Dynamics of degradation of high-quality tropical forage according to levels of nitrogen supplementation.
The present study aimed to evaluate the degradation dynamics of high-quality tropical forage according to the levels of nitrogen supplementation. In this study, 4 rumen-fistulated cows with a body weight of 653 ± 47 kg were used. These animals were distributed in a 4 × 4 Latin square experimental design. Cows were kept under a grazing regime in an area formed by Panicum maximum Jacq. cv. Tanzania. These animals received 4 levels of crude protein (CP) in the supplements (122, 142, 162, and 180 g/kg of CP in DM). The degradability of dry matter (DM), crude protein (CP), and neutral detergent fiber (NDF) was determined by in situ incubation of forage samples at 0, 6, 12, 24, 48, 72, 96, and 120 h. Both the concentration of ammonia nitrogen (NH3-N) and the microbial protein synthesis were affected by CP levels of the supplements (P < 0.05). There was a significant difference (P < 0.05) for fraction b, potential degradability, and effective degradability of DM and NDF, and for the c degradation rate of CP of Tanzania grass which had the highest values at 122 g/kg of CP. Overall, the greatest degradation of nutrients from Tanzania grass occurred in the diet with 122 g/kg of CP and 604 g/kg of NFC in dairy cattle supplements that resulted in the highest rates of nitrogen utilization by rumen microbes.


Impact of Medicaid expansion and state-level racial diversity on breast cancer endocrine therapy prescriptions: A quasi-experimental, comparative interrupted time series study.
To determine whether Medicaid expansion impacted racially more diverse states similarly as racially less diverse states in endocrine therapy (ET) prescriptions. A quasi-experimental, comparative interrupted time series study of Medicaid-financed ET prescriptions from 2011 to 2018 Medicaid State Drug Utilization Database. The exposures were state's Medicaid expansion and racial diversity status. The outcome was state's quarterly number ET prescriptions per 100,000 non-elderly adult females (NAFs). During the year of expansion, ET prescriptions increased sharply in expansion states but remained flat in nonexpansion states (slope: 11.96 vs. 0.43 prescriptions per 100,000 NAFs per quarter, p < 0.001). After that, the slopes were similar between expansion and nonexpansion states (1.75 vs. 0.24, p = 0.057) but the level of prescriptions in expansion states maintained at a higher level. When stratified by state's racial diversity status, the slope of increase in the first year was sharper for raciallymore diverse expansion states (16.49, p = 0.008) than racially less diverse expansion states (8.46, p < 0.001), resulting in significant differences in ET prescriptions between racially more diverse expansion and nonexpansion states but largely nonsignificant differences between racially less diverse expansion and nonexpansion states. Although Medicaid expansion significantly increased ET prescriptions in expansion vs. nonexpansion states, this difference was only observed among raciallymore diverse states. Racially more diverse nonexpansion states had the lowest rates of ET prescriptions and the gaps from racially more diverse expansion states significantly widened after expansion. Our study shows that, before expansion, racially more diverse nonexpansion states had the lowest rates of ET prescriptions. After expansion, the gaps between these states and racially more diverse expansion states significantly widened. These results highlighted the importance of continuing to examine the health impacts of states not expanding Medicaid, including the health equity impacts for low income racial/ethnic minority populations with cancer and other life-threatening diseases.


The mechanism of action of Fangji Huangqi Decoction on epithelial-mesenchymal transition in breast cancer using high-throughput next-generation sequencing and network pharmacology.
Fangji Huangqi Decoction (FHD) is widely used in traditional Chinese medicine (TCM). FHD has been hypothesized to inhibit the epithelial-mesenchymal transition (EMT) process, which may positively impact breast cancer prevention and treatment. However, its exact mechanism of action is still unknown. This study aimed to screen potential targets of FHD for the treatment of EMT in breast cancer through network pharmacology, and to verify their therapeutic effects in vitro experiments and high-throughput second-generation sequencing. The data sets of effective components and targets of FHD were established through the Traditional Chinese Medicine Systems Pharmacology database. The GeneCards and OMIM databases were used to establish breast cancer-related target datasets, which were then matched with the TCM target data. The interaction between key target proteins was analyzed using the STRING database; the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify the associated biological processes and enriched signal pathways, respectively. The active ingredient disease target network was analyzed using Cytoscape. Finally, next generation sequencing was used to verify the related pathways of FHD intervention in EMT in breast cancer. High-content screening was used to identify the genes/pathways affected by FHD. MDA-MB-231 and HCC-1937 breast cancer cell lines were used to evaluate the impact of FHD on migration, invasion, and EMT. Eighty possible significant targets were identified for the treatment of breast cancer EMT with FHD; GO and KEGG were used to identify 173 cell biological processes associated with breast cancer (P < 0.05), including the NF-κB and PI3K-Akt signaling pathways. The high-throughput sequencing and network pharmacology results were highly consistent. The migration and invasion ability of MDA-MB-231 cells was reduced and their EMT status could be reversed by DSHR2 knockdown. The results of morphology and scratch assays showed that FHD could improve the EMT status of HCC-1973. This study provides more evidence to support the clinical application of FHD, which has reliable interventional effects on breast cancer EMT. Its therapeutic effects may involve a multi-target, multi-pathway, and multi-mechanism effect.


Initial fixation strength of interference nail fixation for anterior cruciate ligament reconstruction with patellar tendon graft (experimental study).
The objective of this study was to evaluate initial fixation strength of a new interference nail fixation in anterior cruciate ligament reconstruction using bone-patellar tendon-bone graft. Human cadaver knees were used. Fixation strengths ranged from 500 N to 600 N (mean 550 N). This corresponds to loads in the graft during aggressive rehabilitation. No slippage occurred at fixation site of specimens. Most of the failures appeared from the femoral side with tendon ruptures. With respect to primary fixation strength, interference nail fixation is a reasonable alternative for anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft.


[Atypical atrial fibrillation : Diagnostics and therapy].
In contrast to typical atrial flutter, atypical atrial flutter is a heterogeneous group of right and left atrial macro- or localized reentry tachycardias whose critical component for maintaining tachycardia is not the cavotricuspid isthmus. Atypical atrial flutter occurs more frequently after previous catheter ablation and after cardiac surgery. The intraprocedural success rate during ablation is high, although the recurrence rate depends on structural changes in the atria as well as the underlying mechanism. This article provides an overview of the mechanisms as well as mapping and ablation strategies of the most common forms of right and left atrial atypical atrial flutter. This article is part of the "EP Basics" series for targeted continuing education in invasive electrophysiology. Basics, clinic and therapy of atypical atrial flutter are presented with focus on clinically relevant aspects. Procedures and findings of invasive electrophysiological diagnostics and ablation treatment are the focus of this article.


Quercetin derivatives: Drug design, development, and biological activities, a review.
More studies are needed to develop new drugs for problems associated with drug resistance and unfavorable side effects. The natural flavonoid of quercetin revealed a wide range of biological activities by the modulation of various targets and signaling pathways. However, quercetin's low solubility and poor bioavailability have restricted its applicability; as a result, researchers have attempted to design and synthesize numerous novel quercetin derivatives using various methodologies in order to modify quercetin's constraints; the physico-chemical properties of quercetin's molecular scaffold make it appealing for drug development; low molecular mass and chemical groups are two of these characteristics. Therefore, the biological activities of quercetin derivatives, as well as the relationship between activity and chemical structure and their mechanism of action, were investigated. These quercetin-based molecules could be valuable in the creation and discovery of medications for a number of diseases.


Fantastic niches and where to find them: the current diagnosis and management of uterine niche.
Caesarean section (CS) scar niche is a well recognised complication of caesarean delivery and is defined as an indentation at the site of the CS scar with a depth of at least 2mm. To review systematically the medical literature regarding the current diagnosis and management of uterine niche. We carried out a systematic review using MeSH terms 'niche' OR 'sacculation' OR 'caesarean scar defect' OR 'caesarean section scar' OR 'uterine defect' OR 'isthmocele.' Articles included were peer-reviewed and in English language. Prevalence, symptoms, diagnosis, pathophysiology and management of uterine niche. CS scar niche is common and, in a subgroup, produces a range of symptoms including post-menstrual bleeding, dyspareunia and subfertility. It may be linked to use of locked sutures during CS closure. Niche repair can be achieved laparoscopically or hysteroscopically and appears to improve symptoms, although solid conclusions regarding fertility outcomes cannot be drawn. CS scar niche is associated with a range of symptoms. Repair may aid subfertile patients and those with post-menstrual spotting. The presence of a niche is probably irrelevant in the absence of symptoms. LNG-IUS and surgical repair appear to improve symptoms in those with a niche.


Robot-assisted partial nephrectomy for hilar tumors: perioperative outcomes.
To compare perioperative outcomes of robot-assisted partial nephrectomy (RAPN) for hilar vs nonhilar tumors. The study retrospectively reviewed 364 patients with available computed tomography scans undergoing RAPN. Demographic data and perioperative outcomes results were compared between the hilar (group 1, n = 70) and nonhilar tumors (group 2, n = 294). Multivariate analysis was used to identify predictors of warm ischemia time (WIT), estimated blood loss (EBL), major perioperative complications, and postoperative renal function. There were no differences with respect to demographic variables. Hilar tumors had higher RENAL (radius, exophytic/endophytic properties of the tumor, nearness of tumor deepest portion to the collecting system or sinus, anterior/posterior descriptor and the location relative to polar lines) scores (P <.001) and were larger (3.9 vs 2.6 cm, P <.001). Surgeries for hilar tumors were associated with greater operative time (210 vs 180 minutes, P <.001), longer WIT (27 vs 17 minutes, P <.001), and increased EBL (250 vs 200 mL, P = .04). No differences were noted in transfusion rate, length of stay, complications (overall and major) and positive margins. Postoperative estimated glomerular filtration rate showed no significant difference between hilar vs nonhilar patients on postoperative day 3 (70.12 vs 74.71 mL/min/1.73 m(2), P = .31) or at last follow-up (72.62 vs 75.78 mL/min/1.73 m(2), P = .40), respectively. Multivariate analysis found hilar location was independently associated with increased WIT without significant changes in EBL, major complications, or postoperative renal function. RAPN represents a safe and effective procedure for hilar tumors. Hilar location for patients undergoing RAPN in a high-volume institution seems not be associated with an increased risk of transfusions, major complications, or decline of early postoperative renal function.


