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Synthesis, Antibacterial and Thermal Studies of Cellulose Nanocrystal Stabilized ZnO-Ag Heterostructure Nanoparticles

Synthesis of ZnO-Ag heterostructure nanoparticles was carried out by a precipitation method with cellulose nanocrystals (CNCs) as a stabilizer for antimicrobial and thermal studies. ZnO-Ag nanoparticles were obtained from various weight percentages of added AgNO3 relative to Zn precursors for evaluating the best composition with enhanced functional properties. The ZnO-Ag/CNCs samples were characterized systematically by TEM, XRD, UV, TGA and DTG. From the TEM studies we observed that ZnO-Ag heterostructure nanoparticles have spherical shapes with size diameters in a 9–35 nm range. The antibacterial activities of samples were assessed against the bacterial species Salmonella choleraesuis and Staphylococcus aureus. The CNCs-stabilized ZnO-Ag exhibited greater bactericidal activity compared to cellulose-free ZnO-Ag heterostructure nanoparticles of the same particle size. The incorporation of ZnO-Ag hetreostructure nanoparticles significantly increased the thermal stability of cellulose nanocrystals.

Anti-Bacterial Agents

chemistry

23606890

No circadian rhythms of serotoninergic, alpha-, beta-adrenergic and imipramine binding sites in rat brain regions.

Bmax values of the specific binding of [3H]-WB 4101, [3H]-dihydroalprenolol, [3H]-spiperone and [3H]-imipramine to various rat brain regions were determined at 4 hr intervals over 24 hr under circadian conditions. No significant circadian rhythm of binding sites number was found for any receptor investigated in cerebral cortex, hypothalamus or brain stem. Some methodological issues are discussed.

Brain

metabolism

38463625

The role of 5-HT in postoperative nausea and vomiting.

In this review it has been speculated that PONV is induced by the anaesthetic and by the trauma and perturbations associated with surgery. Indeed, it is unlikely that PONV is caused by any one pathophysiological input, but is multifactorial in origin. These perturbations may be peripheral, central, or both, and involve direct effects on the vomiting system together with afferent inputs in the vagal, splanchnic and trigeminal nerves. A proposed scheme summarizing these inputs is given in figure 1. The precise mechanisms through which 5-HT and 5-HT3 receptors contribute to the control of PONV is unknown, but their involvement is demonstrated by the antiemetic effect of ondansetron.

Postoperative Complications

prevention & control

58539480

Patient perception of automated whole‐breast ultrasound

Automated breast ultrasound is an emerging breast imaging modality which has recently been shown to be a promising aid in the detection of early invasive cancers in women with dense breasts. Given the lack of ionizing radiation, improved detection of small clinically significant invasive breast cancers, and low cost of the imaging modality, automated whole‐breast ultrasound (ABUS) exams are useful in supplemental screening of women with dense breasts, especially women at intermediate risk for breast cancer (NCI lifetime risk of 15%‐19.9%) with dense breasts. There is increasing awareness of breast density due to breast density legislation passed in many states and subsequent requirement of inclusion of the patient's breast density into their mammography results letter. The implementation of automated breast ultrasound as a supplemental breast cancer screening tool for women with dense breasts is expected to increase, considering this modality is known to detect clinically relevant invasive cancers that are mammographically occult in women with dense breasts. Studies are currently lacking as to how patients perceive ABUS. There have also been no studies evaluating the initial levels of anxiety of women presenting for ABUS or whether automated breast ultrasound helps relieve anxiety regarding breast cancer detection. This survey evaluated our patient population to determine which method of communication they prefer regarding breast health education (ie, websites, email, printed pamphlets, face‐to‐face discussion, social media). This research contributes to shared decision making between a patient and their referring health care provider when discussing possible supplemental screening exams for breast cancer. Since automated breast ultrasound is a fairly new modality at our institution, most women in our screening population were experiencing this exam for the first time during this pilot study. We hoped to identify areas of patient misconception so that we could better inform patients and set expectations to make the exam more comfortable and relieve patient anxiety. This HIPAA compliant, IRB approved voluntary survey was completed by 82 women ages 35‐74 years who had been identified as having heterogeneously dense or extremely dense breast tissue presenting for Automated Breast Ultrasound (ABUS). The purpose of the study was to evaluate their level of knowledge and perceptions regarding ABUS before and after undergoing their ABUS exam. Patients were invited to participate in a voluntary 28 question two‐ part survey by the ABUS sonography technologist before and after undergoing their ABUS during the time period of September 1, 2015 through June 1, 2017. Using a test‐feedback method, we measured patient acceptance of this new technology, their expectations of the imaging exam, and gauged future compliance with this supplemental screening exam. A total of 82 patients were invited and also completed both parts of the two‐part voluntary survey; however, certain patients declined to completely answer all of the voluntary questions within the survey. All 82 patients reported their experience with their baseline ABUS exam, with the majority of patients (68 of 82, 82%) reporting their experience as positive. Only two patients (2%) reported a negative experience, and 12 patients (15%) remained neutral toward ABUS. Levels of anxiety about ABUS in patients

Breast Neoplasms

diagnostic imaging

19641488

Rv2477c is an antibiotic-sensitive manganese-dependent ABC-F ATPase in Mycobacterium tuberculosis.

The Rv2477c protein of Mycobacterium tuberculosis (Mtb) belongs to the ATP-binding cassette (ABC) subfamily F that contains proteins with tandem nucleotide-binding domains but lacking transmembrane domains. ABC-F subfamily proteins have been implicated in diverse cellular processes such as translation, antibiotic resistance, cell growth and nutrient sensing. In order to investigate the biochemical characteristics of Rv2477c, we expressed it in Escherichia coli, purified it and characterized its enzymatic functions. We show that Rv2477c displays strong ATPase activity (Vmax = 45.5 nmol/mg/min; Km = 90.5 μM) that is sensitive to orthovanadate. The ATPase activity was maximal in the presence of Mn2+ at pH 5.2. The Rv2477c protein was also able to hydrolyze GTP, TTP and CTP but at lower rates. Glutamate to glutamine substitutions at amino acid residues 185 and 468 in the two Walker B motifs of Rv2477c severely inhibited its ATPase activity. The antibiotics tetracycline and erythromycin, which target protein translation, were able to inhibit the ATPase activity of Rv2477c. We postulate that Rv2477c could be involved in mycobacterial protein translation and in resistance to tetracyclines and macrolides. This is the first report of the biochemical characterization of an ABC-F subfamily protein in Mtb.

Bacterial Proteins

metabolism

4406916

Calcium transient alternans in blood-perfused ischemic hearts: observations with fluorescent indicator Fura Red.

Ischemia produces striking electrophysiological abnormalities in blood-perfused hearts that may be caused, in part, by effects of ischemia on intracellular calcium. To test this hypothesis, intracellular Ca2+ concentration ([Ca2+]i) transients were recorded from the epicardial surface of blood- and saline-perfused rabbit hearts using the long-wavelength indicator Fura Red. Calcium transients were much larger than the movement artifact, representing up to 29% of the total signal. Switching the perfusate from saline to blood did not affect the time course of the transients or the apparent level of [Ca2+]i. Compartmentation of Fura Red fluorescence was estimated by exposure to Mn2+. The results were cytosol 60 ± 3%, organelles 12 ± 2%, and autofluorescence plus partly deesterified Fura Red 29 ± 4%. [Ca2+]itransients were calibrated in situ by perfusion of the extracellular space with high-Ca2+ and Ca2+-free EGTA solutions. Peak systolic [Ca2+]iwas 663 ± 74 nM, and end-diastolic [Ca2+]iwas 279 ± 59 nm. Ischemia was produced by interruption of aortic perfusion for 2.5 min during pacing (150 beats/min). Ischemia produced broadening of the [Ca2+]itransient, along with beat-to-beat alternations in the peak systolic and end-diastolic level of [Ca2+]i(calcium transient alternans). [Ca2+]itransient alternans occurred in 82% of blood-perfused hearts vs. 43% of saline-perfused hearts. The discrepancy between large and small transients (mean alternans ratio) was larger in the blood-perfused hearts (0.23 ± 0.04 vs. 0.07 ± 0.03, P = 0.005). These observations are important because of the apparent relationship of [Ca2+]itransient alternans to electrical alternans and arrhythmias during ischemia.

Calcium

metabolism

16660561

Cognitive regulation of food craving: Effects of three cognitive reappraisal strategies on neural response to palatable foods

Objective:Obese versus lean individuals show greater reward region and reduced inhibitory region responsivity to food images, which predict future weight gain. Thinking of the costs of eating palatable foods and craving suppression have been found to modulate this neural responsivity, but these cognitive reappraisal studies have primarily involved lean participants. Herein we evaluated the efficacy of a broader range of reappraisal strategies in modulating neural responsivity to palatable food images among individuals who ranged from lean to obese and tested whether body mass index (BMI) moderates the effects of these strategies.Materials and methods:Functional magnetic resonance imaging assessed the effects of three cognitive reappraisal strategies in response to palatable food images versus an imagined intake comparison condition in a sample of adolescents (N=21; M age=15.2).Results:Thinking of the long-term costs of eating the food, thinking of the long-term benefits of not eating the food and attempting to suppress cravings for the food increased activation in inhibitory regions (for example, superior frontal gyrus, ventrolateral prefrontal cortex) and reduced activation in attention-related regions (for example, precuneus and posterior cingulate cortex). The reappraisal strategy focusing on the long-term benefits of not eating the food more effectively increased inhibitory region activity and reduced attention region activity compared with the other two cognitive reappraisal strategies. BMI did not moderate the effects.Discussion:These novel results imply that cognitive reappraisal strategies, in particular those focusing on the benefits of not eating the food, could potentially increase the ability to inhibit appetitive motivation and reduce unhealthy food intake in overweight individuals.

Obesity

psychology

796098

The interaction between the maternal BMI and angiogenic gene polymorphisms associates with the risk of spontaneous preterm birth.

Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.

Obesity

genetics

7095944

[Identification of residual antibiotics in the tissues of slaughter animals using electrophoresis bioautography].

An electrophoretic identification chart of the antibiotics penicillin, streptomycin, neomycin, erythromycin, tylosin and tetracyclines was made. Minimum inhibiting concentrations of the above antibiotics were determined for the bacterial tester-strains Bacillus subtilis BGA, Micrococcus luteus ATCC 9341 and Bacillus stearothermophillus v. calidolactis C 953. The obtained results were applied to identify residues of antibacterial substances in the tissues of slaughter animals, milk and other samples, as a follow-up of detection microbiological methods of plate agar diffusion.

Anti-Bacterial Agents

analysis

45777138

Ventricular Enlargement in Poor-Outcome Schizophrenia

BACKGROUND A subset of patients with schizophrenia, defined on the basis of longitudinal deficits in self-care, may show a classic ("Kraepelinian") degenerative course. An independent validator of the phenomenologically defined Kraepelinian subtype might be provided by a structural indicator of possible brain degeneration: ventricular size as measured by computed tomography (CT). METHODS To examine whether Kraepelinian patients would show a differential increase in ventricular size over time, two CT scans were conducted at intervals separated by > 4 years, an average of 5 years. Fifty-three male patients with DSM-III-R diagnoses of chronic schizophrenia were subdivided into Kraepelinian (n = 22; mean age = 42 +/- 6 years) and non-Kraepelinian (n = 31; mean age = 38 +/- 12.2 years) subgroups. Kraepelinian patients were defined on the basis of longitudinal criteria: > 5 years of complete dependence on others for life necessities and care, lack of employment, and sustained symptomatology. Thirteen normal elderly volunteers (mean age = 60 +/- 17.8) were also scanned at 4-year intervals. CT measurements were made by raters without knowledge of subgroup membership. A semiautomated computer program was used to trace the anterior horn, lateral ventricles, and temporal horns for each slice level on which they were clearly seen. RESULTS The ventricles showed a bilateral increase in size over the 4-year interval in the Kraepelinian subgroup, more marked in the left hemisphere than the right. By contrast, neither the non-Kraepelinian subgroup nor the normal volunteers showed significant CT changes from scan 1 to scan 2. CONCLUSIONS Thus, the longitudinal dysfunctions in self-care that characterize the Kraepelinian patients were associated with an independent indicator of brain abnormality.

