Improved electrochemical stability at the surface of La(0.8)Sr(0.2)CoO3 achieved by surface chemical modification.
The degradation of the surface chemistry on perovskite (ABO3) oxides is a critical issue for their performance in energy conversion systems such as solid oxide fuel/electrolysis cells and in splitting of H2O and CO2 to produce fuels. This degradation is typically in the form of segregation and phase separation of dopant cations from the A-site, driven by elastic and electrostatic energy minimization and kinetic demixing. In this study, deposition of Ti at the surface was found to hinder the dopant segregation and the corresponding electrochemical degradation on a promising SOFC cathode material, La(0.8)Sr(0.2)CoO3 (LSC). The surface of the LSC films was modified by Ti (denoted as LSC-T) deposited from a TiCl4 solution. The LSC and LSC-T thin films were investigated by electrochemical impedance spectroscopy, nano-probe Auger electron spectroscopy, and X-ray photoelectron spectroscopy (XPS), upon annealing at 420-530 °C in air up to about 90 hours. The oxygen exchange coefficient, k(q), on LSC-T cathodes was found to be up to 8 times higher than that on LSC cathodes at 530 °C and retained its stability. Sr-rich insulating particles formed at the surface of the annealed LSC and LSC-T films, but with significantly less coverage of such particles on the LSC-T. From this result, it appears that modification of the LSC surface with Ti reduces the segregation of the blocking Sr-rich particles at the surface, and a larger area on LSC surface (with a higher Sr doping level in the lattice) is available for the oxygen reduction reaction. The stabilization of the LSC surface through Ti-deposition can open a new route for designing surface modifications on perovskite oxide electrodes for high temperature electro- and thermo-chemical applications.


DNA copy number changes in childhood acute lymphoblastic leukemia.
Comparative genomic hybridization (CGH) allows the study of DNA copy number changes in a single hybridization from tumor DNA without any cell culture. Three reports of childhood acute lymphoblastic leukemia (ALL) studied by CGH have been published so far, with somewhat discrepant results. In the present study we performed CGH analysis on 36 patients with childhood ALL. The results were compared to those reported earlier on 157 cases. DNA was extracted from bone marrow specimens from 36 patients with childhood ALL. The tumor and reference DNAs were labeled with fluorescein-isothiocyanate conjugated dCTP and dUTP, and Texas red-conjugated dCTP and dUTP. The hybridizations were analyzed using the ISIS digital image analysis system. The most commonly gained chromosomes were X (42%), 4 (31%), 6 (31%), 10 (36%), 14 (28%) and 18 (33%), and the most common losses were at 9p22-pter (6%) and 12p13-pter (14%). The pattern of gains of DNA sequences was very similar in the four reports, but the 9p and 12p deletions were observed only in the present study and one previous report. Our review of the results of 193 patients studied so far shows that the success rate using CGH was close to 100%, whereas cytogenetic analysis failed to reveal any information in 21 patients (11%). Furthermore, in 69 (36%) out of 193 patients CGH gave additional information to the banding analysis. CGH should, therefore, be used to supplement standard cytogenetics in the analysis of childhood ALL patients.


[Evaluation of the global cardiovascular absolute risk: the Progetto CUORE individual score].
To identify individuals at high risk for cardiovascular disease, the function of the Progetto CUORE has been identified and the global cardiovascular risk score has been built using data from different cohorts enrolled in the North, Center and South of Italy between the 80s and the 90s, whose risk factors had been collected using standardised procedures. A follow-up with a median duration of 9.5 years for men and 8.0 years for women has been achieved. Age, systolic blood pressure, total cholesterol, HDL-cholesterol, smoking habit, diabetes and hypertension treatment have been included in the function; the first major coronary or cerebrovascular event was considered as endpoint; 10-year survival has been assessed both for men and women. Out of 20 647 people aged 35-69 years with no previous cardiovascular events, 971 major cardiovascular events (636 coronary and 335 cerebrovascular) have been identified and validated. Risk factors coefficients have been assessed using the Cox proportional hazard model separately for men and women. The individual score is easy to be applied by general practitioners and cardiologists in order to achieve a fast and objective evaluation of the absolute global cardiovascular risk in primary prevention.


Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials.
Several studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery. However, recent randomized controlled trials (RCTs) show potential detrimental effects. The objective of this systematic review is to examine the association between perioperative statin therapy and clinical outcomes in cardiac surgery patients. Electronic databases were searched up to 1 November 2016 for RCTs of preoperative statin therapy versus placebo or no treatment in adult cardiac surgery. Postoperative outcomes were acute kidney injury, atrial fibrillation, myocardial infarction, stroke, infections, and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using fixed-effects meta-analyses. Primary analysis was restricted to trials with low risk of bias according to Cochrane methodology, and sensitivity analyses examined whether the risk of bias of included studies was associated with different results. We performed trial sequential analysis (TSA) to test the strength of the results. We included data from 23 RCTs involving 5102 patients. Meta-analysis of trials with low risk of bias showed that statin therapy was associated with an increase in acute kidney injury (314 of 1318 (23.82%) with statins versus 262 of 1319 (19.86%) with placebo; OR 1.26 (95%CI 1.05 to 1.52); p = 0.01); these results were supported by TSA. No difference in postoperative atrial fibrillation, myocardial infarction, stroke, infections, or mortality was present. On sensitivity analysis, statin therapy was associated with a slight increase in hospital mortality. Meta-analysis including also trials with high or unclear risk of bias showed no beneficial effects of statin therapy on any postoperative outcomes. There is no evidence that statin therapy in the days prior to cardiac surgery is beneficial for patients' outcomes. Particularly, statins are not protective against postoperative atrial fibrillation, myocardial infarction, stroke, or infections. Statins are associated with a possible increased risk of acute kidney injury and a detrimental effect on hospital survival could not be excluded. Future RCTs should further evaluate the safety profile of this therapy in relation to patients' outcomes and assess the more appropriate time point for discontinuation of statins before cardiac surgery.


Clinical outcomes for "suspicious" category in thyroid fine-needle aspiration biopsy: Patient's sex and nodule size are possible predictors of malignancy.
Fine-needle aspiration (FNA) is recommended as an initial screening tool for the diagnosis of thyroid nodules. Approximately 10% of thyroid FNA diagnoses are "suspicious for neoplasm," warranting surgical resection. To examine the role of a patient's age, sex, size of nodule, and morphologic features as possible predictors of malignancy in patients with cytologic diagnosis of "suspicious for neoplasm." Cytopathology slides and reports of 402 consecutive thyroid FNAs from 2000-2005 interpreted as "suspicious" were reviewed. Of these, 180 cases that had subsequent surgical resection were selected. Of the 108 cases suspicious for follicular neoplasm on cytologic evaluation, histologic follow-up showed malignancy in 26 (24%). Of the 37 cases suspicious for Hürthle cell neoplasm, 15 (41%) had malignancy. Of the 35 cases suspicious for malignancy, 29 had malignant histologic diagnoses. Among cases with cytologic diagnoses of "suspicious for follicular or Hürthle cell neoplasm," the rate of malignancy in female patients was 22% as compared to 43% in male patients (P = .02). The rate of malignancy in nodules less than 2 cm was 19% compared to 47% in nodules measuring 2 cm or larger (P < .001). These differences were statistically significant. No statistically significant difference was noted between the age of the patient and the rate of benign versus malignant diagnosis. Malignant tumors were more frequent in male patients with a cytologic diagnosis of "suspicious for follicular or Hürthle cell neoplasm" than in female patients. Risk of malignancy was higher in nodules measuring 2 cm or larger. Age of the patient was not a predictor of malignancy.


Anticonvulsant use, bipolar disorder, and risk of fracture among older adults in the Veterans Health Administration.
To investigate the association between anticonvulsant use and fracture risk among older patients, including those with bipolar disorder (BD), an indicated condition for treatment with this class of medications. A prospective cohort study with 4.5 years of follow-up analyzed using both Cox proportional hazards modeling and propensity score techniques. National sample selected from Veterans Health Administration records. A representative sample of 67,387 Veterans Administration patients aged 50 years and older selected in fiscal year 2002 and followed until 2006, including 29,029 with a diagnosis of BD identified from the Veterans Administration National Psychosis Registry. Pharmacy records identified 19,635 patients who had ever used anticonvulsant medications. Incident fracture at any site and incident hip fracture indicated by administrative data. There were 4,367 fractures over the 4.5-year study period. Approximately two-thirds of patients with BD were prescribed anticonvulsants, and diagnosis of BD was associated with 20% increased risk of fracture independent of anticonvulsant use. Cumulative incidence of fracture was higher among anticonvulsant users relative to never users (35.7 per 1,000 versus 14.2 per 1,000 person-years). In fully adjusted models, anticonvulsant use was associated with over twofold greater risk of fracture (hazard ratio: 2.42, 95% confidence interval: 2.23-2.633). Current use was associated with the greater risk of fracture relative to former use. Duration of anticonvulsant use was significantly associated with increased fracture risk in a graded, nonlinear manner. Use of anticonvulsants is associated with increased risk of fracture among older patients with BD and among those without serious mental illness.


Analysis of myocardial motion based on velocity measurements with a black blood prepared segmented gradient-echo sequence: methodology and applications to normal volunteers and patients.
The paper describes a strategy for measuring and characterizing myocardial motion in terms of velocity parameters derived from measurements with a segmented black blood prepared phase contrast gradient echo sequence. The characteristic parameters are calculated by transforming the velocities measured on a pixel-by-pixel basis across the left ventricle from the laboratory frame of reference into a cylindrical coordinate system, in which the motion velocities within the short axis plane are represented in polar coordinates and which is located at the center of the myocardium and moving with it over the ECG cycle. First results in a study with 12 healthy volunteers gave highly consistent values for the radial (expansion/compression) as well as the rotational velocities. Except for one volunteer, motion at the R wave of the ECG starts with clockwise rotation, followed by contraction and expansion accompanied by counterclockwise rotation. First examinations of patients with global and focal disease demonstrate the potential to detect disturbances in the local as well as the overall motion patterns.


