Esophageal variceal ligation for acute variceal bleeding: results of three years' follow-up.
Endoscopic variceal ligation is widely accepted as the optimum endoscopic treatment for esophageal variceal hemorrhage. However, the rebleeding course and long-term outcome of patients with esophageal variceal hemorrhage after ligation have been poorly defined. Therefore, we conducted a long-term follow-up study to delineate the outcome of ligation. Twenty-one liver cirrhotic patients with endoscopically proven esophageal variceal hemorrhage were treated by endoscopic variceal ligation. These patients received regular follow-up and detailed clinical assessment of at least 24 months. Twenty-one eligible patients were followed up for a mean of 44.45 months (range 33.5-64 months). The mean number of sessions required to obtain eradication was 3.57+/-1.99 (range 1-8). Esophageal varices could be obliterated within 11.57+/-6.8 weeks (range 3-30). The percentage of variceal recurrence during follow-up was 57.14% (12/21) after endoscopic variceal ligation. Recurrence were observed in a mean of 34 months (median 29 months). Rebleeding from esophageal varices appeared in four patients (19.04%). The appearance rates of portal hypertensive gastropathy and fundal gastric varices after varice obliteration were found to be 45.45% (5/11) and 25% (3/12), respectively. Based on the results of long-term follow-up of endoscopic variceal ligation, although the percentage of variceal recurrence was high, endoscopic ligation achieved variceal obliteration faster and in fewer treatment sessions. Furthermore, endoscopic variceal ligation had a lower rate of rebleeding and of development of fundal gastric varices, but high portal hypertensive gastropathy.


Prediction of protein antigenic determinants from amino acid sequences.
A method is presented for locating protein antigenic determinants by analyzing amino acid sequences in order to find the point of greatest local hydrophilicity. This is accomplished by assigning each amino acid a numerical value (hydrophilicity value) and then repetitively averaging these values along the peptide chain. The point of highest local average hydrophilicity is invariably located in, or immediately adjacent to, an antigenic determinant. It was found that the prediction success rate depended on averaging group length, with hexapeptide averages yielding optimal results. The method was developed using 12 proteins for which extensive immunochemical analysis has been carried out and subsequently was used to predict antigenic determinants for the following proteins: hepatitis B surface antigen, influenza hemagglutinins, fowl plague virus hemagglutinin, human histocompatibility antigen HLA-B7, human interferons, Escherichia coli and cholera enterotoxins, ragweed allergens Ra3 and Ra5, and streptococcal M protein. The hepatitis B surface antigen sequence was synthesized by chemical means and was shown to have antigenic activity by radioimmunoassay.


Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89.
The capacity of resident peritoneal macrophages and alveolar macrophages for self-renewal was studied in CD-1 mice depleted of radiosensitive blood monocyte precursors by irradiation of the bone marrow with the bone-seeking isotope 89Sr. Thermoluminescent dosimetry and studies of DNA synthesis showed that significant levels of radiation were absorbed predominantly in anatomical sites in close proximity to bone. Cell proliferation remote from bone marrow was unaffected when quantitated by DNA precursor uptake. Between 10 and 15 days after injecting mice intravenously with 89Sr at 2 microCi per gm. of body weight, monocytes were only rarely detectable in the peripheral blood as determined by morphology, stains for nonspecific esterase and peroxidase, and by latex phagocytosis. Total numbers of resident peritoneal and alveolar macrophages were not significantly decreased and tritiated thymidine incorporation in vivo persisted at normal levels rather than regressing at a predicted rate during profound monocyte depletion. The data, therefore, suggest that local proliferation by resident macrophages in monocytopenic and intact mice is an important mechanism of population renewal.


Evaluation of culture and PCR-based assay for detection of Mycobacterium tuberculosis from sputum collected and stored on filter paper.
We evaluated the use of culture and PCR-based assay for the direct detection of Mycobacterium tuberculosis (MTB) from sputum collected and stored on filter paper at room temperature for 5 days; the results were compared with those of staining and conventional culture of fresh sputum before storage (the 'gold standard'). Out of 231 sputum specimens examined, MTB was recovered from 124 samples by culture before storage. The culture positivity rate was significantly decreased to 70% after 5 days storage. For PCR assay, a fragment of 377 bp of the IS6110 sequence was amplified and detected using three methods: first PCR product combined with agarose gel electrophoresis (AGE); first PCR product with dot blot hybridization (DBH); nested PCR with AGE. Compared with culture, the sensitivity, specificity, and efficiency for first PCR with AGE were 71.8, 100 and 84.9% respectively; PCR with DBH gave results of 89.5, 96.3 and 92.6% respectively; the same values for nested PCR were 96.0, 97.2, and 96.5% respectively. Of these three methods, nested PCR gave excellent sensitivity and specificity with no significant difference (p = 0.727) from conventional culture. The storage of sputum on filter paper and storage at room temperature for 5 days had no apparent effect on the performance of nested PCR. We propose that this collection and storage method be considered for transporting sputum specimens from peripheral health centers or from the field; specimens may be sent by post to a central point for both culture and PCR analysis by trained technicians supervised in accordance with a well-established quality control system.


Long-term efficacy of adding a sharp posterior optic edge to a three-piece silicone intraocular lens on capsule opacification: five-year results of a randomized study.
To compare the intensity of capsule opacification with the sharp and the round optic edge variant of an open-loop hydrophobic silicone intraocular lens (IOL). Randomized, controlled, double-blind clinical trial with intraindividual comparison. Fifty-one patients with bilateral age-related cataract were included (102 eyes). Each patient had had cataract surgery in both eyes and received a Microsil IOL with a sharp optic edge design (model S) in one eye and a Microsil IOL with a round optic edge design (model R) in the fellow eye. Both IOLs had an identical haptic design (nonangulated polymethylmethacrylate) and silicone optic material. The patients were examined at the slit lamp, best-corrected visual acuity was assessed, and standardized high-resolution digital retroillumination images of the posterior capsule were taken 5 years after surgery. The intensity of regeneratory posterior capsule opacification (rPCO), fibrotic PCO (fPCO), and anterior capsule opacification (ACO) was assessed subjectively at the slit lamp, and of rPCO, objectively using automated image analysis software (AQUA). The need for an Nd:YAG laser capsulotomy (Nd:YAG-LCT) was noted. The mean AQUA PCO score was 1.2 for the model S and 2.4 for the model R lens (P = .001). The model S lens also led to less peripheral fPCO (P = .003). Concerning ACO, there was no significant difference between both IOL groups (P = .72). Whereas no capsulotomy was required with the model S, four cases (16%) had been performed in the model R group. Five years postoperatively, the sharp-edged silicone IOL showed less rPCO and fPCO than the round-edged IOL. However, regarding ACO, there was no significant difference between both IOL styles.


Unstable Genome and Transcriptome Dynamics during Tumor Metastasis Contribute to Therapeutic Heterogeneity in Colorectal Cancers.
Genomic and transcriptomic alterations during metastasis are considered to affect clinical outcome of colorectal cancers, but detailed clinical implications of metastatic alterations are not fully uncovered. We aimed to investigate the effect of metastatic evolution on in vivo treatment outcome, and identify genomic and transcriptomic alterations associated with drug responsiveness. We developed and analyzed patient-derived xenograft (PDX) models from 35 patients with colorectal cancer including 5 patients with multiple organ metastases (MOMs). We performed whole-exome, DNA methylation, and RNA sequencing for patient and PDX tumors. With samples from patients with MOMs, we conducted phylogenetic and subclonal analysis and in vivo drug efficacy test on the corresponding PDX models. Phylogenetic analysis using mutation, expression, and DNA methylation data in patients with MOMs showed that mutational alterations were closely connected with transcriptomic and epigenomic changes during the tumor evolution. Subclonal analysis revealed that initial primary tumors with larger number of subclones exhibited more dynamic changes in subclonal architecture according to metastasis, and loco-regional and distant metastases occurred in a parallel or independent fashion. The PDX models from MOMs demonstrated therapeutic heterogeneity for targeted treatment, due to subclonal acquisition of additional mutations or transcriptomic activation of bypass signaling pathway during tumor evolution. This study demonstrated in vivo therapeutic heterogeneity of colorectal cancers using PDX models, and suggests that acquired subclonal alterations in mutations or gene expression profiles during tumor metastatic processes can be associated with the development of drug resistance and therapeutic heterogeneity of colorectal cancers.


Pyothorax and Constrictive Pericarditis after Chemoradiotherapy for Esophageal Cancer: A Case Report.
A 75-year-old man underwent chemoradiotherapy for advanced esophageal cancer. After nine years, he was hospitalized for left pyothorax. Consequently, the patient underwent drainage and window opening surgery. He experienced cardiopulmonary arrest but was resuscitated. Based on cardiac catheterization data, the patient was diagnosed with constrictive pericarditis. Unfortunately, extracorporeal circulation did not improve his condition, and he ultimately died. An autopsy revealed adhesion between the pericardium and pleura, especially the pericardium in contact with the left thoracic cavity, which was markedly thickened. This suggests that constrictive pericarditis, a latent complication of chemoradiotherapy, is aggravated by pyothorax.


On-column protein refolding for crystallization.
One major bottleneck in protein production in Escherichia coli for structural genomics projects is the formation of insoluble protein aggregates (inclusion bodies). The efficient refolding of proteins from inclusion bodies is becoming an important tool that can provide soluble native proteins for structural and functional studies. Here we report an on-column refolding method established at the Berkeley Structural Genomics Center (BSGC). Our method is a combination of an 'artificial chaperone-assisted refolding' method previously proposed and affinity chromatography to take advantage of a chromatographic step: less time-consuming, no filtration or concentration, with the additional benefit of protein purification. It can be easily automated and formatted for high-throughput process.


Clinical trials in hepatocellular carcinoma: an update.
The success of sorafenib has spurred an explosive increase of clinical trials testing novel molecular targets and other agents in the treatment of hepatocellular carcinoma (HCC). The paradigm of the studies has been characterized by three noticeable changes. First, the molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for advanced HCC treatment. Agents targeting EGFR, FGFR, PI3K/Akt/mTOR, TGF-β, c-Met, MEK, IGF signaling, and histone deacetylase have been actively explored. Second, the target indication has shifted from advanced stage to early or intermediate stages of disease. The feasibility of combining locoregional therapies and targeted agents, and the use of novel agents after curative treatments are currently under active investigation. Finally, the therapeutic strategy has shifted from monotherapy to combination targeted therapy. We aim to provide a comprehensive overview of newly disclosed and ongoing clinical trials for the treatment of HCC.


