The management of heart transplant recipients treated with cyclosporine in Ireland: monitoring of cyclosporine concentrations in blood.
Thirty seven cardiac transplants have taken place at the National Cardiac Centre in Ireland since 1985. Data is presented on three still-surviving male patients aged 19 to 42 who received cardiac transplants in 1985 and 1986. Circulating levels of blood cyclosporine were measured by high pressure liquid chromatography and radioimmunoassay; plasma creatinine and bilirubin were also measured. In one of these patients the distribution of cyclosporine in blood was measured by high pressure liquid chromatography in a long term study. For all three patients cyclosporine levels in blood were compared with the daily dose of cyclosporine and biochemical and histopathological parameters.


Effects of chronic ethanol exposure on fatty acids of rat brain glycerophospholipids.
The lipid composition was analysed in forebrain subcellular fractions from rats treated with ethanol for three weeks and control rats. Increased proportions of oleic acid and a decrease in palmitic acid were consistently found in total glycerophospholipid fractions after ethanol exposure. The fatty acid compositions of individual phospholipids were also significantly changed. The proportion of docosahexaenoic acid was decreased in brain phosphatidylserine. In contrast to the decrease in the degree of unsaturation in phosphatidylserine, there was an opposite change in phosphatidylcholine wherein the degree of unsaturation was increased. No changes were produced in total cholesterol or phospholipid concentrations. These results point to a high degree of complexity of the mechanisms behind ethanol-induced changes in membrane lipid composition. The decrease in unsaturation in phosphatidylserine is probably an adaptive effect in order to counteract the fluidizing effect of ethanol. There are two possible explanations for the increase in unsaturation in brain phosphatidylcholine. The change may be due to adaptation to other biophysical effects, e.g., expansion of the membrane surface or be secondary to a change in liver lipid metabolism.


MRI-Based Back Propagation Neural Network Model as a Powerful Tool for Predicting the Response to Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma.
Pretreatment individualized assessment of tumor response to induction chemotherapy (ICT) is a need in locoregionally advanced nasopharyngeal carcinoma (LANPC). Imaging method plays vital role in tumor response assessment. However, powerful imaging method for ICT response prediction in LANPC is insufficient. To establish a robust model for predicting response to ICT in LANPC by comparing the performance of back propagation neural network (BPNN) model with logistic regression model. Retrospective. A total of 286 LANPC patients were assigned to training (N = 200, 43.8 ± 10.9 years, 152 male) and testing (N = 86, 43.5 ± 11.3 years, 57 male) cohorts. T2 -weighted imaging, contrast enhanced-T1 -weighted imaging using fast spin echo sequences at 1.5 T scanner. Predictive clinical factors were selected by univariate and multivariate logistic models. Radiomic features were screened by interclass correlation coefficient, single-factor analysis, and the least absolute shrinkage selection operator (LASSO). Four models based on clinical factors (Modelclinic ), radiomics features (Modelradiomics ), and clinical factors + radiomics signatures using logistic (Modelcombined ), and BPNN (ModelBPNN ) methods were established, and model performances were compared. Student's t-test, Mann-Whitney U-test, and Chi-square test or Fisher's exact test were used for comparison analysis. The performance of models was assessed by area under the receiver operating characteristic (ROC) curve (AUC) and Delong test. P < 0.05 was considered statistical significance. Three significant clinical factors: Epstein-Barr virus-DNA (odds ratio [OR] = 1.748; 95% confidence interval [CI], 0.969-3.171), sex (OR = 2.883; 95% CI, 1.364-6.745), and T stage (OR = 1.853; 95% CI, 1.201-3.052) were identified via univariate and multivariate logistic models. Twenty-four radiomics features were associated with treatment response. ModelBPNN demonstrated the highest performance among Modelcombined , Modelradiomics , and Modelclinic (AUC of training cohort: 0.917 vs. 0.808 vs. 0.795 vs. 0.707; testing cohort: 0.897 vs. 0.755 vs. 0.698 vs. 0.695). A machine-learning approach using BPNN showed better ability than logistic regression model to predict tumor response to ICT in LANPC. 3 TECHNICAL EFFICACY: Stage 2.


The prevalence of indoor allergens in the Baltimore area: house dust-mite and animal-dander antigens measured by immunochemical techniques.
Mattress dust samples from 42 homes in Baltimore, Md., were analyzed by ELISA and rocket immunoelectrophoresis (RIE) for major excrement allergens (P1 [equal to Dp 42], Df 6, and Dm 6) of house dust mites, Dermatophagoides pteronyssinus, D. farinae, and D. microceras, by RIE for cat major epithelial allergen (cat Ag 1) and horse major epithelial antigen (horse Ag 11), and by counter-current immunoelectrophoresis (CCIE) for cat and dog antigens. Dp 42 was detected by ELISA in 24 samples (57%) and Df 6 in 39 samples (92%). All samples were negative to Dm 6. Recorded levels varied from 50 ng of allergen per gram of dust (detection limit) to 15,000 ng/gm. A combined content of Dp 42 and Df 6 greater than 700 ng/gm was associated with a positive reaction in RIE. Concentrations of Dp 42 and Df 6 did not correlate (rS = 0.21; p greater than 0.05). Cat and dog antigens were frequently detected by CCIE (77% and 63%, respectively). CCIE titer to cat correlated well with quantitation of cat Ag 1 by RIE (p less than 0.01). Horse antigen was detected in few homes (5%). None of the specific allergen determinations correlated with levels of human serum albumin determined by RIE.


Implementation of an emergency and disaster medical response training network in the Commonwealth of Independent States.
A standardized curriculum in emergency and disaster medical response for use in the former Soviet Union was implemented under an American International Health Alliance partnership program involving over 60 healthcare and educational institutions in the United States and the Commonwealth of Independent States. The core curriculum was based on U.S. standards and developed in collaboration with local faculty to address emergency and disaster medical needs specific to the region. Local faculty members were trained by U.S. partners using a train-the-trainers methodology at U.S. partner institutions. This partnership program led to the development of 16 regional training centers in 11 countries over an 8-year period. Over 39,000 healthcare workers and first responders have now been trained throughout this network of regional training centers. Wide dissemination of standardized training encourages uniform delivery of medical care within regions and may facilitate provision of mutual aid between regional jurisdictions.


A new supported reagent for the parallel synthesis of primary and secondary O-alkyl hydroxylamines through a base-catalyzed Mitsunobu reaction.
The growing field of applications of O-alkyl hydroxylamines in medicinal chemistry and chemical biology has motivated the search for a parallel synthesis. A solid-phase approach based on the alkylation by alcohols of a new supported N-hydroxyphthalimide reagent using a Mitsunobu reaction followed by methylaminolysis has been optimized. This study points out the importance of the linker and a specific base effect for the Mitsunobu reaction. A large variety of alcohols can be used to give with moderate to high yields diverse O-alkyl hydroxylamines in high purity.


Laser microdissection and RNA analysis.
Microdissection techniques have become an important tool to link histomorphology and pathophysiological events using modern methods of molecular biology. They allow isolation of cell clusters or even single cells precisely under optical control from complex tissue structures for further analysis of DNA, RNA, and proteins. In particular, the fragile RNA molecules can be preserved during microdissection so that gene expression and regulation measurement become feasible in a cell type-specific manner within complex tissues. This report focuses on and outlines the procedures for RNA investigation, from tissue fixation, sectioning, and staining to downstream applications (RT-PCR, mRNA quantification, and mRNA preamplification). Standards for the preparation of RNA from frozen and formalin-fixed tissues are presented. Specific protocols are given for both the isolation of RNA from small numbers of cells (50 cells) as well as for larger cell numbers. While most of the procedures are identical for the microdissection systems, special features of each technique are mentioned.


External validation of the Vulnerable Elder's Survey for predicting mortality and emergency admission in older community-dwelling people: a prospective cohort study.
Prospective external validation of the Vulnerable Elder's Survey (VES-13) in primary care remains limited. The aim of this study is to externally validate the VES-13 in predicting mortality and emergency admission in older community-dwelling adults. Design: Prospective cohort study with 2 years follow-up (2010-2012). 15 General Practices (GPs) in the Republic of Ireland. n = 862, aged ≥70 years, community-dwellers Exposure: VES-13 calculated at baseline, where a score of ≥3 denoted high risk. i) Mortality; ii) ≥1 Emergency admission and ≥1 ambulatory care sensitive (ACS) admission over 2 years. Descriptive statistics, model discrimination (c-statistic) and sensitivity/specificity. Of 862 study participants, a total of 246 (38%) were classified as vulnerable at baseline. Fifty-three (6%) died during follow-up and 246 (29%) had an emergency admission. At the VES-13 cut-point of ≥3 denoting high-risk model discrimination was poor for mortality (c-statistic: 0.61 (95% CI 0.54, 0.67), ≥1 emergency admission (c-statistic: 0.59 (95% CI 0.56, 0.63) and ≥1 ACS emergency admission (c-statistic: 0.63 (95% CI 0.60, 0.67). In this study the VES-13 demonstrated relatively limited predictive accuracy in predicting mortality and emergency admission. External validation studies examining the tool in different health settings and healthier populations are needed and represent an interesting area for future research.


Quantitative analysis of Variolin analog (PM01218) in mouse and rat plasma by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
PM01218 is a novel marine-derived alkaloid and has shown potent growth inhibitory activity against several human cancer cell lines. A rapid and sensitive high performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to quantify PM01218 in mouse and rat plasma. The lower limit of quantitation (LLOQ) was 0.05 ng/mL. The calibration curve was linear from 0.05 to 100 ng/mL (R(2)>0.999). The assay was specifically based on the multiple reaction monitoring (MRM) transitions at m/z 278.4-->184.2, no endogenous material interfaced with the analysis of PM01218 and its internal standard from blank mouse and rat plasma. The mean intra- and inter-day assay accuracy remained below 15 and 8%, respectively, for all calibration standards and QC samples. The intra- and inter-day assay precision was less than 12.8 and 8.5% for all QC levels, respectively. The utility of the assay was demonstrated by pharmacokinetics studies of i.v. (bolus) PM01218 on SD rats.


