Effects of repeated low calcium perfusion on the rat heart: a gradual induction of calcium related damage.", "abstract": "The calcium paradox occurs immediately upon perfusion with calcium-containing medium after a period of calcium-free perfusion. The sequence of events occur so rapidly that it is difficult to distinguish causal factors from resultant. The present study describes a model in which calcium induced damage is produced more gradually. Isolated perfused rat hearts were subjected to brief periods of hypocalcium perfusion (less than 50 microM) alternated with normal calcium perfusion (1.25 mM) over 60 min. Changes in high energy phosphate content were monitored using 31P-NMR. With repeated sequential 2-min periods of alternate hypo- and normocalcium perfusion, there was a gradual reduction in ATP and phosphocreatine with a concomitant loss of function and decline in coronary flow. There was no change in inorganic phosphate content and a small degree of acidosis. Increasing the hypocalcium concentration from 5 to 40 microM resulted in a more gradual depletion in energy stores. Trifluoroperazine (a calmodulin inhibitor) had no effect on the energetic changes. Electron microscopic studies reveal that this model of damage induced by repeated low and normal calcium perfusion has some features in common with the calcium paradox. The extent of damage induced is greater when lower calcium concentrations (5 microM) are used.", "descriptor": "Calcium", "qualifier": "toxicity"}, {"mag_id": 2167882009, "corpus_id": 6193574, "title": "Adjusting for global effects in voxel-based morphometry: Gray matter decline in normal aging", "abstract": "Results from studies that have examined age-related changes in gray matter based on structural MRI scans have not always been consistent. Reasons for this variability likely include small or unevenly-distributed samples, different methods for tissue class segmentation and spatial normalization, and the use of different statistical models. Particularly relevant to the latter is the method of adjusting for global (total) gray matter when making inferences about regionally-specific changes. In the current study, we use voxel-based morphometry (VBM) to explore the impact of these methodological choices in assessing age-related changes in gray matter volume in a sample of 420 adults evenly distributed between the ages of 18\u201377 years. At a broad level, we replicate previous findings, showing age-related gray matter decline in nearly all parts of the brain, with particularly rapid decline in inferior regions of frontal cortex (e.g., insula and left inferior frontal gyrus) and the central sulcus. Segmentation was improved by increasing the number of tissue classes and using less age-biased templates, and registration was improved by using a diffeomorphic flow-based algorithm (DARTEL) rather than a \u201cconstrained warp\u201d approach. Importantly, different approaches to adjusting for global effects \u2013 not adjusting, Local Covariation, Global Scaling, and Local Scaling \u2013 significantly affected regionally-specific estimates of age-related decline, as demonstrated by ranking age effects across anatomical ROIs. Split-half cross-validation showed that, on average, Local Covariation explained a greater proportion of age-related variance across these ROIs than did Global Scaling. Nonetheless, the appropriate choice for global adjustment depends on one's assumptions and specific research questions. More generally, these results emphasize the importance of being explicit about the assumptions underlying key methodological choices made in VBM analyses and the inferences that follow.", "descriptor": "Aging", "qualifier": "physiology"}, {"mag_id": 3001006296, "corpus_id": 210883154, "title": "Morphological alterations of the reticular thalamic nucleus in Engrailed\u20102 knockout mice", "abstract": "The reticular thalamic nucleus (Rt) is a sheet of neurons that surrounds the dorsal thalamus laterally, along its dorso\u2010ventral and rostro\u2010caudal axes. It consists of inhibitory neurons releasing gamma\u2010aminobutyric acid (GABA). This nucleus participates in the circuitry between the thalamus and the cerebral cortex, and its impairment is associated with neuro\u2010psychiatric disorders. In this study, we investigated the Rt anatomy of Engrailed\u20102 knockout mice (En2\u2212/\u2212), a mouse model of autism spectrum disorder (ASD), using parvalbumin as an immunohistochemical marker. We compared 4\u2010 and 6\u2010week\u2010old wild type (WT) and En2\u2212/\u2212 mice using various morphometric parameters: cell area, shape factor, circularity and cell density. Significant differences were present in 6\u2010week\u2010old male mice with different genetic background (WT vs. En2\u2212/\u2212): the Rt neurons of En2\u2212/\u2212 mice showed a bigger cell area, shape factor and circularity when compared with WT. Age (4 weeks vs. 6 weeks) influenced the shape factor of WT females, the circularity and cell density of En2\u2212/\u2212 males, and the shape factor and circularity of En2\u2212/\u2212 females. Gender affected cell density in 4\u2010week\u2010old WT mice, shape factor and cellularity of 6\u2010week\u2010old WT mice, and cell area, shape factor and cell density of En2\u2212/\u2212 at 6 weeks. Intrasubject (left\u2013right) asymmetry of Rt was never observed. These results show for the first time that sex\u2010 and age\u2010related changes occur in the Rt GABAergic neurons of the En2\u2212/\u2212 ASD mouse model.", "descriptor": "Neurons", "qualifier": "metabolism"}, {"mag_id": 2000105889, "corpus_id": 29772601, "title": "The Colorado mental retardation and developmental disabilities research center", "abstract": "The Colorado MRRC was one of the original MRRCs funded and has maintained its focus on genetic and nutritional causes of mental retardation and developmental disabilities. Significant discoveries of the center have included a number of metabolic disorders, including glutaric academia types I and II, electron transport flavoprotein (ETF) deficiency, ETF dehydrogenase deficiency, glycerol kinase deficiency, sphingolipidoses, genetic linkages in dyslexia, phonological deficits in dyslexia, and the importance of the trace mineral Zn in early development. Current research at the center is supported by program of projects grants on inborn errors of metabolism, Down syndrome (DS), autism, and dyslexia.", "descriptor": "Brain", "qualifier": "physiopathology"}, {"mag_id": 2093770018, "corpus_id": 24162488, "title": "Cyclic AMP\u2010Dependent Protein Phosphorylation in Chemosensory Neurons: Identification of Cyclic Nucleotide\u2010Regulated Phosphoproteins in Olfactory Cilia", "abstract": "Abstract Chemosensory dendritic membranes (olfactory cilia) contain protein kinase activity that is stimulated by cyclic AMP and more efficiently by the nonhydrolyzable GTP analog guanosine\u20105\u2032\u2010O\u2010(3\u2010thio)triphosphate (GTP\u03b3S). In control nonsensory (respiratory) cilia, the cyclic AMP\u2010dependent protein kinase is practically GTP\u03b3S\u2010insensitive. GTP\u03b3S activation of the olfactory enzyme appears to be mediated by a stimulatory GTP\u2010binding protein (G\u2010pro\u2010tein) and adenylate cyclase previously shown to be enriched in the sensory membranes. Protein kinase C activity cannot be detected in the chemosensory cilia preparation under the conditions tested. Incubation of olfactory cilia with [\u03b3\u201032P]ATP leads to the incorporation of [32P]phosphate into many polypeptides, four of which undergo covalent modification in a cyclic nucleotide\u2010dependent manner. The phosphorylation of one polypeptide, pp24, is strongly and specifically enhanced by cyclic AMP at concentrations lower than 1 \u03bcM. This phosphoprotein is not present in respiratory cilia, but is seen also in membranes prepared from olfactory neuroepithelium after cilia removal. Cyclic AMP\u2010dependent protein kinase and phosphoprotein pp24 may be candidate components of the molecular machinery that transduces odor signals.", "descriptor": "Neurons", "qualifier": "enzymology"}, {"mag_id": 1994897705, "corpus_id": 30393420, "title": "Accumulation of iron oxide nanoparticles by cultured primary neurons", "abstract": "Magnetic iron oxide nanoparticles (IONPs) are frequently used for biomedical applications. Although nanoparticles can enter the brain, little is known so far on the uptake of IONPs in neurons and on their neurotoxic potential. Hence, we applied dimercaptosuccinate (DMSA)-coated IONPs to cultured primary rat cerebellar granule neurons. These IONPs had average hydrodynamic diameters of around 80\u2009nm and 120\u2009nm when dispersed in incubation medium in the absence and the presence of 10% fetal calf serum, respectively. Acute exposure of neurons with IONPs for up to 6\u2009h did neither alter the cell morphology nor compromise cell viability, although neurons accumulated large amounts of IONPs in a time- and concentration-dependent manner which caused delayed toxicity. For the first 30\u2009min of incubation of neurons at 37\u2009\u00b0C with IONPs the cellular iron content increased proportionally to the concentration of IONPs applied irrespective of the absence and the presence of serum. IONP-exposure in the absence of serum generated maximal cellular iron contents of around 3000\u2009nmol iron/mg protein after 4\u2009h of incubation, while the accumulation in the presence of 10% serum was slower and reached already within 1\u2009h maximal values of around 450\u2009nmol iron/mg protein. For both incubation conditions was the increase in cellular iron contents significantly lowered by reducing the incubation temperature to 4\u2009\u00b0C. Application of inhibitors of endocytotic pathways did not affect neuronal IONP accumulation in the absence of serum, while inhibitors of clathrin-mediated endocytosis lowered significantly the IONP accumulation in the presence of serum. These data demonstrate that DMSA-coated IONPs are not acutely toxic to cultured neurons and that a protein corona around the particles strongly affects their interaction with neurons.", "descriptor": "Neurons", "qualifier": "metabolism"}, {"mag_id": 1859677666, "corpus_id": 34646879, "title": "Germline mutations in the PTEN gene in Israeli patients with Bannayan\u2013Riley\u2013Ruvalcaba syndrome and women with familial breast cancer", "abstract": "Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan\u2013Riley\u2013Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high\u2010risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non\u2010conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.", "descriptor": "Breast Neoplasms", "qualifier": "genetics"}, {"mag_id": 2073620228, "corpus_id": 5684719, "title": "Significance of micrometastases on the survival of women with T1 breast cancer", "abstract": "The most important factor in predicting survival among women with newly diagnosed breast cancer is the status of the axillary lymph nodes. Although straightforward to define, the impact of micrometastases on survival remains to be completely determined.", "descriptor": "Breast Neoplasms", "qualifier": "pathology"}, {"mag_id": 1579734689, "corpus_id": 27780027, "title": "Cloning and expression of the Rhodobacter sphaeroides reaction center H gene", "abstract": "The Rhodobacter sphaeroides structural gene (puhA) for the reaction center H polypeptide has been identified and cloned by using restriction fragements specific for the analogous Rhodobacter capsulatus gene as a heterologous hybridization probe. The presence of puhA on a 1.45-kilobase BamHI restriction fragment was confirmed by partial DNA sequence analysis and by the synthesis of an immunoreactive Mr-28,000 reaction center H polypeptide in an R. sphaeroides coupled transcription-translation system. Approximately 450 base pairs of DNA upstream of the puhA gene were sufficient for expression of this protein in vitro. Northern RNA-DNA blot analysis with an internal puhA-specific probe identified at least two, apparently monocistronic, transcripts present at different cellular levels under physiological conditions known to affect the cellular content of both reaction center complexes and photosynthetic membrane. Northern blot analysis with specific upstream restriction fragment probes revealed that the 1,400-nucleotide puhA-specific mRNA had a 5' terminus upstream of the 1,130-nucleotide transcript. Both puhA-specific mRNA and immunoreactive reaction center H protein were detectable in chemoheterotrophically grown cells which lacked detectable bacteriochlorophyll and photosynthetic membrane.", "descriptor": "Bacterial Proteins", "qualifier": "genetics"}, {"mag_id": 1988764681, "corpus_id": 42743895, "title": "Targeted therapy for multiple myeloma.", "abstract": "Multiple myeloma (MM) remains incurable with conventional treatment approaches, and novel biologically based therapies are therefore urgently needed. Targeted therapies are either under development or already undergoing clinical evaluation predicated upon: identifying genetic abnormalities in myeloma cells to enhance chemoradiosensitivity; interrupting growth or triggering apoptotic signaling cascades in tumor cells; treating both the tumor cell and its microenvironment; enhancing allogeneic and autologous antimyeloma immunity; and characterizing new myeloma antigens for serotherapy. These therapies, alone or in combination with conventional treatments, offer great promise to improve the outcome for patients with MM.", "descriptor": "Antineoplastic Agents", "qualifier": "pharmacology"}, {"mag_id": 2051582749, "corpus_id": 20235801, "title": "Treatment of acute organophosphate poisoning: evidence of a direct effect on central nervous system by 2-PAM (pyridine-2-aldoxime methyl chloride).", "abstract": "Management of acute organophosphate poisoning in man includes rapid treatment with atropine and oximes. Oximes are thought to be unable to enter the central nervous system. We describe a case of parathion poisoning in a 3-1/2 year-old child and the effect of treatment with oxime 2-PAM (34 mg/kg) on EEG activity and clinical symptoms. The prompt improvement of cortical electrical activity documented by EEG could not be explained by any improvement of circulatory or respiratory function and has to be considered a direct effect of oximes on the central nervous system.", "descriptor": "Brain", "qualifier": "drug effects"}, {"mag_id": 2170231988, "corpus_id": 14339846, "title": "In Situ Activation of Helper T Cells in the Lung", "abstract": "ABSTRACT To better understand the lung and systemic responses of helper T cells mediating memory immunity to Mycobacterium tuberculosis, we used three- and four-color flow cytometry to study the surface phenotype of CD4+ lymphocytes. Bronchoalveolar lavage (BAL) fluid and peripheral blood (PB) samples were obtained from a total of 25 subjects, including 10 tuberculosis (TB)-infected subjects, 8 purified-protein-derivative-negative subjects, and 7 purified-protein-derivative-positive subjects. In marked contrast to CD4+ lymphocytes from PB (9% \u00b1 5% expressing CD45RA and CD29), the majority (55% \u00b1 16%) of CD4+ lymphocytes in BAL (ALs) simultaneously expressed CD45RA, a na\u0131\u0308ve T-cell marker, and CD29, members of the very late activation family. Further evaluation revealed that CD4+ ALs expressed both CD45RA and CD45RO, a memory T-cell marker. In addition, the proportion of CD4+ lymphocytes expressing CD69, an early activation marker, was drastically increased in BAL fluid (83% \u00b1 9%) compared to PB (1% \u00b1 1%), whereas no significant difference was seen in the expression of CD25, the low-affinity interleukin 2 receptor (34% \u00b1 15% versus 40% \u00b1 16%). More importantly, we identified a minor population of CD69bright CD25bright CD4+lymphocytes in BAL (10% \u00b1 6%) that were consistently absent from PB (1% \u00b1 1%). Thus, CD4+ lymphocytes in the lung paradoxically coexpress surface molecules characteristic of na\u0131\u0308ve and memory helper T cells as well as surface molecules commonly associated with early and late stages of activation. No difference was observed for ALs obtained from TB-infected and uninfected lung segments in this regard. It remains to be determined if these surface molecules are induced by the alveolar environment or if CD4+ lymphocytes coexpressing this unusual combination of surface molecules are selectively recruited from the circulation. Our data suggest that ex vivo experiments on helper T-cell subsets that display distinctive phenotypes may be pivotal to studies on the human immune response to potential TB vaccines.", "descriptor": "Lung", "qualifier": "immunology"}, {"mag_id": 2089497400, "corpus_id": 85111878, "title": "Protein kinase C\u2010independent sensitization of contractile proteins to Ca2+ in \u03b1\u2010toxin\u2010permeabilized smooth muscle cells from the guinea\u2010pig stomach", "abstract": "Involvement of protein kinase C in receptor\u2010operated Ca2+ sensitization of cell shortening was investigated by use of \u03b1\u2010toxin\u2010permeabilized smooth muscle cells from the fundus of the guinea\u2010pig. Most of the isolated cells responded to 0.6 \u03bcm Ca2+ with a maximal shortening to approximately 65% of the resting cell length. Addition of acetylcholine (ACh) at a maximal concentration (10 \u03bcm) resulted in a marked decrease in the concentration of Ca2+ required to trigger a threshold response from 0.6 \u03bcm to 0.2 \u03bcm. The augmentation of Ca2+ sensitivity by ACh was not inhibited by specific protein kinase C inhibitors, calphostin C and K\u2010252b at a concentration of 1 \u03bcm. These findings suggest that protein kinase C is not involved in the muscarinic receptor\u2010operated augmentation of Ca2+ sensitivity.", "descriptor": "Calcium", "qualifier": "pharmacology"}, {"mag_id": 2039197495, "corpus_id": 24452136, "title": "Animal models of chronic anxiety and \u201cfearlessness\u201d", "abstract": "Three behavioral animal models have been described: a feline and a rodent model of chronic anxiety, and a rodent model of \"fearless\" behavior. The models have been obtained by pre- or perinatal exposure to diazepam (DZ) or RO 15-1788 which produced enduring postnatal deficits or enrichment, respectively, of brain benzodiazepine (BDZ) receptors. The receptor-deficient one-year-old cat progenies showed hyperarousal, unabated restless behavior, delayed acquisition of instrumentally conditioned behavior, bizarre escape responses and absence or reduced alpha-like EEG activity. The receptor-deficient rat progencies, studied at the age of 5-6 months, showed a reduction of time spent in deep slow wave sleep, and inability to habituate to novel environment, such as the radial arm maze. In the maze, the behavior of these progenies was characterized by delayed and incomplete exploratory activity often terminated by sudden escape, numerous fecal deposits and significantly more frequent than normal errors of \"working memory.\" On the other hand, in all aspects, the receptor-enriched progenies were superior to the control animals as well as to the receptor-deficient group, particularly when the animals were challenged by novel and \"intimidating\" visual and/or auditory stimuli. In addition, 12 out of 51 receptor-deficient rats reared for 18 months developed mammary fibroadenomas, while no such tumors were found in the group of 44 vehicle-exposed control animals. Increased density and affinity of BDZ brain receptors was also observed after adult rats were treated with RO 15-1788 administered water for 7 or 14 days.", "descriptor": "Brain", "qualifier": "physiopathology"}, {"mag_id": 1998882362, "corpus_id": 46904, "title": "Recent advances in genetic code engineering in Escherichia coli.", "abstract": "The expansion of the genetic code is gradually becoming a core discipline in Synthetic Biology. It offers the best possible platform for the transfer of numerous chemical reactions and processes from the chemical synthetic laboratory into the biochemistry of living cells. The incorporation of biologically occurring or chemically synthesized non-canonical amino acids into recombinant proteins and even proteomes via reprogrammed protein translation is in the heart of these efforts. Orthogonal pairs consisting of aminoacyl-tRNA synthetase and its cognate tRNA proved to be a general tool for the assignment of certain codons of the genetic code with a maximum degree of chemical liberty. Here, we highlight recent developments that should provide a solid basis for the development of generalist tools enabling a controlled variation of chemical composition in proteins and even proteomes. This will take place in the frame of a greatly expanded genetic code with emancipated codons liberated from the current function or with totally new coding units.", "descriptor": "Escherichia coli", "qualifier": "genetics"}, {"mag_id": 2097653018, "corpus_id": 24048434, "title": "Optimization of the primary recovery of human interferon alpha2b from Escherichia coli inclusion bodies.", "abstract": "The human interferon alpha2b (hu-IFNalpha2b) gene was cloned in Escherichia coli JM109(DE3) and the recombinant protein was expressed as cytoplasmic inclusion bodies (IB). The present work discusses the recovery of hu-IFNalpha2b IB from the E. coli cells. An optimized protocol is proposed based on the sequential evaluation of recovery steps and parameters: (i) cell disruption, (ii) IB recovery and separation from cell debris, (iii) IB washing, and (iv) IB solubilization. Parameters such as hu-IFNalpha2b purity and recovery yield were measured after each step. The optimized recovery protocol yielded 60% of hu-IFNalpha2b with a purity of up to 80%. The protein was renatured at high concentration after recovery and it was found to display biological activity.", "descriptor": "Escherichia coli", "qualifier": "genetics"}, {"mag_id": 1992968278, "corpus_id": 40344953, "title": "Pulmonary chondroma in a dog", "abstract": "PRIMARY pulmoniary tumours of mesenichymal origini are unIcomMOnII in dogs (Moulton 1990, Watson and others 1993). Those of cartilagiinous origin are rare even in humain beiings, and there are fewv reports in domestic animals; pulmonary chondrosar-comiia has previously been described in two dogs (Patnaik 1990, WXeller and others 1992). This short communication describes a case of pulmonary chondroma in a dog. A five-year-old, neutered, female greyhound wvas presenited wvith a four-week history of lethargy, inappetenice and mild sporadic coughing. The dog wvas depressed and pyrexic (39 $8C) with mlode-ate tachvpnoea. Sercni biochemistry, complete blood cell counts and urinalysis results were within normal ranges. Thoracic radiography confirmed the presence of a soft tissuCe I1ass of 10.5 cm diameter in the right dorsal lung field, wvhich exteinded from the sixth to the l0th rib and contained gas lucenciCes suggestive of cavitation. Lateral thoracotomy via the right fifth intercostal spacc revealed the mass in the right caLidal lulng lobe. A right caLidal luing lobectomy was perform-led anid ani enlarged bronchial lymph node was also excised; both secre stored in 10 per cenit neutral buffterecd forimialiin. 