Brain

pathology

8190405

Does Idiopathic Cough Exist?

Despite a meticulous protocol involving diagnostic testing and trials of empirical therapy, there may be no obvious cause for a chronic cough in up to 42% of cases referred for specialist evaluation. In some cases, failure to consider causes that include the asthma/eosinophilic airway syndromes such as eosinophilic bronchitis and atopic cough, or nonacid gastroesophageal reflux disease may explain diagnostic failure. However, a distinct group of patients may be considered to have true idiopathic cough. Current published evidence suggests a certain patient phenotype, namely, middle-aged females with prolonged nonproductive cough and cough reflex hypersensitivity. Almost nothing else is known about this clinical entity and currently no specific therapy exists.

Asthma

complications

24822674

Presence of human papillomavirus sequences in tumour-derived human oral keratinocytes expressing mutant p53.

A series of eight oral epithelial cell lines derived from untreated human oral squamous cell carcinomas, which had arisen in patients with different tobacco histories, were examined for the presence of human papillomavirus (HPV) DNA, expression of stable p53 protein and p53 point mutation. Polymerase chain reaction (PCR)-based screening, but not Southern blot analysis, showed HPV-16 early region sequences to be present at low copy number (< 1 copy per cell) in two cell lines at early passage (3-5) in vitro (H400, T45), implying that only subpopulations of cells harboured viral DNA. HPV sequences were undetectable in cells at later passage (12-15), suggesting that viral sequences had been lost during growth in vitro, or that negative selection of HPV-containing cells had occurred. High levels of p53 were detected in the two HPV-positive cell lines and in three others (H103, H314, H357) by Western blotting, suggesting expression of mutant (stable) p53 molecules. A sixth cell line (H157) expressed a truncated p53. Sequence analysis of exons 2-11 of the p53 gene revealed missense mutations in six cell lines, one of which (H413) did not result in high levels of protein, and nonsense mutations in the remaining two cell lines (H157, H376). The results suggest that p53 mutation is a frequent genetic event in oral cancer. In addition, the expression of mutant p53 in oral cancer cells does not preclude a papillomaviral aetiology for these tumours. Analysis of p53 expression alone may result in underestimation of the frequency of p53 mutations in human cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Squamous Cell

genetics

73455162

Comparison of intestinal ischemia after on-pump versus off-pump coronary artery bypass grafting surgery

Background/aim Acute mesenteric ischemia (AMI), one of the gastrointestinal system complications, which occurs following cardiac surgery, is challenged in the literature with a diminished incidence of AMI by heart surgery without cardiopulmonary bypass (CPB) or with pulsatile CPB. This study aims to compare the incidence and mortality rate of mesenteric ischemia in a series of consecutive patients undergoing coronary artery bypass grafting (CABG) through on-pump and off-pump techniques. Materials and methods This study included patients who underwent CABG between 1 January 2010 and 31 June 2016. All patients were divided into two groups: Group 1 comprised 6396 CABG patients operated on with the off-pump technique. Group 2 included 1210 patients who received CABG with the on-pump technique. Preoperative data were collected on the studied variables. Postoperative data included the development of intestinal ischemia and in-hospital mortality. Results Of 7606 consecutive CABG patients, a total of 31 (0.4%) developed intestinal ischemia. The incidence of postoperative mesenteric ischemia was 0.28% in Group 1 and 1.07% in Group 2 (P = 0.000). The survival rates after AMI were 61.1% in Group 1 (off-pump) and 7.7% in Group 2 (on-pump) (P = 0.003). Time from the first occurrence of nonspecific GI complaints to laparotomy was similar in the off-pump and on-pump groups and had no effect on mortality.Conclusions: With regard to the incidence of mesenteric ischemia and survival after laparotomy, off-pump CABG patients revealed significant improvement compared with those operated on with the on-pump technique.

Postoperative Complications

epidemiology

3964685

Scoulerine affects microtubule structure, inhibits proliferation, arrests cell cycle and thus culminates in the apoptotic death of cancer cells

Scoulerine is an isoquinoline alkaloid, which indicated promising suppression of cancer cells growth. However, the mode of action (MOA) remained unclear. Cytotoxic and antiproliferative properties were determined in this study. Scoulerine reduces the mitochondrial dehydrogenases activity of the evaluated leukemic cells with IC50 values ranging from 2.7 to 6.5 µM. The xCELLigence system revealed that scoulerine exerted potent antiproliferative activity in lung, ovarian and breast carcinoma cell lines. Jurkat and MOLT-4 leukemic cells treated with scoulerine were decreased in proliferation and viability. Scoulerine acted to inhibit proliferation through inducing G2 or M-phase cell cycle arrest, which correlates well with the observed breakdown of the microtubule network, increased Chk1 Ser345, Chk2 Thr68 and mitotic H3 Ser10 phosphorylation. Scoulerine was able to activate apoptosis, as determined by p53 upregulation, increase caspase activity, Annexin V and TUNEL labeling. Results highlight the potent antiproliferative and proapoptotic function of scoulerine in cancer cells caused by its ability to interfere with the microtubule elements of the cytoskeleton, checkpoint kinase signaling and p53 proteins. This is the first study of the mechanism of scoulerine at cellular and molecular level. Scoulerine is a potent antimitotic compound and that it merits further investigation as an anticancer drug.

Antineoplastic Agents

pharmacology

29666589

Ceftriaxone-induced pseudolithiasis in children treated for perforated appendicitis

PurposeCeftriaxone has been associated with development of pseudolithiasis. In our institution, it is used for treatment of perforated appendicitis in children. This study evaluated the occurrence of ceftriaxone-related pseudolithiasis in this population.MethodsAfter obtaining IRB approval, we performed a retrospective chart review over 51 months. We included patients undergoing laparoscopic appendectomy for perforated appendicitis. All patients were treated with ceftriaxone post-operatively. Patients without initial or post-treatment gallbladder imaging available for review were excluded.ResultsThere were 71 patients who met inclusion criteria with a mean (±SD) age of 10.8 ± 3.8 years. Of these, 14 % (n = 10) developed stones or sludge in the gallbladder. The mean duration of ceftriaxone therapy was 8.7 ± 3.8 days. The average time to post-antibiotic imaging was 11.5 ± 10.3 days from initiation of antibiotics. There was no significant difference in duration of ceftriaxone therapy in the children that developed pseudolithiasis or sludge (10.0 ± 4.9 days) compared to those that did not (8.5 ± 3.6, p = 0.26). One child (10 %) with pseudolithiasis went on to become symptomatic, requiring a laparoscopic cholecystectomy.ConclusionsIn our experience, ceftriaxone use for perforated appendicitis is associated with a significant incidence of biliary pseudolithiasis, and is unrelated to duration of ceftriaxone therapy.

Anti-Bacterial Agents

adverse effects

24781773

Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women.

BACKGROUND Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk. Whether mammographic density reflects levels of endogenous sex hormones is unclear. We examined whether these predictors are independently associated with breast cancer risk in a prospective study. METHODS We conducted a nested case-control study within the Nurses' Health Study cohort of 253 case subjects with breast cancer and 520 control subjects. All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography. Plasma levels of estradiol, free estradiol, testosterone, and free testosterone were evaluated. Mammographic density was assessed by use of computer-assisted analysis of mammograms. Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk. The relative risk of breast cancer associated with mammographic density (RR for highest quartile compared with lowest quartile = 3.8, 95% CI = 2.2 to 6.6; P(trend)<.001) changed little when the analysis was adjusted for circulating estradiol (RR = 3.9, 95% CI = 2.2 to 6.9; P(trend)<.001) or circulating testosterone (RR = 4.1, 95% CI = 2.3 to 7.2; P(trend)<.001). Circulating levels of estradiol (RR = 2.4, 95% CI = 1.4 to 4.0) and of testosterone (RR = 2.0, 95% CI = 1.2 to 3.1) were both associated with breast cancer risk, before and after adjustment for mammographic density. In a joint analysis of mammographic density and plasma testosterone, the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both (RR = 6.0, 95% CI = 2.6 to 14.0). A similar pattern was observed in the joint analysis of estradiol and mammographic density (RR = 4.1, 95% CI = 1.7 to 9.8). CONCLUSIONS Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women.

Breast Neoplasms

epidemiology

39929774

Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.

Diabetes Mellitus, Type 2

drug therapy

23129961

Chronic exposure of cultured transformed mouse epidermal cells to transforming growth factor-beta 1 induces an epithelial-mesenchymal transdifferentiation and a spindle tumoral phenotype.

Transformed mouse epidermal keratinocytes of the cell line PDV, when cultured under the presence of transforming growth factor-beta 1 (TGF-beta 1), escaped the block of growth exerted by this factor in normal keratinocytes and underwent marked changes in cell differentiation. TGF-beta 1 induced disruption of epithelial interactions, dispersion of cells, increased local movement, and conversion to a fibroblast-like morphology. These changes were reversible and correlated with down-regulation of epithelial protein markers such as E-cadherin and cytokeratins and upregulation of vimentin. TGF-beta 1-treated cells with a fibroblast-like phenotype induced spindle cell carcinomas upon transplantation in athymic nude mice, whereas untreated PDV cells or fusiform cells reverted to the epithelial phenotype and produced well-differentiated squamous cell carcinomas. Nontumorigenic immortalized epidermal keratinocytes, when grown under the presence of TGF-beta 1, did not transdifferentiate to a mesenchymal phenotype, their proliferation was blocked, and cells finally died. These results suggest a role of TGF-beta 1 in the progression of squamous carcinoma cells to spindle carcinomas in mouse skin carcinogenesis.

Carcinoma, Squamous Cell

chemically induced

22470393

The Leucine Zipper Putative Tumor Suppressor 2 Protein LZTS2 Regulates Kidney Development

Background: The LZTS2 is a novel β-catenin-interacting protein, and its role in development and tumorigenesis is unknown. Results: Lzts2 KO mice show severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis. Conclusion: LZTS2 plays a critical role in kidney and urinary tract development. Significance: A novel mechanism by which LZTS2 regulates β-catenin mediated nephrogenesis is implicated. Members of the leucine zipper putative tumor suppressor (LZTS) family play crucial roles in transcription modulation and cell cycle control. We previously demonstrated that LZTS2 functions as a novel β-catenin-interacting protein and represses β-catenin-mediated transcription on T-cell factor/lymphoid enhancing factor. Here, we investigate the biological role of LZTS2 using newly established Lzts2 KO mice. Homozygosity for loss-of-function of the Lzts2-targeted allele resulted in severe kidney and urinary tract developmental defects, including renal/ureteral duplication, hydroureter, and hydronephrosis, which were visible prenatally. Altered ureteric bud outgrowth was identified in Lzts2 null embryos. Further analysis indicated that β-catenin subcellular localization was altered in fibroblasts isolated from Lzts2 null embryos. In addition, Wnt growth factor-induced β-catenin-mediated transcriptional activity was increased in Lzts2 null fibroblasts, suggesting a direct role for Lzts2 in the Wnt signaling pathway. These data demonstrate a critical role of LZTS2 in renal development and implicate LZTS2 as a critical regulator of β-catenin-mediated nephrogenesis.

