Implementing Natural Image Quality Evaluator for Performance Indicator on Noise Artefacts Recovery in CT Scan.
The two most common evaluators for CT scan denoising are Peak Signal to Noise Ratio (PSNR) and Structural Similarity Index (SSIM). This paper offers an alternative evaluator by utilizing of Natural Image Quality Evaluator (NIQE) assessment to determine the performance of denoising work on noise artefact. The noise artefact was obtained during the cancer screening process and had a particular noise density pattern across the image. NIQE is one of the blind image assessments which rely on the measurable deviation of image patch as a reference; it can determine the improved quality of denoising image. Due to the method of comparison in NIQE, the two parameters: patch size and sharpness threshold, will play an essential part in getting the score compared with the result from the other evaluators (PSNR and SSIM).


Survivorship analysis of cemented high modulus total hip arthroplasty.
Ninety-four high-modulus total hip arthroplasties (THAs) were performed from 1977 to 1982 using the Computer Assist Design (CAD) and HD-2 prostheses. Eighty-six hips were followed for an average of 6.7 years. The cement gun was used throughout the study period, and distal bone or cement plug use was begun in 1979. The results of these arthroplasties were evaluated retrospectively using both survivorship analysis and observed success rates. Using a standard hip rating system, 19 hips were rated as excellent, 44 as good, 15 as fair, and 11 as poor. Failure was defined as definitely visible radiographic migration of either component, or reoperation for revision of one or both components. There was no significant difference between the HD-2 and CAD prostheses. There were five hips revised for aseptic loosening and revision was advised in an additional three hips. One hip with late sepsis required removal of both components. The five- and ten-year survivorships of the acetabular components were 97% +/- 3 and 58% +/- 17, respectively. Those of the femoral components were 93% +/- 5 and 78% +/- 13, respectively. For the components combined, the survivorship at five years was 91% +/- 6 but only 50% +/- 17 at ten years. Survivorship analysis provided a different and more realistic appraisal of the long-term results of the arthroplasties in this series than did the observed success rates. The contemporary cement techniques of the late 1970s and early 1980s may not be sufficient for the long-term survival of high-modulus THAs. Additional techniques may be necessary for improved long-term survival.


Culture methods of diffuse intrinsic pontine glioma cells determine response to targeted therapies.
Diffuse intrinsic pontine glioma (DIPG) is an aggressive type of brainstem cancer occurring mainly in children, for which there currently is no effective therapy. Current efforts to develop novel therapeutics for this tumor make use of primary cultures of DIPG cells, maintained either as adherent monolayer in serum containing medium, or as neurospheres in serum-free medium. In this manuscript, we demonstrate that the response of DIPG cells to targeted therapies in vitro is mainly determined by the culture conditions. We show that particular culture conditions induce the activation of different receptor tyrosine kinases and signal transduction pathways, as well as major changes in gene expression profiles of DIPG cells in culture. These differences correlate strongly with the observed discrepancies in response to targeted therapies of DIPG cells cultured as either adherent monolayers or neurospheres. With this research, we provide an argument for the concurrent use of both culture conditions to avoid false positive and false negative results due to the chosen method.


Evaluating the Prevalence of Pelvic Floor Disorders in Women in Nonmetropolitan Communities.
Prevalence rates of pelvic floor disorders in women in nonmetropolitan communities compared with metropolitan communities are unknown. We hypothesize that the rates are higher in women in nonmetropolitan communities. We accessed the health survey data from the NHANES (National Health and Nutrition Examination Survey) from 2009 to 2010 divided by geocodes into nonmetropolitan (<50,000 inhabitants) and metropolitan communities (>50,000). Responses were analyzed for the following conditions: urinary incontinence and nocturia, bowel urgency and anal incontinence, and symptomatic vaginal bulge. Age-adjusted prevalence rates were estimated using logistic regression. The 2009-2010 NHANES survey was completed nationwide by 302 women in nonmetropolitan communities and 2201 women in metropolitan communities. Overall, prevalence rates of PFDs did not significantly differ between groups. Prevalence rates of urinary incontinence and nocturia at least weekly were similar between metropolitan and nonmetropolitan groups (16.2% vs 14.6%, P = 0.47), with stress incontinence being more common than urgency and other types of incontinence (40% vs 23% and 8%). Women in metropolitan communities reported more bowel urgency than women in nonmetropolitan communities (33.3% vs 26.8%, P = 0.02); however, prevalence rates between both groups are similar with regards to anal incontinence at least once a month or more (9.2% vs 9.0%, P = 0.76). Prolapse symptoms were also not significantly different between the groups (2.4% in both). There was an increase in prevalence in each of the pelvic floor disorder symptoms with age. Pelvic floor disorders are prevalent and increase with age in women in nonmetropolitan communities at rates similar to women in metropolitan communities.


Liver transplantation as last-resort treatment for patients with bile duct injuries following cholecystectomy: a multicenter analysis.
Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy. Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed. Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively. LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes.


Hematologic and biochemical RIs for an aged population of captive African Green monkeys (Chlorocebus aethiops sabaeus).
Established RIs for geriatric African Green monkeys (Chlorocebus aethiops sabaeus) are critical for clinical differentiation of normal aging from disease-related changes in this population. The aim of this study was to establish hematologic and serum biochemical RIs for a Caribbean captive population of geriatric (≥ 15 years of age) African Green monkeys, or Vervets. Inclusion and exclusion criteria were defined for a cohort of 109 healthy, aged (15- to 30-year-old, median 19-year-old) Vervets. Both male (34) and female (75) monkeys were included in RI generation. Complete manual and analyzer-generated blood counts and serum biochemistry profiles were performed at Ross University School of Veterinary Medicine, West Farm, St. Kitts, West Indies. All results were evaluated using Reference Value Advisor. Isolated outliers were identified using Dixon's outlier range statistic and not included in determination of RIs for individual analytes. Reference intervals were determined using parametric and nonparametric methods depending on the distribution. Data, including mean, median, maximum, and minimum values, were tabulated. Of the 109 animals, 12 monkeys were excluded due to abnormal physical examination results (2 monkeys), and ≥ 2 confirmed outliers (9 monkeys), or evidence of disease based on laboratory data (one monkey). This study provides useful RIs for assessment of hematology and serum biochemical variables in a geriatric population of African Green monkeys in the Caribbean.


[Importance of the qualitative composition of dietary proteins in the dietotherapy of ischemic heart disease patients].
The effects of two isocaloric antiatherosclerotic diets (containing 120 g protein) differing in the amino acid composition of protein sources introduced were studied and compared in patients with coronary heart disease. Conventional protein sources were used in the first diet, whereas in the second diet, 15% of protein (by weight) was replaced by soybean protein isolate. A study was also made of the effect of dietetic management on lipid metabolism in blood serum. Hemocoagulation, capillary permeability, the kallikrein-kinin system, and immune responsiveness. An increase in the hypolipidemic effect of the diet was noted together with a decrease in the activity of the kallikrein-kinin system, capillary permeability, and body autosensitization upon introduction into the diet of soybean protein isolate. The increase of the protein quota as well as that attained by means of introducing in the diet of soybean protein isolate reduces the therapeutic effect of the diet on hemostasis.


Predictive value of admission N-terminal pro-B-type natriuretic peptide and renal function in older people hospitalized for dyspnoea.
We investigated the relationship between NT-pro-BNP, glomerular filtration rate (GFR), and all-cause mortality rates in a cohort of older people discharged from an internal medicine unit after admission for dyspnoea. NT-pro-BNP was evaluated in serum samples of 134 patients aged 80 ± 6 years who presented to a single academic centre with worsening dyspnoea. History data and anthropometric, clinical, and biochemical parameters including GFR were collected at the time of admission. 119 out of 134 were discharged alive from hospital and were included in the follow-up of 779 ± 370 days. 35 out of 119 subjects died after a follow-up of 266 ± 251 days. Cox proportional hazards model showed that GFR and Ln (NT-pro-BNP) were predictors for all-cause mortality with estimated hazard ratios of 0.969 (95% confidence interval: 0.950-0.988; P = 0.001) and 2.360 (95% confidence interval: 1.208-4.610; P = 0.012), respectively. Patients characterized by high NT-pro-BNP levels and GFR ≥ 60 mL/min/1.73 m(2) showed a dramatic reduction in survival duration compared with the groups with different combinations of the two variables (P = 0.008). In the elderly, NT-pro-BNP and GFR are predictors of all-cause mortality after admission because of dyspnoea. Since the fact that subjects with high NT-pro-BNP and GFR ≥ 60 mL/min/1.73 m(2) exhibited a reduced survival, high admission NT-pro-BNP suggests future negative outcome.


[The differential diagnosis of sarcoidosis of the respiratory organs using mathematical methods and computers].
A system for detecting sarcoidosis has been proposed on the basis of the results of a primary examination, which comprises a combination of programs for determining whether sarcoidosis may occur in various X-ray syndromes (enlarged intrathoracic lymph nodes, disseminated process, infiltrative or pneumonia-like shadow and cavity formation). The system has been developed with the help of a program-algorithm complex which enables one to make the dialogue system of the decision-make support on the basis of statistical methods of "image recognition" containing basic structural elements of the expert systems. Program development proceeds from the findings obtained in 406 patients with sarcoidosis of respiratory organs and 723 patients having similar clinical and X-ray picture of the disease. The diagnostic efficiency of the system was 89% in disseminated processes, 90% in enlarged intrathoracic lymph nodes and cavitary changes, and 96.2% in infiltrative changes.