'ITlhe lung lobe wsas cccipiecd aind expainded by a firm, wvhite 1 1 x 10 x 7 cIm1 mass adjacent to the Im1ain bronchus, which lhad irregular bLit sWell circucmscribed mai-gins and extended to the pleural SUIrfaCeS (Fig 1). OIn sectioning, the centre of the imiass wvas cavTitatecd aind contained small amIounI1tS of soft, taln debris. RepresentatiWe specimenis wvere processed by routinIe methods and emiibedded in paraffin Wtax. Glass slide-mounted sectioIns (5 pmn) ssere staiined wvith haematoxvlin anid cosill. Histologically, the imiass wvas comiipriscd of miultiple ir'regLilarly-shaped chonidroicd lobules with rouindecd margins. The mass occupiecd onie side of the maiinsteimi bronchus, separated soIm1e of the cartilagte rings and extended into the scirrounldiIng parenchyma. It protruded into the bronchial lumein. Numiierous cluisters of moderately siz'ed lacunae vere observed within the clroicd1ld imiatrix, each of which conitaiined a small, roucid, m1onlon0uclear or occasionally bincucleate tcImOcir cell (Fig 2). The tuLm1ocLr cells had a small amount of vacUlOlatecd, pale-staining, eosinophilic cytoplasimi, wvhich staiined positivelvr for S 1()(). The nuclcei were smI1all, cenitral and ovoid, with finely stippled chromatin and a simiall, central, deeply eosinophilic IucleolCIs. Towards the centre of the mass, incrIotic lobuiles lined a large, cavitated spacc conItaining sim1all am11ouInts of cellulardebris. Bronchioles and alveolar spaces surrounding the tuLm1lour mass contaiined large nimbers of nLeutrophils aind inicr-eased nuimbers of macrophages, with fibrous thickening of the alveolar septa. There swas reactive hyperplasia of the bronchial lymnph node wvith iiiultifocal suppurative inflammiiiiationi and anthracosis. A diaginosis of parenchymal puilmiioniary chondroma wvith associated pneum1o1nia aInd regiOIal lymphadenitis was made on the basis of gross, histological and imimiuinohistochemlical findinigs. Pulmonary choiidroimias are rare tuLmuLirs, which may be parenchymnal or involve the cartilaginous airways, as in this dog. In human beiings they occuir as solitary or multiple lesions in older individuals of either genider, or in yOunlg xvomen with Carney's triad in associatioin with gastric simiootlh muiscle tumouirs anid extra-adrenal pai-againgliomas (Colby aind others 1995). Choindroimias are wvell circumiiscribed, loblulated tumours comprised of benigcn crtilaginois tissue. B3oth proximity to a bronclhus and necrotic cystic degeierationi, as in this casc, are comimiioin features (( olby anid others 1995). FIG 1: Formalin-fixed sample from the right caudal lung lobe containing the pulmonary chondroma, which has been bisected and the two halves placed beside each other", "descriptor": "Lung Neoplasms", "qualifier": "veterinary"}, {"mag_id": 2883371940, "corpus_id": 51702939, "title": "Predictors of Pathological Complete Response in Women with Clinical Complete Response to Neoadjuvant Chemotherapy in Breast Carcinoma", "abstract": "Objective: There is insufficient information on predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast carcinoma that also presented clinical complete response (cCR) evaluated in breast, axilla and breast and axilla. Methods: This retrospective study included 310 women with breast carcinoma who received NAC from 1/1/13 to 12/31/15 with follow-up until 8/31/16. The factors analyzed to predict pCR and cCR were menopausal status, Ki67, estrogen receptor, histologic grade, molecular subtype, tumor size, axilla status, and stage. Results: The cCR/pCR rates were 53.2/16.5% (breast), 76.3/36.8% (axilla) and 50.6/13.9% (breast and axilla). Molecular subtype and HER2-positive were independent predictors to confirm pCR in women with cCR, mainly triple negative (TN) in breast (OR 22.81, 95% CI 7.13\u201372.96) and breast and axilla (OR 36.06, 95% CI 8.77\u2013148.26), but not in axilla. Ki67 \u226550% expression was predictor of cCR in breast (OR 2.00, 95% CI 1.31\u20133.06) and breast and axilla (OR 1.67, 95% CI 1.10\u20131.45). Conclusion: TN subtype and HER2-positive were the main independent predictors of pCR in women who also had cCR to NAC in breast and breast and axilla, but none was predictor in axilla. The Ki67 \u226550% was the independent predictor of cCR in breast and breast and axilla.", "descriptor": "Breast Neoplasms", "qualifier": "drug therapy"}, {"mag_id": 2045893592, "corpus_id": 25813164, "title": "Substrate profiling of Finegoldia magna SufA protease, inhibitor screening and application to prevent human fibrinogen degradation and bacteria growth in vitro.", "abstract": "SufA, which belongs to the subtilisin-like serine protease family, contains a non-canonical Asp-His-Ser catalytic triad. Under in vitro conditions, SufA is capable of human fibrinogen hydrolysis leading to inhibition of fibrin network formation, thus suggesting its important role in the development and progression of Finegoldia magna infections. In addition, it has been demonstrated that SufA can hydrolyze antibacterial peptides such as LL-37 and the chemokine MIG/CXCL 9, hence evading host defence mechanisms. Although the SufA protease from F. magna was discovered several years ago, its optimal substrate preference has not yet been identified. Considering the role of SufA, we have focused on the profiling of its substrate sequence preference spanning S1-S3 binding pockets using the FRET (fluorescence resonance energy transfer) approach. Next, based on the structure of the P1 residue of the developed substrate, we narrowed the inhibitor screening to the phosphonic analogues of amino acids containing an arginine-like side chain. Among all the compounds tested, only Cbz-6-AmNphth(P)(OPh)2 showed any inhibitory activity against SufA displaying k2/Ki value of 10,800 M(-1) s(-1). In addition, it prevented SufA-mediated human fibrinogen hydrolysis in vitro and exhibited potent antibacterial activity against F. magna, Staphylococcus aureus and Escherichia coli. Herein, we report on the substrate specificity, synthesis and kinetic evaluation of phosphonic inhibitors of SufA protease from F. magna which could help to establish its function in pathogenesis development and may lead to the elaboration of new antibacterial drugs.", "descriptor": "Anti-Bacterial Agents", "qualifier": "pharmacology"}, {"mag_id": 2407224156, "corpus_id": 9744552, "title": "Chemotherapy for non-small-cell lung cancer. Part 1: Early-stage disease.", "abstract": "Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of all lung tumors. Patients diagnosed with early-stage disease generally undergo surgery, but up to 50% develop local or distant recurrences. The benefit of chemotherapy in this disease is modest, but new drugs and combined strategies offer hope of improved survival rates. Because the disease recurs outside the chest in 70% of cases, one of the foremost goals of therapy is to prevent distant dissemination. To this end, chemotherapy may be administered preoperatively or after resection of the tumor. The first part of this article, which concludes next month, will address adjuvant and neoadjuvant chemotherapy in early-stage non-small-cell lung cancer.", "descriptor": "Lung Neoplasms", "qualifier": "drug therapy"}, {"mag_id": 2266599206, "corpus_id": 23801603, "title": "Prognosis and role of postmastectomy radiotherapy in patients with T1-T2 breast cancer with one to three positive axillary nodes.", "abstract": "PURPOSE\nTo evaluate the prognosis and role of postmastectomy radiotherapy (PMRT) in T1-T2 breast cancer with one to three positive axillary nodes.\n\n\nMETHODS\nThe 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS) and overall survival (OS) were compared between the NO and 1-3N+ cohorts. The role of PMRT was evaluated in the 1-3N+ cohort.\n\n\nRESULTS\nThe 10-year LRR, DR, DFS, OS rates in NO and the 1-3N+ cohorts were as follows: LRR 7.5% vs 19.4% (p = 0.011); DR 14.4% vs 23.0% (p = 0.029); DFS 71.3% vs 51.2% (p = 0.001) and OS 77.0% vs 58.7% (p = 0.001). Of the 192 1-3N+ patients not treated and treated with PMRT, the outcomes were: LRR 20.1% vs 18.4% (p = 0.047); DR 26.4% vs 21.5% (p = 0.743); DFS 40.2% vs 55.4% (p = 0.260) and OS 40.7% vs 66.0% (p = 0.344), respectively.\n\n\nCONCLUSION\nPMRT reduces the 10-year LRR rate for such patients, but further examination is needed.", "descriptor": "Breast Neoplasms", "qualifier": "radiotherapy"}, {"mag_id": 2286631010, "corpus_id": 32707452, "title": "Clinical Characteristics and Surgical Outcome of Revision Surgery in Patients with Cervical Ossification of the Posterior Longitudinal Ligament.", "abstract": "OBJECTIVE\nTo investigate the clinical characteristics and surgical outcome of revision surgery after first surgical decompression of cervical ossification of posterior longitudinal ligament.\n\n\nMETHODS\nA retrospective analysis was performed of 913 patients who underwent surgical decompression of cervical ossification of posterior longitudinal ligament from 1998 to 2012. Of these patients, 35 underwent revision surgery. Neurologic and surgical outcomes, radiologic findings, surgical procedures, and complications were evaluated. Indications for revision surgery were compared between early (\u226424 months after the first surgery) and delayed (>24 months after the first surgery) revision surgery.\n\n\nRESULTS\nThere was a higher prevalence of male patients with revision surgery (89%) compared with patients without revision surgery (71.2%, P\u00a0= 0.033). Preoperative Japanese Orthopaedic Association score was significantly lower in patients with revision surgery (11.5 vs. 12.7, P < 0.01). Visual analog scale score for neck pain was improved both without revision surgery (from 3.0 to 2.1, P < 0.001) and with revision surgery (from 3.0 to 2.2, P < 0.001) patients. Symptomatic residual stenosis was a more frequent cause of revision surgery in early revision surgery than in delayed revision surgery (75% vs. 25%, P < 0.001). In delayed revision surgery, growth of ossification of posterior longitudinal ligament (50%) was the primary cause of revision surgery.\n\n\nCONCLUSIONS\nClinical outcomes (Japanese Orthopaedic Association and visual analog scale scores) of revision surgery are similar to the outcomes of patients who did not require revision surgery. Residual stenosis after the index surgery is the most common indication for early revision surgery. To avoid early revision surgery, surgeons should carefully consider achieving circumferential decompression of the spinal canal during initial surgery.", "descriptor": "Postoperative Complications", "qualifier": "epidemiology"}, {"mag_id": 2782736912, "corpus_id": 3633939, "title": "Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma", "abstract": "Background: Dupilumab, an anti\u2013IL\u20104 receptor &agr; mAb, inhibits IL\u20104/IL\u201013 signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium\u2010to\u2010high\u2010dose inhaled corticosteroids plus long\u2010acting &bgr;2\u2010agonists. Objective: To examine dupilumab's effect on the 22\u2010item Sino\u2010Nasal Outcome Test (SNOT\u201022) total score and its allergic rhinitis (AR)\u2010associated items in asthma patients with comorbid perennial allergic rhinitis (PAR). Methods: A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE \u22650.35 Ku/L). Results: Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT\u201022 total score (least squares mean difference, \u22125.98; 95% CI, \u221210.45 to \u22121.51; P = .009) and all 4 AR\u2010associated symptoms evaluated (nasal blockage, \u22120.60; 95% CI, \u22120.96 to \u22120.25; runny nose, \u22120.67; 95% CI, \u22121.04 to \u22120.31; sneezing, \u22120.55; 95% CI, \u22120.89 to \u22120.21; postnasal discharge, \u22120.49; 95% CI, \u22120.83 to \u22120.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT\u201022 total score (\u22121.82; 95% CI, \u22126.46 to 2.83; P = .443 vs placebo) and in each AR\u2010associated symptom. In patients without PAR, no differences were observed for these measures versus placebo. Conclusions: Dupilumab 300 mg q2w significantly improved AR\u2010associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.", "descriptor": "Asthma", "qualifier": "drug therapy"}, {"mag_id": 2895922639, "corpus_id": 52972031, "title": "The influence of quaternary structure on the stability of Fenna\u2013Matthews\u2013Olson (FMO) antenna complexes", "abstract": "The trimeric nature of the Fenna\u2013Matthews\u2013Olson (FMO) protein antenna complex from green sulfur phototrophic bacteria was investigated. Mutations were introduced into the protein at positions 142 and 198, which were chosen to destabilize the intra-trimer salt bridges between adjacent monomers. Strains bearing the mutations R142L, R198L, or their combination, exhibited altered optical absorption spectra of purified membranes and fluoresced more intensely than the wild type. In particular, the introduction of the R142L mutation\u00a0resulted in slower culture growth rates, as well as an FMO complex that was not able to be isolated in appreciable quantities, while the R198L mutation yielded an FMO complex with increased sensitivity to sodium thiocyanate and Triton X-100 treatments. Native and denaturing PAGE experiments suggest that much of the FMO complexes in the mutant strains pool with the insoluble material upon membrane solubilization with n-dodecyl \u03b2-d-maltoside, a mild nonionic detergent. Taken together, our results suggest that the quaternary structure of the FMO complex, the homotrimer, is an important factor in the maintenance of the complex\u2019s tertiary structure.", "descriptor": "Bacterial Proteins", "qualifier": "chemistry"}, {"mag_id": 2002090206, "corpus_id": 14842356, "title": "Selenium for the Prevention of Cutaneous Melanoma", "abstract": "The role of selenium (Se) supplementation in cancer prevention is controversial; effects often depend on the nutritional status of the subject and on the chemical form in which Se is provided. We used a combination of in vitro and in vivo models to study two unique therapeutic windows for intervention in the process of cutaneous melanomagenisis, and to examine the utility of two different chemical forms of Se for prevention and treatment of melanoma. We studied the effects of Se in vitro on UV-induced oxidative stress in melanocytes, and on apoptosis and cell cycle progression in melanoma cells. In vivo, we used the HGF transgenic mouse model of UV-induced melanoma to demonstrate that topical treatment with l-selenomethionine results in a significant delay in the time required for UV-induced melanoma development, but also increases the rate of growth of those tumors once they appear. In a second mouse model, we found that oral administration of high dose methylseleninic acid significantly decreases the size of human melanoma xenografts. Our findings suggest that modestly elevation of selenium levels in the skin might risk acceleration of growth of incipient tumors. Additionally, certain Se compounds administered at very high doses could have utility for the treatment of fully-malignant tumors or prevention of recurrence.", "descriptor": "Skin Neoplasms", "qualifier": "prevention & control"}, {"mag_id": 113695330, "corpus_id": 24959157, "title": "Old and new peptide receptor targets in cancer: future directions.", "abstract": "A precise definition of the tumor tissue targets to be selected for in vivo peptide receptor targeting, namely to know which peptide receptor is expressed in which type of cancer, is an important prerequisite for successful clinical application of this technology. In this short review, I give three selected examples of new and promising peptide receptor targets. In the somatostatin receptor field, based on in vitro receptor autoradiography experiments showing that much more sst(2) binding sites are detected in tumors using a (177)Lu-labeled sst(2) antagonist than a (177)Lu-labeled agonist, it can be proposed that, in addition to neuroendocrine tumors, nonneuroendocrine tumors with lower sst(2) levels such as breast carcinomas, renal cell carcinomas, and non-Hodgkin lymphomas may become potential candidates for sst(2) antagonist targeting. In the gastrin-releasing peptide receptor field, recent in vitro data show that not only tumor cells may overexpress gastrin-releasing peptide receptors but also neoangiogenic tumoral vessels, making tumors expressing high levels of gastrin-releasing peptide receptors in tumor vessels, such as ovarian or urinary tract cancers, attractive new candidates for gastrin-releasing peptide receptor targeting. In the incretin receptor field, it was found in vitro that, apart from glucagon-like peptide 1 receptors overexpressed in benign insulinomas, incretin receptors, especially the glucose-dependent insulinotropic polypeptide receptors, can be overexpressed in medullary thyroid cancers, an unexpected finding making also these tumors potential novel candidates for incretin receptor targeting. Due to the abundance of peptide receptors in various cancers, it may be possible in the future to define for each tumor type a corresponding overexpressed peptide receptor suitable for targeting.", "descriptor": "Neoplasms", "qualifier": "radiotherapy"}, {"mag_id": 2076834185, "corpus_id": 11107399, "title": "SNP improves cerebral hemodynamics during normotension but fails to prevent sex dependent impaired cerebral autoregulation during hypotension after brain injury", "abstract": "Traumatic brain injury (TBI) is a leading cause of morbidity in children and boys are disproportionately represented. Hypotension is common and worsens outcome after TBI. Previous studies show that adrenomedullin, a cerebrovasodilator, prevented sex dependent impairment of autoregulation during hypotension after piglet fluid percussion brain injury (FPI). We hypothesized that this concept was generalizable and that administration of another vasodilator, sodium nitroprusside (SNP), may equally improve CBF and cerebral autoregulation in a sex dependent manner after FPI. SNP produced equivalent percent cerebrovasodilation in male and female piglets. Reductions in pial artery diameter, cortical CBF, and cerebral perfusion pressure (CPP) concomitant with elevated intracranial pressure (ICP) after FPI were greater in male compared to female piglets during normotension which was blunted by SNP. During hypotension, pial artery dilation (PAD) was impaired more in the male than the female after FPI. However, SNP did not improve hypotensive PAD after FPI in females and paradoxically caused vasoconstriction in males. SNP did not prevent reductions in CBF, CPP or autoregulatory index during combined hypotension and FPI in either sex. SNP aggravated ERK MAPK upregulation after FPI. These data indicate that despite prevention of reductions in CBF after FPI, SNP does not prevent impairment of autoregulation during hypotension after FPI. These data suggest that therapies directed at a purely hemodynamic increase in CPP will fail to improve outcome during combined TBI and hypotension.", "descriptor": "Brain", "qualifier": "drug effects"}, {"mag_id": 2054274394, "corpus_id": 22239278, "title": "Mechanisms of resistance to antibiotics.", "abstract": "Microbial resistance to antibiotics is manifested by changes in antibiotic permeability, alteration of target molecules, enzymatic degradation of the antibiotics, and efflux of antimicrobials from the cytosol. Bacteria and other microorganisms use all of these mechanisms to evade the toxic effects of antibiotics. Recent research on the molecular aspects of these mechanisms, often informed by atomic resolution structures of proteins, enzymes and nucleic acids involved in these processes, has deepened our understanding of antibiotic action and resistance and, in several cases, spurred the development of strategies to overcome resistance in vitro and in vivo.", "descriptor": "Anti-Bacterial Agents", "qualifier": "pharmacology"}, {"mag_id": 2103500761, "corpus_id": 25895320, "title": "Stimulation of Capacitative Calcium Entry in HL-60 Cells by Nanosecond Pulsed Electric Fields*", "abstract": "Nanosecond pulsed electric fields (nsPEFs) are hypothesized to affect intracellular structures in living cells providing a new means to modulate cell signal transduction mechanisms. The effects of nsPEFs on the release of internal calcium and activation of calcium influx in HL-60 cells were investigated by using real time fluorescent microscopy with Fluo-3 and fluorometry with Fura-2. nsPEFs induced an increase in intracellular calcium levels that was seen in all cells. With pulses of 60 ns duration and electric fields between 4 and 15 kV/cm, intracellular calcium increased 200\u2013700 nm, respectively, above basal levels (\u223c100 nm), while the uptake of propidium iodide was absent. This suggests that increases in intracellular calcium were not because of plasma membrane electroporation. nsPEF and the purinergic agonist UTP induced calcium mobilization in the presence and absence of extracellular calcium with similar kinetics and appeared to target the same inositol 1,4,5-trisphosphate- and thapsigargin-sensitive calcium pools in the endoplasmic reticulum. For cells exposed to either nsPEF or UTP in the absence of extracellular calcium, there was an electric field-dependent or UTP dose-dependent increase in capacitative calcium entry when calcium was added to the extracellular media. These findings suggest that nsPEFs, like ligand-mediated responses, release calcium from similar internal calcium pools and thus activate plasma membrane calcium influx channels or capacitative calcium entry.", "descriptor": "Calcium", "qualifier": "metabolism"}, {"mag_id": 2045158313, "corpus_id": 42201128, "title": "Non\u2010operative management of blunt hepatic trauma", "abstract": "Non\u2010operative management is currently considered the treatment of choice in over 50 per cent of adult patients with blunt liver injury. This report reviews the criteria for non\u2010operative management and its potential downside.", "descriptor": "Liver", "qualifier": "injuries"}, {"mag_id": 2045990252, "corpus_id": 32883057, "title": "Localization and properties of respiratory neurons in the rostral pons of the newborn rat", "abstract": "The distribution and discharge pattern of respiratory neurons in the 'pneumotaxic center' of the rostral pons in the rat has remained unknown. We performed optical recordings and whole-cell patch clamp recordings to clarify respiratory neuron activity in the rostral pons of a brainstem-spinal cord preparation from a newborn rat. Inspiratory nerve activity was recorded in the 4th cervical nerve and used as a trigger signal for optical recordings. Respiratory neuron activity was detected in the limited region of the rostral-lateral pons. The main active region was presumed to be primarily the K\u00f6lliker-Fuse nucleus. The location of respiratory neurons was further confirmed by Lucifer Yellow staining after conducting whole-cell recordings. From a membrane potential analysis of the respiratory neurons in the rostral pons, the respiratory neurons were divided into four types: inspiratory neuron (71.9%), pre-inspiratory neuron (5.3%), post-inspiratory neuron (19.3%), and expiratory neuron (3.5%). A noticeable difference between pontine and medullary respiratory neurons was that post-inspiratory neurons were more frequently encountered in the pons. Application of a mu-opioid agonist, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, transformed the burst pattern of post-inspiratory neurons into that of pre-inspiratory neurons. The electrical stimulation of the sensory root of the trigeminal nerve induced three types of responses in 85% of pontine respiratory neurons: inhibitory postsynaptic potentials (42.7%), excitatory postsynaptic potentials (37.7%) and no response (15.1%). Our findings provide the first evidence in the rat for the presence of respiratory neurons in the rostral pons, with localization in the lateral region approximately overlapping with the K\u00f6lliker-Fuse nucleus.", "descriptor": "Neurons", "qualifier": "physiology"}, {"mag_id": 2100524895, "corpus_id": 1200650, "title": "The Role of Central and Peripheral \u03bc Opioid Receptors in Inflammatory Pain and Edema: A Study Using Morphine and DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic Acid)", "abstract": "The role of opioid receptors located in the central nervous system (CNS) and peripheral nervous system in inflammatory pain is well established. In contrast, although it is has been shown that \u03bc agonists can reduce other manifestations of inflammation, such as edema, the mechanism of action remains unclear. In this study, we have activated \u03bc receptors located centrally, those located peripherally, and those located both centrally and peripherally and compared the effects on pain and edema using the rat carrageenan model of acute inflammation. Activation of \u03bc receptors located only in the periphery, by administration of the peripheralized \u03bc agonist [8-(3,3-diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic acid (DiPOA) or local administration of morphine, resulted in antihyperalgesia (30 mg/kg DiPOA, 83% inhibition; 100 \u03bcg/rat morphine, 75% inhibition) without affecting edema. In contrast, activation of both central and peripheral \u03bc receptors using systemically administered morphine resulted in antihyperalgesia (1 mg/kg, 80% inhibition) and inhibition of edema (10 mg/kg, 54% inhibition). Finally, activation of only receptors located in the CNS, by central administration of DiPOA or systemic administration of morphine after block of only the peripheral \u03bc receptors using q-naltrexone, resulted in a significant reduction in edema. Our findings confirm the role of peripheral \u03bc receptors in the pathology of pain associated with acute inflammation and argue against the involvement of these receptors in edema formation. Furthermore, our data demonstrate that activation of \u03bc receptors in the brain inhibits carrageenan-induced edema and suggest that the antiedematous effect of morphine is due to action at central receptors alone.", "descriptor": "Brain", "qualifier": "physiology"}, {"mag_id": 1470416423, "corpus_id": 37688859, "title": "Age-related progressive increase of lower back pain among male dance sport competitors.", "abstract": "BACKGROUND\nOccurrence of musculoskeletal pain in dance sport dancers is often a cause for longer discontinuation of training, which affects the competition results.\n\n\nOBJECTIVE\nThe aim of the research project was to determine the age-specific pain experience among male dance sport competitors by defining the proportions of pain status of fourteen body regions.\n\n\nMETHODS\nThe subject sample of 200 male dancers from 44 different countries and with international competitive experience was divided into three subsamples according to age. Three online questionnaires translated into eight world languages were used for data collection: (1) basic data questionnaire, (2) self-estimated functional inability because of pain questionnaire designed for dancers, and (3) health care-related questionnaire.\n\n\nRESULTS\nAfter examining the 14 topological regions, it was established that dancers most often report pain in the lower back region (53.5%), followed by knee (43%) and toe regions (40.5%). Significant differences were found using the Chi-square test between the groups of dancers of different ages in the prevalence of pain in the lower back (\u03c7 2 = 12.6), shoulders (\u03c7 2 = 9.7), and hip region (\u03c7 2 = 7), with the highest, age-related progressive differences in the lower back region (36.2-54.9-63.4%) so older dancers had more pain. Often reported reasons for discontinuation of training increased with age are overuse syndrome/tendinitis (6.4-15.9-22.5%) and strain (14.9-29.3-31%). Most common causes for longer discontinuation of training are absence of partner (37%), injuries (24%), and overuse syndrome (10%).\n\n\nCONCLUSION\nLower back pain is propounding health problem in male dancers and increases with age that cannot be resolved by decreasing training intensity. This research reveals that only 28% of male dancers will seek medical help because of occurrence of musculoskeletal pain. Multidisciplinary approach with the aim of long-term health protection and prolongation of dancing careers is required in future studies.", "descriptor": "Aging", "qualifier": "physiology"}, {"mag_id": 2896299079, "corpus_id": 53013869, "title": "Natural History of Obesity Subphenotypes: Dynamic Changes Over Two Decades and Prognosis in the Framingham Heart Study", "abstract": "Context\nThe natural histories of obesity subphenotypes are incompletely delineated.\n\n\nObjectives\nTo investigate dynamic changes in obesity subphenotypes and associations with outcomes.\n\n\nDesign, Setting, Participants, and Measurements\nFramingham Offspring Cohort participants (n = 4291) who attended the examination cycles 2 (1979 to 1983) to 7 (1998 to 2001), which included 26,508 participant observations. Obesity subphenotypes [metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO)] were ascertained based on metabolic health (<2 Adult Treatment Panel III criteria). The outcomes were subclinical cardiovascular disease (CVD), incident diseases [diabetes, hypertension, chronic kidney disease (CKD), CVD], and all-cause mortality.\n\n\nResults\nAt baseline, 4% and 31% of participants exhibited the MHO and MUNO subphenotypes, respectively. Four-year probability of MHO participants becoming MUO was 43% in women and 46% in men. Compared with MHNO, MHO participants had 1.28-fold (95% CI, 0.85 to 1.93) and 1.92-fold (95% CI, 1.38 to 2.68) higher odds of subclinical CVD and coronary artery calcification, respectively; corresponding values for MUNO were 1.95 (1.54 to 2.47) and 1.92 (1.38 to 2.68). During follow-up (median of 14 years), 231 participants developed diabetes, 784 hypertension, 423 CKD, 639 CVD, and 1296 died. Compared with MHNO, MHO conferred higher risks of diabetes [hazard ratio (HR), 4.69; 95% CI, 2.21 to 9.96] and hypertension (HR, 2.21; 95% CI, 1.66 to 2.94). Compared with MUO, MHO conferred lower risks of diabetes (0.21; 0.12 to 0.39), CVD (0.64; 0.43 to 0.95), and CKD (0.44; 0.27 to 0.73), but similar hypertension, cardiovascular mortality, and overall mortality risks.