Kidney

embryology

9412135

Relationship between Phylogenetic Groups, Genotypic Clusters, and Virulence Gene Profiles of Escherichia coli Strains from Diverse Human and Animal Sources

ABSTRACT Escherichia coli strains in water may originate from various sources, including humans, farm and wild animals, waterfowl, and pets. However, potential human health hazards associated with E. coli strains present in various animal hosts are not well known. In this study, E. coli strains from diverse human and animal sources in Minnesota and western Wisconsin were analyzed for the presence of genes coding for virulence factors by using multiplex PCR and biochemical reactions. Of the 1,531 isolates examined, 31 (2%) were found to be Shiga toxin-producing E. coli (STEC) strains. The majority of these strains, which were initially isolated from the ruminants sheep, goats, and deer, carried the stx1c and/or stx2d, ehxA, and saa genes and belonged to E. coli phylogenetic group B1, indicating that they most likely do not cause severe human diseases. All the STEC strains, however, lacked eae. In contrast, 26 (1.7%) of the E. coli isolates examined were found to be potential enteropathogenic E. coli (EPEC) strains and consisted of several intimin subtypes that were distributed among various human and animal hosts. The EPEC strains belonged to all four phylogenetic groups examined, suggesting that EPEC strains were relatively widespread in terms of host animals and genetic background. Atypical EPEC strains, which carried an EPEC adherence factor plasmid, were identified among E. coli strains from humans and deer. DNA fingerprint analyses, done using the horizontal, fluorophore-enhanced repetitive-element, palindromic PCR technique, indicated that the STEC, potential EPEC, and non-STEC ehxA-positive E. coli strains were genotypically distinct and clustered independently. However, some of the potential EPEC isolates were genotypically indistinguishable from nonpathogenic E. coli strains. Our results revealed that potential human health hazards associated with pathogenic E. coli strains varied among the animal hosts that we examined and that some animal species may harbor a greater number of potential pathogenic strains than other animal species.

Escherichia coli

pathogenicity

22086580

Obstacles and Proposed Solutions to Effective Antiretroviral Therapy in Resource-Limited Settings

More than 3 million people were receiving antiretroviral therapy (ART) at the end of 2007, but this number represents only 31% of people clinically eligible for ART in resource-limited settings. The primary objective of this study is to summarize the key obstacles that impede the goal of universal access prevention, care, and treatment. We performed a systematic literature search to review studies that reported barriers to diagnosis and access to treatment of HIV/AIDS in resource-limited countries. Persons living with HIV/ AIDS commonly face economic, sociocultural, and behavioral obstacles to access treatment and care for HIV. A variety of programs to overcome these barriers have been implemented, including efforts to destigmatize HIV/AIDS, enhance treatment literacy, provide income-generation skills, decentralize HIV services, promote gender equality, and adopt a multisectoral approach to optimize limited resources. An understanding of these obstacles and suggested methods to overcome them must be addressed by global policy makers before universal ART access can be achieved.

HIV Infections

drug therapy

1263456

Allergic Inflammation Is Associated With Coronary Instability and a Worse Clinical Outcome After Acute Myocardial Infarction

Background—The role of allergic inflammation in acute coronary syndromes (ACS) has not been clearly defined to date. Aim of this study was to assess eosinophil and basophil activation in ACS and the prognostic role of eosinophil cationic protein in ST-segment–elevation myocardial infarction. Methods and Results—In a cross-sectional study, we prospectively enrolled 51 patients undergoing percutaneous coronary intervention (60.8% patients with ACS and 39.2% with stable angina). Flow cytometry analysis assessed CD66b, CD69, and CD203c median fluorescence intensity expression. In a follow-up study, 181 patients presenting with ST-segment–elevation myocardial infarction, undergoing primary percutaneous coronary intervention, were prospectively enrolled with a follow-up of 24 months. Eosinophil activation (CD66b) was similar in patients with ACS and stable angina (6.61 [4.91–7.72] versus 6.62 [5.27–8.73], P=0.63), whereas eosinophil degranulation (CD69) and basophil activation (CD203c) were higher in ACS patients compared with stable angina patients (1.38 [1.16–1.52] versus 1.17 [1–1.31], P=0.01); 0.97 [0.89–1.11] versus 0.92 [0.87–0.95], P=0.03, respectively). Eosinophil cationic protein serum levels were significantly higher in ST-segment–elevation myocardial infarction patients with major adverse cardiac events as compared with those without (21.1 [10.37–25.65] versus 7.83 [3.37–12.8] &mgr;g/L, P=0.01) and in patients with thrombus score >3 compared with those with thrombus score ⩽3 (15.0 [9.8–24.7] versus 5.2 [3.5–22.9] &mgr;g/L, P=0.006). Eosinophil cationic protein serum levels predicted major adverse cardiac events during follow-up (odds ratio =1.041, 95% confidence interval 1.012–1.071, P=0.005). C-reactive protein serum levels showed a borderline statistical significance (odds ratio =0.904, 95% confidence interval 0.806–1.014, P=0.085). Conclusions—These findings are the first demonstration of in vivo eosinophil degranulation and basophil activation during ACS and of the prognostic role of eosinophil cationic protein in ST-segment–elevation myocardial infarction.

Myocardial Infarction

blood

25107068

[Comprehensive prevention of postoperative thrombosis].

Thromboembolic disease with its high mortality and morbidity is currently one of the most serious postoperative complications. Its occurrence in high-risk patients in surgical wards is 25-50%. Since 1979, the authors have examined 160 risk patients in whom no prevention had been performed. In this group of patients they detected the occurrence of profound venous thrombosis by means of the accumulation fibrinogen test, targeted phlebography under skiascopic control. At the same time the clinical symptomatology was followed in detail. Since the thrombosis is a multifactorial process, the effective preventive measure must affect and normalize as many disturbed homeostatic processes as possible. Into the group of 176 high-risk patients, the authors introduced a complex prevention into surgical routine residing in classical low-dose heparinization by 5000 u.s.c. with the first dose administered 1 hours prior to surgery, preoperational haemodilution with the administration of minimally 500 ml of Dextran and in preoperation administration of antiaggregants (Acylpyrin). by means of this tactic, the greatest antithrombotic effect is brought about preoperatively and in the first postoperative hours while the patient is protected minimally 5 to 7 postoperative days. Both preoperative and postoperative procedures are monitored by means of a complex haemocoagulation examination of the basic 10 haemocoagulation factors. The occurrence of thrombosis in patients without prevention with minimally 5 thrombogenetic risk factors during the control by means of the accumulation fibrinogen test was 32.4% and during the control by means of targeted phlebography is 24%. The differences are not statistically significant. In the group of patients with prevention the occurrence is 5.6%. In this group the screening is represented by the accumulation fibrinogen test and its positivity is verified by its localization by means of selective phlebography. The occurrence of deep vein thrombosis in the group with prevention and in the control groups statistically highly significant p > 0.0005. Haemocoagulation examination is aimed at the determination of the normalization impact of prevention on the state of hypercoagulation ability associated with the depression of spontaneous fibrinolysis in patients without prevention. The thrombi detected in patients with prevention are localized in short segments of crural veins. Clinically more significant bleeding in the group of patients with prevention occurred only in 2 patients, i.e. in 1%. Complex multifactorial prevention is not only simple and safe for patients, but also highly effective in the group of patients with high risk of postoperative thrombosis. The clinical diagnosis is unreliable and misleading with low sensitivity and specificity. (Tab. 2, Fig. 2, Ref. 28.).

Postoperative Complications

prevention & control

27093290

A simplified economic approach to thyroid FNA cytology and surgical intervention in thyroid nodules

Objective Few studies have modelled the economics of thyroid FNA. Methods A simple spreadsheet economic model for delivery of thyroid fine needle aspiration (FNA) cytology is described using the UK Royal College of Pathologists’ Classification for thyroid FNA which is based on The Bethesda System for Reporting Thyroid Cytopathology. Results We show an estimated 27.8% cost treatment reduction per patient if low rates of non-diagnostic for cytological diagnosis (Thy 1) and neoplasm possible atypia/non-diagnostic (Thy 3a) are achieved, which require rapid onsite FNA adequacy assessment of aspiration samples. If we assume that the number of thyroid FNAs performed in the UK annually is around 500 per million, and the UK population is 62 million, this could save the UK National Health Service significant sums, as the additional cost per patient treated in this model varies from £781 for a scenario with ultrasound guided FNA and inclinic cell adequacy assessment to £998 where aspirates are taken in conventional fashion without any inclinic adequacy assessment. Conclusions This model makes a strong economic case for the introduction of rapid onsite assessment of thyroid FNA across cancer networks, to improve the diagnostic efficacy of thyroid FNA.

Neoplasms

pathology

36373877

Different neurons in different regions of human temporal lobe distinguish correct from incorrect identification or memory

Changes in the frequency of neural activity differentiating correct from incorrect responses were identified in extracellular recordings from 113 neurons at 62 sites in temporal lobe of 26 patients undergoing awake neurosurgery, during identification and recent explicit memory for object names, text or auditory words. Activity significantly differentiating correct from incorrect performance was identified in 22 neurons at 16 sites in 12 patients. Different neurons in different regions differentiated identification or memory performance. The 13 neurons differentiating identification performance were overrepresented in medial-basal recordings, the 9 neurons differentiating memory performance in superior temporal gyrus. All memory changes occurred during encoding. For both identification and memory there was separation of neurons showing differentiation early during perception and processing from those showing differentiation late, when output should occur, perhaps reflecting response monitoring. Early differentiating neurons were located more superior-laterally within the different regions related to accuracy of identification or memory.

Neurons

physiology

220631233

Multi-omic Directed Discovery of Cellulosomes, Polysaccharide Utilization Loci, and Lignocellulases from an Enriched Rumen Anaerobic Consortium

The lignocellulolytic ERAC displays a unique set of plant polysaccharide-degrading enzymes (with multimodular characteristics), cellulosomal complexes, and PULs. The MAGs described here represent an expansion of the genetic content of rumen bacterial genomes dedicated to plant polysaccharide degradation, therefore providing a valuable resource for the development of biocatalytic toolbox strategies to be applied to lignocellulose-based biorefineries. ABSTRACT Lignocellulose is one of the most abundant renewable carbon sources, representing an alternative to petroleum for the production of fuel and chemicals. Nonetheless, the lignocellulose saccharification process, to release sugars for downstream applications, is one of the most crucial factors economically challenging to its use. The synergism required among the various carbohydrate-active enzymes (CAZymes) for efficient lignocellulose breakdown is often not satisfactorily achieved with an enzyme mixture from a single strain. To overcome this challenge, enrichment strategies can be applied to develop microbial communities with an efficient CAZyme arsenal, incorporating complementary and synergistic properties, to improve lignocellulose deconstruction. We report a comprehensive and deep analysis of an enriched rumen anaerobic consortium (ERAC) established on sugarcane bagasse (SB). The lignocellulolytic abilities of the ERAC were confirmed by analyzing the depolymerization of bagasse by scanning electron microscopy, enzymatic assays, and mass spectrometry. Taxonomic analysis based on 16S rRNA sequencing elucidated the community enrichment process, which was marked by a higher abundance of Firmicutes and Synergistetes species. Shotgun metagenomic sequencing of the ERAC disclosed 41 metagenome-assembled genomes (MAGs) harboring cellulosomes and polysaccharide utilization loci (PULs), along with a high diversity of CAZymes. The amino acid sequences of the majority of the predicted CAZymes (60% of the total) shared less than 90% identity with the sequences found in public databases. Additionally, a clostridial MAG identified in this study produced proteins during consortium development with scaffoldin domains and CAZymes appended to dockerin modules, thus representing a novel cellulosome-producing microorganism. IMPORTANCE The lignocellulolytic ERAC displays a unique set of plant polysaccharide-degrading enzymes (with multimodular characteristics), cellulosomal complexes, and PULs. The MAGs described here represent an expansion of the genetic content of rumen bacterial genomes dedicated to plant polysaccharide degradation, therefore providing a valuable resource for the development of biocatalytic toolbox strategies to be applied to lignocellulose-based biorefineries.