Smoking as a major risk factor for cervical cancer and pre-cancer: results from the EPIC cohort.
A total of 308,036 women were selected from the European Prospective Investigation into Cancer and Nutrition (EPIC) study to evaluate the association between tobacco smoking and the risk of cervical intraepithelial neoplasia of grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). At baseline, participants completed a questionnaire and provided blood samples. During a mean follow-up time of 9 years, 261 ICC cases and 804 CIN3/CIS cases were reported. In a nested case-control study, the baseline sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11, 16, 18, 31, 33, 35, 45, 52, 58, and antibodies against Chlamydia trachomatis (CT), and Human Herpes Virus 2 (HHV-2). Cervical samples were not available for HPV-DNA analysis in this study. Multivariate analyses were used to estimate associations between smoking and risk of CIN3/CIS and ICC in the cohort and the case-control studies. In the cohort analyses smoking status, duration and intensity showed a two-fold increased risk of CIN3/CIS and ICC, while time since quitting was associated with a two-fold reduced risk. In the nested case-control study, consistent associations were observed after adjustment for HPV, CT and HHV-2 serostatus, in both HPV seronegative and seropositive women. Results from this large prospective study confirm the role of tobacco smoking as an important risk factor for both CIN3/CIS and ICC, even after taking into account HPV exposure as determined by HPV serology. The strong beneficial effect of quitting smoking is an important finding that will further support public health policies for smoking cessation.


Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family--a sticky pursuit.
The agglutinin-like sequence (ALS) family of Candida albicans includes eight genes that encode large cell-surface glycoproteins. The high degree of sequence relatedness between the ALS genes and the tremendous allelic variability often present in the same C. albicans strain complicated definition and characterization of the gene family. The main hypothesis driving ALS family research is that the genes encode adhesins, primarily involved in host-pathogen interactions. Although adhesive function has been demonstrated for several Als proteins, the challenge of studying putative adhesins in a highly adhesive organism like C. albicans has led to varying ideas about how best to pursue such investigations, and results that are sometimes contradictory. Recent analysis of alsdelta/alsdelta strains suggested roles for Als proteins outside of adhesion to host surfaces, and a broader scope of Als protein function than commonly believed. The availability and use of experimental methodologies to study C. albicans at the genomic level, and the ALS family en masse, have advanced knowledge of these genes and emphasized their importance in C. albicans biology and pathogenesis.


Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques.
Although oxidized phosphatidylcholines (oxPCs) play critical roles in numerous pathological events, the type and production sites of endogenous oxPCs remain unknown because of the lack of structural information and dedicated analytical methods. Herein, a library of 465 oxPCs is constructed using high-resolution mass spectrometry-based non-targeted analytical methods and employed to detect 70 oxPCs in mice with acetaminophen-induced acute liver failure. We show that doubly oxygenated polyunsaturated fatty acid (PUFA)-PCs (PC PUFA;O2), containing epoxy and hydroxide groups, are generated in the early phase of liver injury. Hybridization with in-vivo 18O labeling and matrix-assisted laser desorption/ionization-tandem MS imaging reveals that PC PUFA;O2 are accumulated in cytochrome P450 2E1-expressing and glutathione-depleted hepatocytes, which are the major sites of liver injury. The developed library and visualization methodology should facilitate the characterization of specific lipid peroxidation events and enhance our understanding of their physiological and pathological significance in lipid peroxidation-related diseases.


A novel microfluidic microplate as the next generation assay platform for enzyme linked immunoassays (ELISA).
In this work we introduce a novel microfluidic enzyme linked immunoassays (ELISA) microplate as the next generation assay platform for unparalleled assay performances. A combination of microfluidic technology with standard SBS-configured 96-well microplate architecture, in the form of microfluidic microplate technology, allows for the improvement of ELISA workflows, conservation of samples and reagents, improved reaction kinetics, and the ability to improve the sensitivity of the assay by multiple analyte loading. This paper presents the design and characterization of the microfluidic microplate, and its application in ELISA.


Congenital Cytomegalovirus-Associated Sensorineural Hearing Loss in Children: Identification Following Universal Newborn Hearing Screening, Effect of Antiviral Treatment, and Long-Term Hearing Outcomes.
Congenital cytomegalovirus (cCMV) is the most common cause of nongenetic sensorineural hearing loss (SNHL) in children. We examined the longitudinal hearing outcomes of children with cCMV in relation to their newborn hearing screening findings, and their use of antiviral therapy. The study was based on a retrospective chart review using a database of pediatric patients (N = 445) seen at the University of Minnesota Lions clinic. Chart review identified infants with cCMV, and records were reviewed for information about universal newborn hearing screen (UNHS) results, the clinical course of SNHL, and the use of antiviral therapy. A total of 44 children were identified with cCMV. In this group, 33 (75%) had SNHL of varying degree and age at onset. Notably, 17 (39%) children passed UNHS bilaterally. Of those children, 6 (35%) ultimately acquired bilateral or unilateral SNHL, detected at a mean age of 20 months (median age, 12 months). Five out of 10 children (50%) that did not pass UNHS in one ear acquired late-onset hearing loss in the contralateral ear, identified at a mean age of 24 months (median age, 4 months). Eleven (25%) children passed UNHS bilaterally and continued to demonstrate normal hearing in both ears at their most recent follow-up visit at a mean age of 19 months (SD, 18 months). Of the 33 children with cCMV and SNHL, 18 (55%) received antiviral medication (ganciclovir and/or valganciclovir). While, on average, both treated and untreated ears experienced a progression of hearing loss over time, the group that received antiviral treatment experienced less overall hearing change compared with the untreated group (baseline-adjusted expected mean difference, -10.5 dB; 95% confidence interval, -28.1 to 7.2 dB). Among children with cCMV included in this study who passed UNHS in both ears, 35% demonstrated delayed-onset SNHL. Notably, of those children who referred unilaterally, 50% later demonstrated SNHL in the contralateral ear. These findings have implications for audiological monitoring, and potentially antiviral therapy, of children with cCMV. As implementation of universal cCMV screening moves forward, a key aspect of follow-up will be appropriate long-term audiologic monitoring.


Visualized discrimination of ATP from ADP and AMP through collapse of supramolecular gels.
A supramolecular gel was fabricated through mixing of a cationic gelator with methyl orange. The addition of ATP into the gel caused a distinct gel-collapse, whereas ADP and AMP preserved the gel formation. This observation provided a simple visualized way to discriminate ATP from AMP and ADP.


Estimating the incidence of subclinical infections with Legionella Pneumonia using data augmentation: analysis of an outbreak in The Netherlands.
Infections with Legionella bacteria can cause a potentially lethal form of pneumonia known as legionnaires' disease. In 1999 a major outbreak, causing 31 deaths, occurred among visitors and exhibitors of a consumer fair in The Netherlands. The epidemiology of subclinical infections is largely unknown, as there is no reliable method to diagnose such infections. To explore the incidence of subclinical infections, IgG and IgM antibody levels among exhibitors were compared to those among a representative sample of the Dutch population. As exhibitors were assumed to comprise both infected and uninfected individuals, their antibody levels were modelled as a mixture distribution. As infected individuals are expected to cluster around a point source, the spatial aspect of the spread of infections was taken into account. To estimate the distribution of antibody levels among infected individuals and to impute infection status among exhibitors, data augmentation was used. Subclinical infection appeared to be very common and its frequency declined with the distance from the putative source of the outbreak.


[Role of age in the interaction of tetracycline with the subcellular fractions of rat liver homogenate].
The effect of the rat age on the binding of tetracyclines to the subcellular fractions of liver homogenates was studied. The tetracyclines significantly lost their activity after the contact with the cell organoids. The level of the binding was lower in the newborn and old rats, the complex of tetracycline with mitochondria being less stable. The greater part of the antibiotic reduced its activity after washing of the organoids. The deposition of the antibiotics in the cells was the most pronounced in the pubertal animals.


geneBasis: an iterative approach for unsupervised selection of targeted gene panels from scRNA-seq.
scRNA-seq datasets are increasingly used to identify gene panels that can be probed using alternative technologies, such as spatial transcriptomics, where choosing the best subset of genes is vital. Existing methods are limited by a reliance on pre-existing cell type labels or by difficulties in identifying markers of rare cells. We introduce an iterative approach, geneBasis, for selecting an optimal gene panel, where each newly added gene captures the maximum distance between the true manifold and the manifold constructed using the currently selected gene panel. Our approach outperforms existing strategies and can resolve cell types and subtle cell state differences.


Multimodal dynamic imaging of therapeutic biomedical coatings in aqueous medium.
Drug release from therapeutic biomedical films such as drug-polymer composite coatings on drug eluting stents is a highly complex and poorly understood process. The dynamics of drug release and the evolution of surface morphology during release have direct impact on the performance of the device. This information is not easily accessible, and there have been few systematic studies to investigate drug release from biomedical coatings in real time. In this study, the complementary analytical techniques of confocal Raman microscopy, in-liquid atomic force microscopy, scanning electron microscopy, and high performance liquid chromatography were used to examine real-time mobilization and release of the drug rapamycin from polyisobutylene-block-polystyrene thin films, during immersion in buffered saline for 12 h. Each technique was found to have distinct limitations in either temporal or spatial resolution; in combination, however, the overlapping techniques provided a level of detail that is not available using any single approach.