Age and geographic dependence of Zika virus infection during the outbreak on Yap island, 2007.
Intensive surveillance of Zika virus infection conducted on Yap Island has provided crucial information on the epidemiological characteristics of the virus, but the rate of infection and medical attendance stratified by age and geographical location of the epidemic have yet to be fully clarified. In the present study, we reanalyzed surveillance data reported in a previous study. Likelihood-based Bayesian inference was used to gauge the age and geographically dependent force of infection and age-dependent reporting rate, with unobservable variables imputed by the data augmentation method. The inferred age-dependent component of the force of infection was suggested to be up to 3-4 times higher among older adults than among children. The age-dependent reporting rate ranged from 0.7% (5-9 years old) to 3.3% (50-54 years old). The proportion of serologically confirmed cases among total probable or confirmed cases was estimated to be 44.9%. The cumulative incidence of infection varied by municipality: Median values were over 80% in multiple locations (Gagil, Tomil, and Weloy), but relatively low values (below 50%) were derived in other locations. However, the possibility of a comparably high incidence of infection was not excluded even in municipalities with the lowest estimates. The results suggested a high degree of heterogeneity in the Yap epidemic. The force of infection and reporting rate were higher among older age groups, and this discrepancy implied that the demographic patterns were remarkably different between all infected and medically attended individuals. A higher reporting rate may have reflected more severe clinical presentation among adults. The symptomatic ratio in dengue cases is known to correlate with age, and our findings presumably indicate a similar tendency in Zika virus disease.


Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression?
Depression is a disease of growing incidence and economic burden worldwide. In view of increasing treatment resistance, new therapeutic approaches are urgently needed. In addition to its gonadal functions, testosterone has many effects on the central nervous system. An association between testosterone levels and depressive symptoms has been proposed. Many hormones and neurotransmitters are involved in the aetiology and the course of depression including serotonin, dopamine, noradrenaline, vasopressin and cortisol. Testosterone is known to interact with them. Preclinical data suggest that testosterone has antidepressant potential. However, the data from clinical studies have been inconsistent. This review provides a critical overview on the currently available preclinical and clinical literature and concludes with clinical recommendations.


EFFECT OF OXYGEN SUPPLY RATES ON GROWTH OF ESCHERICHIA COLI.
The effect of oxygen-supply rates on bacterial growth was studied in commercially available unbaffled and baffled flasks with the use of Escherichia coli in a synthetic medium as a test system. The amount of growth obtained depended on the oxygen-supply rate. Based on oxygen-absorption rates (OAR) measured by the rate of sulfite oxidation, equal OAR values in different types of flasks did not give equal amounts of growth. However, growth was essentially equal at the equal sulfite-oxidation rates when these were determined in the presence of killed whole cultures. Specific growth rates were reduced only at oxygen-supply rates much lower than those at which the total amount of growth was reduced. For the physical set-up used in this work and with the biological system employed, Bellco 598 flasks and flasks fitted with Biotech stainless-steel baffles gave satisfactory results at workable broth volumes; unbaffled and Bellco 600 flasks did not.


The Daily Experience of Subjective Tinnitus: Ecological Momentary Assessment Versus End-of-Day Diary.
Traditional methods of self-report assessments are susceptible to bias (i.e., memory, recall, and recency). Ecological momentary assessment (EMA) may curb these biases by repeated momentary assessment of the participant throughout the day. High costs and participant burden may, however, impede the use of EMA. End-of-day diary (EDD) provides an attractive alternative to EMA, though no direct comparison has been performed in the tinnitus field. Four thousand seven-hundred thirty-two data entries were collected from nine participants undergoing cognitive behavioral treatment for tinnitus. Eleven equivalent EMA and EDD items were collected for approximately 3 months. Tinnitus experience (i.e., anger, annoyance, avoidance, distraction, fear, invasiveness, pleasantness, and sadness) and well-being (i.e., anxiety, happiness, and stress) were correlated and means compared (t-tests). All variables presented adequate correlation (r > 0.68) between the EMA and EDD counterparts. Small (<3.9%) significant daily mean differences between EMA and EDD were found for six variables (tinnitus anger, invasiveness, pleasantness, sadness, as well as anxiety and stress) with worse results reported in EDD. The small significant effects found may be attributed to the large number of data points. When EMA is not possible or recommended, EDD provides a viable alternative to assess tinnitus experience daily. Further research on the underlying mechanisms of tinnitus experience and recollection is warranted.


Preparation of sustainable photocatalytic materials through the valorization of industrial wastes.
A new value-added material was developed from wastes to aim for appropriate waste management and sustainable development. This paper reports the valorization of industrial sandblasting operation wastes (SOWs) as new photocatalytic materials. This waste is composed of Fe2 O3 (60.7 %), SiO2 (29.1 %), and Al2 O3 (3.9 %) as the main components. The high presence of iron oxides was used to develop photocatalytic properties through their thermal transformation into α-Fe2 O3 . The new product, SOW-T, exhibited a good behavior towards the photochemical degradation of organic dyes. The preparation of advanced photocatalytic materials that exhibit self-cleaning and depolluting properties was possible by the inclusion of SOW-T and TiO2 in a cement-based mortar. The synergy observed between both materials enhanced their photocatalytic action. To the best of our knowledge, this is the first report that describes the use of transformed wastes based on iron oxide for the photochemical oxidation of NOx gases.


A two-step multiple-marker strategy for genome-wide association studies.
Genome-wide association studies raise study-design and analytical issues that are still being debated. Among them, stands the issue of reducing the number of markers to be genotyped without loss of efficiency in identifying trait loci, which can reduce the cost of studies and minimize the multiple testing problem. With this aim, we proposed a two-step strategy based on two analytical methods suited to examine sets of markers rather than single markers: the local score, which screens the genome to select candidate regions in Step 1, and FBAT-LC, a multiple-marker family-based association test used to obtain significance levels of regions at step 2. The performance of this strategy was evaluated on all replicates of Genetic Analysis Workshop 15 Problem 3 simulated data, using the answers to that problem. Overall, seven of the nine generated trait loci were detected in at least 87% of the replicates using a framework designed to handle either association with the disease or association with the severity of disease. This multiple-marker strategy was compared to the single-marker approach. By considering regions instead of single markers, this strategy minimizes the multiple testing problem and the number of false-positive results.


The real-time interactive 3-D-DVA for robust coronary MRA.
A graphical user interface (GUI) has been developed which enables interactive feedback and control to the real-time diminishing variance algorithm (DVA). This interactivity allows the user to set scan parameters, view scan statistics, and view image updates during the course of the scan. In addition, the DVA has been extended to simultaneously reduce motion artifacts in three dimensions using three orthogonal navigators. Preliminary in vivo studies indicate that these improvements to the standard DVA allow for significantly improved consistency and robustness in eliminating respiratory motion artifacts from MR images, particularly when imaging the coronary arteries.


Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection: The Phase 2 DURVAST Study.
Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1-infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies. To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection. The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti-PD-1 or anti-PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy. Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects. Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. A total of 20 HIV-1-infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4+ and CD8+ T-cell counts and plasma HIV-1 viremia remained stable throughout the study. Durvalumab treatment was feasible and safe in HIV-1-infected patients with cancer receiving combination antiretroviral therapy. HIV-1-infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments. ClinicalTrials.gov Identifier: NCT03094286.


Characterization and response of antioxidant systems in the tissues of the freshwater pond snail (Lymnaea stagnalis) during acute copper exposure.
The response of enzymatic (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX and glutathione reductase, GR) and non-enzymatic responses (glutathione, GSH, oxidized glutathione, GSSG and GSH/GSSG) against acute Cu toxicity (2-90μg/mL for 48h) in different tissues of Lymnaea stagnalis were measured. Incubation conditions for enzymatic activity measurements were optimized for L. stagnalis tissues. Three examined tissues, the hepatopancreas, the foot muscle and the mantle, exhibited variable responses in antioxidant parameters as a function of Cu concentrations. The most responsive antioxidant enzymes were GPX and CAT while GR appeared less sensitive. In general antioxidant enzymes at higher Cu concentrations though GSH levels at lower Cu concentrations exhibited the greatest changes in hepatopancreas and foot muscle, respectively. All antioxidant enzymes except GR increased after exposure to the highest Cu concentration in mantle. Total and reduced GSH increased in hepatopancreas but decreased with GSH/GSSG ratios at all Cu concentrations in foot muscle. The present results show that antioxidants respond to acute Cu exposure at concentrations as low as 2μg Cu/L in adult L. stagnalis with variable responses in different tissues. Antioxidants both including enzymatic and non-enzymatic parameters may account, in part, for the high tolerance to acute metal exposure observed in adult L. stagnalis and could form suited biomarkers to evaluate the metal exposure and toxicity in aquatic environment even at relatively low level short term exposure.


Gallium-containing mesoporous bioactive glass with potent hemostatic activity and antibacterial efficacy.
Haemorrhage remains the leading cause of potentially survivable death in both military and civilian populations. Although a large variety of hemostatic agents have been developed, many of them have an inadequate capacity to induce hemostasis and are not effective in killing bacteria. In recent years, mesoporous bioactive glasses (MBGs) were found to be effective in inducing hemostasis. However, the materials may not be considered as ideal hemostats since they do not offer antimicrobial activity. The gallium ion (Ga+3) not only exhibits antibacterial properties but also accelerates the blood coagulation cascade. The aim of this study was to develop MBGs containing various concentrations of Ga2O3 (1, 2 & 3 mol%) via the evaporation-induced self-assembly (EISA) process and investigate whether the addition of Ga3+ would induce both hemostatic and antibacterial effects. The results indicated that the incorporation of lower Ga2O3 content (1 mol%) into the MBG system improved structural properties including the specific surface area, mesopore size and pore volume as well as the release of silicon and calcium ions. The bioactive glass was found to stimulate blood coagulation, platelet adhesion and thrombus generation and exerted an antibacterial effect against both Escherichia coli and Staphylococcus aureus. Likewise, Ga-doped MBGs showed excellent cytocompatibility even after 3 days, with the 1% Ga2O3-containing MBG attaining the best biocompatibility that render them safe hemostatic agents for stopping bleeding. This study demonstrated that the lowest Ga2O3-substituted MBG can be a potent candidate for controlling haemorrhage and wound infection.