\n\n\nConclusion\nOver time, most MHO participants developed metabolic abnormalities and clinical disease. The MHO subphenotype is a harbinger of future risk.", "descriptor": "Obesity", "qualifier": "complications"}, {"mag_id": 2186775488, "corpus_id": 22071662, "title": "Neuroendocrine and oxidoreductive mechanisms of stress-induced cardiovascular diseases.", "abstract": "The review concerns a number of basic molecular pathways that play a crucial role in perception, transmission, and modulation of the stress signals, and mediate the adaptation of the vital processes in the cardiovascular system (CVS). These highly complex systems for intracellular transfer of information include stress hormones and their receptors, stress-activated phosphoprotein kinases, stress-activated heat shock proteins, and antioxidant enzymes maintaining oxidoreductive homeostasis of the CVS. Failure to compensate for the deleterious effects of stress may result in the development of different pathophysiological states of the CVS, such as ischemia, hypertension, atherosclerosis and infarction. Stress-induced dysbalance in each of the CVS molecular signaling systems and their contribution to the CVS malfunctioning is reviewed. The general picture of the molecular mechanisms of the stress-induced pathophysiology in the CVS pointed out the importance of stress duration and intensity as etiological factors, and suggested that future studies should be complemented by the careful insights into the individual factors of susceptibility to stress, prophylactic effects of 'healthy' life styles and beneficial action of antioxidant-rich nutrition.", "descriptor": "Cardiovascular Diseases", "qualifier": "etiology"}, {"mag_id": 2747130347, "corpus_id": 39563745, "title": "Solitary biceps muscle metastasis from breast cancer", "abstract": "Although direct muscle invasion by carcinoma is well recognised, skeletal muscle metastases are rare. Breast cancer very rarely metastasises to skeletal muscles. We present a case of breast cancer that metastasised to the biceps muscle. The woman developed breast cancer in 1990 and then developed axillary subcutaneous metastasis in 2001. In 2015, she presented with pain in the left forearm extending to the hand. Initial imaging showed no abnormalities, but the positron emission tomography-CT scanning revealed a hot spot in the left biceps muscle. Additionally, the nerve conduction study showed feature of carpal tunnel syndrome. The hot spot was deemed inconclusive in the view of normal CT and MRI scans, and the patient was treated with carpal tunnel decompression. A few months later, the patient developed a lump in the left biceps muscle, which appeared to be a metastatic lesion from her primary breast cancer. The patient was treated with radiotherapy and responded satisfactorily.", "descriptor": "Breast Neoplasms", "qualifier": "pathology"}, {"mag_id": 2168859350, "corpus_id": 22013570, "title": "Multilocus sequence typing of Streptococcus pneumoniae clones with unusual drug resistance patterns: genetic backgrounds and relatedness to other epidemic clones.", "abstract": "Six drug-resistant Streptococcus pneumoniae clones were previously identified from day care centers in Portugal, primarily on the basis of common pulsed-field gel electrophoresis (PFGE) patterns. These clones were susceptible to penicillin or had only very low-level resistance to it (most MICs, < or =0.25 microg/mL) and accounted for a large proportion (35%) of all drug-resistant pneumococci colonizing the nasopharynx of healthy children attending day care. Five of the 6 clones were identified among pneumococcal clinical isolates collected in other countries. In this study, we applied multilocus sequence typing (MLST) to describe the genetic background of these clones. MLST confirmed previous findings obtained by PFGE and allowed for the extension of the international clonal relationships by showing that each of the 6 clones was internationally disseminated and was able to cause pneumococcal disease.", "descriptor": "Anti-Bacterial Agents", "qualifier": "pharmacology"}, {"mag_id": 2136892414, "corpus_id": 3655835, "title": "European AIDS Clinical Society Standard of Care meeting on HIV and related coinfections: The Rome Statements", "abstract": "The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future.", "descriptor": "HIV Infections", "qualifier": "complications"}, {"mag_id": 2285157229, "corpus_id": 23634046, "title": "Oxaliplatin: mechanism of action and antineoplastic activity.", "abstract": "Oxaliplatin, a platinum-based chemotherapeutic agent with a 1,2-diaminocyclohexane (DACH) carrier ligand, has shown in vitro and in vivo efficacy against many tumor cell lines, including some that are resistant to cisplatin and carboplatin. The retention of the bulky DACH ring by activated oxaliplatin is thought to result in the formation of platinum-DNA adducts, which appear to be more effective at blocking DNA replication and are more cytotoxic than adducts formed from cisplatin. Studies by the National Cancer Institute (NCI) have suggested that oxaliplatin has a spectrum of activity different from that of either cisplatin or carboplatin, suggesting that it has different molecular targets and/or mechanisms of resistance. Oxaliplatin has been demonstrated to differ in some mechanisms associated with the development of cisplatin resistance. Compared with cisplatin-conditioned cells, deficiencies in mismatch repair (MMR) and increases in replicative bypass, which appear to contribute to cisplatin resistance, have not been shown to induce a similar resistance to oxaliplatin. A decreased likelihood of resistance development makes oxaliplatin a good candidate for first-line therapy. Studies also demonstrate additive and/or synergistic activity with a number of other compounds, however, suggesting the possible use of oxaliplatin in combination therapies.", "descriptor": "Antineoplastic Agents", "qualifier": "pharmacology"}, {"mag_id": 1972989425, "corpus_id": 207094771, "title": "Structural Zn(II) implies a switch from fully cooperative to partly downhill folding in highly homologous proteins.", "abstract": "In the funneled landscape, proteins fold to their native states through a stochastic process in which the free energy decreases spontaneously and unfolded, transition, native, and possible intermediate states correspond to local minima or saddle points. Atomic description of the folding pathway appears therefore to be essential for a deep comprehension of the folding mechanism. In metallo-proteins, characterization of the folding pathways becomes even more complex, and therefore, despite their fundamental role in critical biological processes, little is known about their folding and assembly. The study of the mechanisms through which a cofactor influences the protein folding/unfolding reaction has been the rationale of the present study aimed at contributing to the search for cofactors' general roles in protein folding reactions. In particular, we have investigated the folding pathway of two homologous proteins, Ros87, which contains a prokaryotic zinc finger domain, and Ml452-151, lacking the zinc ion. Using a combination of CD, DSC and NMR techniques, we determined the thermodynamics and the structural features, at an atomic level, of the thermal unfolding of Ros87 and compared them to the behavior of Ml452-151. Our results, also corroborated by NMR (1)H/(2)H exchange measurements, show that the presence of the structural Zn(II) in Ros87 implies a switch from the Ml452-151 fully cooperative to a two-step unfolding process in which the intermediate converts to the native state through a downhill barrierless transition. This observation, which has never been reported for any metal ion so far, may have a significant role in the understanding of the protein misfolding associated with the presence of metal ions, as observed in neurodegenerative diseases.", "descriptor": "Proteins", "qualifier": "chemistry"}, {"mag_id": 2100387410, "corpus_id": 37194107, "title": "Targeted gene conversion in a mammalian CD34+-enriched cell population using a chimeric RNA/DNA oligonucleotide", "abstract": "Abstract\u2002Gene conversion of genetically inherited point mutations is a fundamental methodology for treating a variety of diseases. We tested the feasibility of a new approach using an RNA/DNA chimeric oligonucleotide. The \u03b2-globin gene was targeted at the point mutation causing sickle cell anemia. The chimera is designed to convert an A residue to a T after creating a mismatched basepair. In a CD34+-enriched population of normal cells a 5\u201311% conversion rate was measured using restriction enzyme polymorphism and direct DNA sequence analyses. The closely related \u03b4-globin gene sequence appeared unchanged despite successful conversion at the \u03b2-globin locus.", "descriptor": "DNA", "qualifier": "genetics"}, {"mag_id": 2008683296, "corpus_id": 46462485, "title": "A case of listerial meningitis treated with a regimen containing panipenem-betamipron", "abstract": "Although panipenem-betamipron, which is commercially available only in Japan, is recommended for treatment of pediatric bacterial meningitis by some experts, only a limited number of clinical studies have been reported. In the present report, we describe a 2-year-old boy with meningitis caused by Listeria monocytogenes who was treated with a regimen containing panipenem-betamipron and recovered without any apparent neurological sequelae. On the basis of our experience and previous reports, panipenem-betamipron appears to be effective for the treatment of listerial meningitis.", "descriptor": "Anti-Bacterial Agents", "qualifier": "therapeutic use"}, {"mag_id": 2972654298, "corpus_id": 202574099, "title": "Dependence of connectivity on geometric distance in brain networks", "abstract": "In any network, the dependence of connectivity on physical distance between nodes is a direct consequence of trade-off mechanisms between costs of establishing and sustaining links, processing rates, propagation speed of signals between nodes. Despite its universality, there are still few studies addressing this issue. Here we apply a recently\u2013developed method to infer links between nodes, and possibly subnetwork structures, to determine connectivity strength as a function of physical distance between nodes. The model system we investigate is brain activity reconstructed on the cortex out of magnetoencephalography recordings sampled on a set of healthy subjects in resting state. We found that the dependence of the time scale of observability of a link on its geometric length follows a power\u2013law characterized by an exponent whose extent is inversely proportional to connectivity. Our method provides a new tool to highlight and investigate networks in neuroscience.", "descriptor": "Brain", "qualifier": "physiology"}, {"mag_id": 2410785253, "corpus_id": 77023713, "title": "Hepatic metastases in gestational trophoblastic disease.", "abstract": ": From 1975 to 1983, 195 patients were treated for persistent or metastatic gestational trophoblastic disease. Fifteen patients with liver metastases were analyzed. All were treated with chemotherapy alone, none received hepatic irradiation, and no patient bled from her hepatic metastases. Thus, the need for prophylactic hepatic irradiation to prevent hemorrhage is doubtful. The good results obtained in the studied patients emphasize the significance of using vigorous primary multiagent chemotherapy in high-risk gestational trophoblastic disease patients.", "descriptor": "Liver Neoplasms", "qualifier": "secondary"}, {"mag_id": 2921695473, "corpus_id": 78091110, "title": "Short-Term Exposure to Ambient Air Pollution and Asthma Mortality.", "abstract": "RATIONALE\nShort-term exposure to air pollution has been associated with asthma exacerbation and increased health-care use due to asthma, but its effect on asthma mortality remains largely unknown.\n\n\nOBJECTIVES\nTo quantitatively assess the association between short-term exposure to air pollution and asthma mortality.\n\n\nMETHODS\nWe investigated 4,454 individuals who lived in Hubei province, China and died from asthma between 2013 and 2018. A case-crossover design and conditional logistic regression models were applied for data analyses. Exposures to particulate matter \u2264 2.5 \u00b5m in aerodynamic diameter (PM2.5), PM10, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO) and ozone (O3) were estimated by inverse distance weighted averages of all monitoring stations within 50 km from each case's home address.\n\n\nMEASUREMENTS AND MAIN RESULTS\nEach interquartile range (IQR) increase of PM2.5 (lag 3; IQR: 47.1 \u00b5g/m3), NO2 (lag 03; IQR: 26.3 \u00b5g/m3) and O3 (lag 3; IQR: 52.9 \u00b5g/m3) were positively associated with asthma mortality, with odds ratios (ORs) of 1.07 (95% confidence interval [CI]: 1.01-1.12), 1.11 (95% CI: 1.01-1.22) and 1.09 (95% CI: 1.01-1.18), respectively. There was no evidence of departure from linearity for these associations. Further adjustment for other pollutants did not change the associations materially. We did not observe significant associations between PM10, SO2, CO exposures and asthma mortality. Overall, the estimates remained consistent in various sensitivity analyses.\n\n\nCONCLUSIONS\nOur results provide new evidence that short-term exposures to PM2.5, NO2 and O3 may increase asthma mortality risk. Further studies are needed to confirm our findings in other populations.", "descriptor": "Asthma", "qualifier": "mortality"}, {"mag_id": 1873178192, "corpus_id": 9844447, "title": "Reduced expression of semaphorin 4D and plexin-B in breast cancer is associated with poorer prognosis and the potential linkage with oestrogen receptor.", "abstract": "Involvement of semaphorin 4D (Sema4D) and the receptor proteins of the plexins B family (plexin-B1, -B2 and -B3) in solid tumours suggests they play a role in breast cancer. In the present study, the expression of Sema4D and plexin-Bs was examined in a breast cancer cohort. The expression of Sema4D and plexin-Bs was examined in 147 tumours together with 22 normal mammary tissues using quantitative PCR along with clinicopathological patient data, as well as in MCF-7 and MDA-MB-231 cell lines treated with selective oestrogen receptor modulators (SERMs). The expression of Sema4D, plexin-B1 and -B2 was markedly reduced in tumours with local recurrence, compared to the patients that remained disease-free. The reduced Sema4D expression was associated with poorer disease-free survival (median, 111.6 months, 95% CI, 96.5-126.7), compared to the patients with a higher expression (median, 144.0 months; 95% CI, 130.8-157.3; p=0.033). A reduced expression of plexin-B1 was observed in tumours with poorer differentiation and was associated with poorer overall and disease-free survival. No similar association was identified in relation to plexin-B2 and -B3. A higher expression of Sema4D and plexin-B1 was observed in the ER\u03b1-positive tumours compared to the ER\u03b1-negative tumours. The expression of these molecules was largely regulated in breast cancer cells exposed to SERMs. A decreased expression of Sema4D, plexin-B1 and -B2 was associated with local recurrence and poor prognosis. Response to SERMs indicated potential perspectives of these molecules in clinical assessment and management of diseases.", "descriptor": "Breast Neoplasms", "qualifier": "pathology"}, {"mag_id": 2412605738, "corpus_id": 25026230, "title": "Stimulatory regulation of the large-conductance, calcium-activated potassium channel by G proteins in bovine adrenal chromaffin cells.", "abstract": "G proteins regulate the electrical activity of various cells through their actions on membrane ion channels. In the present study, the effect of G proteins was examined on unitary, large conductance (BK), Ca(2+)-activated K+ channels measured in excised, inside-out patches of membrane obtained from cultured bovine adrenal chromaffin cells. Cytoplasmic application of either guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) or AlF-4 to stimulate G proteins resulted in a > 4-fold increase in the open probability of the BK channel measured at +40 mV in the presence of a 1 microM concentration of Ca2+. A similar stimulatory regulation was observed after the addition of an activated, mixed Gi/Go alpha preparation. The increase in the open probability during G protein stimulation was associated with a large reduction in the duration of a long closed state of the channel and could be observed in the presence of a protein kinase inhibitor. The half-maximal voltage required for steady state activation of the BK channel decreased from +63 mV to +48 mV in the presence of GTP gamma S. In addition, the half-maximal Ca2+ concentration required for channel opening was reduced from 11.7 microM in control measurements to 1.3 microM during regulation by GTP gamma S. Thus, G proteins increase the open probability of the chromaffin BK Ca(2+)-activated K+ channel by shifting the voltage dependence of channel gating to more negative potentials and by enhancing the affinity of the channel for Ca2+. Stimulatory regulation may provide a compensatory mechanism for decreasing the action potential duration during secretagogue-mediated exocytosis.", "descriptor": "Calcium", "qualifier": "pharmacology"}, {"mag_id": 2473113870, "corpus_id": 10827836, "title": "Structural and functional analysis of cationic transfection lipids: the hydrophobic domain.", "abstract": "Cationic lipids (cytofectins) have gained widespread acceptance as pharmaceutical polynucleotide delivery agents for both cultured cell and in vivo transfection, and the cytofectins DOTAP and DC-Cholesterol are being tested in clinical human gene therapy trials. This study reports the effects of modifications in the hydrophobic domain of a prototypic cytofectin (DORI), including modifications in lipid side-chain length, saturation, and symmetry. A panel of related compounds was prepared and analyzed using DNA transfection, electron microscopy, and differential scanning calorimetry (DSC). Lipid formulations were prepared with dioleoylphosphatidylethanolamine (DOPE) as unsonicated preparations and sonicated preparations. Transfection analyses were performed using cultured fibroblasts, human bronchial epithelial, and Chinese hamster ovarian cells as well as a mouse model for pulmonary gene delivery. In general, cytofectins containing dissymmetric hydrophobic domains were found to work as well or better than the best symmetric analogs. Optimal side-chain length and symmetry varied with cell type. Compounds with phase transitions (Tc) above and below physiological temperature (37 degrees C) were tested for DNA transfection activity. In contrast to previous reports, cytofectin Tc was not found to be predictive of transfection efficacy. Pulmonary treatment with free DNA was found to be at least as effective as treatment with commonly used cytofectin:DNA complexes. However, cytofectins that incorporate a hydroxyethylammonium moiety in the polar domain were found to enhance in vivo gene delivery relative to free DNA.", "descriptor": "DNA", "qualifier": "administration & dosage"}, {"mag_id": 2418619242, "corpus_id": 4576278, "title": "TLR9 expression is required for the development of cigarette smoke-induced emphysema in mice.", "abstract": "The expression of Toll-like receptor (TLR)-9, a pathogen recognition receptor that recognizes unmethylated CpG sequences in microbial DNA molecules, is linked to the pathogenesis of several lung diseases. TLR9 expression and signaling was investigated in animal and cell models of chronic obstructive pulmonary disease (COPD). We observed enhanced TLR9 expression in mouse lungs following exposure to cigarette smoke. Tlr9(-/-) mice were resistant to cigarette smoke-induced loss of lung function as determined by mean linear intercept, total lung capacity, lung compliance, and tissue elastance analysis. Tlr9 expression also regulated smoke-mediated immune cell recruitment to the lung; apoptosis; expression of granulocyte-colony stimulating factor (G-CSF), the CXCL5 protein, and matrix metalloproteinase-2 (MMP-2); and protein tyrosine phosphatase 1B (PTP1B) activity in the lung. PTP1B, a phosphatase with anti-inflammatory abilities, was identified as binding to TLR9. In vivo delivery of a TLR9 agonist enhanced TLR9 binding to PTP1B, which inactivated PTP1B. Ptp1b(-/-) mice had elevated lung concentrations of G-CSF, CXCL5, and MMP-2, and tissue expression of type-1 interferon following TLR9 agonist administration, compared with wild-type mice. TLR9 responses were further determined in fully differentiated normal human bronchial epithelial (NHBE) cells isolated from nonsmoker, smoker, and COPD donors, and then cultured at air liquid interface. NHBE cells from smokers and patients with COPD expressed more TLR9 and secreted greater levels of G-CSF, IL-6, CXCL5, IL-1\u03b2, and MMP-2 upon TLR9 ligand stimulation compared with cells from nonsmoker donors. Although TLR9 combats infection, our results indicate that TLR9 induction can affect lung function by inactivating PTP1B and upregulating expression of proinflammatory cytokines.", "descriptor": "Lung", "qualifier": "metabolism"}, {"mag_id": 2435491879, "corpus_id": 33258069, "title": "Sinusoidal fetal heart rate pattern during chemotherapy in a pregnant woman with acute myelogenous leukemia.", "abstract": "A 22-year-old woman was referred to our hospital because of severe anemia in the 20th week of gestation. Acute myelogenous leukemia was diagnosed and she was treated with multiple-agent chemotherapy in the second and third trimesters. Although the patient tolerated the intensive treatment, an intermittent sinusoidal fetal heart rate pattern was detected during chemotherapy. Complete remission was achieved at the 35th week of gestation. An underweight baby boy, suffering from pancytopenia, was delivered by cesarean section at 36 weeks' gestation. The baby recovered well and had adequate growth. No abnormalities where found at examination two months after birth. The fetal sinusoidal heart rate pattern may have been induced by severe anemia due to myelosuppression caused by the transplacental receipt of chemotherapeutic agents.", "descriptor": "Antineoplastic Agents", "qualifier": "adverse effects"}, {"mag_id": 2075504739, "corpus_id": 23109060, "title": "Calmodulin-dependent Regulation of Inducible and Neuronal Nitric-oxide Synthase*", "abstract": "Neuronal and endothelial nitric-oxide synthases depend upon Ca2+/calmodulin for activation, whereas the activity of the inducible nitric-oxide synthase is Ca2+-independent, presumably due to tightly bound calmodulin. To study these different mechanisms, a series of chimeras derived from neuronal and inducible nitric- oxide synthases were analyzed. Chimeras containing only the oxygenase domain, calmodulin-binding region, or reductase domain of inducible nitric-oxide synthase did not confer significant Ca2+-independent activity. However, each chimera was more sensitive to Ca2+ than the neuronal isoform. The calmodulin-binding region of inducible nitric-oxide synthase with either its oxygenase or reductase domains resulted in significant, but not total, Ca2+-independent activity. Co-immunoprecipitation experiments showed no calmodulin associated with the former chimera in the absence of Ca2+. Trifluoperazine also inhibited this chimera in the absence of Ca2+. The combined interactions of calmodulin bound to inducible nitric-oxide synthase calmodulin-binding region with the oxygenase domain may be weaker than with the reductase domain. Thus, Ca2+-independent activity of inducible nitric-oxide synthase appears to result from the concerted interactions of calmodulin with both the oxygenase and reductase domains in addition to the canonical calmodulin-binding region. The neuronal isoform is not regulated by a unique autoinhibitory element in its reductase domain.", "descriptor": "Calcium", "qualifier": "metabolism"}, {"mag_id": 2113115183, "corpus_id": 44934855, "title": "Screening mammography with computer-aided detection: prospective study of 12,860 patients in a community breast center.", "abstract": "PURPOSE\nTo prospectively assess the effect of computer-aided detection (CAD) on the interpretation of screening mammograms in a community breast center.\n\n\nMATERIALS AND METHODS\nOver a 12-month period, 12,860 screening mammograms were interpreted with the assistance of a CAD system. Each mammogram was initially interpreted without the assistance of CAD, followed immediately by a reevaluation of areas marked by the CAD system. Data were recorded to measure the effect of CAD on the recall rate, positive predictive value for biopsy, cancer detection rate, and stage of malignancies at detection.\n\n\nRESULTS\nWhen comparing the radiologist's performance without CAD with that when CAD was used, the authors observed the following: (a) an increase in recall rate from 6.5% to 7.7%, (b) no change in the positive predictive value for biopsy at 38%, (c) a 19.5% increase in the number of cancers detected, and (d) an increase in the proportion of early-stage (0 and I) malignancies detected from 73% to 78%.\n\n\nCONCLUSION\nThe use of CAD in the interpretation of screening mammograms can increase the detection of early-stage malignancies without undue effect on the recall rate or positive predictive value for biopsy.", "descriptor": "Breast Neoplasms", "qualifier": "diagnostic imaging"}, {"mag_id": 288297, "corpus_id": 42474472, "title": "The Working Group on Cardiovascular Nursing: a European forum for international collaboration in cardiac care.", "abstract": "The Working Group on Cardiovascular Nursing : a European forum for international collaboration in cardiac care", "descriptor": "Cardiovascular Diseases", "qualifier": "nursing"}, {"mag_id": 1788181016, "corpus_id": 20036202, "title": "The prelymphatic pathways of the brain as revealed by cervical lymphatic obstruction and the passage of particles.", "abstract": "Light and electron microscopy was used to examine portions of the brain, the circle of Willis, and the internal carotid arteries of normal cats and rabbits, of sham-operated ones, and of those whose cervical lymphatics had been ligated. Carbon was injected into the cerebral cortex of some lymphoedematous animals. It was found that lymphatic ligation produced oedema of the brain, and a dilatation of the prelymphatic spaces around the vessels. Carbon was traced in these from the injection site, around the minor and major vessels, in the adventitia of the internal carotid artery, entering lymphatics adjacent to it, and finally in the draining lymph nodes. The oedema and dilated spaces were not present in the control animals. This was taken to indicate that there is a continuous system of non-endothelialized spaces and potential spaces-the prelymphatics-draining the brain into the cervical lymphatics. The protein in these spaces appeared to be increased if the lymph-oedema had lasted three weeks as compared to 24 hours, indicating that one of the major roles of this system is the removal of protein.", "descriptor": "Brain", "qualifier": "anatomy & histology"}, {"mag_id": 2282572028, "corpus_id": 30667839, "title": "BRAF inhibitor treatment of primary BRAF-mutant ameloblastoma with pathologic assessment of response.", "abstract": "OBJECTIVE\nMolecular characterization of ameloblastoma has indicated a high frequency of driver mutations in BRAF and SMO. Preclinical data suggest that Food and Drug Administration-approved BRAF-targeted therapies may be immediately relevant for patients with ameloblastoma positive for the BRAF V600E mutation.