The relation between price and daily consumption of cigarettes and bidis: findings from the Tobacco Control Policy Evaluation Wave 1 Survey.
In India, 14% of the population use smoked tobacco products. Increasing prices of these products is one of the measures to curb their consumption. This study analyzes "unit price" and "daily consumption" of cigarettes and bidis and investigates their relation with each other. A cross-sectional survey was conducted in four states of India (Bihar, West Bengal, Madhya Pradesh and Maharashtra) as a part of the International Tobacco Control Policy (TCP) Evaluation Project (the TCP India Project) during 2010-2011. Information was collected from adult (aged ≥ 15) daily exclusive smokers of cigarette/bidi regarding (a) last purchase (purchase in pack/loose, brand and price) and (b) daily consumption. Average unit price and daily consumption was calculated for different brands and states. Regression model was used to assess the impact of price on daily consumption. Bidis were much less expensive ([symbol in text]0.39) than cigarettes ([symbol in text]3.1). The daily consumption was higher (14) among bidi smokers than cigarette smokers (8). The prices and daily consumption of bidis ([symbol in text]0.33-0.43; 12-15) and cigarettes ([symbol in text]2.9-3.6; 5-9) varied across the four states. The unit prices of bidis and cigarettes did not influence their daily consumption. Smokers purchasing bidis in packs paid substantially less per unit and purchase of bidis and cigarettes in packs influenced their consumption positively. Cigarettes although more expensive than bidis, seem very cheap if compared internationally. Hence, prices of both cigarettes and bidis do not influence their consumption.


Opioid use potentiates the virulence of hospital-acquired infection, increases systemic bacterial dissemination and exacerbates gut dysbiosis in a murine model of Citrobacter rodentium infection.
Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It was recently demonstrated that morphine treatment results in a significant disruption in gut barrier function, leading to an increased translocation of gut commensal bacteria. Further studies have indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences that are associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital-acquired bacterial infection. Citrobacter rodentium is an ideal murine model of human infections with enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital-acquired bacterial infection. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) an increase in the expression of the virulence factors of C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of the C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and an increased risk of infections, suggesting that the overprescription of opioids may increase the susceptibility to hospital-acquired infection.


Akathisia: prevalence and associated dysphoria in an in-patient population with chronic schizophrenia.
In a sample of 120 long-stay in-patients who fulfilled DSM-III-R criteria for schizophrenia, chronic akathisia and pseudoakathisia were relatively common, with prevalence figures of 24% and 18%, respectively. Compared with patients without evidence of chronic akathisia, those patients with the condition were significantly younger, were receiving significantly higher doses of antipsychotic medication, and were more likely to be receiving a depot antipsychotic. Patients who experienced the characteristic inner restlessness and compulsion to move of akathisia also reported marked symptoms of dysphoria, namely tension, panic, irritability and impatience. The findings support the suggestion that dysphoric mood is an important feature of akathisia. Male patients appeared to be at an increased risk of pseudoakathisia. No significant relation was found between chronic akathisia and tardive dyskinesia, although there was a trend for trunk and limb dyskinesia to be commonest in patients with chronic akathisia while orofacial dyskinesia was most frequently observed in those with pseudoakathisia. Akathisia may mask the movements of tardive dyskinesia in the lower limb. There was no evidence that akathisia was associated with positive or negative symptoms of schizophrenia nor with depression.


Methods of the National Check Bus Project.
Prevention at the worksite is considered increasingly important. This paper describes the methods used in a nationwide prevention campaign performed at a large Swiss bank and a Swiss industrial company. The aim of this project was to encourage general health awareness among company employees. We also aimed to provide the companies with general health analyses of their staff as a basis for future health promotion. Furthermore, new screening methods were evaluated in the field of research. Participation in the programme was voluntary and free of charge. The programme targeted all 25,243 employees of the two companies in all regions of Switzerland. A mobile unit was available on site. The programme included a written health questionnaire and medical examinations (e.g., blood pressure, blood tests, ultrasound of the common carotid artery, osteodensitometry, examinations of the eye, etc). Analysis of individual test results, information brochures, and a telephone information service were also provided. Based on the data of the individuals, the "health status" of the employees of the two companies was analysed. The companies did not have access to the data of the individuals. The programme ran from August 1996 to August 1998. With a total of 10,321 persons taking part in the project, the participation rate was 41%. For the different examinations offered, patterns of participation were identifiable that varied with age, hierarchical status within the concern, body mass index, and number of physical complaints of the employee. Some of the variables showed the same trend for different tests, while others showed opposite trends. Participation in worksite health promotion programmes is dependent on a complex system of individual and structural variables that need to be considered when planning worksite health promotion programmes. Consideration of specific target population characteristics, including motivations and incentives as well as structural constraints is likely to improve participation rates in worksite health promotion programmes among employees.


CRTAM Protects Against Intestinal Dysbiosis During Pathogenic Parasitic Infection by Enabling Th17 Maturation.
The gastrointestinal tract hosts the largest collection of commensal microbes in the body. Infections at this site can cause significant perturbations in the microbiota, known as dysbiosis, that facilitate the expansion of pathobionts, and can elicit inappropriate immune responses that impair the intestinal barrier function. Dysbiosis typically occurs during intestinal infection with Toxoplasma gondii. Host resistance to T. gondii depends on a potent Th1 response. In addition, a Th17 response is also elicited. How Th17 cells contribute to the host response to T. gondii remains unclear. Here we show that class I-restricted T cell-associated molecule (CRTAM) expression on T cells is required for an optimal IL-17 production during T. gondii infection. Moreover, that the lack of IL-17, results in increased immunopathology caused by an impaired antimicrobial peptide production and bacterial translocation from the intestinal lumen to the mesenteric lymph nodes and spleen.


Tobacco sales to underage buyers in France: findings from a mystery shopping study.
In 2017, one in four French 17-year-olds was a daily smoker, even though France prohibited the sale of tobacco to under-18 minors in 2009. This research aims to evaluate the retail violation rate for sale to minors (RVRms) and the associated factors. The study design used is observational mystery shopping study. We conducted a mystery shopping study enlisting 12-year-old and 17-year-old youths in a representative sample of 527 tobacco outlets during three weeks in spring 2019. Multinomial Logit and Probit regressions were estimated on the data collected. The law is not respected. Two of three sellers (65.2%) were willing to make an illegal sale to a 17-year-old minor, and almost one in 12 (8.1%) were willing to sell to a 12-year-old child attempting to buy tobacco. Illegal sales were more likely to be made by male sellers, retailing in big cities, when there were no in-shop queues, and to 17-year-old females. The absence of the mandatory enforcement poster flagging up the ban on the sale of tobacco to minors appears to be a strong factor associated with RVRm. These findings show that progress needs to be made to better enforce tobacco control legislation to help decrease underage smoking in France. Rate of compliance with the law could be improved by stronger enforcement measures and tougher sanctions, but also by training and the provision of age-verification tools for sellers, as demonstrated by experiments in other countries.


Biodegradability of inhaled organic particles in patients with chronic bronchitis.
2 h after the inhalation of monodispersed 99mTc-labeled autologous spherocytes and of commercial human albumin microspheres (HAM), 7 patients with chronic bronchitis underwent bronchofibroscopy. The fate of organic particles along the tracheobronchial tree was verified by scanning electron microscopy and the proteolytic activity (trypsin and PZ peptidase) in mucus samples was assessed. Significant proteolytic activity was detected in bronchial secretions. Thereafter in vitro digestion of labeled spherocytes and HAM was verified after exposure to increasing concentrations of trypsin. While in vitro a similar time-course of tryptic digestion of both particles was observed, in vivo spherocytes seem to be less vulnerable to enzymatic digestion. These findings add another unexpected variable, which may influence the reproducibility of radioaerosol lung mucociliary clearance measurements, and improve its standardization.


Environmental change, shifting distributions, and habitat conservation plans: A case study of the California gnatcatcher.
Many species have already experienced distributional shifts due to changing environmental conditions, and analyzing past shifts can help us to understand the influence of environmental stressors on a species as well as to analyze the effectiveness of conservation strategies. We aimed to (1) quantify regional habitat associations of the California gnatcatcher (Polioptila californica); (2) describe changes in environmental variables and gnatcatcher distributions through time; (3) identify environmental drivers associated with habitat suitability changes; and (4) relate habitat suitability changes through time to habitat conservation plans. Southern California's Western Riverside County (WRC), an approximately 4,675 km2 conservation planning area. We assessed environmental correlates of distributional shifts of the federally threatened California gnatcatcher (hereafter, gnatcatcher) using partitioned Mahalanobis D2 niche modeling for three time periods: 1980-1997, 1998-2003, and 2004-2012, corresponding to distinct periods in habitat conservation planning. Highly suitable gnatcatcher habitat was consistently warmer and drier and occurred at a lower elevation than less suitable habitat and consistently had more CSS, less agriculture, and less chaparral. However, its relationship to development changed among periods, mainly due to the rapid change in this variable. Likewise, other aspects of highly suitable habitat changed among time periods, which became cooler and higher in elevation. The gnatcatcher lost 11.7% and 40.6% of highly suitable habitat within WRC between 1980-1997 to 1998-2003, and 1998-2003 to 2004-2012, respectively. Unprotected landscapes lost relatively more suitable habitat (-64.3%) than protected landscapes (30.5%). Over the past four decades, suitable habitat loss within WRC, especially between the second and third time periods, was associated with temperature-related factors coupled with landscape development across coastal sage scrub habitat; however, development appears to be driving change more rapidly than climate change. Our study demonstrates the importance of providing protected lands for potential suitable habitat in future scenarios.


TNFA -308G>A and IL10 -1082A>G polymorphisms seem to be predictive biomarkers of chronic HCV infection.
Genetic changes may induce dysregulated cytokine production and affect the progression of the chronic disease caused by the hepacivirus C (HCV) because the balance of pro- and anti-inflammatory cytokines determines the outcome of infection. This study evaluated the TNFA -308G>A and IL10 -1082A>G polymorphisms in the susceptibility and progress of chronic hepatitis C. The study included 101 samples from patients with chronic hepatitis C and 300 samples from healthy donors. Polymorphisms were typed by real-time PCR and were analyzed for associations with histopathological parameters (according to METAVIR classification) and HCV viral load. The polymorphic genotype for the TNFA -308G>A variant was not present in the group of patients with chronic hepatitis C and its absence could be associated with protection against HCV infection (p = 0.0477). Patients with the polymorphic genotype of the IL10 -1082A>G polymorphism had higher HCV viral load than wild-type patients (p = 0.0428). Neither polymorphism was associated with different levels of necroinflammatory activity or fibrosis scores. Our results suggest the polymorphic genotype at TNFA -308G>A as protective against chronic HCV infection, and the polymorphic genotype at the IL10 -1082A>G variant associated with higher HCV viral load. Further studies must be performed in order to confirm these associations.