Model for detection of membrane-associated antigens on epithelial cells (HLA-A, -B, -C alloantigens and pemphigus antigens).
Incubation of skin explant culture with HLA-A, -B and -C alloantibodies results in detachment of cells at the periphery of the outgrowth. This detachment can be observed within 1 1/2 h, using the reflection contrast microscope. During the detachment of the epithelial cell, characteristic changes occur, such as disorganization of the filopodia and lifting up of the cell borders from the surface of the Petri dish. The same changes were seen using antibodies against pemphigus antigens.


Activating Selenium Cathode Chemistry for Aqueous Zinc-Ion Batteries.
Aqueous rechargeable zinc-ion batteries (ARZIBs) are a promising next-generation energy-storage device by virtue of the superior safety and low cost of both the aqueous electrolyte and zinc-metal anode. However, their development is hindered by the lack of suitable cathodes with high volumetric capacity that can provide both lightweight and compact size. Herein, a novel cathode chemistry based on amorphous Se doped with transition metal Ru that mitigates the resistive surface layer produced by the side reactions between the Se cathode and aqueous electrolyte is reported. This improvement can permit high volumetric capacity in this system. Distinct from the conventional conversion mechanisms between Se and ZnSe in Se||Zn cells, this strategy realizes synchronous proton and Zn2+ intercalation/deintercalation in the Ru-doped amorphous Se||Zn half cells. Moreover, an unanticipated Zn2+ deposition/stripping process in this system further contributes to the superior electrochemical performance of this new cathode chemistry. Consequently, the Ru-doped amorphous Se||Zn half cells are found to deliver a record-high capacity of 721 mAh g-1 /3472 mAh cm-3 , and superior cycling stability of over 800 cycles with only 0.015% capacity decay per cycle. This reported work opens the door for new chemistries that can further improve the gravimetric and volumetric capacity of ARZIBs.


Rapid and specific detection of Lassa virus by reverse transcription-PCR coupled with oligonucleotide array hybridization.
To facilitate sequence-specific detection of DNA amplified in a diagnostic reverse transcription (RT)-PCR for Lassa virus, we developed an array featuring 47 oligonucleotide probes for post-PCR hybridization of the amplicons. The array procedure may be performed with low-tech equipment and does not take longer than agarose gel detection.


Selenium deficiency causes oxidative stress and activates inflammation, apoptosis, and necroptosis in the intestine of weaned calves.
Selenium performs a variety of biological functions in organisms, including antioxidant and anti-inflammatory effects. This study investigated how selenium deficiency affects weaned calves' intestines. According to Inductively coupled plasma mass spectrometry (ICP-MS) analysis of intestinal selenium concentrations in calves, the Se-D group had a significantly lower concentration of selenium. Hematoxylin-eosin staining showed that the intestinal epithelial cells were detached, the goblet cells were lost, and the intestinal villi were fragmented and loosely arranged in the Se-D group, along with hyperemia and inflammatory infiltration. Of the 22 selenoprotein genes, 9 were downregulated in response to selenium deficiency in Reverse transcription-PCR (RT-PCR), whereas 6 genes were upregulated. In the Se-D group, oxidative stress was detected by measuring redox levels in the intestines. Furthermore, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, RT-PCR, and Western blotting (WB) results indicated that both intrinsic and extrinsic apoptosis pathways are activated in the intestine during selenium deficiency. Selenium deficiency also induced necroptosis in the intestine through upregulation of MLKL, RIPK1, and RIPK3 mRNA levels. In addition, according to hematoxylin-eosin staining and ELISA, selenium-deficient calves had severe inflammation in their intestines. As a result of RT-PCR and WB analyses, we found that selenium deficiency was associated with nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Our study suggested that weaned calves' intestines are affected by selenium deficiency, which causes oxidative stress, inflammation, apoptosis, and necroptosis.


Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.
To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (<age 21 years) depressive and anxiety disorders, adjusting for current age, sex, country, education, and current smoking. Childhood adversities predicted adult-onset asthma with risk increasing with the number of adversities experienced (HRs = 1.49-1.71). Early-onset depressive and anxiety disorders also predicted adult-onset asthma (HRs = 1.67-2.11). Childhood adversities and early-onset depressive and anxiety disorders both predicted adult-onset asthma after mutual adjustment (HRs = 1.43-1.91). Childhood adversities and early-onset depressive/anxiety disorders independently predict adult-onset asthma, suggesting that the mental disorder-asthma relationship is not a function of a shared background of childhood adversity.


A miR-210-3p regulon that controls the Warburg effect by modulating HIF-1α and p53 activity in triple-negative breast cancer.
Reprogrammed energy metabolism, especially the Warburg effect (aerobic glycolysis), is an emerging hallmark of cancer. Different from other breast cancer subtypes, triple-negative breast cancer (TNBC) exhibits high metabolic remodeling, increased aggressiveness and lack of targeted therapies. MicroRNAs (miRNA) are essential to TNBC malignant phenotypes. However, little is known about the contribution of miRNA to aerobic glycolysis in TNBC. Through an integrated analysis and functional verification, we reported that several miRNAs significantly correlates to the Warburg effect in TNBC, including miR-210-3p, miR-105-5p, and miR-767-5p. Ectopic expression of miR-210-3p enhanced glucose uptake, lactate production, extracellular acidification rate, colony formation ability, and reduced serum starvation-induced cell apoptosis. Moreover, GPD1L and CYGB were identified as two functional mediators of miR-210-3p in TNBC. Mechanistically, miR-210-3p targeted GPD1L to maintain HIF-1α stabilization and suppressed p53 activity via CYGB. Ultimately, miR-210-3p facilitated aerobic glycolysis through modulating the downstream glycolytic genes of HIF-1α and p53. Taken together, our results decipher miRNAs that regulate aerobic glycolysis and uncover that miR-210-3p specifically contributes to the Warburg effect in TNBC.


Effects of Artificial Islands Construction on the Spatial Distribution and Risk Assessment of Heavy Metals in the Surface Sediments from a Semi-closed Bay (Longkou Bay), China.
Artificial islands construction can significantly influence the spatial distribution of heavy metals in inshore sediments. In this study, the distribution and contamination of heavy metals (Cd, Co, Cr, Cu, Ni, Pb, Zn, As and Hg) in inshore sediments of the Longkou Bay and artificial island adjacent areas were investigated in 2013 and 2014, respectively. Results showed that the contents of heavy metals increased in the Longkou Bay and decreased in the west of the artificial island in 2014 compared with 2013. The contamination and potential eco-risk of heavy metals in the sediments were higher in 2014 than those in 2013. Cd and Hg showed a high potential eco-risk in LK02, and other metals were in the lower level. The results indicated that after the construction of artificial islands in the Longkou Bay, the contamination and eco-risk of heavy metals in the sediments markedly increased in the Longkou Bay.


An autopsied case of unclassifiable sporadic four-repeat tauopathy presenting with parkinsonism and speech disturbances.
A 48-year-old Japanese woman experienced slow-onset parkinsonism and speech disturbances. Neurological examinations revealed rigidity in the trunk and extremities, bradykinesia and postural instability, although cognitive impairments and psychiatric symptoms were not apparent in the early disease stage. Neuroimaging revealed progressive bilateral frontotemporal lobe atrophy with cerebral blood flow hypoperfusion. No apparent signs of lower motor neuron involvement were observed, such as fasciculation or electromyogram findings. She eventually reached the akinetic mutism state, and gastrostomy and tracheotomy were performed at 4 years after onset. A clinical diagnosis of progressive supranuclear palsy was made prior to her death, which occurred 6 years after onset. Post mortem examinations revealed that the brain weighed 1200 g and showed atrophy of the frontotemporal lobe and brainstem. Severe neuron loss and gliosis were observed in the frontotemporal lobe. The superior and middle frontal gyri were the most severely affected and showed spongiform changes in the superficial layer. The globus pallidus, subthalamic nucleus, cerebellar dentate nucleus, substantia nigra and inferior olivary nucleus also showed neuronal loss with gliosis. Using hyperphosphorylated tau (AT-8) immunostaining, pretangle-like neurons, numerous short threads and glial tau pathology were extensively observed. Using Gallyas-Braak silver staining, thin and short threads were also extensively observed, but considerably fewer than those observed by AT-8 immunostaining. Neither astrocytic plaques nor tuft-shaped astrocytes were observed. Examination by immunoelectron microscopy showed straight fibrils approximately 15 nm in diameter in the neuronal cytoplasmic inclusions in the cerebral cortex and in the fibrillary structures in the cerebral white matter. Western blot analysis of sarkosyl-insoluble tau revealed predominantly four-repeat tau and a banding pattern similar to that seen in progressive supranuclear palsy. No pathogenic mutations were found during the gene analysis of microtubule-associated protein tau. After completing our comprehensive investigation, we diagnosed this patient with unclassifiable four-repeat tauopathy.


Somatization, paranoia, and language.
Somatization and paranoia are circumscribed distortions of reality that are impervious to the normative process of consensual validation. These distortions are often postulated as a means of bolstering lowered self-esteem. We used computerized content analysis of the free speech of patients with these disorders in order to identify and compare dimensions of self-concept reflected in their lexical choices. Interestingly, patients with these disorders differed in the themes prominent in their speech. The higher frequency categories used by the somatization disorder group conveyed an overwhelming sense of negativism, distress, and a preoccupation with an uncertain self-identity. In contrast, the categories used by the paranoid patients portrayed an artificially positive, grandiose self-image and a defensive abstractness. Our exploratory analysis suggests that circumscribed distortions of reality in somatization and paranoid disorders are not associated with the same common defensive style attempting to bolster self-esteem.


The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis.
The exosomal long noncoding RNAs (lncRNAs) have been reported to have cardioprotective effects on ischemia-reperfusion (I/R) injury by hindering ferroptosis, but the role of lncRNA Mir9-3 host gene (Mir9-3hg) in cardiac I/R injury remains unclear. Exosomes were extracted from mouse bone marrow mesenchymal stem cells (BMSCs) and identified by detecting the exosome specific marker levels, and the results showed that Mir9-3hg was highly expressed in BMSCs-Exo. Hypoxia/reoxygenation (H/R)-treated HL-1 mouse cardiomyocytes were incubated with exosomes extracted from BMSCs transfected with Mir9-3hg siRNA. BMSCs-Exo incubation observably facilitated cell proliferation, increased glutathione (GSH) content, and reduced iron ion concentration, reactive oxygen species (ROS) level and ferroptosis marker protein levels in H/R-treated cells, while interfering Mir9-3hg reversed these effects. RNA binding protein immunoprecipitation assay was found that Mir9-3hg bound with pumilio RNA binding family member 2 (Pum2) protein and downregulated Pum2 expression. Silence of Pum2 reversed the effects of Mir9-3hg inhibition on cell functions. Chromatin immunoprecipitation assay was revealed that Pum2 bound with peroxiredoxin 6 (PRDX6) promoter and restrained PRDX6 expression. Silence of PRDX6 reversed the improved effects of Pum2 downregulation on cell functions. Additionally, BMSCs-Exo treatment ameliorated cardiac function in I/R-treated mice by inhibiting cardiomyocyte ferroptosis. BMSCs-Exo treatment attenuates I/R-induced cardiac injury by inhibiting cardiomyocyte ferroptosis through modulating the Pum2/PRDX6 axis, thereby ameliorating cardiac function.