De Novo induction of atherosclerosis by Chlamydia pneumoniae in a rabbit model.
Chlamydia pneumoniae, a bacterial respiratory tract pathogen, has been associated with atherosclerosis in humans. C. pneumoniae infection of the respiratory tracts of rabbits fed a noncholesterol diet induced changes of atherosclerosis of the aorta in 6 (26.1%) of 23 animals after a single inoculum at 3 months. Multiple inocula given three times within 6 weeks resulted in grade III atherosclerosis in 8 (34.8%) of 23 rabbits, with an additional 5 (21. 7%) showing increased myxoid changes in the intima-media junction and exhibiting 8 (34.8%) focal periaortitis. Control animals inoculated with carrier broth (n = 24), HEp-2 cells (n = 12), or another respiratory pathogen, Mycoplasma pneumoniae (n = 32), produced no changes of atherosclerosis after 3 months. The histological changes were dissimilar (fewer foam cells) from those of rabbits fed a 0.5% cholesterol diet but were highly similar to or indistinguishable from changes in rabbits fed a 0.15% cholesterol diet (similar to that of humans). Proinflammatory cytokines and tissue growth factors were more consistently detected in cholesterol-induced aortic lesions than those induced by C. pneumoniae. These data are compatible with de novo induction of atherogenesis by C. pneumoniae in rabbits and suggest that C. pneumoniae may be important in the pathogenesis of atherosclerosis in humans.


Arsenic bioaccumulation in subarctic fishes of a mine-impacted bay on Great Slave Lake, Northwest Territories, Canada.
A subarctic fish community in mine-impacted Yellowknife Bay (Great Slave Lake, Northwest Territories, Canada) was investigated for biological and ecological processes controlling arsenic bioaccumulation. Total concentrations of arsenic, antimony, and metals were measured in over 400 fishes representing 13 species, and primary producers and consumers were included to characterize food web transfer. Yellowknife Bay had slightly more arsenic in surface waters (~3 μg/L) relative to the main body of Great Slave Lake (<1 μg/L), resulting in two-fold higher total arsenic concentrations in muscle of burbot (Lota lota), lake whitefish (Coregonus clupeaformis), and northern pike (Esox lucius). Other mining-associated contaminants, specifically antimony, lead, and silver, were typically below analytical detection in those fish species. No evidence was found for enhanced bioaccumulation of arsenic in long-lived, slow-growing subarctic fishes. Food web biodilution of total arsenic occurred between primary producers, aquatic invertebrates, and fish, although trophic position did not explain arsenic concentrations among fishes. Pelagic-feeding species had higher total arsenic concentrations compared to littoral fishes. Arsenic accumulated in subarctic fishes to comparable levels as fishes from lakes around the world with similar water arsenic concentrations. This first comprehensive study for a subarctic freshwater food web identified the importance of water exposure, biodilution, and habitat-specific feeding on arsenic bioaccumulation.


Hepatitis C virus E2 has three immunogenic domains containing conformational epitopes with distinct properties and biological functions.
Mechanisms of virion attachment, interaction with its receptor, and cell entry are poorly understood for hepatitis C virus (HCV) because of a lack of an efficient and reliable in vitro system for virus propagation. Infectious HCV retroviral pseudotype particles (HCVpp) were recently shown to express native E1E2 glycoproteins, as defined in part by HCV human monoclonal antibodies (HMAbs) to conformational epitopes on E2, and some of these antibodies block HCVpp infection (A. Op De Beeck, C. Voisset, B. Bartosch, Y. Ciczora, L. Cocquerel, Z. Y. Keck, S. Foung, F. L. Cosset, and J. Dubuisson, J. Virol. 78:2994-3002, 2004). Why some HMAbs are neutralizing and others are nonneutralizing is looked at in this report by a series of studies to determine the expression of their epitopes on E2 associated with HCVpp and the role of antibody binding affinity. Antibody cross-competition defined three E2 immunogenic domains with neutralizing HMAbs restricted to two domains that were also able to block E2 interaction with CD81, a putative receptor for HCV. HCVpp immunoprecipitation showed that neutralizing and nonneutralizing domains are expressed on E2 associated with HCVpp, and affinity studies found moderate-to-high-affinity antibodies in all domains. These findings support the perspective that HCV-specific epitopes are responsible for functional steps in virus infection, with specific antibodies blocking distinct steps of virus attachment and entry, rather than the perspective that virus neutralization correlates with increased antibody binding to any virion surface site, independent of the epitope recognized by the antibody. Segregation of virus neutralization and sensitivity to low pH to specific regions supports a model of HCV E2 immunogenic domains similar to the antigenic structural and functional domains of other flavivirus envelope E glycoproteins.


Ontogeny of GH mRNA and GH secretion in male and female rats: regulation by GH-releasing hormone.
Growth hormone-releasing hormone (GHRH) has been shown in vitro to increase proliferation of pituitary somatotrophs, to increase transcription of the GH gene, to promote accumulation of GH mRNA, and to stimulate GH release. The in vivo involvement of hypothalamic GHRH in regulating GH mRNA content had never been clearly documented. We studied pituitary GH mRNA and GH contents and serum concentrations of GH and insulin-like growth factor I (IGF-I) in rats of both sexes during pubertal growth spurt and investigated the effects of GHRH deficiency (brought about by neonatal administration of monosodium glutamate, MSG) and exogenous GHRH administration on these parameters. In both sexes, GH mRNA content increased three- to fourfold between 4 and 12 wk of life and declined thereafter toward 33 wk of life. This was accompanied by virtually parallel changes in pituitary GH content and in serum IGF-I. Neonatal MSG abolished the pubertal increases in GH mRNA, pituitary GH, and serum IGF-I and severely impaired growth rate. Exogenous GHRH (25 micrograms/kg sc every 8 h for 7 days) given to intact animals between 6 and 7 wk of life significantly augmented pituitary GH mRNA content but was less effective in MSG-treated rats. We conclude that 1) pubertal growth spurt in both sexes is associated with rising pituitary GH mRNA content; 2) GHRH deficiency abolishes the puberty-associated increase in GH synthesis and secretion and attenuates somatic growth rate; and 3) exogenous GHRH augments GH mRNA content. Thus puberty-associated augmentation of GHRH secretion is an important mechanism of somatic growth.


Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps (LiCABEDS) and its application on modeling ligand functionality for 5HT-subtype GPCR families.
Advanced high-throughput screening (HTS) technologies generate great amounts of bioactivity data, and this data needs to be analyzed and interpreted with attention to understand how these small molecules affect biological systems. As such, there is an increasing demand to develop and adapt cheminformatics algorithms and tools in order to predict molecular and pharmacological properties on the basis of these large data sets. In this manuscript, we report a novel machine-learning-based ligand classification algorithm, named Ligand Classifier of Adaptively Boosting Ensemble Decision Stumps (LiCABEDS), for data-mining and modeling of large chemical data sets to predict pharmacological properties in an efficient and accurate manner. The performance of LiCABEDS was evaluated through predicting GPCR ligand functionality (agonist or antagonist) using four different molecular fingerprints, including Maccs, FP2, Unity, and Molprint 2D fingerprints. Our studies showed that LiCABEDS outperformed two other popular techniques, classification tree and Naive Bayes classifier, on all four types of molecular fingerprints. Parameters in LiCABEDS, including the number of boosting iterations, initialization condition, and a "reject option" boundary, were thoroughly explored and discussed to demonstrate the capability of handling imbalanced data sets, as well as its robustness and flexibility. In addition, the detailed mathematical concepts and theory are also given to address the principle behind statistical prediction models. The LiCABEDS algorithm has been implemented into a user-friendly software package that is accessible online at http://www.cbligand.org/LiCABEDS/ .


A narrative review and content analysis of functional and quality of life measures used to evaluate the outcome after TSA: an ICF linking application.
Total shoulder arthroplasty (TSA) is considered as the standard reconstructive surgery for patients suffering from severe shoulder pain and dysfunction caused by arthrosis. Multiple patient-reported outcome measures (PROMs) have been developed and validated that can be used to evaluate TSA outcomes. When selecting an outcome measure both content and psychometric properties must be considered. Most research to date has focused on psychometric properties. Therefore, the current study aims to summarize what PROMs are being used to assess TSA outcomes, to classify the type of measure (International society for quality of life (ISOQOL) using definitions of functioning, disability, and health (FDH), quality of life (QoL) and health-related quality of life (HRQoL)) and to compare the content of these measures by linking them to the International Classification of Functioning, Disability and Health (ICF) framework. A literature review was performed in three databases including MEDLINE, EMBASE, and CINAHL to identify PROMs that were used in TSA studies. Meaningful concepts of the identified measures were extracted and linked to the relevant second-level ICF codes using standard linking rules. Outcome measures were classified as being FDH, HRQoL or QoL measures based on the content analysis. Thirty-five measures were identified across 400 retrieved studies. The most frequently used PROM was the American Shoulder and Elbow Society score accounting for 21% (246) of the total citations, followed by the single item pain-related scale like visual analog scale (17%) and Simple Shoulder Test (12%). Twelve PROMs with 190 individual items fit inclusion criteria for conceptual analysis. Most codes (65%) fell under activity and participation categories. The top 3 most predominant codes were: sensation of pain (b280; 13%), hand and arm use (d445; 13%), recreational activity (d920; 8%). Ten PROMs included in this study were categorized as FDH measures, one as HRQoL measure, and one as unknown. Our study demonstrated that there is an inconsistency and lack of clarity in conceptual frameworks of identified PROMs. Despite this, common core constructs are evaluated. Decision-making about individual studies or core sets for outcome measurement for TSA would be advanced by considering our results, patient priorities and measurement properties.


Molecular characterization of a recently identified circovirus in zebra finches (Taeniopygia guttata) associated with immunosuppression and opportunistic infections.
A recently identified circovirus (family Circoviridae) was detected in 14 zebra finches (Taeniopygia guttata) from seven aviaries and hobbyist breeders using polymerase chain reaction followed by sequencing. Full genome sequences of virus strains from six zebra finches consistently revealed characteristic circoviral genomic features such as a stem-loop structure and two major open reading frames (ORFs) encoding the replication-associated protein and the putative capsid protein. One further ORF encoding a protein of unknown function was additionally identified in all six genomes. Based on full genome nucleotide comparison, zebra finch circovirus was most similar to Finch circovirus originating from a Gouldian finch (Chloebia gouldiae) sharing 78% nucleotide identity. High genetic diversity was detected in the circoviruses from individual zebra finches. Comparison of the six full genome sequences revealed two genetic subgroups, which shared pairwise nucleotide identities between 91.4% and 92.7%. Analyses including partial sequences of the replication-associated protein gene of the zebra finch circovirus strains from all 14 birds supported the existence of two main clusters. Clinical diseases associated with circovirus infection were found in nestlings, fledglings and adult birds and varied from mild to severe with high mortality caused by secondary infections. Macrorhabdus ornithogaster was the most frequently detected opportunistic pathogen. Feathering disorders were seen in two birds. Lymphocytic depletion of the spleen and leukocytopaenia were detected in individual birds, suggesting immunosuppression and a pathogenesis common to circovirus infections in other birds.