Bacterial Proteins

metabolism

20678216

Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas

Gastric carcinogenesis involves multiple genetic and epigenetic alterations. Epigenetic silencing of tumor-related genes due to CpG island methylation (CIM) has been recently reported in gastric cancer, but the role in precursor lesions is not well understood. We analysed the methylation status of the tumor suppressor gene p16, the DNA mismatch repair gene hMLH1, and four CpG islands (MINT1, MINT2, MINT25, and MINT31) using methylation-specific polymerase chain reaction in 35 polypoid adenomas and 46 flat dysplasias unassociated with carcinoma, 34 early adenocarcinomas (T1N0M0) and associated adenomas/dysplasias, and corresponding adjacent non-neoplastic mucosa. The extent of CIM was defined by the fraction of methylated loci (methylation index), and compared with previously characterized genetic alterations (microsatellite instability (MSI) and APC gene mutation). We found that methylation of p16 was more frequent in adenocarcinoma-associated dysplasias/adenomas (29%) and adenocarcinomas (44%) as compared to flat dysplasias (4%) and adenomas (18%) unassociated with adenocarcinoma (P=0.001). The mean methylation index increased from normal/chronic gastritis (CG) mucosa (0.09) to intestinal metaplasia (IM) (0.16), flat dysplasias (0.40) or polypoid adenomas (0.41) unassociated with carcinoma, dysplasias/adenomas associated with carcinoma (0.44), and adenocarcinomas (0.44). There was no difference in frequencies of high-level CpG island methylation (CIM-H, methylation index ⩾0.5) among flat dysplasias (50%) and polypoid adenomas (51%) unassociated with carcinoma, dysplasias/adenomas associated with adenocarcinoma (47%), and adenocarcinoma (47%). CIM-H was present in 15% of IM, but not in normal/CG mucosa. There was a significant correlation between methylation of hMLH1 and high-level of microsatellite instability (MSI-H): methylation of hMLH1 was present in 71% of MSI-H tumors, but only 8% of MSI-low tumors and 13% of microsatellite-stable tumors (P=0.0001). There was no statistical difference between methylation index and APC mutation. Our results indicate that concurrent promoter methylation is an early and frequent event in gastric tumorigenesis, including both MSI-H and microsatellite-stable neoplasms. Methylation of the p16 gene may contribute to the malignant transformation of gastric precursor lesions.

Adenocarcinoma

genetics

37639782

Oncolytic viruses: perspectives on clinical development.

Developing a live anti-cancer agent derived in most cases from human pathogens presents a unique set of challenges to clinical development versus those anticipated with standard chemotherapeutics and small molecules. The selection of therapeutic targets for oncolytic virus (OV) clinical development, as is true with the development of any agent for cancer therapy, requires careful consideration beyond preclinical and early clinical data, especially when multiple indications may initially appear equally promising. Further, the added complexity of the potential for infectious complications following OV therapy must be anticipated in order to efficiently and safely conduct clinical studies. As more OV enter the clinic, these issues will become increasingly important to successful OV drug development.

Neoplasms

therapy

205924013

Lifestyle risk factors for progesterone-related diabetes mellitus in elkhounds - a case-control study.

OBJECTIVES This study aims to investigate lifestyle risk factors for the development of progesterone-related diabetes mellitus in female elkhounds. METHODS Owners of 48 diabetic elkhounds and 58 healthy elkhounds were interviewed by phone concerning lifetime diet and exercise routines. A logistic model was developed to assess the impact of diet and exercise on diabetes diagnosis. The agreement between lifetime owner-perceived body condition score (BCS) and veterinary-perceived BCS at inclusion was estimated in healthy control dogs using the Kappa statistic. RESULTS The model showed that diabetic dogs had increased odds for having been overweight (before diagnosis) compared with controls (OR=2·8, 95% confidence interval 1·1-7·5, P=0·034). Although feeding other food than commercial dog feed was associated with diabetes case status, the effect was not significant after BCS was entered into the model. The overall agreement between lifetime owner- and veterinary-perceived BCS at inclusion in the study was 75% and had a Kappa statistic of 0·16 (P=0·12). CLINICAL SIGNIFICANCE This study indicates that a high owner-perceived lifetime BCS is associated with progesterone-related diabetes in elkhounds.

Obesity

veterinary

89450087

[Molecular epidemiologic characteristics of HIV-1 variants isolated in the Lipetsk region].

: Molecular epidemiologic study of HIV-1 variants isolated in the Lipetsk region during 1994 - 2006 period was performed. It has been shown that 3 env-subtypes (A, B, and C) and 3 gag-subtypes (A, B, and C) are widespread in the region. The virus was transmitted both sexually and by injecting drug users. Phylogenetic analysis of gag and env genes nucleotide sequences was performed, which revealed that 4 variants of HIV-1 with genotypes gagA/envA, gagB/envB, gagC/envC, and recombinant gagA/envB are circulating in the region.

HIV Infections

epidemiology

205216576

RE: DNA damage detected by the alkaline comet assay in the liver of mice after oral administration of tetrachloroethylene. (Mutagenesis, 25, 133-138, 2010).

The recently published paper by Cederberg et al. (1) discusses the induction of DNA damage in an in vivo comet assay in mice dosed with tetrachloroethylene. The authors concluded that tetrachloroethylene induced significant DNA damage in the liver, but this conclusion was heavily dependent on statistical analysis. The laboratory that performed the study (Covance Laboratories Limited) concluded that tetrachloroethylene did not induce DNA damage in the liver. Cederberg et al. (1) presented and discussed the Covance opinion, but this discrepancy in the conclusions merits further discussion. It is our opinion that the paper does not accurately report the Covance evaluation criteria used to assess these data. Firstly, when assessing any genotoxicity data, including comet data, it is important to evaluate the biological relevance of the results as well as any statistical findings. In fact, most OECD guidelines state that statistical significance should not be the only criterion for conclusion of a positive result. We believe, and it is common practice, that statistical analysis should be used as an aid to interpretation and not the sole criterion. Groups of mice treated with tetrachloroethylene exhibited tail moments and tail intensities that were similar to the concurrent vehicle control group. The maximum group mean increase was only 1.43-fold above the vehicle control group and that was for tail intensity in the 2000 mg/kg group. The increase in tail moment in this group was only 1.36-fold above the vehicle control group. Although Covance had limited historical control comet data for mouse liver, a validation study on mouse liver had been performed before the tetrachloroethylene study, and all tail moment and tail intensity values for tetrachloroethylene were comparable to the validation data for the mouse liver. Covance had considerably more historical control data for rat liver, and all of the tail moment and tail intensity values for tetrachloroethylene fell within the laboratory’s rat historical control range for the liver. The variation observed within groups for tail intensity is of a similar magnitude to that observed between groups and the values observed in the vehicle and test article-treated groups overlap. This supports the opinion that the increases observed are of a magnitude considered to be due to biological variation and not indicative of DNA damage. Thus, Covance concluded that the tetrachloroethylene data did not demonstrate a biologically significant effect. The choice of statistical analysis also deserves comment. Of course, there are often many different opinions regarding the most appropriate statistical test to perform with a given data set. However, it is interesting that the expert working group of the International Workshop on Genotoxicity Tests (2) concluded the following:

Liver

drug effects

23653877

Childhood Maltreatment Among Hispanic Women in the United States

Prevalence rates of childhood maltreatment among Hispanic women in the United States are presented separately for nativity status and ethnic origin subgroups, and the associations between different types of maltreatment and the development of anxiety and depressive disorders are examined. Analyses used self-report data from 1,427 Hispanic women who participated in the National Latino and Asian American Survey. Foreign-born Hispanic women compared to U.S.-born Hispanic women reported significantly lower rates of sexual assault and witnessing interpersonal violence, and a significantly higher rate of being beaten. Ethnic subgroups reported similar rates of maltreatment, with the exception of rape. Bivariate analyses were remarkably consistent in that regardless of nativity status or ethnic subgroup, each type of maltreatment experience increased the risk of psychiatric disorder. In multivariate models controlling for all types of victimization and proxies of acculturation, having been beaten and witnessing interpersonal violence remained significant predictors of both disorders, but sexual abuse increased risk of anxiety only. A significant interaction effect of family cultural conflict and witnessing violence on anxiety provided very limited support for the hypothesis that acculturation moderates the influence of maltreatment on mental health outcomes. Implications for culturally relevant prevention and intervention approaches are presented.

Mental Disorders

ethnology

45734831

Notch‐3 receptor activation drives inflammation and fibrosis following tubulointerstitial kidney injury

Kidney diseases impart a vast burden on affected individuals and the overall health care system. Progressive loss of renal parenchymal cells and functional decline following injury are often observed. Notch‐1 and ‐2 receptors are crucially involved in nephron development and contribute to inflammatory kidney diseases. We specifically determined the participation of receptor Notch‐3 following tubulointerstitial injury and in inflammatory responses. Here we show by heat map analyses that Notch‐3 transcripts are up‐regulated in human kidney diseases. A similar response was corroborated with kidney cells following TGF‐β exposure in vitro. The murine unilateral ureteral obstruction (UUO) model mirrors hallmarks of tubulointerstitial injury and damage. A subset of tubular and interstitial cells demonstrated up‐regulated Notch‐3 receptor expression in diseased animals. We hypothesized a relevance of Notch‐3 receptors for the chemotactic response. To address this question, animals with genetic ablation of receptor Notch‐3 were analysed following UUO. As a result, we found that Notch‐3‐deficient animals are protected from tubular injury and cell loss with significantly reduced interstitial collagen deposition. Monocytic cell infiltration was significantly reduced and retarded, likely due to abrogated chemokine synthesis. A cell model was set up that mimics enhanced receptor Notch‐3 expression and activation. Here a pro‐mitogenic response was seen with activated signalling in tubular cells and fibroblasts. In conclusion, Notch‐3 receptor fulfils non‐redundant roles in the inflamed kidney that may not be replaced by other Notch receptor family members. Thus, specific blockade of this receptor may be suitable as therapeutic option to delay progression of kidney disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Kidney

physiopathology

5765677

[Viable myocardium revealed by contrast echocardiography].

In patients with acute ischemic syndrome left ventricular dysfunction may indicate necrotic myocardium as well as viable tissue. Among the well known non-invasive techniques like dobutamine echocardiography, rest-redistribution thallium scintigraphy or positron emission tomography a new method, contrast echocardiography is evolving. In the presented case stunning resulting in left ventricular aneurysm formation was confirmed after intravenous injection of contrast agent and the use of intermittent harmonic imaging in the acute phase of ischemia. The negative coronary angiography and the complete restoration of the left ventricular function confirmed the results of contrast echocardiography. With the development of new second generation contrast agents and new techniques contrast echocardiography will become a feasible method for detection of viable myocardium after intravenous injection.

Myocardial Infarction

diagnostic imaging

34029367

Effects of benidipine hydrochloride on autonomic nervous activity in hypertensive patients with high- and low-salt diets.

The effects of benidipine hydrochloride (CAS 91559-74-5, Coniel) on autonomic nervous activity in hypertensive patients with high- and low-salt diets were investigated. Six patients having a urinary sodium excretion of 80 mEq/day or less (low salt group) and 6 patients having a urinary sodium excretion of 200 mEq/day or more (high salt group) were orally given benidipine hydrochloride (4 mg). Before and four weeks after the treatment with benidipine, 24-h circadian variation in blood pressure and 24-h Holter electrocardiogram (ECG) were recorded. The low frequency power spectrum of heart rate (LF power; 0.04-0.15 Hz), high frequency power spectrum of heart rate (HF power; 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) were calculated, and these parameters were averaged every hour in every subject. HF power was significantly lower and LF/HF ratio was significantly higher in the high-salt group than in the low-salt group before the treatment. However, the benidipine treatment significantly increased the HF power in both groups, particularly in the high-salt group, and significantly decreased the LF/HF ratio in both groups. Moreover, there was no significant difference in the antihypertensive effect of benidipine between the high- and low-salt intake groups. These results suggest that benidipine favourably influences blood pressure and autonomic nervous activity in hypertensive patients with a high-salt intake. It is concluded that benidipine may be useful for improving the development of salt-induced hypertension and its accompanying haemodynamic responses.

Hypertension

physiopathology

21420133

[Synthesis and antibacterial activity of (S) -5-acetylaminomethyl-3-[(4-substituted-aminomethyl) phenyl] -2-oxazolindinone derivatives].