Age alters expression and inducibility of heme oxygenase isozymes in mice.
Heme oxygenase (HO) performs the rate limiting step in heme degradation and is induced by cell injury or stress. We wished to determine if dietary fatty acid composition, increased age and/or an induced oxidative stress would alter the expression of HO-1 (constitutive and inducible isozyme) or of HO-2 (constitutive isozyme), in mouse liver, spleen and brain. Six-and 24-month-old male B6C3F1 mice were fed AIN-76A diets containing either 5% corn oil (CO, moderately unsaturated, n=5 per age group) or 19% menhaden fish oil plus 1% corn oil (FO, highly polyunsaturated, n=20 per age group). After 2 weeks, 5 CO and 5 FO fed mice in each age group were sacrificed. The remaining FO diet mice (n=15 per age group) were then challenged with a systemic oxidative stress by intraperitoneal injection of 125 mg iron/kg body weight as iron dextran. Five stressed mice from each age group were sacrificed 1, 5, and 24 hours post injection; liver, spleen and brain were removed. Part of each tissue was fixed in formalin, and microsomal protein isolated from the remaining tissue. HO-1 and HO-2 were detected by immunoblot of microsomal protein and by immunohistochemical staining of fixed tissue in the liver and spleen, but only HO-2 was detected in the brain. There was no significant difference in HO-1 or HO-2 expression due to diet. The liver of old unstressed mice had significantly more HO-1 than young mice. However, HO-1 was significantly induced in the livers of young mice, but not of old mice, following oxidative stress. Spleen HO-1 expression was not significantly altered by age or oxidative stress. HO-2 expression was not significantly altered by age or induced oxidative stress in any tissue examined. Age-related alterations in liver HO-1 isozyme expression and inducibility may contribute to increased susceptibility to exogenous stress and disease.


Less Surgical Experience Has no Impact on Mortality and Morbidity After Laparoscopic Cholecystectomy: A Prospective Cohort Analysis.
The number of cholecystectomies required to be fully educated as a surgeon has not yet been established. The European Association for Endoscopic Surgery, however, claims that inadequate experience is a risk factor for bile duct injury. The objective was to investigate surgical experience as a risk factor after laparoscopic cholecystectomy. A prospective cohort study using the Danish Cholecystectomy Database to generate a cohort including adults treated with laparoscopic cholecystectomy from 2006 to 2011. The relationship between surgeons' level of experience and outcomes were evaluated. Surgical inexperience was not a risk factor for mortality and morbidity. The risk of conversion was however higher when the patients were operated by more experienced surgeons with an odds ratio of 1.80 (95% confidence interval, 1.51-2.14). Surgical inexperience was not a risk factor for bile duct injury. We found that low surgical experience did not by itself increase the risk of mortality or morbidity.


Thermal detection thresholds in 5-year-old preterm born children; IQ does matter.
Experiencing pain at newborn age may have consequences on one's somatosensory perception later in life. Children's perception for cold and warm stimuli may be determined with the Thermal Sensory Analyzer (TSA) device by two different methods. This pilot study in 5-year-old children born preterm aimed at establishing whether the TSA method of limits, which is dependent of reaction time, and the method of levels, which is independent of reaction time, would yield different cold and warm detection thresholds. The second aim was to establish possible associations between intellectual ability and the detection thresholds obtained with either method. A convenience sample was drawn from the participants in an ongoing 5-year follow-up study of a randomized controlled trial on effects of morphine during mechanical ventilation. Thresholds were assessed using both methods and statistically compared. Possible associations between the child's intelligence quotient (IQ) and threshold levels were analyzed. The method of levels yielded more sensitive thresholds than did the method of limits, i.e. mean (SD) cold detection thresholds: 30.3 (1.4) versus 28.4 (1.7) (Cohen'sd=1.2, P=0.001) and warm detection thresholds; 33.9 (1.9) versus 35.6 (2.1) (Cohen's d=0.8, P=0.04). IQ was statistically significantly associated only with the detection thresholds obtained with the method of limits (cold: r=0.64, warm: r=-0.52). The TSA method of levels, is to be preferred over the method of limits in 5-year-old preterm born children, as it establishes more sensitive detection thresholds and is independent of IQ.


Goal-related planning constraints in bimanual grasping and placing of objects.
Our primary objective was to examine the possible interplay of the end-state comfort effect and bimanual temporal and spatial coupling constraints in a grasp-to-place task. Unimanual and bimanual grasping and placing tasks were employed with manipulations on initial comfort (by use of potentially interfering obstacles) and target goals (using various demands on end goal object orientations). Confirming previous temporal findings, incongruent bimanual tasks were considerably slower in initiation time and movement time than congruent ones, reflecting costs in conceptualizing, planning, and completion of the task. With respect to spatial constraints, when the same goal was present for both hands there was strong evidence of the influence of both end-state comfort and bimanual constraints. This was often not the case when the task demands differed for the two hands, although the primary task goals were still attained. We suggest that the implementation of constraints is not based on a strict hierarchy; rather, certain constraints become dominant depending on the task and situation.


Chondrodysplasia punctata. Report of two cases.
Chondrodysplasia punctata is a rare familial disorder characterized by punctate calcifications in the epiphyseal regions. The radiological picture is typical, but early diagnosis is important as the characteristic calcifications disappear within the first year of life. Three subtypes with different clinical, radiological, and hereditary characteristics have been separated. Detailed diagnosis is crucial for effective genetic counselling. However, the autosomal dominant Conradi-Hünermann type is very heterogeneous and a lethal nonrhizomelic subtype has been suggested as well. Two cases of chondrodysplasia punctata are presented to demonstrate the wide range of radiological appearances. One of the cases represents the Conradi-Hünermann type and the other may represent the lethal nonrhizomelic subtype of Conradi-Hünermann.


Determination of phytonadione in elemental diets by TLC-spectrophotodensitometry.
The quantitative analysis of phytonadione in several elemental diet formulations at levels ranging from 90 to 150 ppb is described. After extraction with petroleum either, the sample is cleaned up by silica gel column chromatography and separated on a TLC plate; phytonadione is determined by reflectance densitometry. Recovery data show that the method is accurate (X = 97%) and has a precision (RSD) of +/- 6%.


Design, synthesis and evaluation of a novel fluorescent probe to accurately detect H2S in hepatocytes and natural waters.
Design and synthesis of fluorescent probe with fast response, excellent water solubility and good hepatocyte-targeting capacity to detect hydrogen sulfide (H2S) in hepatocytes and water samples is of great significance. Here, a novel fluorescent probe QL-Gal-N3 for detection of H2S was designed and synthesized based on H2S-mediated azide reduction strategy. This sensor demonstrated low toxicity, fast response (within 1 min), high selectivity and low detection limit (as low as 126 nM in water) for the detection of H2S. HeLa, A549 and HepG-2 cells were chosen to investigate the hepatocyte-targeting ability of QL-Gal-N3 respectively. The results indicated that the specific recognition of ASGPR over-expressed in hepatocytes by galactose group was an important reason for the good targeting ability of probe QL-Gal-N3. Furthermore, due to the introduction of glycosyl moiety, the water solubility of fluorescent probe was enhanced obviously. It was successfully applied for the detection of H2S in environmental water samples including river water, tap water, lake water and waste water.


[Impact of delayed discharge for nonmedical reasons in a tertiary hospital internal medicine department].
Delayed discharge occurs from a clinical point of view when a patient is considered medically fit for discharge but continues occupying a bed due to a nonmedical problem. This circumstance overloads the care system, however, its real frequency and loss of useful days of hospitalization have not being evaluated in Spain up to date. To analyze the frequency of hospital delayed discharges due to non-medical reasons in a tertiary hospital Internal Medicine Department and to determine the clinical and socio-familial factors related to this situation. An observational and prospective study was performed to analyze the characteristics of the patients whose discharge was delayed for nonmedical reason over a 12-month period. There were 4850 discharges in the Internal Medicine Department, 170 (3.5%) of which were delayed because of nonmedical problems. This accounted for a loss of 1603 useful days of hospitalization for other patients within one year. The median delay was 5 days (range: 3-12). Patients with delayed discharges were elder and had a higher prevalence of acute cerebrovascular disease as well as alcohol or benzodiazepines use related problems. The main causes were the overload or inability of the family to care for the patient and the impossibility to combine patient care with the family's working life (51.8%), and lack of family or social support network (21.8%). Delayed discharges for nonmedical reasons are frequent and mainly motivated by social-familiar problem to take charge of the patients after their hospitalization. This accounts for a significant overload for the hospitals.


Modulation by lipid mediators of immune complex-induced lung inflammation in mice.
The present study characterized a murine model of immune complex-induced pneumonitis and investigated the role of platelet-activating factor (PAF) and eicosanoids as mediators of lung neutrophil infiltration and hemorrhagic lesions. Rabbit antibodies to bovine serum albumin were injected into the airways and bovine serum albumin was injected intravenously into C3H/HePas and BALB/c mice. After 24 h, a significant increase in neutrophil infiltration and hemoglobin concentration in the bronchoalveolar lavage fluid and lung parenchyma was observed in both strains despite the C3H/HePas strain being 10 times more sensitive to PAF. Neutrophil influx and vascular lesions were not affected by pre-treatment of the mice with the PAF receptor antagonist, WEB 2170 (5-(2-chlorphenyl)carbonyl)-3,4-dihydro- 10-methyl-3-((4-morpholinyl)-2H,7H-cyclopenta(4,5)thieno(3,2-f)(1,2,4)-t riazolo-(4,3-a)(1,4)-diazepine). In contrast, neutrophil influx and vascular lesions were increased by the cyclo-oxygenase inhibitor, indomethacin, and reduced by the inhibitor of leukotriene synthesis, MK 886 (3-[1-(4-chlorobenzyl-3-t-butyl-thio-t-isopropyl-indol-2y-1]-2-2-+ ++dimethylpropanoic acid) and by the leukotriene B4 receptor antagonist, RO 0254094 (2-[(5-carboxypentyl)-6-[6-[3,4-dihidro-4-oxo-8-propyl-2H-1-benzop yran-7-yl)hexyl] benzenepropanoic acid). Increased levels of leukotriene B4, leukotriene C4/D4, thromboxane B2 were found in bronchoalveolar lavage fluid 4 h after induction of the reaction. There is also a tendency to increased prostaglandins E2 levels. Neutrophil infiltration and vascular lesions in immune complex-induced pneumonitis in mice are mediated by leukotriene B4.


