Prevalence of herpes simplex virus-1 in hospitalized adult patients with clinical diagnosis of meningoencephalitis using real-time polymerase chain reaction: A single-center, cross-sectional study.
Early diagnosis of herpes simplex virus-1 (HSV-1) meningoencephalitis is very important because antiviral therapy significantly decreases mortality and morbidity. Polymerase chain reaction (PCR) is a reliable method with high sensitivity and specificity in detection of HSV-1. The aim of this study is to determine the prevalence of HSV-1 in patients with diagnosis of meningoencephalitis using real-time PCR. The cerebrospinal fluid samples were collected from 126 patients with clinical diagnosis of HSV-1 meningoencephalitis in Alzahra Referral Hospital in Isfahan, Iran. After deoxyribonucleic acid (DNA) extraction, real-time PCR was performed by fluorescence resonance energy transfer assay and participants underwent brain magnetic resonance imaging, as well. Among 126 patients, 68.3% were male and 31.7% were female. The mean age of the participants was 41.96 ± 22.36 years. Most of the participants were in the age group of 20-29 years. Three patients (2.4%) had positive and 123 patients (97.6%) had negative HSV-1 DNA test. Among three positive cases, two were in the age group of 20-29 years and one in the age group of ≥80 years. No HSV-2 DNA was detected. According to the estimated prevalence of HSV-1 meningoencephalitis in the current study, it seems that the prevalence of HSV-1 meningoencephalitis is not too high in our community; therefore, initial empiric acyclovir therapy is frequently overused.


The transfer test: a new screening procedure for thrombotic diseases.
The transfer test (TT) measures by means of thromboelastography the capacity of a plasma to shorten the coagulation time of a control plasma. The value of the TT was compared to that of fibrin(ogen), degradation products (FDP), and ethanol gelatin test (EGT) in various diseases (group I), in confirmed deep venous thrombosis (group II), and in confirmed pulmonary embolism (group III). In 211 consecutive patients admitted for various diseases the results of the TT, FDP, and EGT were abnormal in 12.3, 11.3, and 66.6%, respectively, of the cases. In 59 consecutive patients with deep venous thrombosis confirmed by radiological phlebography the results of TT, FDP, and EGT were abnormal at admission time in 96.6, 89.8, and 44%, respectively, of the cases. In 45 consecutive patients with pulmonary embolism confirmed by lung scintigraphy the results of TT, FDP, and EGT were abnormal at admission time in 97.7, 97.6, and 88%, respectively, of the cases. Among the three parameters which were evaluated, the TT seems to be the most sensitive screening procedure for thrombotic diseases. A normal result of TT is a strong argument against a recent thrombotic venous phenomenon.


BASIC programs to analyse minimal inhibitory concentration (MIC) antimicrobial susceptibility results.
BASIC programs have been written to analyse minimal inhibitory concentration (MIC) antimicrobial susceptibility results for large numbers of organisms and a wide variety of antimicrobials. The output of the programs lists the numbers, percentages, cumulative numbers and cumulative percentages of organisms inhibited at different concentrations. The distribution of MICs are additionally printed as a histogram. The range, MIC for 50% and 90% of organisms (MIC50 and MIC90 respectively), and the geometric mean MIC of each drug are also calculated.


Potential prebiotic effect of fruit and vegetable byproducts flour using in vitro gastrointestinal digestion.
Fruit and vegetable byproducts (FVBP) present high content of bioactive compounds and dietary fibers and have demonstrated a positive modulatory effect upon gut microbiota composition. In the present study, the prebiotic potential of a FVBP flour obtained from solid byproducts after fruit and vegetable processing was evaluated after in vitro gastrointestinal digestion. An initial screening with three strains of Lactobacillus (Lactobacillus casei 01, Lactobacillus rhamnosus R11 and Lactobacillus acidophilus LA-5®) and one Bifidobacterium strain (Bifidobacterium animalis spp. lactis BB12®) was carried out and then the prebiotic effect of FVBP flour was performed with fecal samples of five donors. The changes in gut microbiota were evaluated at 0, 12, 24 and 48 h of fermentation by the real-time polymerase chain reaction (qPCR) method with 16S rRNA-based specific primers. The pH and short chain fatty acids (SCFA) production at each fermentation time were assessed. The fructooligosaccharides (FOS) were used as positive control. The impact of FVBP flour upon cell viability was also evaluated. FVBP flour showed higher prebiotic effect than FOS on growth enhancement of Lactobacillus after 48 h of fermentation and similar bifidogenic effect as FOS on Bifidobacterium growth at 12, 24 and 48 h of fermentation. SCFA production was observed when FVBP flour was used as carbon source, including butyrate, which supports the prebiotic potential of this flour. Additionally, it was observed that after in vitro gastrointestinal digestion, the FVBP flour at 3% promoted cell metabolism of Caco-2 cell line up to 67%. Thus, the present study demonstrates the viability of using a fruit and vegetable byproducts flour as a potential sustainable prebiotic source.


Switzerland's Narcotics Regulation Jungle: Off-Label Use, Counterfoil Prescriptions, and Opioid Agonist Therapy in the French-Speaking Cantons.
The word "narcotic" is often first associated with "illicit drugs". Yet, many "narcotic" and psychotropic substances are, in fact, medicines. Controlled medicines (CM) are products that meet the legal definition of both a "narcotic" under the Swiss Narcotics Act and of a medicine under the Therapeutic Products Act. We aim to examine how similar and how different, respectively, the implementation of CM regulations is throughout French-speaking Switzerland. Based on a legal analysis of the cantonal regulations, we conducted semi-structured interviews with cantonal pharmacists and cantonal physicians. We asked them how they perceive and implement the federal legal requirements. We find that some of these requirements have fallen into disuse, notably the federal duty to notify off-label use of CM. We observe that counterfoil prescriptions in their current paper format are a veritable data graveyard in the sense that they are not actively used to monitor or supervise the market. Moreover, we detect different conditions for opioid agonist treatment authorization. Some cantons require additional physicians' training or written commitments by the person treated. Our mapping of the CM regulation implementation can serve as a basis for cantons to review their practices.


Prevalence of levamisole and benzimidazole resistance in oesophagostomum populations of pig-breeding farms in North Rhine-Westphalia, Germany.
The objective of this cross-sectional study was to estimate the prevalence of anthelmintic resistance in porcine strongylid populations in northern North Rhine-Westphalia. A random, weighted sample of 144 pig-breeding farms, stratified by organisation and herd size, was selected from a total of 706 farms with at least ten sows associated with three breeding organisations. On 61 of all visited farms, no or insufficient strongylid eggs were found in the faecal samples. Eighty-three farms were surveyed for resistance by a larval development test (LDT) using a cut-off concentration of 0.58 microg ml(-1) for levamisole and of 0.0113 microg ml(-1) for thiabendazole. The results indicated resistance to levamisole and benzimidazole in Oesophagostomum spp on one and two farms, respectively. Quantitative LDT showed increased LD50 values of levamisole (0.24 microg ml(-1)) and thiabendazole (0.01-0.015 microg ml(-1)) for these field populations when compared with a drug susceptible laboratory strain of O. dentatum (0.084 microg ml(-1) levamisole; 0.0093 microg ml(-1) thiabendazole). Faecal egg count reduction tests using single standard doses of levamisole and flubendazole corroborated the LDT results. Thus, the prevalence of levamisole and benzimidazole resistance was estimated to be 2-3.5% in sow herds of northern North Rhine-Westphalia. The economic importance of these data is assessed.


Global deposition of airborne dioxin.
We present a global dioxin model that simulates one year of atmospheric emissions, transport processes, and depositions to the earth's terrestrial and marine habitats. We map starting emission levels for each land area, and we also map the resulting deposits to terrestrial and marine environments. This model confirms that 'hot spots' of deposition are likely to be in northern Europe, eastern North America, and in parts of Asia with the highest marine dioxin depositions being the northeast and northwest Atlantic, western Pacific, northern Indian Ocean and the Mediterranean. It also reveals that approximately 40% of airborne dioxin emissions are deposited to marine environments and that many countries in Africa receive more dioxin than they produce, which results in these countries being disproportionately impacted. Since human exposure to dioxin is largely through diet, this work highlights food producing areas that receive higher atmospheric deposits of dioxin than others.


Transcriptional regulation of the GLAST/EAAT-1 gene in rat and man.
Various acute and chronic brain diseases result in disturbed expression of the glial glutamate transporters, GLAST/EAAT-1 and GLT-1/EAAT-2, and subsequent secondary neuronal cell death. The idea that glutamate-induced brain damage can be prevented by restoring glutamate homeostasis in the injured brain, focussed previous efforts on identifying the network controlling astrocytic glutamate transport. Since most of this work was performed with rat astrocytes, we now sought to compare the transcriptional regulation of the GLAST/EAAT-1 gene in rat and man. Reporter gene assay demonstrated that the human GLAST/EAAT-1 promoter comprises the 2.3 kb region immediately flanking the 5'-end of the human GLAST/EAAT-1 gene. Cloning of the previously unknown promoter of rat GLAST/EAAT-1 gene demonstrated maximal reporter gene activity with a sequence comprising the 1.5 kb region flanking the 5'-end of the gene as well as non-coding exon 1, and intron 1-2. Although the promoter regions from both species lacked sequence homology, they contained numerous identical consensus motifs. In human promoter constructs, dbcAMP, PACAP, EGF, and TGFα, which represent potent stimulators of endogenous GLAST/EAAT-1 expression, only further increased reporter gene activity in the presence of the GLAST/EAAT-1 3'-UTR. By contrast, the rat GLAST/EAAT-1 3'-UTR only mediated the stimulatory increases of dbcAMP. Moreover, the GLAST/EAAT-1 3'-UTR repressed constitutive GLAST/EAAT-1 expression in man, but enhanced GLAST/EAAT-1 transcription in rat. Together, our findings suggest the existence of close functional similarities of the GLAST/EAAT-1 promoter regions in man and rat and further point to a species-specific function of the GLAST/EAAT-1 3'-UTR in constitutive and regulated GLAST/EAAT-1 expression.