\n\n\nMETHODS\nA neoadjuvant treatment regime of dabrafenib was given to a patient with recurrent BRAF-mutant mandibular ameloblastoma. The patient subsequently underwent left mandible composite resection of the tumor and pathologic evaluation of treatment response.\n\n\nRESULTS\nThe ameloblastoma had a slow but dramatic response with >90% tumor volume reduction. The inner areas of the tumor underwent degeneration and squamous differentiation, and intact ameloblastoma was present in the outer areas associated with bone.\n\n\nCONCLUSIONS\nTargeted neoadjuvant therapy for ameloblastoma may be useful in certain clinical settings of primary ameloblastoma. These might include tumors of advanced local stage when a neoadjuvant reduction could alter the extent of surgery and instances of local recurrence when surgical options are limited.", "descriptor": "Antineoplastic Agents", "qualifier": "therapeutic use"}, {"mag_id": 1986194578, "corpus_id": 22832031, "title": "Antibacterial activity and increased bone marrow stem cell functions of Zn-incorporated TiO2 coatings on titanium.", "abstract": "In this work, zinc was incorporated into TiO2 coatings on titanium by plasma electrolytic oxidation to obtain the implant with good bacterial inhibition ability and bone-formability. The porous and nanostructured Zn-incorporated TiO2 coatings are built up from pores smaller than 5 \u03bcm and grains 20-100 nm in size, in which the element Zn exists as ZnO. The results obtained from the antibacterial studies suggest that the Zn-incorporated TiO2 coatings can greatly inhibit the growth of both Staphylococcus aureus and Escherichia coli, and the ability to inhibit bacteria can be improved by increasing the Zn content in the coatings. Moreover, the in vitro cytocompatibility evaluation demonstrates that the adhesion, proliferation and differentiation of rat bone marrow stem cells (bMSC) on Zn-incorporated coatings are significantly enhanced compared with Zn-free coating and commercially pure Ti plate, and no cytotoxicity appeared on any of the Zn-incorporated TiO2 coatings. Moreover, bMSC express higher level of alkaline phosphatase activity on Zn-incorporated TiO2 coatings and are induced to differentiate into osteoblast cells. The better antibacterial activity, cytocompatibility and the capability to promote bMSC osteogenic differentiation of Zn-incorporated TiO2 coatings may be attributed to the fact that Zn ions can be slowly and constantly released from the coatings. In conclusion, innovative Zn-incorporated TiO2 coatings on titanium with excellent antibacterial activity and biocompatibility are promising candidates for orthopedic and dental implants.", "descriptor": "Anti-Bacterial Agents", "qualifier": "pharmacology"}, {"mag_id": 3004677482, "corpus_id": 211086796, "title": "Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases", "abstract": "The intricate relationships between innate immunity and brain diseases raise increased interest across the wide spectrum of neurodegenerative and neuropsychiatric disorders. Barriers, such as the blood\u2013brain barrier, and innate immunity cells such as microglia, astrocytes, macrophages, and mast cells are involved in triggering disease events in these groups, through the action of many different cytokines. Chronic inflammation can lead to dysfunctions in large-scale brain networks. Neurodegenerative diseases, such as Alzheimer\u2019s disease, Parkinson\u2019s disease, Huntington\u2019s disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are associated with a substrate of dysregulated immune responses that impair the central nervous system balance. Recent evidence suggests that similar phenomena are involved in psychiatric diseases, such as depression, schizophrenia, autism spectrum disorders, and post-traumatic stress disorder. The present review summarizes and discusses the main evidence linking the innate immunological response in neurodegenerative and psychiatric diseases, thus providing insights into how the responses of innate immunity represent a common denominator between diseases belonging to the neurological and psychiatric sphere. Improved knowledge of such immunological aspects could provide the framework for the future development of new diagnostic and therapeutic approaches.", "descriptor": "Mental Disorders", "qualifier": "immunology"}, {"mag_id": 2022758533, "corpus_id": 22025234, "title": "HIV-related Eye Disease in Patients Presenting to a Tertiary Care Government Hospital in Turkey", "abstract": "Aim: To document the ocular involvement in HIV-infected individuals in Turkey and to compare the findings with those from other centers throughout the world. Methods: In this cross-sectional study, patients with HIV infection being monitored in a tertiary hospital in Istanbul were enrolled. Ocular examination was performed, and the prevalence of ocular manifestations determined. Results: In total, 93 patients were enrolled, of whom 37.6% had ocular pathology. HIV retinopathy was the most frequent retinal finding, affecting 8.6% of the enrolled patients, but none of the affected individuals had any ophthalmic complaints. There were no ocular lesions suggestive of cytomegalovirus (CMV) retinitis. Discussion: In contrast to the case in the developed world, sight-threatening infections are uncommon in Turkish HIV+ patients. The reasons for this are not clear, but it is possible that there are some genetic or environmental protective factors against CMV retinitis in the population studied.", "descriptor": "HIV Infections", "qualifier": "epidemiology"}, {"mag_id": 2583114732, "corpus_id": 3342296, "title": "Connectivity strength\u2010weighted sparse group representation\u2010based brain network construction for MCI classification", "abstract": "Brain functional network analysis has shown great potential in understanding brain functions and also in identifying biomarkers for brain diseases, such as Alzheimer's disease (AD) and its early stage, mild cognitive impairment (MCI). In these applications, accurate construction of biologically meaningful brain network is critical. Sparse learning has been widely used for brain network construction; however, its l1\u2010norm penalty simply penalizes each edge of a brain network equally, without considering the original connectivity strength which is one of the most important inherent linkwise characters. Besides, based on the similarity of the linkwise connectivity, brain network shows prominent group structure (i.e., a set of edges sharing similar attributes). In this article, we propose a novel brain functional network modeling framework with a \u201cconnectivity strength\u2010weighted sparse group constraint.\u201d In particular, the network modeling can be optimized by considering both raw connectivity strength and its group structure, without losing the merit of sparsity. Our proposed method is applied to MCI classification, a challenging task for early AD diagnosis. Experimental results based on the resting\u2010state functional MRI, from 50 MCI patients and 49 healthy controls, show that our proposed method is more effective (i.e., achieving a significantly higher classification accuracy, 84.8%) than other competing methods (e.g., sparse representation, accuracy\u2009=\u200965.6%). Post hoc inspection of the informative features further shows more biologically meaningful brain functional connectivities obtained by our proposed method. Hum Brain Mapp 38:2370\u20132383, 2017. \u00a9 2017 Wiley Periodicals, Inc.", "descriptor": "Brain", "qualifier": "physiopathology"}, {"mag_id": 2120488893, "corpus_id": 37000423, "title": "The impact of the number of cores on tissue microarray studies investigating prostate cancer biomarkers.", "abstract": "Most tissue microarray studies have used a single 0.6-mm tissue core per             donor tissue. It has been suggested that multiple cores per donor can increase             the representativity of tissue microarray studies. To estimate the potential benefit             of multiple cores, we analyzed Ki67 and p53 in triplet cores taken from three             different areas of 3,261 prostate cancer tissue blocks. Both p53 and Ki67 labeling             index were linked to advanced tumor stage (p<0.0001 each), Gleason score (p<0.0001),             and early PSA recurrence (p<0.0001) independently of whether the 3 tissue spots             were analyzed separately or combined for a consensus result. The rate of positive             findings increased with the amount of analyzed tissue. The average Ki67 labeling             index was higher in tumors with 3 interpretable spots (5.3\u00b15.6) as compared to             two (4.1\u00b14.7) or one interpretable spot (4.1\u00b14.2, p<0.0001). For p53, tumors             with three interpretable spots were positive in 3.8% of cases, and tumors with             1 or 2 interpretable spots in 1.9% only (p=0.003). These data demonstrate that             using multiple cores in a tissue microarray does not necessarily increase the             ability to identify associations of biomarkers with tumor phenotype and prognosis             but has always the disadvantage of additional work and tissue requirements. Multiple             cores may even lead to statistical problems if unequal amounts of tissue are analyzed             per tumor.", "descriptor": "Prostatic Neoplasms", "qualifier": "chemistry"}, {"mag_id": 3012404803, "corpus_id": 212732652, "title": "Pulmonary CD103+ dendritic cells: key regulators of immunity against infection", "abstract": "Since the discovery of dendritic cells (DCs) by the Nobel laureate Professor Ralph Steinman et al. in 1973, a plethora of literature has accumulated on the functional roles of DCs in humans and animal models. DCs are involved in the innate sensing and modulation of adaptive immunity to pathogens. CD103+ DCs constitute a classical nonlymphoid DC subset that has an important role in generating immunity and maintaining tolerance. Pulmonary CD103+ DCs (CD103+ PDCs), which reside in close association with the airway epithelium, are particularly critical in controlling Tcell immunity against lung infections. In this article, we discuss recent evidence that shines light on the role and mechanism of CD103+ PDCs in modulating CD8+ and CD4+ T-cell responses against various pathogens, including bacteria and viruses. A deeper understanding of CD103+ PDC function may provide new translational avenues for the development of vaccines and therapeutics against infectious diseases. Mouse CD103+ PDCs are phenotypically characterized by the expression of \u03b1E(CD103)\u03b27, CD11c , CD207, MHC-II, TLR3, XCR1, and Clec9a/DNGR1 but not CD64 and CD11b. The transcription factors Batf3 and Irf8 are critical for the development of CD103+ PDCs, as shown by the lack of these DCs in Batf3or Irf8-deficient mice. Following pulmonary infection, CD103+ PDCs upregulate costimulatory molecules (CD40, CD80, and CD86), produce large quantities of several cytokines (IL-4, IL-13, IL-12, IL-10, IL-23, and IL6), migrate to the lung-draining mediastinal lymph nodes, and prime naive CD4+ and CD8+ T cells to induce antigen-specific immune responses. Recent studies indicate that CD103+ DCs, along with lymphoid CD8\u03b1+ DCs, form a new class of DCs referred to as type 1 DCs (DC1s), which express the chemokine receptor XCR1 and perform the unique function of cross-presenting exogenous antigens with MHC-I molecules to CD8+ T cells. Owing to similar phenotypic and functional characteristics, human CD141/BDCA-3+ DCs are considered equivalent to murine DC1s. Overall, these DCs constitute a unified DC subset in mice and humans that is developmentally and functionally related. An accumulating wealth of evidence stemming from mouse studies has focused on the function of CD103+ PDCs during viral and bacterial infections. Upon challenge with respiratory influenza A virus or poxvirus infection, mice that lack CD103+ DCs, such as Batf3 and Clec9A\u2212 diphtheria toxin receptor transgenic mice, failed to induce protective immunity, in contrast to control mice, suggesting a protective role for CD103+ PDCs in viral infections. Following influenza A virus infection, CD103+ PDCs acquired and processed apoptotic cell-associated viral antigens in their endocytic compartment, migrated to the mediastinal lymph nodes, and cross-presented the antigens on MHC-I molecules to naive CD8+ T cells to elicit protective virusspecific cytotoxic responses. Interestingly, CD103+ PDCs could cross-present antigens from virally infected cells because of their ability to resist infection by influenza virus via a type I interferonmediated antiviral state. On the other hand, ablation of CD103+ PDCs resulted in decreased production of IFN-\u03b3 by CD8+ T cells and reduced expression of the activation and transcription markers Ki67, CD25, and T-bet in these cells after respiratory vaccinia virus infection. Liang Ng et al. have further shown that CD103+ PDCs not only control cross-priming of CD8+ T cells but also regulate their migration, viability, and memory responses during influenza infection. In doing so, CD103+ PDCs induce upregulated levels of sphingosine-1-phosphate receptor, which is important for egress of lymphocytes from the lymph nodes, on activated CD8+ T cells. Moreover, adoptive transfer of bone marrow-derived CD103+ DCs in CD103+ DC-ablated mice promoted the survival of virus-specific effector CD8+ T cells. In addition, CD103+ PDCs purified from the lungs of influenza virus-infected mice expressed an enhanced level of IL-15, which is a critical cytokine for the maintenance of naive and memory T cells. Thus, CD103+ PDCs occupy a central position in regulating various aspects of CD8+ T-cell responses against viral infections. Hemann et al. recently elucidated the immune mechanism that directs CD103+ PDCs to modulate antiviral CD8+ T-cell immunity. Mice lacking the receptor (Ifnlr1) of type III interferon (IFN-\u03bb), which is an immune-modulatory cytokine that has the ability to promote CD8+ T-cell immunity against influenza A virus, showed a significant reduction in migratory CD103+ PDCs, along with CD8\u03b1+ DCs, in the mediastinal lymph nodes after influenza A virus infection. Furthermore, specific deletion of IFN-\u03bb receptor 1 in CD11c+ DCs in a conditional knockout mouse model mirrored the global immune phenotype of Ifnlr1 mice, particularly the diminished CD8+ T-cell responses. Taken together, these findings indicate that IFN-\u03bb signaling has an important role in programming CD103+ PDCs for migration from the lungs to the lymph nodes and induction of an optimal CD8+ T-cell response against influenza A virus. Provided the importance of the CD103+ PDC-IFN-\u03bb-CD8+ T-cell axis in adaptive immunity, it may be prudent to exploit IFN-\u03bb as a vaccine adjuvant against influenza infection. Most information on how CD103+ PDCs control CD4+ T-cell responses comes from studies using bacterial and fungal pathogens. Analysis of CD103+ PDCs from Klebsiella pneumoniae-infected mice showed that the PDCs imparted enhanced antigen-specific CD4+ T-cell responses in an in vitro", "descriptor": "Lung", "qualifier": "pathology"}, {"mag_id": 2060073940, "corpus_id": 33684152, "title": "A core region of the mafK gene IN promoter directs neurone\u2010specific transcription in vivo", "abstract": "MafK serves as a required subunit of erythroid transcription factor NF\u2010E2 and also functions with various heterodimeric CNC family proteins. MafK expression begins in early mesoderm and is observed in mesenchymal and haematopoietic cells, as well as in neurones during mouse development. In mesodermal descendants, MafK mRNA begins with a distal first exon (called IM), whereas the mRNA in neurones begins with a proximal first exon (IN).", "descriptor": "Neurons", "qualifier": "metabolism"}, {"mag_id": 1907782207, "corpus_id": 23233687, "title": "A first case of protease codon 35 amino acid insertion in a HIV-1 subtype B sequence detected in the Bauru region, state of S\u00e3o Paulo, Brazil: case report.", "abstract": "Amino acid insertions in the protease have rarely been described in HIV-infected patients. One of these insertions has recently been described in codon 35, although its impact on resistance remains unknown. This study presents a case of an HIV variant with an insertion in codon 35 of the protease, described for the first time in Bauru, State of Sao Paulo, Brazil, circulating in a 38-year-old caucasian male with asymptomatic HIV infection since 1997. The variant isolated showed a codon 35 insertion of two amino acids in the protease: a threonine and an aspartic acid, resulting in the amino acid sequence E35E_TD.", "descriptor": "HIV Infections", "qualifier": "virology"}, {"mag_id": 2058817869, "corpus_id": 11895748, "title": "Weight reduction in adolescents.", "abstract": "A weight reduction diet with 700 kcal (90 g protein, 50 g carbohydrates and 15 g fat) and one to two intermittent fasting days per week proved successful for 15 obese, physically inactive adolescents:", "descriptor": "Obesity", "qualifier": "therapy"}, {"mag_id": 2070901413, "corpus_id": 9844436, "title": "Nanog: A Potential Biomarker for Liver Metastasis of Colorectal Cancer", "abstract": "BackgroundAt present, the relationship between Nanog expression and the biological behavior and prognosis of colorectal cancer is still unclear.AimThe purpose of this study was to evaluate the expression and regulatory effects of Nanog in colorectal cancer and the correlation between Nanog protein expression and the prognosis of patients with colorectal cancer.Materials and MethodsThe differential expression of genes between CD133+ tumor cells and CD133\u2212 tumor cells were detected using RT2 Profiler\u2122 PCR Array. The Nanog mRNA expression level was detected by RT-PCR and the protein level was detected using immunohistochemistry staining. The relationship between Nanog expression and clinicopathological parameters of colorectal cancer was determined.ResultsNanog were expressed significantly higher in CD133+ tumor cells compared to CD133\u2212 tumor cells. It was observed that 72 (20.00\u00a0%) of the 360 cases positively expressed Nanog. Univariate analyses indicated that Nanog expression was related to histological grade, lymph node metastasis, TNM stage, and liver metastasis (P\u00a0=\u00a00.005, 0.001, 0.001 and 0.012, respectively). Spearman correlation analysis showed that Nanog expression has a linear correlation to liver metastasis (P\u00a0=\u00a00.001). After conducting multivariate analysis, histological grade, TNM stage, and Nanog were found to be related to liver metastasis (P\u00a0=\u00a00.020, 0.01 and 0.001, respectively). In the Cox regression test, the histological grade, Lymph node metastasis, TNM stage, liver metastasis, and Nanog were detected as the independent prognostic factors (P\u00a0=\u00a00.02, 0.045, 0.01, 0.001 and 0.001, respectively).ConclusionsNanog protein may be a potential biomarker for postoperative liver metastasis of colorectal cancer.", "descriptor": "Liver Neoplasms", "qualifier": "secondary"}, {"mag_id": 1997367272, "corpus_id": 205222075, "title": "A stable core region of the tra operon mRNA of plasmid R1-19.", "abstract": "The degradation of the polycistronic tra-mRNA of the resistance plasmid R1-19 leads to the accumulation of a well defined series of stable mRNA species. The majority of the most stable mRNAs contains the message for the traA gene only. The differently sized stable mRNAs possess a common 3'terminus within the traL gene but vary at their 5' ends. The 3'terminus probably results from protection against exoribonucleases by a secondary structural feature. We propose that the 5' ends are generated by endoribonucleolytic cleavage. The stability of this part of the tra-mRNA exceeds 30 minutes and probably increases the rate of expression of the traA gene product propilin, the precursor of the sex pilus subunit. The expression of propilin and its processing into a protein of the molecular weight of mature pilin is demonstrated with the isolated gene. The sequence of the so far unknown genes traL and traE of R1-19 is presented.", "descriptor": "Escherichia coli", "qualifier": "genetics"}, {"mag_id": 2170247437, "corpus_id": 25394897, "title": "Characterization of neurokinin-1 receptors in the submucosal plexus of guinea pig ileum.", "abstract": "This study combined immunohistochemical double-labeling techniques with functional studies to characterize the neurokinin-1 (NK1) receptors mediating neuronal and vasodilator responses in submucosal guinea pig ileum. NK1 receptor distribution in whole mount preparations of the submucosa was examined using a rabbit polyclonal antibody directed against the COOH terminus of the rat NK1 receptor. Results showed that 97% of neuropeptide Y immunoreactive submucosal neurons colocalized NK1 receptor immunoreactivity, whereas vasoactive intestinal polypeptide immunoreactive neurons were not NK1 immunoreactive. Intracellular recordings were made using neurobiotin-filled electrodes to enable reidentification of recorded neurons for immunohistochemical study. The selective NK1 agonists [Sar9,Met(O2)11]substance P (SP) and septide depolarized S-type submucosal neurons. Of these neurons, 36% were NK1 immunoreactive and 64% were not. NK1 immunoreactivity was not observed on submucosal arterioles, but superfusion of [Sar9,Met(O2)11]SP and septide dilated preconstricted submucosal arterioles. Agonist-evoked responses in both neurons and blood vessels were blocked by the selective NK1 antagonist CP-99994. These findings suggest that NK1 receptors are found on submucosal neurons and arterioles and that electrophysiological and immunohistochemical techniques may identify conformational variants of the receptor.", "descriptor": "Neurons", "qualifier": "physiology"}, {"mag_id": 2808624400, "corpus_id": 49182792, "title": "Generation of HER2-specific antibody immunity during trastuzumab adjuvant therapy associates with reduced relapse in resected HER2 breast cancer", "abstract": "BackgroundResected HER2 breast cancer patients treated with adjuvant trastuzumab and chemotherapy have superior survival compared to patients treated with chemotherapy alone. We previously showed that trastuzumab and chemotherapy induce HER2-specific antibodies which correlate with improved survival in HER2 metastatic breast cancer patients. It remains unclear whether the generation of immunity required trastuzumab and whether endogenous antibody immunity is associated with improved disease-free survival in the adjuvant setting. In this study, we addressed this question by analyzing serum anti-HER2 antibodies from a subset of patients enrolled in the NCCTG trial N9831, which includes an arm (Arm A) in which trastuzumab was not used. Arms B and C received trastuzumab sequentially or concurrently to chemotherapy, respectively.MethodsPre-and post-treatment initiation sera were obtained from 50 women enrolled in N9831. Lambda IgG antibodies (to avoid detection of trastuzumab) to HER2 were measured and compared between arms and with disease-free survival.ResultsPrior to therapy, across all three arms, N9831 patients had similar mean anti-HER2 IgG levels. Following treatment, the mean levels of antibodies increased in the trastuzumab arms but not the chemotherapy-only arm. The proportion of patients who demonstrated antibodies increased by 4% in Arm A and by 43% in the Arms B and C combined (p\u2009=\u20090.003). Cox modeling demonstrated that larger increases in antibodies were associated with improved disease-free survival in all patients (HR\u2009=\u20090.23; p\u2009=\u20090.04).ConclusionsThese results show that the increased endogenous antibody immunity observed in adjuvant patients treated with combination trastuzumab and chemotherapy is clinically significant, in view of its correlation with improved disease-free survival. The findings may have important implications for predicting treatment outcomes in patients treated with trastuzumab in the adjuvant setting.Trial registrationClinicalTrials.gov, NCT00005970. Registered on July 5, 2000.", "descriptor": "Breast Neoplasms", "qualifier": "drug therapy"}, {"mag_id": 1818863325, "corpus_id": 14810809, "title": "Selective Immunolesions of Cholinergic Neurons in Mice: Effects on Neuroanatomy, Neurochemistry, and Behavior", "abstract": "The ability to selectively lesion mouse basal forebrain cholinergic neurons would permit experimental examination of interactions between cholinergic functional loss and genetic factors associated with neurodegenerative disease. We developed a selective toxin for mouse basal forebrain cholinergic neurons by conjugating saporin (SAP), a ribosome-inactivating protein, to a rat monoclonal antibody against the mouse p75 nerve growth factor (NGF) receptor (anti-murine-p75). The toxin proved effective and selective in vitro andin vivo. Intracerebroventricular injections of anti-murine-p75-SAP produced a dose-dependent loss of choline acetyltransferase (ChAT) activity in the hippocampus and neocortex without affecting glutamic acid decarboxylase (GAD) activity. Hippocampal ChAT depletions induced by the immunotoxin were consistently greater than neocortical depletions. Immunohistochemical analysis revealed a dose-dependent loss of cholinergic neurons in the medial septum (MS) but no marked loss of cholinergic neurons in the nucleus basalis magnocellularis after intracerebroventricular injection of the toxin. No loss of noncholinergic neurons in the MS was apparent, nor could we detect loss of noncholinergic cerebellar Purkinje cells, which also express p75. Behavioral analysis suggested a spatial learning deficit in