Health care professionals' attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.
Ovarian cancer is usually diagnosed at a late stage when outcomes are poor. Personalised ovarian cancer risk prediction, based on genetic and epidemiological information and risk stratified management in adult women could improve outcomes. Examining health care professionals' (HCP) attitudes to ovarian cancer risk stratified management, willingness to support women, self-efficacy (belief in one's own ability to successfully complete a task), and knowledge about ovarian cancer will help identify training needs in anticipation of personalised ovarian cancer risk prediction being introduced. An anonymous survey was distributed online to HCPs via relevant professional organisations in the UK. Kruskal-Wallis tests and pairwise comparisons were used to compare knowledge and self-efficacy scores between different types of HCPs, and attitudes toward population-based genetic testing and risk stratified management were described. Content analysis was undertaken of free text responses concerning HCPs willingness to discuss risk management options with women. One hundred forty-six eligible HCPs completed the survey: oncologists (31%); genetics clinicians (30%); general practitioners (22%); gynaecologists (10%); nurses (4%); and 'others'. Scores for knowledge of ovarian cancer and genetics, and self-efficacy in conducting a cancer risk consultation were generally high but significantly lower for general practitioners compared to genetics clinicians, oncologists, and gynaecologists. Support for population-based genetic testing was not high (<50%). Attitudes towards ovarian cancer risk stratification were mixed, although the majority of participants indicated a willingness to discuss management options with patients. Larger samples are required to investigate attitudes to population-based genetic testing for ovarian cancer risk and to establish why some HCPs are hesitant to offer testing to all adult female patients. If ovarian cancer risk assessment using genetic testing and non-genetic information including epidemiological information is rolled out on a population basis, training will be needed for HCPs in primary care to enable them to provide appropriate support to women at each stage of the process.


Single-shot proteomics using capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry with production of more than 1250 Escherichia coli peptide identifications in a 50 min separation.
Capillary zone electrophoresis (CZE)-electrospray ionization-tandem mass spectrometry (ESI-MS/MS) was optimized and applied for analysis of 1-100 ng Escherichia coli protein digests in a single run (single-shot analysis). The system employed an electrokinetically pumped nanospray interface, a coated capillary, and stacking conditions for sample injection. More than 1 250 peptides were identified by optimized single-shot CZE-ESI-MS/MS with 100 ng digest loaded and 50 min analysis time. When 10 ng and 1 ng digests were loaded, about 1 000 and 600 peptides were identified in a single-shot analysis, respectively. Compared with single-shot ultraperformance liquid chromatography (UPLC)-ESI-MS/MS, CZE-ESI-MS/MS produced fewer peptide IDs (1 377 ± 128 vs 1 875 ± 32) for large sample loading amounts (100 ng) with the same mass spectrometer time (50 min). However, when the loaded digest was mass limited (1 ng), CZE-ESI-MS/MS generated many more peptide identifications than UPLC-ESI-MS/MS (627 ± 38 vs 342 ± 113). In addition, CZE-ESI-MS/MS and UPLC-ESI -MS/MS provided complementary peptide level identifications. These results suggest that CZE-ESI-MS/MS may be useful for large-scale, comprehensive, and confident proteomics analysis.


Colonic Diverticulitis Complicated by Stenosis Causing Bowel Obstruction.
Colonic diverticulitis is one of the most common gastrointestinal diseases. There are several complications in colonic diverticulitis, such as stenosis, perforation, and abscess. Stenosis is a rare complication and can cause bowel obstruction. We report a case of colonic diverticulitis complicated by stenosis causing bowel obstruction. A 66-year-old Japanese man was referred to our hospital for abdominal pain. Computed tomography (CT) scans showed the presence of diverticula, concentric wall thickening, and pericolic fat stranding in the descending colon. He was diagnosed with descending colon diverticulitis. His abdominal pain improved with fasting and intravenous antibiotics. However, after three months, diverticulitis complicated by stenosis occurred in the descending colon. The stenosis was severe and was treated with left hemicolectomy. Histologic examination revealed diverticula, chronic inflammation, and fibrosis in the stenosis, with no malignancy. Stenosis caused by colonic diverticulitis can cause bowel obstruction. Conservative treatment may lead to recurrence, and surgical treatment is preferable.


Heterozygosities of 735 microsatellite markers and background linkage disequilibrium in the Korean population.
Suitability of a specific population for linkage disequilibrium mapping studies of complex traits may be assessed by investigating the background linkage disequilibrium (BLD). We are unaware of studies for quantifying the degree of BLD in the Korean population, although the population may be a good candidate for mapping of complex trait genes through whole-genome association studies. It is useful to investigate the properties of genetic isolates in East Asia and to compare them to genetic isolates in Europe. We analyzed the extent of BLD in the Korean population using 735 microsatellite markers and compared the results with the Icelander population, which is one of the European expanded genetic isolates. The Korean population exhibited a level of BLD comparable with the Icelander population. The inference of population structure using the model with admixture showed that each individual has allele copies originating from K populations in equal proportions. Therefore, we believe that factors other than genetic distance, such as recent admixture, have not contributed to the level of BLD. Our results showed that the Korean population, which is an expanded population with no evidence of admixture, has a BLD level comparable with the Icelander population. Therefore, the Korean population can be used for fine mapping of either complex traits or monogenic diseases.


Expression of TNFα Receptors on Immunocompetent Cells Is Increased in Atopic Dermatitis.
Expression levels of cytokine and growth factor receptors have been found to be important in the regulation of their action. Tumor necrosis factor-α (TNFα) is actively involved in inflammation processes in atopic dermatitis (AD), but the role of TNFα membrane receptors (TNFR) and their regulatory function in AD remains unclear. We aimed to determine the associations of parameters of TNFRα expression on immunocompetent cells with disease severity before and after therapy in AD patients. TNFRα expression on T cells, B cells, and monocytes was evaluated by flow cytometry. To determine receptor numbers on the cells, Quantibrite PE beads were used. The content of soluble mediators was evaluated by ELISA. To reveal linear relationships between the index scoring AD (SCORAD) and the studied parameters, multiple linear regression model building was used. TNFR1 and TNFR2 expression in lymphocyte and monocyte populations of AD patients was higher than in healthy individuals (HI). At the same time an increased percentage of positive cells was not associated with high receptor density, and vice versa. Serum content of TNFα, both soluble receptors, the number of TNFR2/T cells, and the percentage of TNFR2+ monocytes were found to be strongly associated with the SCORAD index. AD patients had increased TNFR expression on immune cells. Changes in the parameters of TNFRα expression compared to HI were associated with the disease severity index SCORAD.


Lack of the CD8+ cell anti-HIV factor in CD8+ cell granules.
In HIV infection, CD8+ cells show cytotoxic and noncytotoxic anti-HIV activity. The latter function is mediated, at least in part, by a secreted antiviral protein, the CD8+ cell antiviral factor (CAF). Because antiviral effector molecules, such as perforin and granzymes, reside in the exocytic granules of CD8+ T cells, we examined the possibility that granules contain CAF-like activity. CD8+ cells from HIV-infected individuals showing strong CAF-mediated antiviral activity were induced to release their granule constituents into culture media. Within 1 hour of stimulation, high levels of granzyme B (a primary granule constituent) were found in the culture fluids of previously activated CD8+ cells. The same culture fluids contained no or very low amounts of CAF activity, as measured with HIV-infected CD4+ cells. Maximal levels of CAF activity were not observed until 5 or 7 days after stimulation, consistent with typical CAF production kinetics. In addition, extracts of granules purified from antiviral CD8+ cells did not show any CAF activity, whereas the cytoplasmic fraction of these cells showed substantial levels of antiviral activity. These findings suggest that CAF does not reside at appreciable levels in the exocytic granules of antiviral CD8+ T cells.


Fluoroquinolone antibiotics in a hospital sewage line; occurrence, distribution and impact on bacterial resistance.
In hospital sewage lines, human faecal bacteria are exposed to antibiotics, posing a risk for selection of antibiotic resistant microorganisms. We constructed a system for continuous sampling in a hospital sewage line that allowed us to study longitudinal establishment of bacteria, concentrations of antibiotics, and selection of bacterial resistance in waste water, sediment and biofilm. The focus in this study was on fluoroquinolones, a widely used group of antibiotics with increasing resistance problems. We found low levels of ciprofloxacin and ofloxacin in waste water but high concentrations in sediment. Despite the high levels of fluoroquinolones bound to sediment, we did not find any development of resistance against fluoroquinolones in Enterobacteriacae spp. and faecal enterococci isolated from sediment.


Modification of tissue-factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells.
Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations. In unperturbed human vascular endothelial cells, tissue factor mRNA and expression of the functional protein were undetectable and were not induced by 10-12 days of exposure to 30 mM glucose. In thrombin-stimulated cultures, tissue-factor expression was related inversely to cellular density, with confluent cultures producing (per 10(5) cells) half the amount of tissue factor measured in sparse cultures. Cells exposed to high glucose and studied when cell number and thymidine incorporation were identical to control cells manifested increased tissue-factor mRNA level and functional protein production in response to thrombin (P = .002). This effect was not attributable to hypertonicity and was not observed after short exposure to high glucose. In contrast, the tissue-factor response to interleukin 1, a modulator of endothelial function in the context of host defense, was decreased in cells cultured in high glucose (P = .04). These findings indicate that exposure to high glucose can alter tissue-factor gene expression in perturbed vascular endothelium. The reciprocal effects of high glucose on the tissue-factor response to thrombin and interleukin 1 points to different pathways of tissue-factor stimulation by the two agents and suggests functional consequences pertinent to the increased thrombin activity and compromised host-defense mechanisms observed in diabetes.


