Notes

The Encouraging Treatment Wants of Cancer malignancy Patients: a planned out Evaluate.
Dabrafenib, as an inhibitor of RIPK3, may be an effective treatment to limit the progression of the tubulointerstitial fibrosis.Background The importance of promoting child participation in school health has been emphasized internationally. This study examined ways in which Japan's school health system involves children, and factors enabling child participation in this system. Additionally, we suggest strategies to promote child participation in school health in developing countries. Methods We conducted a document review for clarifying the importance of and recent trends in child participation in school health. We summarized the system of child participation in school health in Japan and examined factors enabling child participation. Results We identified the following four factors that enable child participation in school health in Japan 1) having an explicit legal basis of participatory activities at the national level, 2) having clear notification of the necessity of children's voluntary participation in relevant administrative documents at the prefectural and municipal levels, 3) establishing a system for teachers to provide support for participatory activities at the school level, and 4) having a shared understanding among stakeholders about the pedagogical importance of participatory activities in school health. Conclusion In order to promote child participation in school health activities in developing countries, it is necessary to describe clearly the importance, benefits, impacts and purposes of child participation in relevant legal and administrative documents at relevant administrative levels. Additionally, schools should ensure that stakeholders have a common understanding of the educational benefits of child participation considering the cultural context of each country. Furthermore, it is helpful to conduct appropriate training for teachers to enable them to facilitate child participation.A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the clinical evidence behind current renal impairment dosage recommendations for pediatric patients in a standard pediatric dosing handbook. The sources of recommendations and comparisons included the pediatric dosing handbook (Lexicomp), the U.S. Food and Drug Administration-approved manufacturer's labels, and published studies in the literature. One hundred twenty-six drugs in Lexicomp had pediatric renal dosing recommendations. Only 14% (18 of 126) of Lexicomp pediatric renal dosing recommendations referenced a pediatric clinical study, and 15% of manufacturer's labels (19 of 126) described specific dosing regimens for renally impaired pediatric patients. Forty-two products had published information on pediatric renal dosing, but 19 (45%) were case studies. When pediatric clinical studies were not referenced in Lexicomp, the renal dosing recommendations followed the adult and pediatric dosing recommendations on the manufacturer's label. Clinical evidence in pediatric patients does not exist for most renal dosing recommendations in a widely used pediatric dosing handbook, and the adult renal dosing recommendations from the manufacturer's label are currently the primary source of pediatric renal dosing information.Alpha-gal syndrome (AGS) describes a wide spectrum of hypersensitivity reactions mediated by specific IgE to the α-gal epitope (galactose-α-1,3-galactose) ubiquitously expressed on glycolipids/glycoproteins of most mammals. This fascinating new entity has completely changed the paradigms of allergy as allergic response is directed against an oligosaccharide and the reactions can be both immediate and delayed. They appear to be stimulated only by tick bites which induce production of α-gal specific IgE antibodies that lead to (at times fatal) hypersensitivity response. AGS is completely different to previously described anaphylaxis to tick saliva. It provides unique insight into the interplay between different arms of the immune system and the role of ectoparasites in the development of anaphylaxis to food and medication in patients at risk of tick bites including travellers. This review summarises recent advances in our understanding of its clinical presentation, pathomechanism and role of various tick species in the development of AGS.Doxorubicin is the most effective single agent in the treatment of non Hodgkin's lymphoma (NHL). Its use is limited because of the cardiac toxicity primarly in elderly patients (pts) and in pts with history of cardiac disease. Liposomal doxorubicin has been proven to reduce cardiotoxicity. The aim of this retrospective study was the use of non-peghylated liposomal doxorubicin (NPLD) in term of efficacy, response rate and incidence of cardiac events. We retrospectively collected the experience of 33 Hematological Italian Centers in using non-peghylated