AIM To synthesize oxazolindinone derivatives and test their antibacterial activities. METHODS 3-Halo-4-methylaniline was acylated with benzyl chloroformate, followed by cyclization with (R)-glycidyl butyrate, acylation with methanesulfonyl chloride, substitution with NaN3, reduction with H2 + Pd/C or P(OMe)3 + HCl, acylation with Ac2O, and bromination with NBS to form bromides VIIIa and VIIIb, Substitution of the bromides with various amines including aliphatic amine and aromatic amine provided the target compounds IXa and IXb. The in vitro antibacterial activity of the target compounds was tested. RESULTS Fifty one new compounds were designed and synthesized. And their structures were confirmed by 1H NMR and elemental analyses or MS. Some physical constants such as [alpha]D25 were reported also. Compounds VIIb, IXa1, IXa2, IXa7, IXb1, IXb3, IXb10, IXb16 and IXb23 had moderate in vitro antibacterial activity against G+ bacteria but they were less active than linezolid or norfloxacin. CONCLUSION Insertion of methylene group between 4-position of phenyl and morpholinyl group in linezolid derivatives can not increase the antibacterial activity.

Anti-Bacterial Agents

chemical synthesis

12601434

A randomized clinical trial of mupirocin in the eradication of Staphylococcus aureus nasal carriage in human immunodeficiency virus disease.

Seventy-six human immunodeficiency virus (HIV)-infected patients with Staphylococcus aureus nasal carriage were randomized to treatment groups receiving intranasal mupirocin or placebo twice daily for 5 days. Nasal cultures for S. aureus were obtained at 1, 2, 6, and 10 weeks after therapy. At 1 week, 88% of mupirocin-treated patients had negative nasal cultures compared with 8% in placebo patients (P<.001). The percentage of mupirocin-treated patients with persistently negative nasal cultures decreased over time (63%, 45%, and 29% at 2, 6, and 10 weeks, respectively) but remained significantly greater than the placebo group (3% at 2, 6, and 10 weeks). In mupirocin-treated patients, most (16/19) instances of nasal recolonization were with pretreatment strains (determined by means of by pulsed field gel electrophoresis); mupirocin resistance was not observed. Five days of treatment with mupirocin eliminated S. aureus nasal carriage in HIV-infected patients for several weeks; however, since the effect waned over time, intermittent dosing regimens should be considered for long-term eradication.

Anti-Bacterial Agents

therapeutic use

27962742

The application of brachial-ankle pulse wave velocity as a clinical tool for cardiovascular risk assessment.

I read with interest the article of Vlachopoulos et al1, which evaluated the usefulness of brachial-ankle elasticity index (also known as brachial-ankle pulse wave velocity [baPWV], which is the term more commonly used in Japan) for predicting future cardiovascular (CV) events by meta-analysis.⇓ I would like to describe here the applicability of baPWV as a clinical tool for CV risk assessment. The concept that increased large arterial stiffness is one of the novel players in the initiation and/or progression …

Cardiovascular Diseases

mortality

5024043

Alarming results of nosocomial bloodstream infections surveillance in Polish intensive care units

INTRODUCTION Nosocomial bloodstream infections (BSI) among patients in intensive care units (ICU) are the most common form of nosocomial infections and they are serious complications of the treatment process. The etiological factors of these infections and the proper antibiotic therapy can influence the effects of patient treatment. The aim of the study was to analyze the epidemiology, microbiology and antibiotic therapy of nosocomial BSI in Polish ICU patients. MATERIALS AND METHODS The retrospective study covered patients hospitalized in seven ICUs for adults with a general profile, located in southern Poland. The studied units participated in a multicentre standardized infection control program in 2013-2015. 2,547 patients hospitalized more than 48 hours in ICUs were qualified to the study. The study was conducted in accordance with the methodology recommended by the European Center for Disease Prevention and Control (ECDC) as part of the European Healthcare-Associated Infections Surveillance Network (HAI-Net): protocols and the criteria for BSI recognition were standardized. RESULTS The incidence of BSI was 7.2% per 100 admissions and the incidence density was 9.2 per 1000 persondays of hospitalization. Among 184 BSI cases, 65 cases (35.3%) were primary BSI; 87 cases were secondary BSI (47.3%) (related to an infection occurring elsewhere in the patient’s body), the remaining 32 cases (17.4%) were classified as BSI of unknown origin. Mortality was 20%. The dominant etiological factors in BSI related to central venous catheter were coagulase-negative staphylococci in 20.8% of cases, but in secondary BSI it was Acinetobacter baumannii in 34.5% of cases. Klebsiella pneumoniae showed resistance to third-generation cephalosporins in 96.0% of cases; Acinetobacter baumannii showed resistance to imipenem in 78.8% of cases. Other beta-lactam antibiotics J01D (31.0%) and other antibiotics J01X (26.6%) were most commonly used in the treatment. CONCLUSIONS The BSI incidence in the studied Polish ICUs was twice as high as in other European countries, and secondary BSI were also more frequent – especially secondary to urinary tract infections. The obtained results indicate the necessity of intervention not only in BSI prevention, but also in the field of prevention of urinary tract infections. In addition, microbial etiology and drug resistance indicate the need for urgent actions for their prevention.

Anti-Bacterial Agents

therapeutic use

25880434

Identification of the polyamine-induced protein as a periplasmic oligopeptide binding protein.

The physiological function of the polyamine-induced protein (PI protein), whose synthesis is stimulated at an early stage after the addition of putrescine to growing cells of a polyamine-requiring mutant of Escherichia coli (Mitsui, K., Igarashi, K., Kakegawa, T., and Hirose, S. (1984) Biochemistry 23, 2679-2683), has been studied. The following findings clearly show that the PI protein is a binding protein of an oligopeptide transport system. (a) PI protein was found in a periplasmic fraction. (b) When the restriction map of a clone for the PI protein gene was compared with Kohara's physical map (Kohara, Y., Akiyama, K., and Isono, K. (1987) Cell 50, 495-508), the gene was found at 27 min of the E. coli chromosome, where genes for an oligopeptide transport system were located. (c) The clone contained a 1,629-nucleotide open reading frame encoding a 543-amino acid protein whose calculated Mr was 60,901, and the predicted amino acid sequence from this open reading frame was quite similar to that of an oligopeptide binding protein of Salmonella typhimurium. (d) When the transport activity of a tripeptide, Gly-Leu-125I-Tyr, was measured in a polyamine-requiring mutant of E. coli growing both in the presence and absence of putrescine, the activity was higher in the cells growing in its presence. (e) Polyamine stimulation of cell growth was greater when an oligopeptide rather than corresponding amino acids was added to the medium. These results suggest that the polyamine stimulation of PI protein synthesis at the early stage after the addition of putrescine contributes to the polyamine stimulation of cell growth through the supply of nutrients.

Escherichia coli

genetics

20679281

[Tinidazole versus cefazolin in antibiotic prophylaxis of vaginal and abdominal hysterectomy].

PURPOSE to compare the efficacy of tinidazole and cephazolin on the febrile and infectious morbidity of post vaginal and abdominal hysterectomy antibiotic prophylaxis. METHODS randomized clinical study, where women admitted to hospital for hysterectomy were randomly allocated in one of the following antibiotic prophylaxis groups: Group C (2 g of IV cephazolin in the anesthetic induction); Group T (2 g of tinidazole orally, 12 hours before the surgery); or Group C+T (2 g of tinidazole orally 12 hours before the surgery and 2g of IV cephazolin in the anesthetic induction). Cervicovaginal smears were collected for specific cultures and the diagnosis of bacterial vaginosis (BV) was based in Amsel and Nugent's criteria. The patients were reevaluated 7 and 30 days after the surgery for signs of febrile and/or infectious morbidity. The chi2 or the Fisher's exact test was used to assess differences among the three groups, with a significance level of 5%. The sample power (1-beta) was calculated through the SAS program. RESULTS seven days after the hysterectomy, infectious morbidity was diagnosed in 6.6% of the women, but with no significant difference among the three groups studied (p=0.12). There was no febrile or infectious morbidity at the immediate post-surgical period or after 30 days from the surgery. BV ratio at the pre-surgical period was significantly higher among the women submitted to vaginal hysterectomy, rather than among the ones submitted to abdominal hysterectomy (27 versus 7%, p=0.02). BV ratio was also higher after 30 days, among the women submitted to vaginal hysterectomy (20 versus 8%), though without statistical significance (p=0.19). CONCLUSIONS the use of tinidazole, isolated or associated with cephazolin has not presented higher efficacy, than the use of cephazolin, alone to prevent febrile or infectious morbidity post hysterectomy. The high ratio of BV at the immediate pre-surgery period among the women submitted to vaginal hysterectomy suggests that this infection must be better investigated and properly treated before the surgery.

Anti-Bacterial Agents

therapeutic use

22789152

S100A4 is an independent prognostic factor for patients with lung cancer: a meta-analysis.

OBJECTIVE To evaluate the association of S100A4 levels with the prognosis of lung cancer (LC). METHODS The RevMan 5.0 software was utilized to perform literature retrieval, data collection, and statistical analysis according to its guidelines. Literature-based searching was guided to gather data, and the fixed-effect model was used to pool the hazard ratio (HR) in this study. RESULTS A total of 10 eligible studies that included 1364 LC patients were analyzed. About 72.6% of patients had positive expression of S100A4 according to the criteria defined by the authors. The HR of positive expression for overall survival (OS) was 1.30 times of that of negative expression in LC patients (HR=1.30, 95% confidence interval: 1.04 to 1.61, p=0.02). CONCLUSION Patients with positive expression of S100A4 appear to have a poorer OS compared with those with negative expression of S100A4.

Lung Neoplasms

metabolism

54522310

Uncertain diagnosis and prognosis in advanced melanoma: a qualitative study of the experiences of bereaved carers in a time of immune and targeted therapies

Recent advances in advanced melanoma therapies are associated with improved survival for some patients. However, how patients with diagnoses of advanced disease and their carers experience this expanding treatment paradigm is not well understood.

Skin Neoplasms

diagnosis

1322156

[Hypertonic central nervous system complications from the viewpoint of the pathologist].

Based on 2130 autopsies with a hypertension it is reported on the hypertensive CNS-lesions. The frequency of encephalomalacia was 12%. By 9.7% was founded brain haemorrhages. The relapse rate of haemorrhages was about 5%. The encephalomalacia existed by way of secondary finding in 24.7%, and the haemorrhage in 2.2%. The investigations showed an important arteriosclerosis by 39.8% in haemorrhages and by 51.6% in brain infarct. It was remarkable by the hypertensive brain haemorrhages a dominant right hemisphere.

Hypertension

pathology

8309727

Identification and characterization of a novel human hepatocellular carcinoma-associated gene

To investigate liver cancer-associated genes and to explore the molecular basis of liver cancer genesis, we have cloned a novel hepatocellular carcinoma (HCC)-related gene with a transcript of 2520 base pairs in length named HCCA2 by mRNA differential display polymerase chain reaction (DDPCR) and screening a placenta cDNA library. No significant homologous protein with known genes was found. Western blot analysis showed that HCCA2 could be expressed in transfected 293 cells. Northern hybridization analysis showed that HCCA2 mRNA was expressed in 79% (34/43) patients with HCC, most of whom had significantly high expression in HCC tissues, while not expressed in corresponding noncancerous liver tissues. The clinical pathological data showed that the HCCA2 was significantly associated with the invasion of tumour capsule (P= 0.0007) and the expression of ki-67 protein (P= 0.0022). Immunohistochemical staining confirmed that the HCCA2 protein was localized in cytoplasm of liver cancer tissues. According to amino acid analysis of the protein and its localization, it may play a role in a cascade of intracellular signal transduction because the protein was characterized with two Src homology 3 (SH3) binding-domains and several functional motifs of phophorylation. © 2001 Cancer Research Campaign http://www.bjcancer.com

Liver Neoplasms

genetics

20767285

Accelerated onsets of gastric hamartomas and hepatic adenomas/carcinomas in Lkb1+/−p53−/− compound mutant mice

Germline mutations in the LKB1 gene are responsible for Peutz–Jeghers syndrome (PJS), which is characterized by gastrointestinal hamartomas and increasing risk of cancer. Mice with Lkb1+/− mutation develop gastric hamartomas after >20 weeks of age, and hepatocellular adenomas and carcinomas >30 weeks. It has been reported that, in PJS patients, carcinomas progressed from hamartomas contain p53 mutations, and that LKB1 regulates p53-dependent apoptosis. To investigate the roles of LKB1 and p53 mutations in tumorigenesis, we constructed compound mutant mice of Lkb1 and p53 genes. In the Lkb1+/−p53−/− mice, formation of gastric hamartomas and hepatic tumors was accelerated. However, histopathology of hamartomas was similar between Lkb1+/−p53−/− and Lkb1+/− mice, and Lkb1 genotype remained heterozygous, suggesting that the p53 mutation affected hamartoma initiation. Contrary to the heterozygous hamartomas in the stomach and duodenum, the hepatic adenomas in Lkb1+/−p53−/− mice showed loss of Lkb1 heterozygosity (LOH), suggesting that lack of p53 stimulated Lkb1 LOH and tumor initiation in the liver. Taken together, these results indicate that lack of p53 causes earlier onsets of gastric hamartomas and hepatic tumors in Lkb1+/−p53−/− mice.