anti-murine-p75-SAP-lesioned mice, based on a correlation between a loss of hippocampal ChAT activity and impairment in Morris water maze performance. Our results indicate that we have developed a specific cholinergic immunotoxin for mice. They also suggest possible functional differences in the mouse and rat cholinergic systems, which may be of particular significance in attempts to develop animal models of human diseases, such as Alzheimer's disease, which are associated with impaired cholinergic function.", "descriptor": "Neurons", "qualifier": "drug effects"}, {"mag_id": 1529624219, "corpus_id": 10460271, "title": "Revised Interpretation of the Origin of the pSC101 Plasmid", "abstract": "Data are presented indicating that the pSC101 plasmid was not derived by recircularization of a mechanically sheared fragment of R6-5 plasmid deoxyribonucleic acid, as was originally believed.", "descriptor": "Escherichia coli", "qualifier": "genetics"}, {"mag_id": 2557261470, "corpus_id": 35244973, "title": "Big Data: Contributions, Limitations, and Implications for Cardiovascular Nurses.", "abstract": "Big data is a catch phrase applied to large volumes of highvelocity, complex, and variable data that require advanced techniques and technologies to enable the capture, storage, distribution, management, and analysis of the information. Applied to healthcare, big data can be defined as combining and analyzing large amounts of data to identify associations and make predictions that can inform improvements in quality of healthcare delivery and patient outcomes. Healthcare data sources include electronic health records, machine-generated information garnered from devices such as cardiac monitors and ActiGraphs, social media including Facebook status updates and Twitter Posts, and genome data. The availability of healthcare data is growing exponentially as electronic health records, the use of wearable devices, social media and Internet use, and genomic information continue to expand. Examining data from real-world clinical care to evaluate therapies is a powerful alternative to costly and often impractical randomized controlled trials. Although big data analytics have the potential to significantly contribute to cardiovascular nursing science and practice, it is important to understand the limitations and how nurses can contribute to ensuring big data findings are effectively used to improve patient care.", "descriptor": "Cardiovascular Diseases", "qualifier": "nursing"}, {"mag_id": 2144225938, "corpus_id": 206097059, "title": "Improvement of vessel visibility in time\u2010of\u2010flight MR angiography of the brain", "abstract": "To improve vessel visibility in time\u2010of\u2010flight MR angiography (TOF\u2010MRA) by careful consideration of coil choice, coil position, and frequency offset and profile of the nonspatially selective chemical shift selective (CHESS) presaturation pulse.", "descriptor": "Brain", "qualifier": "blood supply"}, {"mag_id": 1966956977, "corpus_id": 31429562, "title": "Adult survivors of childhood cancer employment and insurance issues in different age groups", "abstract": "Survivors of adult forms of cancer have noted discrimination in obtaining employment appropriate to their abilities/training and in securing comprehensive, affordable health and life insurance. Among survivors of childhood cancer, these problems are complicated, because most survivors of childhood cancer have no employment record and only family\u2010related insurance before the onset of cancer. Relative to these issues, adults who are survivors of childhood cancer can be divided into two groups, i.e., those who are younger and those older than 30 years of age. In the older age group (30\u201350 years), the general indicators of economic achievement and insurability are similar to those of control subjects. Exceptions in this age group include denial of entry into the uniformed services and rejection of applications for life insurance. Survivors who are 20\u201329 years of age have a wider range of areas in which there is variance from control subjects, including educational achievement, employment, workplace relationships, and the ability to obtain health and life insurance.", "descriptor": "Neoplasms", "qualifier": "mortality"}, {"mag_id": 1969954895, "corpus_id": 31168828, "title": "Alveolar Soft Part Sarcoma of the Pulmonary Vein", "abstract": "Alveolar soft part sarcoma of the lung seen in a 42\u2010year\u2010old female is reported. In the partial pneumonectomy specimen, there was a 3x2.5 cm tumor arising from the pulmonary vein at the level of the right lung hilus, with tumor thrombus formation. The transition between the tumor and venous smooth muscle layer was microscopically confirmed. At autopsy, performed 18 months after surgery, metastases were noted in the left lung and brain. No primary focus was identified in the soft tissue. The alveolus\u2010forming clear tumor cells contained diastase\u2010resistant periodic acid\u2010Schiff\u2010reactive granules. Immunohistochemically, granular cytoplasmic reactivities with monoclonal antibodies against pan\u2010actin and alpha\u2010sar\u2010comeric actin were demonstrated, whereas other muscle markers such as desmin, alpha\u2010smooth muscle actin, myoglobin, fast skeletal myosin, and the mm\u2010isozyme of creatine kinase were negative. Ultrastructurally, crystallized structures were occasionally identified in the membrane\u2010bound, electron lucent granules, which often filled the tumor cell cytoplasm. The muscle cell nature of the neoplasm is discussed. Acta Pathol Jpn 41: 771\u2010777, 1991.", "descriptor": "Lung Neoplasms", "qualifier": "pathology"}, {"mag_id": 2412887281, "corpus_id": 11874888, "title": "Overexpression, purification, and characterization of the ADP-ribosyltransferase (gpAlt) of bacteriophage T4: ADP-ribosylation of E. coli RNA polymerase modulates T4 \"early\" transcription.", "abstract": "The bacteriophage T4 Alt gene product is a component of the phage head and enters the host cell in the process of infection together with the phage DNA. It immediately ADP-ribosylates host RNA polymerase, presumably at only one of the two alpha-subunits. Transcription from T4 \"early\" promoters, therefore, might be catalyzed, at least in part, by an altered RNA polymerase. The T4 alt gene was cloned into the expression vector pBluescript. E. coli cells, transformed with this recombinant vector, overexpressed the 76 kDa Alt gene product, which was purified to homogeneity. The purified enzyme not only ADP-ribosylates the alpha-subunit of RNA polymerase, but also subunits beta and beta', as well as the sigma 70-factor. The recombinant enzyme behaved like the native enzyme isolated from mature phage particles. The effect of the ribosylation reaction on the transcription activity of host RNA polymerase was investigated in vivo. It results in a modulation of T4 \"early\" promoter strengths, presumably, in a number of cases, leading to an overexpression of T4 \"early\" genes. The degree of overexpression, in some cases, should reach 50%, and seems to be well dosed for each promoter, controlling an individual transcription unit.", "descriptor": "Escherichia coli", "qualifier": "metabolism"}, {"mag_id": 2418303856, "corpus_id": 26361100, "title": "Hypertension in Blacks: a literature review.", "abstract": "Hypertension is a major risk factor for heart disease and stroke, the first and third-leading causes of death in the United States. This review discusses the magnitude of the problem, its epidemiology, and the evaluation and management of hypertension as recommended by the reports of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Activities related to the control of this disorder are also highlighted. Data from the Third National Health and Nutrition Examination Survey, 1998-1994, (NHANESIII) suggest approximately three-quarters (75%) of Black hypertensives are aware of their diagnosis, but only 57% are treated and just 25% have their blood pressure under control (<140 mm Hg systolic and <90 mm Hg diastolic). Although substantial evidence indicates a significant increase in awareness of hypertension over the past three decades, control rates are remarkably low, particularly among Blacks. This review serves to emphasize and reiterate the burden of hypertension among Blacks and acts as a reminder of the need for additional research to determine if culturally competent interventions are appropriate to prevent, treat, and control this disease within this population.", "descriptor": "Hypertension", "qualifier": "epidemiology"}, {"mag_id": 2003786053, "corpus_id": 24144969, "title": "An experimental assessment of toxic potential of nanoparticle preparation of heavy metals in streptozotocin induced diabetes.", "abstract": "Nanoparticle preparations of heavy metals have attracted enormous scientific and technological interest. Biologically produced nanoparticle preparations of heavy metals are elaborately described in traditional texts and being widely prescribed. The underlying interactions of nano preparations within the physiological fluids are key feature to understand their biological impact. In this perspective, we performed an experimental assessment of the toxicity potential of a marketed metallic preparation named Vasant Kusumakar Ras (VKR), wherein different heavy metals in composite form are reduced to nanoparticle size to produce the desired effect in diabetes and its complications. VKR (50mg/kg) was administered to Albino Wistar rats rendered diabetic using streptozotocin (90mg/kg) in 2 days old neonates. Anti-hyperglycemic effect was observed with VKR along with increased levels of plasma insulin. Renal variables including total proteins and albumin along with glomerular filtration rate were found to improve biochemically. The results were supplemented by effects on different inflammatory and growth factors like TNF-\u03b1, nitric oxide, TGF-\u03b2 and VEGF. However, the results observed in kidney histopathology were not in accordance with the biochemical parameters. Inflammation observed in kidney was confirmed by immunostaining metallothionein, which was due to the accumulation of heavy metals. Furthermore, mercury accumulation in kidney further confirmed by autometallography, which activated mononuclear phagocyte system, which generated an immune response. This was further supported by increase in the extent of apoptosis in kidney tissues. In conclusion, nanoparticle preparations of heavy metals can be toxic to kidney if it is not regulated with respect to its surface chemistry and dosage.", "descriptor": "Kidney", "qualifier": "drug effects"}, {"mag_id": 2044905785, "corpus_id": 23650006, "title": "Hlx homeo box gene is essential for an inductive tissue interaction that drives expansion of embryonic liver and gut.", "abstract": "The divergent murine homeo box gene Hlx is expressed in restricted hematopoietic cell types and, during embryogenesis, prominently in visceral mesenchyme of the developing liver, gall bladder, and gut. Targeted disruption of the gene has now established that it plays a key role in visceral organogenesis. Embryos homozygous for the mutation died around embryonic day 15 with anemia and severe hypoplasia of the liver and gut. Liver ontogeny commenced normally with formation of the liver diverticulum and differentiation of hepatocytes, but the organ failed to expand and reached only 3% of normal size. The apparent liver hypoplasia was not associated with a notable increase in apoptotic cells. Gut development also began normally, but the intestines failed to undergo extensive elongation and looping and reached only a quarter of normal length. The anemia resulted from a deficiency in the fetal form of hematopoiesis, which occurs in the liver, but no intrinsic defect in Hlx-/- hematopoietic cells was observed in vitro, and liver-derived Hlx-/- hematopoietic stem cells that were transplanted to irradiated normal mice could fully reconstitute hematopoiesis. The impaired fetal hematopoiesis therefore reflects insufficient support function provided by the minute liver. Hlx is normally expressed in visceral mesenchyme lying adjacent to the developing liver and gut epithelia affected by the mutation, but not in the epithelia themselves. Hence, Hlx regulates a mesenchymal-epithelial interaction that drives a vital growth phase in visceral organogenesis. Moreover, because mutation of Hlx blocked liver growth but not its specification, early morphogenesis, or differentiation, development of this organ appears to occur by step-wise inductive interactions under separate genetic control.", "descriptor": "Liver", "qualifier": "embryology"}, {"mag_id": 1998174102, "corpus_id": 19821308, "title": "Induction of ZEB Proteins by Inactivation of RB Protein Is Key Determinant of Mesenchymal Phenotype of Breast Cancer*", "abstract": "Background: Inactivation of RB is a key event for induction of EMT in cancers. Results: ZEB proteins are markedly up-regulated through the reduction of miR-200 family of microRNAs in RB-inactive cancer cells. Conclusion: RB/ZEB pathway plays a pivotal role in mesenchymal and aggressive phenotype in breast cancers. Significance: Suppressing ZEB1 by cyclin-dependent kinase inhibitors provides a novel therapeutic strategy for RB-inactive breast cancers. We previously showed that depletion of the retinoblastoma protein (RB) induces down-regulation of the adhesion molecule E-cadherin and thereby triggers the epithelial-mesenchymal transition. To further characterize the effect of RB inactivation on the phenotype of cancer cells, we have now examined RB expression in human breast cancer cell lines and clinical specimens. We found that RB-inactive cells exhibit a mesenchymal-like morphology and are highly invasive. We also found that ZEB proteins, transcriptional repressors of the E-cadherin gene, are markedly up-regulated in these cells in a manner sensitive to the miR-200 family of microRNAs. Moreover, depletion of ZEB in RB-inactive cells suppressed cell invasiveness and proliferation and induced epithelial marker expression. These results implicate ZEB in induction of the epithelial-mesenchymal transition, as well as in maintenance of the mesenchymal phenotype in RB-inactive cells. We also developed a screening program for inhibitors of ZEB1 expression and thereby identified several cyclin-dependent kinase inhibitors that blocked both ZEB1 expression and RB phosphorylation. Together, our findings suggest that RB inactivation contributes to tumor progression not only through loss of cell cycle control but also through up-regulation of ZEB expression and induction of an invasive phenotype.", "descriptor": "Breast Neoplasms", "qualifier": "metabolism"}, {"mag_id": 1859863282, "corpus_id": 30567000, "title": "A protective surface protein from type V group B streptococci shares N-terminal sequence homology with the alpha C protein", "abstract": "Infection by group B streptococci (GBS) is an important cause of bacterial disease in neonates, pregnant women, and nonpregnant adults. Historically, serotypes Ia, Ib, II, and III have been most prevalent among disease cases; recently, type V strains have emerged as important strains in the United States and elsewhere. In addition to type-specific capsular polysaccharides, many GBS strains possess surface proteins which demonstrate a laddering pattern on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and resistance to trypsin digestion. These include the alpha C protein, the R proteins, and protein Rib. Some of these proteins elicit protective antibodies in animals. We demonstrate a trypsin-resistant laddering protein purified from a type V GBS strain by mutanolysin extraction and column chromatography. This protein contains a major 90-kDa band and a series of smaller bands spaced approximately 10 kDa apart on SDS-PAGE. Cross-reactivity of the type V protein with the alpha C protein and with R1 was demonstrated on Western blot (immunoblot). N-terminal sequence analysis of the protein revealed residue identity with 17 of 18 residues at corresponding positions on the alpha protein. Western blot of SDS extracts of 41 clinical type V isolates with rabbit antiserum to the protein demonstrated a homologous protein in 25 isolates (61%); two additional strains exhibited a heterologous pattern which was also demonstrated with 4G8, a monoclonal antibody directed to the alpha C protein repeat region. Rabbit antiserum raised to the type V protein conferred protection in neonatal mice against a type V strain bearing a homologous protein. These data support the hypothesis that there exists a family of trypsin-resistant, laddering GBS surface proteins which may play a role in immunity to GBS infection.", "descriptor": "Bacterial Proteins", "qualifier": "immunology"}, {"mag_id": 2139898424, "corpus_id": 31187741, "title": "Classification of Epithelial Canine Mammary Tumors in a Defined Population", "abstract": "Ductal carcinomas accounted for nearly all metastases seen in epithelial canine mammary tumors submitted to the Tulsa Registry of Canine and Feline Neoplasms in a 4-year period from a defined canine population. Lobular and squamous cell carcinomas were the only other metastatic carcinomas seen. Early ductal carcinoma was used to indicate nonmetastatic ductal carcinoma with a favorable post-surgical prognosis. Benign epithelial tumors were categorized as adenoma, ductal papilloma and squamous cell papilloma. Progressive transformation of well defined adenomas and papillomas to carcinoma was not evident in histologic preparations. Squamous metaplasia was seen in many ductal papillomas and ductal carcinomas. Inclusion of pseudocartilage and pseudoosteoid and osteoid, cartilage and bone with ductal carcinomas, adenomas and ductal papillomas seemed related to secretions escaping from neoplastic epithelial cells into stroma or between proliferating tumor cells. There was proliferation and perhaps even neoplastic transformation of myoepithelial cells in some of these tumors. Changes in myoepithelium, however, appeared to be secondary to neoplastic transformation of epithelium. Bone and cartilage in these tumors were considered heterotopic with no neoplastic potential.", "descriptor": "Neoplasms", "qualifier": "veterinary"}, {"mag_id": 2416775290, "corpus_id": 32321142, "title": "Homocysteine level in patients with established transmural myocardial infarction.", "abstract": "OBJECTIVE\nTo evaluate the levels of serum total homocysteine in patients suffering from established transmural myocardial infarction and normal healthy subjects of local population.\n\n\nDESIGN\nA case control study.\n\n\nPLACE AND DURATION OF STUDY\nThe present study was carried out at Dr. Hafiz Muhammad Ilyas (HMI) Institute of Pharmacology and Herbal Sciences in collaboration with National Institute of Cardiovascular Diseases, Karachi, from June 2001 to December 2001.\n\n\nPATIENTS AND METHODS\nEighty-four persons were included in a case control study. Sixty-three patients were cases suffering from transmural myocardial infarction of anterior wall and 21 normal healthy subjects were controls having no history of IHD ever before. Fasting venous serum was analyzed for total homocysteine using fluorescence polarization immunoassay (FPIA) while lipid parameters and plasma glucose were estimated by enzymatic colorimetric method.\n\n\nRESULTS\nMean serum total homocysteine and low density lipoprotein cholesterol (LDL-C) levels [19.43+/-2.46 umol/L, 124.97+/-45.31 mg/dl respectively] were found to be significantly higher in cases as compared to controls. The mean serum High density lipoprotein cholesterol (HDL-C) [27.57+/-15.31 mg/dl] was found to be significantly lower as compared to control. Mean serum glucose, total cholesterol and serum triacylglycerol [84.32+/-2.46 mg/dl, 174.35+/-27.08 mg/dl and 148.49+/-43.12 mg/dl respectively] were higher in patients as compared to control but difference was insignificant statistically.\n\n\nCONCLUSION\nSignificantly high levels of total homocysteine along with high levels of LDL-C and low levels of HDL-C appear to be the factors responsible for the increase risk of coronary artery disease in our local population.", "descriptor": "Myocardial Infarction", "qualifier": "blood"}, {"mag_id": 2006292802, "corpus_id": 2163358, "title": "Effect of age, sex, and hormonal state on tritiated thymidine uptake by rat pituitary.", "abstract": "PITUITARY tumours may arise spontaneously as certain strains of female rat become old, or they may be induced in rodents by a variety of experimental methods, chiefly involving hormonal imbalance. Less is known, however, of the factors which control the magnitude of cell division and growth in the pituitary, for mitotic figures are rare and conventionally the normal gland is regarded as a stable population of cells. A more accurate assessment of normal pituitary cell growth dynamics is obtained if tritiated (3H) thymidine is used to localize by autoradiography nuclei in the DNA synthetic (S) phase of the nuclear cycle. A previous study with this technique showed that age and sex were important variables influencing 3H-thymidine labelling of the rat anterior pituitary, but these results were complicated by the fact that they were obtained from animals with various forms of experimental hypertension (Crane, Dutta and Ingle, 1965). Accordingly the experiments reported here were designed to study the influence of age, sex, the ovary and oestrus cycle, and the adrenal on the numbers of DNAsynthesizing nuclei in the rat pituitary, and to define more precisely the relationship of these factors to pituitary tumour induction.", "descriptor": "DNA", "qualifier": "biosynthesis"}, {"mag_id": 1993669370, "corpus_id": 29042735, "title": "Prostate carcinoma", "abstract": "The development and progression of a prostate carcinoma from prediagnosis to death can be characterized as a series of clinical states. The states are milestones that can be used to assess prognosis, define therapeutic objectives, and assess outcomes. The antitumor effects of hormone therapies and cytotoxic agents in patients with prostate carcinoma are placed in context along with the bidrectional tumor\u2010host interactions that contribute to the growth and resistance of osseous lesions. Identifying the factors that contribute to the growth of the disease at different points in the illness has lead to novel, systemic approaches. Proving the benefit of these approaches requires a series of unique trials with unique endpoints relevant to the clinical state of the patients and the specific therapy under evaluation. Cancer 2003;97(3 Suppl):758\u201371. \u00a9 2003 American Cancer Society.", "descriptor": "Prostatic Neoplasms", "qualifier": "therapy"}, {"mag_id": 1924843208, "corpus_id": 32629082, "title": "Energy behaviour for DNA translocation through graphene nanopores.", "abstract": "Nanoparticles have considerable promise for many applications in electronics, energy storage, bioscience and biotechnologies. Here we use applied mathematical modelling to exploit the basic principles of mechanics and the 6-12 Lennard-Jones potential function together with the continuum approach, which assumes that a discrete atomic structure can be replaced by an average constant atomic surface density of atoms that is assumed to be smeared over each molecule. We identify a circular hole in a graphene sheet as a nanopore and we consider the molecular interaction energy for both single-strand and double-strand DNA molecules assumed to move through the circular hole in a graphene sheet to determine the radius b of the hole that gives the minimum energy. By minimizing the interaction energy, we observe that the single-strand DNA and double-strand DNA molecules penetrate through a graphene nanopore when the pore radii b> 7.8\u00c5 and b> 12.7\u00c5, respectively. Our results can be adopted to offer new applications in the atomic surface processes and electronic sensing.", "descriptor": "DNA", "qualifier": "chemistry"}, {"mag_id": 2017230178, "corpus_id": 20966773, "title": "Spermine selectively inhibits high-conductance, but not low-conductance calcium-induced permeability transition pore.", "abstract": "The permeability transition pore (PTP) is a large channel of the mitochondrial inner membrane, the opening of which is the central event in many types of stress-induced cell death. PTP opening is induced by elevated concentrations of mitochondrial calcium. It has been demonstrated that spermine and other polyamines can delay calcium-induced swelling of isolated mitochondria, suggesting their role as inhibitors of the mitochondrial PTP. Here we further investigated the mechanism by which spermine inhibits the calcium-induced, cyclosporine A (CSA) -sensitive PTP by using three indicators: 1) calcium release from the mitochondria detected with calcium green, 2) mitochondrial membrane depolarization using TMRM, and 3) mitochondrial swelling by measuring light absorbance. We found that despite calcium release and membrane depolarization, indicative of PTP activation, mitochondria underwent only partial swelling in the presence of spermine. This was in striking contrast to the high-amplitude swelling detected in control mitochondria and in mitochondria treated with the PTP inhibitor CSA. We conclude that spermine selectively prevents opening of the high-conductance state, while allowing activation of the lower conductance state of the PTP. We propose that the existence of lower conductance, stress-induced PTP might play an important physiological role, as it is expected to allow the release of toxic levels of calcium, while keeping important molecules (e.g., NAD) within the mitochondrial matrix.", "descriptor": "Calcium", "qualifier": "metabolism"}, {"mag_id": 1983632922, "corpus_id": 21386842, "title": "Adaptive biological image-guided IMRT with anatomic and functional imaging in pharyngo-laryngeal tumors: impact on target volume delineation and dose distribution using helical tomotherapy.", "abstract": "BACKGROUND AND PURPOSE\nAdaptive image-guided IMRT appears to be a promising approach for dose escalation in pharyngo-laryngeal tumors. In this framework, we assessed in a proof of concept study the impact of anatomic and functional imaging modalities acquired prior and during radiotherapy on the target volume delineation and the dose distribution using helical tomotherapy.\n\n\nMATERIALS AND METHODS\nTen patients with pharyngo-laryngeal squamous cell carcinoma were treated by concomitant chemo-radiation delivered in 7 weeks. CT, T2-MRI, fat suppressed T2-MRI, and static and dynamic FDG-PET were acquired for each patient before the start of treatment and during radiotherapy, after mean prescribed doses of 14, 25, 35 and 45 Gy. GTVs were manually delineated on CT and MRI images while PET images were automatically segmented by means of a gradient-based method. From these volumes, CTVs and PTVs were derived using consistent guidelines. Simultaneous integrated boost IMRT planning was performed using helical tomotherapy.