TGF-beta1 inhibits T-bet induction by IFN-gamma in murine CD4+ T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1.
TGF-beta1 prevents the development of autoimmune disease by restraining the development of autoreactive Th1 cells. TGF-beta1 inhibits Th1 development in part by suppressing the expression of T-bet, an IFN-gamma-induced transcription factor that promotes Th1 differentiation, but how TGF-beta1 suppresses T-bet is not known. In this study we show that TGF-beta1 suppresses IFN-gamma-induced T-bet expression through the hemopoietic protein tyrosine phosphatase (PTP) Src homology region 2 domain-containing phosphatase-1 (Shp-1). In murine CD4+ T cells, IFN-gamma rapidly induced the expression of T-bet as well as of IFN regulatory factor-1, another transcription factor important for Th1 development. TGF-beta1 antagonized the effects of IFN-gamma, inhibiting IFN-gamma's induction of both Th1 transcription factors. In the presence of IFN-gamma, TGF-beta1 rapidly induced in Th cells the synthesis of the PTP Shp-1, but did not induce Shp-2 or several members of the suppressor of cytokine signaling family of Jak-Stat inhibitors. We tested the requirement for Shp-1 by using T cells from the Shp-1-deficient me(v)/me(v) mouse strain. Shp-1 was required for TGF-beta1's suppressive effects, because its suppression of T-bet and IFN regulatory factor-1 was completely abrogated in me(v)/me(v) CD4+ T cells. Receptor-proximal responses to IFN-gamma, such as the induction of Jak-Stat phosphorylation, were inhibited by TGF-beta1 in wild-type T cells, but not in me(v)/me(v) T cells. Consistent with a direct role for Shp-1, TGF-beta1's inhibition of IFN-gamma-induced Stat1 phosphorylation was sensitive to the general PTP inhibitor pervanadate. Together, these data show that TGF-beta1 suppresses IFN-gamma signaling and transcriptional responses in CD4+ T cells through the PTP Shp-1.


Role of topology in determining the precision of a finite thermometer.
Temperature fluctuations of a finite system follow the Landau bound δT^{2}=T^{2}/C(T) where C(T) is the heat capacity of the system. In turn, the same bound sets a limit to the precision of temperature estimation when the system itself is used as a thermometer. In this paper, we employ graph theory and the concept of Fisher information to assess the role of topology on the thermometric performance of a given system. We find that low connectivity is a resource to build precise thermometers working at low temperatures, whereas highly connected systems are suitable for higher temperatures. Upon modeling the thermometer as a set of vertices for the quantum walk of an excitation, we compare the precision achievable by position measurement to the optimal one, which itself corresponds to energy measurement.


G protein-coupled estrogen receptor-1 enhances excitatory synaptic responses in the entorhinal cortex.
Activation of estrogen receptors is thought to modulate cognitive function in the hippocampus, prefrontal cortex, and striatum by affecting both excitatory and inhibitory synaptic transmission. The entorhinal cortex is a major source of cortical sensory and associational input to the hippocampus, but it is unclear whether either estrogens or progestogens may modulate cognitive function through effects on synaptic transmission in the entorhinal cortex. This study assessed the effects of the brief application of either 17-β estradiol (E2) or progesterone on excitatory glutamatergic synaptic transmission in the female rat entorhinal cortex in vitro. Rats were ovariectomized on postnatal day (PD) 63 and also received subdermal E2 implants to maintain constant low levels of circulating E2 on par with estrus. Electrophysiological recordings from brain slices were obtained between PD70 and PD86, and field excitatory postsynaptic potentials (fEPSPs) reflecting the activation of the superficial layers of the entorhinal cortex were evoked by the stimulation of layer I afferents. The application of E2 (10 nM) for 20 min resulted in a small increase in the amplitude of fEPSPs that reversed during the 30-min washout period. The application of the ERα agonist propylpyrazoletriol (PPT) (100 nM) or the β agonist DPN (1 μM) did not significantly affect synaptic responses. However, the application of the G protein-coupled estrogen receptor-1 (GPER1) agonist G1 (100 nM) induced a reversible increase in fEPSP amplitude similar to that induced by E2. Furthermore, the potentiation of responses induced by G1 was blocked by the GPER1 antagonist G15 (1 μM). Application of progesterone (100 nM) or its metabolite allopregnanolone (1 μM) did not significantly affect synaptic responses. The potentiation of synaptic transmission in the entorhinal cortex induced by the activation of GPER1 receptors may contribute to the modulation of cognitive function in female rats.


Dermatopontin, a novel player in the biology of the extracellular matrix.
Dermatopontin is a widely distributed small molecular weight protein in the extracellular matrix (ECM) and today its homologues are known in five mammals and several invertebrates. The structures of these homologues are relatively well conserved among the species. In the skin, dermatopontin is located mainly on the surface of the collagen fibers. It is found in the conditioned medium and also in the cytoplasm of cultured fibroblasts. Early studies focused on ECM assembly (collagen fibrillogenesis) and interactions (with the proteoglycan decorin). Subsequently, a targeted disruption of dermatopontin resulted in a phenotype similar to Ehlers-Danlos syndrome. In addition, a cell adhesion activity of this protein for dermal fibroblasts and several other cells was found, and this activity might suggest this protein's involvement in wound healing. The expression of dermatopontin around an infarct zone of experimental myocardial infarction may support this possibility. In invertebrates, dermatopontin homologues act mainly as adhesion/agglutination molecules. In addition, we found that transforming growth factor-beta1 interacts with dermatopontin and the function of this cytokine is modified by dermatopontin. Recently, the involvement of this protein in cell proliferation has been indicated. In this review we describe the reported functions of this protein and speculate on the multiple roles of this largely uncharacterized matrix molecule.


Predictors of Depression and Anxiety in Family Members 3 Months After Child's Admission to a Pediatric ICU.
Family members of children admitted to intensive care units (ICUs) suffer from severe stress, which sometimes results in long-term psychological problems. We aimed to identify associations between demographic and psychosocial variables at early stages of a child's admission to the ICU and depression and anxiety in family members at approximately 3 months after admission. We also explored predictive models for depression and anxiety at 3 months after admission. This study is a secondary analysis of data from a previous clinical trial of palliative care for family members in ICUs, in which 380 family members of 220 children reported demographic and psychosocial status at approximately 1 week after ICU admission (baseline), at discharge from the ICUs, and at 3 months after the child's admission to the ICU. Clinical data were extracted from the children's medical records. We used linear regression models and stepwise linear regression for the analyses. After controlling for significant confounders of gender (female) and child mortality, worse psychological status at baseline, represented by reported depression, anxiety, and acute stress symptoms, was associated with more severe depression and anxiety at 3 months. Also, a better family relationship at baseline was associated with lower depression and anxiety at 3 months. We suggest a need to screen family members of children admitted to the ICU with validated scales and intervening with those at high risk of depression and anxiety. Registry number NCT02144779 on ClinicalTrials.gov . https://clinicaltrials.gov/ct2/show/NCT02144779?term=NCT02144779&rank=1 .


Zenkeramide: a new iso-benzofuranone propanamide and urease inhibitory constituents of Celtis zenkeri Engl stem bark (Ulmaceae).
A new iso-benzofuranone propanamide: 3-(3-oxo-1, 3-dihydroisobenzofuran-1-yl) propanamide (zenkeramide) (1) along with three known compounds: Trans-N-coumaroyltyramine (2), β-Sitosterol (3) and β-sitosterol-3-0-β-D-glucopyranoside (4) were isolated from the ethyl acetate fraction of the stem-bark of Celtis zenkeri Engl (Ulmaceae). The structure of the new compound was elucidated by extensive spectroscopic analysis. The compounds were examined for Urease Inhibitory Activity. Compounds 1 and 2 showed moderate activities (IC50 values (μM) of 42.3 ± 0.19 and 45.2 ± 0.55, respectively), while compounds 3 and 4 were potent inhibitors of the Jack bean urease (IC50 values (μM) of 20.3 ± 0.37and 27.6 ± 0.52, respectively), when compared to the standard inhibitor (thiourea- IC50 21.5 ± 0.47). The isolation of all the compounds from C. zenkeri and the urease activity of compounds 1 and 2 are reported for the first time.


Universal Super-Resolution Multiplexing by DNA Exchange.
Super-resolution microscopy allows optical imaging below the classical diffraction limit of light with currently up to 20× higher spatial resolution. However, the detection of multiple targets (multiplexing) is still hard to implement and time-consuming to conduct. Here, we report a straightforward sequential multiplexing approach based on the fast exchange of DNA probes which enables efficient and rapid multiplexed target detection with common super-resolution techniques such as (d)STORM, STED, and SIM. We assay our approach using DNA origami nanostructures to quantitatively assess labeling, imaging, and washing efficiency. We furthermore demonstrate the applicability of our approach by imaging multiple protein targets in fixed cells.


Expressional analysis of immune-related miRNAs in breast milk.
Immune-related miRNAs in breast milk are extracellular miRNAs that are related to immune organ development and regulation of the immune function in infants and young animals. The goal of this study was to compare the expression levels of five immune-related miRNAs in breast milk in black goats, humans, and dairy cattle. The miRNAs from milk were extracted and the expression levels were assessed using quantitive RT-PCR methods. MiR-146, miR-155, miR-181a, miR-223, and miR-150 were all detected in Dazu black goat milk, and these miRNAs were significantly more highly expressed in colostrum than in mature milk of goats (P < 0.01), except for miR-150. Further, all five miRNAs were expressed in human colostrum, but patterns differed from those in goats: miR-146 and miR-155 were highly expressed (P < 0.01) in human colostrum, whereas miR-223 was abundant in goat colostrum (P < 0.01). In addition, five miRNAs were significantly higher in bovine mature milk than in goat milk (P < 0.01). Taken together, these results confirm that immune-related miRNAs are rich in breast milk with different expression levels depending on the lactation phase and species.