Liver Neoplasms

genetics

1189073

Are branched chain fatty acids the natural substrates for P450(BM3)?

Branched chain fatty acids are substrates for cytochrome P450(BM3) (CYP102) from Bacillus megaterium; oxidation of C15 and C17 iso and anteiso fatty acids by P450(BM3) leads to the formation of hydroxylated products that possess high levels of regiochemical and stereochemical purity.

Bacterial Proteins

chemistry

12189843

Cystic pulmonary metastases from epithelioid cell sarcoma.

A patient with cystic pulmonary metastases, from epithelioid sarcoma of the thigh, resulting in bilateral pneumothoraces is presented. The pulmonary metastases superficially resembled pneumomatoceles and were not visible on radiography. Computed tomography examinations over a 10-month period showed no change in the size or number of the cystic metastases, though air fluid levels and pericystic nodular consolidation (probably due to pulmonary hemorrhage) did occur and regress. This case report serves to emphasize that bullous type lesions on thoracic computed tomography in patients with a known sarcoma should be interpreted with particular caution.

Lung Neoplasms

secondary

27636014

The Effect of Water Hardness on Mortality of Zebrafish (Danio rerio) During Exposure to Oxytetracycline

AbstractMarking of fish otoliths with oxytetracycline and tetracycline is a widely used method to evaluate the effectiveness of stocking operations. Available protocols for the labeling of fish specify a number of factors influencing mark quality and potential risk for fish during marking. This study investigates the influence of water hardness on mortality of freshwater fish during marking with OTC. In order to pursue this question complexation of OTC with Mg2+ and Ca2+ cations was measured spectrophotometrically. Furthermore, zebrafish (Danio rerio) were immersed in OTC solutions (1200 mg/L; 48 h immersion) combined with varying levels of water hardness (5.5, 15.5, 25.5, 32.5°dH). The amount of OTC-Mg–Ca-complexes was positively correlated to water hardness. Moreover, it could be demonstrated that mortality of zebrafish during marking varied as a factor of water hardness. Highest mortalities occurred at the lowest (5.5°dH) and the highest (32.5°dH) tested levels during marking with OTC.

Anti-Bacterial Agents

pharmacology

212621743

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumor microenvironment, but also to increase invasiveness and resistance to anticancer drugs such as chemotherapy. This review collects clinical evidence of autophagy deregulation during cholangiocarcinogenesis together with preclinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggest an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Preclinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer.

Antineoplastic Agents

pharmacology

33921258

Urinary continence after radical prostatectomy: the patient perspective.

INTRODUCTION To compare the commonly used 0-1 pad definition of urinary continence for postoperative functional outcome after radical prostatectomy and the correlation with self-reported urinary continence and to determine whether a patient questionnaire can deliver more accurate continence status rates. MATERIAL AND METHODS We evaluated a cohort of 873 men who underwent radical prostatectomy (RP) at the General Hospital in Vienna between 1998 and 2006. Patients were surveyed with a questionnaire regarding their postoperative outcome and postoperative urinary incontinence. Baseline and pathological factors were examined to determine whether or not they had an impact on the continence status. RESULTS AND LIMITATIONS A total of 65.2% of men (n = 337) reported themselves to be continent, in contrast 85.1% were continent if the pad definition was applied. Of those using no pads, 93.4% considered themselves continent, while 24.5% of patients using one pad/day did. Overall, 86.5%, 9.8% and 3.7% of continent patients regained continence within 6 months, 6 to 12 months and after 1 year of RP, respectively. A total of 71.5% of men under 65 years old reported full urinary continence, while only 57.0% of men older than 65 considered themselves continent. Men < 65 years recovered full urinary control significantly faster than men older than 65 years- 3.6 versus 4.7 months. Neurovascular bundle resection has a negative effect on continence. CONCLUSIONS The ultimate continence status should be measured with self-administered disease specific questionnaires at 24 months after RP, as it differs from standard physician reported methods. Age and neurovascular bundle resection are variables affecting continence. We believe that patients' subjective reports of their continence are crucial and that multiple outcomes should be objectively measured. Therefore we suggest that validated questionnaires dealing with the patients' perspective postoperatively should be included in routine follow up.

Prostatic Neoplasms

surgery

9590776

Future challenges and therapeutic opportunities in type 2 diabetes: Changing the paradigm of current therapy

Most algorithms for type 2 diabetes mellitus (T2DM) do not recommend treatment escalation until glycated haemoglobin (HbA1c) fails to reach the recommended target of 7% (53 mmol/mol) within approximately 3 months on any treatment regimen (“treat to failure”). Clinical inertia and/or poor adherence to therapy contribute to patients not reaching glycaemic targets when managed according to this paradigm. Clinical inertia exists across the entire spectrum of anti‐diabetes therapies, although it is most pronounced when initiating and optimizing insulin therapy. Possible reasons include needle aversion, fear of hypoglycaemia, excessive weight gain and/or the need for increased self‐monitoring of blood glucose. Studies have suggested, however, that early intensive insulin therapy in newly diagnosed, symptomatic patients with T2DM with HbA1c >9% (75 mmol/mol) can preserve beta‐cell function, thereby modulating the disease process. Furthermore, postprandial plasma glucose is a key component of residual dysglycaemia, evident especially when HbA1c remains above target despite fasting normoglycaemia. Therefore, to achieve near normoglycaemia, additional treatment with prandial insulin or a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) is often required. Long‐ or short‐acting GLP‐1 RAs offer effective alternatives to basal or prandial insulin in patients inadequately controlled with other therapies or basal insulin alone, respectively. This review highlights the limitations of current algorithms, and proposes an alternative based on the early introduction of insulin therapy and the rationale for the sequential or fixed combination of GLP‐1 RAs with insulin (“treat‐to‐success” paradigm).

Diabetes Mellitus, Type 2

therapy

1291182

Borna disease virus interference with neuronal plasticity.

Viruses able to infect the central nervous system (CNS) are increasingly being recognized as important factors that can cause mental diseases by interfering with neuronal plasticity. The mechanisms whereby such infections disturb brain functions are beginning to emerge. Borna disease virus (BDV), which causes a persistent infection of neurons without direct cytolysis in several mammalian hosts, has recently gained interest as a unique model to study the mechanisms of viral interference with neuronal plasticity. This review will summarize several hypotheses that have been put forward to explain possible levels of BDV interference with brain function.

Neurons

virology

22660736

Virologic Characterization of HIV Type 1 With a Codon 70 Deletion in Reverse Transcriptase

We identified a deletion at codon 70 (Δ70) of HIV-1 reverse transcriptase (RT) occurring together with L74V and Q151M mutations in a sample from a tenofovir (TFV)- and abacavir (ABC)-treated patient with extensive prior antiretroviral treatment. To investigate the characteristics of this mutant, we studied the drug susceptibility, relative infectivity, and fitness of viruses carrying Δ70 and associated RT mutations. The Δ70, L74V, and Q151M mutations were introduced into Hxb2 RT by site-directed mutagenesis and expressed in HIV-1 recombinants. The Δ70 mutation increased resistance to lamivudine and emtricitabine alone and in combination with various resistance mutations and augmented resistance to ABC and didanosine when present together with L74V. A recombinant virus expressing RT from the original clinical viral sample (Δ70-PRT) exhibited greater fitness than one in which the deletion had been repaired (K70-PRT). The Δ70 mutation also increased fitness of Hxb2 wild-type and 74V and Q151M mutants. Recombinants carrying Δ70-PRT showed greater relative infectivity in the presence of ABC (but not TFV) compared with K70-PRT recombinants. These results show that Δ70 enhances resistance to certain purine and pyrimidine analogues and contributes to multinucleoside resistance in the appropriate viral genetic background.

HIV Infections

virology

13271259

The mass, but not the frequency, of insulin secretory bursts in isolated human islets is entrained by oscillatory glucose exposure.

Insulin is secreted in discrete insulin secretory bursts. Regulation of insulin release is accomplished almost exclusively by modulation of insulin pulse mass, whereas the insulin pulse interval remains stable at approximately 4 min. It has been reported that in vivo insulin pulses can be entrained to a pulse interval of approximately 10 min by infused glucose oscillations. If oscillations in glucose concentration play an important role in the regulation of pulsatile insulin secretion, abnormal or absent glucose oscillations, which have been described in type 2 diabetes, might contribute to the defective insulin secretion. Using perifused human islets exposed to oscillatory vs. constant glucose, we questioned 1) whether the interval of insulin pulses released by human islets is entrained to infused glucose oscillations and 2) whether the exposure of islets to oscillating vs. constant glucose confers an increased signal for insulin secretion. We report that oscillatory glucose exposure does not entrain insulin pulse frequency, but it amplifies the mass of insulin secretory bursts that coincide with glucose oscillations (P < 0.001). Dose-response analyses showed that the mode of glucose drive does not influence total insulin secretion (P = not significant). The apparent entrainment of pulsatile insulin to infused glucose oscillations in nondiabetic humans in vivo might reflect the amplification of underlying insulin secretory bursts that are detected as entrained pulses at the peripheral sampling site, but without changes in the underlying pacemaker activity.

Diabetes Mellitus, Type 2

physiopathology

30683628

The NH2-terminal residues of Bacillus subtilis proteins.

Abstract The NH2-terminal residues of Bacillus subtilis soluble and ribosomal proteins were determined by the dinitrophenyl method. A nonrandom distribution of amino acids was observed. Alanine occurred most frequently, followed by methionine, serine, threonine, glutamic acid, and aspartic acid; smaller quantities of leucine, isoleucine, valine, and glycine were also found at the terminal position. A marked difference between these results and those obtained for Escherichia coli was noted. A slight difference in the frequency of distribution of the amino acids was also detected between log and stationary phase soluble proteins. An analysis of radioactive proteins newly synthesized by B. subtilis cells also indicated a preferential incorporation of alanine into the NH2-terminal residues.

Proteins

analysis

206090549

Susceptibility to excitotoxicity in aged hippocampal cultures and neuroprotection by non‐steroidal anti‐inflammatory drugs: role of mitochondrial calcium

Brain damage after insult and cognitive decline are related to excitotoxicity and strongly influenced by aging, yet mechanisms of aging‐dependent susceptibility to excitotoxicity are poorly known. Several non‐steroidal anti‐inflammatory drugs (NSAIDs) may prevent excitotoxicity and cognitive decline in the elderly by an unknown mechanism. Interestingly, after several weeks in vitro, hippocampal neurons display important hallmarks of neuronal aging in vivo. Accordingly, rat hippocampal neurons cultured for several weeks were used to investigate mechanisms of aging‐related susceptibility to excitotoxicity and neuroprotection by NSAIDs. We found that NMDA increased cytosolic Ca2+ concentration in young, mature and aged neurons but only promoted apoptosis in aged neurons. Resting Ca2+ levels and responses to NMDA increased with time in culture which correlated with changes in expression of NMDA receptor subunits. In addition, NMDA promoted mitochondrial Ca2+ uptake only in aged cultures. Consistently, specific inhibition of mitochondrial Ca2+ uptake decreased apoptosis. Finally, we found that a series of NSAIDs depolarized mitochondria and inhibited mitochondrial Ca2+ overload, thus preventing NMDA‐induced apoptosis in aged cultures. We conclude that mitochondrial Ca2+ uptake is critical for age‐related susceptibility to excitotoxicity and neuroprotection by NSAIDs.