Calcium release from two fractions of sarcoplasmic reticulum from rabbit skeletal muscle.
Calcium release from sarcoplasmic reticulum vesicles presumably derived from longitudinal tubules (LSR) and terminal cisternae (HSR) of rabbit skeletal muscle was investigated by dual wavelength spectrophotometry using the calcium-indicator antipyrylazo III. In 120 mM KCl, 5 mM MgCl2, 30 microM, CaCl2, 50 microM MgATP, 100 microM antipyrylazo III, 40 mM histidine (pH 6.8, 25 degrees C), LSR and HSR sequestered approx. 115 nmol calcium/mg, and then spontaneously released calcium. Analysis of ATP hydrolysis and phosphoenzyme level during LSR and HSR calcium sequestration indicated that this calcium release process was passive, occurring in the virtual absence of ATP and phosphoenzyme. Moreover, subsequent addition of ATP reinitiated the calcium sequestration-release sequence. Calcium release by HSR was more than 4-times faster than that by LSR. Analysis of the calcium release phase demonstrated a biexponential decay for both LSR (0.10 and 0.63 min-1) and HSR (0.26 and 1.65 min-1), suggestive of heterogeneity within each fraction. Replacement of 120 mM KCl with either 120 mM choline chloride, 240 mM sucrose, or H2O reduced maximal calcium sequestration by LSR, but had less effect on LSR calcium release rate constants. In the case of HSR, these changes in the ionic composition of the medium drastically reduced calcium release rate constants with little effect on calcium content. These marked differences between LSR and HSR are consistent with the hypothesis that the calcium permeability of the terminal cisternae is greater and more sensitive to the ionic environment than is that of the longitudinal tubules of sarcoplasmic reticulum.


Comparison of interpolation methods for the estimation of groundwater contamination in Andimeshk-Shush Plain, Southwest of Iran.
Selection of appropriate interpolation methods for the conversion of discrete samples into continuous maps is a controversial issue in the environmental researches. The main objective of this study was to analyze the suitability of three interpolation methods for the discrimination of groundwater with respect to the water quality index (WQI). The groundwater quality data consisted of 17 variables associated with 65 wells located in Andimeshk-Shush Plain. Three spatial interpolation methods including ordinary kriging (OK), empirical Bayesian kriging (EBK), and inverse distance weighting (IDW) were utilized for modeling the groundwater contamination. In addition, different cross-validation indicators were applied to assess the performance of different interpolation methods. The results showed that the performance differed slightly among different methods, although the best performed interpolation method in this study was the empirical Bayesian kriging. Among the interpolation methods, IDW with weighting power of 4 estimated the most contaminated area, while OK estimated the lowest contaminated area. The weighting power of IDW had a significant influence on the estimation, meaning that the estimated contaminated area was increased when a greater weighting power was selected. The subtraction results indicated that there are slightly spatial differences among the contamination assessment results. Results of both standard deviation (SD) and coefficient of variation (CV) also showed that uncertainty was highest in the southern part of the study area, where the distribution of wells were more intensive than that of the northern part.


Cognitive behavioural group therapy as addition to psychoeducation and pharmacological treatment for adolescents with ADHD symptoms and related impairments: a randomised controlled trial.
Cognitive behavioural therapy (CBT) is recommended for attention-deficit/hyperactivity-disorder (ADHD) in adolescents. However, all CBTs are not created equal, and the guidelines do not specify which CBT interventions are the most effective for this patient group. This study examines the efficacy of a group CBT without parent involvement as follow-up treatment compared to no additional CBT in adolescents with persistent and impairing ADHD symptoms after a short psychoeducational intervention and medical treatment. The authors conducted a two-arm parallel randomized controlled trial in two child and adolescent mental health outpatient clinics in Norway. One hundred patients aged 14-18 years with a diagnosis of ADHD (66%) or subthreshold ADHD (34%) were randomized to either a 12-week group CBT program (N = 50) or a non-CBT control condition (N = 50). Assessments were made at admission to the clinic, two weeks before and two weeks after treatment. The primary outcomes were parent-, teacher- and self-ratings of ADHD symptoms (ADHD Rating Scale-IV), and the secondary outcomes were ratings of ADHD symptom severity, executive function, functional impairment, and emotional problems. Evaluators blinded to group allocation rated ADHD symptom severity with the Clinical Global Impression Scale for Severity (CGI-S) at baseline and post-treatment. Analyses using mixed-effects models showed no difference between the treatment arms from baseline to post treatment in primary and secondary outcomes. Contrary to our hypothesis, we found no incremental treatment effect on the part of a group CBT as follow-up to psychoeducation and pharmacological treatment on ADHD symptoms and accompanying impairments. Limitations with the CBT was the large number and low dosage of treatment components, causing restricted time for practice. Unlike evidence-based, individualized targeted CBTs with parent involvement, a group CBT directed solely at the adolescents with no parent involvement does not appear effective for treating ADHD. NCT02937142 , 18/10/2016.


The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies.
Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined.


Glucose sensor using a microfabricated electrode and electropolymerized bilayer films.
A new type miniaturized glucose sensor with good selectivity and stable current response has been developed. The structure consists of a recessed rectangular microfabricated platinum electrode, inner layer of two electropolymerized nonconducting films, and outer bilayer of poly(tetrafluoroethylene) (Teflon) and polyurethane (PU) films. Glucose oxidase (GOx) is entrapped during the electropolymerization of a poly(m-phenylenediamine) (PMPD) film in an acetate buffer (AB) solution, on which a highly interference-resistive PMPD film is deposited in a phosphate buffered saline (PBS) solution. The second PMPD film causes no significant decrease in accessibility of glucose to GOx. The inner layer maintains less than 1% permeability to acetaminophen for 12 days. The fairly adhesive outer layer allows stable current response. Due to high permeability, the information about enzyme activity can be obtained without serious error in spite of outer layer intervening between enzymes and solution. The apparent Michaelis-Menten constant and the maximum steady-state current density were 24 mM and 80 microA cm(-2), respectively.


Cohort design and natural language processing to reduce bias in electronic health records research.
Electronic health record (EHR) datasets are statistically powerful but are subject to ascertainment bias and missingness. Using the Mass General Brigham multi-institutional EHR, we approximated a community-based cohort by sampling patients receiving longitudinal primary care between 2001-2018 (Community Care Cohort Project [C3PO], n = 520,868). We utilized natural language processing (NLP) to recover vital signs from unstructured notes. We assessed the validity of C3PO by deploying established risk models for myocardial infarction/stroke and atrial fibrillation. We then compared C3PO to Convenience Samples including all individuals from the same EHR with complete data, but without a longitudinal primary care requirement. NLP reduced the missingness of vital signs by 31%. NLP-recovered vital signs were highly correlated with values derived from structured fields (Pearson r range 0.95-0.99). Atrial fibrillation and myocardial infarction/stroke incidence were lower and risk models were better calibrated in C3PO as opposed to the Convenience Samples (calibration error range for myocardial infarction/stroke: 0.012-0.030 in C3PO vs. 0.028-0.046 in Convenience Samples; calibration error for atrial fibrillation 0.028 in C3PO vs. 0.036 in Convenience Samples). Sampling patients receiving regular primary care and using NLP to recover missing data may reduce bias and maximize generalizability of EHR research.


Evaluation of the immediate effects of a single transcranial direct current stimulation session on astrocyte activation, inflammatory response, and pain threshold in naïve rats.
Transcranial direct current stimulation (tDCS) has demonstrated clinical benefits such as analgesia, anti-inflammatory, and neuroprotective effects. However, the mechanisms of action of a single tDCS session are poorly characterized. The present study aimed to evaluate the effects of a single tDCS session on pain sensitivity, inflammatory parameters, and astrocyte activity in naive rats. In the first experiment, sixty-day-old male Wistar rats (n = 95) were tested for mechanical pain threshold (von Frey test). Afterward, animals were submitted to a single bimodal tDCS (0.5 mA, 20 min) or sham-tDCS session. According to the group, animals were re-tested at different time intervals (30, 60, 120 min, or 24 h) after the intervention, euthanized, and the cerebral cortex collected for biochemical analysis. A second experiment (n = 16) was performed using a similar protocol to test the hypotheses that S100B levels in the cerebrospinal fluid (CSF) are altered by tDCS. Elisa assay quantified the levels of tumor necrosis factor-alfa (TNF-α), interleukin-10 (IL10), S100 calcium-binding protein B (S100B), and Glial fibrillary acidic protein (GFAP). Data were analyzed using ANOVA and independent t-test (P < 0.05). Results showed that tDCS decreased pain sensitivity (30 and 60 min), cerebral TNF-α and S100B levels (30 min). CSF S100B levels increased 30 min after intervention. There were no differences in IL10 and GFAP levels. TCDS showed analgesic, anti-inflammatory, and neuroprotective effects in naive animals. Therefore, this non-invasive and inexpensive therapy may potentially be a preemptive alternative to reduce pain, inflammation, and neurodegeneration in situations where patients will undergo medical procedures (e.g., surgery).


Factors Influencing the Hepcidin Response to Exercise: An Individual Participant Data Meta-analysis.
Hepcidin, the master iron regulatory hormone, has been shown to peak 3-6 h postexercise, and is likely a major contributor to the prevalence of iron deficiency in athletes. Although multiple studies have investigated the hepcidin response to exercise, small sample sizes preclude the generalizability of current research findings. The aim of this individual participant data meta-analysis was to identify key factors influencing the hepcidin-exercise response. Following a systematic review of the literature, a one-stage meta-analysis with mixed-effects linear regression, using a stepwise approach to select the best-fit model, was employed. We show that exercise is associated with a 1.5-2.5-fold increase in hepcidin concentrations, with pre-exercise hepcidin concentration accounting for ~ 44% of the variance in 3 h postexercise hepcidin concentration. Although collectively accounting for only a further ~ 3% of the variance, absolute 3 h postexercise hepcidin concentrations appear higher in males with lower cardiorespiratory fitness and higher pre-exercise ferritin levels. On the other hand, a greater magnitude of change between the pre- and 3 h postexercise hepcidin concentration was largely attributable to exercise duration (~ 44% variance) with a much smaller contribution from VO2max, pre-exercise ferritin, sex, and postexercise interleukin-6 (~ 6% combined). Although females tended to have a lower absolute 3 h postexercise hepcidin concentration [1.4 nmol·L-1, (95% CI [- 2.6, - 0.3]), p = 0.02] and 30% less change (95% CI [-54.4, - 5.1]), p = 0.02) than males, with different explanatory variables being significant between sexes, sample size discrepancies and individual study design biases preclude definitive conclusions. Our analysis reveals the complex interplay of characteristics of both athlete and exercise session in the hepcidin response to exercise and highlights the need for further investigation into unaccounted-for mediating factors.