Tabrizicola piscis sp. nov., isolated from the intestinal tract of a Korean indigenous freshwater fish, Acheilognathus koreensis.
A novel Gram-negative, obligately aerobic, rod-shaped and non-motile bacterium, designated strain K13M18T, was isolated from the intestinal tract of a Korean indigenous fish, oily bitterling (Acheilognathus koreensis). Strain K13M18T formed creamy-pink colonies on a marine agar plate. Results of phylogenetic analysis based on the 16S rRNA gene sequence similarity indicated that strain K13M18T was most closely related to Tabrizicola sediminis DRYC-M-16T, sharing 97.62 % similarity with that strain. Strain K13M18T belonged to the genus Tabrizicola, which formed a cluster with Tabrizicola aquatica RCRI19T, Tabrizicola fusiformis SY72T, Tabrizicola sediminis DRYC-M-16T and Tabrizicola alkalilacus DJCT in a phylogenetic tree based on the 16S rRNA gene sequences. Strain K13M18T grown optimally in 0 % (w/v) NaCl, at pH 7 and 30 °C, in a marine broth medium. The predominant cellular fatty acids were C18 : 1 ω7c and C18 : 1 ω6c. The major respiratory isoprenoid quinone was ubiquinone Q-10. Polar lipids of strain K13M18T contained phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, diphosphatidylglycerol, six unidentified aminophospholipids, one unidentified aminolipid and an unidentified lipid. Based on genome sequencing, the DNA G+C content of strain K13M18T was 64.08 mol %, with an average nucleotide identity value, calculated by a comparative genomic analysis of strains K13M18T and T. sediminis DRYC-M-16T, of 74.82 %. Based on the phylogenetic, genotypic, and phenotypic information, strain K13M18T is proposed to be a novel species of the genus Tabrizicola. The type strain is K13M18T (=KCTC 62659T=JCM 33230T).


Genomic Diagnosis of Rare Pediatric Disease in the United Kingdom and Ireland.
Pediatric disorders include a range of highly penetrant, genetically heterogeneous conditions amenable to genomewide diagnostic approaches. Finding a molecular diagnosis is challenging but can have profound lifelong benefits. We conducted a large-scale sequencing study involving more than 13,500 families with probands with severe, probably monogenic, difficult-to-diagnose developmental disorders from 24 regional genetics services in the United Kingdom and Ireland. Standardized phenotypic data were collected, and exome sequencing and microarray analyses were performed to investigate novel genetic causes. We developed an iterative variant analysis pipeline and reported candidate variants to clinical teams for validation and diagnostic interpretation to inform communication with families. Multiple regression analyses were performed to evaluate factors affecting the probability of diagnosis. A total of 13,449 probands were included in the analyses. On average, we reported 1.0 candidate variant per parent-offspring trio and 2.5 variants per singleton proband. Using clinical and computational approaches to variant classification, we made a diagnosis in approximately 41% of probands (5502 of 13,449). Of 3599 probands in trios who received a diagnosis by clinical assertion, approximately 76% had a pathogenic de novo variant. Another 22% of probands (2997 of 13,449) had variants of uncertain significance in genes that were strongly linked to monogenic developmental disorders. Recruitment in a parent-offspring trio had the largest effect on the probability of diagnosis (odds ratio, 4.70; 95% confidence interval [CI], 4.16 to 5.31). Probands were less likely to receive a diagnosis if they were born extremely prematurely (i.e., 22 to 27 weeks' gestation; odds ratio, 0.39; 95% CI, 0.22 to 0.68), had in utero exposure to antiepileptic medications (odds ratio, 0.44; 95% CI, 0.29 to 0.67), had mothers with diabetes (odds ratio, 0.52; 95% CI, 0.41 to 0.67), or were of African ancestry (odds ratio, 0.51; 95% CI, 0.31 to 0.78). Among probands with severe, probably monogenic, difficult-to-diagnose developmental disorders, multimodal analysis of genomewide data had good diagnostic power, even after previous attempts at diagnosis. (Funded by the Health Innovation Challenge Fund and Wellcome Sanger Institute.).


Modelling of anisotropic growth in biological tissues. A new approach and computational aspects.
In this contribution, we develop a theoretical and computational framework for anisotropic growth phenomena. As a key idea of the proposed phenomenological approach, a fibre or rather structural tensor is introduced, which allows the description of transversely isotropic material behaviour. Based on this additional argument, anisotropic growth is modelled via appropriate evolution equations for the fibre while volumetric remodelling is realised by an evolution of the referential density. Both the strength of the fibre as well as the density follow Wolff-type laws. We however elaborate on two different approaches for the evolution of the fibre direction, namely an alignment with respect to strain or with respect to stress. One of the main benefits of the developed framework is therefore the opportunity to address the evolutions of the fibre strength and the fibre direction separately. It is then straightforward to set up appropriate integration algorithms such that the developed framework fits nicely into common, finite element schemes. Finally, several numerical examples underline the applicability of the proposed formulation.


2014 reports of the Regional Associations.
Includes the 2014 reports of the following Regional Associations: Eastern Psychological Association; Midwestern Psychological Association; New England Psychological Association; Rocky Mountain Psychological Association; Southeastern Psychological Association; Southwestern Psychological Association; Western Psychological Association; and the Southern Society for Philosophy and Psychology. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


Coverage and care consequences for families in which children have mixed eligibility for public insurance.
Public health insurance for low-income children in the United States is primarily available through Medicaid and the Children's Health Insurance Program (CHIP). Mixed eligibility occurs when there is a mix of either "Medicaid- and CHIP-eligible" children or a mix of "eligible (for public insurance) and ineligible (for public insurance)" children in the family. We used data from the Medical Expenditure Panel Survey (MEPS) Household Component for 2001-12 to examine insurance coverage, access to care, and health care use for eligible children in families with mixed-eligible siblings compared to those in families where all siblings were eligible for one program. We found that mixed eligibility has a significant dampening effect for eligible children in families with a mix of eligible and ineligible siblings. These children were more likely to be uninsured and less likely to have a usual source of care, less likely to have any preventive dental or well-child visits during the year, and less likely to fully adhere to recommended preventive dental and well-child visits than eligible children with all-Medicaid- or all-CHIP-eligible siblings. We found no significant impact for eligible children living in Medicaid-CHIP-mixed families.


Peptide inhibitors of viral assembly: a novel route to broad-spectrum antivirals.
We investigated the potential of small peptide segments to function as broad-spectrum antiviral drug leads. We extracted the α-helical peptide segments that share common secondary-structure environments in the capsid protein-protein interfaces of three unrelated virus classes (PRD1-like, HK97-like, and BTV-like) that encompass different levels of pathogenicity to humans, animals, and plants. The potential for the binding of these peptides to the individual capsid proteins was then investigated using blind docking simulations. Most of the extracted α-helical peptides were found to interact favorably with one or more of the protein-protein interfaces within the capsid in all three classes of virus. Moreover, binding of these peptides to the interface regions was found to block one or more of the putative "hot spot" regions on the protein interface, thereby providing the potential to disrupt virus capsid assembly via competitive interaction with other capsid proteins. In particular, binding of the GDFNALSN peptide was found to block interface "hot spot" regions in most of the viruses, providing a potential lead for broad-spectrum antiviral drug therapy.


Quality of Life and Sexual Distress in Women With Erosive Vulvovaginal Lichen Planus.
Erosive vulvovaginal lichen planus (EVLP) is a chronic and painful genital dermatosis. Little is published about its impact on quality of life. This study aimed to evaluate quality of life and sexual function in women with EVLP. Women with genital dermatoses were surveyed using the Dermatology Life Quality Index (DLQI) and Hospital Depression and Anxiety Scales. A subgroup completed the Female Sexual Distress Scale and Female Sexual Function Index subscales. Patient characteristics including age, diagnosis, and current treatment were recorded. Results from women with EVLP were compared with other diagnoses. Data from 77 women who participated between March 2013 and March 2014 were analyzed. Of these, 17 had EVLP. Comparator groups included women with vulval lichen sclerosus (n = 48) and vulval dermatitis (n = 12). In women with EVLP, 59% reported at least moderate impact on quality of life; mean DLQI scores: EVLP, 7.18; lichen sclerosus, 3.79; dermatitis, 8.67; p = .008. Overall, scores suggested depression in 14% and anxiety in 16% of participants. Sexual distress scores 11 or higher were recorded by 69% of women with EVLP, 63% of women with lichen sclerosus, and 56% of women with dermatitis. In those completing all sections of the survey (n = 40), DLQI was significantly correlated with depression (p = .004), sexual distress (p = .001), and sexual satisfaction (p = .01). Sixty-nine percent of women with EVLP reported sexual distress. Women with EVLP reported lesser quality of life than those with lichen sclerosus. Quality of life, anxiety and depression, sexual distress, and sexual function were all related in these participants.


Genetic variations in peroxisome proliferator-activated receptor gamma expression affect blood pressure.
Metabolic syndrome, a clustering of conditions including obesity, insulin resistance, and hypertension, is a risk factor for cardiovascular morbidity and mortality. Because peroxisome proliferator-activated receptor gamma (PPARgamma) regulates adipocyte differentiation and lipid metabolism and is the molecular target of a class of insulin sensitizers, genetic variants that alter Pparg gene expression are potential contributors to the metabolic syndrome. To test this possibility, we generated mice having 182% of the normal steady-state level of PPARgamma mRNA by replacing the 3'-UTR of the natural Pparg gene with that of the beta-globin gene, thereby stabilizing the Pparg transcripts. This increase in PPARgamma mRNA level had no apparent consequences in various physiological parameters, except that the mice repeatedly showed a trend toward lower blood pressures (by about 3 mm Hg) than their WT littermates. In contrast, the opposite trend, toward increased blood pressure, was observed in mice with genetically reduced levels of PPARgamma mRNA as a consequence of insertion of an allele with an mRNA-destabilizing sequence into the endogenous 3'-UTR of the Pparg gene. By combining 12 sets of blood pressure measurements in more than 350 mutant mice having PPARgamma expression levels varying from 28% to 182% and more than 280 WT littermates, we show that a 2-fold genetic increase (or decrease) in PPARgamma expression levels decreases (or increases) blood pressure by about 2.8 mm Hg. Thus, our experiments demonstrate that quantitative variants causing decreased Pparg expression are a potential causative risk factor for essential hypertension.