Double figure-of-eight reconstruction technique for chronic anterior sternoclavicular joint dislocation.
Sternoclavicular joint dislocations account for <5 % of all dislocations of the shoulder girdle. Whereas most cases of anterior dislocation do not experience symptoms, some patients with anterior instability remain symptomatic and require reconstructive surgery to stabilize the sternoclavicular joint. We present the case of a 57-year-old male diagnosed with sternoclavicular joint anterior dislocation and unusual swallowing difficulty while bending the neck forward. The patient was treated using a new and effective surgical technique of sternoclavicular joint reconstruction named "double figure-of-eight" using the ipsilateral gracilis tendon. Surgical outcome was successful, based on the Rockwood SC joint rating scale, and the patient maintained excellent stability even after 2 years. This new surgical technique offers superior stability, without harvest site morbidity, to patients with rare, severe, and chronic sternoclavicular joint dislocation. Level of evidence IV.


Needs Assessment Using a Structured Prioritization Schema: An Open Letter to PACS Vendors.
The aim of this work was to prioritize in a quaternary academic environment necessary elements of a replacement PACS. This quality improvement work was conducted at one academic medical center and was "not regulated" by the institutional review board. Three workgroups (10-15 members each) with unique resident, fellow, and attending radiologists; IT specialists; and departmental leaders convened in 2018 to prioritize elements for a PACS replacement project, including integrated IT tools. Each workgroup met two or three times and represented one of three missions (clinical, research, and education). Six elements assigned the highest priority were distilled from each workgroup. The resulting 18 elements were condensed into survey format and distributed to all department residents, fellows, and faculty members for 5-point Likert-type prioritization stratified by mission. Data were collected over 2 weeks. The survey response rate was 37% (71 of 192; 17 of 44 residents, 3 of 27 fellows, and 51 of 121 faculty members). Self-reported work effort was 63 ± 26% clinical, 14 ± 11% education, 15 ± 21% research, and 8 ± 14% administration. Aggregate priority ratings across all domains were highest for "stable system with predictable behavior" (mean, 4.51), "minimizes repetitive non-value-added work" (mean, 4.40), "interoperability" (mean, 4.12), and "near-instantaneous load times" (mean, 4.07). Clinical-specific ratings for these elements were even higher (means, 4.85-4.90). The lowest aggregate scores were mobile device compatibility (mean, 3.03), connectivity to nonaffiliated sites (mean, 3.01), and integrated instant messaging (mean, 2.87). The department prioritized a stable and interoperable system that minimized non-value-added work. In other words, participants wanted a functioning PACS. PACS vendors should prioritize a reliable experience over niche add-ons.


What influences self-perceived competence and confidence in dementia care home staff? A systematic review.
Dementia care staff working in long-term care settings are often exposed to a variety of complex situations that can be emotionally challenging, and a lack of adequate support and limited training opportunities may contribute to high levels of staff turnover in this area. Good-quality training may be beneficial for improving the quality of care provided, and in improving staff confidence and morale. This systematic review aimed to establish how dementia care home staff perceived their own competence and confidence in relation to the care they deliver, whether there are any specific interventions that improve these feelings, and whether feeling more competent and confident impacts on care delivery. A search of the literature focusing on staff perceptions of competence and confidence identified 14 873 studies. Following the removal of duplicates and papers that did not meet the inclusion criteria, 19 studies were included in the review and subject to quality assessment. Studies varied in terms of quality and design, and were categorised as either intervention or non-intervention studies. Four studies found a significant increase in feelings of competence and confidence following intervention, although many studies did not statistically analyze their data. The most successful interventions seemed to be those that involved practical support alongside education, and non-intervention studies highlighted the importance of specific dementia and palliative care training with regard to feelings of competence and confidence. Teaching alone may not be an adequate method of training dementia care staff, and the most successful interventions were those where practical support was also provided. Most studies suggested that improvements in competence and confidence also had benefits for care delivery and staff wellbeing. More research needs to be done using validated outcome measures and with competence and confidence as the primary aim.


Examining the Energy-Environmental Kuznets Curve in OECD Countries Considering their Population.
This research aims to examine the validity of the Environmental Kuznets Curve (EKC) hypothesis in 37 Organization for Economic Co-operation and Development (OECD) countries over the period from 1960 to 2019. Panel Quantile Regressions (QR) show that for the lower quartile, economic growth does not impact emissions; for the central quartile a U-shaped curve emerges; while for the upper quartile, an N-shaped curve is found. In addition, cointegrating regressions highlight that economic growth, fossil fuel consumption, and population exert a detrimental effect on the environment, while renewable energy consumption reduces carbon dioxide (CO2) emissions. These results are confirmed by panel causality tests since a feedback mechanism is found between CO2 emissions and the remaining series. Furthermore, single-country estimates provide evidence of great variability in the sample.


Four polymorphisms of the CAPN 10 gene and their relationship to polycystic ovary syndrome susceptibility: a meta-analysis.
To investigate the association between CAPN 10 gene polymorphism and polycystic ovary syndrome (PCOS) susceptibility. Meta-analysis of published case-control studies of four single nucleotide polymorphisms (SNPs) in CAPN 10 and PCOS susceptibility. Women with PCOS. Odds ratios (ORs) and 95% confidence intervals (CIs) for heterozygous, homozygous, dominant model, recessive model and allele. A total of 11 studies were involved in the meta-analysis. UCSNP-63 was significantly associated with PCOS, with homozygous carriers (TT vs CC: OR = 0·64; 95% CI: 0·45-0·90) and recessive model (TT vs CC and CT: OR = 0·64; 95% CI: 0·45-0·90) being protective factors. In addition, UCSNP-19 was significantly associated with PCOS, with recessive model (ins/ins vs del/del and del/ins: OR = 0·72, 95% CI: 0·59-0·88) and insert allele (ins vs del: OR = 0·85, 95% CI: 0·76-0·96) being protective factors, while heterozygous carriers (del/ins vs del/del: OR = 1·56, 95% CI: 1·24-1·94) and deletion allele (del vs ins: OR = 1·18, 95% CI: 1·04-1·32) being risk factors. However, no significant associations were found between UCSNP-44, -43 and PCOS. Moreover, the results of the Rotterdam criteria subgroup analysis were similar with that of overall analysis. This is the first report on the association between CAPN 10 UCSNP-63 and PCOS in genotype, with homozygous carriers and recessive model being protective factors. Additionally, insert allele and recessive model of UCSNP-19 are protective factors, while deletion allele and heterozygous genotype are risk factors for PCOS development.


Reliability, responsiveness, and validity of slow walking speed in community dwelling older adults.
Independent ambulation requires adaptability. Self-selected and maximum walking speeds are often both assessed to demonstrate the ability to adapt speed to different tasks and environments. However, purposefully walking at a slow speed (slowWS) could also be an appropriate adaptation in certain situations but has rarely been investigated. The purpose of this study was to assess the reliability, responsiveness, and concurrent validity of slowWS in community-dwelling older adults. This was an observational, cross-sectional study of 110 community-dwelling older adults. Test-retest and inter-rater reliabilities of slowWS were assessed with intra-class correlation coefficients. Standard error of measurement (SEM) and minimal detectable change (MDC95) were calculated to determine responsiveness. Concurrent validity was assessed with Spearman rank-order correlations between slowWS and a battery of tests previously shown to be related to walking speed. Walking speed measurement for slowWS was shown to have excellent test-retest and interrater reliability (ICCs values of 0.971-0.997). Standard error of measurement value was small (0.015 m/sec) and MDC95 was 0.04 m/sec. SlowWS was not found to significantly correlate to any other study variable. Walking speed, whether self-selected, maximum, or slow, can be measured reliably with a stopwatch and specific verbal commands. While slowWS could be beneficial for certain tasks or environments, walking slowly was not associated with age, sex, comorbidity, or measures of cognition, depression, strength, balance, disability, or life-space in this sample.


Facile and rapid generation of 3D chemical gradients within hydrogels for high-throughput drug screening applications.
We propose a novel application of dielectrophoresis (DEP) to make three-dimensional (3D) methacrylated gelatin (GelMA) hydrogels with gradients of micro- and nanoparticles. DEP forces were able to manipulate micro- and nanoparticles of different sizes and materials (i.e., C2C12 myoblasts, polystyrene beads, gold microparticles, and carbon nanotubes) within GelMA hydrogels in a rapid and facile way and create 3D gradients of these particles in a microchamber. Immobilization of drugs, such as fluorescein isothiocyanate-dextran (FITC-dextran) and 6-hydroxydopamine (6-OHDA), on gold microparticles allowed us to investigate the high-throughput release of these drugs from GelMA-gold microparticle gradient systems. The latter gradient constructs were incubated with C2C12 myoblasts for 24h to examine the cell viability through the release of 6-OHDA. The drug was released from the microparticles in a gradient manner, inducing a cell viability gradient. This novel approach to create 3D chemical gradients within hydrogels is scalable to any arbitrary length scale. It is useful for making anisotropic biomimetic materials and high-throughput platforms to investigate cell-microenvironment interactions in a rapid, simple, cost-effective, and reproducible manner.


Metabolism and endocrine secretion in response to a test meal in normal-weight bulimic women.
This study assessed metabolism and endocrine secretion in normal-weight bulimic women by monitoring several digestion-related measures in the fasting state and in response to two test meals that were isocaloric but varied in degree of forbiddenness. No consistent physiological disturbances were apparent in bulimics. Their fasting electrolytes, plasma glucose, insulin, and free fatty acids were normal. Furthermore, while the two test meals resulted in different profiles of postabsorptive glucose and postprandial secretion, the two groups did not differ in their profiles. The results suggest that physiological disturbances such as disturbed glucose homeostasis or insulin secretion generally attributed to populations with eating disorders may not be apparent in normal-weight bulimics. The relevance of these findings to the etiology and treatment of normal-weight bulimia is discussed.