Learning of grasp control in children with hemiplegic cerebral palsy.
This study examined whether children with hemiplegic cerebral palsy (CP) have anticipatory control of fingertip forces during lifts of familiar objects, and what type of practice (blocked or random) best enhances the retention of anticipatory control during lifts of novel objects. Eighteen children with hemiplegic CP (7 females, 11 males; 7 to 14 years of age, mean age 10 years, SD 1.8) and 18 age-matched typically developing children (8 males, 10 females; mean age 10.4 years, SD 1.7) participated in the study. In the first experiment the children lifted familiar objects of various weights and sizes five times each, while the vertical lifting (load) force was measured. Most participants demonstrated higher rates of load force increase for heavier (and larger) objects already during the first lift, indicating anticipatory control. Furthermore, the load force rates generally were similar across the five lifts for each object, suggesting that they had stable representations of the objects' properties. In the second experiment children lifted three novel objects varying in weight (but identical in volume) 27 times each, in either a blocked or a random order, followed by nine immediate and nine delayed (24 hours) retention trials. Blocked practice resulted in greater differentiation of the force rates between objects during acquisition than did random practice. Both practice schedules resulted in similar retention. These findings suggest that children with hemiplegic CP have a priori internal representations used for anticipatory force scaling with familiar objects. Furthermore, the results indicate that these children can form and retain internal representations of novel objects for anticipatory control, irrespective of the type of practice schedule employed. Thus, clinically based practice sessions that incorporate lifts with novel objects may enhance anticipatory force scaling and related prehensile function in children with hemiplegic CP.


HIV-1 coreceptor usage, transmission, and disease progression.
HIV-1 coreceptor usage is believed to play a critical role in pathogenesis. To initiate infection, HIV-1 interacts with two cell surface receptors; CD4 is the primary receptor and the beta-chemokine receptors CCR5 and CXCR4 usually serve as secondary receptors. HIV-1 strains transmitted in vivo generally use CCR5. Viruses that use CCR5 (R5 viruses) appear to be associated with relatively stable infection. Years after chronic infection is established, CXCR4 utilizing strains emerge in approximately 50% of infected individuals. Viruses that use the coreceptor CXCR4 (X4 viruses) are associated with rapid CD4+ cell decline and disease progression. However, the mechanism by which X4 viruses are associated with accelerated disease progression has never been properly elucidated. For example, the association between X4 virus and acceleration of HIV-1 disease progression has been ascribed to the expanded spectrum of CXCR4+ precursor cells susceptible to infection by X4 strains. It has also been postulated that the decline of the host immune system associated with clinical AIDS may allow X4 viruses to evolve and replicate freely in late-stage infection. Discriminating between these and other alternatives is central to increasing our understanding of the fundamental pathogenic processes involved in HIV-1 infection. In this article, we critically review those studies published over the last few years that purport to examine the relationship between HIV-1 coreceptor usage, transmission, CD4+ T-cell depletion, and disease progression.


Bradykinin stimulates IL-6 and IL-8 production by human lung fibroblasts through ERK- and p38 MAPK-dependent mechanisms.
Bradykinin (BK) is a major kinin with well-documented pharmacological properties including vascular leakage and induction of a variety of cytokines. However, the intracellular signalling mechanisms by which BK induced proinflammatory cytokine production have not been fully elucidated. This study investigated the role of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) in the BK-induced interleukin (IL)-6 and IL-8 production by human lung fibroblasts. Lung fibroblasts were stimulated with BK in the presence or in the absence of PD98059, a specific MAPK/ERK kinase-1 inhibitor, or SB203580, a specific p38 MAPK inhibitor, and IL-6 or IL-8 production and their gene expression was examined. BK-induced ERK 1/2 or p38 MAPK phosphorylation was also analysed by Western blot analysis. BK at nanomolar concentrations stimulated lung fibroblasts to produce IL-6 and IL-8 along with increased ERK 1/2 and p38 MAPK phosphorylation. BK-induced IL-6 and IL-8 synthesis was inhibited by a B2-type BK receptor antagonist. Furthermore, PD98059 or SB203580 significantly suppressed BK-induced IL-6 and IL-8 production and their gene expression. These results indicate that bradykinin-induced interleukin-6 and interleukin-8 production are at least partly mediated through the extracellular signal-related protein kinase 1/2 and p38 mitogen-activated protein kinase pathway-dependent activation in human lung fibroblasts, and suggest that bradykinin appears to be involved in the inflammatory reaction leading to acute lung injury through stimulating interleukin-6 and interleukin-8 production by lung fibroblasts.


Bpag1 localization to actin filaments and to the nucleus is regulated by its N-terminus.
Plakins are a family of giant cytoskeleton binding proteins. One member of this group is bullous pemphigoid antigen 1 (Bpag1)/dystonin, which has neuronal and muscle isoforms that consist of actin-binding and microtubule-binding domains at either end separated by a plakin domain and several spectrin repeats. The better-characterized epithelial isoform has only the plakin domain in common with the neuronal and muscle isoforms. Here, we have analyzed the localization of muscle/neuronal (Bpag1a/b) isoforms and the epithelial (Bpag1e) isoform within C2C12 myoblast cells. Although an antibody specific to Bpag1a/b isoform 2 detected protein co-aligning actin stress fibers, this same antibody and two Bpag1e antibodies predominantly detected protein in the nuclei. A Bpag1a/b isoform 2 N-terminal fusion protein containing the plakin domain also localized to actin stress fibers and to nuclei. Within the plakin domain, we characterized a functional nuclear localization signal, which was responsible for localization of the fusion protein to the nucleus. Bpag1a/b isoform 1 N-terminal fusion proteins differed in their interaction with the actin cytoskeleton and with their ability to localize to the nucleus, suggesting that Bpag1 isoforms with different N-termini have differing roles. These results show the importance of N-terminal domains in dictating the localization and function of Bpag1 isoforms. We provide the first indication that Bpag1 is not strictly a cytoplasmic/membrane protein but that it can also localize to the nucleus.


A Novel Approach to Bone Reconstruction: The Wafer Technique.
This study presents a novel technique based on guided bone regeneration and onlay grafts for three-dimensional bone augmentation. This two-stage technique uses an autogenous cortical bone plate and collagen membranes to form a barrier containing a mixture of deproteinized bovine bone matrix, autologous blood, and bone grafted from intraoral sites. Five patients were treated. At 6 months postsurgery, a mean increase in bone volume of 1,062 mm³ was shown. Mean maximum linear augmentation was 3.65 mm. Histologic analysis of the regenerated areas revealed the presence of compact newly formed bone with no sign of inflammation. A total of 13 implants were placed. The patients were satisfied, and complications were not observed.


Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: A trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group.
To compare the efficacy and tolerability of etoposide, leucovorin, and bolus fluorouracil (ELF) or infusional fluorouracil plus cisplatin (FUP) with that of the reference protocol of fluorouracil, doxorubicin, and methotrexate (FAMTX) in advanced gastric cancer. A total of 399 patients with advanced adenocarcinoma of the stomach were randomized and analyzed for toxicity, tumor response, and progression-free and overall survival. Only reviewed and confirmed responses were considered. The analysis of remission was based on assessable patients with documented measurable lesions. The intent-to-treat principle, log-rank test, and Cox regression model were used for the statistical analysis of time-to-event end points. The overall response rate for 245 eligible patients with measurable disease was 9% with ELF, 20% with FUP, and 12% with FAMTX, with no significant differences. One hundred twelve patients were eligible for efficacy in assessable, nonmeasurable disease. No change was observed in 66% of patients treated with ELF, 56% with FUP, and 55% with FAMTX. Two patients achieved a complete tumor regression (one each for ELF and FAMTX). With a median follow-up time of 4.5 years, the median survival times were 7.2 months with ELF, 7.2 months with FUP, and 6.7 months with FAMTX, respectively, with no significant differences. Nonhematologic and hematologic toxicities of ELF, FUP, and FAMTX were acceptable, with neutropenia being the major toxicity for all three regimens. Seven treatment-related deaths occurred (two with FUP and five with FAMTX). All three investigated regimens demonstrate modest clinical efficacy and should not be regarded as standard treatment for advanced gastric cancer. New strategies should be considered to achieve a better clinical efficacy in the treatment of advanced gastric cancer.


Atherosclerotic risk factors, vascular cognitive impairment, and Alzheimer disease.
The involvement of vascular factors in Alzheimer dementia was first appreciated over 100 years ago. Recently, significant advances in our understanding of these brain-vascular relationships have taken place. Vascular cognitive impairment is now recognized as a distinct group of interrelated vascular-based neurological insults that can accumulate and lead to dementia. Importantly, the pathology of vascular cognitive impairment extends far beyond brain destruction wrought by major stroke. Other subtle changes may also arise that contribute to vascular cognitive impairment and dementia, including subclinical stroke, white-matter changes such as hyperintensities and lipohyalinosis, small lacunar infarcts, cerebral hypoperfusion, and compromise of the blood-brain barrier. In this review we critically examine the emerging body of evidence that relates atherosclerotic risk factors, brain functioning, and Alzheimer disease.


Psychological aspects of female sterilisation--assessment of subsequent regret.
In order to study subsequent regret as a complication of female sterilisation, hospital records of women requesting reversal of their sterilisation were compared with women who had not requested a reversal. Regret was more likely in women sterilised at a younger age, but was not associated with lower parity. Women requesting reversal were interviewed to determine the psychosocial factors likely to produce later regret. The clinical implications are discussed.