Increased brachial-ankle pulse wave velocity is independently associated with risk of cerebral ischemic small vessel disease in elderly hypertensive patients.
Increased arterial stiffness is an independent predictor of cardiovascular diseases in hypertensive patients. Hypertension and aging can cause similar damage to small vessel walls. The objective of this study was to determine relationship between arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) and the risk of cerebral small vessel disease (SVD) in elderly people with hypertension. We studied 196 elderly subjects with hypertension (> or =50 years of age) who had neither large vessel stroke nor cardiac embolism. These patients were divided into three groups based on the results of brain MRI: (1) those with first-ever small vessel stroke; (2) those with asymptomatic subcortical ischemia; and (3) a control group with hypertension. The baPWV was significantly increased in the patients with first-ever small vessel stroke or asymptomatic subcortical infarction when compared to the control group, after adjusting for systolic blood pressure (SBP), pulse pressure (PP), and hs-CRP (p=0.005). Among subjects with SVD on MRI, the number of lacunar infarcts (LIs)> or =5 was significantly related to a higher baPWV (p=0.02). The relationship between the severity of periventricular white matter hyperintensities (PWMH) and the degree of baPWV became insignificant after adjustment for age. Increased baPWV was significantly associated with the risk of SVD in elderly persons with hypertension. Therefore, the measurement of baPWV could be used to predict SVD.


Microvascular imaging of the unstained human superior colliculus using synchrotron-radiation phase-contrast microtomography.
Characterizing the microvasculature of the human brain is critical to advance understanding of brain vascular function. Most methods rely on tissue staining and microscopy in two-dimensions, which pose several challenges to visualize the three-dimensional structure of microvessels. In this study, we used an edge-based segmentation method to extract the 3D vasculature from synchrotron radiation phase-contrast microtomography (PC-μCT) of two unstained, paraffin-embedded midbrain region of the human brain stem. Vascular structures identified in PC-μCT were validated with histology of the same specimen. Using the Deriche-Canny edge detector that was sensitive to the boundary between tissue and vascular space, we could segment the vessels independent of signal variations in PC-μCT images. From the segmented volumetric vasculature, we calculated vessel diameter, vessel length and volume fraction of the vasculature in the superior colliculi. From high resolution images, we found the most frequent vessel diameter to be between 8.6-10.2 µm. Our findings are consistent with the known anatomy showing two types of vessels with distinctive morphology: peripheral collicular vessels and central collicular vessels. The proposed method opens up new possibilities for vascular research of the central nervous system using synchrotron radiation PC-μCT of unstained human tissue.


Relationships of sleep disturbance, intestinal microbiota, and postoperative pain in breast cancer patients: a prospective observational study.
Our study was designed to examine the possible relationship between gut microbiota, sleep disturbances, and acute postoperative pain. Using 16S rRNA sequencing, we analyzed preoperative fecal samples from women undergoing breast cancer surgery. Preoperative sleep disturbance was evaluated with the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Peak and average pain at rest and movement were evaluated 24 h after surgery, using a numerical rating scale (NRS). Preoperative symptoms of depression and anxiety were assessed with the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Inflammation was measured using white blood cell and neutrophil counts, together with platelet-lymphocyte ratio, and neutrophil-lymphocyte ratio. Preoperative sleep disturbance was associated with more severe acute postoperative pain. At the phylum level, women with poor sleep quality had higher relative abundance of Firmicutes (p = 0.021) and lower relative abundance of Bacteroidetes (p = 0.013). At the genus level, women with poor sleep quality harbored higher relative abundance of Acidaminococcus and lower relative abundance of several genera. The genus Alloprevotella was negatively associated with peak pain at movement during the first 24 h (r = - 0.592, p < 0.001). The genus Desulfovibrio was negatively associated with symptoms of anxiety (r = - 0.448, p = 0.006). However, partial correlations suggested that the relationship between Alloprevotella and peak pain at movement during the first 24 h was not statistically significant after controlling for sleep (r = - 0.134, p = 0.443). These findings suggest that the changed gut microbiota may be involved in sleep-pain interaction and could be applied as a potential preventive method for postoperative pain. The present clinical study has been registered on Chinese Clinical Trial Registry ( www.chictr.org.cn ); the clinical trial registration number is ChiCTR1900021730; the date of registration is March 7, 2019.


Uric acid associates with cognition in Parkinson's disease.
Cognitive dysfunction is common in Parkinson's disease (PD). Low plasma uric acid level is a risk factor for PD but its association with cognitive impairment in PD has not been previously studied. In the present study urine uric acid level as well as plasma uric acid- and homocysteine levels were measured in 40 patients with PD. Comprehensive neuropsychological tests including computerized tasks were performed on all. Both low plasma and low urine uric acid levels associated with decreased neuropsychological performance. In multiple linear regression low urine uric acid level predicted worse performance in the Picture completion subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (p=0.003) and in the Rule shift cards test of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) (p=0.04). Low plasma uric acid level predicted worse performance both in the Picture completion (p=0.02) and Similarities subtest of the WAIS-R (p=0.02). Reaction time and the time spent on cognitive processing in the Statement verification task were inversely correlated with the uric acid levels (p=0.0001). There was no correlation between the homocysteine level and neuropsychological performance. Instead, the plasma uric acid and homocysteine levels correlated significantly and their possible association in PD is discussed.


Molecular cloning of the NP and L genes of simian virus 5: identification of highly conserved domains in paramyxovirus NP and L proteins.
We have molecularly cloned and determined the nucleotide sequence of the 3' and 5' regions of the genomic RNA of the paramyxovirus simian virus 5 (SV5), including the 3' leader sequence, nucleocapsid protein (NP) gene, large (L) protein gene, and 5' anti-genomic leader (trailer) sequence. The vRNA 3' proximal leader sequence contains 55 nucleotides. The NP gene is 1725 nucleotides in length and encodes a negatively charged protein consisting of 509 residues (MW 56,534). A comparison of the amino acid sequences of 10 paramyxovirus NP proteins indicates a region of high sequence identity near the middle of the protein, and a C-terminal region which is enriched in negatively charged residues. Overall, the SV5 NP protein showed the highest degree of sequence identity with the NP proteins of parainfluenza type 2 virus (58%) and mumps virus (56%). The L gene extends 6804 nucleotides and encodes a positively charged protein consisting of 2255 residues (MW 255,923). The 5' proximal region of the vRNA consists of a 31 nucleotide trailer RNA. The SV5 L protein sequence showed 62% overall identity with the parainfluenza type 2 L protein. Although little overall sequence identity was found between the SV5 and other paramyxovirus L protein sequences, short stretches of extensive amino acid identity were found near the middle of each of the known paramyxovirus L protein sequences, and these common regions may represent sites important for enzymatic activity.


Heterozygous nonsense variants in laminin subunit 3α resulting in Ebstein's anomaly.
Ebstein's anomaly is a rare congenital heart disease characterized by tricuspid valve downward displacement and is associated with additional cardiac phenotypes such as left ventricle non-compaction. The genetic basis of Ebstein's anomaly has yet to be fully elucidated, although several genes (e.g., NKX2-5, MYH7, TPM1, and FLNA) may contribute to Ebstein's anomaly. Here, in two Ebstein's anomaly families (a three-generation family and a trio), we identified independent heterozygous nonsense variants in laminin subunit 3 α (LAMA3), cosegregated with phenotypes in families with reduced penetrance. Furthermore, knocking out Lama3 in mice revealed that haploinsufficiency of Lama3 led to Ebstein's malformation of the tricuspid valve and an abnormal basement membrane structure. In conclusion, we identified a novel gene-disease association of LAMA3 implicated in Ebstein's anomaly, and the findings extended our understanding of the role of the extracellular matrix in Ebstein's anomaly etiology.


ApoA-I Mimetic Peptide 4F Reduces Age-Related Lipid Deposition in Murine Bruch's Membrane and Causes Its Structural Remodeling.
Accumulation of lipoprotein-derived lipids including esterified and unesterified cholesterol in Bruch's membrane of human eyes is a major age-related change involved in initiating and sustaining soft drusen in age-related macular degeneration (AMD). The apolipoprotein (apo) A-I mimetic peptide 4F is a small anti-inflammatory and anti-atherogenic agent, and potent modifier of plasma membranes. We evaluated the effect of intravitreally-injected 4F on murine Bruch's membrane. We tested single intravitreal injections of 4F doses (0.6 µg, 1.2 µg, 2.4 µg, and placebo scrambled peptide) in ApoEnull mice ≥10 months of age. After 30 days, mice were euthanized. Eyes were processed for either direct immunofluorescence detection of esterified cholesterol (EC) in Bruch's membrane whole mounts via a perfringolysin O-based marker linked to green fluorescent protein or by transmission electron microscopic visualization of Bruch's membrane integrity. Fluorescein isothiocyanate-conjugated 4F was traced after injection. All injected eyes showed a dose-dependent reduction of Bruch's membrane EC with a concomitant ultrastructural improvement compared to placebo treated eyes. At a 2.4 µg dose of 4F, EC was reduced on average by ~60% and Bruch's membrane returned to a regular pentalaminar structure and thickness. Tracer studies confirmed that injected 4F reached intraocular targets. We demonstrated a highly effective pharmacological reduction of EC and restoration of Bruch's membrane ultrastructure. The apoA-I mimetic peptide 4F is a novel way to treat a critical AMD disease process and thus represents a new candidate for treating the underlying cause of AMD.


Response of nuclear polyhedrosis virus-resistant Spodoptera frugiperda larvae to other pathogens and to chemical insecticides.
Selection in the laboratory for Spodoptera frugiperda (Sf) resistant to nuclear polyhedrosis virus (NPV) affected the susceptibility of the insect to certain other mortality agents, including a chemical insecticide. Median lethal concentrations (LC50S) and associated statistics were compared for several mortality agents between colonies of NPV-resistant and -susceptible (control) insects. Compared to the susceptible insects, the NPV-resistant insects were cross-resistant to the S. frugiperda granulosis virus and to the Autographa californica NPV based on nonoverlap of 95% fiducial limits of the LC50S. The NPV-resistant insects were significantly more susceptible to methyl parathion than the control insects. The two colonies of S. frugiperda did not differ significantly in their response to Bacillus thuringiensis, Vairimorpha necatrix, or carbaryl. The cross-resistance experiments were based on per os exposure of the insects to the pathogens and insecticides; the susceptibility of the resistant and control insects did not differ significantly when the Sf NPV was injected into the hemocoel or when methyl parathion was applied topically.


Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer's dementia.
Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer's dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain α-amylase activity. The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 ± 5.9, females 58.2%) from the Malmö diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 ± 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between α-amylase activity or α-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Individuals with very high ( ≥10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41-0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1-5) (HR = 0.74, 95% CI 0.53-1.02). A tendency towards a positive correlation between brain α-amylase activity and AMY1A copy number was found, and females showed higher brain α-amylase activity compared to males. Our study suggests that the degree of α-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.


Structural insight into substrate binding of Acinetobacter baumannii polyphosphate-AMP phosphotransferase (PPK2), a novel drug target.
Acinetobacter baumannii is an opportunistic pathogen known for high morbidity and mortality. It causes life-threatening infections, such as ventilator-associated pneumonia (VAP), bacteremia, meningitis, wound and urinary tract infections (UTI). Increase in carbapenem resistance exhibited by A. baumannii has accentuated the need for novel targets for effective treatment. Despite the pronounced relevance of PPK2 as a pathogenicity determinant in several pathogens, it has not been explored as a drug target in A. baumannii. The present study was piloted to investigate the substrate binding by A. baumannii PPK2 (AbPPK2), a two-domain Class II polyphosphate kinase 2. A homology model of AbPPK2 was developed and validated for molecular docking of ATP and ADP in the predicted binding pocket. Further analysis of AbPPK2 revealed a set of common residues in the catalytic cleft interacting with ATP and ADP which would be useful for the screening of inhibitors against A. baumannii.


Endovascular Hepatic Artery Stents in the Modern Management of Postpancreatectomy Hemorrhage.
Postoperative hemorrhage is a potentially lethal complication of pancreatoduodenectomy. This study reports on the use of endovascular hepatic artery stents in the management of postpancreatectomy hemorrhage. This is a retrospective analysis of a prospectively maintained, consecutive dataset of 440 patients undergoing pancreatoduodenectomy over 68 months. Data are presented on bleeding events and outcomes, and contextualized by the clinical course of the denominator population. International Study Group of Pancreatic Surgery terminology was used to define postpancreatectomy hemorrhage. Sixty-seven (15%) had postoperative hemorrhage. Fifty (75%) were male and this gender difference was significant (P = 0.001; 2 proportions test). Postoperative pancreatic fistulas were more frequent in the postoperative hemorrhage group (P = 0.029; 2 proportions test). The median (interquartile range [IQR]) delay between surgery and postoperative hemorrhage was 5 days (2-14 days). Twenty-six (39%) required intervention comprising reoperation alone in 12, embolization alone in 5, and endovascular hepatic artery stent deployment in 5. Four further patients underwent more than 1 intervention with 2 of these having stents. Endovascular stent placement achieved initial hemostasis in 5 of 7 (72%). Follow-up was for a median (IQR) of 199 days (145-400 days) poststent placement. In 2 patients, the stent remained patent at last follow-up. The remaining 5 stents occluded with a median (IQR) period of proven patency of 10 days (8-22 days). This study shows that in the specific setting of postpancreatoduodenectomy hemorrhage with either a short remnant gastroduodenal artery bleed or a direct bleed from the hepatic artery, where embolization risks occlusion with compromise of liver arterial inflow, endovascular hepatic artery stent is an important hemostatic option but is associated with a high risk of subsequent graft occlusion.


Ultrastructural characterization of the central component of the medial preoptic nucleus.
The fine structure of the sexually dimorphic central part of the medial preoptic nucleus was studied in male and female rats. Neurons of this subnucleus are characterized by having convoluted nuclear membranes and fibrillar nuclear inclusions. Within the perinuclear domain there is a well developed neurosecretory apparatus, i.e., Golgi complexes, assorted types of secretory granules, and lysosome-like bodies, whereas the marginal cytosol contains stacked cisterns of rough endoplasmic reticulum, nucleolus-like inclusions, and few mitochondria. The neuropil is made up of thick dendrites, fascicles of thin unmyelinated axons, and few small myelinated axons. Additionally four types of synaptic boutons were found according to the morphology of their vesicular contents. No apparent qualitative sex differences were noted. These cytologic features which suggest secretory activity, coupled with reports that have shown the presence of several neurohormones and peptides within the central part of the medial preoptic nucleus lend further support to the neuroendocrine nature of these neurons.


A Passive Radio-Frequency Identification (RFID) Gas Sensor With Self-Correction Against Fluctuations of Ambient Temperature.
Uncontrolled fluctuations of ambient temperature in the field typically greatly reduce accuracy of gas sensors. In this study, we developed an approach for the self-correction against fluctuations of ambient temperature of individual gas and vapor sensors. The main innovation of our work is in the temperature correction which is accomplished without the need for a separate uncoated reference sensor or a separate temperature sensor. Our sensors are resonant inductor-capacitor-resistor (LCR) transducers coated with sensing materials and operated as multivariable passive (battery-free) radio-frequency identification (RFID) sensors. Using our developed approach, we performed quantitation of an exemplary vapor over the temperature range from 25 to 40 °C. This technical solution will be attractive in numerous applications where temperature stabilization of a gas sensor or addition of auxiliary temperature or uncoated reference sensors is prohibitive.


Novel role for Grainy head in the regulation of cytoskeletal and junctional dynamics during epithelial repair.
Tissue repair is critical for the maintenance of epithelial integrity and permeability. Simple epithelial repair relies on a combination of collective cell movements and the action of a contractile actomyosin cable at the wound edge that together promote the fast and efficient closure of tissue discontinuities. The Grainy head family of transcription factors (Grh in flies; GRHL1-GRHL3 in mammals) are essential proteins that have been implicated both in the development and repair of epithelia. However, the genes and the molecular mechanisms that it controls remain poorly understood. Here, we show that Grh knockdown disrupts actomyosin dynamics upon injury of the Drosophila pupa epithelial tissue. This leads to the formation of an ectopic actomyosin cable away from the wound edge and impaired wound closure. We also uncovered that E-Cadherin is downregulated in the Grh-depleted tissue around the wound, likely as a consequence of Dorsal (an NF-κB protein) misregulation, which also affects actomyosin cable formation. Our work highlights the importance of Grh as a stress response factor and its central role in the maintenance of epithelial characteristics necessary for tissue repair through regulating cytoskeleton and E-Cadherin dynamics.


Mutagenic and alkylating activities of organophosphate impurities of commercial malathion.
The purpose of this study was to determine if 4 major organophosphate impurities of malathion were active as alkylators of nitrobenzylpyridine (NBP) or as mutagens in the Salmonella typhimurium bioassay. Malathion, isomalathion, O,O,O-trimethyl phosphorothioate, O,O,S-trimethyl phosphorothioate, and O,S,S-trimethyl phosphorodithioate produced alkylated NBP at varying rates. In order of increasing NBP reactivity, the compounds ranked: O,O,O-trimethyl phosphorothioate = O,O,S-trimethyl phosphorothioate less than O,S,S-trimethyl phosphorodithioate less than isomalathion = malathion. At 37 degrees C, the most reactive compounds produced an NBP alkylation rate equal to approximately 25% of the rate produced by methyl methanesulfonate, a potent Salmonella mutagen. However, none of the organophosphates were mutagenic in S. typhimurium TA97, TA98 and TA100 when tested by the standard plate-incorporation method or by the preincubation modification of the plate-incorporation method. The possible relationships between NBP reactivity and the biological activities of these organophosphates are discussed.


Structural alterations of chromosome 2 in Leishmania major as evidence for diploidy, including spontaneous amplification of the mini-exon array.
We have utilized pulsed field electrophoresis to characterize several karyotypic alterations in Leishmania major. Promastigotes of the LT252 line contain three small chromosomes, of 300, 350 and 385 kb. Quantitative densitometry of ethidium bromide-stained gels suggest that these chromosomes are present in equal levels (2:2:2). Two derivatives of this line, one appearing spontaneously (LT252 delta) and one obtained following selection with methotrexate (11-MTXR20), exhibit altered levels of these chromosomes, in the ratio of 2:1:3, respectively. The variant pattern in both lines is due to an increase in size of chromosome 2, yielding a new chromosome similar in size to chromosome 3. The enlarged chromosome 2 of the LT252 delta line is a result of amplification of the mini-exon gene array normally located on this chromosome, which increases from about 93 to 150 copies of the 0.44-kb mini-exon tandem repeat, as shown by quantitative hybridization and sizing of the mini-exon array. In contrast, the increased size of chromosome 2 within the methotrexate-resistant mutant 11-MTXR20 is not due to mini-exon amplification. In both variant lines, there are equal levels of the wild-type and enlarged chromosome 2, and the wild-type chromosome 2 is now present at 50% of the level of chromosome 1. These and other data suggest that Leishmania is diploid for chromosomes bearing housekeeping genes such as the mini-exon locus.


[Effect of 1,25-(OH)2D3 on expression of TIM-4 in the lungs of asthmatic mice].
To establish a mouse model of asthmatic airway remodeling and investigate the effects of 1,25-(OH)2D3 on airway structure and T cell immunoglobulin mucin protein-4 (TIM-4) expression in asthmatic mice. Thirty female mice (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)2D3 intervention groups. An asthmatic mouse model was induced using ovalbumin. Lung tissue of the mice was collected, mRNA expression of TIM-4 was evaluated by RT-PCR and airway remodeling and protein expression of TIM-4 were observed by hematoxylineosin staining and immunohistochemistry. Typical airway remodeling was found in the asthma group, and TIM-4 expression in this group was significantly higher than in the control group (105±9 vs 42±5; P<0.05). Compared with the asthma group, the 1,25-(OH)2D3 intervention group showed improvement in airway remodeling and a decrease in TIM-4 expression (78±6) (P<0.05). TIM-4 may be involved in the airway remodeling of mice. As a new type of immunoregulator, 1,25-(OH)2D3 can downregulate expression of TIM-4 in the lungs and improve airway remodeling in asthmatic mice.


Generation of Footprint-Free Induced Pluripotent Stem Cells from Human Fibroblasts Using Episomal Plasmid Vectors.
Human induced pluripotent stem cells (hiPSCs) have provided novel insights into the etiology of disease and are set to transform regenerative medicine and drug screening over the next decade. The generation of human iPSCs free of a genetic footprint of the reprogramming process is crucial for the realization of these potential uses. Here we describe in detail the generation of human iPSC from control and disease-carrying individuals' fibroblasts using episomal plasmids.