[Coronary endarterectomy].
From July, 1984, to December, 1986, coronary bypass grafting was performed in 314 patients, 70 (22%) requiring coronary endarterectomy (RCA; 48 pts, LAD; 10 pts, LAD + RCA; 10 pts, Others; 2 pts). Coronary endarterectomy patients (END group) were younger and often with the risk factor of hyperlipidemia than non-endarterectomy patients (NON group). The over-all hospital mortality rate of END group was 7 per cent; perioperative myocardial infarction occurred in 7 per cent of patients. Early postoperative angiogram (4 weeks after the operation) was performed in 54 patients. The patency rate of RCA endarterectomy was 81.8 per cent, and that of LCA endarterectomy was 75 per cent. This result was poor compared with the patency rate of non-endarterectomy graft (86.6%). However without endarterectomy, with all likelihood the patency rate of those grafts would have been poorer. The results of right coronary endarterectomy are satisfactory and better than those of the left coronary artery system. This experience suggests that coronary endarterectomy is safe and an useful adjunct of saphenous vein bypass grafting procedures in the management of diffuse coronary disease, especially in RCA lesions.


Retinal vasoreactivity as a marker for chronic ischemic white matter disease?
The cerebral microvasculature cannot be easily studied non-invasively. Because the retina and brain share embryological, anatomical and physiological similarities, studies of retinal blood vessels may prove to be useful as a surrogate marker for cerebrovascular disease. In epidemiological studies abnormal retinal arteriovenous ratios (AVRs) predict the risk of stroke and vascular dementia. However, the association between retinal vasoreactivity, cerebral small vessel ischemic disease, and cerebral blood vessel function remains unknown. To examine (1) the association between cerebral ischemic white matter disease (WMD) and retinal microvessel behavior and (2) the relationship between retinal blood vessel reactivity and measures of cerebrovascular function. Cohort study of 12 patients with ischemic WMD and 14 healthy controls. Retinal vasoreactivity was measured following high frequency flicker light stimulation. Middle cerebral artery (MCA) vasoreactivity was measured using transcranial Doppler ultrasound (TCD). Magnetic resonance imaging scans (MRIs) were reviewed for evidence of ischemic WMD. Patients with ischemic WMD had attenuated retinal venous (2.2% ± 0.27 SD, vs. controls 6% ± 0.7 SD, p=0.002, CI 95%) and arterial (1.9% ± 0.8 SD, vs. controls 4.9% ± 0.8 SD, p=0.004, CI 95%) vasoreactivity compared to controls. An attenuated retinal venous light flicker response was associated with a significant decrease of MCA vasoreactivity (r=0.45, p=0.05, CI 95%). Decreased AVRs, an indicator for altered retinal vessel architecture in patients with cerebral chronic ischemic WMD, were also significantly correlated with dysfunction of cerebral vasoreactivity (r=0.69, p=0.001, CI 95%). In this study functional and structural impairment of the retinal microvasculature were associated with ischemic WMD and measures of cerebral vascular function. Microvascular dysfunction in the eye may predict cerebral small vessel disease, but validation by larger studies is needed.


Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson's disease treated with L-DOPA.
Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Areas covered: In this review, the authors describe the preclinical and clinical development of opicapone. In PD patients with motor fluctuations, once daily opicapone administration was well-tolerated and consistently reduced OFF-time and increased ON-time without increasing the frequency of troublesome dyskinesia, and these benefits were maintained over at least a year of continued open-label therapy. Expert commentary: With its convenient once-daily regimen, adjunct opicapone should be considered as an effective option for use in L-DOPA treated PD patients experiencing motor fluctuations.


Recent Expedition in Pd- and Rh-Catalyzed C(Ar) -B Bond Formations and Their Applications in Modern Organic Syntheses.
Transition metal-catalyzed borylation has emerged as a powerful and versatile strategy for synthesizing organoboron compounds. These compounds have found widespread applications in various aspects, including organic synthesis, materials science, and medicinal chemistry. This review provides a concise summary of the recent advances in palladium- and rhodium-catalyzed borylation from 2013 to 2023. The review covers the representative examples of catalysts, substrates scope and reaction conditions, with particular emphasis on the development of catalyst systems, such as phosphine ligands, NHC-carbene, and more. The diverse array of borylative products obtained for further applications in Suzuki-Miyaura coupling, and other transformations, are also discussed. Future directions in this rapidly evolving field, with the goal of designing more efficient, selective borylation methodologies are highlighted, too.


Quantitative precision of an automated image cytometric system for the measurement of DNA content and distribution in cells labeled with fluorescent nucleic acid stains.
An automated image cytometric system is described for the measurement of DNA content and distribution in cells stained with fluorescent DNA binding or intercalating compounds. The quantitative precision of integrated optical intensity (IOI) measurements using this system was estimated to be 2.0%, based on the coefficient of variation (cv) of the IOI of DNA check beads. Using peripheral blood lymphocytes stained with 4'-6-diamidino-2-phenylindole (DAPI), the cv of IOI was found to be 3.5%. Slide to slide variability of the IOI for peripheral blood lymphocytes (cv over 10 slides of the mean IOI) was found to be 2%. The most important sources of error in these measurements were glare, illumination instability, image calibration instability, and staining non-uniformity. These errors were investigated and minimized.


Mediation from multilevel to structural equation modeling.
The purpose of this article is to outline multilevel structural equation modeling (MSEM) for mediation analysis of longitudinal data. The introduction of mediating variables can improve experimental and nonexperimental studies of child growth in several ways as discussed throughout this article. Single-mediator individual-level and multilevel mediation models illustrate several current issues in the estimation of mediation with longitudinal data. The strengths of incorporating structural equation modeling (SEM) with multilevel mediation modeling are described. SUMMARY AND KEY MESSAGES: Longitudinal mediation models are pervasive in many areas of research including child growth. Longitudinal mediation models are ideally modeled as repeated measurements clustered within individuals. Further, the combination of MSEM and SEM provides an ideal approach for several reasons, including the ability to assess effects at different levels of analysis, incorporation of measurement error and possible random effects that vary across individuals.


Synthesis and Structural Reassignment of Plakinidone.
In connection with its first synthesis, plakinidone was structurally revised to a five-membered lactone. The key evidence for the previous assignment of this natural product as a perlactone was proven to be a misinterpretation of the MS data because of unawareness of a facile air oxidation. The synthetic samples also allowed for detection of differences in (13)C NMR for diastereomers of remote stereogenic centers, along with the influence of the air oxidation on the optical rotation.


[A self-retaining intraurethral device as an alternative to indwelling catheter and prostatectomy].
A new, original self-retaining intraurethral catheter (IUC), 30-60 mm long, was inserted into the urethra and bladder neck in 34 patients with urinary retention due to benign prostatic hyperplasia. The placement of the IUC is easily done under local anesthesia in the outpatient clinic. Before insertion, all the patients had had an indwelling catheter for weeks or months. In 29 patients (85.3%) the IUC was left in place from 2-38 weeks (mean 13.8). These patients voided satisfactorily and were fully continent. In 5 (14.7%) the IUC had to be removed after several days because of severe frequency or residual urine, the result of improper placement of the IUC. In 4 other patients (11.8%) the IUC was removed after 3-12 weeks because of obstruction by stones after extracorporeal shock wave lithotripsy, or because of difficulty in voiding during therapeutic diuresis for pulmonary edema. Based on our experience, it is suggested that this new device may avoid the use of the standard indwelling catheter in patients with urinary retention caused by intravesical obstruction. It may also be an alternative to prostatectomy in patients at high risk for surgery.


1999 ICP Distinguished Scientist Award. The history of positron emission tomography.
The history of Positron Emission Tomography (PET) is rich in technological achievements and advancements. The advancements that have benchmarked PET progress are the result of key components that include human intellect and passion for PET technology, relentless persuasion of key political forces to eliminate the barriers precluding PET usage, tireless efforts to raise awareness about PET and a crucial network of support throughout the PET community. This article sets forth a timeline of significant events that have contributed to the development of PET as it is known today. It introduces the earliest physicist and physician, for instance, who were responsible for the first medical applications for positron emitting radioisotopes using a simple brain probe that utilized coincidence to localize brain tumors. Additionally, it identifies landmark technological achievements that have helped pave the way to modern PET. This study includes historical accounts surrounding the use of the first human PET tomograph, discovery of the Bismuth Germanate (BGO) scintillator, development of the Fluorodeoxyglucose (FDG) PET method, the design of the first PET medical cyclotron with automated chemistry and operated by a PC and a technologist, Food and Drug Administration's approval of FDG, HCFA reimbursement, and the capacity of Lutetium Oxyorthosilicate (LSO) to produce a revolutionary advance in PET scanners. The main thrust of this article is to recognize via a timeline of PET accomplishments the noteworthy work of scientists, physicians and others who have been key players in various aspects of the continuous activity to move PET technology forward from invention to research, and to become a major clinical imaging modality.


Cloning of a cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase from rat liver and its regulation by thyroid hormones.
A full-length 2.4-kb cDNA for the FAD-linked glycerol-3-phosphate dehydrogenase (EC 18.104.22.168) was cloned from rat liver using PCR techniques. The cloned gene encodes a protein of 727 amino acids. The calculated molecular mass of 80,898 Da is higher than the apparent molecular mass observed by SDS/PAGE (74,000 Da) of the purified enzyme. This result indicates that the enzyme is synthesized as a precursor with a putative mitochondrial signal sequence. mRNA for this gene was detected in liver, heart, muscle, brain, testes, and pancreas. With the exception of testes, basal expression levels were very low in all tissues examined. However, application of thyroid hormones led to a 10- to 15-fold increase in liver glycerol-3-phosphate dehydrogenase mRNA, whereas hypothyroidism further decreased the mRNA level.


Thymic peptides and preparations: an update.
The possibilities of thymic peptides in human therapy are still being described. Here, we focus on their general characteristics and on recent advances in this area.


Toward Robust Discriminative Projections Learning Against Adversarial Patch Attacks.
As one of the most popular supervised dimensionality reduction methods, linear discriminant analysis (LDA) has been widely studied in machine learning community and applied to many scientific applications. Traditional LDA minimizes the ratio of squared l2 norms, which is vulnerable to the adversarial examples. In recent studies, many l1 -norm-based robust dimensionality reduction methods are proposed to improve the robustness of model. However, due to the difficulty of l1 -norm ratio optimization and weakness on defending a large number of adversarial examples, so far, scarce works have been proposed to utilize sparsity-inducing norms for LDA objective. In this article, we propose a novel robust discriminative projections learning (rDPL) method based on the l1,2 -norm trace-ratio minimization optimization algorithm. Minimizing the l1,2 -norm ratio problem directly is a much more challenging problem than the traditional methods, and there is no existing optimization algorithm to solve such nonsmooth terms ratio problem. We derive a new efficient algorithm to solve this challenging problem and provide a theoretical analysis on the convergence of our algorithm. The proposed algorithm is easy to implement and converges fast in practice. Extensive experiments on both synthetic data and several real benchmark datasets show the effectiveness of the proposed method on defending the adversarial patch attack by comparison with many state-of-the-art robust dimensionality reduction methods.