A review of instruments developed to measure outcomes for carers of people with mental health problems.
Community-based care for mental disorders places considerable burden on families and carers. Measuring their experiences has become a priority, but there is no consensus on appropriate instruments. We aimed to review instruments carers consider relevant to their needs and assess evidence for their use. A literature search was conducted for outcome measures used with mental health carers. Identified instruments were assessed for their relevance to the outcomes identified by carers and their psychometric properties. Three hundred and ninety two published articles referring to 241 outcome measures were identified, 64 of which were eligible for review (used in three or more studies). Twenty-six instruments had good psychometric properties; they measured (i) carers' well-being, (ii) the experience of caregiving and (iii) carers' needs for professional support. Measures exist which have been used to assess the most salient aspects of carers outcome in mental health. All require further work to establish their psychometric properties fully.


Essential pathogenetic role for interferon (IFN-)gamma in concanavalin A-induced T cell-dependent hepatitis: exacerbation by exogenous IFN-gamma and prevention by IFN-gamma receptor-immunoglobulin fusion protein.
We have studied the effects of either exogenously-administered interferon (IFN-)gamma or of a nonimmunogenic mouse IFN-gamma receptor-Immunoglobulin (IFN-gamma R-Ig) fusion protein on the development of Concanavalin (Con)A-induced hepatitis in NMRI mice. PBS-treated control mice injected with 20 mg/kg ConA developed classical serological and histological signs of hepatitis with elevation of transaminases in the blood and infiltration of the liver by mononuclear cells and neutrophils. Treating the mice with rat IFN-gamma 24 h prior to and 1 h after ConA-challenge markedly exacerbated these signs of hepatitis in a dose-dependent fashion. Moreover, mice injected with lower, non hepatitogenic, doses of ConA (10, 5 mg/kg) became fully susceptible to develop hepatitis upon similar treatment with IFN-gamma. Concordantly, ConA-induced hepatitis was abrogated by either IFN-gamma R-Ig fusion protein or anti-IFN-gamma mAb. These data provide further evidence for the central pathogenetic role of endogenous IFN-gamma in ConA-induced hepatitis and demonstrate the feasibility to prevent disease development by means of a non immunogenic IFN-gamma R-Ig fusion protein.


Immune Modulatory Therapy Causing Acute Coronary Syndrome.
Intravenous immunoglobulin (IVIG) is a therapeutic preparation of pooled polyspecific IgG used effectively in immune thrombocytopenic purpura (ITP), autoimmune diseases, and inflammatory diseases. We present a case of a 67-year-old male who presented with diffuse petechiae and was diagnosed with immune thrombocytopenic purpura with platelet count less than 10,000 per milliliter. Treatment was initiated with IVIG. When the third dose of IVIG was being administered he developed hypertensive urgency and non-ST segment elevation myocardial infarction. He was deemed not to be a candidate for cardiac catheterization and was treated conservatively. IVIG can cause major thrombotic adverse events such as deep vein thrombosis, myocardial infarction and stroke, which are attributed to thrombosis and hyperviscocity. Decreasing the dosage of IVIG, administration of anticoagulants are proposed treatments for such events. We propose that patients receiving high-dose IVIG with previous coronary artery disease require meticulous cardiac monitoring. Further research is needed to determine the true adverse effects of high-dose IVIG and prophylaxis regimens to decrease the risk.


Training surgeon status is not associated with an increased risk of early or late mortality after isolated aortic valve replacement surgery.
Few studies have addressed the effect of "trainee surgeon" status on outcomes after isolated aortic valve replacement (AVR). A retrospective analysis of data, collected by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program between June 2001 and December 2009 was performed. Patient demographics, intra-operative characteristics and early morbidity were compared between trainee and staff cases. Multivariate analyses were used to determine the independent association of training status with 30-day and late mortality. Isolated AVR was performed in 2747 patients; of these, 369 (13.4%) were by trainees. Compared to staff cases, trainee cases were less likely to present with renal failure (1.1% vs. 3.7%, p = 0.010) or in a critical preoperative state (1.4% vs. 3.7%, p = 0.020). The mean EuroSCORE was lower in trainee patients, compared to staff patients (8.11 ± 2.80 vs. 8.81 ± 3.09, p < 0.001). Trainee cases had longer mean perfusion (117.9 min vs. 98.9 min, p < 0.001) and cross-clamp (88.8 min vs. 73.2 min, p < 0.001) times. The incidence of early complications was similar between the two groups, except for post-operative myocardial infarction (1.1% vs. 0.3%, p = 0.008) and red blood cell transfusion (43.9 vs. 40.0%, p = 0.006). On multivariate analysis, trainee status was not associated with an increased risk of 30-day mortality (2.2% vs. 2.4%, p = 0.823). Moreover, there was no significant difference in long-term outcomes and 5-year survival was comparable in both groups (89.9% vs. 84.8%, p = 0.274). Isolated AVR can be safely and effectively performed by trainee surgeons who are strictly supervised in the operating theatre especially during the technically complex parts of the procedure.


Effect of aqueous extract of Bulbine natalensis (Baker) stem on the sexual behaviour of male rats.
The phytochemical constituents of aqueous extract of Bulbine natalensis (Baker) stem and its effect on male rat sexual behaviour were evaluated for 7 days. Phytochemical screening revealed the presence of saponins, cardiac glycoside, tannins, alkaloids and anthraquinones. Administration of the extract at the doses of 25 and 50 mg/kg body weight resulted in the significant increase (p < 0.05) in mount frequency, intromission frequency, ejaculatory latency, ejaculation frequency, serum testosterone and luteinizing hormone concentrations, computed indices of sexual behaviour, erection, quick flips, long flips and total penile reflexes whereas the mount latency, intromission latency and post-ejaculatory interval were significantly decreased (p < 0.05) throughout the experimental period. The 100 mg/kg body weight of the extract produced contrasting pattern to the lower doses of the extract in all the parameters of sexual behaviour monitored throughout the experimental period. The results are indicative of prosexual stimulatory potentials of Bulbine natalensis in male rats. The aqueous extract of Bulbine natalensis stem at these doses (25 and 50 mg/kg body weight) may be used in the management of disorders of desire/libido, premature ejaculation and erectile dysfunction in males.


UT-B is expressed in bovine rumen: potential role in ruminal urea transport.
The UT-A (SLC14a2) and UT-B (SLC14a1) genes encode a family of specialized urea transporter proteins that regulate urea movement across plasma membranes. In this report, we describe the structure of the bovine UT-B (bUT-B) gene and characterize UT-B expression in bovine rumen. Northern analysis using a full-length bUT-B probe detected a 3.7-kb UT-B signal in rumen. RT-PCR of bovine mRNA revealed the presence of two UT-B splice variants, bUT-B1 and bUT-B2, with bUT-B2 the predominant variant in rumen. Immunoblotting studies of bovine rumen tissue, using an antibody targeted to the NH2-terminus of mouse UT-B, confirmed the presence of 43- to 54-kDa UT-B proteins. Immunolocalization studies showed that UT-B was mainly located on cell plasma membranes in epithelial layers of the bovine rumen. Ussing chamber measurements of ruminal transepithelial transport of (14)C-labeled urea indicated that urea flux was characteristically inhibited by phloretin. We conclude that bUT-B is expressed in the bovine rumen and may function to transport urea into the rumen as part of the ruminant urea nitrogen salvaging process.


[Insulin signaling: mechanisms altered in insulin resistance].
Insulin has a major anabolic function leading to storage of lipidic and glucidic substrates. All its effects result from insulin binding to a specific membrane receptor which is expressed at a high level on the 3 insulin target tissues: liver, adipose tissue and muscles. The insulin receptor exhibits a tyrosine-kinase activity which leads, first, to receptor autophosphorylation and then to tyrosine phosphorylation of substrates proteins, IRS proteins in priority. This leads to the formation of macromolecular complexes close to the receptor. The two main transduction pathways are the phosphatidylinositol 3 kinase pathway activating protein kinase B which is involved in priority in metabolic effects, and the MAP kinase pathway involved in nuclear effects, proliferation and differentiation. However, in most cases, a specific effect of insulin requires the participation of the two pathways in a complex interplay which could explain the pleiotropy and the specificity of the insulin signal. The negative control of the insulin signal can result from hormone degradation or receptor dephosphorylation. However, the major negative control results from phosphorylation of serine/threonine residues on the receptor and/or IRS proteins. This phosphorylation is activated in response to different signals involved in insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from adipose tissue, which are transformed inside the cell in acyl-CoA. A deleterious role for molecules issued from the adipose tissue is postulated in the resistance to insulin of the liver and muscles present in type 2 diabetes, obesity and metabolic syndrome.


The cell-end marker TeaA and the microtubule polymerase AlpA contribute to microtubule guidance at the hyphal tip cortex of Aspergillus nidulans to provide polarity maintenance.
In the absence of landmark proteins, hyphae of Aspergillus nidulans lose their direction of growth and show a zigzag growth pattern. Here, we show that the cell-end marker protein TeaA is important for localizing the growth machinery at hyphal tips. The central position of TeaA at the tip correlated with the convergence of the microtubule (MT) ends to a single point. Conversely, in the absence of TeaA, the MTs often failed to converge to a single point at the cortex. Further analysis suggested a functional connection between TeaA and AlpA (an ortholog of the MT polymerase Dis1/CKAP5/XMAP215) for proper regulation of MT growth at hyphal tips. AlpA localized at MT plus-ends, and bimolecular fluorescence complementation assays suggested that it interacted with TeaA after MT plus-ends reached the tip cortex. In vitro MT polymerization assays showed that AlpA promoted MT growth up to sevenfold. Addition of the C-terminal region of TeaA increased the catastrophe frequency of the MTs. Thus, the control of the AlpA activity through TeaA might be a novel principle for MT growth regulation after reaching the cortex. In addition, we present evidence that the curvature of hyphal tips also could be involved in the control of MT growth at hyphal tips.