Calcium

physiology

20952023

[Four cases of adult Listeria monocytogenes infection in the last 5 years--hepatic necrotic foci in the adult septic case].

We have reported on the clinical courses of 4 cases of adult Listeria monocytogenes (Lm) infection, and the autopsy findings of 2 cases, those we have observed over the past 5 years. They were 2 cases of meningitis, 1 case of meningitis and sepsis and 1 case of sepsis. These 4 cases had CML, neoplastic angioendotheliosis, SLE and post-renal transplant condition, as their underlying diseases, and all were receiving immunosuppressive therapy. One meningitis patient who recovered showed mild liver dysfunction during her clinical course. The other 3 patients who died had jaundice at the time of onset and severe liver dysfunction. The 2 cases those were autopsied were the sepsis cases. The one with an acute course and hepatic failure showed multiple miliary necrotic foci in the liver, where the presence of Lm in the cells could be verified. The other autopsy case, which had received adequate antibiotic therapy and the Lm infection had been cured, showed no necrotic foci in the liver. The case that had necrotic foci in the liver was the first such adult case in Japan. We have discussed the hepatic Lm infection in adult compromised hosts, which conventionally has not been considered a serious problem.

Liver

pathology

42783998

Effect of metabolic inhibitors on 45Ca fluxes and ATP content of myelinated nerve.

The effects of metabolic inhibitors on ATP levels and on 45Ca fluxes were studied in desheathed tibial nerves of Rana pipiens. ATP levels were significantly reduced and Ca influx and efflux increased following exposure to cyanide, mersalyl, azide, dinitrophenol, iodoacetate or ethacrynic acid. The efflux changes were relatively small compared to squid axons but are not attributable to depolarization of the cell or to changes in the transmembrane Na gradient. The magnitude of the effluxes are consistent with ideas about the amount of labile Ca sequestered in energy-dependent Ca pools. The efflux stimulated by metabolic inhibitors is reduced by removing extracellular Na or Ca, indicating that a large portion of Ca efflux in the poisoned state is mediated by Na-Ca countertransport. In the nominal absence of both these cations Ca efflux can be stimulated by metabolic inhibitors, suggesting that mechanisms in addition to countertransport participate in Ca efflux.

Calcium

metabolism

22085006

Regulation of CD8+ T-cell cytotoxicity in HIV-1 infection.

Understanding the mechanisms involved in cellular immune responses against control of human immunodeficiency virus (HIV) infection is key to development of effective immunotherapeutic strategies against viral proliferation. Clear insights into the regulation of cytotoxic CD8+ T cells is crucial to development of effective immunotherapeutic strategies due to their unique ability to eliminate virus-infected cells during the course of infection. Here, we reviewed the roles of transcription factors, co-inhibitory molecules and regulatory cytokines following HIV infection and their potential significance in regulating the cytotoxic potentials of CD8+ T cells.

HIV Infections

immunology

39074803

A bovine seminal plasma inhibitor of actin-stimulated myosin adenosine triphosphatase.

During attempts to isolate bovine sperm actin, persistent low molecular weight proteinaceous (LMWP) contaminants were found. A LMWP fraction was prepared by gel filtration chromatography on Sephadex G150. The LMWP was found in extracts of washed bovine ejaculated spermatozoa and in clarified bovine seminal plasma. It was substantially reduced in amount in bovine epididymal spermatozoa, indicating that it originated from secondary sex gland secretions. The LMWP inhibited rabbit muscle actin-stimulated myosin adenosine triphosphatase (actin-myosin ATPase) activity. The LMWP:actin ratio for 50% inhibition of actin-myosin ATPase was 2.6 +/- 0.12 mg LMWP per mg actin. The LMWP interfered with actin inhibition of deoxyribonuclease, indicating that LMWP interacted with actin. The LMWP from seminal plasma had an estimated molecular weight of 8300 and consisted of several acidic components. It had negligible protease activity and its inhibition of actin-myosin ATPase was independent of divalent cations. The LMWP appears to readily aggregate with itself and other proteins, which may be related to its physiological role in semen.

Proteins

physiology

36706041

Regulated exocytosis in neurons and neurosecretory cells: Structural events and expression competence

This paper summarizes the contribution of the laboratory first in the development of the 'kiss-and-run model' of exocytosis, with its fascinating aspects of specificity and rapidity, then in proposing the existence of 'competence factors' that appear to govern the appearance of the secretory vesicles and exocytic process in neurosecretory cells.

Neurons

physiology

4861900

Rapid, simple and inexpensive production of custom 3D printed equipment for large-volume fluorescence microscopy

Graphical abstract

Brain

pathology

22178342

Therapeutic advances in local-regional therapy for stage III non-small-cell lung cancer: evolving role of dose-escalated conformal (3-dimensional) radiation therapy.

Lung cancer is the leading cause of cancer-related death among men and women in the United States. Approximately 80%-85% of lung cancer cases are non-small-cell lung cancer, and approximately 30%-40% of these patients have unresectable stage IIIA/B disease at diagnosis. The standard of care for locally advanced disease in patients with a good performance status consists of combined modality therapy, chemotherapy and radiation therapy (RT). Despite improved survival with combined modality therapy, local-regional recurrences and the development of distant metastases are still problematic. The radiation dose of 60 Gy for inoperable stage III non-small-cell lung cancer, established by Radiation Therapy Oncology Group trials 7301 and 7302, has remained the standard until the present time. More recently, trials suggest that local-regional control can be improved with RT dose escalation, improved tumor targeting (eg, 3-dimensional planning and intensity-modulated RT), and altered RT fractionation. Improvements in local-regional control could translate into an overall survival benefit. This article reviews the rationale for aggressive therapy and techniques to improve local disease control. It also provides an overview of trials that utilize such techniques, with a focus on efficacy, toxicity, and overall survival. Further well-designed clinical trials that examine RT dose escalation, improved tumor targeting, altered fractionation, and incorporation of biologic agents are crucial for progress in this disease.

Lung Neoplasms

radiotherapy

199540797

Overcoming multidrug resistance by activating unfolded protein response of the endoplasmic reticulum in cisplatin-resistant A2780/CisR ovarian cancer cells

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.

Antineoplastic Agents

pharmacology

40488029

[Double blind randomized trial of metopimazine: for postoperative nausea and vomiting after cholecystectomy].

Eighty-four patients submitted to cholecystectomy were randomly assigned in a double-blind study either to an intravenous dose of 10 mg of metopimazine, three times D-1, for two days or to an identically administered placebo. A definite superiority of metopimazine as an anti-emetic drug was demonstrated. General acceptance was excellent, but arterial pressure might be looked over closely when metopimazine was administered intravenously immediately after a general anesthesia.

Postoperative Complications

drug therapy

13539091

Perceived family health in persons with prostate cancer and their family members.

AIMS AND OBJECTIVES To describe perceived family health in persons with prostate cancer and their family members. An additional purpose was to describe the associations between the background variables of persons with prostate cancer and their family members and perceived family health. BACKGROUND Prostate cancer in one family member affects the health of the whole family. It is important to study perceived family health in families of persons with prostate cancer and associated factors. DESIGN A cross-sectional study. METHOD Data were collected using the Family Functioning, Health and Social Support (FAFHES) scale, modified for use in this study. Questionnaires were distributed to 100 persons with prostate cancer treated with surgery or radiation therapy and 100 family members at one Finnish university hospital in April-October 2009. Responses were received from 76 persons and 71 family members, a response rate of 74%. RESULTS Persons with prostate cancer and family members rated family health good despite prostate cancer. Family members reported higher levels of illness-related ill-being than persons with prostate cancer. Family health was associated with the person's age, basic education, employment status, number of family member's visits to the hospitalised patient, first symptom of prostate cancer and previous hospitalisations were associated with. Family health was associated with the family member's basic and vocational education. CONCLUSIONS The results show that nursing care should pay attention to family members of persons with prostate cancer and that support to them should be a natural part of a good care of persons with prostate cancer. RELEVANCE TO CLINICAL PRACTICE The quality of prostate cancer care should be improved to provide more individualised and family-focussed services.

Prostatic Neoplasms

physiopathology

37475030

Correlation between magnetic resonance perfusion weighted imaging of radiation brain injury and pathology.

We used magnetic resonance perfusion weighted imaging and pathological evaluation to examine different stages of radiation-induced brain injury and to investigate the correlation between the relative cerebral blood volume (rCBV) ratio and vascular endothelial growth factor (VEGF). Thirty adult rats were randomly divided into 2 groups: control and radiation group. The control group was not subjected to irradiation. The irradiation group rats were examined by magnetic resonance imaging and magnetic resonance perfusion weighted imaging at 1, 3, 6, 9, and 12 months after radiation treatment. We measured the rCBV, mean transit time, and time to peak. Hematoxylin and eosin staining, immunohistochemical staining, and electron microscopy were performed. VEGF absorbance was evaluated by immunohistochemical staining. Compared with the control group, the differences in rCBV, mean transit time, time to peak, and VEGF absorbance after 3 months were statistically significant (P < 0.05). rCBV was positively correlated with VEGF (r = 0.94, P < 0.05). Magnetic resonance perfusion weighted imaging can reflect pathophysiological changes in brain tissue after irradiation. Decreased expression of VEGF plays a critical role in the pathogenesis of radiation-induced brain injury.

Brain

pathology

37512235

Age-related increase in wall stress of the human abdominal aorta: an in vivo study.

BACKGROUND The regulation of wall stress in the abdominal aorta (AA) of humans might be of specific interest, because the AA is the most common site for aneurysm formation in which wall stress seems to be an important pathophysiological factor. We studied the age-related changes in wall stress of the AA in healthy subjects, with the common carotid artery (CCA) as a comparison. METHODS A total of 111 healthy subjects were examined with B-mode ultrasonography to determine the lumen diameter and intima-media thickness (IMT) in the AA and the CCA. RESULTS Aortic IMT was affected by age in men and by both age and lumen diameter in women. Carotid IMT was affected by age and pulse pressure in both men and women. Wall stress was higher in the AA than in the CCA (P < .001), and men had higher wall stress than women in both the AA (P < .001) and the CCA (P < .05). Furthermore, wall stress was constant during life in the CCA of men and women and in the AA of women. In the male aorta, however, wall stress increased with age (P < 0.01). CONCLUSIONS Arterial diameters increase with age, and a compensatory thickening of the arterial wall prevents the circumferential wall stress from increasing. However, this compensatory response is insufficient in the male AA and results in an increase in stress with age. These findings might explain the propensity for aneurysms to develop in the AA of men.

Aging

physiology

10402005

Turkish female academician self-esteem and health beliefs for breast cancer screening.

PURPOSE This study aimed to analyse female academician health beliefs for breast cancer screening and levels of self-esteem. MATERIALS AND METHODS This cross-sectional study was conducted between October 2010 and March 2011, covering female academicians working in all faculties and vocational schools at Ondokuz Mayis University, except for the ones in the field of health (n=141). Data was collected using a questionnaire developed by researchers in the light of the related literature, the Champion's Health Belief Model Scale for Breast Cancer, and the Coopersmith Self-Esteem Inventory. Descriptive statistics, the t-test, Mann-Whitney U and correlation analysis were used to analyze the data with the SPSS 13.0 statistical package. RESULTS 53.8% of the participants were single, 58.6% did not have children, 80.7% had regular menstrual cycles, 28.3% was taking birth control pills, 17.9% were undergoing hormone therapy, 11% suffered breast problems, 8.3% had relatives with breast cancer, 78,6% knew about breast self-examination (BSE), 68.3% was performing BSE, 16.2% were performing BSE monthly, 17.9% had had mammograms, and 30.3% had undergone breast examinations conductedby physicians. The women who had breast physical examinations done by physicians had higher susceptibility, self-efficacy and health motivation, and fewer barriers to mammography than those who did not have breast physical examinations. CONCLUSIONS There was a relationship between the female academician self-esteem and their perceived seriousness of breast cancer, perceived barriers to BSE and health motivation. Our Turksih female academicians had medium levels of self-esteem.