Altered topological properties of the intrinsic functional brain network in patients with right-sided unilateral hearing loss caused by acoustic neuroma.
Neuroimaging studies have identified alterations in functional connectivity between specific brain regions in patients with unilateral hearing loss (UHL) and different influence of the side of UHL on neural plasticity. However, little is known about changes of whole-brain functional networks in patients with UHL and whether differences exist in topological organization between right-sided UHL (RUHL) and left-sided UHL (LUHL). To address this issue, we employed resting-state fMRI (rs-fMRI) and graph-theoretical approaches to investigate the topological alterations of brain functional connectomes in patients with RUHL and LUHL. Data from 44 patients with UHL (including 22 RUHL patients and 22 LUHL patients) and 37 healthy control subjects (HCs) were collected. Functional brain networks were constructed for each participant, following by graph-theoretical network analyses at connectional and global (e.g., small-worldness) levels. The correlations between brain network topologies and clinical variables were further studied. Using network-based analysis, we found a subnetwork in the visual cortex which had significantly lower connectivity strength in patients with RUHL as compared to HCs. At global level, all participants showed small-world architecture in functional brain networks, however, significantly lower normalized clustering coefficient and small-worldness were observed in patients with RUHL than in HCs. Moreover, these abnormal network metrics were demonstrated to be correlated with the clinical variables and cognitive performance of patients with RUHL. Notably, no significant alterations in the functional brain networks were found in patients with LUHL. Our findings demonstrate that RUHL (rather than LUHL) is accompanied with aberrant topological organization of the functional brain connectome, indicating different pathophysiological mechanisms between RUHL and LUHL from a viewpoint of network topology.


Sexual orientation disparities in developmental assets among youth: The mediating role of bullying victimization.
Navigating the developmental transition from adolescence to young adulthood while simultaneously integrating the emergence of a sexual minority identity can be overwhelming for lesbian, gay, bisexual, and questioning youth as the developmental tasks pose tremendous challenges to the cultivation of developmental assets, which are the building blocks necessary for fostering positive youth development and thriving. The present study aimed to estimate the sexual orientation disparities in bullying victimization and developmental assets, investigate whether these sexual orientation differences varied by sex assigned at birth, and examine the mediating role of bullying victimization in the association between sexual orientation and developmental assets. This study included a national sample of 3020 Chinese youth (51.5 % assigned male at birth; 48.5 % assigned female at birth) with a mean age of 15.71 years. They completed a self-report questionnaire on experiences of bullying victimization and developmental assets. Sexual minority and questioning youth showed significantly lower levels of developmental assets than heterosexual youth. The sexual orientation differences in developmental assets did not significantly differ by sex assigned at birth. In addition, sexual minority youth were at heightened risk of relational bullying than heterosexual youth. The results obtained from the structural equation modeling indicated that bullying victimization mediated the association of sexual orientation with developmental assets. Compared to heterosexual youth, sexual minority youth were more likely to be subjected to bullying, which was linked to lower levels of developmental assets. The study shows sexual orientation disparities in developmental assets among youth in China and reveals that the positive development of sexual minority youth may be hindered by their experiences of bullying victimization. The implications for positive psychological interventions and anti-bullying policies in Chinese educational settings are discussed.


Histological observation of the reproductive system in a viviparous teleost Xenotoca eiseni Rutter 1896 (Cyprinodontiformes: Goodeidae).
Xenotoca eiseni is a viviparous teleost belonging to the family Goodeidae. Here, we report histological observations of the reproductive organs in an adult male, an adult female, a pregnant female with intraovarian embryo and an extracted embryo of X. eiseni. High-resolution images of haematoxylin-eosin-stained sagittal sections revealed the detailed structure of gonads, gametes and reproductive components of the mother-embryo relationship. In the male, mature spermatozoa in the epididymis formed sperm packages. In the female, oogenesis proceeded asynchronously in the ovarian wall, and various stages of oocytes were observed in single ovary. In both sexes, genital openings were located between the anus and anal fin. Developing embryos were observed in an ovary of the pregnant female. Fine structures of components of the mother-to-embryo nutrient supply, ovarian septum and trophotaenia were observed in the pregnant ovary. An immature gonad prior to gamete formation was identified in the extracted embryo. With the aim of supporting the development and extension of studies on this viviparous teleost, we have shared our histological images as raw data in an open online archive, the 'NAGOYA repository (http://hdl.handle.net/2237/00032456)'. Our goal is a comprehensive understanding of the viviparous system in fish using both histological observation and molecular biology methods including genomics and proteomics.


Effect of scopolamine and HP 029, a cholinesterase inhibitor, on long-term potentiation in hippocampal slices of the guinea pig.
The effect of scopolamine and a cholinesterase inhibitor on long-term potentiation (LTP) of population spikes was studied in a guinea pig hippocampal slice preparation. After brief application of each drug (10 min), LTP in CA1 and CA3 was induced by tetanus stimulation delivered to commissural/associational fibers and mossy fibers, respectively. Scopolamine at concentration of 10 microM had no effect on LTP in CA1 but significantly suppressed LTP in CA3. The cholinesterase inhibitor, 9-amino-1,2,3,4-tetrahydroacridine-1-ol maleate (HP 029) at concentration of 10 microM significantly enhanced LTP both in CA1 and CA3. These results suggest that the cholinergic system is involved in producing LTP in CA3. Another mechanism of the effect of HP 029 on LTP in CA1 is discussed.


Women's oral health awareness and care-seeking characteristics: a pilot study.
The authors designed a pilot study to examine issues that affect women's oral health. They found a substantial lack of awareness regarding important oral health issues, and that 44 percent of the participants reportedly did not have regular dental care. High perceived dental need was reported concurrently with low dental care attendance. Additionally, reported lack of dental insurance and self-perception of low income and of poor dental health were important explanatory factors for the women who reportedly did not have regular dental care.


The causal effect of serum 25-hydroxyvitamin D levels on epilepsy: A two-sample Mendelian randomization study.
Observational studies have shown an association between 25-hydroxyvitamin D (25 (OH) D) and epilepsy, but it is unclear whether the association is causal. Therefore, we applied Mendelian randomization (MR) analysis to determine the causal relationship between serum 25 (OH) D levels and epilepsy. We conducted a two-sample Mendelian randomization (TSMR) study to investigate the association between serum 25 (OH) D levels and epilepsy using pooled statistics from genome-wide association studies (GWAS). Data for 25 (OH) D came from a GWAS comprising 417,580 participants, and data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium. Five methods were used to analyze TSMR, including the inverse variance weighting method, MR Egger method, weighted median method, simple model, and weighted model. In the sensitivity analysis, MR Egger and MR PRESSO methods were used to test for pleiotropy, inverse variance weighting and MR Egger in Cochran's Q statistics were used to test for heterogeneity. MR analyzed the relationship between 25 (OH) D and different types of epilepsy, and the results showed that a 1 standard deviation increase in natural log-transformed serum 25 (OH) D levels was associated with reduced risk for juvenile absence epilepsy (IVW OR = 0.985; 95% confidence interval [CI]: 0.971-0.999; P-value = 0.038). There was no apparent heterogeneity and horizontal gene pleiotropy. Higher serum levels of 25 (OH) D were a protective factor for adolescent absence epilepsy, but had no effect on other types of epilepsy.


Use of waste ash from palm oil industry in concrete.
Palm oil fuel ash (POFA), a by-product from the palm oil industry, is disposed of as waste in landfills. In this study, POFA was utilized as a pozzolan in concrete. The original size POFA (termed OP) was ground until the median particle sizes were 15.9 microm (termed MP) and 7.4 microm (termed SP). Portland cement Type I was replaced by OP, MP, and SP of 10%, 20%, 30%, and 40% by weight of binder. The properties of concrete, such as setting time, compressive strength, and expansion due to magnesium sulfate attack were investigated. The results revealed that the use of POFA in concretes caused delay in both initial and final setting times, depending on the fineness and degree of replacement of POFA. The compressive strength of concrete containing OP was much lower than that of Portland cement Type I concrete. Thus, OP is not suitable to be used as a pozzolanic material in concrete. However, the replacement of Portland cement Type I by 10% of MP and 20% of SP gave the compressive strengths of concrete at 90 days higher than that of concrete made from Portland cement Type I. After being immersed in 5% of magnesium sulfate solution for 364 days, the concrete bar mixed with 30% of SP had the same expansion level as that of the concrete bar made from Portland cement Type V. The above results suggest that ground POFA is an excellent pozzolanic material and can be used as a cement replacement in concrete. It is recommended that the optimum replacement levels of Portland cement Type I by MP and SP are 20% and 30%, respectively.


Reentrant circuits and the effects of heptanol in a rabbit model of infarction with a uniform anisotropic epicardial border zone.
The purpose was to study reentry in a rabbit model of infarction. A model of an infarct epicardial border zone was produced in Langendorff perfused rabbit hearts by freezing the inner two thirds of the left ventricular wall, allowing only a thin epicardial muscle layer to survive. Reentrant circuits causing stable ventricular tachycardia occurred in the surviving rim of epicardial muscle as shown by mapping impulse propagation with a 196-electrode array. The circuits were functional, and reentry did not occur around an anatomical obstacle. Slow conduction in the circuits was caused by the anisotropic properties of the epicardial muscle. Activation in the circuits was slow transverse to the long axis of the fiber bundles and rapid parallel to the long axis. Other features of the circuits, including orientation of the central functional line of block parallel to the fiber long axis, and an oval shape are also characteristic of anisotropic reentry. Since the slow conduction causing reentry is a result of poor transverse intercellular coupling, we determined whether the "uncoupler" heptanol would cause block in the circuits and terminate tachycardia. Heptanol in concentrations up to 1.2 mM slowed conduction in the transverse and longitudinal directions in the circuits and sometimes extended the central line of functional block. It did not, however, stop reentry because the reentrant impulse was still able to conduct around the ends of the block line. Drugs that decrease intercellular coupling may not be effective antiarrhythmic agents when uniform anisotropy causes functional reentry.


A gene cluster for fatty alcohol synthesis from a Reinekea-related bacterium that accumulates fatty alcohols.
This study reports on a marine bacterium that accumulates fatty alcohols (C14,16,18 ) at more than 1% (w/w) of the dry cell weight. This unique bacterium, designated as strain 1-4, is related to the genus Reinekea. A novel gene cluster for fatty alcohol synthesis, phsAB, is identified from strain 1-4. The phsA product shows significant homology to fatty acyl-CoA reductase (51% identity), whereas the phsB product shows very low homology to lipases. Interestingly, phsA alone causes Escherichia coli to accumulate fatty alcohols at 19% (w/w) of the dry cell weight. Moreover, the phsA-containing E. coli accumulate more fatty alcohols (24%) and grow faster after phsB is introduced, indicating that phsAB could greatly assist the mass production of fatty alcohols.