RNAi-mediated resistance to whitefly (Bemisia tabaci) in genetically engineered lettuce (Lactuca sativa).
RNA interference (RNAi)-based transgenic technologies have evolved as potent biochemical tools for silencing specific genes of plant pathogens and pests. The approach has been demonstrated to be useful in silencing genes in insect species. Here, we report on the successful construction of RNAi-based plasmid containing an interfering cassette designed to generate dsRNAs that target a novel v-ATPase transcript in whitefly (Bemisia tabaci), an important agricultural pest in tropical and sub-tropical regions. The presence of the transgene was confirmed in T0 and T1 generations of transgenic lettuce lines, segregating in a Mendelian fashion. Seven lines were infested with whiteflies and monitored over a period of 32 days. Analysis of mortality showed that within five days of feeding, insects on transgenic plants showed a mortality rate of 83.8-98.1%. In addition, a reduced number of eggs (95 fold less) was observed in flies feeding on transgenic lettuce plants than insects on control lines. Quantitative reverse transcription PCR showed decreased expression level of endogenous v-ATPase gene in whiteflies feeding on transgenic plants. This technology is a foundation for the production of whitefly-resistant commercial crops, improving agricultural sustainability and food security, reducing the use of more environmentally aggressive methods of pest control.


Position of Orifice of Distobuccal Canal of Maxillary Second Molars Using Cone-Beam Computed Tomography.
This study aimed to assess the position of distobuccal canal orifice of maxillary second molars using cone-beam computed tomography (CBCT). A total of 301 CBCT scans of patients were retrieved from the archives of a radiology clinic, and the distance between the orifices of distobuccal and mesiobuccal root canals, the distance between the orifices of distobuccal and palatal root canals and the angle between the orifices of mesiobuccal, distobuccal and palatal root canals in the axial plane were measured on CBCT scans. Of 301 maxillary second molars evaluated in this study, 202 (67.1%) had three canals and 99 (32.9%) had four canals. The distance between the distobuccal and mesiobuccal canal orifices (DM) ranged from 1.10 to 4.40 mm (mean: 2.1831±0.6370 mm). The distance between the distobuccal and palatal canal orifices (DP) ranged from 1.20 to 6.20 mm (mean: 3.8704±0.84944 mm). The mean angle between the mesiobuccal, distobuccal and palatal orifices (MDP) was 106.37±12.12075°. Around one-third of maxillary second molars had four canals; the rest had three canals. No maxillary second molar with two canals was found. The orifice of distobuccal canal was located at 2 mm distance from the mesiobuccal canal orifice in distopalatal direction in the majority of cases. It had 3 to 4 mm distance from the palatal canal orifice in most cases. CBCT is recommended to find the orifice of distobuccal canal in cases in whom negotiation of this canal is challenging.


[Efficacy of herb-separated moxibustion combined with sulfasalazine enteric-coated tablets for ankylosing spondylitis with cold-dampness obstruction type].
To compare the clinical efficacy between herb-separated moxibustion and conventional moxibustion on ankylosing spondylitis (AS) based on oral administration of sulfasalazine enteric-coated tablets. A total of 64 patients with AS of cold-dampness obstruction type were randomly divided into an herb-separated moxibustion group and a conventional moxibustion group, 32 cases in each one. Based on oral administration of sulfasalazine enteric-coated tablets, the patients in the conventional moxibustion group were treated with moxibustion at the area with Dazhui (GV 14) to Changqiang (GV 1) as center and about 10 cm in width; the moxibustion was given for 1 hour. In the herb-separated moxibustion group, the gauze was soaked in the medicinal liquor and ginger juice, and placed on the same moxibustion area as the conventional moxibustion group, followed by moxibustion for 1 hour. The treatment in the two groups was given once a week, three treatments constituted a course and totally three courses were given. The symptom quantification score, occipital-wall distance, Schober test, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were observed before and after treatment in the two groups, and the clinical efficacy was evaluated. Compared before treatment, the symptom quantification score, occipital-wall distance, CRP and ESR levels were lower but the Schober test was higher after treatment in the two groups (all P<0.05). The symptom quantification score, Schober test, CRP and ESR levels in the herb-separated moxibustion group were superior to those in the conventional moxibustion group (all P<0.05), but no significant difference was observed on occipital-wall distance (P>0.05). The total effective rate was 90.0% (27/30) in the herb-separated moxibustion group, which was higher than 73.3% (22/30) in the conventional moxibustion group (P<0.05). The herb-separated moxibustion combined with sulfasalazine enteric-coated tablets has significant efficacy for AS with cold-dampness obstruction type, which could obviously relieve pain symptoms, improve occipital-wall distance, Schober test and other physical signs, and improve the quality of life.


[Inhibition of the aquaporin-1 gene expression by RNA interference: experiment with cultured rat pleural mesothelial cells].
To investigate the influence of RNA interference (RNAi) on the expression of aquaporin-1 (AQP1) gene and to investigate the feasibility of gene therapy for pleural effusion. Two recombinant plasmids with shRNAs targeting the AQP1 gene, AQP1-1-pGenesil and AQP1-2-pGenesil-1 were constructed. Pleural mesothelial cells were obtained from rats, cultured, and randomly divided into 5 groups: blank control group, Lipofectamine 2000 control group, HK negative control group, AQP1-1-pGenesil-1 transfected group, and AQP1-2-pGenesil-1 transfected group. RT-PCR and Western blotting were used to detect the mRNA and protein expression of AQP1. The mRNA expression levels of aquaporin-1 of the AQP1-1-pGenesil-1 and AQP1-2-pGenesil-1 transfected groups were inhibited by 83.5% and 90.9% respectively, and the protein expression levels of the AQP1-1-pGenesil-1 and AQP1-2-pGenesil-1 transfected groups were inhibited by 41.2% and 67.6% respectively. RNAi can successfully inhibit the expression of AQP1 and has the feature of sequence correlation of shRNA in the cultured rat pleural mesothelial cells. It may be used as a potential new approach for gene therapy of pleural effusion.


Cytotoxicity and Bioactivity of Calcium Silicate Cements Combined with Niobium Oxide in Different Cell Lines.
The aim of this study was to evaluate the cytotoxicity and bioactivity of calcium silicate-based cements combined with niobium oxide (Nb2O5) micro and nanoparticles, comparing the response in different cell lines. This evaluation used four cell lines: two primary cultures (human dental pulp cells - hDPCs and human dental follicle cells - hDFCs) and two immortalized cultures (human osteoblast-like cells - Saos-2 and mouse periodontal ligament cells - mPDL). The tested materials were: White Portland Cement (PC), mineral trioxide aggregate (MTA), white Portland cement combined with microparticles (PC/Nb2O5µ) or nanoparticles (PC/Nb2O5n) of niobium oxide (Nb2O5). Cytotoxicity was evaluated by the methylthiazolyldiphenyl-tetrazolium bromide (MTT) and trypan blue exclusion assays and bioactivity by alkaline phosphatase (ALP) enzyme activity. Results were analyzed by ANOVA and Tukey test (a=0.05). PC/Nb2O5n presented similar or higher cell viability than PC/Nb2O5µ in all cell lines. Moreover, the materials presented similar or higher cell viability than MTA. Saos-2 exhibited high ALP activity, highlighting PC/Nb2O5µ material at 7 days of exposure. In conclusion, calcium silicate cements combined with micro and nanoparticles of Nb2O5 presented cytocompatibility and bioactivity, demonstrating the potential of Nb2O5 as an alternative radiopacifier agent for these cements. The different cell lines had similar response to cytotoxicity evaluation of calcium silicate cements. However, bioactivity was more accurately detected in human osteoblast-like cell line, Saos-2.


Seed Endophyte bacteria enhance drought stress tolerance in Hordeum vulgare by regulating, physiological characteristics, antioxidants and minerals uptake.
Growth stimulating bacteria help remediate dry arid soil and plant stress. Here, Pseudomonas sp. and Pantoea sp. we used to study the stress ecology of Hordeum vulgare and the environmental impact of water deficit on soil characteristics, growth, photosynthesis apparatus, mineral acquisition and antioxidiant defense. Plants inoculated with Pseudomonas or Pantoea had significantly higher (about 2 folds) soil carbon flux (soil respiration), chlorophyll levels (18%), net photosynthetic rate (33% in Pantoea and 54% in Pseudomonas), (44%) stomatal conductance than uninoculated plants in stressed conditions. Both bacterial strains improved leaf growth (23-29%) and root development under well-watered conditions but reduced around (25%) root biomass under drought. Plants inoculated with Pseudomonas or Pantoea under drought also increased of about 27% leaf respiration and transpiration (48%) but decreased water use efficiency, photoinhibition (91%), and the risk of oxidative stress (ETR/A) (49%). Drought stress increased most of the studied antioxidant enzymatic activities in the plants inoculated with Pseudomonas or Pantoea, which reduce the membrane damage and protect plants form oxidative defenses. Drought stress increased K+ acquisition around 50% in both shoots inoculated with Pseudomonas or Pantoea relative to non-stressed plants. Plants inoculated with Pseudomonas or Pantoea increased shoot Na+ while root Na+ only increased in plants inoculated with Pseudomonas in stressed conditions. Drought stress increased shoot Mg2+ in plants inoculated with Pseudomonas or Pantoea but did not affect Ca2+ relative to non-stressed plants. Drought stress increased about 70% K+/Na+ ratio only in plants inoculated with Pseudomonas relative to non-stressed plants. Our results indicate that inoculating barley with the studied bacterial strains increases plant biomass and can therefore play a role in the environmental remediation of drylands for food production.


Tunable multiwavelength mode-locked Tm/Ho-doped fiber laser based on a nonlinear amplified loop mirror.
We propose and demonstrate a tunable multiwavelength mode-locked Tm/Ho-doped fiber laser based on a nonlinear amplified loop mirror (NALM). Without using polarization-maintaining fiber, only passive fibers with low birefringence were inserted into the NALM to help overcome mode competition and realize mode-locking. The spacing between adjacent channels was measured to be ∼6 nm. By adjusting the polarization controllers (PCs) to an appropriate position, self-started mode-locking was achieved, which further overcame the mode competition in the fiber laser. A multiwavelength mode-locked fiber laser with at least three available channels were tunable in the widest range of 30 nm (from 1935 to 1965 nm) with a 3 dB channel bandwidth of ∼1.6 nm. This multiwavelength mode-locked fiber laser is quite stable with the maximum peak fluctuation within 0.47 dB in long-term observations.