Tumor induction in BALB/c mice after fractionated or protracted exposures to fission-spectrum neutrons.
This study has examined the effect of dose rate or fractionation on the carcinogenic effects of fission neutrons with emphasis on the dose range below 50 rad. The induction of lung adenocarcinomas, mammary adenocarcinomas, and ovarian tumors in female BALB/c mice was examined after whole-body neutron irradiation delivered at a high dose rate as a single exposure, or delivered as two equal fractions separated by intervals of 24 hr or 30 days and compared these effects to those after neutron irradiation at low dose rates. The dose responses for ovarian tumorigenesis after the split-dose fractionation regimen were similar to that observed after single high-dose-rate neutron exposure. However, lowering the dose rate reduced the incidence over the dose range of 0-50 rad. For lung and mammary tumors the results were more complex. These data suggest that fractionation and dose-rate effects are different for different tumor types presumably because of the different mechanisms of tumorigenesis that may be involved.


Management of colorectal cancer in the era of COVID-19: Challenges and suggestions.
The Coronavirus (COVID-19) pandemic had a huge impact on all sectors around the world. In particular, the healthcare system has been subject to an enormous pressure that has surpassed its ability in many instances. Additionally, the pandemic has called for a review of our daily medical practices, including our approach to colorectal cancer management where treatment puts patients at high risk of virus exposure. Given their higher median age, patients are at an increased risk for severe symptoms and complications in cases of infection, especially in the setting of immunosuppression. Therefore, a review of the routine colorectal cancer practices is needed to minimize risk of exposure. Oncologists should weigh risk of exposure versus the patient's oncologic benefits when approaching management. In addition, treatment protocols should be modified to minimize hospital visits and admissions while maintaining the same treatment efficacy. In this review, we will focus on challenges that colorectal cancer patients face during the pandemic, while highlighting the priority in each case. We will also discuss the evidence for potential modifications to existing treatment plans that could reduce infectious exposure without compromising care. Finally, we will discuss the impact of the socio-economic difficulties faced by Lebanese patients due to a poor economy toppled by an unexpected pandemic.


[Experimental paratuberculosis: pathogenicity of mycobactin-dependent mycobacteria strains to calves].
The pathogenicity for calves of two strains of wood-pigeon mycobacteria isolated in our laboratory, one strain isolated in the United Kingdom, one strain isolated from a Roe-deer in Denmark and three strains of M. paratuberculosis, were compared. Seven groups of four 3 to 4 week-old calves were infected by the intravenous route using 10(6) to 10(9) viable units. They were slaughtered one year after the exposure or earlier if their state required it. The macroscopic and microscopic lesions and cultures from the mesenteric lymph nodes, ileon and caecum were studied. At necropsy, the post-mortem findings were hardly significant. However, the histopathological studies showed lesions identical to the classical aspects of paratuberculosis in cattle, both in animals inoculated with M. paratuberculosis and those inoculated with wood-pigeon mycobacteria. The isolation of the bacteria showed that all animals were infected. The experimental infection was able to reproduce a disease resembling paratuberculosis with M. paratuberculosis (except the strain 2103) and with wood-pigeon mycobacteria, but it has not been able to distinguish the disease caused by M. paratuberculosis from the one caused by wood-pigeon mycobacteria.


Functional significance of ion channels during macropinosome resolution in immune cells.
Macropinocytosis is a unique type of endocytosis accompanied by membrane ruffle formation. Closure of membrane ruffles leads to the uptake of large volumes of fluid phase and, subsequently, the formation of large vacuoles termed macropinosomes. Immune cells, such as dendritic cells, T cells, and macrophages, endocytose the surrounding amino acids and pathogens via macropinocytosis either constitutively or in a stimulus-dependent fashion. This process is critical for cell migration, mammalian target of rapamycin complex 1 (mTORC1) activation, and antigen presentation. Large vacuoles are fragmented into tubules and smaller vesicles during the progression and maturation of macropinosomes in immune cells. This process is called "macropinosome resolution" and requires osmotically driven shrinkage of macropinosomes, which is controlled by ion channels present in them. The crenation of membranes on shrunken macropinosomes is recognized by curvature-sensing proteins and results in intracellular membrane trafficking. In this mini review, we highlight the recent progress in research on macropinosome resolution in macrophages, with a focus on ion channels (TPC1/2 for Na+ and TMEM206 for Cl-) that is required for macropinosome resolution. We also discuss the potential contribution of membrane lipids to this process.


Local anaesthetic block copolymer system undergoing phase transition on dilution with water.
The possibility of formulating a local anaesthetic system displaying in situ gelation on dilution with water, as well as its dependence on concentration of active ingredients and pH was investigated. For this purpose Lutrol F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in different ratios and investigated using crossed polarisers, small-angle X-ray diffraction, rheology, conductivity and NMR self-diffusion measurements. In particular, an isotropic phase of low viscosity turning into a high viscous hexagonal phase upon dilution with water was found. The increase in viscosity is only weakly dependent on temperature in the temperature range of 20-37 degrees C. The rheology and in vitro drug release of these systems were studied and the elastic modulus was found to be fairly independent of concentration of active ingredients and pH in the investigated region. The in vitro release of lidocaine and prilocaine was found to increase with increasing concentration of the active ingredients and with decreasing pH, the latter as a consequence of the pH-dependent ionisation of these substances. The behaviour of the system is promising from a pharmaceutical point of view, since the isotropic low-viscous phase can be injected into, e.g. a periodontal pocket where the presence of saliva will cause a temporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a result of longer application time or rinsing with water, the hexagonal phase is effectively dissolved through transformation to a water-rich micellar phase.


Having too little or too much time is linked to lower subjective well-being.
Many people living in modern society feel like they do not have enough time and are constantly searching for more. But is having limited discretionary time actually detrimental? And can there be downsides of having too much discretionary time? In two large-scale data sets spanning 35,375 Americans and two experiments, we explore the relationship between the amount of discretionary time individuals have and their subjective well-being. We find and internally replicate a negative quadratic relationship between discretionary time and subjective well-being. These results show that whereas having too little time is indeed linked to lower subjective well-being caused by stress, having more time does not continually translate to greater subjective well-being. Having an abundance of discretionary time is sometimes even linked to lower subjective well-being because of a lacking sense of productivity. In such cases, the negative effect of having too much discretionary time can be attenuated when people spend this time on productive activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Effects of protein deprivation on alpha1(I) and alpha1(III) collagen and its degrading system in rat skin.
Protein malnutrition affects the status of dermal collagen, the major structural protein in the skin. However, the molecular mechanism underlying the alteration of collagen fibers in the skin by protein deficiency remains unknown. In the present study, the effect of dietary protein deprivation on collagen metabolism was studied by analyzing the status of the synthesis and degradation of collagen in the dorsal skin of rats. Feeding on a protein-free diet for 8 days caused a dramatic decrease in both types I and III tropocollagen with a concomitant decrease in their mRNA levels, with type III collagen being more severely affected. The active form of collagenase was significantly decreased by protein deprivation, whereas the latent form was not affected. The mRNA levels of collagenase and its inhibitors (TIMP-1 and 2) were also decreased by protein deprivation. These results suggest that both the synthesis and degradation of types I and III collagen were affected by protein deficiency.


Time-dependent clinical results of rotating-platform total knee arthroplasty according to mechanical axis deviation.
We hypothesized that the low contact stress (LCS) posterior stabilization system in knees with ≤3° deviation of coronal alignment would provide more favorable clinical outcomes and survival rate over the course of time. A retrospective study was performed on 253 consecutive cases of primary total knee arthroplasty (TKA). Patients were classified according to the degree of deviation of coronal alignment on the initial postoperative radiograph as Group 1 (≤3° deviation) and Group 2 (>3° deviation). The clinical assessments were performed using the Knee Society score and Hospital for Special Surgery systems and Western Ontario and McMaster Universities index. The survival rate was 97.4% in Group 1 and 96.8% in Group 2. No statistically significant intergroup difference was observed in the clinical scores before surgery and since 1 year after surgery (p>0.05). However, a significant intergroup difference was noted between 6 months to 1 year after surgery (p<0.001). Less than 2 mm radiolucent lines were found more frequently in Group 2. Time-dependent improvement was noted within one year after TKA in both groups. Most of the expected improvements were achieved at 6 months after surgery in Group 1 and at 1 year after surgery in Group 2. The present study suggests that the LCS system yields time-dependent improvement regardless of coronal alignment deviation.


Differential expression of members of the annexin multigene family in Arabidopsis.
Although in most plant species no more than two annexin genes have been reported to date, seven annexin homologs have been identified in Arabidopsis, Annexin Arabidopsis 1-7 (AnnAt1--AnnAt7). This establishes that annexins can be a diverse, multigene protein family in a single plant species. Here we compare and analyze these seven annexin gene sequences and present the in situ RNA localization patterns of two of these genes, AnnAt1 and AnnAt2, during different stages of Arabidopsis development. Sequence analysis of AnnAt1--AnnAt7 reveals that they contain the characteristic four structural repeats including the more highly conserved 17-amino acid endonexin fold region found in vertebrate annexins. Alignment comparisons show that there are differences within the repeat regions that may have functional importance. To assess the relative level of expression in various tissues, reverse transcription-PCR was carried out using gene-specific primers for each of the Arabidopsis annexin genes. In addition, northern blot analysis using gene-specific probes indicates differences in AnnAt1 and AnnAt2 expression levels in different tissues. AnnAt1 is expressed in all tissues examined and is most abundant in stems, whereas AnnAt2 is expressed mainly in root tissue and to a lesser extent in stems and flowers. In situ RNA localization demonstrates that these two annexin genes display developmentally regulated tissue-specific and cell-specific expression patterns. These patterns are both distinct and overlapping. The developmental expression patterns for both annexins provide further support for the hypothesis that annexins are involved in the Golgi-mediated secretion of polysaccharides.