[Change of secondhand smoke levels in a public hospital in Budapest after implementation of anti-smoking policy in 2011].
Our previous 2009 study demonstrated high secondhand smoke levels throughout a public hospital in Budapest. To compare changes in indoor air pollution level between 2009 and 2012, before and after the Hungarian anti-smoking policy legislation adopted in 2011. TSI SidePak AM510 Personal Aerosol Monitor was used. In-patient care department PM2.5 levels declined by 92% from 87.7 μg/m3 to 6.9 μg/m3. Non-patient care area PM2.5 level increased by 67% from 64.8 μg/m3 to 108.0 μg/m3. The increase was driven entirely by a large increase in the level in public toilets. Excluding these, there was a 83% drop in PM2.5 in non-patient care areas from 64.8 μg/m3 to 11.1 μg/m3. PM2.5 decreased significantly due to the 2011 law. However, smoking still occurred in the hospital, albeit in less frequently visited areas. A stricter enforcement of this beneficial law is needed to reach a comprehensive smoke-free hospital environment.


Prospective randomized controlled study on bestatin in resectable gastric cancer--third report.
The efficacy of Bestatin as adjuvant immunochemotherapy for patients with resectable gastric cancer was investigated. Ninety-six patients with similar background factors were randomized into two groups; a control group and an experimental group, the patients in the experimental group receiving a daily oral dose of 60 mg Bestatin over a long period. All 96 patients were treated with a bolus intravenous injection of mitomycin C (MMC) plus oral administration of tegafur (FT-207, FT). The survival rate of the patients in the MMC + FT + Bestatin group was more favorable than that of the patients in the MMC + FT group, but the difference was not statistically significant. The survival rates of the MMC + FT + Bestatin group patients in the stratification of stage III + IV and positive histological serosal invasion, ps(+), were significantly superior to those of the MMC + FT group patients (Logrank test: p less than 0.05). Moreover, in patients with positive histological serosal invasion, the recurrence of peritoneal dissemination was significantly suppressed in the MMC + FT + Bestatin group.


Isolation and structural characterization of twenty-one sialyloligosaccharides from galactosialidosis urine. An intact N,N'-diacetylchitobiose unit at the reducing end of a diantennary structure.
Galactosialidosis urine was fractionated by gel-permeation chromatography on Bio-Gel P-6. The obtained sialic acid-containing carbohydrate fractions were purified by reversed-phase chromatography and separated according to charge by medium-pressure anion-exchange chromatography on Mono Q. The Mono Q fractions, being mixtures of sialyloligosaccharides differing mainly in sialic acid-linkage type (alpha 2-3/alpha 2-6), were subfractionated by high-performance liquid chromatography on Lichrosorb-NH2. The purified compounds were analysed by 500-MHz 1H-NMR spectroscopy. Twenty-one fully and partially sialylated N-acetyllactosamine-type compounds include mono-, di-, tri- and tetra-antennary structures. All structures have the sequence Man beta 1-4Glc-NAc at the reducing terminus in common, except one diantennary structure bearing an intact N,N'-diacetylchitobiose unit at the reducing end, which is a new feature in human glycoproteinosis urine.


MasterPATH: network analysis of functional genomics screening data.
Functional genomics employs several experimental approaches to investigate gene functions. High-throughput techniques, such as loss-of-function screening and transcriptome profiling, allow to identify lists of genes potentially involved in biological processes of interest (so called hit list). Several computational methods exist to analyze and interpret such lists, the most widespread of which aim either at investigating of significantly enriched biological processes, or at extracting significantly represented subnetworks. Here we propose a novel network analysis method and corresponding computational software that employs the shortest path approach and centrality measure to discover members of molecular pathways leading to the studied phenotype, based on functional genomics screening data. The method works on integrated interactomes that consist of both directed and undirected networks - HIPPIE, SIGNOR, SignaLink, TFactS, KEGG, TransmiR, miRTarBase. The method finds nodes and short simple paths with significant high centrality in subnetworks induced by the hit genes and by so-called final implementers - the genes that are involved in molecular events responsible for final phenotypic realization of the biological processes of interest. We present the application of the method to the data from miRNA loss-of-function screen and transcriptome profiling of terminal human muscle differentiation process and to the gene loss-of-function screen exploring the genes that regulates human oxidative DNA damage recognition. The analysis highlighted the possible role of several known myogenesis regulatory miRNAs (miR-1, miR-125b, miR-216a) and their targets (AR, NR3C1, ARRB1, ITSN1, VAV3, TDGF1), as well as linked two major regulatory molecules of skeletal myogenesis, MYOD and SMAD3, to their previously known muscle-related targets (TGFB1, CDC42, CTCF) and also to a number of proteins such as C-KIT that have not been previously studied in the context of muscle differentiation. The analysis also showed the role of the interaction between H3 and SETDB1 proteins for oxidative DNA damage recognition. The current work provides a systematic methodology to discover members of molecular pathways in integrated networks using functional genomics screening data. It also offers a valuable instrument to explain the appearance of a set of genes, previously not associated with the process of interest, in the hit list of each particular functional genomics screening.


Organizational leaders grapple with nutrition education issues.
The leaders of four food service organizations met recently in Chicago to exchange information about nutrition education. Highlights of that conference are described herein, including a presentation on the AHA's Center for Health Promotion.


Synthetic pheromones and plant volatiles alter the expression of chemosensory genes in Spodoptera exigua.
Pheromone and plant odorants are important for insect mating, foraging food sources and oviposition. To understand the molecular mechanisms regulating pheromone and odorant signaling, we employed qRT-PCR to study the circadian rhythms of ABP, OBP, PBP, and OR gene expression in the beet armyworm, Spodoptera exigua and their responses after a pre-exposure to sex pheromone compounds or plant volatiles. The neuronal responses of male S. exigua to 20 chemical compounds were recorded at three specific time periods using the electroantennogram. The results showed a circadian rhythm in the expression profiles of some chemosensory genes in the antennae similar to their behavioral rhythm. The expression profiles of OR3, OR6, OR11, OR13, OR16, OR18, Orco, ABP2, OBP1, OBP7, and PBP1, and EAG responses to chemical compounds, as well as their circadian rhythm were significantly affected after exposure to synthetic sex pheromones and plant volatiles. These findings provide the first evidence that the gene expression of chemosensory genes and olfactory sensitivity to sex pheromones are affected by pre-exposing insects to pheromone compounds and plant volatiles. It helps to understand the molecular mechanisms underlying pheromone activity, and the application of sex pheromones and plant volatiles in mating disruption or mass trapping.


Dynamic balance in older persons: effects of reduced visual and proprioceptive input.
Understanding the motor and sensory contributions to balance function in older persons is important in order to design effective interventions to prevent falls and loss of mobility. We tested the contributions of visual and proprioceptive input, muscle strength, and age to balance performance in 110 subjects free of clinical evidence of neurologic disease (mean age 80 years). The EquiTest Sensory Organization Test was used to present sequential conditions that altered sensory input in a 2 (tactile/proprioceptive input) x 3 (visual input) design. Center of force and shear force data were recorded from the platform; the primary outcomes were loss of balance (LOB) and anterior-posterior center of force (COF) displacement as a proportion of foot length (COFD). Subjects had 3.5 +/- 2.7 LOB during testing. Reduction of vision input increased the odds ratio of a LOB 5.7 fold (3.9, 8.4, 95% CI) in unstable surface conditions, but adaptation with repeated trials was substantial. The adjusted odds ratio of a LOB was 0.65 and 0.45 in the second and third trials, respectively, compared to the first. Muscle strength and age were independent predictors of LOB. Gait velocity, single stance balance, and reported difficulty with ambulation, mobility, and instrumental activities of daily living were also associated with LOB. Performance on clinical tests of strength, balance, and gait was associated with performance on a challenging balance test which reduced sensory input and effectiveness of motor responses. Adaptation to challenging balance conditions was substantial in this group of older subjects, but was diminished in the oldest subjects.


Intestinal cholesterol esterase: intracellular enzyme or contamination of cytosol by pancreatic enzymes?
The location of cholesterol esterase in rabbit intestine was re-evaluated. In three different experiments that were designed to eliminate contaminating mucus and pancreatic enzymes from the lumen of the small intestine, it was observed that the activities of cholesterol esterase and amylase in intestinal cytosol and whole homogenate decreased in parallel fashion. After the mucus was carefully wiped from the intestinal mucosa prior to the preparation of cytosol, amylase and cholesterol esterase activities decreased sevenfold. The recovery of the total activity of both enzymes in the cytosol was approximately 15%. When the lumen of the small intestine was filled with phosphate buffer and incubated at 37 degrees C for 20 min, cholesterol esterase and amylase activities in the cytosol prepared from this segment were further decreased. Moreover, the activities of amylase and cholesterol esterase were completely recovered from the lumen. Amylase and cholesterol esterase activities in the cytosol were eliminated if dithiothreitol was used as a mucolytic agent to prepare intestinal mucosa for the isolation of intestinal cells. In whole homogenates prepared from these intestinal segments, approximately 10-15% of the total cholesterol esterase activity remained. This activity, which could not be accounted for by pancreatic contamination, was associated with intestinal nuclei and cellular debris. Progesterone, ethinyl estradiol, and 25-hydroxycholesterol regulated microsomal acyl CoA:cholesterol acyltransferase activity and caused similar directional changes in the rate of cholesteryl ester synthesis in isolated intestinal cells. These same sterols, however, failed to affect cytosolic cholesterol esterase activity in vitro.


Neural networks are useful tools for drug design.
A profound understanding of molecular recognition processes and the underlying molecular interaction patterns is a prerequisite for future progress and success in rational drug design. Neural networks could play an important role in guiding the Drug Discovery process through the extraction of relevant molecular features.