Key to Chinese species of Copidosoma (Hymenoptera: Encyrtidae), with new records and three new species.
Six species of Copidosoma (Hymenoptera: Encyrtidae) from Southwestern China are reviewed, including three new species (C. heinitane sp. nov., C. linzhiensis sp. nov., C. longchuane sp. nov.) and two species newly recorded from China (C. longiclavatum Kazmi Hayat and C. recurvariae Sharkov). Copidosoma serricorne (Dalman) is newly recorded from Xizang, southwestern part of China. A key to all the Chinese species of the genus based on females is given.


Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women with epilepsy.
To compare the proportions of unintended pregnancies, prenatal vitamin or folic acid (PNVF) use, adequate prenatal care visits, and breastfeeding among women with epilepsy (WWE) to women without epilepsy (WWoE). The Pregnancy Risk Assessment Monitoring System (PRAMS) is an annual survey of randomly sampled postpartum women administered by the Centers for Disease Control and Prevention. We used PRAMS data from 13 states from 2009 to 2014 to compare the primary outcomes in WWE and WWoE, as well as our secondary outcomes of contraception practices, newborn outcomes, and time to recognition of pregnancy. We adjusted for maternal age, race, ethnicity, and socioeconomic status (SES), and we calculated odds ratios for these outcomes using logistic regression. This analysis included 73,619 women, of whom 541 (0.7%) reported epilepsy, representing 3,442,128 WWoE and 26,635 WWE through weighted sampling. In WWE, 55% of pregnancies were unintended compared to 48% in WWoE. After adjustment for covariates, epilepsy was not associated with unintended pregnancy or with inadequate prenatal care. WWE were less likely to report breastfeeding but more likely to report daily PNVF use. Newborns of WWE had higher rates of prematurity. Although planning for pregnancy is of utmost importance for WWE, more than half the pregnancies in WWE were unintended. Maternal age and SES differences likely contribute to the higher rates in WWE compared to WWoE. The proportion of women reporting breastfeeding is lower in WWE despite studies indicating the safety of breastfeeding in WWE.


Novel Process for 3D Printing Decellularized Matrices.
3D bioprinting aims to create custom scaffolds that are biologically active and accommodate the desired size and geometry. A thermoplastic backbone can provide mechanical stability similar to native tissue while biologic agents offer compositional cues to progenitor cells, leading to their migration, proliferation, and differentiation to reconstitute the original tissues/organs1 , 2. Unfortunately, many 3D printing compatible, bioresorbable polymers (such as polylactic acid, PLA) are printed at temperatures of 210 °C or higher - temperatures that are detrimental to biologics. On the other hand, polycaprolactone (PCL), a different type of polyester, is a bioresorbable, 3D printable material that has a gentler printing temperature of 65 °C. Therefore, it was hypothesized that decellularized extracellular matrix (DM) contained within a thermally protective PLA barrier could be printed within PCL filament and remain in its functional conformation. In this work, osteochondral repair was the application for which the hypothesis was tested. As such, porcine cartilage was decellularized and encapsulated in polylactic acid (PLA) microspheres which were then extruded with polycaprolactone (PCL) into filament to produce 3D constructs via fused deposition modeling. The constructs with or without the microspheres (PLA-DM/PCL and PCL(-), respectively) were evaluated for differences in surface features.


Characterisation of N-(Octadecyl)-1,8-naphthalimide Monolayer Compression Using Molecular Dynamics and Experimental Approaches.
The development of luminescent surfaces is an active area of supramolecular chemistry, particularly for the development of new sensing platforms. One particularly useful surface deposition method is the Langmuir-Blodgett technique where organic amphiphilic fluorophores (e.g. 1,8-naphthalimides) can form ordered monolayers at an air-water interface before being deposited onto solid supports. The ability to simulate monolayer formation and consequently develop predictability over film formation would allow for significant advances in the luminescent materials field where synthesis might be directed by simulation data. Here, we compare pressure-area isotherms of N-(octadecyl)-1,8-naphthalimide determined experimentally, using the Langmuir-Blodgett technique, and computationally, using three different simulation techniques. We find that all three simulation techniques are able to describe the liquid-condensed/liquid-expanded region of the isotherm, and that the isotherms are highly similar in this region, although the NγT ensemble performs best. Experimental isotherms showed film formation properties that align with the simulation data, suggesting that simulations are a viable means to direct synthesis. Investigation of the underlying structural details disclosed by the simulations reveals the compression-induced ordering at atomic-level detail, which will allow prediction of how functionalisation of the naphthalimides will alter the monolayer compression and mounting process.


Cerebrospinal fluid in the differential diagnosis of Alzheimer's disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic.
Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias. We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls. Patients fulfilled consensus criteria for AD (n = 156), DLB (n = 20), behavioural variant frontotemporal dementia (bvFTD; n = 45), progressive non-fluent aphasia (PNFA; n = 17), and semantic dementia (SD; n = 7); approximately 10% were pathology/genetically confirmed (n = 26). Global tests based on generalised least squares regression were used to determine differences between groups. Non-parametric receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were used to quantify how well each biomarker discriminated AD from each of the other diagnostic groups (or combinations of groups). CSF cut-points for the major biomarkers found to have diagnostic utility were validated using an independent cohort which included causes of AD (n = 104), DLB (n = 5), bvFTD (n = 12), PNFA (n = 3), SD (n = 9), and controls (n = 10). There were significant global differences in Aβ1-42, T-tau, T-tau/Aβ1-42 ratio, P-tau-181, NFL, AβX-42, AβX-42/X-40 ratio, APPα, and APPβ between groups. At a fixed sensitivity of 85%, AβX-42/X-40 could differentiate AD from controls, bvFTD, and SD with specificities of 93%, 85%, and 100%, respectively; for T-tau/Aβ1-42 these specificities were 83%, 70%, and 86%. AβX-42/X-40 had similar or higher specificity than Aβ1-42. No biomarker or ratio could differentiate AD from DLB or PNFA with specificity > 50%. Similar sensitivities and specificities were found in the independent validation cohort for differentiating AD and other dementias and in a pathology/genetically confirmed sub-cohort. CSF AβX-42/X-40 and T-tau/Aβ1-42 ratios have utility in distinguishing AD from controls, bvFTD, and SD. None of the biomarkers tested had good specificity at distinguishing AD from DLB or PNFA.


Placental abruption.
Placental abruption complicates approximately 1% to 2% of all pregnancies and remains a significant cause of both maternal and fetal morbidity. Proposed pathophysiology of both acute placental abruption and the more common partial placental separation are discussed. The contribution of placental abruption to both preterm labor and preterm premature rupture of membranes is discussed. Recent evidence supporting maternal hypertensive disorders, maternal tobacco and cocaine use, age and parity, multiple gestations, maternal thrombophilias, and an unexplained elevated maternal serum alphafetoprotein as risk factors for abruption is reviewed. Emergency management of acute abruption is outlined. Finally, particular emphasis is given to the management of partial placental separation, including both immediate and delayed delivery and the use of tocolysis. Obstetricians and Gynecologists, Family Physicians. After completion of this article, the reader will be able to define the condition of placental abruption, list the conditions associated with abruption, and outline potential management options for patients with placental abruption.


[Researches of autonomic regulation of blood circulation in the condition of long-term space flight].
In the article is presented five-year experience of experimentation in autonomic regulation of blood circulation onboard the International space station. The heart rate variability (HRV) analysis was the basic methodical approach in the researches. We described probabilistic approach created on the basis of HRV analysis to an estimation of risk of pathology development in the conditions of long space flight. The individual type of autonomic regulation had essential value during the analysis of results. It is shown that the type of regulation, which is inherent in every cosmonaut in the conditions of weightlessness, remains even during following flights. We obtained the new scientific data on connection of character of adaptable reaction of an organism to the space flight factors with individual type of autonomic regulation. It is shown that staying in weightlessness is connected with changeover of regulatory systems and with transition in a zone of prenosological states. Adaptable reactions in weightlessness are characterized by tension growth of regulatory systems at preservation of sufficient functional reserves. The mobilization of additional resources after returning to the Earth is required and consequently functional reserve of mechanisms of regulation decreases. Cosmonauts with vagotonic and normo-sympatotonic types of autonomic regulation appear to be the most resistant. Knowing the type of autonomic regulation we will be able to foresee possible reaction of the cosmonaut to the factors of space flight. As a result of HRV analysis during the flight of the past few months likelihood estimations were calculated and risk categories were defined. Consequently, 3 groups of risk of pathology development were distinguished. In conclusion, theoretical and applied relevance of the conducted experiments were considered.


Gender solidarity in hierarchical organizations.
Previous research has suggested that promotion decisions in hierarchical organizations may vary as a function of the decision maker's sex. In particular, it has been argued that women may be more likely to support a same-sex other than men due to higher levels of identification with their gender in-group. This paper reports findings from two experiments which examine gender identification and candidate promotion strategies amongst university students (N = 116) and public servants (N = 136) in hypothetical organizations which manipulated the participants' personal status and that of their gender in-group. In the university sample women did identify more strongly with their sex than men. This was not generally the case in the public service sample, although here women with high personal status tended to show greater identification than men in a similar position. However, in both studies there was little evidence that gender identification was associated with preferential treatment of in-group candidates in promotion-related decisions. These decisions were generally influenced by norms of fairness qualified by the participants' personal status. Implications for the self-categorization process are discussed.


Idiopathic scoliosis in three dimensions. A radiographic and morphometric analysis.
Eleven articulated scoliotic spines were examined radiographically and morphometrically. Measurement of the curve on anteroposterior radiographs of the specimens gave a mean Cobb angle of 70 degrees, though true anteroposterior radiographs of the deformity revealed a mean Cobb angle of 99 degrees (41% greater). Lateral radiographs gave the erroneous impression that there was a mean kyphosis of 41 degrees while true lateral projections revealed a mean apical lordosis of 14 degrees. Morphometric measurements confirmed the presence of a lordosis at bony level, the apical vertebral bodies being significantly taller anteriorly (P less than 0.02). There were significant correlations (P less than 0.01) between the true size of the lateral scoliosis, the amount of axial rotation and the size of the apical lordosis. This study illustrates the three-dimensional nature of the deformity in scoliosis and its property of changing in character and magnitude according to the plane of radiographic projection.


MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry.
A substantial percentage of patients with mitral regurgitation (MR) in need of mitral valve repair are currently considered not suitable for conventional surgery. In Germany, the largest cohort of patients studied to date has been treated using a percutaneous, catheter-based approach. We report the acute outcomes of patients enrolled in the investigator-initiated German transcatheter mitral valve interventions (TRAMI) registry. Between January 2009 and August 2011, 486 patients [median age 75 (interquartile range 70-80) years; 200 women (41%)] were enrolled in the registry (309 retrospectively and 177 prospectively), with 481 patients (99%) having undergone percutaneous edge-to-edge therapy for MR using the MitraClip. At baseline, 93% of patients were in New York Heart Association (NYHA) functional class III or IV and 71% of patients had a left ventricular ejection fraction (LVEF) ≤50%. Two-thirds of patients presented with functional MR. Procedural success was achieved in 94% of patients, with grade III present in 93% of patients at baseline yet only 6% post-intervention. Retrospective patients were followed for a median of 183 days, prospective patients for a median of 44 days. The periprocedural complication rate was low, with only minor bleedings as the most significant event. In-hospital and post-discharge mortality was 2.5% and 12.5%, respectively. Data from the German TRAMI registry suggest that MitraClip therapy is a viable treatment option in daily clinical routine for high surgical risk patients with significant MR.


Preparation, structures and some reactions of novel diynyl complexes of iron and ruthenium.
Reactions between HC triple bond CC triple bond CSiMe3 and several ruthenium halide precursors have given the complexes Ru(C triple bond CC triple bond CSiMe3)(L2)Cp'[Cp'= Cp, L = CO (1), PPh3 (2); Cp' = Cp*, L2= dppe (3)]. Proto-desilylation of 2 and 3 have given unsubstituted buta-1,3-diyn-1-yl complexes Ru(C triple bond CC triple bond CH)(L2)Cp'[Cp'= Cp, L = PPh3 (5); Cp'= Cp*, L2 = dppe (6)]. Replacement of H in 5 or 6 with Au(PR3) groups was achieved in reactions with AuCl(PR3) in the presence of KN(SiMe3)2 to give Ru(C triple bond CC triple bond CAu(PR3)](L2)Cp'[Cp' = Cp, L = PPh3, R = Ph (7); Cp' = Cp*, L2= dppe, R = Ph (8), tol (9)]. The asymmetrically end-capped [Cp(Ph3P)2Ru]C triple bond CC triple bond C[Ru(dppe)Cp*] (10) was obtained from Ru(C triple bond CC triple bond CH)(dppe)Cp* and RuCl(PPh3)2Cp. Single-crystal X-ray structural determinations of and are reported, with a comparative determination of the structure of Fe(C triple bond CC triple bond CSiMe3)(dppe)Cp* (4), and those of a fifth polymorph of [Ru(PPh3)2Cp]2(mu-C triple bond CC triple bond C) (12), and [Ru(dppe)Cp]2(mu-C triple bond CC triple bond C) (13).


Influence of a beta-adrenoceptor stimulant, KWD 2131, in nasal histamine provocation tests. Rhinomanometric evaluations in normal persons and patients with hay fever.
Nasal histamine provocation was performed in ll asymptomatic (out of season) patients with hay fever and in ll normal controls. Posterior rhinomanometry was used for objective evaluation. The histamine challenges caused nasal symptoms as well as increased nasal airway resistance. The differences in response between the two groups of subjects were not significant. KWD 2131, a beta-adrenoceptor-stimulating drug which was ascribed an antiallergic effect in a previous allergen provocation study, did not block the effects of histamine challenge in a randomized, placebo-controlled, double-blind, crossover evaluation. The absence of protective action against histamine-induced effects with KWD 2131, supports a mast-cell-stabilizing effect of the substance in allergen provocation.


Oncocytic tumors are marked by enhanced mitochondrial content and mtDNA mutations of complex I in Chinese patients.
Oncocytic tumors are composed of oncocytes characterized by acidophilic granular and reticular cytoplasm. Such features have been attributed to the distinctive aggregation of abnormal mitochondria. Sporadic mitochondrial DNA (mtDNA) mutations, particularly those in complex I subunit genes, have been identified as one of the most noticeable alterations. We reviewed 11,051 cases of patients with thyroid tumors who visited the First Affiliated Hospital of Wenzhou Medical University from January 2011 to August 2017, and we were able to identify 123 cases as oncocytic tumors. We found that older people are at higher risk (P < 0.001) for oncocytic tumors. We confirmed an increased mitochondrial mass in representative samples. Furthermore, a comprehensive analysis of the mitochondrial genomes in patients with oncocytomas revealed 1) haplogroups D5 and A exhibit increased risk of oncocytomas; 2) 60% of mtDNA mutations are in genes encoding respiratory complex subunits while 8% occur in rRNA and 4% in tRNA regions; 3) among mutations in coding regions, 50% are in Complex I genes, including most of the disruptive mutations; 4) 64% of mtDNA mutations are heteroplasmic. Our studies imply a tumorigenesis mechanism for oncocytomas involving mitochondrial alterations mediated by genome instability and modified by mitochondrial haplogroups.


Spread of resistant gram negatives in a Sri Lankan intensive care unit.
Infections with multi drug resistant (MDR) organisms are a major problem in intensive care units (ICUs). Proper infection control procedures are mandatory to combat the spread of resistant organisms within ICUs. Well stablished surveillance programmes will enhance the adherence of the staff to infection control protocols. The study was conducted to assess the feasibility of using basic molecular typing methods and routine hospital data for laboratory surveillance of resistance organisms in resource limited settings. A retrospective study was conducted using consecutive Gram negative isolates obtained from an ICU over a six month period. Antibiotic sensitivity patterns and random amplified polymorphic DNA (RAPD) based typing was performed on the given isolates. Of the seventy isolates included in the study, seven were E.coli. All E.coli were MDRs and Extended Spectrum β lactamse (ESBL) producers carrying bla CTX-M. Fourteen isolates were K.pneumoniae, and all were MDRs and ESBL producers. All K.pneumoniae harboured bla SHV while 13 harboured bla CTX-M. The MDR rate among P.aeruginosa was 13% (n=15) while all acinetobacters (n=30) were MDRs. Predominant clusters were identified within all four types of Gram negatives using RAPD and the ICU stay of patients overlapped temporally. We propose that simple surveillance methods like RAPD based typing and basic hospital data can be used to convince hospital staff to adhere to infection control protocols more effectively, in low and middle income countries.


Assessing methylphenidate preference in ADHD patients using a choice procedure.
Methylphenidate (MPH) is widely used in the treatment of attention deficit hyperactivity disorder (ADHD) and is associated with positive clinical effects across a wide range of domains. Despite the clinical effectiveness of MPH, concern has arisen with respect to its abuse potential. To assess MPH preference in adults diagnosed with ADHD using a choice procedure and to evaluate the relationship among drug preference, therapeutic efficacy, and abuse potential in a clinical sample. Participants were ten volunteers (ages 18-22 years) with ADHD who were receiving MPH treatment. Preference was assessed using a double-blind choice procedure with four sampling sessions wherein subjects received either placebo or MPH and eight choice sessions when they chose either capsule or no capsules. Overall, MPH was chosen significantly more often than placebo (chi2=52.5; P<0.001) and participants were equally separated into groups of those who chose MPH reliably (MPH choosers) and those who did not (MPH non-choosers). MPH decreased ADHD symptoms and resulted in lower ratings of stimulant effects among MPH choosers. MPH choosers also reported higher levels of baseline ADHD symptoms. Despite higher preference of MPH than placebo in this clinical sample, other measures of abuse potential were not elevated, and MPH choosers were more symptomatic than non-choosers. As such, MPH preference in ADHD populations likely reflects therapeutic efficacy rather than abuse potential. Future work should examine MPH choice in diagnosed and non-diagnosed populations to further explore the role of clinical efficacy in the preference of this stimulant drug.


Synthesis and characterization of blood compatible surfaces. Part I. Dynamic tube test applied to heparinized surfaces.
A 3 yr study has shown that this test procedure can monitor subtle differences in surface chemistry with a high degree of reproducibility. Based on the present studies, the test appears to be a valid screening tool for examining materials in a dynamic flow situation without the need for animal sacrifice often associated with blood testing. Also, due to the small amount of blood required, numerous samples can be run on the same animal which is extremely advantageous when comparing treatment methods. In addition, the simplicity of the test should make it easily adaptable to most blood testing laboratories.


Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats.
Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials. To evaluate potential synergistic neuroprotective effects of prolonged citicoline treatment and early N-methyl-D-aspartate (NMDA) antagonist therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone and in combination in a rat model of temporary focal ischemia. Four groups of Sprague-Dawley rats (n = 12 per group) underwent 90 minutes of temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals were randomly and blindly assigned to one of four treatment groups: (1) saline, vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride staining was used to assess postmortem infarct volume. Neurological scores were determined daily. Premature mortality between days 2 and 4 was 33.3% in group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct volume was significantly reduced in group 4 compared with the others (175.2 +/- 89.3 mm3 in group 1, 179.1 +/- 78.5 mm3 in group 2, 163.9 +/- 73.7 mm3 in group 3, and 84.7 +/- 56.8 mm3 in group 4 [P < .02, ANOVA and P < .05, Scheffé's test for group 1 versus group 4]). Mean infarct volume in animals dying prematurely was significantly (P < .05, Student's t test) larger in group 1 than those surviving for 7 days (247.2 +/- 89.5 versus 139.2 +/- 68.2 mm3), but there was no significant difference in infarct volume in groups 2, 3, and 4 between animals dying prematurely and those surviving for 7 days. These results demonstrate synergistic neuroprotective effects of citicoline and an NMDA antagonist in temporary experimental focal ischemia.