Breast Neoplasms

diagnosis

30824568

Breast cancer association studies in a Han Chinese population using 10 European-ancestry-associated breast cancer susceptibility SNPs.

BACKGROUND Genome-wide association studies (GWAS) have identified various genetic susceptibility loci for breast cancer based mainly on European-ancestry populations. Differing linkage disequilibrium patterns exist between European and Asian populations. METHODS Ten SNPs (rs2075555 in COL1A1, rs12652447 in FBXL17, rs10941679 in 5p12/MRPS30, rs11878583 in ZNF577, rs7166081 in SMAD3, rs16917302 in ZNF365, rs311499 in 20q13.3, rs1045485 in CASP8, rs12964873 in CDH1 and rs8170 in 19p13.1) were here genotyped in 1009 Chinese females (487 patients with breast cancer and 522 control subjects) using the Sequenom MassARRAY iPLEX platform. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95% CI) for each SNP. Stratification analyses were carried out based on the estrogen receptor (ER) and progesterone receptor (PR) status. RESULTS Among the 10 SNPs, rs10941679 showed significant association with breast cancer when differences between the case and control groups in this Han Chinese population were compared (30.09% GG, 45.4% GA and 23.7% AA; P = 0.012). Four SNPs (rs311499, rs1045485, rs12964873 and rs8170) showed no polymorphisms in our study. The remaining five SNPs showed no association with breast cancer in the present population. Immunohistochemical tests showed that rs2075555 was associated with ER status; the AA genotype showed greater association with ER negative than ER positive (OR = 0.54, 95% CI, 0.29-0.99; P = 0.046). AA of rs7166081 was also associated with ER status, but showed a greater association with ER positive than negative (OR = 1.59, 95% CI = 1.04-2.44; P = 0.031). However, no significant associations were found among the SNPs and PR status. CONCLUSION In this study using a Han Chinese population, rs10941679 was the only SNP associated with breast cancer risk, indicating a difference between European and Chinese populations in susceptibility loci. Therefore, confirmation studies are necessary before utilization of these loci in Chinese.

Breast Neoplasms

genetics

13211582

Off-pump anteroapical aneurysm plication for left ventricular post-infarction aneurysm: long-term results.

BACKGROUND The temporal response to off-pump anteroapical aneurysm plication has not been well defined. We have evaluated the long-term clinical and functional results of this technique and compared the efficacy with the patch modeling repair. METHODS From March 2005 to May 2010, 163 (115 men and 48 women) consecutive patients were operated on for post-infarction left ventricular aneurysm (LVA), 54 patients underwent patch remodeling (group A) and 109 patients underwent off-pump anteroapical aneurysm plication repair (group B). All patients had simultaneous coronary revascularization, other operative procedures included septoplasty in eight and ablation of ventricular tachycardia in six. Follow-up ranged from 1 to 5 years, short-term and mid-term outcomes, including complications, cardiac function, and mortality, were assessed. RESULTS Early mortality was 1.8% for all patients (group A 1 death vs. group B 2 deaths, not significant (NS)). Peri-operative support included intraaortic balloon pumping in 16 (9.8%), (group A 6 patients vs. group B 10 patients, NS) and inotropic drugs in 84 (51.5%), (group A 34 vs. group B 50, NS). During a mean follow-up of (3.7±0.8) years, eight patients died, with four due to cardiac-related causes. No patient required transplantation, and two required use of an implantable cardioverter-defibrillator for ventricular tachycardia. Survival at 1 and 5 years was 95% and 86%, respectively. It did not differ significantly between group A and group B. Functional class improved from 2.90 ± 0.59 to 1.65 ± 0.54 among the mid-term survivors (P < 0.001), with no significant difference between the two groups. Pre-operative risk factors for mortality or poor function were ejection fraction (EF) < 0.35 (OR = 7.9, 95%CI 1.6 - 40.0); congestive heart failure (CHF) (OR = 4.4, 95%CI 1.0 - 19.0); end-systolic volume index (ESVI) > 80 ml/m(2) (OR = 3.7, 95%CI 1.0 - 14.0); and advanced age > 70 years (OR = 2.4, 95%CI 1.0 - 12.0). CONCLUSIONS The technique of off-pump anteroapical aneurysm plication associated with coronary grafting can be performed with low operative mortality, providing good symptomatic relief and long-term survival, and similar results can be achieved with patch modeling repair.

Myocardial Infarction

surgery

20510718

The frequency of micronuclei in lymphocytes of dogs with osteosarcoma: a predictive variable for tumor response during cisplatin chemotherapy.

To our knowledge, there are no features identifiable at the time of diagnosis or during treatment that can assist the clinician in predicting the response to cisplatin therapy in dogs with osteosarcoma. In this study, we describe a direct relationship between the percentage of G0 lymphocytes containing micronuclei following exposure to one dose of cisplatin in vivo and tumor response in dogs with osteosarcoma. The response of tumors to chemotherapy is thought to be a function of the drug's pharmacological properties (e.g., peak plasma concentration and elimination half-life); however, a relationship between platinum DNA adduct levels in leukocyte DNA and tumor response has been observed by others, suggesting that clinical resistance to platinum drugs is attributable to DNA repair functions of the host, and thus the degree of cytotoxicity is similar across all cell types. Our results support this hypothesis. Those dogs receiving cisplatin chemotherapy and having a micronuclear frequency of greater than 10% had median remission and survival times of 68.3 and 79.0 weeks, respectively, whereas those dogs with a micronuclear frequency of less than 10% had median remission and survival times of 14.1 and 17.9 weeks, respectively.

Antineoplastic Agents

therapeutic use

21291364

The impact of motion artifacts on the reproducibility of repeated coronary artery calcium measurements

The purpose of this study is, using a 16-section multidetector-row helical computed tomography (MDCT) scanner with retrospective reconstruction, to compare variability in repeated coronary calcium scoring and qualitative scores of the motion artifacts. One hundred forty-four patients underwent two subsequent scans using MDCT. According to Agatston and volume algorithms, the coronary calcium scores during mid-diastole (the center corresponding to 70% of the R-R cycle) were calculated and the inter-scan variability was obtained. Motion artifacts from coronary artery calcium were subjectively evaluated and classified using a 5-point scale: 1, excellent; no motion artifacts; 2, fine, minor motion artifacts; 3, moderate, mild motion artifacts; 4, bad, severe motion artifacts; 5, poor, doubling or discontinuity. Each reading was done by vessels (left main, left descending, left circumflex and right coronary arteries) and the motion artifact score (mean of the scales) was determined per patient. The variability in the low (1.2±0.2) and high (2.4±0.6) motion artifact score groups was 7±6 (median, 6)% and 19±15 (16)% on the Agatston score (P<0.01) and 7±7 (6)% and 16±13 (14)% on the volume score (P<0.01), respectively. In conclusion, motion has a significant impact on the reproducibility of coronary calcium scoring.

Calcium

analysis

53210727

DNA transfer in forensic science: A review.

Understanding the variables impacting DNA transfer, persistence, prevalence and recovery (DNA-TPPR) has become increasingly relevant in investigations of criminal activities to provide opinion on how the DNA of a person of interest became present within the sample collected. This review considers our current knowledge regarding DNA-TPPR to assist casework investigations of criminal activities. There is a growing amount of information available on DNA-TPPR to inform the relative probabilities of the evidence given alternative scenarios relating to the presence or absence of DNA from a specific person in a collected sample of interest. This information should be used where relevant. However, far more research is still required to better understand the variables impacting DNA-TPPR and to generate more accurate probability estimates of generating particular types of profiles in more casework relevant situations. This review explores means of achieving this. It also notes the need for all those interacting with an item of interest to have an awareness of DNA transfer possibilities post criminal activity, to limit the risk of contamination or loss of DNA. Appropriately trained forensic practitioners are best placed to provide opinion and guidance on the interpretation of profiles at the activity level. However, those requested to provide expert opinion on DNA-related activity level issues are often insufficiently trained to do so. We advocate recognition of DNA activity associated expertise to be distinct from expertise associated with the identification of individuals. This is to be supported by dedicated training, competency testing, authorisation, and regular fit for purpose proficiency testing. The possibilities for experts to report on activity-related issues will increase as our knowledge increases through further research, access to relevant data is enhanced, and tools to assist interpretations are better exploited. Improvement opportunities will be achieved sooner, if more laboratories and agencies accept the need to invest in these aspects as well as the training of practitioners.

DNA

isolation & purification

20138171

Increasing Prevalence of Gastrointestinal Colonization With Ceftazidime-Resistant Gram-Negative Bacteria Among Intensive Care Unit Patients

Background. The occurrence of nosocomial infections due to third-generation cephalosporin–resistant gram-negative bacteria is increasing. Gastrointestinal colonization is an important reservoir for antibiotic-resistant bacteria, and it often precedes clinical infection. Objective. To estimate the prevalence of gastrointestinal colonization with ceftazidime-resistant gram-negative bacteria among intensive care unit (ICU) patients at a university-affiliated tertiary-care hospital during 2 distinct periods and to assess whether, at any time during the index hospitalization, colonized patients had a clinical culture positive for the same organism that was recovered from surveillance culture. Setting. Two ICUs at the University of Maryland Medical Center, a 656-bed tertiary-care hospital located in Baltimore, Maryland. Both ICUs provide care to adult patients. Methods. We performed a cross-sectional study of adult patients admitted to the medical ICU or the surgical ICU from June 14 to July 14, 2003, and from June 14 to July 14, 2006. Perirectal swab samples were obtained for surveillance culture on admission to the intensive care unit, weekly thereafter, and at discharge. Each culture sample was plated onto MacConkey agar supplemented with ceftazidime. Results. In 2003, a total of 33 (18.8%) of 176 patients were colonized with ceftazidime-resistant gram-negative bacilli; in 2006, 60 (31.4%) of 191 patients were (P<.01). This increase was largely driven by an increase in ceftazidime-resistant Klebsiella isolates (which accounted for 6.4% of isolates in 2003 and for 22.8% in 2006; P<.01). In 2003, a total of 16 (48.5%) of 33 colonized patients had a clinical culture positive for the same organism that was recovered from the perirectal surveillance culture, compared with 22 (36.6%) of 60 colonized patients in 2006 (P = .28). Conclusion. Our data suggest that gastrointestinal colonization with ceftazidime-resistant gram-negative bacilli is common, that its prevalence is increasing, and that colonization may result in clinical cultures positive for these bacilli.

Anti-Bacterial Agents

therapeutic use

221200420

Psychological Aspects of Pregnancy and Lactation in Patients with Breast Cancer.

Young breast cancer patients face numerous challenges during the cancer trajectory. As in the last decade, women tend to delay pregnancies to a later time in life, and clinicians are often faced with young breast cancer patients who want to start a family or complete it. Becoming a mother is a delicate developmental process in which the woman redefines and restructures her identity as she gets prepared for her new role and responsibilities. When there is a history of cancer or cancer diagnosis is communicated during the pregnancy, fears, worries, and concerns emerge and specific support may be necessary. Follow-ups during the post-partum period are also recommended as lactation issues should not be overlooked. In this chapter, we analyze the psychological aspects of cancer survivors and women with pregnancy-associated breast cancer, and the management of these issues.

Breast Neoplasms

psychology

45735146

Synthesis and antiproliferative activity of benzofuran-based analogs of cercosporamide against non-small cell lung cancer cell lines.

A novel series of 3-methyl-1-benzofuran derivatives were synthesized and screened in vitro for their antiproliferative activity against two human NSCLC cell lines (NSCLC-N6 mutant p53 and A549 wild type p53). Most promising compounds presented a structural analogy with the west part of cercosporamide, a natural product of biological interest. In particular, compounds 10, 12 and 31 showed cytotoxic activities at micromolar concentrations (IC₅₀ < 9.3 μM) and compounds 13, 18 and 32 displayed moderate IC₅₀ values (25-40 μM).

Lung Neoplasms

drug therapy