Genetic loci of Staphylococcus aureus associated with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides.
The proteinase 3 (PR3)-positive anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) granulomatosis with polyangiitis (GPA) has been associated with chronic nasal S. aureus carriage, which is a risk factor for disease relapse. The present study was aimed at comparing the genetic make-up of S. aureus isolates from PR3-ANCA-positive GPA patients with that of isolates from patients suffering from myeloperoxidase (MPO)-ANCA-positive AAV, and isolates from healthy controls. Based on a DNA microarray-based approach, we show that not only PR3-ANCA-positive GPA patients, but also MPO-ANCA-positive AAV patients mainly carried S. aureus types that are prevalent in the general population. Nonetheless, our data suggests that MPO-ANCA-associated S. aureus isolates may be distinct from healthy control- and PR3-ANCA-associated isolates. Furthermore, several genetic loci of S. aureus are associated with either PR3-ANCA- or MPO-ANCA-positive AAV, indicating a possible role for pore-forming toxins, such as leukocidins, in PR3-ANCA-positive GPA. Contrary to previous studies, no association between AAV and superantigens was detected. Our findings also show that a lowered humoral immune response to S. aureus is common for PR3-ANCA- and MPO-ANCA-positive AAV. Altogether, our observations imply that the presence or absence of particular virulence genes of S. aureus isolates from AAV patients contributes to disease progression and/or relapse.


Viral small nuclear ribonucleoproteins bind a protein implicated in messenger RNA destabilization.
Herpesvirus saimiri (HVS) is one of several primate viruses that carry genes for small RNAs. The five H. saimiri-encoded U RNAs (HSURs) are the most abundant viral transcripts expressed in transformed marmoset T lymphocytes. They assemble with host proteins common to spliceosomal small nuclear ribonucleoproteins (snRNPs). HSURs 1, 2, and 5 exhibit sequences at their 5' ends identical to the AUUUA motif, which targets a number of protooncogene, cytokine, and lymphokine mRNAs for rapid degradation. We show that a 32-kDa protein previously demonstrated to bind to the 3' untranslated region of several unstable messages can be UV crosslinked specifically to HSUR 1, 2, and 5 transcripts in vitro, as well as to endogenous HSUR snRNPs. Our results suggest an unusual role for these viral snRNPs: HSURs may function to attenuate the rapid degradation of certain cellular mRNAs, thereby facilitating viral transformation of host T lymphocytes.


Comparison of Bone-Patellar Tendon-Bone Graft, Semitendinosus-Gracilis Graft and Semitendinosus-Gracilis with Preserved Tibial Insertion Graft in Anterior Cruciate Ligament Reconstruction in Sports Persons.
Bone-patellar tendon-bone (BPTB) and semitendinosus-gracilis (STG) are the commonest grafts used for ACL reconstruction. However even after having been debated for years, there is no consensus about the ideal graft. Moreover, the literature is deficient about STG graft with preserved tibial insertion (STGPI) which preserves the proprioception. Our aim is to compare the outcome of BPTB, free STG and STGPI grafts after ACL reconstruction in professional sports persons. We compared the outcome in terms of mechanical stability, functional outcome, return to sports activity and degenerative changes. Professional sports persons aged between 16-50 years operated for ACL tear using BPTB, free STG and STGPI grafts with minimum follow-up of two years were identified from hospital records. Patients with associated knee injuries were excluded. Patients, divided in three groups according to graft used, were compared in terms of mechanical stability (arthrometric examination KT-1000 score), functional outcome (Lysholm Score), return to sports activity (Tegner score and difference in thigh circumference) and degenerative changes (KL grading). BPTB graft group was found to be better than free STG and STGPI graft groups in terms of KT-1000 score. There was no statistically significant difference among the groups in terms of Lysholm score, Tegner score, difference in thigh circumference and KL grading. BPTB graft is better than free STG and STGPI grafts in terms of knee stability. When compared for patient reported outcome, return to sports activity, osteoarthritic changes and graft failure there is no significant difference among the three types of grafts.


Twist of Tubular Mechanical Metamaterials Based on Waterbomb Origami.
Origami-inspired mechanical metamaterials have recently drawn increasing attention since their flexible mechanical performance has been greatly enhanced by introducing origami patterns to the thin-shell structures. As a typical origami pattern, the waterbomb tube could be adopted to the design of mechanical metamaterials. However, existing designs predominantly make use of the radial expansion/contraction motion of the structure, thereby limiting its full potential to be explored. Here we report a twist motion of tubular mechanical metamaterials based on waterbomb origami that is previously undiscovered. We demonstrate through a detailed kinematic analysis that the initial twist is a rigid-origami motion if the corresponding row of the tube under twist is fully squeezed with both line and plane symmetry, whereas all the subsequent twist motion requires material deformation. The twist angle per axial strain and its relationship with the geometrical parameters of the tube are revealed. Experimental results show the enhancement in stiffness of the tube with the occurrence of the continuous twist motion. We envisage that this finding could greatly expand the application of the waterbomb tube in the design of origami metamaterials with programmable and tuneable mechanical properties.


Pediatric isolated thoracic and/or lumbar transverse and spinous process fractures.
OBJECTIVE Isolated transverse and spinous process fractures (TPFx and SPFx) in the thoracic and/or lumbar region have been deemed clinically insignificant in the adult population. This same rule is often applied to the pediatric population; however, little evidence exists in this younger group. The goal of this study was to describe the clinical, radiographic, and long-term data on isolated TPFx and SPFx in an exclusively pediatric population. METHODS A retrospective chart review at Monroe Carell Jr. Children's Hospital at Vanderbilt University identified 82 pediatric patients with isolated TPFx and/or SPFx following a traumatic event between January 2000 and December 2013. Patient demographic information, presenting symptoms, radiographic characteristics, and follow-up data were collected. Follow-up was used to determine the outcome (presence of neurological deficits) of such injuries via complete physical examination and, when available, radiographic evidence. RESULTS In the 82 identified patients, the mean age was 15.5 ± 3.1 years (mean is expressed ± SD throughout), with 72 injuries (87.8%) resulting from a motor vehicle, motorcycle, or all-terrain vehicle accident. There was a mean of 1.7 ± 1.0 fractured vertebral levels involved and a mean of 1.8 ± 1.1 fractures was identified per patient. Seventy-one patients (86.6%) needed bedside pain control, 7 (8.5%) were prescribed a brace, and 4 patients (4.9%) received a collar. Physical therapy was recommended for 12 patients (14.6%). A total of 84.1% had follow-up, and the mean length of follow-up was 19 ± 37 months. No patients had true neurological deficits at presentation or follow-up as a result of their isolated fractures, whereas 95.1% had other associated system injuries. CONCLUSIONS These data shows that there is no appreciable long-term complication associated with isolated thoracic and/or lumbar TPFx and/or SPFx in an exclusively pediatric population. Because these fractures are, however, associated with high-energy blunt trauma, they often result in associated soft-tissue or other skeletal injury. All pediatric patients in the cohort benefited from conservative management and aggressive treatment of their comorbidities.


Clinical disorders responsible for plasma hyperviscosity and skin complications.
In this brief review, we have examined some clinical disorders which are associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be, in fact, observed in patients with primary plasma hyperviscosity such as multiple myeloma, Waldenstrom macroglobulinemia, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia and connective tissue diseases. It must be underlined that the altered hemorheological pattern is not the only responsible for this skin complication but, as it worsens the microcirculatory flow, it contributes to determine the occurrence of the skin ulcers.


De novo 8p23.1 deletion in a patient with absence epilepsy.
The 8p23.1 deletion syndrome is a rare multisystem disorder with high penetrance and a variable phenotypic spectrum that includes congenital heart disease (CHD), intellectual disability, behavioural problems, microcephalia, and sometimes epilepsy. Genomic copy number variations (CNVs) constitute an important genetic risk factor for common genetic generalised epilepsy syndromes (GGEs) and absence seizures. These variations, resulting either from copy loss (microdeletion) or copy gain (duplications), disrupt genes associated with neuronal development. Herein, we report an epilepsy patient who was affected by developmental delay, microcephalia, behavioural problems, CHD, and childhood-onset absence seizures. The patient had a 4-Mb de novo microdeletion at 8p23.1. Some of the genes in this region, particularly XKR6 and MIR597, may be involved in the pathogenesis of absence seizures, suggesting that epilepsy may possibly be part of the phenotypic spectrum of the syndrome rather than a comorbid disorder. Thus, CNV screening for GGE plus patients may have important implications in clinical practice with regards to diagnostic classification, clinical management of the syndromic multisystem disorders, and, potentially, genetic counselling.


Robust machine learning algorithms for predicting coastal water quality index.
Coastal water quality assessment is an essential task to keep "good water quality" status for living organisms in coastal ecosystems. The Water quality index (WQI) is a widely used tool to assess water quality but this technique has received much criticism due to the model's reliability and inconsistence. The present study used a recently developed improved WQI model for calculating coastal WQIs in Cork Harbour. The aim of the research is to determine the most reliable and robust machine learning (ML) algorithm(s) to anticipate WQIs at each monitoring point instead of repeatedly employing SI and weight values in order to reduce model uncertainty. In this study, we compared eight commonly used algorithms, including Random Forest (RF), Decision Tree (DT), K-Nearest Neighbors (KNN), Extreme Gradient Boosting (XGB), Extra Tree (ExT), Support Vector Machine (SVM), Linear Regression (LR), and Gaussian Naïve Bayes (GNB). For the purposes of developing the prediction models, the dataset was divided into two groups: training (70%) and testing (30%), whereas the models were validated using the 10-fold cross-validation method. In order to evaluate the models' performance, the RMSE, MSE, MAE, R2, and PREI metrics were used in this study. The tree-based DT (RMSE = 0.0, MSE = 0.0, MAE = 0.0, R2 = 1.0 and PERI = 0.0) and the ExT (RMSE = 0.0, MSE = 0.0, MAE = 0.0, R2 = 1.0 and PERI = 0.0) and ensemble tree-based XGB (RMSE = 0.0, MSE = 0.0, MAE = 0.0, R2 = 1.0 and PERI = +0.16 to -0.17) and RF (RMSE = 2.0, MSE = 3.80, MAE = 1.10, R2 = 0.98, PERI = +3.52 to -25.38) models outperformed other models. The results of model performance and PREI indicate that the DT, ExT, and GXB models could be effective, robust and significantly reduce model uncertainty in predicting WQIs. The findings of this study are also useful for reducing model uncertainty and optimizing the WQM-WQI model architecture for predicting WQI values.