How well do policymakers address stigma surrounding substance use disorders: lessons from a qualitative review of Scottish Alcohol and Drug Partnerships' strategic plans.
Stigma is a significant barrier to the successful implementation of public health policies which aim to reduce harm from substance use disorders. Despite attention being given to stigma in the literature for at least a decade, evidence on what works to reduce it is limited and inconclusive. Without clear guidance, policymakers could be limited in their ability to develop evidence-informed strategies for reducing stigma. In response to a steep incline in drug-related deaths in Scotland since 1996, the Scottish Government has committed to tackling stigma in national drug policy. Scotland's 31 Alcohol and Drug Partnerships are responsible for developing local strategies that aim to tackle harm from substance use disorders. This qualitative review explored how well these strategies respond to stigma and identified approaches mentioned that could have implicit implications for tackling stigma. The strategic plans of Alcohol and Drug Partnerships across Scotland were identified and thematically analysed to identify key themes relating to stigma. Content of strategic plans was initially coded under a coding scheme of four broad categories: content that explicitly mentioned stigma; identity, status and power; deservedness of support; and attribution of responsibility for SUDs. Twenty-four strategic plans were identified and analysed, with four themes emerging: (1) limited clarity and consistency on how stigma will be directly tackled by ADPs; (2) recognition of the positive contribution that people with substance use disorders can make towards decisions about treatment and support; (3) diversion of people with substance use disorders away from the criminal justice system towards quality support underpinned by human rights; and (4) recognition of the complex determinants of substance use disorders and that everyone has a role to play. Alcohol and Drug Partnerships acknowledged the importance of tackling stigma in their strategic plans but provide limited clarity on how this will be done. This review calls for the inclusion of more evidence-informed strategies for tackling stigma within the Scottish local policymaking context. This requires academic, policymaking and lived experience communities to collaborate to test and evaluate innovative responses to tackling in stigma to strengthen understanding of what works in which contexts.


Classification of cultured mammalian cells by shape analysis and pattern recognition.
We have developed a method for classifying cultured cells on the basis of shape characteristics. High-resolution optical information on three-dimensional shape was obtained by anodic oxide interferometry. Each interference order formed in a cell was considered as a closed figure; measurement of 37 mathematical descriptors was carried out for each figure. The individual cells were classified according to the values of their descriptors. We used standard principles of pattern recognition, such as hierarchical cluster analysis and nearest neighbor analysis, as a basis for ordering the cells into groups. Alternatively, linear discriminant functions could be used, but they provided only a slight improvement in correct classification of the cells. We anticipate that the method will be appropriate for classification of cultured cell lines and for determination of the magnitude and direction of cell shape changes implicated in various biological processes.


Intestinal bifidobacteria that produce trans-9, trans-11 conjugated linoleic acid: a fatty acid with antiproliferative activity against human colon SW480 and HT-29 cancer cells.
Bifidobacterium breve species of human intestinal origin have the ability to synthesize cis-9, trans-11 (c9, t11) conjugated linoleic acid (CLA) from free linoleic acid. In this study, the ability of Bifidobacterium species to isomerize C(18) polyunsaturated fatty acids was investigated, and the antiproliferative activities of the two main microbially produced CLA isomers were assessed. Linoleic acid was converted principally to c9, t11 CLA and lesser amounts of t9, t11 CLA, whereas c9, t11 CLA was converted mainly to t9, t11 CLA. Likewise, t10, c12 CLA was converted principally to t9, t11 CLA, which was incorporated into the bacterial cell membranes. To examine the antiproliferative effect of the two main CLA isomers formed, SW480 and HT-29 human colon cancer cells were cultured in the presence of c9, t11 CLA and t9, t11 CLA. The t9, t11 CLA had a more potent antiproliferative effect than c9, t11 CLA. It is tempting to suggest that the ability of Bifidobacterium to produce such bioactive metabolites may be associated with the beneficial effects of bifidobacteria present in the human gastrointestinal tract.


Effect of CMB Carrying PTX and CRISPR/Cas9 on Endometrial Cancer Naked Mouse Model.
Endometrial cancer, one of the most common gynecological cancers in women. Patients with advanced or recurrent disease have poor long-term outcomes. The current experiment explore the roles of cationic microbubbles (CMBs) carrying paclitaxel (PTX) and CRISPR/Cas9 plasmids on the xenotransplantation model of mice with endometrial cancer. The tumor histology, tumor cell viability, cell cycle, and invasion ability were investigated. Meanwhile, the P27, P21, GSK-3, Bcl-2 associated death promoter (Bad), mammalian target of rapamycin (mTOR), and C-erbB-2 expressions were evaluated by qRT-PCR and western blotting, respectively. CMB-PTX-CRISPR/Cas9 had an inhibitory action on the tumor growth, tumor cell viability, cell cycle, and invasion ability of the mouse xenograft model of endometrial cancer. The CMB-PTX-CRISPR/Cas9 increased the GSK-3, P21, P27, and Bad expression levels, while reduced the C-erbB-2 and mTOR expressions. CMBs loaded with both PTX and CRISPR/Cas9 plasmids may be a new combination treatment with much potential. CMB-PTX-CRISPR/Cas9 may regulate the tumor cell viability, invasion, and metastasis of endometrial cancer naked mouse model by upregulating expressions of GSK-3, P21, P27, and Bad.


Canonical and Novel Non-Canonical Cholinergic Agonists Inhibit ATP-Induced Release of Monocytic Interleukin-1β via Different Combinations of Nicotinic Acetylcholine Receptor Subunits α7, α9 and α10.
Recently, we discovered a cholinergic mechanism that inhibits the adenosine triphosphate (ATP)-dependent release of interleukin-1β (IL-1β) by human monocytes via nicotinic acetylcholine receptors (nAChRs) composed of α7, α9 and/or α10 subunits. Furthermore, we identified phosphocholine (PC) and dipalmitoylphosphatidylcholine (DPPC) as novel nicotinic agonists that elicit metabotropic activity at monocytic nAChR. Interestingly, PC does not provoke ion channel responses at conventional nAChRs composed of subunits α9 and α10. The purpose of this study is to determine the composition of nAChRs necessary for nicotinic signaling in monocytic cells and to test the hypothesis that common metabolites of phosphatidylcholines, lysophosphatidylcholine (LPC) and glycerophosphocholine (G-PC), function as nAChR agonists. In peripheral blood mononuclear cells from nAChR gene-deficient mice, we demonstrated that inhibition of ATP-dependent release of IL-1β by acetylcholine (ACh), nicotine and PC depends on subunits α7, α9 and α10. Using a panel of nAChR antagonists and siRNA technology, we confirmed the involvement of these subunits in the control of IL-1β release in the human monocytic cell line U937. Furthermore, we showed that LPC (C16:0) and G-PC efficiently inhibit ATP-dependent release of IL-1β. Of note, the inhibitory effects mediated by LPC and G-PC depend on nAChR subunits α9 and α10, but only to a small degree on α7. In Xenopuslaevis oocytes heterologously expressing different combinations of human α7, α9 or α10 subunits, ACh induced canonical ion channel activity, whereas LPC, G-PC and PC did not. In conclusion, we demonstrate that canonical nicotinic agonists and PC elicit metabotropic nAChR activity in monocytes via interaction of nAChR subunits α7, α9 and α10. For the metabotropic signaling of LPC and G-PC, nAChR subunits α9 and α10 are needed, whereas α7 is virtually dispensable. Furthermore, molecules bearing a PC group in general seem to regulate immune functions without perturbing canonical ion channel functions of nAChR.


Glutamine-supplemented tube feedings versus total parenteral nutrition in children receiving intensive chemotherapy.
Although enteral nutrition is generally advocated in the care of children with cancer, those patients receiving intensive chemotherapy alone or in combination with bone marrow transplantation often require total parenteral nutrition (TPN). Two patients are presented illustrating some differences between enteral and parenteral feedings in children receiving intensive chemotherapy. Nasogastric glutamine-supplemented tube feedings were well tolerated both in the hospital and at home. The cost of care for the enterally supported child was less than one third of the TPN-supported child. Although TPN appears to be beneficial in some patients with cancer, it is expensive and is associated with several significant disadvantages. Among these are an increased incidence of both gram-positive and gram-negative infections and an increased incidence of gastrointestinal symptoms. Enteral nutrition is less costly than TPN and maintains the structural and functional integrity of the intestinal mucosa. The addition of certain substrates such as glutamine, arginine and omega-3 fatty acids may improve the body's immune response as well. We hypothesize that early glutamine supplemented tube feedings in children receiving intensive chemotherapy alone or in combination with bone marrow transplantation will result in improved nutrition with fewer infections and lower cost than TPN-supplemented patients. In addition, a shorter hospital stay and improved quality of life are anticipated.


Rayleigh matches in carriers of inherited color vision defects: the contribution from the third L/M photopigment.
The mother or daughter of a male with an X-chromosome-linked red/green color defect is an obligate carrier of the color deficient gene array. According to the Lyonization hypothesis, a female carrier's defective gene is expressed and thus carriers may have more than two types of pigments in the L/M photopigment range. An open question is how a carrier's third cone pigment in the L/M range affects the postreceptoral neural signals encoding color. Here, a model considered how the signal from the third pigment pools with signals from the normal's two pigments in the L/M range. Three alternative assumptions were considered for the signal from the third cone pigment: it pools with the signal from (1) L cones, (2) M cones, or (3) both types of cones. Spectral-sensitivity peak, optical density, and the relative number of each cone type were factors in the model. The model showed that differences in Rayleigh matches among carriers can be due to individual differences in the number of the third type of L/M cone, and the spectral sensitivity peak and optical density of the third L/M pigment; surprisingly, however, individual differences in the cone ratio of the other two cone types (one L and the other M) did not affect the match. The predicted matches were compared to Schmidt's (1934/1955) report of carriers' Rayleigh matches. For carriers of either protanomaly or deuteranomaly, these matches were not consistent with the signal from the third L/M pigment combining with only the signal from M cones. The matches could be accounted for by pooling the third-pigment's response with L-cone signals, either exclusively or randomly with M-cone responses as well.