Mechanisms of cerebral vasospasm in subarachnoid haemorrhage.
Cerebrovascular spasm is a slowly developing constriction of the cerebral arteries, which frequently follows subarachnoid haemorrhage and is associated with considerable morbidity and mortality. The condition has been studied by use of models of subarachnoid haemorrhage in the whole animal and examination of isolated blood vessels or vascular smooth muscle cells in culture. The condition probably arises from the action of haemoglobin released from erythrocytes trapped in the subarachnoid clots, although the mechanism of action of haemoglobin remains uncertain. Systemic pharmacotherapy to avert or reverse vasospasm is still experimental.


Molecular mechanisms controlling the cell cycle in embryonic stem cells.
Embryonic stem (ES) cells are originated from the inner cell mass of a blastocyst stage embryo. They can proliferate indefinitely, maintain an undifferentiated state (self-renewal), and differentiate into any cell type (pluripotency). ES cells have an unusual cell cycle structure, consists mainly of S phase cells, a short G1 phase and absence of G1/S checkpoint. Cell division and cell cycle progression are controlled by mechanisms ensuring the accurate transmission of genetic information from generation to generation. Therefore, control of cell cycle is a complicated process, involving several signaling pathways. Although great progress has been made on the molecular mechanisms involved in the regulation of ES cell cycle, many regulatory mechanisms remain unknown. This review summarizes the current knowledge about the molecular mechanisms regulating the cell cycle of ES cells and describes the relationship existing between cell cycle progression and the self-renewal.


Potentiometric study of binary complexes of methyl 2-pyridyl ketone oxime, phenyl 2-pyridyl ketone oxime and diacetyl monooxime with some transition and heavy metal ions in aqueous solution.
The complexation reaction between some oximes including methyl-2-pyridylketone oxime (MPKO), phenyl-2-pyridylketone oxime (PPKO) and diacetyl monooxime (DMO) with some transition and heavy metal ions Co2+, Ni2+, Zn2+, Pb2+, Fe2+, Fe3+, Cr3+ and La3+ has been studied potentiometrically in aqueous solution at 25+/-0.1 degrees C and ionic strength (mu) of 0.1M supported by KCl. The overall stability constants logbeta's of respective species were obtained by computer refinement of pH-volume data using BEST program. The best model among the several proposed models was selected according to the lowest sigma(fit) value. The main species in binary systems are ML, ML2, MLH, MLH2, ML2H, ML2H2, MOHL, M(OH)2L, M(OH)L2 and M(OH)2L2 (L = MPKO or PPKO or DMO).


Machine learning and disease prediction in obstetrics.
Machine learning technologies and translation of artificial intelligence tools to enhance the patient experience are changing obstetric and maternity care. An increasing number of predictive tools have been developed with data sourced from electronic health records, diagnostic imaging and digital devices. In this review, we explore the latest tools of machine learning, the algorithms to establish prediction models and the challenges to assess fetal well-being, predict and diagnose obstetric diseases such as gestational diabetes, pre-eclampsia, preterm birth and fetal growth restriction. We discuss the rapid growth of machine learning approaches and intelligent tools for automated diagnostic imaging of fetal anomalies and to asses fetoplacental and cervix function using ultrasound and magnetic resonance imaging. In prenatal diagnosis, we discuss intelligent tools for magnetic resonance imaging sequencing of the fetus, placenta and cervix to reduce the risk of preterm birth. Finally, the use of machine learning to improve safety standards in intrapartum care and early detection of complications will be discussed. The demand for technologies to enhance diagnosis and treatment in obstetrics and maternity should improve frameworks for patient safety and enhance clinical practice.


Synthesis of type II collagen is decreased in cartilage cultured with interleukin 1 while the rate of intracellular degradation remains unchanged.
The effect of interleukin 1 (IL1) on the synthesis and degradation of collagen was examined in explants of cultured cartilage. IL1 induced a reversible, dose-dependent (10-100 pM) inhibition of type II collagen synthesis. The proportion of collagen produced decreased selectively from 7% to 1.2% of total protein after 72 h exposure to IL1 (100pM). There was no change in the rate of degradation of newly synthesized collagen. Analysis of newly synthesized material showed that the type II collagen synthesized in the presence of IL1 had the same characteristics as that extracted from unstimulated cartilage. The relative amounts of type II procollagen mRNA were estimated by Northern blot hybridization. The levels were decreased in cartilage cultured with IL1 to a similar extent as that seen for the type II collagen protein. Exposure to IL1 (10-350pM) for 3 days did not induce increased resorption of extracellular collagen in the cultured explants. These data demonstrate that decreased collagen production in cartilage exposed to IL1 is due primarily to decreased amounts of type II procollagen mRNA.


Association between early preterm birth and periodontitis according to USA and European consensus definitions.
Prospective case-control study assessing the association between maternal periodontitis according to the recently issued USA and European consensus definitions and early preterm delivery (<35 weeks gestation). Cases were women delivering between 22 and 34(6/7) weeks of gestation (n = 84) and controls were women delivering at term (≥ 37 weeks) (n = 345). Periodontal examination at the immediate postpartum period identified periodontitis according to both consensus definitions. A multivariate logistic model was used to assess the association between early preterm delivery and the presence of periodontitis adjusted for confounders. All women had periodontitis by the European consensus definitions. When using the USA definitions, more cases had severe periodontitis than controls (34.5% vs. 17.72%); p = 0.003. After adjustment for main confounders, the association between severe (OR: 2.38; 95% CI: 1.36-4.14) periodontitis and early preterm delivery persisted. The only other independent factor associated with early preterm delivery was vaginal bleeding during pregnancy. Early preterm delivery is associated with periodontitis when the USA consensus definitions are used. The European definitions revealed inadequate for the study population because of the lack of discrimination power.


Mercurius solubilis: actions on macrophages.
Macrophages play central roles in homeostasis as well as host defence in innate and acquired immunity, auto-immunity and immunopathology. Our research group has demonstrated the effects of highly diluted toxic substances in macrophages. To investigate if highly diluted Mercurius solubilis (Merc sol), can activate or modulate macrophage functions. We evaluated the effects of Merc sol in the 6, 12, 30 and 200 centesimal high dilutions (CH) potencies on mice peritoneal macrophages (in vitro and in vivo). Merc sol was added to mice's drinking water for 7 days (in vivo treatment) and animals were euthanised and cells were collected. In vitro treatment was performed on macrophages and bone-marrow cell cultures. Macrophages showed activated morphology, both when Merc sol was added directly to the cell culture and to drinking water. The in vitro experiments showed enhanced morphological activation, increased interferon (IFN)γ release in the supernatant at lower dilutions and interleukin (IL)-4 production at higher dilutions. Increase in nitric oxide and decrease in superoxide (O(2)(-)) and hydrogen peroxide (H(2)O(2)) were also observed. In vivo treatment caused a decrease in O(2)(-) and increase in H(2)O(2) production by macrophages. Taken together, the results allow us to conclude that highly diluted Merc sol modulates reactive oxygen species (ROS), reactive nitrogen species (RNS) and cytokine secretion, which are central mediators of the immune system, wound healing and body homeostasis.


Changes in physicochemical properties of organic matter by uranium irradiation: A case study from the Ordos Basin in China.
Carbonaceous debris (CD) are exclusively disseminated in sandstones of uranium-bearing strata from the Dongsheng uranium ore field of the northern Ordos Basin, northern China. Physicochemical properties of CD were investigated through a series of tests including element analyses, Fourier transform infrared spectroscopy (i.e., FTIR) and organic carbon isotope (i.e., δC13) as well as specific surface area. The results show that δC13 of the samples from uranium-bearing strata range from -22.86‰ to -25.82‰, indicating that the CD is from the same origin. The average values of C, H, O and N are 54.54%, 4.55%, 39.15% and 0.49%, respectively, and H/C as well as O/C atomic ratios vary from 0.77 to 1.26 and 0.36 to 1.72, respectively, implying that CD is mostly composed of C and O, followed by H, and is grouped into Type Ⅲ kerogen at an immature to low mature stage. Compared with the samples without uranium enrichment, C, H, N and δ13C of the uranium-bearing samples increase by 13.66%, 5.32%, 12.50% and 0.98‰, respectively, while decrease by 18.50%, 7.84% and 33.33%, respectively, for O, H/C as well as O/C atomic ratios. As the intensity of uranium enrichment increases, H/C atomic ratios and aliphaticity decrease, and aromaticity increases. Besides, uranium-bearing samples are of smaller specific surface area than those without uranium enrichment. Alpha irradiation energy released by uranium and its daughters could cause the crosslinking in n-alkanes and long-chain polymers through a free-radical mechanism, which is supported by a decrease in O, aliphaticity and an increase in aromaticity. Hence, it results in polycondensation of molecular structure with a decrease in side chain length, function groups as well as specific surface area, and changes in physicochemical properties of organic matter, which is instructive in prospecting.


An evaluation of Tamm-Horsfall protein glycans in kidney stone formers using novel techniques.
Tamm-Horsfall protein (THP) is theorized to play a critical role in preventing kidney stone formation. There is conflicting literature on THP analysis in kidney stone patients; therefore, this study was conducted using sensitive and specific bio-analytical techniques to better understand differences in THP, which play a potential role in nephrolithiasis pathogenesis. THP was isolated from urine samples of 34 male and 19 female kidney stone patients and 30 male and 24 female control subjects using diatomaceous earth. Protein was quantified by Superdex-200 size-exclusion chromatography. Sialic acid was determined by 1,2-diamino-4,5-methylenedioxybenzene high-performance liquid chromatography. Neutral and amino sugars were determined by high pH anion-exchange chromatography (HPAEC) with pulsed amperometric detection. THP N-glycans were derivatized with 2-aminobenzamide (2-AB) and profiled by HPAEC with fluorescence detection. N-glycan structures were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results indicate that kidney stone patients had 32% lower protein content compared to controls, while sialic acid content was lower by 29 and 24% in male and female kidney stone patients, respectively, compared to controls. The neutral and amino sugars were also lower by 18 and 20% for male and female kidney stone patients, respectively, compared to controls. All results were statistically significant (p<0.001). These results are supported by 2-AB profiling of THP N-glycans and by MALDI-TOF MS of highly sialylated N-glycans in the range of m/z 3000-6000. This study demonstrates quantitative and qualitative differences in THP, which can be crucial contributing factors for nephrolithiasis.