Combinatorial and antagonistic effects of tubulin glutamylation and glycylation on katanin microtubule severing.
Microtubules have spatiotemporally complex posttranslational modification patterns. How cells interpret this tubulin modification code is largely unknown. We show that C. elegans katanin, a microtubule severing AAA ATPase mutated in microcephaly and critical for cell division, axonal elongation, and cilia biogenesis, responds precisely, differentially, and combinatorially to three chemically distinct tubulin modifications-glycylation, glutamylation, and tyrosination-but is insensitive to acetylation. Glutamylation and glycylation are antagonistic rheostats with glycylation protecting microtubules from severing. Katanin exhibits graded and divergent responses to glutamylation on the α- and β-tubulin tails, and these act combinatorially. The katanin hexamer central pore constrains the polyglutamate chain patterns on β-tails recognized productively. Elements distal to the katanin AAA core sense α-tubulin tyrosination, and detyrosination downregulates severing. The multivalent microtubule recognition that enables katanin to read multiple tubulin modification inputs explains in vivo observations and illustrates how effectors can integrate tubulin code signals to produce diverse functional outcomes.


Gastric emptying of mixed solid-liquid meal in patients with intestinal pseudoobstruction.
Gastric emptying of solids and liquids was evaluated simultaneously in 11 patients with intestinal pseudoobstruction. Despite a normal upper gastrointestinal series in most patients, over two thirds of the patients had abnormal gastric emptying of solids and/or liquids. Half these patients exhibited delayed emptying of solids and accelerated emptying of liquids. Alterations in motility patterns were observed in the four patients tested including decreased frequency or absence of migrating motor complexes originating in the stomach, shortening or absence of phase I, and loss of distinct fasted and fed patterns. Both basal values and mean postprandial increments in serum gastrin concentrations were lower in the patients, whereas no significant difference was found for pancreatic polypeptide concentrations when compared to normals. Our findings emphasize the functional heterogeneity of patients with intestinal pseudoobstruction. In addition, in contrast to previous reports which used barium meals to access gastric function, we observed a high prevalence of gastric emptying disturbances in these patients, suggesting that the motility disturbance is not restricted to the small intestine.


Bioactivation of dinitrobenzamide mustards by an E. coli B nitroreductase.
A nitroreductase isolated and purified from Escherichia coli B has been demonstrated to have potential applications in ADEPT (antibody-directed enzyme prodrug therapy) by its ability in vitro to reduce dinitrobenzamides (e.g. 5-aziridinyl 2,4-dinitrobenzamide, CB 1954 and its bischloroethylamino analogue, SN 23862) to form cytotoxic derivatives. In contrast to CB 1954, in which either nitro group is reducible to the corresponding hydroxylamine, SN 23862 is reduced by the nitroreductase to form only the 2-hydroxylamine. This hydroxylamine can react with S-acetylthiocholine to form a species capable of producing interstrand crosslinks in naked DNA. In terms of ADEPT, SN 23862 has a potential advantage over CB 1954 in that it is not reduced by mammalian DT diaphorases. Therefore, a series of compounds related to SN 23862 has been synthesized, and evaluated as potential prodrugs both by determination of kinetic parameters and by ratio of IC50 against UV4 cells when incubated in the presence of prodrug, with and without the E. coli enzyme and cofactor (NADH). Results from the two studies were generally in good agreement in that compounds showing no increase in cytotoxicity in presence of enzyme and cofactor were not substrates for the enzyme. None of the analogues were activated by DT diaphorase isolated from Walker 256 carcinoma cells. For those compounds which were substrates for the E. coli nitroreductase, there was a positive correlation between kcat and IC50 ratio. Two compounds showed advantageous properties: SN 25261 (with a dihydroxypropylcarboxamide ring substituent) which has a more than 10-fold greater aqueous solubility than SN 23862 whilst retaining similar kinetic characteristics and cytotoxic potency; and SN 25084, where a change in the position of the carboxamide group relative to the mustard resulted in an increased cytotoxicity ratio and kcat compared with SN 23862 (IC50 ratios 214 and 135; kcat values of 75 and 26.4 sec-1, respectively). An analogue (SN 25507) incorporating both these structural changes had an enhanced kcat of 576 sec-1. This study elucidates some of the structural requirements of the enzyme and aids identification of further directions in the search for suitable prodrugs for an ADEPT nitroreductase system.


Consecutive use of mini-implants in the palate to treat skeletal maxillary constriction and Class II malocclusion in an adult case.
This report describes the successful use of two multifunctional mini-implants that were inserted into the palate in the treatment of an 18-year-old woman in whom the maxilla was skeletally narrowed and the molars have migrated mesially on both sides. Three different appliances were used in sequence in the course of treatment: first, an appliance supported by bone and teeth (hybrid hyrax) for surgically-assisted rapid maxillary expansion (SARME); second, a distalization device supported by mini-implants to achieve molar distalization; and third, a transpalatal arch (TPA) stabilized by mini-implants to allow indirect anchorage during retraction of the incisors. The mini-implants in the palate led to a reduction in the adverse effects of the SARME procedure and made treatment with cervical headgear unnecessary. TPA stabilized by the mini-implant was also used to retract the anterior teeth en masse, with no need for alterations in the treatment mechanism and using routine orthodontic methods.


The source of fluid deep to the iliotibial band: documentation of a potential intra-articular source.
To determine whether there is a consistent extension of the lateral synovial recess under the iliotibial band (ITB) in an unembalmed cadaveric model. A prospective laboratory investigation. A procedural skills laboratory of a tertiary medical center. Twelve unembalmed cadaveric knee specimens. The suprapatellar recess, ITB, and region deep to the ITB were examined sonographically to document the absence of fluid in each knee. Thereafter, 60 mL of normal saline solution was injected into each knee to distend the joint recesses. Postinjection sonographic examination of the ITB at the level of the lateral femoral epicondyle was repeated at 0°, 25°, and 45° of knee flexion to detect and characterize any fluid visualized in the region of the ITB. The location of fluid in relation to the ITB was recorded as anterior, deep, posterior, or a combination of these positions. Fluid was observed anterior and deep to the ITB in 100% of 12 specimens. In 2 specimens, fluid also was noted posterior to the ITB. The presence and location of the fluid did not appear to change as a function of knee position. Using dynamic sonographic evaluation, we could track the fluid deep to the ITB back to the knee joint. The lateral synovial recess appears to regularly extend beneath the anterior ITB. Fluid deep to the ITB should precipitate further evaluation of the knee joint when clinically indicated. Although distention of the lateral synovial recess is not always symptomatic, synovial irritation may be a pathoetiologic factor in the production of lateral knee pain syndromes, including ITB syndrome.


Iron pentacarbonyl as a precursor for molecule-based magnets: formation of Fe[TCNE](2) (T(c) = 100 K) and Fe[TCNQ](2) (T(c) = 35 K) magnets.
The reaction of tetracyanoethylene (TCNE) and 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) with Fe(CO)(5) leads to formation of magnetically ordered materials of Fe[TCNE](2) (T(c) = 100 K) and Fe[TCNQ](2) (T(c) = 35 K) composition, respectively. In contrast, the reaction with 1,2-dichloro-5,6-dicyanobenzoquinone (DDQ) leads to a paramagnetic material.


Draft Genome Sequences of Sphingomonadaceae Strains Isolated from a Freshwater Lake.
We isolated two bacterial strains (Sphingomonadaceae family) from Lake Biwa, Japan. Based on whole-genome sequencing results, one strain (BSN-002) was assigned to the Sphingopyxis genus and the other (BSN-004) to Sphingomonas aquatilis.


Methylcholanthrene induced murine primitive neuroectodermal tumor: ultrastructure and nuclear RNA polymerase activity.
The histology, ultrastructure, and nuclear RNA polymerase activity are described in a murine primitive neuroectodermal tumor derived by serial transplantation from a tumor originally induced with methylcholanthrene and classified as an ependymoblastoma. The light microscope and ultrastructural studies show that this tumor does not contain the distinguishing morphological features of differentiated ependymal cells which are also commonly seen in human ependymomas. One outstanding feature is the size and number of the nucleoli. The mean number of nucleoli/nucleus is 4 which is two to four times that of the normal neuroglial cell. The nucleolar diameter is about twice that found in normal neuroglial cells. The nucleolar diameter is about twice that found in normal neuroglial cells. The nuclear RNA synthesizing activity is the highest of the chemically induced animal tumors we have studied. The alpha amanitin inhibition is the lowest seen in any of these tumors which suggests that RNA polymerases inhibited by alpha amanitin contribute less to the total nuclear RNA synthesis. Adriamycin significantly inhibits the nuclear RNA polymerase activity of this tumor.


Predictive value of nonspecific symptoms for acute illness in nursing home residents.
To examine the predictive value of nonspecific symptoms for acute illness in nursing home residents. Prospective, observational study. Academic nursing home located in an urban setting. Two hundred two newly admitted residents. Eleven nonspecific symptoms were ascertained by review of observations documented by nursing home staff in the medical record. Research staff independently identified acute illness according to previously established criteria from nurse report and medical record review. Follow-up was divided into 10-day intervals, and concordance between nonspecific symptoms and acute illness within these intervals was determined. Predictive values were calculated according to standard formulae. Nonspecific symptoms and acute illnesses occurred in 21.7% and 12.5% of 10-day intervals, respectively. Positive predictive values (PPVs) were highest for lethargy, weakness, and decreased appetite, each of which correctly predicted the presence of an acute illness one out of two times the symptoms were reported. Agitation and disorientation predicted an acute illness one out of three times, and falls predicted an acute illness one out of four times. Overall, the PPV of the occurrence of any nonspecific symptom was 0.24, and the negative predictive value of the absence of nonspecific symptoms was 0.91. Hypoactive nonspecific symptoms are more likely than other nonspecific symptoms to be signs of incipient acute illness. Studies are needed to determine whether an intervention in residents with these nonspecific symptoms can enable earlier detection and treatment of acute illness.