\n\n\nRESULTS\nGTVs significantly decreased throughout the course of RT for all imaging modalities (p<0.001). Clinically non-significant differences and high correlations were found between GTVs delineated on CT and MRI, irrespective of the sequence used. By contrast, FDG-PET-based GTVs segmented from pre- and per-treatment images were significantly smaller compared to anatomical imaging modalities, without any difference existing between static and dynamic acquisition. These differences in GTVs translated into parallel reductions of both prophylactic and therapeutic CTVs and PTVs. Resulting FDG-PET-based and adaptive IMRT planning reduced the irradiated volumes by 15-40% compared to pre-treatment CT planning (V(90), V(95) and V(100)), but did marginally impact on doses to the OAR such as the spinal cord and the parotid glands.\n\n\nCONCLUSIONS\nAdaptive IMRT with FDG-PET images has a significant impact on the delineation of TVs and on the dose distribution in pharyngo-laryngeal tumors. Such an approach might thus be considered for dose escalation strategies.", "descriptor": "Carcinoma, Squamous Cell", "qualifier": "radiotherapy"}, {"mag_id": 1780179166, "corpus_id": 23498440, "title": "Immunological Status of Chronic Myelogenous Leukemia Patients with Complete Cytogenetic Response after Treatment", "abstract": "Background The aim of this study was to compare the T lymphocyte subsets of chronic myelogenous leukemia (CML) patients who had a complete cytogenetic response (CCyR) after treatment with imatinib (IM) or homoharringtonine (HHT). Methods T and Th lymphocyte subsets in CCyR patients treated with HHT (n = 15) or IM (n = 16) were assayed with flow cytometry. Results It was found that there were no differences in T lymphocyte subset proportions at the time of achieving CCyR0 and also no difference in the CD8+T cell proportions at the 12th month after CCyR (CCyR12), between the 2 groups. The values of CD3+T, CD4+T, CD8+T, CD4+T/CD8+T, Th1 and Th2 cells were 54.21% \u00b1 6.12% vs. 44.32% \u00b1 4.85%, 29.83% \u00b1 5.53% vs. 22.27% \u00b1 3.22%, 24.66 \u00b1 4.91 vs. 25.41% \u00b1 5.72%, 1.11 \u00b1 0.23 vs. 0.92 \u00b1 0.19, 10.23% \u00b1 4.24% vs. 8.34% \u00b1 3.45% and 11.12% \u00b1 3.91% vs. 13.67% \u00b1 4.78%, respectively in the HHT group and IM group at CCyR12, which meant that the proportions of CD3+T, CD4+T and Th1 cells and the ratio of CD4+T to CD8+T cells were higher and the CD8+T and Th2 cell proportions were lower in the HHT group than in the IM group. Conclusions HHT has a weaker immunodepression effect on T lymphocyte subsets compared with IM.", "descriptor": "Antineoplastic Agents", "qualifier": "therapeutic use"}, {"mag_id": 2409066819, "corpus_id": 34696909, "title": "OBRA--its effect on the mentally ill in South Dakota nursing homes.", "abstract": "Mental illness is quite prevalent in the nursing home population. The Omnibus Budget Reconciliation Act of 1987 (OBRA), as it relates to nursing homes, has many facets including preadmission screening, periodic assessment, formalized patient rights, and gives reviewers a broader list of sanctions for offending facilities. OBRA does away with the designation of skilled and intermediate levels of care. It provides for evaluation of special needs of the mentally retarded and developmentally disabled and expects relocation of residents in need of specialized treatments. Similarly, it requires evaluation of the mentally ill in nursing homes for appropriateness of placement and discourages admission of potential nursing home residents with mental illness. This last aspect of OBRA and its potential effect of the long term care system, the mental health system, and the budget of the state of South Dakota are the subject of this paper.", "descriptor": "Mental Disorders", "qualifier": "diagnosis"}, {"mag_id": 2065299478, "corpus_id": 26195887, "title": "EUS 2008 Working Group document: evaluation of EUS-guided injection therapy for tumors.", "abstract": "The current treatment options for locally advanced pancreatic cancer include supportive care, chemotherapy (single or combination), and chemotherapy plus radiation therapy. Studies of gemcitabine combined with other cytotoxic agents have not shown a survival advantage over gemcitabine alone. A study of gemcitabine combined with the epidermal growth factor receptor antagonist, erlotinib, revealed a statistically significant, albeit modest, survival advantage in patients with advanced pancreatic cancer. Currently, studies of gemcitabine combined with other targeted therapies (eg, cetuximab and panitumumab) are in progress. For patients with \u2018\u2018borderline\u2019\u2019 resectable pancreatic cancer, the best strategy seems to be aggressive downstaging of the tumor with local, including radiation therapy, and systemic agents. Varadhachary et al concluded that, in their experience, patients with tumors that respond to neoadjuvant therapy have a better chance of R0 resection, which usually translates to increased survival. Local therapy historically has been essentially limited to external-beam radiation. With combination chemoradiation, tumor response is seen in a small number of patients, and the median survival remains disappointing. Brachytherapy (iodine, gold, and iridium) delivered by percutaneous approaches to the pancreatic tumor has not been effective. Percutaneous intratumoral injection with radioactive phosphorus P 32 has also been reported but with disappointing", "descriptor": "Antineoplastic Agents", "qualifier": "administration & dosage"}, {"mag_id": 2055492924, "corpus_id": 33170976, "title": "Value of Clinical Screening for Detection of Asymptomatic Hemodialysis Vascular Access Stenoses", "abstract": "Measurement of recirculation and intradialytic venous line pressures may aid in the detection of hemodialysis vascular access stenoses. The authors screened 29 consecutive asymptomatic patients for recirculation values exceed ing 15% or venous pressures greater than 150 mmHg. All 13 patients requiring and agreeing to angiography on the basis of the screening protocol proved to have high-grade stenoses of their vascular access outflow or inflow. Asympto matic vascular access pathology is common. High-risk asymptomatic popula tions may be detected by simple screening procedures.", "descriptor": "Postoperative Complications", "qualifier": "diagnostic imaging"}, {"mag_id": 2146286061, "corpus_id": 19929992, "title": "Women's views on reminder letters for screening mammography: Mixed methods study of women from 23 family health networks.", "abstract": "OBJECTIVE\nTo explore women's perspectives on the acceptability and content of reminder letters for screening mammography from their family physicians, as well as such letters' effect on screening intentions.\n\n\nDESIGN\nCross-sectional mailed survey followed by focus groups with a subgroup of respondents.\n\n\nSETTING\nOntario.\n\n\nPARTICIPANTS\nOne family physician was randomly selected from each of 23 family health networks and primary care networks participating in a demonstration project to increase the delivery of preventive services. From the practice roster of each physician, up to 35 randomly selected women aged 50 to 69 years who were due or overdue for screening mammograms and who had received reminder letters from their family physicians within the past 6 months were surveyed.\n\n\nMAIN OUTCOME MEASURES\nRecall of having received reminder letters and of their content, influence of the letters on decisions to have mammograms, and interest in receiving future reminder letters. Focus group interviews with survey respondents explored the survey findings in greater depth using a standardized interview guide.\n\n\nRESULTS\nThe response rate to the survey was 55.7% (384 of 689), and 45.1% (173 of 384) of responding women reported having mammograms in the past 6 months. Among women who recalled receiving letters and either making appointments for or having mammograms, 74.8% (122 of 163) indicated that the letters substantially influenced their decisions. Most respondents (77.1% [296 of 384]) indicated that they would like to continue to receive reminders, and 28.9% (111 of 384) indicated that they would like to receive additional information about mammograms. Participants in 2 focus groups (n = 3 and n = 5) indicated that they thought letters reflected a positive attitude of physicians toward mammography screening. They also commented that newly eligible women had different information needs than women who had had mammograms done in the past.\n\n\nCONCLUSION\nReminder letters were considered by participants to be useful and appeared to influence women's decisions to undergo mammography screening.", "descriptor": "Breast Neoplasms", "qualifier": "prevention & control"}, {"mag_id": 2912921771, "corpus_id": 73425157, "title": "Evaluation of the impact of waterpipe tobacco smoke exposure on the activity and expression of rat hepatic CYP450: a pharmacokinetic study", "abstract": "Abstract Waterpipe smoke contains many toxic constituents that can alter drug pharmacokinetics. This study assessed the effect of waterpipe smoke exposure on the activity and expression of CYP450 enzymes in rats. Animals (n\u2009=\u200910/group) were exposed to either waterpipe smoke or side-stream cigarette smoke for 1\u2009h/day (6 days/week) for 31 days, or fresh air (control). An intragastric cocktail solution containing three probe drugs, phenacetin, chlorzoxazone and testosterone was administered to assess the activity of CYP1A2, CYP2E1 and CYP3A, respectively. Serum concentrations were determined using LC-MS/MS and the pharmacokinetic parameters were calculated. The mRNA expression of hepatic enzymes was also quantified. Waterpipe and cigarette smoke exposure did not significantly alter the pharmacokinetics of phenacetin, chlorzoxazone and testosterone. For example, the clearance and drug exposure values were comparable among groups for all probe drugs. Additionally, there was no significant effect of waterpipe and cigarette smoke on mRNA expression of hepatic CYP1A2, CYP2E1 and CYP3A2. The results demonstrate that waterpipe smoke exposure had no effect on the functional expression of three key CYP450 isoforms in rats. Future research is required with longer exposure periods to waterpipe smoke. Such work serves to enhance current understanding of effect of waterpipe smoke exposure on pharmacokinetics.", "descriptor": "Liver", "qualifier": "enzymology"}, {"mag_id": 2172069758, "corpus_id": 15297964, "title": "Three-dimensional digital angiography: new tool for simultaneous three-dimensional rendering of vascular and osseous information during rotational angiography.", "abstract": "Three-dimensional (3D) digital subtraction angiography (DSA) is the latest development in the neurovascular imaging armamentarium. 3D-DSA combines the anatomic resolution of DSA with 3D visualization abilities previously offered by only CT or MR angiography. 3D-DSA provides more detailed information than does DSA alone in the evaluation of neurovascular lesions, such as cerebral aneurysms. However, the inability of 3D-DSA to simultaneously image osseous and vascular structures is noted as a weakness of this technique compared with CT angiography. We describe a new 3D digital angiography reconstruction algorithm that allows the concurrent display of the cerebral vasculature and the osseous landmarks.", "descriptor": "Brain", "qualifier": "blood supply"}, {"mag_id": 2118211999, "corpus_id": 29581192, "title": "Smoking and central blood pressure: a metabolic interaction?", "abstract": "S moking is a well-known major cardiovascular risk factor, which can also influence blood pressure and metabolic profile. In this issue of American Journal of Hypertension, Minami et al.1 investigated the relationship between smoking and blood pressure by evaluating the influence of smoking habits on brachial and central blood pressure and radial augmentation index, a marker of peripheral wave reflection, in a population of Japanese healthy men. Metabolic syndrome incidence according to smoking was also assessed. Augmentation index was found to be higher in current as compared to never smokers and also in current heavy as compared to former smokers. Central systolic blood pressure was lower in never smokers than other groups, while this behavior was less evident for brachial blood pressure. Smoking status was an independent predictor of augmentation index and central systolic blood pressure, but not of peripheral blood pressure. These results might suggest that smoking-associated alteration in wave reflection causes an increased central blood pressure. However, causality for this cannot be concluded upon the cross-sectional design of the study. Furthermore, this hypothesis cannot be completely supported because central arterial stiffness, the other major determinant of central systolic blood pressure,2 was not assessed in this study. Indeed, aortic pulse wave velocity rather than central blood pressure and augmentation index has been suggested to have independent predictive value for cardiovascular morbidity and mortality in high risk patients and in the general population.2 It should be also pointed out that differences in peripheral blood pressure varied in parallel with central hemodynamic parameters, although they did not reach statistical significance,1 possibly influencing the changes in central systolic blood pressure and augmentation index.2,3 Another important result of the study is that the prevalence of metabolic syndrome was found to be higher in smokers as compared to subject who never smoked.1 It is well known that heavy smokers have greater incidence of central obesity and lipid changes typical of insulin resistance.4 Augmentation index and central systolic blood pressure were also independently related to waist circumference or body mass index and high-density lipoprotein levels, which therefore can deeply contribute to the incidence of metabolic syndrome in smokers and/or to the effect of central blood pressure and wave reflection.1 Other risky behaviors, such physical activity inactivity or poor diet, which are associated with smoking4 and not investigated in the study, might also influence the findings. Finally, results are not representative of female gender. However, it has been showed that increased augmentation index is selectively impaired in female hypertensive patients in the presence of the metabolic syndrome.3 Despite these limitations, results of the study of Minami et al.1 are of importance for a possible additive pathogenetic mechanism to explain why metabolic syndrome is a major determinant of ischemic cardiovascular disease among middleaged Japanese men and women, in particular among smokers.5 Future intervention studies in large populations would confirm whether smoking cessation reduce cardiovascular risk by reducing central blood pressure, wave reflection, and metabolic syndrome prevalence.", "descriptor": "Hypertension", "qualifier": "etiology"}, {"mag_id": 2043834785, "corpus_id": 31369727, "title": "Nicotinic autoreceptor function in rat brain during maturation and aging: possible differential sensitivity to organophosphorus anticholinesterases.", "abstract": "Acetylcholine (ACh) release is modulated pre-synaptically by both muscarinic and nicotinic receptor-mediated processes. While muscarinic autoreceptors inhibit ACh release, nicotinic autoreceptors enhance ACh release and thus disruption of these processes could potentially affect cholinergic toxicity following exposure to anticholinesterases. Marked age-related differences in sensitivity to some organophosphorus (OP) anticholinesterases have been reported. We compared nicotinic autoreceptor function (NAF) during maturation and aging and evaluated its potential modulation by the common OP insecticide, chlorpyrifos (CPF). Cortical synaptosomes were pre-loaded with [3H]choline, superfused (0.6 ml/min) with physiological buffer and [3H]ACh release was evoked with potassium (KCl, 9 mM), with or without co-addition of exogenous ACh to stimulate nicotinic autoreceptors. Fractions of perfusate were subsequently collected and area under the curve (AUC) for [3H] was analyzed by scintillation counting. The difference in evoked release due to co-addition of exogenous ACh was defined as NAF. Under these conditions, atropine (ATR, 0.1 microM) appeared requisite for NAF; thus this muscarinic antagonist was subsequently added to all perfusion buffers. In synaptosomes from adult tissues, exogenous ACh (3-100 microM) significantly increased release in a concentration-dependent manner. The nicotinic antagonist mecamylamine (MEC, 100 microM) substantially reduced the potassium-evoked release elicited by co-addition of ACh (10 microM). Interestingly, the nicotinic agonists nicotine (NIC) and dimethylphenylpiperazinium (DMPP; 0.1-10 microM) had no effect on release. The active metabolite of CPF (i.e. chlorpyrifos oxon (CPO), 1-10 microM) inhibited NAF in vitro. Maturation-related expression of NAF was noted (AUC with co-addition of 10 microM ACh: 7-day rats, 7+/-6; 21-day rats, 44+/-6; 90-day rats, 196+/-37; 24-month rats, 173+/-52). NAF was substantially reduced (67-91%) 96 h after maximum tolerated dosages of CPF in adult and aged rats (279 mg/kg, sc) but not in juveniles (127 mg/kg, sc), even though AChE inhibition was similar among the age groups (>80%). Together these data suggest that NAF is differentially expressed during maturation and that this neuromodulatory process may be selectively altered by some OP insecticides, potentially contributing to age-related differences in response to AChE inhibitors. As NAF has been postulated to be activated under conditions of 'impaired' cholinergic function, selective alteration of this pre-synaptic process by OP anticholinesterases may be also important in age-related conditions associated with cholinergic hypofunction.", "descriptor": "Aging", "qualifier": "metabolism"}, {"mag_id": 2136260767, "corpus_id": 8491917, "title": "Performance of the Amplicor human immunodeficiency virus type 1 PCR and analysis of specimens with false-negative results", "abstract": "Over a 4-year period, the Roche Amplicor kit was used in a United Kingdom reference laboratory for the detection or confirmation of human immunodeficiency virus (HIV) type 1 infection, particularly in infants born to HIV-infected mothers. Of 408 specimens from adults and older children tested, the 122 seronegative specimens were all Amplicor negative. Of the 286 seropositive specimens, 268 were Amplicor positive. On the basis of these results, the Amplicor assay has a specificity of 100% and a sensitivity of 93.7%. In addition, for 247 specimens from infants and young children, serological results may not have been diagnostic because of placental transfer of maternal antibodies. Forty-eight were Amplicor positive, and of the 199 Amplicor-negative specimens, 19 were assumed to be false negative on the basis of clinical data, serological markers (including p24 antigen), and/or results for previous or follow-up specimens. This represents a sensitivity of 75% for the Amplicor test for specimens from patients under 2 years of age. Of these 37 false-negative specimens plus 2 specimens from other laboratories, 31 could be characterized by amplifying extracted material from them by an in-house nested gag PCR spanning the Amplicor target region. The amplicons were sequenced and found to represent subtypes A (35.5%), B (22.6%), C (22.6%), D (16.1%), and G (3.2%). False-negative results by the Amplicor assay may be ascribed to low-target copy number, the physical behavior of one primer (SK462), and sequence variation in the target region of the other primer (SK431).", "descriptor": "HIV Infections", "qualifier": "diagnosis"}, {"mag_id": 2741197011, "corpus_id": 3939900, "title": "Preoperative CT findings of subclinical hernia can predict for postoperative inguinal hernia following robot-assisted laparoscopic radical prostatectomy", "abstract": "PurposeTo evaluate preoperative CT features that predict the development of postoperative inguinal hernia after robot-assisted laparoscopic radical prostatectomy (RALRP).MethodsWe enrolled 160 men who underwent CT, subsequent RALRP, and at least three years of follow-up. CT was retrospectively reviewed in consensus by two radiologists for the presence of asymmetric spermatic cord fat and scrotal fluid collection. The diagnostic power of each CT feature for the development of postoperative inguinal hernia was calculated. Multiple logistic regression was performed to evaluate the association between CT features, clinical variables, and postoperative inguinal hernia.ResultsSurgically confirmed postoperative inguinal hernia developed in 17 patients. Asymmetric spermatic cord fat was demonstrated in 13 patients, and scrotal fluid collection was seen in 59 patients. The diagnostic values of asymmetric spermatic cord fat and scrotal fluid collection for postoperative inguinal hernia were 58.8% and 88.2% sensitivity, 97.9% and 69.2% specificity, 76.9% and 25.4% positive predictive value, 95.2% and 98.0% negative predictive value, and 93.8% and 71.3% accuracy, respectively. On multiple logistic regression analysis, asymmetric spermatic cord fat, scrotal fluid collection, and low BMI were significant predictive factors for the development of postoperative inguinal hernia (odds ratios: 135.8, 31.6, and 0.7, respectively).ConclusionThe presence of asymmetric spermatic cord fat or scrotal fluid collection was significantly associated with the development of postoperative inguinal hernia.", "descriptor": "Postoperative Complications", "qualifier": "diagnostic imaging"}, {"mag_id": 2419465597, "corpus_id": 8909666, "title": "Association of psychosis and movement disorders in the elderly.", "abstract": "There are a number of different relationships among aging, psychosis and movement disorders, most of which have been proposed to involve the neurotransmitter dopamine. Dopamine content and dopamine receptors have been shown to decrease with age, which may relate to the time of onset of different motor and psychotic disorders, as well as to the appearance of these disorders. For example, some so-called senile movement disorders, such as senile tremor and senile chorea, may relate to alterations in dopaminergic transmission with age, as might the general findings of increased slowing of movements and mildly increased rigidity with age, although it is not clear how common some of these changes are in the medically healthy elderly. Decrease in dopamine with age may also be associated with the findings that choreiform and psychotic disorders (which have been proposed to be related to excess dopaminergic activity) tend to predominate at younger ages, whereas parkinsonism is more common at later ages. Certain findings support this notion, such as the appearance of both dyskinesia and psychosis in patients treated with L-dopa, the finding that psychosis may be less common in patients with later-onset Huntington's disease, and the fact that neuroleptic-induced parkinsonism is often more severe in the elderly. However, the situation is more complicated than this, because there are a number of phenomena that do not fit the pattern, including the observation of an increased incidence of tardive dyskinesia in the elderly. Age-related changes in other transmitters are undoubtedly important in both movements disorders and psychosis, and even dopamine has been proposed to have both trophic and toxic properties over the aging process. In general, care is warranted in the use of any psychotropic medications in the elderly, because there can be widespread and often unpredictable effects of these drugs on both motor and mental function.", "descriptor": "Aging", "qualifier": "physiology"}, {"mag_id": 1968399151, "corpus_id": 39745930, "title": "Efficacy and tolerability of lovastatin in hypercholesterolemia in patients with systemic hypertension.", "abstract": "A previously published study reported on an open-label, multicenter study of the efficacy and tolerability of lovastatin in the management of nonfamilial primary hypercholesterolemia. In the present report the results from the 213 hypercholesterolemic patients with systemic hypertension are presented. At baseline mean +/- SD of total serum cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, and the ratio of total serum cholesterol to HDL cholesterol were 268 +/- 24, 189 +/- 22 and 43 +/- 10 mg/dl and 6.6 +/- 1.6, respectively. Of the 213 hypertensive patients only 24 were not receiving antihypertensive or related cardiac medication. Baseline mean systolic and diastolic blood pressures were 140 +/- 20 and 84 +/- 9 mm Hg, respectively. Within 1 month of lovastatin therapy the observed significant reductions in total serum cholesterol, low-density lipoprotein cholesterol and the ratio of total to HDL cholesterol were 19, 27 and 24%, respectively. HDL cholesterol was increased by 6%. Diastolic blood pressure did not change significantly during this 1-month period. The 1-month lipid results were maintained over the full 6 months of the study. The dosage of lovastatin was 20 mg/day for the first month of therapy and could subsequently be adjusted to response, up to a maximum of 80 mg/day. Again, without changes in diastolic blood pressure, lovastatin was generally effective in improving the serum lipids of hypercholesterolemic hypertensive patients regardless of the type of antihypertensive medications received (including diuretics and beta blockers). Lovastatin was generally well tolerated.", "descriptor": "Hypertension", "qualifier": "complications"}, {"mag_id": 2131679191, "corpus_id": 42319377, "title": "Nursing interventions in inpatient psychiatry.", "abstract": "The successful application of the Nursing Interventions Classification (NIC) in inpatient psychiatry depends on whether the classification adequately describes nursing care in this setting. The present study aimed to identify nursing interventions mentioned in journal articles on psychiatric inpatient nursing care and to compare these with the labels, definitions and activities described in the NIC to elucidate how well the classification covers these interventions. The MedLine, PsychInfo, Cochrane and CINAHL databases were searched for journal articles about nursing care in the adult inpatient setting. A qualitative content analysis approach was used to indentify nursing