Effect of oxybutynin on the QTc interval in elderly patients with urinary incontinence.
1. Terodiline, an anticholinergic drug with calcium antagonist properties, is associated with QT prolongation and ventricular arrhythmias. It is not known if oxybutynin, a drug with a similar pharmacological profile, causes QT prolongation. ECGs were obtained before and at least 4 weeks after commencement of oxybutynin (mean daily dose 7.6, range 2.5-10 mg), in 21 elderly (mean age 75, range 58-88 years) patients treated for urinary incontinence. Heart rate, (mean +/- s.d.) 74 +/- 11 vs 69 +/- 11 beats min-1, -6 (-13,2), before vs during oxybutynin therapy, mean difference (95% confidence intervals); PR interval, 168 +/- 27 vs 156 +/- 27 ms, -11 (-26,3); QTc 454 +/- 27 vs 447 +/- 31 ms1/2, -9 (-23,5), and QTc dispersion, QTc max-QTc min, 68 +/- 24 vs 63 +/- 26 ms1/2, -1 (-15,14) were all unaltered by oxybutynin therapy. The lack of an effect on resting heart rate suggests that oxybutynin has little anticholinergic action at cardiac M2 receptors at usually administered doses. Oxybutynin therapy is not associated with QTc interval prolongation and is unlikely to produce ventricular arrhythmias.


Screening of Newborn Hearing at a Tertiary Care Hospital in South India.
Hearing loss can have a devastating impact on the cognitive development and psychological well-being of children and their families. Newborn hearing screening should be given special attention especially in a country like ours where the burden of this disability is heavy. Screening all newborns irrespective of risk factors helps in better detection, and hence further management can be initiated at appropriate time. To implement newborn hearing screening at Vanivilas hospital and to estimate the incidence of hearing loss among the high risk groups. To create awareness about the need for detecting childhood deafness among parents and general population. To develop a centre of excellence for evaluation, intervention and rehabilitation for hearing impaired in a tertiary care hospital. Prospective study. All neonates born in Vanivilas Hospital attached to Bangalore Medical College and Research Institute underwent hearing screening using four stage protocols with otoacoustic emission (OAE) tests and final confirmation with Brainstem evoked response audiometry (BERA) tests. May 2015-May 2017. Number of newborns screened were 26,487, and 19 (0.717/1000) newborns were detected to have hearing impairment. The incidence of hearing loss among high risk group was 0.188/1000, and among the non risk group was 0.528/1000. Newborn hearing screening must be made mandatory and multi-staged protocol based screening for hearing loss should be implemented. This will make newborn screening programme more efficient and also will help in initiating treatment at an early stage so that further damage can be prevented.


Spatial relationships between Eurasian badgers (Meles meles) and cattle infected with Mycobacterium bovis in Northern Spain.
Recent studies suggest that badgers may be a potential reservoir of Mycobacterium bovis infection for cattle in Northern Spain. The objective of this study was to investigate potential epidemiological links between cattle and badgers. Culture and molecular typing data were available for cattle culled during the national tuberculosis (TB) eradication campaigns between 2008 and 2012, as well as from 171 necropsied badgers and 60 live animals trapped and examined over the same time period. Mycobacterium tuberculosis complex strains were isolated from pooled tissues of 14 (8.2%) necropsied badgers, of which 11 were identified as M. bovis: six different spoligotypes of M. bovis were subsequently identified. In two geographical locations where these isolates were shared between cattle and badgers, infected cattle herds and badgers lived in close contact. Although it remains unclear if badgers are a maintenance or spill-over host of M. bovis in this setting, it would appear prudent to have precautionary measures in place to reduce contact between cattle and badgers.


SUCLG1 mutations and mitochondrial encephalomyopathy: a case study and review of the literature.
The mitochondrial encephalomyopathies represent a clinically heterogeneous group of neurodegenerative disorders. The clinical phenotype of patients could be explained by mutations of mitochondria-related genes, notably SUCLG1 and SUCLA2. Here, we presented a 5-year-old boy with clinical features of mitochondrial encephalomyopathy from Iran. Also, a systematic review was performed to explore the involvement of SUCLG1 mutations in published mitochondrial encephalomyopathies cases. Genotyping was performed by implementing whole-exome sequencing. Moreover, quantification of the mtDNA content was performed by real-time qPCR. We identified a novel, homozygote missense variant chr2: 84676796 A > T (hg19) in the SUCLG1 gene. This mutation substitutes Cys with Ser at the 60-position of the SUCLG1 protein. Furthermore, the in-silico analysis revealed that the mutated position in the genome is well conserved in mammalians, that implies mutation in this residue would possibly result in phenotypic consequences. Here, we identified a novel, homozygote missense variant chr2: 84676796 A > T in the SUCLG1 gene. Using a range of experimental and in silico analysis, we found that the mutation might explain the observed phenotype in the family.


Psoriasis: a fresh look.
Psoriasis is a disease characterized by scaly skin lesions secondary to keratinocyte hyperplasia. The presence of active T cells in the lesions, experimental observations on disease transfer, and therapeutic efficacy of specific immunosuppressive drugs have led to the identification of the activated T lymphocyte as the primary factor for keratinocyte stimulation. Understanding the pathways of pathogenesis is fundamental in evolving therapies for intervention at different points in the pathogenic model and for curtailing the process. Advances in biotechnological methods have helped to create designer molecules and proteins that specifically recognize target receptors and chemicals that modify their actions. These drugs, termed "biologic response modifiers," are now being studied as specific immunosuppressive agents producing different T-cell and cytokine effects in psoriasis.


Prosaposin in the rat oviductal epithelial cells.
Prosaposin (PSAP) has two forms: a precursor and a secreted form. The secreted form has neurotrophic, myelinotrophic, and myotrophic properties. The precursor form is a precursor protein of saposins A-D. Although the distribution of PSAP in male reproductive organs is well known, its distribution in female reproductive organs, especially in the oviduct, is unclear. Immunoblots and immunohistochemistry of oviducts showed that oviductal tissues contain PSAP proteins, and a significant increase in PSAP was observed in the estrus-metestrus phase compared to the diestrus-proestrus phase in the ampulla. To identify PSAP trafficking in cells, double-immunostaining was performed with antibodies against PSAP in combination with sortilin, mannose 6 phosphate receptor (M6PR), or low-density lipoprotein receptor-related protein 1 (LRP1). PSAP and sortilin double-positive reactions were observed near the nuclei, as well as in the apical portion of microvillous epithelial cells, whereas these reactions were only observed near the nuclei of ciliated epithelial cells. PSAP and M6PR double-positive reactions were observed near the nuclei of microvillous and ciliated epithelial cells. PSAP and M6PR double-positive reactions were also observed in the apical portion of microvillous epithelial cells. PSAP and LRP1 double-positive reactions were observed in the plasma membrane and apical portion of both microvillous and ciliated epithelial cells. Immunoelectron staining revealed PSAP immunoreactive small vesicles with exocytotic features at the apical portion of microvillous epithelial cells. These findings suggest that PSAP is present in the oviductal epithelium and has a pivotal role during pregnancy in providing an optimal environment for gametes and/or sperm in the ampulla.


Cryopreservation of local black rabbit spermatozoa in the Mekong delta region of Vietnam: Evaluating cryoprotectant effectiveness.
Rabbit production is well developed in the Mekong Delta and Vietnam, with increased consumption of rabbit meat in both urban and rural areas. Consequently, meat rabbit breeds have become popular in almost all provinces in Vietnam, resulting in a decline in the population of Local Black rabbits over the years. To support breeding programs, there is a crucial need to develop a cryopreservation method. The objective of this study was to develop sperm cryopreservation protocols and determine the optimal cryoprotectant for Local Black rabbit spermatozoa. Rabbit spermatozoa were obtained and diluted with TCG-EggYolk freezing medium containing 5%, 8%, and 10% glycerol or DMSO in a 1:1 ratio. Glycerol and DMSO-free mediums served as the controls. Samples were put into 0.5-mL straws, cooled to 15°C and 5°C, then placed on nitrogen vapour for 15 min and directly immersed in liquid nitrogen at -196°C. Samples were thawed at 37°C for 60 s after being frozen for 72 h Sperm quality measures, such as viability, motility, and membrane integrity, were assessed both before and after freezing. The results showed that the average viability, average motility, and average membrane integrity were 61.9%, 53.9%, and 42.9%, respectively, after thawing with 5% glycerol, which was higher than the two higher concentrations of glycerol (8% and 10%) (p < .05). Similarly, with 8% DMSO, the average viability, average motility, and membrane integrity were 59.2%, 51.0%, and 41.8%, respectively, which were higher than the two concentrations of DMSO (5% and 10%) (p < 0.05). Therefore, the cryopreservation of local black rabbit sperm with 5% glycerol or DMSO 8% resulted in high sperm quality, but considering the practical aspect of minimizing the volume of the preservative, a concentration of 5% glycerol may be the best option.


Use of hydrogen peroxide in combination with nisin, sodium lactate and citric acid for reducing transfer of bacterial pathogens from whole melon surfaces to fresh-cut pieces.
Hydrogen peroxide (2.5%) alone or hydrogen peroxide (1%) in combination with nisin (25 microg/ml), sodium lactate (1%), and citric acid (0.5%) (HPLNC) were investigated as potential sanitizers for reducing Escherichia coli O157:H7 or Listeria monocytogenes populations on whole cantaloupe and honeydew melons. Whole cantaloupes inoculated with E. coli O157:H7 and L. monocytogenes at 5.27 and 4.07 log10 CFU/cm2, respectively, and whole honeydew melons inoculated with E. coli O157:H7 and L. monocytogenes at 3.45 and 3.05 log10 CFU/cm2, respectively, were stored at 5 degrees C for 7 days. Antimicrobial washing treatments were applied to inoculated whole melons on days 0 or 7 of storage and surviving bacterial populations and the numbers transferred to fresh-cut pieces were determined. At days 0 and 7 treatment with HPLNC significantly (p<0.05) reduced the numbers of both pathogens, by 3 to 4 log CFU/cm2 on both types of whole melon. Treatment with HPLNC was significantly (p<0.05) more effective than treatment with 2.5% hydrogen peroxide. While fresh-cut pieces prepared from stored whole melons were negative for the pathogens by both direct plating and by enrichment, fresh-cut pieces from cantaloupe melons treated with 2.5% hydrogen peroxide were positive for both pathogens and pieces from honeydew melons were positive for E. coli 0157:H7. The native microflora on fresh-cut melons were also substantially reduced by HPLNC treatment of whole melons. The results suggest that HPLNC could be used to decontaminate whole melon surfaces and so improve the microbial safety and quality of fresh-cut melons.