Dependence of eosinophil granulocyte infiltration into nodules on the presence of microfilariae producing Onchocerca volvulus.
Onchocercomata with a single live or dead worm were analyzed to elucidate the infiltration of eosinophils. Females were classified according to the presence or absence of microfilariae in their uteri and in the nodular tissues. Immunohistochemical staining was performed using antibodies against eosinophil cationic protein, peroxidase, and major basic protein. Very few eosinophils were detected in nodules containing females without microfilariae or male or dead worms only, whereas eosinophils were abundant in all nodules with females producing microfilariae. The occurrence of eosinophils was not related to the age of the worm. Occasionally, degenerated or dead microfilariae attacked by activated eosinophils were found. By examination of onchocercomata with or without microfilariae from the same patient, it was excluded that the occurrence of eosinophils was dependent mainly on the host's immune status. In conclusion, live adult Onchocerca volvulus do not elicit an invasion of eosinophils as long as they do not produce microfilariae. The absence of eosinophilia does not exclude onchocerciasis.


The impact of four widely used neonicotinoid insecticides on Tetragonisca angustula (Latreille) (Hymenoptera: Apidae).
Application of neonicotinoid insecticides on crops can reduce the pollination services and population levels of the stingless bee Tetragonisca angustula (Latreille) (Hymenoptera: Apidae) in Neotropical agroecosystems. However, the impact of these insecticides on this bee has not been fully investigated. This study assessed the susceptibility levels of T. angustula to four neonicotinoid insecticides (acetamiprid, imidacloprid, thiacloprid and thiamethoxam), widely used to manage pests on different crops, and their effects on locomotion of the bee. Neonicotinoids with the cyano radical caused lower bee mortality (assessed by mean lethal concentration, LC50), while those compounds with the nitro radical were highly harmful to T. angustula. Locomotion activity was strongly impaired in bees treated with thiacloprid and imidacloprid, while acetamiprid did not affect the locomotion activity, which was similar to the control. Application of thiamethoxam caused hyperactivity, as observed by increases of ∼4.5 and 5.0-fold in mean speed and distance traveled, respectively. These results suggest that applications of neonicotinoid insecticides can negatively affect the pollination activity of T. angustula. These results can also help to develop strategies to conserve these pollinators in agroecosystems.


Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model.
It is imperative to identify new targets for improved vaccines and therapeutics against influenza. One such target is the relatively conserved stalk region of the influenza A hemagglutinin (HA) surface protein. We conducted a randomized, double-blind, phase 2, placebo-controlled trial of a monoclonal antibody that targets the HA stalk (CR6261) in a H1N1pdm09 healthy volunteer human challenge model. A single 50 mg/kg dose of CR6261 was infused 24 hours after challenge. The primary efficacy outcome was area under the curve (AUC) of viral RNA detection over time. Ninety-one healthy volunteers were randomized and underwent influenza challenge; 49 received CR6261 and 42 received placebo. CR6261 had no statistically significant effect on AUC (AUC, 48.56 log [copies/mL] × days, interquartile range [IQR], 202 vs AUC, 25.53 log [copies/mL] × days, IQR, 155; P = .315) and no clinically significant effect on influenza disease measures including number of symptoms, duration of symptoms, or inFLUenza Patient-Reported Outcome (FLU-PRO) scores. Preexisting anti-NA antibody titers were most predictive of reduced influenza disease. CR6261 reached a mean peak serum concentration of 1 × 106 ng/mL 15 minutes after infusion and a mean peak of 5.97 × 102 ng/mL in the nasal mucosa 2-3 days after infusion. The results of this study suggest that a monoclonal anti-stalk approach to prevent or treat influenza infection may be limited in efficacy. Future approaches should consider including and evaluating anti-stalk antibodies as part of a multifaceted strategy rather than as a stand-alone therapeutic. NCT02371668.


Treatment of psoriatic arthritis with anti-TNF agents: a systematic review and meta-analysis of efficacy, effectiveness and safety.
We did a systematic review and meta-analysis on the efficacy and safety of the anti-TNF drugs adalimumab, etanercept, golimumab and infliximab used in psoriatic arthritis (PsA) adult treatment. Additionally, we present results of anti-TNF use in real life settings. We searched Embase, Medline, Cochrane Central and LILACS, from inception to 11/08/2013, for studies comparing anti-TNFs with each other or with controls. We included nine randomized controlled trials and six observational studies. ACR20, ACR50, PsARC and PASI75 responses were achieved by more users of anti-TNF than control after up to 24 weeks of treatment. More participants who used etanercept and infliximab achieved ACR70. After all patients originally randomized to anti-TNF or placebo had used anti-TNF for at least 24 weeks, we observed difference only with regard to ACR70 response. Radiographic end points were achieved by more patients in anti-TNF group, and they seem to be time dependent-the longer patients use the drug the better the results. Etanercept and infliximab had worse results on application site reactions, but in general anti-TNF drugs in the regimens studied were as safe as control/placebo. There seems to be no difference in efficacy and effectiveness among anti-TNFs, but superiority head-to-head studies are still needed. Meanwhile, other factors should be taken into account in the choice of medication, such as costs and patient convenience.


The promises and perils of hospital autonomy: reform by decree in Viet Nam.
This article investigates impacts of hospital autonomization in Viet Nam employing a "decision-space" framework that examines how hospitals have used their increased discretion and to what effect. Analysis suggests autonomization is associated with increased revenue, increasing staff pay, and greater investment in infrastructure and equipment. But autonomization is also associated with more costly and intensive treatment methods of uncertain contribution to the Vietnamese government's stated goal of quality healthcare for all. Impacts of autonomization in district hospitals are less striking. Despite certain limitations, the analysis generates key insights into early stages of hospital autonomization in Viet Nam.


Lipoprotein lipase activity in human adipose tissue during induced hypertriglyceridaemia.
Needle biopsies of adipose tissue and blood samples were obtained before and at short intervals after a "bolus" injection of 10% Intralipid. Lipoprotein lipase activities were measured in acetone--ether extracts of the tissue samples. Levels of serum triglyceride began to fall less than 5 min after the injection of the Intralipid with a half-life of 20 min. During this time interval, no significant changes were observed in the activities of lipoprotein lipase in adipose tissue. A patient with a severe hypertriglyceridaemia (Type V) underwent plasma exchange with a reduction in serum triglyceride levels from 11 to 4 mm/l. There was a parallel fall in adipose tissue lipoprotein lipase activity. We conclude that lipoprotein lipase in adipose tissue is unaltered during experimental hypertriglyceridaemia and that the activity of the enzyme in adipose tissue is probably not reduced as a secondary feature of an elevated plasma triglyceride level.


Patient-individualized resection planning in liver surgery using 3D print and virtual reality (i-LiVR)-a study protocol for a prospective randomized controlled trial.
A multitude of different diseases-benign and malign-can require surgery of the liver. The liver is an especially challenging organ for resection planning due to its unique and interindividually variable anatomy. This demands a high amount of mental imagination from the surgeon in order to plan accordingly - a skill, which takes years of training to acquire and which is difficult to teach. Since the volume of the functional remnant liver is of great importance, parenchyma sparing resections are favoured. 3D reconstructions of computed tomography imaging enable a more precise understanding of anatomy and facilitate resection planning. The modality of presentation of these 3D models ranges from 2D monitors to 3D prints and virtual reality applications. The presented trial compares three different modes of demonstration of a 3D reconstruction of CT scans of the liver, which are 3D print, a demonstration on a regular computer screen or using a head-mounted virtual reality headset, with the current gold standard of viewing the CT scan on a computer screen. The group size was calculated with n=25 each. Patients with major liver resections in a laparoscopic or open fashion are eligible for inclusion. Main endpoint is the comparison of the quotient between planned resection volume and actual resection volume between these groups. Secondary endpoints include usability for the surgical team as well as patient specifics and perioperative outcome measures and teaching issues. The described study will give insight in systematic planning of liver resections and the comparison of different demonstration modalities of 3D reconstruction of preoperative CT scans and the preference of technology. Especially teaching of these demanding operations is underrepresented in prior investigations. Prospective trials registration at the German Clinical Trials register with the registration number DRKS00027865 . Registration Date: January 24, 2022.


Determination of acid phosphatase in biological fluids using a new substrate, 2,6-dichloro-4-nitrophenyl phosphate.
A new substrate, 2,6-dichloro-4-nitrophenyl phosphate (DCNP-P), is used for the determination of acid phosphatase (EC 126.96.36.199) in serum and urine. It was hydrolyzed by acid phosphatase to 2,6-dichloro-4-nitrophenol (DCNP) and phosphoric acid. At a pH of 4.5-6.0, the absorption of DCNP liberated by acid phosphatase was much higher than that of p-nitrophenol, which is commonly used as an aglycone in the acid phosphatase assay. By using DCNP-P as a substrate for acid phosphatase activity, determinations can be made without the colour reaction which requires the addition of an alkaline solution, and can be determined by the rate assay that does not require measurement of sample blanks in serum or urine. This method using DCNP-P is highly sensitive and is the most suitable for the rate assay of acid phosphatase activity in biological fluids.


Extremely high relative growth rate makes the cabbage white, Pieris rapae, a global pest with highly abundant and migratory nature.
The small cabbage white butterfly, Pieris rapae, is an extraordinarily abundant migratory pest of cabbage that causes severe damage worldwide without known reasons. I here show that the average relative growth rate (RGR: the ratio of the daily increase of biomass to total biomass) of herbivore (Gh; an indicator of the growth speed of herbivore) of P. rapae on cabbage during the larval period is larger by far than those of all other insect-plant pairs tested. It exceeds 1.15 (/day),-meaning that the biomass more than doubles each day-compared to 0.1-0.7 for most insect-plant pairs, including that of Pieris melete, a sibling of P. rapae which never becomes a pest of cabbage. My data further showed the RGR in the larval stage (larval Gh), positively correlates with abundance and/or migratoriness of insect herbivores. These results together with my mathematical food web model suggest that the extraordinarily high larval Gh of P. rapae is the primary reason for its ubiquitously severe pest status accompanied with its abundance and migratoriness, and that the RGR of herbivores, Gh, characterizing the plant-herbivore interface at the bottom of the food webs is an important factor affecting whole ecosystems, including animal abundance, fauna size, plant damage levels, competitiveness among herbivorous species, determination of hostplant, invasiveness, and the evolution of animal traits involved in the so-called r/K strategy, such as migratoriness. Knowledge about Gh will be crucial to controlling pests and improving the negative effects of human activity on ecosystems including faunal decline (or defaunation).