interventions in the articles. About 84% of the statements (terms and definitions) are encompassed by the interventions listed by the NIC. Very few interventions need to be added to the NIC classification or necessitate a reorganization of the taxonomy. Nevertheless, the further development of the NIC will promote its use in the daily work of psychiatric nurses and enhance the quality of nursing care in the inpatient setting.", "descriptor": "Mental Disorders", "qualifier": "nursing"}, {"mag_id": 2106787867, "corpus_id": 39974335, "title": "Effects of aerosol ipratropium bromide on cardiac vagal tone.", "abstract": "Thirty-one adult asthmatic subjects, aged 18 to 40 years, were administered both ipratropium bromide and placebo, in two sessions, held at least 2 days apart, in balanced order. Pulmonary function, heart period (milliseconds between heart beats), and respiratory sinus arrhythmia (a measure of cardiac vagal tone) were assessed before drug administration and 45 min thereafter. Ipratropium bromide had no significant effect on cardiac vagal tone, while it did produce improvement in pulmonary function.", "descriptor": "Asthma", "qualifier": "physiopathology"}, {"mag_id": 2129536258, "corpus_id": 10660906, "title": "Diabetic versus non-diabetic colour vision after cataract surgery", "abstract": "AIMS To examine whether the colour vision abnormalities found in phakic patients with diabetes mellitus is preserved after removal of the lens by cataract surgery. METHODS 21 diabetic (16 IDDM and five NIDDM) and 19 non-diabetic patients of comparable age, postoperative visual acuity, and sex distribution, all aphakic or pseudophakic following cataract surgery, had their monocular colour vision examined using the Farnsworth-Munsell 100 hue test. The fundus status of the diabetic patients ranged from no retinopathy to photocoagulation treated proliferative diabetic retinopathy. Patients with macular oedema were specifically excluded from the study. RESULTS The error scores of both the diabetic (mean 146 (SD 94)) and the non-diabetic patients (83 (79)) did not deviate significantly from the age related normal range. The error score in the diabetic group was significantly higher than in the non-diabetic group (p=0.02) but the amplitude of the difference was small in comparison with previous studies of phakic subjects. The error scores in the diabetic group were not correlated with the degree of retinopathy (p>0.2). CONCLUSION After cataract surgery only a minor difference exists between the colour vision scores of diabetic and non-diabetic patients. This indicates that accelerated yellowing of the lens in diabetes is the predominant cause of the colour vision anomaly found in phakic diabetic patients.", "descriptor": "Diabetes Mellitus, Type 2", "qualifier": "complications"}, {"mag_id": 1984268193, "corpus_id": 31708201, "title": "Identification of cancer genes by mutational profiling of tumor genomes", "abstract": "It is now widely accepted that cancer is a genetic disease and that alterations in the DNA sequence underlie the development of every neoplasm. The identification of mutated genes that are causally implicated in oncogenesis (\u2018cancer genes\u2019) has been a major goal in medical sciences for the last two decades. The availability of the human genome sequence coupled to the introduction of high throughput sequencing technologies has created an unprecedented opportunity in this field. It is now possible to perform mutational studies of entire cancer genomes thus providing a complete description of mutations underlying human oncogenesis. The recent identification of high frequency mutations in the BRAF and PI3K genes suggests that many more cancer genes remain to be discovered. In this review, we consider how the systematic mutational analysis of gene families in individual neoplasms has led to the identification of a number of cancer genes and how this information is influencing the treatment of cancer.", "descriptor": "Neoplasms", "qualifier": "genetics"}, {"mag_id": 2979831816, "corpus_id": 203926771, "title": "Long-Term Patterns of Oral Anticancer Agent Adoption, Duration, and Switching in Patients With CML.", "abstract": "BACKGROUND\nOral tyrosine kinase inhibitors (TKIs) have been the standard of care for chronic myeloid leukemia (CML) since 2001. However, few studies have evaluated changes in the treatment landscape of CML over time. This study assessed the long-term treatment patterns of oral anticancer therapies among patients with CML.\n\n\nMETHODS\nThis retrospective cohort study included patients newly diagnosed with CML between January 1, 2000, and December 31, 2016, from 10 integrated healthcare systems. The proportion of patients treated with 5 FDA-approved oral TKI agents-bosutinib, dasatinib, imatinib, nilotinib, and ponatinib-in the 12 months after diagnosis were measured, overall and by year, between 2000 and 2017. We assessed the use of each oral agent through the fourth-line setting. Multivariable logistic regression estimated the odds of receiving any oral agent, adjusting for sociodemographic and clinical characteristics.\n\n\nRESULTS\nAmong 853 patients with CML, 81% received an oral agent between 2000 and 2017. Use of non-oral therapies decreased from 100% in 2000 to 5% in 2005, coinciding with imatinib uptake from 65% in 2001 to 98% in 2005. Approximately 28% of patients switched to a second-line agent, 9% switched to a third-line agent, and 2% switched to a fourth-line agent. Adjusted analysis showed that age at diagnosis, year of diagnosis, and comorbidity burden were statistically significantly associated with odds of receiving an oral agent.\n\n\nCONCLUSIONS\nA dramatic shift was seen in CML treatments away from traditional, nonoral chemotherapy toward use of novel oral TKIs between 2000 and 2017. As the costs of oral anticancer agents reach new highs, studies assessing the long-term health and financial outcomes among patients with CML are warranted.", "descriptor": "Antineoplastic Agents", "qualifier": "therapeutic use"}, {"mag_id": 2803746504, "corpus_id": 21731582, "title": "Endoscopic mucosa-sparing lateral dissection for treatment of gastric submucosal tumors: a prospective cohort study.", "abstract": "BACKGROUND\nIn our previous work, we developed a modified method for the removal of gastric submucosal tumors (SMTs), called endoscopic mucosa-sparing lateral dissection (EMSLD). This prospective study aimed to evaluate the efficacy and postoperative outcomes of EMSLD.\n\n\nMETHODS\nWe prospectively enrolled 25 consecutive patients with gastric SMTs, who received EMSLD treatment. Clinicopathological characteristics and operation-related outcomes were analyzed.\n\n\nRESULTS\nThe mean age of patients was 49.3\u200a\u00b1\u200a9.7 years, and the mean tumor size was 14.6\u200a\u00b1\u200a6.1\u200amm. En bloc resection was achieved in all cases. The mean procedure time was 47.3 \u00b1 25.9 minutes, and the estimated blood loss was 4.8\u200a\u00b1\u200a3.5\u200amL. Endoscopic full-thickness resection was performed in six patients (24\u200a%) because the tumors originated from the deep muscularis propria layer. All perforations and resection defects were successfully closed by the retained mucosa and endoclips. No serious complications related to EMSLD were encountered during or after the procedure.\n\n\nCONCLUSIONS\nEMSLD was reliable and effective for the removal of gastric SMTs. However, large-scale randomized controlled trials are needed.", "descriptor": "Postoperative Complications", "qualifier": "epidemiology"}, {"mag_id": 1969492598, "corpus_id": 31522622, "title": "Clinical Applications of VEGF\u2010Trap (Aflibercept) in Cancer Treatment", "abstract": "&NA; Angiogenesis is one of the key acquired characteristics or \u201challmarks\u201d essential for the growth and development of all solid tumor types. The antiangiogenic agent vascular endothelial growth factor\u2010Trap (VEGF\u2010Trap) (aflibercept), which is a composite decoy receptor based on VEGF receptor\u20101 and VEGF receptor\u20102 fused to an Fc segment of immunoglobulin G1 that binds specifically to VEGF, has demonstrated preclinical efficacy in a range of different tumor types. VEGF\u2010Trap exerts its antiangiogenic effects through regression of tumor vasculature, remolding or normalization of surviving vascu\u2010lature, and inhibition of new tumor vessel growth. Preclinical and clinical studies have reported that VEGF\u2010Trap can be combined effectively with both chemotherapy and radiotherapy. This review examines the main effects of VEGF\u2010Trap on tumor vasculature and on different types of solid tumors, and explores the preclinical and clinical benefits of incorporating VEGF\u2010Trap into anticancer treatment strategies.", "descriptor": "Neoplasms", "qualifier": "drug therapy"}, {"mag_id": 2123426734, "corpus_id": 205426736, "title": "Growth differences between North American and European children at risk for type 1 diabetes", "abstract": "To evaluate the relationships between early growth and regional variations in type 1 diabetes (T1D) incidence in an international cohort of children with familial and genetic risk for T1D.", "descriptor": "Obesity", "qualifier": "epidemiology"}, {"mag_id": 2395266652, "corpus_id": 10233553, "title": "[Treatment with nutrition and fluids in patients with non-curable cancer].", "abstract": "Patients with non-curable cancer represent a large and heterogeneous group in which malnutrition and weight loss is a frequent finding. This article is based on relevant literature and our own clinical experience. For every patient a thorough examination of possible underlying causes should be explored and corrected as soon as possible (secondary cachexia). However, in many patients primary cachexia is the cause, a catabolic condition where muscle protein and lipids are degraded and even aggressive nutrition will not reverse the process. This condition is very different from starvation. Metoclopramide, corticosteroids and gestagens can relieve symptoms as anorexia, chronic nausea and asthenia which frequently occur in patients with cachexia. Treatments that may maintain or increase muscle function and modulate inflammatory processes are new approaches, such as eicosapentaneoic acid, adenosine triphosphate, specific amino acids and nonsteroidal antiinflammatory drugs. Nutrition is an integrated part of supportive therapy to all cancer patients, unless expected survival is short. At this time in life, nutrition will not influence survival and focus should be on symptom control.", "descriptor": "Neoplasms", "qualifier": "therapy"}, {"mag_id": 2900130789, "corpus_id": 53248080, "title": "\"As Long as You Ask\": A Qualitative Study of Biobanking Consent-Oncology Patients' and Health Care Professionals' Attitudes, Motivations, and Experiences-the B-PPAE Study.", "abstract": "INTRODUCTION\nConsent to biobanking remains controversial, with little empirical data to guide policy and practice. This study aimed to explore the attitudes, motivations, and concerns of both oncology patients and health care professionals (HCPs) regarding biobanking.\n\n\nMATERIALS AND METHODS\nQualitative interviews were conducted with oncology patients and HCPs purposively selected from five Australian hospitals. Patients were invited to give biobanking consent as part of a clinical trial and/or for future research were eligible. HCPs were eligible if involved in consenting patients to biobanking or to donate specimens to clinical trials.\n\n\nRESULTS\nTwenty-two patients participated, with head and neck (36%) and prostate (18%) the most common cancer diagnoses; all had consented to biobanking. Twenty-two HCPs participated, from across eight cancer streams and five disciplines. Themes identified were (a) biobanking is a \"no brainer\"; (b) altruism or scientific enquiry; (c) trust in clinicians, science, and institutions; (d) no consent-just do it; (e) respecting patient choice (\"opt-out\"); (f) respectful timing of the request; (g) need for emotional/family support; (h) context of the biobanking request matters; and (i) factors for biobanking success.\n\n\nDISCUSSION\nThese findings reinforced previous findings regarding high public trust in, and support for, biobanking. An initial opt-in consent approach with the option of later opt-out was favored by patients to respect and recognize donor generosity, whereas HCPs preferred an upfront opt-out model. Factors impacting biobanking success included the context of the request for use in a trial or specific research question, pre-existing patient and HCP rapport, a local institution champion, and infrastructure.\n\n\nIMPLICATIONS FOR PRACTICE\nPatients and health care professionals (HCPs) who experienced cancer biobanking consent were overwhelmingly supportive of biobanking. The motivations and approaches to seeking consent were largely mirrored between the groups. The findings of this study support the opt-in model of biobanking favored by patients; however, HCPs preferred an opt-out model. Both groups recognize the importance of making the request for biobanking at an appropriate time, preferably with emotional or family support, and respecting the timing of the request and privacy of the patient. Biobanking success can be promoted by hospital departments with a research focus by identifying an institutional biobanking champion and ensuring local infrastructure is available.", "descriptor": "Neoplasms", "qualifier": "pathology"}, {"mag_id": 2149053200, "corpus_id": 21228890, "title": "Diagnostic Pregnancy Tests in Patients Treated with Tranquillizers", "abstract": "may result from or be the cause of amenorrhoea, and in either case may lead to severe anxiety or more serious psychological illness. D-lusions of pregnancy, with or without signs of pseudopregnancy, are not uncommon, and are a further source of confusion. Diagnosis of pi egnancy may be impossible by physical examination alone for the first few weeks after conception, and speed may be important if serious psychiatric breakdown is to be prevented or therapeutic abortion contemplated. In these cases, therefore, reliance may be placed upon laboratory pregnancy tests. In the past these depended upon the detection of increased chorionic gonadotrophic activity in urine", "descriptor": "Mental Disorders", "qualifier": "drug therapy"}, {"mag_id": 2061087806, "corpus_id": 28109541, "title": "Suppression of asthma, weight gain, and linear growth in children receiving fluprednisolone.", "abstract": "Abstract Fluprednisolone has been employed in the treatment of 45 children with bronchial asthma. Adequate control of asthma was attained in each child. The dose required varied considerably but was, in general, approximately one twentieth that of cortisone, one fourth that of prednisone, and one third that of methylprednisolone. Prominent side effects of prolonged treatment included suppression of rate of both weight gain and linear growth. Retardation of rate of weight gain has not been commonly observed in children receiving prednisone, methylprednisolone, and cortisone and may represent a unique and sometimes useful effect of fluprednisolone.", "descriptor": "Asthma", "qualifier": "therapy"}, {"mag_id": 2792250728, "corpus_id": 3957220, "title": "High-grade atrioventricular block in patients with acute myocardial infarction. Insights from a contemporary multi-center survey.", "abstract": "High-grade atrioventricular block (HAVB) is a frequent complication of acute myocardial infarction (AMI) and is associated with increased morbidity and mortality. We aimed to evaluate the incidence, predictors, and prognostic significance of HAVB in a contemporary cohort of patients with AMI, in the recent era of early reperfusion. Patients with acute coronary syndromes (n=11,487) during the years 2000-2010 were included. Patients were divided into two groups: with HAVB (n=308, 2.7%) and without HAVB (n=11,179, 97.3%). The incidence of HAVB decreased from 4.2% in 2000 to 2.1% in 2010 (p for trend<0.01). Patients with HAVB were more likely to develop in-hospital complications. Independent predictors of developing HAVB were older age, ST-elevation myocardial infarction (STEMI), smoking and Killip class\u22652 on admission. 30-day and 1-year mortality rates were significantly higher in the HAVB as compared to the non-HAVB group (24% vs. 4.9%, p<0.01, 33.5% vs. 10%, p<0.01, respectively). Multivariable logistic regression analysis revealed that, HAVB was associated with increased 30-day (OR - 3.97; 95% CI - 1.96-8.04) and 1-year mortality risk (HR - 2.02; 95% CI - 1.3-3.1). Similar estimates were obtained for STEMI and non-STEMI (NSTEMI). In conclusion, although the incidence of HAVB decreased over the last decade, the associated morbidity and mortality are still high in these patients despite early reperfusion therapy.", "descriptor": "Myocardial Infarction", "qualifier": "complications"}, {"mag_id": 1986200628, "corpus_id": 30023620, "title": "The effect of quinolinic acid on the content and distribution of hepatic metabolites.", "abstract": "Abstract The effect of quinolinic acid treatment on the hepatic metabolite profile and the flux of glucose through the alternative pathways of metabolism have been measured, and the distribution of metabolites between the cytosolic and mitochondrial compartments has been calculated. Marked increases of the total-cell polycarboxylic anions were found and these were, in order of magnitude: malate, citrate, isocitrate, aspartate, 2-oxoglutarate, and glutamate. Calculation of the compartmented values suggested that the major increase was in the mitochondrial compartment: cytosolic glutamate, 2-oxoglutarate, and oxaloacetate were decreased and only aspartate increased in this compartment. The changes of the mitochondrial/cytosolic anion ratio was most marked, 60-fold, in the case of 2-oxoglutarate. It is suggested that inhibition of transport of 2-oxoglutarate by quinolinic acid could, by blocking the operation of the aspartate shuttle, contribute to the inhibition of gluconeogenesis from lactate. Metabolite and flux data suggest an increase in the rate of lipogenesis in quinolinic acid-treated rats with the decrease of long-chain acyl CoAs, caused by this treatment, being the possible effector for this activation.", "descriptor": "Liver", "qualifier": "metabolism"}, {"mag_id": 2078004733, "corpus_id": 37008626, "title": "GABA and Bicuculline\u2010Induced Blood Pressure Changes in Spontaneously Hypertensive Rats", "abstract": "The brain GAB Aergic system was previously shown to influence blood pressure (BP) maintenance in rats which may in part be accomplished by disruption of the central renin-angiotensin system (RAS). We examined the potential role of GABA in sustaining the high BP exhibited by the spontaneously hypertensive rat (SHR) model of human essential hypertension. Intracerebroven-tricular (i.e.v.) infusion of GABA produced decreases in BP in members of three rat strains, including Wistar-Kyoto (WKY) and Sprague-Dawley normotensive controls and SHR. The SHR were significantly more sensitive to GABA than the normotensive strains. Next, the GABA receptor antagonist bicuculline (BMI) was infused i.e.v. and produced increases in BP in members of each strain. Finally, i.e.v. pretreatment with the specific angiotensin receptor antagonist [Sar1, Thr8]AII (sarthran), blocked subsequent GABA-induced decreases in BP in members of all three strains, and there was a trend toward sarthran attenuation of BMI-induced increases in BP. These results encourage the hypothesis that the hypotensive effects produced by central application of GABA are mediated by the brain angiotensin system.", "descriptor": "Hypertension", "qualifier": "drug therapy"}, {"mag_id": 1992934413, "corpus_id": 15482212, "title": "Diet quality, physical activity, body weight and health-related quality of life among grade 5 students in Canada", "abstract": "Abstract Objective To assess how diet quality, physical activity and body weight are related to health-related quality of life (HRQOL) among children in the Canadian province of Alberta. Design In 2008, we surveyed 3421 grade 5 students and their parents from 148 randomly selected schools. Students completed the Harvard Food Frequency Questionnaire, questions on physical activities, and had their height and weight measured. The HRQOL of the students was assessed using the EQ-5D-Y. Parents completed questions on socio-economic background and children's lifestyle. We applied multilevel regression methods to examine the importance of children's diet quality, physical activity and weight status for the EQ-5D-Y Visual Analogue Scale and for the EQ-5D-Y dimensions. Setting The province of Alberta, Canada. Subjects Grade 5 students. Results Students with better diet quality, higher physical activity levels and normal body weights were statistically significantly more likely to report better HRQOL than students who ate less healthily, were less active or were overweight or obese. Conclusions The importance of diet quality, physical activity and body weight status for HRQOL may help justify broader implementation of school health programmes that promote healthy eating and active living, as these programmes will help reduce the burden of childhood obesity and improve quality of life.", "descriptor": "Obesity", "qualifier": "epidemiology"}, {"mag_id": 2236011748, "corpus_id": 6258618, "title": "Training of Attentional Filtering, but Not of Memory Storage, Enhances Working Memory Efficiency by Strengthening the Neuronal Gatekeeper Network", "abstract": "Memory training (MT) in older adults with memory deficits often leads to frustration and, therefore, is usually not recommended. Here, we pursued an alternative approach and looked for transfer effects of 1-week attentional filter training (FT) on working memory performance and its neuronal correlates in young healthy humans. The FT effects were compared with pure MT, which lacked the necessity to filter out irrelevant information. Before and after training, all participants performed an fMRI experiment that included a combined task in which stimuli had to be both filtered based on color and stored in memory. We found that training induced processing changes by biasing either filtering or storage. FT induced larger transfer effects on the untrained cognitive function than MT. FT increased neuronal activity in frontal parts of the neuronal gatekeeper network, which is proposed to hinder irrelevant information from being unnecessarily stored in memory. MT decreased neuronal activity in the BG part of the gatekeeper network but enhanced activity in the parietal storage node. We take these findings as evidence that FT renders working memory more efficient by strengthening the BG\u2013prefrontal gatekeeper network. MT, on the other hand, simply stimulates storage of any kind of information. These findings illustrate a tight connection between working memory and attention, and they may open up new avenues for ameliorating memory deficits in patients with cognitive impairments.", "descriptor": "Brain", "qualifier": "diagnostic imaging"}, {"mag_id": 1524235451, "corpus_id": 45013496, "title": "Characterization of cDNA and genomic sequences corresponding to an embryonic myosin heavy chain.", "abstract": "We report here the isolation and characterization of cDNA and genomic sequences corresponding to a rat embryonic myosin heavy chain (MHC) protein. This gene, which is present as a single copy in the rat genome, comprises about 25 kilobase pairs of DNA and contains approximately 80% intronic sequences. The embryonic MHC gene belongs to a highly conserved multigene family, and exhibits a high degree of nucleotide and amino acid sequence conservation with other sarcomeric MHC genes from nematode to man. S1 nuclease mapping experiments using cDNA and genomic probes show that this MHC gene is transiently expressed during skeletal muscle development. Its mRNA is detected in fetal skeletal muscle during early development and persists up to 2 weeks after birth with the overlapping expression of neonatal and adult skeletal MHC mRNAs. However, this MHC is not expressed in the adult skeletal muscle with the exception of extraocular muscle fibers. The transient expression during muscle development of the isoform produced by this gene and its sequential replacement by other MHCs raises interesting questions about the mechanism controlling MHC isozyme transitions and the physiological significance of the individual MHCs in muscle fibers.", "descriptor": "DNA", "qualifier": "analysis"}, {"mag_id": 2909502867, "corpus_id": 73463130, "title": "Repositioning of fluoroquinolones from antibiotic to anti-cancer agents: An underestimated truth.", "abstract": "Increasing development costs and higher failure rate in clinical trials has reduced the repertoire of newer drugs in the market for clinical use. The most appropriate approach to end the search for newer drugs is \"Repositioning\", as it requires less time and money to explore new indication of existing drug or failed drug. In the past, several drugs have been repositioned for different indication but the full potential remains unharnessed. With rise in cancer prevalence and treatment costs, it is imperative to search for newer drugs and the use of repositioning approach may help us. Fluoroquinolones has been used as antibiotics for over four decades now, but recent research highlighted their use as pharmacological compounds with multifaceted implication. Repositioning of fluoroquinolones into anti-cancer molecule seems to be a highly plausible option owing to their profound immunomodulatory, pro-apoptotic, anti-proliferative and anti-metastatic potential. The present review provides a comprehensive account of the recent and past explorations pertaining to the anti-cancer activity of fluoroquinolones and also discusses the various approaches that are being considered to remodel them for the treatment of cancer.", "descriptor": "Neoplasms", "qualifier": "drug therapy"}, {"mag_id": 20005317, "corpus_id": 40116446, "title": "Lung cancer in developed and developing countries.", "abstract": "After the first five years of life, cancer, cardiovascular diseases, and accidents are the three main causes of death in both developed and developing countries [1], Developing countries account for approximately 2.3 million of the global 4.3 million cancer deaths and for 3.2 million of the 6.3 million new cancer cases worldwide each year [2,3]. Thus, in absolute figures, the majority of the world\u2019s cancer patients are in the developing countries.", "descriptor": "Lung Neoplasms", "qualifier": "epidemiology"}, {"mag_id": 2429974847, "corpus_id": 77408500, "title": "[Infective endocarditis of staphylococcal etiology: clinical process and antibacterial therapy].", "abstract": ": Characteristics of the clinical process of staphylococcal endocarditis in 115 inpatients and the adequacy of various regimens for their antibiotic therapy within a period of 10 years were analysed. Four clinical criteria for prognosis of staphylococcal endocarditis were determined: intravenous narcomania, splenomegalia, leukocytosis and hemorrhagic skin eruption. The analysis of the Russian and foreign findings showed that the use of betalactams (oxacillin, the 1st and 3rd generation cephalosporins) and lincomycin provided the adequate therapy resulting in eradication of the pathogen in case of oxacillin resistant staphylococci, whereas the use of ciprofloxacin and vancomycin was inexpedient. In case of MRSA it was recommended to use vancomycin and in case of endocarditis due to S. aureus with intermediate resistance to vancomycin (VISA, MIC > 0.5 mcg/ml) the use of linezolid was recommended.", "descriptor": "Anti-Bacterial Agents", "qualifier": "administration & dosage"}, {"mag_id": 2113344792, "corpus_id": 7372220, "title": "Nutritional issues in palliative care.", "abstract": "OBJECTIVES\nTo present current information on nutritional problems and management during the palliative care period.