An immunological method to determine antigenic variation in three strains of myxoma virus.
A technique is described for the purification of soluble antigens of three strains of myxoma virus. Radioimmunoassays were used to study the antigenic differences between the three strains. Results show that the soluble antigens isolated from Lu and G.V. strains do not cross-react in rabbits tested, suggesting that rabbits infected with Lu and G.V. strains of the myxoma virus can be readily distinguished. Antigen isolated from the U.F.S. strain cross-reacted with sera from both Lu- and G.V.-infected rabbits.


[Systemic lupus erythematosus and HIV infection. A case report and review of the literature].
Although HIV infection is often associated with several rheumatic diseases, the coexistence of this retroviral infection and systemic lupus erythematous is extremely uncommon. Etiopathogenetic relationship between these disorders is very complex and still problematic, so that diagnostic workout, because of their extensive clinical and serological overlap. Generally, HIV-related immunosuppression improves lupus-associated symptoms, and antiretroviral therapy may lead to an autoimmune disease flare, subsequent to the increase of circulating CD4+ cell number. A HIV-infected female patient with systemic lupus erythematosus, occurred few months after the highly active anti-retroviral therapy initiation, is described.


Ruptured arteriovenous malformation mortality: Incidence, risk factors, and inpatient outcome score.
Limited literature exists on the morbidity and mortality of AVM associated intracerebral hemorrhage (ICH) compared with non-AVM ICH. We examine morbidity and mortality in cAVM in a large nationwide inpatient sample to create a prognostic inpatient ruptured AVM mortality score. This retrospective cohort study from 2008 to 2014 compares outcomes in cAVM related hemorrhages and ICH utilizing the National Inpatient Sample database. Diagnostic codes for ICH and AVM underlying ICH were identified. We compared case fatality according to medical complications. Multivariate analysis was used to derive hazard ratios and 95% confidence intervals to assess odds of mortality. We identified 6496 patients with ruptured AVMs comparing them to 627,185 admitted with ICH. Mortality was lower for ruptured AVMs (11%) compared to ICH (22%) [p < 0.01]. Mortality associated factors were liver disease (OR 2.64, CI 1.81-3.85, p < .001), diabetes mellitus (OR 2.42, CI 1.38-4.22, p = 0.002), alcohol abuse (OR 1.81, CI 1.31-2.49, p = 0.001), hydrocephalus (OR 3.35 CI 2.81-4.00, p < 0.001), cerebral edema (OR 1.5, 1.25-1.85, p < 0.001), cardiac arrest (OR 15, CI 7.9-30, p < 0.001), and pneumonia (OR 1.93, CI 1.51-2.47, p < 0.001). A 0-5 ruptured AVM mortality score was developed: Cardiac arrest (=3), age >60 (=1), Black race (=1), chronic liver failure (=1) diabetes mellitus (=1), pneumonia (=1), alcohol abuse (=1) and cerebral edema (=1). Mortality increased with score. No patient with 5 or more points survived. The Ruptured AVM Mortality Score allows for risk stratification on patients with ICH due to ruptured AVM. This scale could prove useful in prognostication and patient education.


An improved method of 18F peptide labeling: hydrazone formation with HYNIC-conjugated c(RGDyK).
Radiolabeled alpha(v)beta(3)-integrin antagonists are increasingly investigated as a means of imaging angiogenesis. Several methods of labeling alpha(v)beta(3)-integrin binding peptide with (18)F have been reported recently. In the present study, we devised a straightforward means for labeling Arg-Gly-Asp (RGD) peptide with (18)F via hydrazone formation between c(RGDyK)-hydrazinonicotinic acid (HYNIC) (3) and 4-[(18)F]-fluorobenzaldehyde ([(18)F]4). The resulting reaction mixture was purified by HPLC to give 4'-[(18)F]-fluorobenzylidenehydrazone-6-nicotinamide-c(RGDyK) ([(18)F]5). The conjugation efficiency of 3 and 4 to form [(18)F]5 was 95.2%, and the radiochemical purity of [(18)F]5 after purification was >99%. The specific activity of [(18)F]5 estimated by radio-HPLC was 20.5 GBq/mumol (end of synthesis). Competitive binding assay of c(RGDyK) (1) and 5 was performed using [(125)I]iodo-c(RGDyK) as a radioligand, and K(i) values were found to be 2.8 and 21.7 nM, respectively. For the biodistribution study, the angiogenic mouse model was established by inducing unilateral ischemia on the left hindlimbs of ICR mice after femoral artery ablation. Seven days after inducing ischemia, [(18)F]5 was administered to the mice through the tail vein. Ischemic muscle uptake of [(18)F]5 was significantly higher than that of normal muscle (P<.01). Specific uptake was confirmed by coinjection of 1 with [(18)F]5. Here, we successfully labeled RGD peptide with (18)F via hydrazone formation between 3 and 4, resulting to [(18)F]5. [(18)F]5 was found to have high affinity for alpha(v)beta(3)-integrin and to accumulate specifically in ischemic hindlimb muscle of mice. We suggest that (18)F labeling via formation of hydrazone between HYNIC peptide and [(18)F]4 is a useful method for labeling c(RGDyK), which can be applied for imaging angiogenesis.


Accuracy of yellow fever case definition of epidemiologic surveillance, São Paulo, 2018.
To evaluate the accuracy of yellow fever (YF) suspected case definitions from the Brazilian Ministry of Health (BMH) and World Health Organization (WHO), as well as propose and evaluate new definitions of suspected cases, considering confirmed and discarded cases. The retrospective study was conducted at the Instituto de Infectologia Emílio Ribas (IIER), using the Epidemiologic Surveillance Form of YF cases. From the confirmed and discarded cases of YF, a logistic regression model was developed. The independent variables were used in a proposed definition of a suspected case of YF and its accuracy was evaluated. In total, 113 YF suspect cases were reported, with 78 confirmed (69.0%). The definitions by BMH and WHO presented low sensitivity, 59% and 53.8%, and reduced accuracy, 53.1% and 47.8%, respectively. Predictive factors for YF were thrombocytopenia, leukopenia, and elevation of transaminases greater than twice normal. The definition including individual with acute onset of fever, followed by elevation of ALT or AST greater than twice the reference value AND leukopenia OR thrombocytopenia presented high sensitivity (88.3%), specificity (62.9%), and the best accuracy (80.4%), as proposed in the model. The YF suspected case definitions of the BMH and the WHO have low sensitivity. The inclusion of nonspecific laboratory tests increases the accuracy of YF definition.


Granulocyte colony-stimulating receptor promotes beta1-integrin-mediated adhesion and invasion of bladder cancer cells.
To determine whether granulocyte colony-stimulating factor receptor (G-CSFR) autocrine signaling promotes endothelial cell adhesion and invasion of bladder cancer cells through a beta1-integrin-mediated pathway. A significant fraction of invasive bladder carcinomas express both G-CSF and G-CSFR. Bladder carcinoma cell line 5637 constitutively secretes G-CSF but lacks G-CSFR expression. Thus, we studied the effects of G-CSFR expression on cell adhesion and invasion in this unique model system. Flow cytometry and adhesion assay were performed to detect expression of beta1-integrin in G-CSFR-expressing 5637 cells and adhesion of these cells to human umbilical vein endothelial cell, respectively. Furthermore, an invasion chamber assay was done with the 5637 cells. Next, we used the G-CSF-specific antibody, siRNA, and a truncated version of G-CSFR (GR19) to block G-CSFR autocrine loop in these cells. We also used a beta1-integrin-specific neutralizing antibody in the adhesion and invasion assays with the 5637 cells. G-CSFR-mediated increased expression (approximately threefold) of beta1-integrin is significantly abrogated by G-CSF specific antibody or siRNA in 5637 cells. GR19 also completely blocked beta1-integrin expression. G-CSFR signaling increased adhesion (approximately 2.5-fold) of 5637 cells to human umbilical vein endothelial cells, which are potently blocked by beta1-integrin-specific antibody. G-CSF/G-CSFR autocrine signaling significantly increased the invasiveness of 5637 cells (approximately 10-fold), which was reduced by either attenuating G-CSF production (G-CSF-specific antibody and siRNA) or interfering with G-CSFR signaling (GR19). Furthermore, beta1-integrin-specific antibody completely blocked G-CSFR-mediated invasion of 5637 cells. Autocrine G-CSF/G-CSFR signaling in bladder cancer can significantly contribute to cancer cell adhesion and invasion in a beta1-integrin-dependent manner.


Corticotropin-releasing factor inhibits gastric emptying in dogs.
The purpose of the present study was to evaluate the effect of ovine corticotropin-releasing factor (CRF) on the gastric emptying of a saline meal in conscious dogs. Intravenous infusion of CRF (220-880 pmol . kg-1 . h-1), induced a significant linear dose dependent inhibition of gastric emptying (16-71%). CRF action was not modified by naloxone and not associated with vomiting or other side effects. Intravenous infusion of sulfated cholecystokinin octapeptide (CCK-8, 50-200 pmol . kg-1 . h-1) inhibited gastric emptying by 29-52%. The relative potency of CRF with respect to CCK-8 is 4 times less. These studies demonstrated that CRF given intravenously in picomolar amount inhibits gastric emptying of a liquid meal in dogs through a mechanism unrelated to opiates. The role of endogenous CRF in stress-induced inhibition of gastric emptying needs to be investigated.


Isolation of cell nuclei in microchannels by short-term chemical treatment via two-step carrier medium exchange.
Separation/purification of nuclei from cells is a critical process required for medical and biochemical research applications. Here, we report a flow-through microfluidic device for isolating cell nuclei by selectively digesting the cell membrane by using the concept of hydrodynamic filtration (HDF). When a cell suspension is continuously introduced into a microchannel (main channel) possessing multiple side channels, cells flow through the main channel, whereas the carrier medium of the cells is drained through the side channels. Introductions of a cell treatment solution containing a surfactant and a washing buffer enable the two-step exchange of the carrier-medium and the cell treatment by the surfactant for a short span of time. The precise control of the treatment time by changing the flow rate and/or the size of the microchannel enables the selective digestion of cell membranes, resulting in the isolation of cell nuclei after separation from membrane debris and cytoplasmic components according to size. We examined several surfactant molecules and demonstrated that Triton X-100 exhibited high efficiency regarding nucleus isolation for both adherent (HeLa) and nonadherent (JM) cells, with a recovery ratio of ~80 %. In addition, the isolation efficiency was evaluated by western blotting. The presented flow-through microfluidic cell-nucleus separator may be a useful tool for general biological applications, because of its simplicity in operation, high reproducibility, and accuracy.