Matrix stiffness exacerbates the proinflammatory responses of vascular smooth muscle cell through the DDR1-DNMT1 mechanotransduction axis.
Vascular smooth muscle cell (vSMC) is highly plastic as its phenotype can change in response to mechanical cues inherent to the extracellular matrix (ECM). VSMC may be activated from its quiescent contractile phenotype to a proinflammatory phenotype, whereby the cell secretes chemotactic and inflammatory cytokines, e.g. MCP1 and IL6, to functionally regulate monocyte and macrophage infiltration during the development of various vascular diseases including arteriosclerosis. Here, by culturing vSMCs on polyacrylamide (PA) substrates with variable elastic moduli, we discovered a role of discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that binds collagens, in mediating the mechanical regulation of vSMC gene expression, phenotype, and proinflammatory responses. We found that ECM stiffness induced DDR1 phosphorylation, oligomerization, and endocytosis to repress the expression of DNA methyltransferase 1 (DNMT1), very likely in a collagen-independent manner. The DDR1-to-DNMT1 signaling was sequentially mediated by the extracellular signal-regulated kinases (ERKs) and p53 pathways. ECM stiffness primed vSMC to a proinflammatory phenotype and this regulation was diminished by DDR1 inhibition. In agreement with the in vitro findings, increased DDR1 phosphorylation was observed in human arterial stiffening. DDR1 inhibition in mouse attenuated the acute injury or adenine diet-induced vascular stiffening and inflammation. Furthermore, mouse vasculature with SMC-specific deletion of Dnmt1 exhibited proinflammatory and stiffening phenotypes. Our study demonstrates a role of SMC DDR1 in perceiving the mechanical microenvironments and down-regulating expression of DNMT1 to result in vascular pathologies and has potential implications for optimization of engineering artificial vascular grafts and vascular networks.


The association of serum leptin with the reduction of food intake and body weight during electroacupuncture in rats.
Previous studies indicate that acupuncture or electroacupuncture (EA) treatment reduces body weight and food intake in rats by increasing the level of anoretic peptides and decreasing that of orexigenic peptides in the hypothalamus. Considering a well-established role of leptin as a major regulator for feeding behavior in the hypothalamus, we hypothesized that EA might exert its effect via increasing serum leptin levels. In this study, we tested our hypothesis by evaluating the effects of EA on food intake and body weight, as well as on serum leptin levels in rats. Rats were randomly divided into 3 groups: AL (fed ad libitum with no treatments), Holder (fed ad libitum with daily holder restraint) and EA (fed ad libitum with daily holder restraint and 100 Hz EA stimulation) groups. During the four-week experimental period, daily food intake and body weight were measured. At the end of the experiment, levels of serum leptin and corticosterone, and plasma epinephrine (Epi) and norepinephrine (NE) were determined. Here we demonstrate that EA treatment indeed led to reduction of food intake and body weight, and to an increase of serum leptin levels. The level of Epi, NE, and corticosterone increased in the Holder group, but such increase in the level of aforementioned stress hormones was not observed in the EA group. Overall, our results suggest that EA treatment reduces food intake and body weight in rats possibly through increasing leptin levels, and that this effect of EA is not due to the stress caused by the daily holder restraint.


Rationale and design of a multicenter randomized study comparing the efficacy and safety of esaxerenone versus trichlormethiazide in patients with uncontrolled essential hypertension: EXCITE-HT study.
The next-generation mineralocorticoid receptor blocker (MRB) esaxerenone has favorable antihypertensive effects in patients who do not respond to treatment with first-line antihypertensive agents and may be beneficial as a second-line treatment. However, MRBs are currently considered a fourth-line treatment as there is no clinical evidence comparing the efficacy of esaxerenone with other classes of antihypertensive agents. The multicenter, randomized, open-label, parallel-group EXCITE-HT study will evaluate the efficacy and safety of esaxerenone as a second-line agent in the treatment of Japanese patients with uncontrolled essential hypertension. After a 4-week run-in period, patients will receive either esaxerenone or trichlormethiazide for 12 weeks per the package insert and the Japanese Society of Hypertension Guidelines for the Management of Hypertension. At Weeks 4 and 8, the dose of esaxerenone or trichlormethiazide may be increased. Blood pressure (home [morning and bedtime] and office), serum biomarkers, and urinary biomarkers will be measured. The primary efficacy endpoint is the change from baseline in morning home systolic blood pressure/diastolic blood pressure to the end of treatment. The EXCITE-HT study is expected to validate the non-inferiority of esaxerenone to trichlormethiazide and provide the first evidence for the early use of esaxerenone as a second-line agent in the treatment of Japanese patients with uncontrolled essential hypertension instead of its current use as a fourth-line agent.


Cell Wall Modifications in Giant Cells Induced by the Plant Parasitic Nematode Meloidogyne incognita in Wild-Type (Col-0) and the fra2 Arabidopsis thaliana Katanin Mutant.
Meloidogyne incognita is a root knot nematode (RKN) species which is among the most notoriously unmanageable crop pests with a wide host range. It inhabits plants and induces unique feeding site structures within host roots, known as giant cells (GCs). The cell walls of the GCs undergo the process of both thickening and loosening to allow expansion and finally support nutrient uptake by the nematode. In this study, a comparative in situ analysis of cell wall polysaccharides in the GCs of wild-type Col-0 and the microtubule-defective fra2 katanin mutant, both infected with M. incognita has been carried out. The fra2 mutant had an increased infection rate. Moreover, fra2 roots exhibited a differential pectin and hemicellulose distribution when compared to Col-0 probably mirroring the fra2 root developmental defects. Features of fra2 GC walls include the presence of high-esterified pectic homogalacturonan and pectic arabinan, possibly to compensate for the reduced levels of callose, which was omnipresent in GCs of Col-0. Katanin severing of microtubules seems important in plant defense against M. incognita, with the nematode, however, to be nonchalant about this "katanin deficiency" and eventually induce the necessary GC cell wall modifications to establish a feeding site.


An overview of the role of genotyping in the diagnosis of the primary hyperoxalurias.
The aim of this paper is to give an overview of our current state of knowledge with respect to genotyping for the primary hyperoxalurias and the role of molecular genetics alongside the more traditional biochemical and enzymatic tests for the diagnosis and prognosis of these disorders. The published literature was reviewed to establish the frequency of different mutations and thus the value of testing for a limited number of these mutations in patients with clinical suspicion of primary hyperoxaluria (PH). This approach was compared with whole gene sequencing of the AGXT and GRHPR genes. A limited genetic screen can provide a first line test for PH1 and PH2 in symptomatic patients and can provide a full diagnosis in approximately a third of cases. Molecular genetic analysis is essential for carrier testing and prenatal diagnosis. The value of molecular genetics in prognosis requires a wider evidence base.


Analysis of tear proteins by one- and two-dimensional thin-layer iosoelectric focusing, sodium dodecyl sulfate electrophoresis and lectin blotting. Detection of a new component: cystatin C.
Isoelectric focusing (IEF) of tear proteins has not yet been carried out in a satisfactory way. Two-dimensional (2D) electrophoresis, especially in the combination of IEF with SDS, is able to differentiate between proteins in detail. The purpose of this study was therefore to analyze tear proteins by 1D IEF alone and in combination with a 2D pattern, and by IEF followed by lectin staining. Ampholines, covering a broad range from pH 3 to pH 10, were applied. After IEF, semi-dry blotting and incubation with a group II lectin and two group V lectins was performed. Tear proteins could be separated into 31 single bands. Tear-specific pre-albumin (TSPA), lactoferrin, sIgA, IgG and lysozyme were found to be main components. Isoelectric points (IEPs, pls) of all proteins separated were determined by comparison with IEF standards. 2D patterns of IEF and SDS electrophoresis were obtained for the main subunit components of lactoferrin, sIgA, TSPA, and lysozyme. An additional new component of considerable concentration was focused at pI 8.6 with a subunit MW of 14 kDa. With s-WGA a component at an IEP of 5.2 was visualized, representing transferrin. With SNA, lactoferrin stained as a sharp main band at pI 5.1 with three additional weaker bands at IEPs from 4.8 to 4.9. At IEPs between 4.4 and 6.1, multiple components of sIgA were stained with MAA. The sugar specificity of transferrin at pI 5.2 was beta-GlcNAc. Lactoferrin showed glycation with NANA-alpha-2-6-Gal or NANA-alpha-2-6-GalNAc, whereas the sugar specificity of sIgA was NANA-alpha-2-3-Gal. The investigative strategy applied here, including IEF alone, in combination with SDS-electrophoresis, and SDS-electrophoresis followed by lectin staining proved to be a reproducible method for tear protein analysis of hitherto unexperienced capacity. Lectin-stained bands of native tear proteins are not uniformly glycated by one sugar residue, but show various sugar specificities. IgA as a whole molecule is specifically glycated with NANA-alpha-2-3-Gal.


Wilms' tumor gene 1 (WT1) in endometrial carcinoma.
Wilms' tumor gene (WT1), located on chromosome 11, encodes a transcription factor that contributes to the carcinogenesis of uterine sarcomas. To expand the knowledge on the biological role of WT1 in other uterine cancers, we focused on its detection in endometrial carcinoma. In total, 36 paraffin-embedded tumors were available for WT1 immunohistochemical (IHC) analysis including endometrial endometrioid carcinoma (n=24), serous carcinoma (n=9) and clear cell carcinoma (n=3). Three slides from different sites of the tumor were analysed. Of these tumors, 32 snap frozen tissue samples were available for RT-PCR (endometrioid carcinoma (23), serous carcinoma (7) and clear cell carcinoma (2)). To compare, WT1 expression was also evaluated by IHC in benign endometrium (12) and benign endometrial polyps (5). WT1 positivity was noticed in tumor cells and endothelial cells, lining the intratumoral blood vessels. Overall, 72% (26/36) of tumors stained positive for WT1. RT-PCR results showed WT1 positivity in 75% (24/32) of samples. Comparing the staining patterns of the 3 different bioptic sites, tumor heterogeneity was demonstrated in the majority (72%) of samples. Although WT1 is expressed in a majority of endometrial carcinomas, a heterogeneous staining pattern is observed. This information is important for WT1-directed immunotherapy.