Social health insurance: a knowledge-do gap in eastern Nepal.
Health care costs, and those for inpatient care in particular, pose a barrier to seeking health care, and cost be a major cause of indebtedness and impoverishment, particularly among the poor. The Ministry of Health in Nepal intends to initiate alternative financing schemes such as community and social health insurance schemes as a means to supplement the government health sector financing source. Social Health Insurance (SHI) is a mechanism for financing and purchasing / delivering health care to workers in the formal sector regulated by the government. Considering all these facts BP Koirala Institute of Health Sciences (BPKIHS) has introduced SHI scheme in 2000 as an alternative health care financing mechanism to the community people of Sunsari and Morang districts. In the beginning small area was elected as a pilot project to launch the scheme. A major objective of SHI is to reduce poverty caused by paying for health care and to prevent already vulnerable families from falling into deeper poverty when facing health problems. A total of 26 organizations with 19799 populations are at present in SHI scheme. Sixteen rural based organizations with 14,047 populations and 10 urban based organizations with 5752 people are the beneficiaries in this scheme. BPKIHS SHI Scheme is the outcome of the visionary thinking on social solidarity and as an alternative health care financing mechanism to the community. BPKIHS is mobilizing people's organizations and is offering health services through its health insurance scheme at subsidized expenses. This has helped people to avail with health facilities who otherwise would have been left vulnerable because of their penetrating health needs. There is huge gap between premium collection and expenditures. The expenditures are more and this may be due to knowledge - do gap in the program. If conditions are unsuitable, SHI can lead to higher costs of care, inefficient allocation of health care resources, inequitable provision and dissatisfied patients. It can also be more difficult to realize the potential advantages of SHI in future. The future challenges confronting the scheme are to give the continuity and sustainability of the program to its catchments areas. This might entail a shift in its program operation mechanism. People's active involvement is required, which will further provide a sense of ownership in the scheme amongst the people.


Preoperative characteristics of patients undergoing LASIK in 1997 versus 2004 at one surgical eye center in China.
To compare the preoperative characteristics of LASIK patients undergoing surgery in 1997 versus 2004 at one of the principal eye surgical centers in China. Preoperative data of patients who underwent LASIK in 1997 and 2004 were recorded and retrospectively compared. In 1997, the mean spherical equivalent refraction of the 824 eyes of 428 patients undergoing LASIK surgery was -7.30 +/- 4.65 diopters (D), with a mean patient age of 24.67 +/- 6.76 years. Students represented 45.05% of patients undergoing surgery in 1997. In 2004, the mean spherical equivalent refraction of the 8434 eyes of 4286 patients undergoing LASIK surgery was -6.66 +/- 3.31 D, with a mean patient age of 25.20 +/- 6.59 years. Students represented >50% of patients undergoing surgery in 2004. There were significant differences in the constitution ratio of occupation and the spherical equivalent refractions between 1997 and 2004 (t=-2.712, chi-squared=25.117, respectively, P<.05). At our center in China, the majority of LASIK patients are young and have myopia ranging from -3.00 to -10.00 D. Students were much more likely than any other occupation to undergo LASIK. The number of patients undergoing LASIK at our center in China has increased exponentially from 1997 to 2004, with an average annual increase in surgical volume of approximately 40%.


Artificial intelligence in radiotherapy.
Artificial intelligence (AI) has already been implemented widely in the medical field in the recent years. This paper first reviews the background of AI and radiotherapy. Then it explores the basic concepts of different AI algorithms and machine learning methods, such as neural networks, that are available to us today and how they are being implemented in radiotherapy and diagnostic processes, such as medical imaging, treatment planning, patient simulation, quality assurance and radiation dose delivery. It also explores the ongoing research on AI methods that are to be implemented in radiotherapy in the future. The review shows very promising progress and future for AI to be widely used in various areas of radiotherapy. However, basing on various concerns such as availability and security of using big data, and further work on polishing and testing AI algorithms, it is found that we may not ready to use AI primarily in radiotherapy at the moment.


Combination of deep learning and 2D CARS figures for identification of amyloid-β plaques.
In vivo imaging and accurate identification of amyloid-β (Aβ) plaque are crucial in Alzheimer's disease (AD) research. In this work, we propose to combine the coherent anti-Stokes Raman scattering (CARS) microscopy, a powerful detection technology for providing Raman spectra and label-free imaging, with deep learning to distinguish Aβ from non-Aβ regions in AD mice brains in vivo. The 1D CARS spectra is firstly converted to 2D CARS figures by using two different methods: spectral recurrence plot (SRP) and spectral Gramian angular field (SGAF). This can provide more learnable information to the network, improving the classification precision. We then devise a cross-stage attention network (CSAN) that automatically learns the features of Aβ plaques and non-Aβ regions by taking advantage of the computational advances in deep learning. Our algorithm yields higher accuracy, precision, sensitivity and specificity than the results of conventional multivariate statistical analysis method and 1D CARS spectra combined with deep learning, demonstrating its competence in identifying Aβ plaques. Last but not least, the CSAN framework requires no prior information on the imaging modality and may be applicable to other spectroscopy analytical fields.


Family Presence During Resuscitation After Trauma.
The purpose of this study was to examine the effects of family presence during resuscitation (FPDR) in patients who survived trauma from motor vehicle crashes (MVC) and gunshot wounds (GSW). A convenience sample of family members participated within three days of admission to critical care. Family members of 140 trauma patients (MVC n = 110, 79%; GSW n = 30, 21%) participated. Family members ranged in age from 20-84 years (M = 46, SD = 15, Mdn = 47). The majority were female (n = 112, 80%) and related to the patient as spouse (n = 46, 33%). Participating in the FPDR option reduced anxiety (t = -2.43, p =.04), reduced stress (t = -2.86, p = .005), and fostered well-being (t = 3.46, p = .001). Results demonstrate the positive initial effects of FPDR on family members of patients surviving trauma injury.


scaRNAs and snoRNAs: Are they limited to specific classes of substrate RNAs?
Posttranscriptional modifications of rRNA occur in the nucleolus where rRNA modification guide RNAs, or snoRNAs, concentrate. On the other hand, scaRNAs, the modification guide RNAs for spliceosomal snRNAs, concentrate in the Cajal body (CB). It is generally assumed, therefore, that snRNAs must accumulate in CBs to be modified by scaRNAs. Here we demonstrate that the evidence for the latter postulate is not consistent. In the nucleus, scaRNA localization is not limited to CBs. Furthermore, canonical scaRNAs can modify rRNAs. We suggest that the conventional view that scaRNAs function only in the CB needs revision.


Benefits of video games for people with schizophrenia: a literature review.
In spite of the overwhelming concerns about the deleterious impact of exposure to video games, a growing body of evidence suggests that it may be of potential interest for therapeutic purposes, particularly in schizophrenia. As literature is rapidly evolving, we carried out a systematic review of recent articles on this issue. We identified seven studies published from 2017 to 2022 exploring the benefits of commercial video games in people with schizophrenia and related disorders regarding symptoms, cognition and functional outcome. Six studies used an RCT design. Associations between gaming and better outcomes were found in three main areas: physical condition (walking speed, aerobic fitness), neurocognition (processing speed, memory and executive functions), and social functioning, self-efficacy in daily life activities and quality of life. Active use of video games is associated with better aerobic fitness and cognitive performances. Video gaming may contribute to better functional outcome and quality of life in patients suffering from cognitive impairments and difficulties in social functioning. Persons with schizophrenia may benefit from using commercial video games because of their potential therapeutic impact on functioning and cognition.


Respiratory viruses and chronic rejection in lung transplant recipients.
BACKGROUND; Chronic rejection manifested as obliterative bronchiolitis (OB) and bronchiolitis obliterans syndrome (BOS) continue to be major causes of morbidity and mortality after lung transplantation. Community respiratory virus (CRV) infection, including respiratory syncytial virus, parainfluenza virus, and influenza virus, can infect and also cause morbidity in lung transplant recipients. Because CRV and OB/BOS affect the small airways, we sought to determine whether CRV infections predisposed patients to OB/BOS. To determine whether CRV predisposed to OB/BOS, a proportional hazards regression analysis of time to OB/BOS was performed with CRV as a time-dependent covariate. To determine the influence of OB/BOS on the subsequent development of CRV infection, we reversed the outcome and time-dependent covariate. To illustrate the effect of CRV on OB/BOS and the effect of OB/BOS on CRV, landmark plots were generated at specific time points. Time to development of OB/BOS was then compared using the Kaplan-Meier method. In our institution, we documented 40 infections caused by CRV in 33 lung transplant recipients during an 11-year period. Community respiratory virus infections occurred predominantly during seasonal community outbreaks, except for parainfluenza infections, which occurred throughout the year. The diagnosis of OB/BOS occurred throughout the year and was not associated with seasonal outbreaks of CRV. Community respiratory virus infection involving both upper and lower respiratory tracts did not predispose to OB or BOS (relative risk [RR], 1.1; 95% confidence interval [CI], 0.52-2.3; p = 0.81). However, patients with documented CRV infection of the lower respiratory tract were predisposed to high-grade BOS development (RR, 2.3; 95% CI, 1.1-4.9; p = 0.04). In addition, a patient with pre-existing OB or BOS was predisposed to developing both upper and lower respiratory tract infection with CRV (RR, 4.2; 95% CI, 1.9-9.4; p < 0.001). Patients with CRV infection of the lower respiratory tract were predisposed to high-grade BOS development, and patients with OB and BOS were predisposed to CRV infections.


Downregulation of the 18-kDa translocator protein: effects on the ammonia-induced mitochondrial permeability transition and cell swelling in cultured astrocytes.
Hepatic encephalopathy (HE) is a major neurological complication in patients with severe liver disease. While the pathogenesis of HE is unclear, elevated blood and brain ammonia levels are believed to be major etiological factors, and astrocytes appear to be the primary target of its toxicity. A notable feature of ammonia neurotoxicity is an upregulation of the 18-kDa translocator protein (TSPO) (formerly referred to as the peripheral benzodiazepine receptor or PBR), which is found on the outer mitochondrial membrane. However, the precise significance of this upregulation is unclear. To examine its potential role in ammonia-induced astrocyte dysfunction, we downregulated the TSPO using antisense oligonucleotides, and examined whether such downregulation could alter two prominent features of ammonia gliotoxicity, namely, the mitochondrial permeability transition (MPT) and astrocyte swelling. Nontransfected cultures treated with NH4Cl (5 mM; 48 h) showed a significant increase in astrocyte cell volume (37.5%). In cultured astrocytes transfected with TSPO antisense oligonucleotides, such cell swelling was reduced to 17%, but this change was not significantly different from control cell volume. Similarly, nontransfected cultures treated with NH4Cl (5 mM; 24 h) exhibited a 40% decline in the cyclosporin A-sensitive mitochondrial inner membrane potential (DeltaPsi(m)) (P < 0.01) (a measure of the MPT). By contrast, cells transfected with TSPO antisense oligonucleotides did not display a significant loss of the DeltaPsi(m) following ammonia exposure. Our findings highlight the important role of the TSPO in the mechanism of ammonia neurotoxicity.