Effect of epithermal neutrons on viability of glioblastoma tumor cells in vitro.
We studied in vitro effect of epithermal neutrons in various doses on viability of glioblastoma U87 tumor cells. Increasing the dose from 1.9 to 4.1 Sv promoted cell death. Cytofluorimetric analysis revealed no activation of apoptosis in the irradiated cells, which attested to necrotic death of the tumor cells exposed to epithermal neutron radiation.


E2F1-miR-20a-5p/20b-5p auto-regulatory feedback loop involved in myoblast proliferation and differentiation.
miR-17 family microRNAs (miRNAs) are crucial for embryo development, however, their role in muscle development is still unclear. miR-20a-5p and miR-20b-5p belong to the miR-17 family and are transcribed from the miR-17~92 and miR-106a~363 clusters respectively. In this study, we found that miR-20a-5p and miR-20b-5p promoted myoblast differentiation and repressed myoblast proliferation by directly binding the 3' UTR of E2F transcription factor 1 (E2F1) mRNA. E2F1 is an important transcriptional factor for organism's normal development. Overexpression of E2F1 in myoblasts promoted myoblast proliferation and inhibited myoblast differentiation. Conversely, E2F1 inhibition induced myoblast differentiation and repressed myoblast proliferation. Moreover, E2F1 can bind directly to promoters of the miR-17~92 and miR-106a~363 clusters and activate their transcription, and E2F1 protein expression is correlated with the expression of pri-miR-17~92 and pri-miR-106a~363 during myoblast differentiation. These results suggested an auto-regulatory feedback loop between E2F1 and miR-20a-5p/20b-5p, and indicated that miR-20a-5p, miR-20b-5p and E2F1 are involved in myoblast proliferation and differentiation through the auto-regulation between E2F1 and miR-20a-5p/20b-5p. These findings provide new insight into the mechanism of muscle differentiation, and further shed light on the understanding of muscle development and muscle diseases.


ASL-MRI-guided evaluation of multiple burr hole revascularization surgery in Moyamoya disease.
Moyamoya (MM) disease is characterized by progressive intracranial arterial stenosis. Patients commonly need revascularization surgery to optimize cerebral blood flow (CBF). Estimation of CBF and cerebrovascular reserve (CVR) is therefore necessary before and after surgery. However, assessment of CBF before and after indirect revascularization surgery with the multiple burr hole (MBH) technique in MM has not been studied extensively. In this study, we describe our initial experience using arterial spin labeling magnetic resonance perfusion imaging (ASL-MRI) for CBF and CVR assessment before and after indirect MBH revascularization surgery in MM patients. Eleven MM patients (initial age 6-50 years, 1 male/10 female) with 19 affected hemispheres were included. A total of 35 ASL-MRI examinations were performed using a 3D-pCASL acquisition before and after i.v. acetazolamide challenge (1000 mg in adults and 10 mg/kg in children). Twelve MBH procedures were performed in seven patients. The first follow-up ASL-MRI was performed 7-21 (mean 12) months after surgery. Before surgery, CBF was 46 ± 16 (mean ± SD) ml/100 g/min and CVR after acetazolamide challenge was 38.5 ± 9.9 (mean ± SD)% in the most affected territory (middle cerebral artery). In cases in which surgery was not performed, CVR was 56 ± 12 (mean ± SD)% in affected hemispheres. After MBH surgery, there was a relative change in CVR compared to baseline (preop) of + 23.5 ± 23.3% (mean ± SD). There were no new ischemic events. Using ASL-MRI we followed changes in CBF and CVR in patients with MM. The technique was encouraging for assessments before and after revascularization surgery.


Preclinical validation: LV/IL-12 transduction of patient leukemia cells for immunotherapy of AML.
Interleukin-12 (IL-12) is a potent cytokine that may be harnessed to treat cancer. To date, nearly 100 IL-12-based clinical trials have been initiated worldwide. Yet systemic administration of IL-12 is toxic. Different strategies are being developed to reduce such toxicities by restricting IL-12 distribution. Our previous studies employed lentivector-mediated expression of murine IL-12 in tumor cells and demonstrated effective protection in both mouse leukemia and solid tumor challenge models. In this study, we carried out preclinical validation studies using a novel lentivector to engineer expression of human IL-12 in acute myeloid leukemia blast cells isolated from 21 patients. Acute myeloid leukemia cells were transduced with a bicistronic lentivector that encodes the human IL-12 cDNA as a fusion, as well as a LNGFR (ΔLNGFR)/mutant thymidylate kinase cassette as a marking and cell-fate control element. A range of 20-70% functional transduction efficiencies was achieved. Transduced acute myeloid leukemia cells produced bioactive IL-12 protein and displayed dose-dependent sensitivity to the prodrug 3'-azido-3'-deoxythymidine. In vitro immortalization assays using transduced mouse hematopoietic stem cells demonstrated minimal genotoxic risk from our IL-12 vector. Scale-up transduction and cell processing was subsequently validated in a GMP facility to support our (now approved) Clinical Trial Application (CTA).


Preliminary Results of a Novel Hybrid Cage Glenoid Compared to an All-Polyethylene Glenoid in Total Shoulder Arthroplasty.
The aim of this study was to evaluate the preliminary outcomes of a hybrid cage glenoid design in comparison to pegged all-polyethylene glenoid components in anatomic total shoulder arthroplasty (aTSA). Ninety-two patients undergoing primary anatomic total shoulder arthroplasty with minimum two-year follow-up were reviewed. Forty-six patients had an ultra-high molecular weight polyethylene (UHMWPE) cemented pegged glenoid component, and 46 had a hybrid cage glenoid component. Patient data was retrospectively reviewed from prospectively acquired data in a multi-institutional IRB approved database. These age, gender, and follow-up matched patients were evaluated and scored preoperatively and a latest follow-up using the SST, UCLA, ASES, Constant, and SPADI scoring metrics. Additional measures included active abduction, elevation, and external rotation. Radiolucent line assessment of the glenoid was performed by use of a Grashey and axillary radiograph at latest follow-up. A Student's two tailed, unpaired t-test was used to identify differences in preoperative and postoperative results, where p < 0.05 denoted a significant difference. All patients demonstrated significant improvements in pain and function following treatment with the primary aTSA. The database contained three complications for the aTSA patients with a cage glenoid, and three complications for patients with a UHMWPE pegged glenoid. Radiographic data was available for 37 of 46 cage glenoid patients and 29 of 46 UHMWPE pegged glenoid patients. Five of 37 cage glenoid patients had a radiolucent line (13.5%) with an average radiographic line score of 0.22. Eight of 29 UHMWPE peg glenoid patients had a radiolucent line (27.6%) with an average radiographic line score of 0.57. Cage aTSA patients were associated with significantly less blood loss than aTSA UHMWPE pegged glenoid patients (avg. blood loss = 242 vs. 337; p = 0.022). At minimum two-year follow-up, hybrid cage aTSA components show equal clinical outcomes to UHMWPE pegged glenoids. However, the hybrid cage components had significantly fewer radiolucent lines and less intra-operative blood loss. Additional and longer-term clinical and radiographic follow-up is necessary to confirm these promising early results.


[Meta-analysis of group comparison and meta-analysis of reliability generalization of the State-Trait Anxiety Inventory Questionnaire (STAI)].
Since its creation the STAI has been cited in more than 14,000 documents, with more than 60 adaptations in different countries. In some adaptations this instrument has no clinical scores. The aim of this work is to determine if the State-Trait Anxiety Inventory (STAI) has higher scores in patients diagnosed with anxiety than in general population. In addition, we want to examine if the internal consistency is adequate in anxious patient samples. We performed a literature search in Tripdatabase, Cochrane, Web of Knowledge, Scopus, PyscINFO and Scholar Google, for documents published between 2008 y 2012. We selected 131 scientific articles to compare between patients diagnosed with anxiety and general population, and 25 for the generalization of reliability. For the analysis we used Cohen's d for means comparisons (random-effects method) and Cronbach's alpha for the reliability generalization (fixed-effects method). In the groups comparision the differences in state anxiety (d=1.39; CI95%: 1.22-1.56) and in the trait anxiety (d=1.74; CI95%:1.56-1.91) were significants. The reliability for patients of some anxiety disorder was between 0.87 and 0.93. So it seems that the STAI is sensitive to the level of anxiety of the individual and reliable for patients with diagnosis of panic attack, specific phobia, social phobia, generalized social phobia, generalized anxiety disorder, post-traumatic stress disorder, obsessive compulsive disorder or acute Stress disorder.


Performance and Ratings Based Measures of Executive Function in School-Aged Children with Down Syndrome.
We examined performance-based laboratory tasks and ratings-based assessments of executive function (EF) in school-aged children with Down syndrome and mental-age matched peers along with adaptive functioning. A battery of assessments including EF laboratory tasks was collected. The DS group performed both working memory/inhibition and planning laboratory tasks with significant challenges. Moderate correlations were evident only between some laboratory tasks and ratings-based EF domains. However, ratings-based EF better predicted adaptive function than performance on an EF laboratory-based task. Findings underscore the need to address early and targeted EF intervention in children with DS.


Myocyte volume and function in response to osmotic stress: observations in the presence of an adenosine triphosphate-sensitive potassium channel opener.
Hypothermic hyperkalemic cardioplegia results in significant myocyte swelling and impaired contractility. These detrimental effects may be eliminated by the addition of an adenosine triphosphate-sensitive potassium (KATP) channel opener. This study evaluated the hypothesis that a KATP channel opener (diazoxide) would benefit volume homeostasis by limiting volume and subsequent contractility changes during osmotic stress. Isolated rabbit ventricular myocyte volume and contractility were evaluated using video microscopy and field stimulation after exposure to osmotic stress at 37 degrees C. Myocytes were exposed to Tyrode's physiological solution for 20 minutes and test solution for 20 minutes, and then reexposed to Tyrode's for 20 minutes. Test solutions included control Tyrode's (1T) and osmotically altered Tyrode's (2.6T, 0.9T, and 0.6T) solutions with or without the KATP channel opener diazoxide. Severe osmotic stress (2.6T and 0.6T) resulted in significant cell shrinkage and swelling, respectively. This was unchanged by the addition of diazoxide. Mild hyposmotic stress (0.9T) resulted in significant cell swelling that was eliminated by the addition of diazoxide. Cell swelling was associated with reduced contractility. Cell swelling, but not shrinkage, was detrimental to myocyte contractility. Diazoxide eliminated volume change due to mild hyposmotic stress, similar to that previously noted with hyperkalemic cardioplegia, but did not alter volume change secondary to severe osmotic stress.