A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.
Endoscopic variceal ligation (EVL) plus nonselective β-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB. After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%). EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation.


GABA can improve acoustic contrast in the rat ventral cochlear nucleus.
The effect of microiontophoretically applied gamma-aminobutyric acid (GABA) and its agonists and antagonists on the response pattern of single units in the ventral cochlear nucleus (VCN) of the rat was examined in order to study GABA's physiological function in auditory processing. The effects of the drugs were judged by changes of spontaneous and sound-evoked activity in peristimulus-time histograms (PSTHs) of at least 20 consecutive presentations of acoustic stimuli. GABA inhibited the discharge activity of the majority of neurons. All response types found in the VCN except onset-I responders were sensitive to GABA. The GABAergic inhibition is most probably mediated by GABAA receptors, since the GABAA-receptor agonist muscimol, but not the GABAB-receptor agonist baclofen, mimicked the effect of GABA. The GABAA-receptor antagonists, bicuculline and picrotoxin, had an excitatory effect on the neurons' spontaneous activity, suggesting a tonic endogeneous release of GABA which exerts a permanent inhibition on VCN neurons. Although inhibitory, iontophoresis of GABA emphasized the response to stimulus onset in the PSTHs by means of a stronger inhibition of spontaneous activity. When using iontophoretical currents which did not suppress the neuronal activity completely, a strong inhibition of spontaneous activity was accompanied by only a small inhibition of tone-evoked activity. Under these conditions, the response to tone onset was frequently not inhibited at all. Therefore, GABA's physiological function is possibly to improve the contrast between transient acoustic signals and ongoing background activity. In order to test this hypothesis, the test tone was masked by continuous background noise. Indeed, GABA reduced the noise-evoked discharge more than the tone-evoked discharge, leaving the onset peak in the PSTHs almost unchanged. Thus, GABAergic input improves the signal-to-noise ratio for acoustic transients in VCN neurons. Our data suggest that a functional role of GABA in the VCN is to act as a transmitter within a descending inhibitory feedback loop of the auditory brainstem which serves to improve the transmission of relevant acoustic signals in constant background noise.


Possible induction by blood transfusion of immunological tolerance against growth of transplanted tumors in mice.
That blood transfusions aid kidney graft survival is well known. Our data show that blood transfusions, except for the red blood cell component, promote growth of transplanted tumors in mice. These clinical and experimental observations suggest that blood transfusions may induce some immunological tolerance.


Optimization of experimental conditions for functional in vitro characterization of humanized antibodies specific for staphylococcal enterotoxin B.
Staphylococcus aureus is a common nosocomial infection and its resistance to penicillin and methicillin antibiotics is a growing clinical problem. We previously described the development of a humanized anti-Staphylococcus enterotoxin B (SEB) antibody derived from the mouse antibody made by the 20B1 hybridoma. This antibody was humanized and characterized kinetically by surface plasmon resonance demonstrating that the humanized clones retained binding to SEB. Clones were then functionally characterized in an in vitro assay demonstrating that the murine 20B1, chimeric and humanized antibodies potently inhibited SEB-induced murine splenocyte proliferation assay. Here, we describe a human cell-based screening assay, optimized by varying multiple experimental parameters that resulted in an assay that was used to demonstrate full and potent neutralization by the parental, chimeric and humanized antibodies. The replacement of fetal bovine serum (FBS) with normal human serum (NHS) was found to be a crucial factor in the performance of the human cell based screening assay that enabled the calculation of mAb efficacy and potency. In addition, we found that anti-SEB antibodies showed similar efficacy and potency with a triple mutant Fc region (designed to be effector function null) or a wild-type Fc region, which is in contrast to previously described studies.


[Non-standard genetic codes and translation termination].
Genetic code is not universal. Various non-standard versions of the code were found in mitochondrial, prokaryotic and eukaryotic genomes. Stop codons are used to signal the ribosome stop translation of the coding sequence and prone to reassignment to sense codons. Class-1 termination factors recognize stop codons and promote hydrolysis of the peptidyl-tRNA in ribosome (RF1, RF2 in prokaryotes and eRF1 in eukaryotes). The class-1 factor termination specificity is changed in non-standart codes organisms. Pyrrolysine and selenocysteine use dissimilar decoding strategies. The various non-standart code origin hypotheses are described. It was proposed that specificity alteration of the class-1 release factor was a starting point for stop codon reassignment.


Cell shape change and invagination of the cephalic furrow involves reorganization of F-actin.
Invagination of epithelial sheets to form furrows is a fundamental morphogenetic movement and is found in a variety of developmental events including gastrulation and vertebrate neural tube formation. The cephalic furrow is a deep epithelial invagination that forms during Drosophila gastrulation. In the first phase of cephalic furrow formation, the initiator cells that will lead invagination undergo apicobasal shortening and apical constriction in the absence of epithelial invagination. In the second phase of cephalic furrow formation, the epithelium starts to invaginate, accompanied by both basal expansion and continued apicobasal shortening of the initiator cells. The cells adjacent to the initiator cells also adopt wedge shapes, but only after invagination is well underway. Myosin II does not appear to drive apical constriction in cephalic furrow formation. However, cortical F-actin is increased in the apices of the initiator cells and in invaginating cells during both phases of cephalic furrow formation. These findings suggest that a novel mechanism for epithelial invagination is involved in cephalic furrow formation.


[Pathohistological criteria in the treatment of stage I a cervical carcinoma (author's transl)].
The work is an attempt to define the stage Ia of squamous carcinoma of the cervix on the basis of morphological criteria. These criteria, with the collaboration of pathologist and gynecologist, would allow the best treatment. They are based on the evaluation of the cellular type, mitotic activity, the pattern of invasion, the tissue defense reaction, the presence of lymphatic and vascular spread, and the size of carcinomatous tissue.


Role of Politics, Guilds and Pedagogy in defining Policies in Medical Education: The Pakistan Scenario.
Politics in education is not a new concept and has been a sore point of discussion between academia and policy makers. The politics of medical education has led to the formation of informal guilds that have taken control over medical education. Policy decisions concerning medical/dental education affecting the lives of the community, at large are implemented without giving due consideration to the pedagogy of medical education. This paper delves into the definitions of politics, pedagogy and guilds and with evidence identifies that major policy decisions in medical education are strongly influenced by politics. The paper will discuss that politics of medical education is not necessarily a bad thing if it ensures public safety and is based on best evidence medical education. In the same context the guilds formed for medical education reforms should uphold the principles of pedagogy.


Vinyl acetate induces intracellular acidification in mouse oral buccal epithelial cells.
Vinyl acetate exposure in drinking water has been associated with tumor formation in the upper gastrointestinal tract of rats and mice. One potential mechanism for inducing carcinogenesis involves acidification of the intracellular environment due to the metabolism of vinyl acetate to acetic acid. Prolonged intracellular acidification is thought to produce cytotoxic and/or mitogenic responses that are the sentinel pharmacodynamic steps toward cancer. To determine whether exposure to vinyl acetate affects the intracellular pH of intact oral cavity tissue, isolated mouse oral buccal epithelium was loaded with the pH-sensitive dye BCECF, and then exposed to vinyl acetate concentrations ranging from 10 to 1000 microM for up to 4 min. Extracellular vinyl acetate exposure induced a progressive intracellular acidification that was reversible upon removal of the vinyl acetate. The rate of the acidification was concentration-dependent and increased exponentially within the concentration range tested. The magnitude of the vinyl acetate-induced acidification was inhibited by pretreatment with the carboxylesterase inhibitor bis(p-nitrophenyl)phosphate. These results are consistent with the hypothesis that vinyl acetate contributes to the generation and progression of oral cavity tumors via a process of intracellular acidification. Such a process has been proposed to have practical dose-response thresholds below which the intracellular environment can be maintained within homeostatic bounds and the contribution of exposure to carcinogenic risk is negligible.


Design, synthesis and antiviral activity of novel quinazolinones.
HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well as mechanistically different. Herein, a series of quinazolinones were designed and synthesized as novel HIV-1 inhibitors. The new synthetic route provides a practical method for the preparation of 5-hydroxy quinazolinones. Primary bioassay results indicated that most of the quinazolinones possess anti-HIV activity, especially for compound 11b with 77.5% inhibition rate at 10 μM emerged as a new active lead. Most of the synthesized compounds were also found to exhibit good anti-TMV activity, of which compo und 9a showed similar in vivo anti-TMV activity to commercial plant virucide Ribavirin. This work provides a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration and optimization of previously reported antiviral agents.


5-hydroxytryptamine 2C receptors in the dorsal striatum mediate stress-induced interference with negatively reinforced instrumental escape behavior.
Uncontrollable stress can interfere with instrumental learning and induce anxiety in humans and rodents. While evidence supports a role for serotonin (5-HT) and serotonin 2C receptors (5-HT(2C)R) in the behavioral consequences of uncontrollable stress, the specific sites of action are unknown. These experiments sought to delineate the role of 5-HT and 5-HT(2C)R in the dorsal striatum (DS) and the lateral/basolateral amygdala (BLA) in the expression of stress-induced instrumental escape deficits and exaggerated fear, as these structures are critical to instrumental learning and fear behaviors. Using in vivo microdialysis, we first demonstrated that prior uncontrollable, but not controllable, stress sensitizes extracellular 5-HT in the dorsal striatum, a result that parallels prior work in the BLA. Additionally, rats were implanted with bi-lateral cannula in either the DS or the BLA and exposed to uncontrollable tail shock stress. One day later, rats were injected with 5-HT(2C)R antagonist (SB242084) and fear and instrumental learning behaviors were assessed in a shuttle box. Separately, groups of non-stressed rats received an intra-DS or an intra-BLA injection of the 5-HT(2C)R agonist (CP809101) and behavior was observed. Intra-DS injections of the 5-HT(2C)R antagonist prior to fear/escape tests completely blocked the stress-induced interference with instrumental escape learning; a partial block was observed when injections were in the BLA. Antagonist administration in either region did not influence stress-induced fear behavior. In the absence of prior stress, intra-DS administration of the 5-HT(2C)R agonist was sufficient to interfere with escape behavior without enhancing fear, while intra-BLA administration of the 5-HT(2C)R agonist increased fear behavior but had no effect on escape learning. Results reveal a novel role of the 5-HT(2C)R in the DS in the expression of instrumental escape deficits produced by uncontrollable stress and demonstrate that the involvement of 5-HT(2C)R activation in stress-induced behaviors is regionally specific.