Assembly of Helical Nanostructures: Solvent-Induced Morphology Transition and Its Effect on Cell Adhesion.
Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self-assembly mechanism. Two simple l/d-phenylalanine-based derivatives (L/DPFM) have been designed, and their solvent-dependent morphology evolutions are illustrated. It was found that, as the content of H2 O in aqueous ethanol solutions was increased, LPFM self-assembles first into right-handed nanofibers, then flat fibrous structures, and finally inversed left-handed nanofibers. Assemblies in ethanol and H2 O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology-dependent cell adhesion and proliferation behaviors are further characterized. Left-handed nanofibers are found to be more favorable for cell adhesion than right-handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left-handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left-handed nanofibrous films, which indicates better flexibility. The difference in cell-substrate interactions might lead to different effects on cell behavior.


Resolution of migraine following bromocriptine treatment of a prolactinoma (pituitary microadenoma).
A 39-year-old male physician with a 27-year history of chronic severe migraine had a prolactin-secreting pituitary microadenoma diagnosed as an incidental finding following an automobile accident. Treatment of the prolactinoma with bromocriptine provided complete and lasting resolution of the migraine as well, suggesting a possible etiologic relationship between these two prevalent conditions, and the possibility of treating at least some cases of migraine with bromocriptine.


Nonmyeloablative conditioning with busulfan before matched littermate bone marrow transplantation results in reversal of the disease phenotype in canine leukocyte adhesion deficiency.
Leukocyte adhesion deficiency (LAD)-1, a primary immunodeficiency disease caused by molecular defects in the leukocyte integrin CD18 molecule, is characterized by recurrent, life-threatening bacterial infections. Myeloablative hematopoietic stem cell transplantation is the only curative treatment for LAD-1. Recently, canine LAD (CLAD) has been shown to be a valuable animal model for the preclinical testing of nonmyeloablative transplantation regimens for the treatment of children with LAD-1. To develop new allogeneic transplantation approaches for LAD-1, we assessed a nonmyeloablative conditioning regimen consisting of busulfan as a single agent before matched littermate allogeneic bone marrow transplantation in CLAD. Three CLAD dogs received busulfan 10 mg/kg intravenously before infusion of matched littermate bone marrow, and all dogs received posttransplantation immunosuppression with cyclosporin A and mycophenolate mofetil. Initially, all 3 dogs became mixed chimeras, and levels of donor chimerism sufficient to reverse the CLAD phenotype persisted in 2 animals. The third dog maintained donor microchimerism with an attenuated CLAD phenotype. These 3 dogs have all been followed up for at least 1 year after transplantation. These results indicate that a nonmyeloablative conditioning regimen with chemotherapy alone is capable of generating stable mixed chimerism and reversal of the disease phenotype in CLAD.


Rab7: role of its protein interaction cascades in endo-lysosomal traffic.
Protein-protein interaction cascades are crucial for cellular signaling pathways and cell morphogenesis. Membrane traffic along the secretory and endocytic pathways is similarly governed by regulated protein-protein interactions of diverse machineries, which are inter-regulated, assembled and disassembled sequentially to drive membrane budding, vesicle transport, membrane fission and fusion. Rab7, the key regulator in endo-lysosomal trafficking investigated extensively in the past decades, is emerging to govern early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades. We summarize here the key protein interaction cascades of Rab7 by focusing on endo-lysosomal trafficking regulated by its interaction with HOPs, RILP, ORP1L, FYCO1 and Mon1/Sand1-CCZ1 complex.


Alloys Used in Different Temporomandibular Joint Reconstruction Replacement Prostheses Exhibit Variable Microstructures and Electrochemical Properties.
Metallic temporomandibular joint replacement (TMJR) systems vary depending on design, material composition, and manufacturing methods such as casting, forging, and additive manufacturing. Therefore, the purpose of this study was to measure the association between manufacturing process of TMJR systems in terms of microstructure and electrochemical properties. The sample was composed of new or surgically retrieved TMJ replacement devices of either titanium alloy (Ti6Al4V) or cobalt-chromium-molybdenum (CoCrMo) alloy from 8 different manufacturers. The primary predictor variable was alloy type, according to its manufacturing process (wrought, cast, additively manufactured [AM]). The primary outcome variables were 1) microstructure (grain size, aspect ratio, and phase content) and 2) corrosion potential and current, polarization resistance, and capacitance. Differences between alloy groups were determined by t tests, Kruskal-Wallis, and Mann-Whitney tests. We demonstrated that the TMJR CoCrMo and Ti6Al4V alloy microstructures can vary broadly within American Society for Testing and Materials specifications, where the components made of Ti6Al4V had 3 types of microstructures (equiaxial, bimodal, and martensitic) out of 10 samples, and the components made of CoCrMo had 2 types of microstructure (equiaxial and dendritic) out of 16 samples. Some CoCrMo alloys exhibited preferential corrosion sites, while wrought Ti6Al4V alloys trended toward a superior corrosion behavior (corrosion rate: 2 × 10-9 A/cm2, polarization resistance: 5,000,000 kΩcm2, and capacitance: 10 μSsa/cm2) compared with AM alloys (39 × 10-9 A/cm2, 1676 kΩcm2, 36 μSsa/cm2, respectively), where 4 samples of each group were tested and repeated 5 times. Among four AM devices, two exhibited a significantly inferior corrosion behavior. Although AM is an exciting emerging new technology that allows manufacturing of custom-made TMJR, their corrosion behavior is still inferior in comparison to that of traditional wrought alloys. Preventing corrosion is crucial because it can cause surface defects that may lead to implant fracture.


Wireless transmission of ECG signal.
In this study, the ECG signal were measured as noiseless with Ag/AgCl electrodes, then converted digital data using pulse code modulation (PCM) technique. The digital data were then sent to receiver where it is in 433 MHz FM/FSK transmitter, which has 10 mW output power and 9.6 Kps transmission speed. At the receiver, the digital data were reconverted to analog signal to monitor and record on the PC with Sonic Foundry Sound Forge 6.0 program. The power spectrum of measured ECG signal was formed using Matlab program. As a result, the medical supporting system is realized for monitoring the ECG signal on PC of human with chronic heart disease in their living surroundings.


Cloning and expression of secreted antigens of Clostridium difficile in Escherichia coli.
The feasibility of the cloning and expression of Clostridium difficile antigens in Escherichia coli was investigated. The expression of a limited number of cloned clostridial antigens under the control of clostridial promoter elements in E. coli was observed.


Identification of a novel immunodominant cytotoxic T lymphocyte epitope derived from human factor VIII in a murine model of hemophilia A.
Gene therapy of hemophilia A could be complicated by the development of immune responses against the vector as well as the Factor VIII (FVIII) transgene. Previous efforts have been focused on identifying FVIII inhibitor antibody epitopes, whereas the cytotoxic T lymphocyte (CTL) epitopes have not been characterized. CTL would kill cells expressing such epitopes and thus limit the efficacy of gene therapy. To investigate CTL responses against human FVIII in a mouse model of hemophilia A, a computer algorithm program (BIMAS) was employed to predict CTL epitopes of human FVIII. The potential binding of these predicted peptides to MHC class I K(b) was evaluated in a TAP-deficient cell line. When recombinant vaccinia virus expressing B domain-deleted human FVIII (vv-FVIII) was used to immunize E16 hemophilia A mice, a specific CTL response against FVIII152-159 was generated. In contrast, a CTL response to four other FVIII peptides was not detected. Therefore, FVIII152-159 represents a dominant CTL epitope. Identification of this epitope raises the possibility that CTL response to FVIII gene-transduced cells can be diminished by deliberatively mutating the dominant CTL epitope while retaining the biologic function of FVIII for hemophilia A gene therapy.


From evidence to clinical practice in blood and marrow transplantation.
Clinical practice in the field of blood and marrow transplantation (BMT) has evolved over time, as a result of thousands of basic and clinical research studies. While it appears that scientific discovery and adaptive clinical research may be well integrated in case of BMT, there is lack of sufficient literature to definitively understand the process of translation of evidence to practice and if it may be selective . In this review, examples from BMT and other areas of medicine are used to highlight the state of and potential barriers to evidence uptake. Strategies to help improve knowledge transfer are discussed and the role of existing framework provided by the Center for International Blood and Marrow Transplant Registry (CIBMTR) to monitor uptake and BMT Clinical Trials Network (BMT CTN) to enhance translation of evidence into practice is highlighted.


Transvaginal vs transobturator approach for synthetic sling placement in patients with stress urinary incontinence.
We present comparative short-term experience with the transvaginal (TVT) and the transobturator (TVT-O) approaches for the treatment of stress urinary incontinence (SUI). We studied 315 women with SUI, treated with a tension-free tape placement. The TVT approach was applied in 265 women, while 50 women were treated by the TVT-O approach. The mean operation time was 25 and 17 min in the TVT and TVT-O group, respectively (p<0.001). In the TVT group, continence rates were 87% after 1 year, while in the TVT-O group, the continence rate was 94%. Postoperative pain was reported in 14.4 and 28% of the TVT and TVT-O patients, respectively (p=0.02). Complications such as bladder perforation, retropubic hematoma, and urinary retention took place only in the TVT group. Urinary tract infections were recorded in 20 and 8% of the TVT and TVT-O patients, respectively (p=0.04), while vaginal erosion took place in 1.5 and 2% and de novo urgency in 14 and 8%. Both approaches show high rates of cure at the first postoperative year, while complications are less with the TVT-O procedure.


Vesicovaginal fistulae.
The aetiology, methods of repair and results are described in 616 patients with vesicovaginal fistulae (26 also had rectovaginal fistulae). The cure rate was 81%.