Aspirin potentiates the effect of ephedrine on the thermogenic response to a meal in obese but not lean women.
The effect of ephedrine (30 mg) and aspirin (300 mg) on the acute thermogenic response to a liquid meal (250 kcal) was investigated in lean and obese women (n = 10 each group). Resting metabolic rate (RMR) was measured prior to each of the following treatments: meal only (M), meal plus ephedrine (ME) or meal plus ephedrine and aspirin (MEA). Eight post-treatment measurements of metabolic rate were made over a total of 160 minutes. Rise in post-treatment metabolic rate was compared to the baseline RMR. Following the M treatment, the mean increase in metabolic rate was 0.17 +/- 0.01 and 0.13 +/- 0.02 kcal/min in the lean and obese groups respectively, with the corresponding rises being 0.21 +/- 0.02 and 0.19 +/- 0.02 kcal/min following the ME, and 0.23 +/- 0.03 and 0.23 +/- 0.01 kcal/min following the MEA. The increase in post-prandial thermogenesis with the ephedrine or ephedrine plus aspirin was significant in the obese group (P less than 0.03 and P less than 0.001 respectively) but not the lean. Furthermore, the post-treatment rise in metabolic rate, following the MEA treatment compared to the ME, was significantly greater for the obese group (P less than 0.05) but not the lean. It was concluded that aspirin potentiates the stimulatory effect of ephedrine on the thermogenic response to a meal in obese but not lean women.


Diagnostic importance of Clostridium perfringens enterotoxin analysis in recurring enteritis among elderly, chronic care psychiatric patients.
A series of Clostridium perfringens-related gastrointestinal outbreaks occurred over a period of several months among elderly, chronic care patients in a psychiatric hospital. Several serotypes of C. perfringens and many nontypeable isolates were found. The distribution of certain serotypes and the incidence of detection of enterotoxin in fecal extracts were related to wards on which patients were resident (six wards were involved). Several patients were reported to have chronic or recurring fecal incontinence or diarrhea or both. With a background of elevated spore counts of several serotypes and chronic diarrhea, only detection of enterotoxin could provide definitive evidence of C. perfringens etiology in gastoenteritis cases.


Pharmacological and therapeutic directions in ADHD: Specificity in the PFC.
Recent directions in the treatment of ADHD have involved both a broadening of pharmacological perspectives to include nor-adrenergic as well as dopaminergic agents. A review of animal and human studies of pharmacological and therapeutic directions in ADHD suggests that the D1 receptor is a specific site for dopaminergic regulation of the PFC, but optimal levels of dopamine (DA) are required for beneficial effects on working memory. Animal and human studies indicate that the alpha-2A receptor is also important for prefrontal regulation, leaving open the question of the relative importance of these receptor sites. The therapeutic effects of ADHD medications in the prefrontal cortex have focused attention on the development of working memory capacity in ADHD. The actions of dopaminergic vs noradrenergic agents, currently available for the treatment of ADHD have overlapping, but different actions in the prefrontal cortex (PFC) and subcortical centers. While stimulants act on D1 receptors in the dorsolateral prefrontal cortex, they also have effects on D2 receptors in the corpus striatum and may also have serotonergic effects at orbitofrontal areas. At therapeutic levels, dopamine (DA) stimulation (through DAT transporter inhibition) decreases noise level acting on subcortical D2 receptors, while NE stimulation (through alpha-2A agonists) increases signal by acting preferentially in the PFC possibly on DAD1 receptors. On the other hand, alpha-2A noradrenergic transmission is more limited to the prefrontal cortex (PFC), and thus less likely to have motor or stereotypic side effects, while alpha-2B and alpha-2C agonists may have wider cortical effects. The data suggest a possible hierarchy of specificity in the current medications used in the treatment of ADHD, with guanfacine likely to be most specific for the treatment of prefrontal attentional and working memory deficits. Stimulants may have broader effects on both vigilance and motor impulsivity, depending on dose levels, while atomoxetine may have effects on attention, anxiety, social affect, and sedation via noradrenergic transmission. At a theoretical level, the advent of possible specific alpha-2A noradrenergic therapies has posed the question of the role of working memory in ADHD. Head to head comparisons of stimulant and noradrenergic alpha-2A, alpha-2B and alpha-2C agonists, utilizing vigilance and affective measures should help to clarify pharmacological and therapeutic differences.


[Mollusks associated to the submerged roots of the red mangrove, Rhizophora mangle (L.), in the Gulf of Santa Fe, Sucre State, Venezuela].
A qualitative and quantitative monthly study of the mollusks community associated to the submerged roots of the red mangrove, Rhizophora mangle (L.), between October of 1998 and September of 1999, in six stations of the Gulf of Santa Fe, (Sucre State, Venezuela). Were collected 4,704 specimens, 45 species of mollusks were identified (22 gastropods, 15 bivalves and 8 chitons). The most abundant species were: Crassostrea rhizophorae, Isognomon bicolar, I. alatus and Brachidontes exustus. The highest values in diversity and evenness, and the smallest dominant values, were in the stations three and four, while the opposed happened in the stations one and two. The analysis of likeness showed that in the first five stations the space variations in the composition of the community are bigger than the temporary variations, while in the station six the temporary differences prevail. They were factors that could be important to determine the structure of the community, as vicinity to other ecosystems and/or specific biological aspects of the species like adaptations to fluctuating conditions, nutritious habits and migration in search of shady and protected atmospheres.


Identification of ligand-specific G protein-coupled receptor states and prediction of downstream efficacy via data-driven modeling.
Ligand binding stabilizes different G protein-coupled receptor states via a complex allosteric process that is not completely understood. Here, we have derived free energy landscapes describing activation of the β2 adrenergic receptor bound to ligands with different efficacy profiles using enhanced sampling molecular dynamics simulations. These reveal shifts toward active-like states at the Gprotein-binding site for receptors bound to partial and full agonists, and that the ligands modulate the conformational ensemble of the receptor by tuning protein microswitches. We indeed find an excellent correlation between the conformation of the microswitches close to the ligand binding site and in the transmembrane region and experimentally reported cyclic adenosine monophosphate signaling responses. Dimensionality reduction further reveals the similarity between the unique conformational states induced by different ligands, and examining the output of classifiers highlights two distant hotspots governing agonism on transmembrane helices 5 and 7.


The effects of early weaning on innate immune responses of Holstein calves.
The objectives of this study were to compare innate immune responses of calves weaned early (EW; n=23; weaned at 23.7 ± 2.3 d of age) with those of conventionally weaned calves (CW; n=22; weaned at 44.7 ± 2.3 d of age). All calves were fed 3.8L of colostrum within 12h of birth and were subsequently fed milk replacer twice daily. The weaning process began by withdrawal of the afternoon milk-replacer feeding. Milk was fully withdrawn, and the calf was considered completely weaned when it consumed 900 g of calf starter as-fed for 2 consecutive days. Blood samples were collected from all calves at 24, 27, 31, 45, 48, 52, and 66 ± 2.3 d of age. Early weaned calves took a variable amount of time to completely wean from milk replacer; therefore, data were also analyzed by comparing calves grouped by latency to completely weaned (fast=1 to 5 d; intermediate=6 to 8 d; slow=15 to 17 d). Slow-EW calves weighed less than either the fast- or intermediate-EW calves before initiating weaning. At 27 d of age, circulating neutrophils were greater among EW calves than CW calves. Moreover, fast-EW calves had lower neutrophil:mononuclear cell ratios at 45 d of age than other EW calves. Slow-EW calves had lower TNF-α concentrations from whole blood stimulated with endotoxin at 27 and 31 d of age compared with fast- and intermediate-EW calves. All EW calves had decreased neutrophil L-selectin at d 27 and increased neutrophil L-selectin at 31 d of age. At 31 d of age, neutrophil β(2)-integrin was the greatest among the fast-EW calves. All EW calves had decreased neutrophil oxidative burst at 27 and 31 d of age. Three days after CW calves were weaned they had higher neutrophils, hematocrit percentages, and circulating cortisol than EW calves. In addition, 3 d after CW calves were weaned they had decreased neutrophil oxidative burst responses to Escherichia coli. Weaning, irrespective of age, suppressed many innate immune responses. In addition, early weaning transiently suppressed L-selectin expression on neutrophils; however, the immunological significance in the context of the resistance to disease is unknown because EW calves likely had greater protection from passively derived immunoglobulins when they were weaned. Finally, calves with lower BW around 24 d of age may not be suitable for early weaning programs as evident in the suppressed secretion of TNF-α from whole blood cultures during the week following the initiation of weaning.


Male calling song provides a reliable signal of immune function in a cricket.
A critical prediction of the immunocompetence handicap hypothesis is that the expression of secondary sexual traits should be positively correlated with pathogen resistance ability This correlation is necessary if females are to be able to use a particular sexual trait as an indicator of a male's resistance ability. In this study we document a positive correlation between a sexually selected component of the calling song of male house crickets (the number of syllables per chirp) and haemocyte load, an important determinant of the ability to encapsulate pathogens in insects. The results indicate that, by favouring males which produce more syllables per chirp, females may also select males with higher pathogen resistance ability, potentially generating either direct or indirect selection on female mating preferences.