Environmental cardiovascular disease.
The last decade has seen a remarkable growth in the evidence establishing exposure to environmental agents as a risk factor for cardiovascular disease (CVD). Most of this has come from research linking exposure to ambient particulate matter with CVD, although more recent evidence suggests that the ozone might also be contributing factor. Research on the cardiovascular toxicity of other pollutants, notably arsenic, has also grown during this period. In addition to their effects in adults, environmental agents, such as dioxin, have also been shown to adversely affect development of the heart in laboratory animals. Taken together, these results suggest that environmental exposure must be considered as an important risk factor for CVD and that further research to determine mechanisms of action and susceptible populations is needed. This research will require interdisciplinary approaches, and should yield data not only on the toxic effects of pollutants on the cardiovascular system, but on the basic pathophysiology of cardiovascular diseases as well.


Evaluation of indoor exposition to benzene, toluene, ethylbenzene, xylene, and styrene by passive sampling with a solid-phase microextraction device.
A solid-phase microextraction (SPME) sampling method is developed to evaluate indoor exposure to benzene, toluene, ethylbenzene, xylene, and styrene with gas chromatography and flame ionization detection for quantitative analysis. An SPME holder with a 100-pm polydimethylsiloxane (PDMS) and 65-pm PDMS-divinylbenzene fiber coating is tested in different air relative humidity conditions. The method gives good resolution, shows a linear response, is repeatable, and presents high sensitivity. This method is compared with National Institute of Occupational Safety and Health (NIOSH) active sampling.


Retraction: Circ_0075960 targets the miR-202-5p/CTNND1 axis to promote the growth and migration of endometrial carcinoma cells via regulating Wnt/β-catenin signaling activity.
This corrects the article on p.e11 in vol.34 , PMID: 36424704.


Typology of reactions to intimate partner violence among men and women arrested for partner violence.
This study examined behavioral and emotional responses to partner-initiated violence reported by men and women court-ordered to domestic violence counseling. Respondents provided Likert-type ratings of behavioral and emotional responses to their partners' initiated violence. Cluster analysis to determine heterogeneity of emotional and behavioral responses resulted in a three-cluster solution. The profile for Cluster 1, predominantly male, showed no specific behavioral or emotional reaction pattern. Cluster 2 respondents, evenly split between males and females, but comprising a high proportion of all of the female participants, reported frequently doing what the partner wanted and attempting to escape. Emotional responses experienced by Cluster 2 respondents were anger, insult, and fear. Cluster 3, predominantly male, reported a frequent tendency to use force in response and escape when their partners initiated physical violence. Emotionally, Cluster 3 participants reported experiencing high levels of anger and insult, and relatively low levels of fear and low levels of amusement. Implications of these findings for development of gender-based intervention strategies will be discussed.


Describing weak interactions of biomolecules with dispersion-corrected density functional theory.
Interaction energies of the biomolecules in the JSCH-2005 database are calculated with density functional theory using the exchange-correlation functional BLYP augmented with dispersion-corrected atom-centered potentials (DCACPs). The results are in excellent agreement with extrapolated CCSD(T) complete basis set limit references with unsigned mean errors of less than 1.6 kcal mol(-1). Geometry optimisations all reach stable configurations that are close to the MP2-optimised reference geometries.


An analysis of the processing of intramodal and intermodal time intervals.
In this 3-experiment study, the Weber fractions in the 300-ms and 900-ms duration ranges are obtained with 9 types of empty intervals resulting from the combinations of three types of signals for marking the beginning and end of the signals: auditory (A), visual (V), or tactile (T). There were three types of intramodal intervals (AA, TT, and VV) and 6 types of intermodal intervals (AT, AV, VA, VT, TA, and TV). The second marker is always the same during Experiments 1 (A), 2 (V), and 3 (T). With an uncertainty strategy where the first marker is 1 of 2 sensory signals being presented randomly from trial to trial, the study provides direct comparisons of the perceived length of the different marker-type intervals. The results reveal that the Weber fraction is nearly constant in the three types of intramodal intervals, but is clearly lower at 900 ms than at 300 ms in intermodal conditions. In several cases, the intramodal intervals are perceived as shorter than intermodal intervals, which is interpreted as an effect of the efficiency in detecting the second marker of an intramodal interval. There were no significant differences between the TA and VA intervals (Experiment 1) and between the AV and TV intervals (Experiment 2), but in Experiment 3, the AT intervals were perceived as longer than the VT intervals. The results are interpreted in terms of the generalized form of Weber's law, using the properties of the signals for explaining the additional nontemporal noise observed in the intermodal conditions.


Transformer based deep learning denoising of single and multi-delay 3D Arterial Spin Labeling.
To present a Swin Transformer-based deep learning (DL) model for denoising of single-delay and multi-delay 3D arterial spin labeling (ASL) and compare its performance with convolutional neural network (CNN) methods. Swin Transformer and CNN-based spatial denoising models were developed for single-delay ASL. The models were trained on 59 subjects (104 scans) and tested on 44 subjects (57 scans) from 3 different vendors. Spatiotemporal denoising models were developed using another dataset (6 subjects, 10 scans) of multi-delay ASL. A range of input conditions was tested for denoising single and multi-delay ASL respectively. The performance was evaluated using similarity metrics, spatial signal-to-noise ratio (SNR) and quantification accuracy of cerebral blood flow (CBF) and arterial transit time (ATT). Swin Transformer outperformed CNN-based networks, whereas pseudo-3D models showed better performance than 2D models for denoising single-delay ASL. The similarity metrics and image quality (SNR) improved with more slices in pseudo-3D models, and further improved when using M0 as input but introduced greater biases for CBF quantification. Pseudo-3D models with 3 slices as input achieved optimal balance between SNR and accuracy, which can be generalized to different vendors. For multi-delay, spatiotemporal denoising models had better performance than spatial-only models with reduced biases in fitted CBF and ATT maps. Swin Transformer DL models provided better performance than CNN methods for denoising both single and multi-delay 3D ASL data. The proposed model offers flexibility to improve image quality and/or reduce scan time for 3D ASL to facilitate its clinical use.


[Bioelectrical activity of the uterus of white rats with intrauterine streptococcal infection and exposed to the use of pulsing, local negative pressure with oxygen].
Intrauterine streptococcal infection of albino rats hematogenically during pregnancy (implantation, placentation) leads to different disorders of the bioelectrical activity of the uterus, which become normalized after the institution of pulsating local negative pressure with periodic oxygen supply.


Effect of the presence of trophectoderm vesicles on blastocyst in relation to in vitro hatching, clinical pregnancy, and miscarriage rates.
Trophectoderm vesicles (TVs) are observed in some blastocysts that penetrate cells from the zona pellucida to the outer margin. Therefore, we compared this incidence in relation to hatching, pregnancy, and miscarriage rates between conventional in vitro fertilization (c-IVF) and intracytoplasmic sperm injection (ICSI). Vitrified/warmed blastocysts (n = 112) were derived from surplus embryos. The blastocysts were then observed using time-lapse cinematography to resolve the relationship between hatching and implantation. Another study was conducted that comprised 681 embryo transfer cycles in 533 patients who received a single vitrified/warmed blastocyst from our clinic. The incidence of TV was significantly higher in embryos inseminated by ICSI compared with c-IVF [ICSI: 51/56 (91 %); c-IVF: 25/56 (45 %); P < 0.01]. The successful hatching rate was significantly lower in ICSI than in c-IVF [ICSI: 11/56 (20 %); c-IVF: 29/56 (52 %); P < 0.01]. In addition, the hatching rate was significantly lower when TVs were present (14/76; 18 %) than in non-TV embryos (26/36; 72 %) (P < 0.01). In regard to the clinical study results, no significant differences were found between the groups in the pregnancy rate (TV present group: 107/183, 58.5 %; TV absent group: 273/498, 54.8 %) and miscarriage rate (TV present group: 21/107, 19.6 %; TV absent group: 53/273, 19.4 %). In vivo, we hypothesized that hatching and hatched would occur naturally by assisting protease action in the uterus; therefore, these results suggest that the presence of TV has no effect on pregnancy rates in the clinical setting.


"Sex change" in skeletal remains: Assessing how heat-induced changes interfere with sex estimation.
The true impact of heat-induced changes in human bone regarding their sex estimation has not been comprehensively documented having a potentially negative impact on forensic anthropology. The objective of this paper was to evaluate how heat exposure affects sex estimation based on both morphological and metric features. The study focused in both low-to-medium intensity burns and high intensity burns. Selected sexually dimorphic features were analysed in 51 experimentally burnt skeletons from the 21st Century Identified Skeletal Collection. Bones were burnt to maximum temperatures between 450 °C and 1050 °C achieved after 75 to 257 min. Morphological methods tested in this study comprised the recommendations for hipbone features from Buikstra and Ubelaker (1994) and from Bruzek (2002). On the other hand, metric references tested here were the ones from Wasterlain (2000), Curate et al. (2016) and Gonçalves et al. (2013) focused on the humerus, femur, calcaneus and talus. Agreement was tested with Gwet's AC1 test and was further assessed by calculating the relative amount of perfect agreements. Results demonstrated that heat-induced changes affected not only the scoring of morphological features burnt at high temperatures but also the scoring of features burnt at lower intensities. On the other hand, metric features were only considerably affected in high intensity burns, no major changes being documented for low-to-medium intensity burns. For low-to-medium intensity burns, the Bruzek and Curate et al. methods revealed a better agreement between the pre- and post-burning scores. For high intensity burns, better agreement was obtained by using the Bruzek (2002) and Gonçalves et al. (2013) methods. As expected, heat-induced warping, fracture and metric change had a major impact on the pre- and post-observations' agreement. Contrary to what has been systematically assumed over the years, this impact is also quite substantial in bones burnt at low-to-medium burn intensities so caution is advised during the analysis of this kind of burnt skeletal material.