A new genus: Sporopachydermia.
In two species of the yeast genus Cryptococcus ascospores have been found. A genus is described to accommodate the two species, because the spore wall is extraordinarily thick and its ultrastructure differs from that found in all other yeast genera. The spores are easily liberated from the ascus at maturation. The name Sporopachydermia is proposed for the genus and the names S. lactativora and S. cereana are proposed for the species.


MicroRNA-506-3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/β-catenin in serous ovarian cancers.
Chemo-resistance is an important barrier to effective treatment of ovarian cancer. Poly (ADP-ribose) polymerase (PARP) inhibitors are currently promising targeted drugs used to treat BRCA-mutant ovarian cancer. Ovarian cancer patients with BRCA 1/2 mutations appear to benefit better from PARP inhibitors and chemotherapy. Understanding the mechanisms underlying PARP inhibitors and chemotherapy resistance is urgently needed. There is increasing evidence that microRNAs (miRNAs) are involved in drug resistance. MiR-506-3p is an effective inhibitor of the epithelial-to-mesenchymal transition (EMT), and can enhance chemotherapy and olaparib response in high-grade serous ovarian cancer (HGS-OvCa). Enhancer of Zeste Homolog 2 (EZH2) is considered as a direct target of miR-506-3p. The silencing of EZH2 mimics the inhibitory effects of miR-506-3p on chemo-resistance and olaparib response. Rescue of EZH2 prevented the functions of miR-506-3p. Moreover, EZH2 activates the β-catenin pathway. MiR-506-3p overexpression decreased the level of β-catenin, and the sensitivity to olaparib and cisplatin mediated by miR-506-3p was partially reversed by regulating β-catenin expression in ovarian cancer. Our results suggest that miR-506-3p increases response to PARP inhibitors and cisplatin in serous ovarian cancer by targeting EZH2/β-catenin signal pathway, which opens the possibility of using miR-506-3p overexpression as a potential therapeutic for ovarian cancer.


[Primary closure of split thickness skin donor sites using surgical foil].
The advantages of using an operation foil for wound dressing when split thickness skin grafts have been taken are presented. For some years we have used an air and steam permeable plastic foil for wound dressing in cases where split thickness skin grafts have been taken. The advantages of this procedure in our opinion are: It minimizes postoperative pain. It allows inspection of the wound whenever it appears desirable because of the transparency of the foil. It reduces the cost of wound dressing and also nursing procedures.


Evaluation of immunoglobulin adsorption on the hydrophobic charge-induction resins with different ligand densities and pore sizes.
Hydrophobic charge-induction chromatography (HCIC) is a novel technology for antibody purification. The ligand densities and pore properties of HCIC resins have significant effects on the separation behavior of protein, however, the understandings are quite limited. In the present work, new HCIC ligand, 2-mercapto-1-methylimidazole (MMI) was coupled to three agarose matrices with different pore sizes. A series of MMI resins with different ligand density and pore size was prepared by the control of ligand coupling. The adsorption isotherms and kinetics on the series of MMI resins were investigated with bovine serum immunoglobulin as the model IgG, and the effects of salt addition were studied. The Langmuir equation and pore diffusion model were used to fit the experimental data, and the influences of ligand density, pore size and salt addition on the saturated adsorption capacity, the dissociation constant and the effective diffusivity were discussed. It was found that the adsorption capacities and the effective pore diffusion coefficient increased with the increase of ligand density and pore size. The effects of salt addition on the adsorption behaviors were dependent on the ligand density. For low ligand density the IgG adsorption was salt-promoted, while the resins with high ligand density showed a salt-independent property. The results indicated that for a given protein the ligand density and pore size of HCIC resins should be optimized for improving the protein adsorption.


Current progress in clinical trials of aldose reductase inhibitors in Japan.
In addition to the results of our clinical trial of epalrestat in diabetic retinopathy (the open study), the current progress in the clinical trials of aldose reductase inhibitors for the 'triopathy' of complications (neuropathy, retinopathy and nephropathy) in Japan is reported. No data from the placebo-controlled double-blind studies in Japan are shown because a detailed analysis of the effects of epalrestat on diabetic neuropathy and retinopathy is now under way. However, it must be stressed that in the phase III placebo-controlled double-blind studies in neuropathy and retinopathy, epalrestat was effective.


Hemispheric contributions to drawing.
The drawings of 69 consecutive stroke patients with single cerebral lesions on CT and of 33 normal controls, were analyzed by two independent observers using a standardized scoring system. The drawings of left brain damaged subjects (LBD) were more impaired overall than those of right brain damaged subjects (RBD). RBD drawings displayed hemispatial neglect and impaired spatial relationships. LBD drawings were simplified and exhibited low level errors of execution. Lesion size correlated significantly with drawing impairment in RBD but not in LBD. No relationship between intrahemispheric lesion location and drawing quality was found. However, severity of hemiparesis correlated significantly with drawing impairment in LBD. Performance on a visuospatial perceptual task correlated better with overall drawing quality for RBD than for LBD. Our data suggest that neglect and a visuospatial deficit impair drawing in RBD while dominant hand paresis and a conceptual impairment which parallels comprehension impairment contribute to LBD drawing disability.


Epidemiology, physiopathology, and experimental therapeutics of acute spinal cord injury.
This article analyzes the epidemiological factors relating to acute spinal cord injury. It also delineates the anatomical and rheological characteristics of the spinal cord and denotes the latest concepts in autoregulation of spinal cord blood flow. The physiopathology of spinal cord injury is examined in terms of existing animal models, responses of the white and grey matter, and biochemical and biomechanical correlates. Experimental and clinical therapeutic modalities ranging from hypothermia to opioid antagonists, and adrenergic blockers to free radical scavengers are evaluated.


C(α) torsion angles as a flexible criterion to extract secrets from a molecular dynamics simulation.
Given the increasing complexity of simulated molecular systems, and the fact that simulation times have now reached milliseconds to seconds, immense amounts of data (in the gigabyte to terabyte range) are produced in current molecular dynamics simulations. Manual analysis of these data is a very time-consuming task, and important events that lead from one intermediate structure to another can become occluded in the noise resulting from random thermal fluctuations. To overcome these problems and facilitate a semi-automated data analysis, we introduce in this work a measure based on C(α) torsion angles: torsion angles formed by four consecutive C(α) atoms. This measure describes changes in the backbones of large systems on a residual length scale (i.e., a small number of residues at a time). Cluster analysis of individual C(α) torsion angles and its fuzzification led to continuous time patches representing (meta)stable conformations and to the identification of events acting as transitions between these conformations. The importance of a change in torsion angle to structural integrity is assessed by comparing this change to the average fluctuations in the same torsion angle over the complete simulation. Using this novel measure in combination with other measures such as the root mean square deviation (RMSD) and time series of distance measures, we performed an in-depth analysis of a simulation of the open form of DNA polymerase I. The times at which major conformational changes occur and the most important parts of the molecule and their interrelations were pinpointed in this analysis. The simultaneous determination of the time points and localizations of major events is a significant advantage of the new bottom-up approach presented here, as compared to many other (top-down) approaches in which only the similarity of the complete structure is analyzed.


Pilot-scale study of sludge pretreatment by microwave and sludge reduction based on lysis-cryptic growth.
To evaluate the performance of microwave (MW)-chemical hybrid sludge treatment system, a pilot scale MW disintegration unit (treatment capacity of 500L/d) was constructed. The results showed that organic matter, nitrogen, and phosphorus were effectively released from the MW-pretreated sludge. The values of COD released were 15.91%, 15.07%, 13.83%, 19.35%, and 15.07% for the MW, MW-acid, MW-alkali, MW-H2O2, and MW-H2O2-alkali treatment processes, respectively. Additionally, for a wastewater treatment system with a capacity of 200m(3)/d, when coupled with a MW sludge pretreatment unit, the sludge production and sludge yield were greatly reduced by 38.60% and to 0.35kg VSS/kg CODconsumed, respectively. The total operating cost of the lysis-cryptic growth system was 13.64% lower than that of the CAS system without a MW unit.


Factors affecting the outcome of patients undergoing corrective surgery for craniosynostosis: a retrospective analysis of 95 cases.
Surgical procedures for correction of craniosynostosis are often performed in pediatric patients who have a small blood volume; it represents major surgery. Literature is scarce on factors affecting blood loss, intensive care unit (ICU) and hospital stay in these patients. To identify the factors which directly affect the outcome of craniosynostosis surgery. A detailed review of records pertaining to preanesthetic evaluation, associated anomalies, intraoperative course, and postoperative follow-up was done for patients who underwent craniosynostosis surgery between June 2000 and June 2010. The correlation between different variables was evaluated using Spearman's rank correlation. During the study period 95 patients (mean age 29 months, range: 3 months-13 years) underwent corrective surgery for craniosynostosis. Hospital stay was found to be significantly associated with type of surgery and postoperative complications (P<0.001) Factors such as number of associated medical conditions, number of postoperative complications, type of induction of anesthesia, duration of surgery, type of recovery affected the ICU stay in these patients (P = 0.01). The outcome of patients undergoing craniosynostosis in terms of ICU and hospital stay is affected by the number of medical and postoperative conditions, type of anesthesia induction, duration of surgery and type of recovery.


A concept of quantitative reproductive senility: application to the hard clam, Mercenaria mercenaria (L.)?
Quantitative reproductive senility occurs when older age classes achieve less reproductive effort than expected from the allometric (power) curve relating body size to reproductive effort among younger adults. Quantitative senility can be detected by analyzing whether age explains any of the residual variance around the linear regression of log reproductive effort on log body size among all adults. In each of two collections of m. mercenaria made early in successive (1980 and 1981) breeding seasons, variation in mass of gonads (reproductive effort) was better explained by clam length than by clam age, and age failed to explain a significant amount of residual variance in the regression of log gonad mass on log body length. Among M. mercenaria from North Carolina (USA) up to age 19, there is no evidence of either absolute or quantitative reproductive senility.