Prognostic Value of Plasma Long Noncoding RNA ANRIL for In-Stent Restenosis.
BACKGROUND In-stent restenosis (ISR) remains a major cause of failure of contemporary percutaneous revascularization therapies. Invasive biomarkers to improve the prognosis of ISR should be considered. This study aimed to investigate the association between plasma ANRIL expression and ISR. MATERIAL AND METHODS A total of 444 patients were included in this research. Serial coronary angiography was performed at baseline (before and after intervention) and within 36 months' follow-up. ISR was defined as >50% diameter stenosis at follow-up. ANRIL expression was quantified using reverse transcription-PCR. An area under the ROC curve (auROC) was generated to assess the diagnostic values of ANRIL. Logistic regression models were used to assess the independent risk factors for ISR. RESULTS Plasma ANRIL expression was significantly increased in patients with ISR, as compared with that in patients without ISR (1.6 [1.1-2.5] vs. 0.9 [0.6-1.3], P<0.001). The auROC (95% confidence interval [CI]) of plasma ANRIL in diagnosing ISR was 0.745 (0.687-0.811). Multiple logistic regression models indicated that drinking (odds ratio [OR]=2.09, 95% CI: 1.08-4.04, P=0.028), hypertension (OR=2.01, 95% CI: 1.14-3.57, P=0.017), diabetes (OR=3.15, 95% CI: 1.63-3.57, P<0.001), low-density lipoprotein (OR=3.14, 95% CI: 1.57-6.31, P=0.001), and ANRIL (OR=2.21, 95% CI: 1.68-2.92, P<0.001) were the independent risk factors for ISR. CONCLUSIONS We found that higher ANRIL expression is associated with ISR, indicating that ANRIL may be an optimal prognostic factor for ISR.


Role of steroids in secretion--modulating effect of triamcinolone and estradiol on protein synthesis and secretion from the rat exocrine pancreas.
Following adrenalectomy of male rats, or adrenalectomy and ovariectomy of females, there was marked depletion of zymogen granules in acinar cells of the pancreas. Within 9 h after treatment with either triamcinolone or 17 beta-estradiol, complete restoration of these secretory vesicles was observed. This repletion was not inhibited by actinomycin-D. Supernatant fractions (100,000 g, 60 min) of rat pancreas, from both normal and surgically altered animals, contained proteins that bound [3H]-triamcinolone and [3H]-estradiol, suggesting that the action of these hormones is exerted directly on the pancreas. Binding of both steroid hormones required the presence of an additional coligand referred to as accessory factor. In addition, the binding proteins for [3H]-triamcinolone and [3H]-estradiol eluted in similar positions after Sephadex G-200 and CM Affi-gel Blue chromatography. It is uncertain, however, whether a single protein binds both steroid hormones since they had different binding isotherms. Scatchard analysis of binding of [3H]-estradiol yielded a single straight line of negative slope from which it was calculated that there were about 4.4 pmol of binding sites per mg protein, having an average apparent Kd of about 5 X 10(-8) M. Similar analysis of the data for [3H]-triamcinolone yielded a straight line of zero slope indicating nonsaturable binding of hormone at concentrations as high as 10 microM. Since both [14C]-L-leucine incorporation into protein and amylase secretion were affected markedly by the steroid-hormonal status of the animal, it is presumed that steroid-bound complexes in acinar cells of the pancreas modulate synthesis and secretion of protein.


Ribonucleoprotein complexes in neurologic diseases.
Ribonucleoprotein (RNP) complexes regulate the tissue-specific RNA processing and transport that increases the coding capacity of our genome and the ability to respond quickly and precisely to the diverse set of signals. This review focuses on three proteins that are part of RNP complexes in most cells of our body: TAR DNA-binding protein (TDP-43), the survival motor neuron protein (SMN), and fragile-X mental retardation protein (FMRP). In particular, the review asks the question why these ubiquitous proteins are primarily associated with defects in specific regions of the central nervous system? To understand this question, it is important to understand the role of genetic and cellular environment in causing the defect in the protein, as well as how the defective protein leads to misregulation of specific target RNAs. Two approaches for comprehensive analysis of defective RNA-protein interactions are presented. The first approach defines the RNA code or the collection of proteins that bind to a certain cis-acting RNA site in order to lead to a predictable outcome. The second approach defines the RNA map or the summary of positions on target RNAs where binding of a particular RNA-binding protein leads to a predictable outcome. As we learn more about the RNA codes and maps that guide the action of the dynamic RNP world in our brain, possibilities for new treatments of neurologic diseases are bound to emerge.


Competency level in radiotherapy across EU educational programmes: A cross-case study evaluating stakeholders' perceptions.
The education of Therapeutic Radiographers (TRs) is regulated in some countries but is not standardised across the EU, leading to differences in competencies between and within member states. This study aimed to explore stakeholders' perceptions regarding underdeveloped competencies of TRs practising on the linear accelerator, identified in a previous study by the same research team. Interviews with stakeholders from four countries (selected based on the characteristics of their degrees) were performed as part of this cross-case study. Stakeholders were asked to provide their perception regarding the least developed competencies identified in a previous study. The 27 stakeholders confirmed that Pharmacology, Quality Assurance (QA), Management and Leadership, Research (from the previous study) were underdeveloped and identified Image Verification and Critical Thinking as additional underdeveloped competencies. Suggested causes included: lack of regulation of required competencies at the national level, lack of training dedicated to radiotherapy (RT) (taught within generic modules) and lack of time within the degree programme. The ideal academic level to develop these competencies and whether they are essential varied between country and stakeholder. It is essential to regulate learning outcomes at the national level to ensure a high level of care is provided to all RT patients and, ideally, standardise it across Europe. Education institutions should review their curricula to ensure that sufficient time is dedicated to RT and that the essential competencies are developed. Due to time constraints within some programmes, some competencies must be developed after graduation. Lack of regulation of learning outcomes (at European level and national level in many countries) and lack of RT-specific training lead to underdeveloped competencies that may compromise patient care.


spliceJAC: transition genes and state-specific gene regulation from single-cell transcriptome data.
Extracting dynamical information from single-cell transcriptomics is a novel task with the promise to advance our understanding of cell state transition and interactions between genes. Yet, theory-oriented, bottom-up approaches that consider differences among cell states are largely lacking. Here, we present spliceJAC, a method to quantify the multivariate mRNA splicing from single-cell RNA sequencing (scRNA-seq). spliceJAC utilizes the unspliced and spliced mRNA count matrices to constructs cell state-specific gene-gene regulatory interactions and applies stability analysis to predict putative driver genes critical to the transitions between cell states. By applying spliceJAC to biological systems including pancreas endothelium development and epithelial-mesenchymal transition (EMT) in A549 lung cancer cells, we predict genes that serve specific signaling roles in different cell states, recover important differentially expressed genes in agreement with pre-existing analysis, and predict new transition genes that are either exclusive or shared between different cell state transitions.


In vitro antimycoplasmal activity of six Jordanian medicinal plants against three Mycoplasma species.
The in vitro effect of six Jordanian traditional medicine plant methanolic extracts were tested against 32 isolates of Mycoplasma species; Mycoplasma mycoides subsp. mycoides LC (6), Mycoplasma capricolum subsp. capricolum (8) and M. putrefaciens (18), all isolated from either nasal swabs or milk, from sheep and goats in different regions in Jordan. All Mycoplasma species showed susceptibility to Artemisia herba-alba and Artemisia arborescens with MIC ranges from 3.125-12.5 mg/ml. Allium sativum and Punica grantum showed limited activity against some Mycoplasma isolates. Olea europea and Citrullus colocynthis showed no in vitro activity against any of the Mycoplasma species tested. Artemisia herba-alba and Artemisia arborescens may therefore be useful for the treatment of mycoplasma infections.


Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis.
Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta-analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%-12.6%). In antipsychotic-naïve participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%-4.8%). There were no significant diagnostic subgroup differences. A comparative meta-analysis established that multi-episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45-2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20-1.69, p<0.001). Multi-episode (versus first-episode) status was the only significant predictor for T2DM in a multivariable meta-regression analysis (r(2) =0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices.


My journey to photosynthesis.
I provide here both my personal and scientific autobiography. After giving a background and summary of most of my research, I present information on my parents, my childhood, schooling, university education, and postdoctoral research, all in Australia. This is followed by a presentation of my life and research in Cambridge, UK and then at the Commonwealth Scientific and Industrial Research Organisation (CSIRO), in Australia, since 1955, where most of my research was done, especially on photosynthesis which included the following areas: Purification of a protochlorophyllide-protein complex; separation of the photochemical systems of photosynthesis; development of photochemical activity in photosynthesis; protein synthesis in plants; comparative photosynthesis of sun and shade plants; role of chlorophyll b in photosynthesis; photochemical properties of C4 plants; molecular interaction of thylakoid membranes; electron transport and ATP formation; and solar energy conversion in photosynthesis. In addition to research on the basics and applications of photosynthesis, I also mention at the end my service as a member of the executive of CSIRO.


Analyzing the lncRNA, miRNA, and mRNA-associated ceRNA networks to reveal potential prognostic biomarkers for glioblastoma multiforme.
Glioblastoma multiforme (GBM) is the most seriously brain tumor with extremely poor prognosis. Recent research has demonstrated that competitive endogenous RNA (ceRNA) network which long noncoding RNAs (lncRNAs) act as microRNA (miRNA) sponges to regulate mRNA expression were closely related to tumor development. However, the regulatory mechanisms and functional roles of ceRNA network in the pathogenesis of GBM are remaining poorly understood. In this study, we systematically analyzed the expression profiles of lncRNA and mRNA (GSE51146 dataset) and miRNA (GSE65626 dataset) from GEO database. Then, we constructed a ceRNA network with the dysregulated genes by bioinformatics methods. The TCGA and GSE4290 dataset were used to confirm the expression and prognostic value of candidate mRNAs. In total, 3413 differentially expressed lncRNAs and mRNAs, 305 differentially expressed miRNAs were indentified in GBM samples. Then a ceRNA network containing 3 lncRNAs, 5 miRNAs, and 60 mRNAs was constructed. The overall survival analysis of TCGA databases indicated that two mRNAs (C1s and HSD3B7) were remarkly related with the prognosis of GBM. The ceRNA network may increase our understanding to the pathogenesis of GBM. In general, the candidate mRNAs from the ceRNA network can be predicted as new therapeutic targets and prognostic biomarkers for GBM.