Giant Bullous Emphysema With Placental Transmogrification: A Case Report of a 14-Year-Old With Right Middle- and Lower-Lobe Involvement.
Giant bullous emphysema with placental transmogrification is an extremely rare entity, with 30 previously reported cases. Of these reported cases, it is typically identified with varied clinical and radiological impressions, presents in young adulthood to elderly, is always unilateral, and usually involves just one lobe. Despite the unknown pathogenesis, this diagnosis carries an excellent prognosis and is curative with complete resection. The pulmonary placental transmogrification is histologically indistinguishable from placental origin. Although not necessary to utilize because of the male predominance and no reported association, immunohistochemical stains can be used to prove lung origin. We report an extremely rare case of 2-lobe involvement of giant bullous emphysema with placental transmogrification in a boy 14 years of age, who is the youngest diagnosed patient with this lung abnormality.


Management of a Combined Femoral Head and Neck Fracture: A Case Report.
A 19-year-old woman sustained a traumatic hip injury with dislocation and fractures of the femoral head and neck. A modified Gibson approach with trochanteric flip osteotomy was performed. We describe the management technique used to reduce and stabilize the femoral head and neck fractures during surgical hip dislocation. The stabilization of the femoral head to the femoral neck was performed primarily in a retrograde manner. Retrograde fixation of combined femoral head and neck fractures can be safely performed during surgical hip dislocation with satisfactory results.


General and dietary oxalate restriction advice reduces urinary oxalate in the stone clinic setting.
Idiopathic hyperoxaluria is a risk factor for developing calcium oxalate nephrolithiasis. Dietary oxalate's effect on urinary oxalate is not well studied. The aim of this study is to assess the effect of advice focused on reducing dietary oxalate in a cohort of idiopathic hyperoxaluric patients. Patients referred to the Groote Schuur Hospital Stone Clinic from 2015 to 2017 were considered eligible, if they were an idiopathic hyperoxaluric stone former, excreting > 40 mg/d of urinary oxalate on a pre-intervention 24-hour stone study urinalysis. Patients were asked to adhere to a diet sheet which included general stone prevention advice (low salt diet, increased fluid intake and moderate protein intake) and specific low oxalate diet advice. A post-intervention 24-hour urinalysis was performed at six weeks. Nineteen patients had hyperoxaluria (eight men and 11 women) with a mean age of 49 years (range 25-76 years). The mean BMI of the group was 28.4 kg/m2 (17.4-50). All patients had mean number of 1.9 range prior stone episodes (range 1-6 stone episodes). Fourteen (14/19) patients completed the study. The mean pre-dietary advice urinary oxalate was 53.2 mg/24 hours (n = 14), SD while the post-intervention was 29.6 mg/24 hours SD (p = 0.0002). Only 3/14 patients who completed the assessment failed to normalise their urinary oxalate on the diet. In the stone clinic setting, general advice of low salt diet, increased water intake, moderate protein intake and specific oxalate restriction can significantly reduce oxalate excretion in hyperoxaluric stone formers. Sustained reduction of oxalate excretion and longitudinal clinical benefit are worthy of study in larger cohorts.


Inhibiting Glycogen Synthase Kinase-3 Mitigates the Hematopoietic Acute Radiation Syndrome in a Sex- and Strain-dependent Manner in Mice.
The Radiation and Nuclear Countermeasures Program at the National Institute of Allergy and Infectious Diseases (NIAID) mandated that medical countermeasures for treating Acute Radiation Syndrome (ARS) must have efficacy when administered at least 24 h after radiation exposure. At this time point, many cells within key target tissues, such as the hematopoietic system and the gastrointestinal (GI) tract, will already be dead. Therefore, drugs that promote the regeneration of surviving cells may improve outcomes. The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) regulates stem and progenitor cell self-renewal and regeneration in the hematopoietic and GI compartments. We tested inhibition of GSK-3β by SB216763 24 h after total body irradiation (TBI) and sub-total body irradiation (SBI). Here, we show that subcutaneous administration of SB216763 promotes the regeneration of surviving hematopoietic stem/progenitor cells (HSPCs), including myeloid progenitor cells, and improves survival of C57Bl/6 male mice when administered 24 h after TBI. However, these results were not recapitulated in female C57Bl/6 animals, suggesting a sex difference in GSK-3β signaling in HSPCs. Subcutaneous administration of SB216763 in male mice stimulated activation of Sox2 transcription but failed to induce Sox2 transcription in female C57Bl/6 mice. Using TCF/lef-GFP reporter mice, we examined Wnt signaling in HSPCs of irradiated male and female mice treated with SB216763. GSK-3 inhibition elevated Wnt reporter activity in HSPCs isolated from male but not female mice. SB216763 did not mitigate hematopoietic ARS in males or females of a second strain of wild-type mice, C3H. In addition, administration of SB216763 did not mitigate hematopoietic ARS beyond the currently available standard approved therapy of ciprofloxacin and granulocyte-colony stimulating factor (G-CSF) in male C57Bl/6 mice. Further, SB216763 did not mitigate GI-ARS after SBI in C57Bl/6 male mice. The lack of efficacy in both sexes and multiple strains of mice indicate that SB216763 is not suitable for further drug development as a mitigator of ARS. Our studies demonstrate that activation of Wnt signaling in HSPCs promotes hematopoietic regeneration following radiation exposure, and targeting this pathway downstream of GSK-3β may mitigate ARS in a sex- and strain-independent manner.


Nerve stripper-assisted sural nerve harvest.
Sural nerve has the favorite length and size for nerve graft interposition. Here two techniques, that is, "stocking seam" and "stair-step" or "stepladder," have been used for harvesting sural nerve. The first technique results in an unsightly scar at the posterior calf, and the latter one takes a long time to perform and exert undue traction to the graft during harvesting. The purpose of this article is to describe our experience in harvesting the sural nerve by a nerve stripper. A nerve stripper was used for harvesting sural nerve in 35 adult patients (in 6 patients, sural harvesting was done bilaterally), 27 men and 8 women. Thirty-one sural nerve harvests were done by closed technique (i.e., harvesting of sural nerve only by two incisions, one in the posterior of the lateral malleolus and the other in popliteal fossa), in 8 others by limited open technique, and in 2 cases, there was early laceration of the sural nerve at the beginning of the study. The contralateral sural nerve was harvested in one patient and medial antebrachial nerve in another by open technique. The mean length of the retrieved sural nerve was 34.5 cm in the closed technique group and 35 cm in the limited open technique group. We detected advancing Tinel's sign in all nerve stripper-assisted sural nerve harvested group members in both the closed and limited open groups. Sural nerve harvesting by the nerve stripper is a reliable and simple technique, and it is applicable as a routine technique. Applying controlled rotatory movements of the nerve stripper instead of pushing can result in satisfactory harvesting of the sural nerve without early laceration.


Changes in family structure in early childhood in the Millennium Cohort Study.
This article develops a typology of family change over the first five years of children's lives using data from the Millennium Cohort Study. It examines the changes over time of parental living arrangements and describes a range of social, economic and well-being indicators. It shows that nearly three quarters of this sample of young children have not experienced changes in family structures. The most advantaged group appears to be children living with continuously married parents, followed by those who live with cohabiting parents who marry. Children who experienced changes in family structure are a diverse group. Coupled parents who separate suffer the largest drop in income over five years. Lone parents who partner gain the most income. However, their incomes are still much lower than continuously partnered parents. This article suggests that using static or overly simplified measures of family structure hides important variations in the experiences of children.


Microbial efflux systems and inhibitors: approaches to drug discovery and the challenge of clinical implementation.
Conventional antimicrobials are increasingly ineffective due to the emergence of multidrug-resistance among pathogenic microorganisms. The need to overcome these deficiencies has triggered exploration for novel and unconventional approaches to controlling microbial infections. Multidrug efflux systems (MES) have been a profound obstacle in the successful deployment of antimicrobials. The discovery of small molecule efflux system blockers has been an active and rapidly expanding research discipline. A major theme in this platform involves efflux pump inhibitors (EPIs) from natural sources. The discovery methodologies and the available number of natural EPI-chemotypes are increasing. Advances in our understanding of microbial physiology have shed light on a series of pathways and phenotypes where the role of efflux systems is pivotal. Complementing existing antimicrobial discovery platforms such as photodynamic therapy (PDT) with efflux inhibition is a subject under investigation. This core information is a stepping stone in the challenge of highlighting an effective drug development path for EPIs since the puzzle of clinical implementation remains unsolved. This review summarizes advances in the path of EPI discovery, discusses potential avenues of EPI implementation and development, and underlines the need for highly informative and comprehensive translational approaches.


A mutated PtsG, the glucose transporter, allows uptake of D-ribose.
Mutations arose from an Escherichia coli strain defective in the high (Rbs/ribose) and low (Als/allose and Xyl/xylose) affinity D-ribose transporters, which allow cells to grow on D-ribose. Genetic tagging and mapping of the mutations revealed that two loci in the E. coli linkage map are involved in creating a novel ribose transport mechanism. One mutation was found in ptsG, the glucose-specific transporter of phosphoenolpyruvate:carbohydrate phosphotransferase system and the other in mlc, recently reported to be involved in the regulation of ptsG. Five different mutations in ptsG were characterized, whose growth on D-ribose medium was about 80% that of the high affinity system (Rbs+). Two of them were found in the predicted periplasmic loops, whereas three others are in the transmembrane region. Ribose uptakes in the mutants, competitively inhibited by D-glucose, D-xylose, or D-allose, were much lower than that of the high affinity transporter but higher than those of the Als and Xyl systems. Further analyses of the mutants revealed that the rbsK (ribokinase) and rbsD (function unknown) genes are involved in the ribose transport through PtsG, indicating that the phosphorylation of ribose is not mediated by PtsG and that some unknown metabolic function mediated by RbsD is required. It was also found that D-xylose, another sugar not involved in phosphorylation, was efficiently transported through the wild-type or mutant PtsG in mlc-negative background. The efficiencies of xylose and glucose transports are variable in the PtsG mutants, depending on their locations, either in the periplasm or in the membrane. In an extreme case of the transmembrane change (I283T), xylose transport is virtually abolished, indicating that the residue is directly involved in determining sugar specificity. We propose that there are at least two domains for substrate specificity in PtsG with slightly altered recognition properties.