On the recovery of the electroretinogram after removal of intravitreal copper particles.
This report details the influence of the time lapse and surface area size of intravitreal copper foreign bodies on the electroretinogram (ERG) and the recovery of the potentials after removal of the particles. Pure copper wires were implanted temporarily into the vitreous body of rat eyes in the area of the ora serrata and the values of the ERG were compared with those of the intact fellow eyes. In three different procedures with groups of 12 animals each the following results were obtained: (1) The metal toxicity of small copper particles (0.3 mm2) remaining one day in the vitreous body reduced the amplitudes of the a1-, a2-, and b-wave only 10% by the end of the observation time of 260 days, (2) The loss of ERG amplitudes increased to about 25% under the influence of larger copper particles (1.3 mm2; time lapse one day); and (3) Copper particles with an active surface of 1.3 mm2 remaining two days in the vitreous body caused a permanent loss of about 50%.


Single-molecule tracking of perfringolysin O assembly and membrane insertion uncoupling.
We exploit single-molecule tracking and optical single channel recording in droplet interface bilayers to resolve the assembly pathway and pore formation of the archetypical cholesterol-dependent cytolysin nanopore, Perfringolysin O. We follow the stoichiometry and diffusion of Perfringolysin O complexes during assembly with 60 ms temporal resolution and 20 nm spatial precision. Our results suggest individual nascent complexes can insert into the lipid membrane where they continue active assembly. Overall, these data support a model of stepwise irreversible assembly dominated by monomer addition, but with infrequent assembly from larger partial complexes.


Chemical cross-linking of arginyl-glycyl-aspartic acid peptides to an adhesion receptor on platelets.
A chemical cross-linking approach has been used to characterize the interaction of platelets with small peptides of 7 and 14 residues containing the arginyl-glycyl-aspartic acid (RGD) sequence recognized by a variety of cellular adhesion receptors. The radioiodinated peptides were bound to platelets, and chemical cross-linking was attained by subsequent addition of bifunctional reagents. Three different cross-linking reagents coupled the RGD-containing peptides to platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa), and both subunits of this platelet membrane glycoprotein became radiolabeled with the RGD peptides. Platelet stimulation with agonists including thrombin, phorbol myristrate acetate, and ADP increased the extent of cross-linking by predominantly enhancing the coupling of the RGD peptides to the GPIIIa subunit. Cross-linking of the labeled RGD peptides to GPIIb and GPIIIa on stimulated and nonstimulated platelets exhibited structural specificity and was inhibited by excess nonlabeled RGD peptides. The interactions were inhibited by nonlabeled RGD peptides and a peptide with an amino acid sequence corresponding to the carboxyl terminus of the gamma chain of fibrinogen but less effectively by an arginyl-glycyl-glutamic acid peptide. Cross-linking of the RGD peptides to GPIIb-IIIa was divalent ion-dependent and, on stimulated platelets, was inhibited by the adhesive proteins fibrinogen and fibronectin, but not by albumin. These results indicate that the RGD-binding sites on platelets reside in close proximity to both subunits of GPIIb-IIIa and that platelet stimulation alters the topography of these sites such that the peptides become more efficiently cross-linked to GPIIIa.


The effects of physical exercise training and cardiac education on levels of anxiety and depression in the rehabilitation of coronary artery bypass graft patients.
to evaluate whether an exercise and education-based rehabilitation programme is sufficient treatment for individuals with clinically significant levels of anxiety or depression following coronary artery bypass graft (CABG) surgery. follow-up and repeated assessment after surgery. outpatient cardiac rehabilitation programme. all 88 attenders after CABG surgery. structured interview and Hospital Anxiety and Depression (HAD) scale (using 8 as the cut-off) administered by rehabilitation nurses at start of course and HAD repeated at 12 weeks and 6 and 12 months (by post after discharge). return rates of 76 and 80% at 6- and 12-month assessments, respectively; statistically significant reductions in levels of anxiety and depression found between first and all subsequent assessments; subdividing into groups revealed significant reduction in anxiety and depression in the anxious and depressed groups at 12 weeks and 6 months, respectively, but at 12 months there was no significant reduction. there is a need to address the problems of anxiety and depression directly by screening and treatment, and to provide more psychologically-orientated cardiac rehabilitation programmes.


Integrating rehabilitation services into primary health care: policy options for Iran.
Providing rehabilitation services in primary health care (PHC) is associated with numerous health, social, and economic benefits. Therefore, low and middle-income countries, such as Iran, should benefit from the advantages of integrating rehabilitation services into PHC. We conducted a qualitative study to determine policy solutions that could facilitate the integration of rehabilitation services into Iran's PHC network. Semi-structured interviews were conducted with 38 participants, including health policymakers, rehabilitation managers, faculty members, and rehabilitation practitioners. Purposive and snowball sampling strategies were adopted to recruit participants. The WHO Health System building blocks framework analysis was applied to analyze the collected data. Participants' perspectives and experiences outlined potential policy options including: (1) stewardship: increasing political support, strengthening the leadership of the rehabilitation sector, and promoting inter-sectoral collaborations; (2) service delivery: increasing the knowledge of healthcare professionals, using local volunteers, deploying mobile rehabilitation teams, using telerehabilitation, and improving referral pathways; (3) financing: increasing government funding, preparing a package of rehabilitation services, and using appropriate payment mechanisms; (4) human resources: expanding rehabilitation workforce, training rehabilitation assistants, and enhancing employment and social opportunities; (5) information systems: establishing a comprehensive information system and an effective surveillance system; and (6) technologies: facilitating access to a range of rehabilitation equipment and raw materials, especially for prosthetics and orthotics services. Based on the WHO six building blocks framework, this study identified several policy options for integrating rehabilitation services into the Iranian PHC Network. Some of the policy options include increasing political support, promoting inter-sectoral collaborations, increasing the skills and knowledge of healthcare workers, establishing effective referral pathways, strengthening team-working, and increasing government funding.


Unprecedented plastic-made personal protective equipment (PPE) debris in river outlets into Jakarta Bay during COVID-19 pandemic.
Increased plastic uses during COVID-19 pandemic challenges efforts to reduce marine plastic debris. Despite recent observations of increased plastic-made personal protection equipment (PPE) waste in coastal areas, comparative data before and during the pandemic lacked. We present in situ monitoring data on riverine debris releases into Jakarta Bay, Indonesia, during COVID-19 pandemic relative to the 2016 baseline data. River debris at two river outlets - the Cilincing and Marunda Rivers, revealed a 5% increase in the abundance of debris and a 23-28% decrease in the weight of debris releases in March-April 2020 compared to March-April 2016, suggesting a compositional shift towards lighter debris. Plastics continued to dominate river debris at 46% (abundance) or 57% (weight). Unique to the pandemic, we observed an unprecedented presence of PPE (medical masks, gloves, hazard suits, face shields, raincoats) that accounted for 15-16% of the collected river debris of 780 ± 138 items (abundance) or 0.13 ± 0.02 tons (weight) daily. The observed increased plastic-made PPE in river outlets urges for improved medical waste management of domestic sources during the prolonged pandemic.


Using recombinant activated factor VII, B-Lynch compression, and reversible embolization of the uterine arteries for treatment of severe conservatively intractable postpartum hemorrhage: new method for management of massive hemorrhage in cases of placenta increta.
To investigate a new method for management of massive postpartum hemorrhage in cases of abnormal placenta adhesion. Case report. University hospital. An 18-year-old nullipara presented with fulminant postpartum bleeding after cesarean section due to placenta increta. The patient developed hemorrhagic and septic shock associated with disseminated intravascular coagulation. Treatment with uterotonic drugs like oxytocin and prostaglandins and conservative procedures like transfusion of packed red cells and fresh frozen plasma failed to control the diffuse bleeding. Further intervention consisted of B-Lynch sutures, recombinant activated factor VII, and reversible embolization of the uterine arteries. The bleeding stopped after operative B-Lynch compression and recombinant activated factor VII. In the interval, the bleeding continued under therapeutically resistant disseminated intravascular coagulation, and finally bilateral reversible embolization of the uterine arteries was performed to avoid an emergency hysterectomy to preserve fertility in this young woman. This is a case of abnormal placenta adhesion with massive postpartum hemorrhage in which different conservative and operative treatments were combined to avoid a hysterectomy with loss of fertility and major psychological impact for the young mother.


Genomic insights into the phylogeny and biomass-degrading enzymes of rumen ciliates.
Understanding the biodiversity and genetics of gut microbiomes has important implications for host physiology and industrial enzymes, whereas most studies have been focused on bacteria and archaea, and to a lesser extent on fungi and viruses. One group, still underexplored and elusive, is ciliated protozoa, despite its importance in shaping microbiota populations. Integrating single-cell sequencing and an assembly-and-identification pipeline, we acquired 52 high-quality ciliate genomes of 22 rumen morphospecies from 11 abundant morphogenera. With these genomes, we resolved the taxonomic and phylogenetic framework that revised the 22 morphospecies into 19 species spanning 13 genera and reassigned the genus Dasytricha from Isotrichidae to a new family Dasytrichidae. Comparative genomic analyses revealed that extensive horizontal gene transfers and gene family expansion provided rumen ciliate species with a broad array of carbohydrate-active enzymes (CAZymes) to degrade all major kinds of plant and microbial carbohydrates. In particular, the genomes of Diplodiniinae and Ophryoscolecinae species encode as many CAZymes as gut fungi, and ~80% of their degradative CAZymes act on plant cell-wall. The activities of horizontally transferred cellulase and xylanase of ciliates were experimentally verified and were 2-9 folds higher than those of the inferred corresponding bacterial donors. Additionally, the new ciliate dataset greatly facilitated rumen metagenomic analyses by allowing ~12% of the metagenomic sequencing reads to be classified as ciliate sequences.


Sociocultural factors in hallucinations.
Sociocultural factors affect both the definition and the sense organs involved in hallucinations. It is suggested that, in addition to the importance of audition in communication on the human level, other sociocultural factors may affect the choice of sense organs in the expression of hallucinatory experience. As compared with non-Western societies, Western attitudes consider hallucinations more shameful and frightening (symptoms of mental illness) and this tend to be more liable to concealment and chronicity. It is proposed that the psychoanalytical approached to the interpretation of dreams or behavioural techniques could be used to overcome the concomitants of Western attitudes toward hallucinations.