Current Clinical Application of Mesenchymal Stem Cells in the Treatment of Severe COVID-19 Patients: Review.
Coronavirus-2019 disease is a newly diagnosed infectious disease, which is caused by the severe acute respiratory syndrome corona virus-2. It spreads quickly and has become a major public health problem throughout the world. When the viral structural spike protein binds to the angiotensin-converting enzyme-2 receptor of the host cell membrane, the virus enters into host cells. The virus primarily affects lung epithelial cells or other target cells that express angiotensin-converting enzyme-2 receptors in COVID-19 patients. Chemokines released by the host cells stimulate the recruitment of different immune cells. A cytokine storm occurs when a high amount of pro-inflammatory cytokines are produced as a result of the accumulation of immune cells. In COVID-19 patients, cytokine storms are the leading cause of severe acute respiratory distress syndrome. Mesenchymal stem cells are multipotent and self-renewing adult stem cells, which are obtained from a variety of tissues including bone marrow, adipose tissue, Warthon's jelly tissue, and amniotic fluid. Mesenchymal stem cells primarily exert their important therapeutic effects through 2 mechanisms: immunoregulatory effects and differentiation capacity. Mesenchymal stem cells can release several cytokines via paracrine mechanism or by direct interaction with white blood cells such as natural killer cells, T-lymphocytes, B-lymphocytes, natural killer cells, and macrophages, resulting in immune system regulation. Mesenchymal stem cells may help to restore the lung microenvironment, preserve alveolar epithelial cells, prevent lung fibrosis, and treat pulmonary dysfunction that is caused by COVID-19 associated pneumonia. Mesenchymal stem cells therapy may suppress aggressive inflammatory reactions and increase endogenous restoration by improving the pulmonary microenvironment. Furthermore, clinical evidence suggests that intravenous injection of mesenchymal stem cells may radically reduce lung tissue damage in COVID-19 patients. With the advancement of research involving mesenchymal stem cells for the treatment of COVID-19, mesenchymal stem cells therapy may be the main strategy for reducing the recent pandemic.


Bioavailability of five hydrophobic organic compounds to earthworms from sterile and non-sterile artificial soils.
Bioaccumulation factors (BAFs) of organic pollutants to soil biota, often required by risk assessment, are mostly obtained in non-sterile laboratory-contaminated artificial soils. However, microbial degradation has been indicated by many authors to influence the fate of hydrophobic organic compounds (HOCs) in soils. A question arises if the microbial community of peat which is used for artificial soil preparation affects the measured values of BAFs. In this study the effect of soil microorganisms on bioavailability of HOCs was studied and a portion of each soil was sterilized by gamma irradiation. Results indicated that the sterilization process significantly affected the fate of polycyclic aromatic hydrocarbons (PAHs; phenanthrene and pyrene) and increased bioavailability of these compounds to earthworms with BAFs several times higher in the sterile soils compared to their non-sterile variants. This suggests that sterilization of soils can be used as the "worst-case scenario" for laboratory tests of toxicity or bioaccumulation of biodegradable HOCs such as PAHs. It represents a situation of limited microbial degradation resulting in higher bioavailable fractions to other organisms (e.g. invertebrates). This may be the case in soils where microbial communities face stresses caused by contamination or land management. The bioavailability of chlorinated HOCs (lindane, 4,4'-DDT and PCB 153) was not affected by sterilization, as their BAFs were similar in the sterile and non-sterile soils during the experiment.


COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies.
The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.


New insights into the metal specificity of the Pseudomonas aeruginosa pyoverdine-iron uptake pathway.
Pyoverdine (PvdI) is the major siderophore secreted by Pseudomonas aeruginosa PAOI in order to get access to iron. After being loaded with iron in the extracellular medium, PvdI is transported across the bacterial outer membrane by the transporter, FpvAI. We used the spectral properties of PvdI to show that in addition to Fe(3+), this siderophore also chelates, but with lower efficiencies, all the 16 metals used in our screening. Afterwards, FpvAI at the cell surface binds Ag(+), Al(3+), Cd(2+), Co(2+), Cu(2+), Fe(3+), Ga(3+), Hg(2+), Mn(2+), Ni(2+) or Zn(2+) in complex with PvdI. We used Inductively Coupled Plasma-Atomic Emission Spectrometry to monitor metal uptake in P. aeruginosa: TonB-dependent uptake, in the presence of PvdI, was only efficient for Fe(3+). Cu(2+), Ga(3+), Mn(2+) and Ni(2+) were also transported into the cell but with lower uptake rates. The presence of Al(3+), Cu(2+), Ga(3+), Mn(2+), Ni(2+) and Zn(2+) in the extracellular medium induced PvdI production in P. aeruginosa. All these data allow a better understanding of the behaviour of the PvdI uptake pathway in the presence of metals other than iron: FpvAI at the cell surface has broad metal specificity at the binding stage and it is highly selective for Fe(3+) only during the uptake process.


[Outpatient bioresonance treatment of gonarthrosis].
Comparative effectiveness of gonarthrosis treatment with standard methods alone and in combination with bioresonance. The trial entered 75 patients with verified osteoarthrosis of the knee joints (stage I-III by Y. Kellgren). They were divided into two groups. 40 patients of group I received standard combined therapy with nonsteroid antiinflammatory drugs, reducers of trophic processes, physiotherapy. 35 patients of group 2 received the above standard therapy plus bioresonance treatment (BRT). The treatment course in both the groups took 5-6 weeks. There were no statistical differences between the groups in age, sex, duration and severity of the disease. The response was assessed by changes in clinical and laboratory, arthrological and arthrosonographic parameters before the treatment and 3, 5-6 weeks, 12 months after it. The response to treatment was significantly higher in group II (57.5 against 94%). Symptoms of synovitis and tendenitis relieved more also in group 2 (32.5 against 75%). Group 2 patients retained mild pain at rest for a year, while in group I pains intensified by month 6 after the treatment. The addition of BRT to standard therapy of gonarthrosis potentiates anesthetic, antiinflammatory and antiexudative effects; prolongs therapeutic action. BRT was well tolerated. Side effects were absent.


Prevalence and risk factors of chronic kidney disease in an african semi-urban area: Results from a cross-sectional survey in Gueoul, Senegal.
Chronic kidney disease (CKD) is a public health priority worldwide; however, its prevalence and incidence are difficult to assess. In Africa, few studies have been conducted on the prevalence of CKD. This study sought to describe the epidemiological characteristics and profile of CKD, as well as the related risk factors in Guéoul, a semi-urban zone in Senegal. An observational, cross-sectional, and descriptive study was conducted in Guéoul city in Senegal from November 1, 2012, to December 10, 2012, according to the WHO STEPS approach. People older than 35 years living in Guéoul city were included in the study. Cardiovascular and renal disease risk factor screening was conducted for this population. Data were analyzed using the 3.5.1 version of Epi Info software. The significance level was a P <0.05. One thousand four hundred and eleven participants with a mean age of 48 ± 12.68 years and a sex ratio of 0.34 were included in the study (359 men/1052 women). The prevalence of renal disease was 36.5%. Sixty-eight people showed proteinuria greater than two cross with urinary dipsticks. Two hundred and six people had a glomerular filtration rate <60 mL/min, and among them, 201 were in stage III, two in stage IV, and three in stage V according to the modification of diet in renal disease formula. Ninety-eight participants had morphological abnormalities. Cardiovascular risk factors found among participants with renal disease were obesity (25.2%), hypertension (55.5%), diabetes (2.3%), and renal and metabolic syndrome (32.43%). Those that statistically significantly correlated with renal disease were obesity (P = 0.0001), hypertension (P = 0.0001), and diabetes (P = 0.021). This study assessed the extent of renal disease in the population of Guéoul city. Being aware of the prevalence of CKD in the general population of Senegal is mandatory for defining appropriate strategies for the management of these risk factors and progression of renal diseases.


Paraphilic Thoughts, Behaviors and Sex Addiction in a Sample of Persons Who Use Drugs: A Cross-Sectional Study.
The aim of this study was to evaluate the prevalence of paraphilic thoughts/behaviors (including paraphilic disorders) with and without sexual addiction and sexual-related conditions in a sample of substance disorder patients. This was a cross-sectional study of substance-dependent individuals who sought outpatient treatment in São Paulo, Brazil. Data included sociodemographic information, drug of choice, responses to questions about sexual behavior, and to the following standardized questionnaires: (a) Sexual Addiction Screening Test, and (b) Childhood Trauma Questionnaire. The sample comprised 134 persons who use drug, predominantly men (76.1%), 39.6% were aged between 18 and 29 years, and 54.9% were single. Most were persons who use polydrug, 73.9% were alcohol and cocaine users, 63.4% marijuana users, 81.1% tobacco users, and 5.2% steroid users. Prevalence of paraphilic thoughts/behaviors (including paraphilic disorders) with and without sexual addiction was 47%. The HPV/herpes and hepatitis B rates were 7.9% (P = 0.021) and 6.3% (P = 0.046) respectively. Paraphilic and nonparaphilic thoughts/behaviors were associated to the presence of childhood physical neglect (odds ratios [OR] = 4.7, 95% confidence interval [CI] 1.0 to 21.9), low educational level (OR = 7.2, 95% CI 1.4 to 36), heterosexuality (OR = 3.8, 95% CI 1.1 to 12.8) and youth (age 18 to 20 years) (OR = 5.6, 95% CI 1.4 to 11.8). The high prevalence of paraphilic thoughts/behaviors with or without sex addiction in persons who use drugs may be related to the experience of physical and emotional neglect during childhood and this possibility should routinely be investigated in clinical practice.


Dynamics of cognitive control: Theoretical bases, paradigms, and a view for the future.
Cognitive control (with the closely related concepts of attention control and executive function) encompasses the collection of processes that are involved in generating and maintaining appropriate task goals and suppressing task goals that are no longer relevant, as well as the way in which current goal representations are used to modify attentional biases to improve task performance. Here, we provide a comprehensive but nonexhaustive review of this complex literature, with an emphasis on the contributions made by techniques for studying human brain function. The review is divided into five sections: (a) overview and historical perspective of cognitive control, its subcomponent processes, and its neural substrate; (b) most common types of tasks used to assess and/or manipulate the level of control; (c) main research findings obtained with various imaging methodologies, with a focus on ERP data, and briefer overviews of oscillatory (event-related spectral perturbations) and fMRI data; (d) major theories of cognitive control; and (e) discussion of open questions regarding how to integrate the various dimensions of control, as well as the faster versus slower temporal dynamics informing this complex and multifaceted concept.