\n\n\nDATA SOURCES\nResearch and review articles from three computerized databases, the table of contents of an on-line nursing journal, and pursuit of pertinent references in articles reviewed.\n\n\nCONCLUSIONS\nControversies continue on the most appropriate management of intake in the palliative care period from both physical and ethical perspectives.\n\n\nIMPLICATIONS FOR NURSING PRACTICE\nUntil the literature is conclusive on the amount and type of suffering incurred by patients who are ceasing intake, nurses will need to stay current with the research literature and approach each case individually in determining appropriate care.", "descriptor": "Neoplasms", "qualifier": "nursing"}, {"mag_id": 2735907094, "corpus_id": 3927356, "title": "The essential role of exercise in the management of type 2 diabetes", "abstract": "Exercise is typically one of the first management strategies advised for patients newly diagnosed with type 2 diabetes. Together with diet and behavior modification, exercise is an essential component of all diabetes and obesity prevention and lifestyle intervention programs. Exercise training, whether aerobic or resistance training or a combination, facilitates improved glucose regulation. High-intensity interval training is also effective and has the added benefit of being very time-efficient. While the efficacy, scalability, and affordability of exercise for the prevention and management of type 2 diabetes are well established, sustainability of exercise recommendations for patients remains elusive.", "descriptor": "Diabetes Mellitus, Type 2", "qualifier": "therapy"}, {"mag_id": 2087411348, "corpus_id": 24330823, "title": "Aldosterone nuclear receptors in kidneys of chick embryo.", "abstract": "We have studied the properties of the nuclear receptors for aldosterone in kidneys of chick embryo. Aliquots of 0.4 M KCl nuclear extracts were incubated with [3H]aldosterone with or without 1 microM RU28362, a potent glucocorticoid analog. Scatchard analyses of binding data revealed two classes of binding sites with Ka of 0.26 and 0.03 X 10(9) M-1 and Nmax of 330 fmol and 620 fmol/mg DNA respectively. In presence of RU28362, however, we observed only a single class of binding sites with a Ka of 1.02 X 10(8) M-1 and a Nmax of 90 fmol/mg DNA. Competition studies performed in presence of RU28362 showed that aldosterone was the more effective competitor followed by corticosterone, progesterone, deoxycorticosterone, dexamethasone, cortisol, triamcinolone acetonide and cortisone. The nuclear complexes had a sedimentation coefficient in the area of 8 S which changed to 4-5 S in the presence of 0.4 M KCl. This effect of KCl was prevented by the addition of 10 mM sodium molybdate. Always in the presence of the glucocorticoid analog, by DEAE-c chromatography we observed a major specific aldosterone-binding fraction which was eluted with 0.2 M KCl. This fraction sedimented at 8.4 S in the absence of sodium molybdate and KCl. In the absence of RU28362, DNA-c columns retained only a small portion of the nuclear complexes which were eluted with KCl. These complexes sedimented, on sucrose gradient, at 4.6 and 3.1 S, whereas those which did not bind to DNA-c had a sedimentation coefficient of 8 S. In the presence of RU28362, the majority of bound [3H]aldosterone remained in the column flow-through fraction; when this fraction was further analyzed on DEAE-c, complexes were eluted with 0.2 and 0.3 M KCl. These data indicate that nuclear receptors for aldosterone are present in small number in kidneys of chick embryo and that they are mostly in the 8 S form.", "descriptor": "Kidney", "qualifier": "metabolism"}, {"mag_id": 2171826505, "corpus_id": 42063778, "title": "Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease.", "abstract": "Angiogenin, a potent inducer of neovascularization, is the only angiogenic molecule known to exhibit ribonucleolytic activity. Its overall structure, as determined at 2.4 A, is similar to that of pancreatic ribonuclease A, but it differs markedly in several distinct areas, particularly the ribonucleolytic active center and the putative receptor binding site, both of which are critically involved in biological function. Most strikingly, the site that is spatially analogous to that for pyrimidine binding in ribonuclease A differs significantly in conformation and is \"obstructed\" by glutamine-117. Movement of this and adjacent residues may be required for substrate binding to angiogenin and, hence, constitute a key part of its mechanism of action.", "descriptor": "Proteins", "qualifier": "ultrastructure"}, {"mag_id": 2083093728, "corpus_id": 35534226, "title": "Fractionation of polypeptides and proteins on dextran gels.", "abstract": "Abstract A bed of particulate dextran gel (Sephadex) acts as a molecular sieve thus permitting rapid removal of salts, amino acids and other compounds of low molecular weight from protein solutions. By use of dextran gels of different degrees of cross-linkage in consecutive operations, very efficient purifications of peptides of intermediate size can also be achieved. Even proteins are sometimes retarded on dextran gel and may thus be considerably purified.", "descriptor": "Proteins", "qualifier": "chemistry"}, {"mag_id": 1980008462, "corpus_id": 42453696, "title": "Total synthesis of (-)-laulimalide.", "abstract": "(-)-Laulimalide (1), a structurally novel macrolide isolated in trace amounts from marine sponges, promotes abnormal tubulin polymerization and apoptosis in vitro, with a similar mode of action to that of Taxol(R), but with potentially less susceptibility to multidrug resistance. Herein, a flexible and convergent asymmetric synthesis of (-)-laulimalide is described. This synthesis featured a highly diastereoselective Sakurai reaction of 2 with 3 and a regioselective macrolactonization of an unprotected vicinal diol. Laulimalide was synthesized in 25 steps (longest linear; 36 overall) in 3.5% overall yield, providing a uniquely short and efficient route to 1 and its analogues.", "descriptor": "Antineoplastic Agents", "qualifier": "chemical synthesis"}, {"mag_id": 2593920623, "corpus_id": 3814086, "title": "Multiregional dissemination of KPC-producing Klebsiella pneumoniae ST258/ST512 genotypes in Poland, 2010\u201314", "abstract": "Objectives\nIn 2008-09, the KPC carbapenemase epidemiology in Poland was dominated by a Klebsiella pneumoniae ST258 KPC-2 outbreak in Warsaw and its administrative region. The aim of this study was to analyse the situation in 2010-14, with a focus on new outbreaks in other parts of the country.\n\n\nMethods\nKPCs were detected in all suspected isolates by PCR. The detailed study was performed on 173 isolates from 2010 to 2012, and included PFGE and MLST, PCR identification of K. pneumoniae clonal group CG258 clades and potential specificity markers ( pilv-1 , IS 66 and prp ), PCR mapping of Tn 4401 transposons, and plasmid analysis by nuclease S1 profiling and PCR-based replicon typing.\n\n\nResults\nSix hundred and eight KPC cases were identified in Poland in 2010-14, almost half of which occurred in the Warsaw region, and another half in four other areas. The new outbreaks were caused by four K. pneumoniae CG258 genotypes, different from each other and from the organisms spreading in Warsaw. The new lineages were ST258 or ST512 of clade II, and had specific compositions of potential ST258/ST512 clonal markers. The isolates produced KPC-3 encoded by Tn 4401 a or Tn 4401 b elements on plasmids with single or multiple replicons, including I2, FII K (+/-FIB K ), 'FII Y -like', X3 and R. Of other species, Citrobacter freundii ST17 and Enterobacter cloacae ST254 with KPC-2 were identified in a Warsaw hospital.\n\n\nConclusions\nThe study showed remarkable changes in the KPC epidemiology in Poland in 2010-14, which, following the localized regional spread in the early phase, has converted into multiregional dissemination.", "descriptor": "Bacterial Proteins", "qualifier": "biosynthesis"}, {"mag_id": 2401264283, "corpus_id": 20212257, "title": "Assessment of the inhalation technique in asthmatic patients: a comparative study of three aerosol devices.", "abstract": "Local administration of drugs by means of aerosol device is widely used in the treatment of asthma. Nevertheless, the effectiveness of this method depends on an adequate inhalation technique (IT), which available evidence has shown to be rather problematic. The aim of this study was to assess IT in out-patients with bronchial asthma who frequently use aerosol therapy with Pressurized Metered dose inhalers (MDI), pressurized inhalers with spacer (MDI-S) and the Astra-Draco Turbuhaler system (TH). A sample of 150 adults with asthma were evaluated. These patients had been followed up for than two years and they often used one of the devices mentioned above. The IT has broken down into several steps for each procedure. Percentages of patients with one error in the IT were 50%, 44% and 42% for MDI, MDI-S and TH procedures, respectively. 18%, 20% and 14% of patients committed three errors in the IT, respectively. Differences detected were not significant. Seven patients committed errors in every step of the IT. In conclusion, the level of errors found in our study is high, similar to that cited in the existing literature. It is also roughly equivalent for the three devices tested. We believe that the proper teaching monitoring of IT skills is highly important in the treatment of bronchial asthma.", "descriptor": "Asthma", "qualifier": "drug therapy"}, {"mag_id": 2152346792, "corpus_id": 17171258, "title": "Calibrated functional MRI: mapping the dynamics of oxidative metabolism.", "abstract": "MRI was extended to the measurement of changes in oxidative metabolism in the normal human during functionally induced changes in cellular activity. A noninvasive MRI method that is model-independent calibrates the blood oxygen level dependent (BOLD) signal of functional MRI (fMRI) against perfusion-sensitive MRI, using carbon dioxide breathing as a physiological reference standard. This calibration procedure provides a regional measurement of the expected sensitivity of the fMRI BOLD signal to changes in the cellular activity of the brain. Maps of the BOLD signal calibration factor showed regional heterogeneity, indicating that the magnitude of functionally induced changes in the BOLD signal will be dependent on both the local change in blood flow and the local baseline physiology of the cerebral cortex. BOLD signal magnitude is shown to be reduced by 32% from its expected level by the action of oxygen metabolism. The calibrated fMRI technique was applied to stimulation of the human visual cortex with an alternating radial checkerboard pattern. With this stimulus oxygen consumption increased 16% whereas blood flow increased 45%. Although this result is consistent with previous findings of a significant difference between the increase in blood flow and oxygen consumption, it does indicate clearly that oxidative metabolism is a significant component of the metabolic response of the brain to functionally induced changes in cellular activity.", "descriptor": "Brain", "qualifier": "physiology"}, {"mag_id": 1987304112, "corpus_id": 26816499, "title": "Optimizing the initial 12-lead electrocardiographic diagnosis of acute myocardial infarction.", "abstract": "AIMS\nThe optimum definition of ST elevation for diagnosis of acute myocardial infarction, with respect to both the minimum height and the minimum numbers of leads, is unknown. Furthermore, only 50% of patients with acute myocardial infarction present with ST elevation. We thus quantified the sensitivity and specificity of different ST elevation criteria for diagnosis of acute myocardial infarction, and determined whether models incorporating multiple QRST features in addition to ST elevation, could improve detection of acute myocardial infarction.\n\n\nMETHODS AND RESULTS\nThe study population comprised 1190 subjects: 1041 consecutive patients presenting with chest pain (335 with acute myocardial infarction) and 149 controls without chest pain. Subjects were randomly divided into a training set (587) and a validation set (603). ECG prediction models for acute myocardial infarction incorporating different ST elevation criteria and/or additional QRST features (Q waves, ST depression, T wave inversion, bundle branch block, axes deviations, and left ventricular hypertrophy) were developed in training set patients using forward stepwise multiple logistic regression. Models were then prospectively tested in the validation set patients. The optimum ST elevation model (based on > or =1 mm ST elevation in > or = 1 inferior/lateral leads, or > or =2 mm ST elevation in > or =1 anteroseptal leads) correctly classified 83.1% of subjects (55.8% sensitivity, 94. 0% specificity). The choice of ST elevation definition had marked influence on the sensitivity (45.4-68.6%) and specificity (81.2-98. 1%) for diagnosis of acute myocardial infarction. The addition of multiple QRST variables only marginally improved overall classification but did result in high specificity (92.6-96.1%).\n\n\nCONCLUSION\nDifferent definitions of 'significant' ST elevation led to marked variations in sensitivity and specificity for diagnosis of acute myocardial infarction. Multiple QRST features in addition to ST elevation only marginally improved overall classification.", "descriptor": "Myocardial Infarction", "qualifier": "diagnosis"}, {"mag_id": 2345347808, "corpus_id": 732322, "title": "Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals", "abstract": "Despite recent breakthroughs in identifying mucosal-associated invariant T (MAIT) cell antigens (Ags), the precise requirements for in vivo MAIT cell responses to infection remain unclear. Using major histocompatibility complex\u2013related protein 1 (MR1) tetramers, the MAIT cell response was investigated in a model of bacterial lung infection employing riboflavin gene-competent and -deficient bacteria. MAIT cells were rapidly enriched in the lungs of C57BL/6 mice infected with Salmonella Typhimurium, comprising up to 50% of \u03b1\u03b2-T cells after 1 week. MAIT cell accumulation was MR1-dependent, required Ag derived from the microbial riboflavin synthesis pathway, and did not occur in response to synthetic Ag, unless accompanied by a Toll-like receptor agonist or by co-infection with riboflavin pathway-deficient S. Typhimurium. The MAIT cell response was associated with their long-term accumulation in the lungs, draining lymph nodes and spleen. Lung MAIT cells from infected mice displayed an activated/memory phenotype, and most expressed the transcription factor retinoic acid\u2013related orphan receptor \u03b3t. T-bet expression increased following infection. The majority produced interleukin-17 while smaller subsets produced interferon-\u03b3 or tumor necrosis factor, detected directly ex vivo. Thus the activation and expansion of MAIT cells coupled with their pro-inflammatory cytokine production occurred in response to Ags derived from microbial riboflavin synthesis and was augmented by co-stimulatory signals.", "descriptor": "Lung", "qualifier": "immunology"}, {"mag_id": 3000562087, "corpus_id": 210922741, "title": "NiO nanocomposites/rGO as a heterogeneous catalyst for imidazole scaffolds with applications in inhibiting the DNA binding activity.", "abstract": "Herein, we report a facile approach to synthesize a new highly versatile heterogeneous catalyst by spontaneous aerial oxidation based on nickel oxide nanocomposites immobilized on surface-functionalized reduced graphene oxide sheets. NiO nanocomposite/reduced graphene oxide (rGO-NiO-NC) is a highly efficient, cost-effective, reusable, selective, and eco-friendly nano-catalyst that does not lose any activity even after five reaction cycles. Nickel loading on the rGO-NiO nanocomposite was found to be 3.3 at%, which contributes to the effective and efficient use of rGO-NiO-NCs as a nano-catalyst for the synthesis of imidazole derivatives. Consequently, a series of imidazole derivatives were synthesized, catalyzed by rGO-NiO-NCs, in 60 min with high yields (86% to 96%) under green conditions. Furthermore, the present synthetic methodology was used for the synthesis of highly aromatic imidazole derivatives (B1-B3) whose calf thymus-DNA binding affinities suggest their superior inhibition ability to displace ethidium bromide (EB), which was further confirmed by molecular docking studies. Additionally, the green chemistry matrix of the synthesis reaction was found to be very close to ideal values, such as carbon efficiency (82.32%), E-factor (0.51), atom economy (77.86%), process mass intensity (1.51), and reaction mass efficiency (66.14%).", "descriptor": "DNA", "qualifier": "chemistry"}, {"mag_id": 2344683958, "corpus_id": 36988832, "title": "Thrombotic thrombocytopenic purpura: MR findings.", "abstract": "Neurologic manifestations occur in over 90% of patients with thrombotic thrombocytopenic purpura. Neuropathologically, thrombi produce occlusion of terminal arterioles and capillaries resulting in diffuse small infarcts. In the great majority of surviving patients, brain CT does not disclose any abnormalities. The authors report a case of thrombotic thrombocytopenic purpura in which brain MR examination showed multiple punctate lesions in the white matter.", "descriptor": "Brain", "qualifier": "pathology"}, {"mag_id": 1592810995, "corpus_id": 23463268, "title": "Influence of high\u2010grade prostatic intra\u2010epithelial neoplasia on total and percentage free serum prostatic specific antigen", "abstract": "\u2002To analyse the influence of high\u2010grade prostatic intra\u2010epithelial neoplasia (HGPIN) on total and percentage free serum prostatic specific antigen (PSA).", "descriptor": "Prostatic Neoplasms", "qualifier": "diagnosis"}, {"mag_id": 2774552053, "corpus_id": 3830139, "title": "[Experience with third, fourth and fifth kidney transplants and their complications.]", "abstract": "OBJECTIVES\nKidney transplant may be a good choice to treat chronic renal failure even in patients with two or more previous renal grafts. However, there might be several surgical complications and other difficulties we have to deal with. The aim of this report is to analyze the third, fourth and fifth transplants performed in our center focusing on the surgical complications and graft and patient survivals.\n\n\nMETHODS\nWe performed a retrospective analysis of the 73 third, fourth and fifth kidney transplants performed in our center between February 1975 and December 2015. Statistical analysis has been performed with IBM SPSS 23.0 software.\n\n\nRESULTS\n62 patients received a third graft, 10 received a fourth one and one patient received a fifth graft. The median age of the recipients was 48 years, while for donors it was 50. Median cold ischemia time was 21 hours. Transplantectomy was not necessary in 49.31% of the cases. In 59.7% of the cases the graft vessels were anastomosed to the external iliac vessels. There were 21 cases of relevant postoperative complications (27.4% of the total grafts). Vascular thrombosis appeared in 5.5%. After 49 months of follow-up, the 1-, 3-, and 5-year graft survival were 64.3%, 56.16% and 50.69%, respectively.\n\n\nCONCLUSIONS\nA new renal transplant in patients with two or more previous grafts is feasible, being necessary to individualize the cases. In spite of being more complex operations than previous transplants with a higher complication rate, we can obtain both acceptable graft and patient survival outcomes with an appropriate approach.", "descriptor": "Postoperative Complications", "qualifier": "epidemiology"}, {"mag_id": 2091205767, "corpus_id": 1260483, "title": "Scorpion (Odontobuthus doriae) venom induces apoptosis and inhibits DNA synthesis in human neuroblastoma cells", "abstract": "Scorpion and its organs have been used to cure epilepsy, rheumatism, and male impotency since medieval times. Scorpion venom which contains different compounds like enzyme and non-enzyme proteins, ions, free amino acids, and other organic inorganic substances have been reported to posses antiproliferative, cytotoxic, apoptogenic, and immunosuppressive properties. We for the first time report the apoptotic and antiproliferative effects of scorpion venom (Odontobuthus doriae) in human neuroblastoma cells. After exposure of cells to medium containing varying concentrations of venom (10, 25, 50, 100, and 200\u00a0\u03bcg/ml), cell viability decreased to 90.75, 75.53, 55.52, 37.85, and 14.30%, respectively, after 24\u00a0h. Cells expressed morphological changes like swelling, inhibition of neurite outgrowth, irregular shape, aggregation, rupture of membrane, and release of cytosolic contents after treatment with venom. Lactate dehydrogenase (LDH) level increased in 50 and 100\u00a0\u03bcg/ml as compared to control, but there was no significant increase in LDH level at a dose of 10 and 20\u00a0\u03bcg/ml. Two concentrations viz. 50 and 100\u00a0\u03bcg/ml were selected because of the profound effect of these concentrations on the cellular health and population. Treatment with these two concentrations induced reactive nitrogen intermediates and depolarization in mitochondria. While caspase-3 activity increased in a concentration-dependent manner, only 50\u00a0\u03bcg/ml was able to fragment DNA. It was interesting to note that at higher dose, i.e., 100\u00a0\u03bcg/ml, the cells were killed, supposedly by acute necrosis. DNA synthesis evidenced by bromodeoxyuridine (BrdU) incorporation was inhibited in a concentration-dependent manner. The cells without treatment incorporated BrdU with high affinity confirming their cancerous nature whereas very less incorporation was noticed in treated cells. Our results show apoptotic and antiproliferative potential of scorpion venom (O. doriae) in human neuroblastoma cells. These properties make scorpion venom a valuable therapeutic agent in cancer research.", "descriptor": "Antineoplastic Agents", "qualifier": "pharmacology"}, {"mag_id": 1978159040, "corpus_id": 22987676, "title": "Evaluation of cationic liposomes for delivery of diphtheria toxin A-chain gene to cells infected with bovine leukemia virus.", "abstract": "We investigated whether cationic liposomes are efficient at delivering the gene for diphtheria toxin A-chain (DT-A) under the control of the long terminal repeat (LTR) of bovine leukemia virus (BLV) (pLTR-DT) into BLV-infected cells and are also suitable for in vivo use. The transfection activity of the cationic liposomes composed of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride (TMAG), dioleoyl phosphatidylethanolamine (DOPE) and dilauroyl phosphatidylcholine (DLPC) (1:2:2, molar ratio) (TMAG-liposome) and liposomes composed of phosphatidylserine (PS) (PS-liposome) was evaluated by the luciferase assay using a plasmid which contains the coding sequence of firefly luciferase under the control of the SR alpha promoter (pSR alpha/L-A delta 5). The TMAG-liposome gave highly efficient transfection in the presence of serum. On the other hand, PS-liposome showed inferior efficiency. When BLV-infected cells were co-transfected with a fixed amount of pSR alpha/L-A delta 5-entrapped TMAG-liposome and various amount of pLTR-DT-containing TMAG-liposome, the luciferase activity in the BLV-infected cells was inhibited by the addition of pLTR-DT-entrapped TMAG-liposome dose-dependently. The cationic TMAG-liposome containing pLTR-DT was successively added to BLV-infected cells in culture. The number of viable cells was markedly reduced by the cationic TMAG-liposome containing pLTR-DT. On the other hand, TMAG-liposome containing pSR alpha/L-A delta 5 showed no such effect. pLTR-DT entrapped by the cationic TMAG-liposome was not digested by the treatment with DNase I and with serum. These results suggest that the cationic liposomes, such as TMAG-liposome, may be efficient transfection reagent for the BLV-infected cells and can be utilized for DT-A gene delivery into the BLV-infected cells in vivo.", "descriptor": "Kidney", "qualifier": "virology"}, {"mag_id": 2134172788, "corpus_id": 205093366, "title": "Bardoxolone methyl and kidney function in CKD with type 2 diabetes.", "abstract": "BACKGROUND\nChronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined.\n\n\nMETHODS\nIn this phase 2, double-blind, randomized, placebo-controlled trial, we assigned 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m(2) of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the estimated GFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks.\n\n\nRESULTS\nPatients receiving bardoxolone methyl had significant increases in the mean (\u00b1SD) estimated GFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m(2) of 8.2\u00b11.5 ml in the 25-mg group, 11.4\u00b11.5 ml in the 75-mg group, and 10.4\u00b11.5 ml in the 150-mg group; P<0.001). The increases were maintained through week 52, with significant differences per minute per 1.73 m(2) of 5.8\u00b11.8 ml, 10.5\u00b11.8 ml, and 9.3\u00b11.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl.\n\n\nCONCLUSIONS\nBardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone methyl may have promise for the treatment of CKD. (Funded by Reata Pharmaceuticals; BEAM ClinicalTrials.gov number, NCT00811889.).", "descriptor": "Diabetes Mellitus, Type 2", "qualifier": "physiopathology"}]
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