The loss of an electrostatic contact unique to AMPA receptor ligand binding domain 2 slows channel activation.
Ligand-gated ion channels undergo conformational changes that transfer the energy of agonist binding to channel opening. Within ionotropic glutamate receptor (iGluR) subunits, this process is initiated in their bilobate ligand binding domain (LBD) where agonist binding to lobe 1 favors closure of lobe 2 around the agonist and allows formation of interlobe hydrogen bonds. AMPA receptors (GluAs) differ from other iGluRs because glutamate binding causes an aspartate-serine peptide bond in a flexible part of lobe 2 to rotate 180° (flipped conformation), allowing these residues to form cross-cleft H-bonds with tyrosine and glycine in lobe 1. This aspartate also contacts the side chain of a lysine residue in the hydrophobic core of lobe 2 by a salt bridge. We investigated how the peptide flip and electrostatic contact (D655-K660) in GluA3 contribute to receptor function by examining pharmacological and structural properties with an antagonist (CNQX), a partial agonist (kainate), and two full agonists (glutamate and quisqualate) in the wildtype and two mutant receptors. Alanine substitution decreased the agonist potency of GluA3(i)-D655A and GluA3(i)-K660A receptor channels expressed in HEK293 cells and differentially affected agonist binding affinity for isolated LBDs without changing CNQX affinity. Correlations observed in the crystal structures of the mutant LBDs included the loss of the D655-K660 electrostatic contact, agonist-dependent differences in lobe 1 and lobe 2 closure, and unflipped D(A)655-S656 bonds. Glutamate-stimulated activation was slower for both mutants, suggesting that efficient energy transfer of agonist binding within the LBD of AMPA receptors requires an intact tether between the flexible peptide flip domain and the rigid hydrophobic core of lobe 2.


Anesthetic type and hospital outcomes after carotid endarterectomy from the Vascular Quality Initiative database.
Studies on the safety of carotid endarterectomy (CEA) under different anesthetic techniques are sometimes contradictory. The aim of this study was to compare real-world outcomes of CEA under general anesthesia (GA) vs regional or local anesthesia (RA/LA). A retrospective analysis of the Vascular Quality Initiative database (2003-2017) was performed. Primary outcomes included perioperative stroke, death, and myocardial infarction (MI) occurring during the hospital stay. Univariate and multivariate analyses were used. To minimize selection bias and to evaluate comparable groups, patients were matched on baseline variables using coarsened exact matching. Of 75,319 CEA cases, 6684 (8.9%) were performed under RA/LA. These patients were more likely to be older (median age, 72 vs 71 years) and male (62.5% vs 60.2%), with higher American Society of Anesthesiologists class (class 3-5, 94.2% vs 93.0%) than those undergoing CEA-GA (all P < .001). CEA-GA had higher crude rates of in-hospital cardiac outcomes including MI mainly diagnosed clinically or on electrocardiography (0.5% vs 0.2%; P = .01), dysrhythmia (1.6% vs 1.2%; P < .001), acute congestive heart failure (CHF; 0.5% vs 0.2%; P < .001), and hemodynamic instability (27.0% vs 20.0%; P < .001) compared with CEA-RA/LA. No difference in perioperative stroke or death was seen between the two groups. On multivariate analysis, CEA-GA was associated with twice the odds of in-hospital MI (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.59; P = .03), 4 times the odds of acute CHF (aOR, 3.92; 95% CI, 1.84-8.34; P < .001), and 1.5 times the odds of hemodynamic instability (aOR, 1.54; 95% CI, 1.44-1.66; P < .001). Patients undergoing CEA-GA had 1.8 times the odds of staying in the hospital for >1 day (aOR, 1.80; 95% CI, 1.67-1.93; P < .001). Coarsened exact matching confirmed our results. Risk factors associated with increased cardiac complications (MI and CHF) under GA included female gender, increased age, Medicaid insurance, history of smoking, medical comorbidities (such as hypertension, diabetes, coronary artery disease, and CHF), prior ipsilateral carotid intervention, and urgent/emergent procedures. Patients undergoing CEA under GA have higher odds of postoperative MI, acute CHF, and hemodynamic instability compared with those undergoing CEA under RA/LA. They are also more likely to stay in the hospital for >1 day. However, the overall risk of cardiac adverse events after CEA was low, which made the differences clinically irrelevant. The choice of anesthesia approach to CEA should be driven by the team's experience and the patient's risk factors and preference.


The influence of composite resin restorations and lining on radiographic diagnosis and decision-making: an in vitro investigation.
The objective of this study was to evaluate the influence of resin-based restorations on the interpretation of digital and conventional radiographic images and to correlate the proposed diagnosis with decision-making. Class II cavities were prepared in one of the proximal surfaces of extracted human molars. Teeth were divided into five groups (n = 10) according to the restoratives used: Natural Flow (NF) and Filtek Supreme (FS); Filtek Flow (FF) and FS; Tetric Flow (TF) and FS; Protect Liner F (PLF) and FS; and FS alone. Bitewing radiographs were taken using conventional and digital systems. Subjective analysis was performed for each surface: no restoration; restored teeth; or restored teeth with gap. Based on the given diagnosis, clinical conduct was then indicated. Material radiopacity was determined according to ISO 4049. A Fisher exact test evaluated the influence of the restoratives on the diagnosis. Means were compared using ANOVA and the Games-Howell test. A Friedman test was used to analyze the influence of the systems on the diagnosis, and a binomial test was used to analyze the association between the presence of gaps and the decision to replace the restoration (P = 0.05). For each system, TF+FS was significantly associated with a high percentage of correct diagnoses. The opposite was the case for PLF+FS, which differed from all other groups. Radiographic systems presented similar behaviors, except for NF+FS. Apart from PLF, adequate radiopacity was observed. Diagnosis was influenced by restorative materials, regardless of the radiographic system used. The low radiopacity of PLF led to a greater number of erroneous diagnoses. Moreover, the decision-making process was influenced strongly by the given diagnosis.


Alterations in DNA Damage Repair Genes in Primary Liver Cancer.
Alterations in DNA damage repair (DDR) genes produce therapeutic biomarkers. However, the characteristics and significance of DDR alterations remain undefined in primary liver cancer (PLC). Patients diagnosed with PLC were enrolled in the trial (PTHBC, NCT02715089). Tumors and matched blood samples from participants were collected for a targeted next-generation sequencing assay containing exons of 450 cancer-related genes, including 31 DDR genes. The OncoKB knowledge database was used to identify and classify actionable alterations, and therapeutic regimens were determined after discussion by a multidisciplinary tumor board. A total of 357 patients with PLC were enrolled, including 214 with hepatocellular carcinoma, 122 with ICC, and 21 with mixed hepatocellular-cholangiocarcinoma. A total of 92 (25.8%) patients had at least one DDR gene mutation, 15 of whom carried germline mutations. The most commonly altered DDR genes were ATM (5%) and BRCA1/2 (4.8%). The occurrence of DDR mutations was significantly correlated with a higher tumor mutation burden regardless of the PLC pathologic subtype. For DDR-mutated PLC, 26.1% (24/92) of patients possessed at least one actionable alteration, and the actionable frequency in DDR wild-type PLC was 18.9% (50/265). Eight patients with the BRCA mutation were treated by olaparib, and patients with BRCA2 germline truncation mutations showed an objective response. The landscape of DDR mutations and their association with genetic and clinicopathologic features demonstrated that patients with PLC with altered DDR genes may be rational candidates for precision oncology treatment.


The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.
Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb uses the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT), which induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential coenzyme NAD(+). Expression or injection of a noncatalytic TNT mutant showed no cytotoxicity in macrophages or in zebrafish zygotes, respectively, thus demonstrating that the NAD(+) glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a new NAD(+) glycohydrolase fold of TNT, the founding member of a toxin family widespread in pathogenic microorganisms.


Isolation of fungi from dung of wild herbivores for application in bioethanol production.
Producing biofuels such as ethanol from non-food plant material has the potential to meet transportation fuel requirements in many African countries without impacting directly on food security. The current shortcomings in biomass processing are inefficient fermentation of plant sugars, such as xylose, especially at high temperatures, lack of fermenting microbes that are able to resist inhibitors associated with pre-treated plant material and lack of effective lignocellulolytic enzymes for complete hydrolysis of plant polysaccharides. Due to the presence of residual partially degraded lignocellulose in the gut, the dung of herbivores can be considered as a natural source of pre-treated lignocellulose. A total of 101 fungi were isolated (36 yeast and 65 mould isolates). Six yeast isolates produced ethanol during growth on xylose while three were able to grow at 42°C. This is a desirable growth temperature as it is closer to that which is used during the cellulose hydrolysis process. From the yeast isolates, six isolates were able to tolerate 2g/L acetic acid and one tolerated 2g/L furfural in the growth media. These inhibitors are normally generated during the pre-treatment step. When grown on pre-treated thatch grass, Aspergillus species were dominant in secretion of endo-glucanase, xylanase and mannanase.


Computed tomographic and bronchoscopic diagnosis of Oslerus osleri infection in a dog.
A 16-month-old Sarplaninac Shepherd cross dog presented for a 1-month history of a productive cough that was unresponsive to an empirical 10-day course of cephalexin. Thoracic computed tomography (CT) showed multifocal, well-defined, smoothly marginated, soft tissue attenuating, minimally contrast enhancing nodular airway mural thickenings protruding into the airway lumen in the caudal trachea and principal bronchi. These nodules were also visualized on bronchoscopy, and cytology revealed parasitic larvae consistent with Oslerus osleri. The dog was treated with oral fenbendazole for 26 days. Clinical signs resolved within 3 weeks of treatment initiation and had not relapsed at 7-month follow-up.