liposomal doxorubicin (NPLD). Nine hundred and forty-six consecutive pts treated with R-COMP (doxorubicin was substituted with NPLD, Myocet®) were collected. Median age was 74 years, the reasons for use of NPLD were age (466 pts), cardiac disease (298 pts), uncontrolled hypertension (126 pts), other reasons (56 pts). According to clinicians' evaluation, 49,9% of pts would not have used standard doxorubicin for different situations (age, cardiomyopathy, previous use of doxorubicin, uncontrolled hypertension). Overall 687 pts (72,6%) obtained a complete remission (CR). About 5% (n=51) of subjects developed major cardiotoxic events including heart failure (N=31), ischemic heart disease (N=16), acute heart attack (N=3), and acute pulmonary oedema (N=1). After a median follow-up of 32 months, 651 pts were alive and the overall survival (OS) was 72%. After a median observation period of 23 months Disease Free Survival (DFS) was 58%. Either in univariate or in multivariate analysis OS and DFS were not significantly affected by age or cardiac disease. Our findings strongly support that including R-COMP is effective and safe when the population is at high risk of cardiac events and negatively selected. Moreover, the use of this NPLD permitted that about half of our population had the opportunity to receive the best available treatment. This article is protected by copyright. All rights reserved.Background Compositae plant sensitization in children is relatively frequent. From 1995 to 2006, we found a prevalence of 1.8% sesquiterpene lactone (SL) mix/parthenolide patch test positives among consecutive eczema patients under 18 years. Objectives To report the results of patch test screening for Compositae sensitization in patients under 18 years in the last 13 years. Methods Children/adolescents under 18 years, diagnosed with Compositae sensitization between 2007 and 2019, were included. Results Among 388 tested, 12 (3%) were Compositae-sensitized, and 11(2.8%) had positive reactions to SL mix. Compositae mix 5% pet. elicited positive reactions in 6 of 7 tested, and dandelion extract 2.5% pet. in 6 of 10 tested. The mean age of the 5 girls was 9.4 years and 11.7 years in the 7 boys. Eleven children had a personal and 1 a family history of atopy, and 11 children had hand eczema. Only 2 were mono-sensitized to Compositae. Conclusions SL mix is a suitable screening agent among children/adolescents in our area, well supplemented with Compositae mix 5% and dandelion extract. The study emphasizes the importance of Compositae screening in children with a personal/family history of atopy, hand eczema or widespread, airborne dermatitis, summer exacerbation, and plant exposure. This article is protected by copyright. All rights reserved.A hyperinflammatory response to SARS-CoV-2 infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with COVID-19. Agents that inhibit components of the pro-inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the pro-inflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus-associated kinase (JAK)-inhibitor that interrupts the signaling of multiple cytokines implicated in COVID-19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin-converting-enzyme-2 up regulation. However, baricitinib's immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients' immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events which is concerning given the proclivity towards a hyper-coagulable state in COVID-19 patients. In this article we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety and current progress in COVID-19 clinical trials.Asthma is a common lung condition that makes breathing difficult through the inflammation and constriction of the lung airways. Epidemiological evidence supports the presence of a positive association between prenatal maternal psychological stress (PMPS) and asthma in the offspring, suggesting the disease may have developmental origins. T-helper 2 (Th2) cells are a major subtype of T-helper cells, producing Th2 cytokines, which may be the main drivers of asthma symptoms. A Th2 dominant blood cytokine profile may therefore indicate an increased risk of asthma, as studies have shown a link between PMPS and a T-helper 2 (Th2) cytokine profile in offspring. The mechanism by which PMPS may cause Th2 cytokine dominance in the offspring is unclear. Epigenetic modifications in utero can lead to long-lasting effects that persist postnatally, and have therefore been implicated in this relationship. Increased maternal blood cortisol levels due to PMPS may increase transfer of cortisol to the fetus, where the temporarily increased levels may induce changes in the epigenome. Evidence from animal studies suggests that genes controlling cytokine production in T-cells can be epigenetically modified in a way that increases Th2 cytokine production. Other evidence suggests that methylation of the NR3C1 gene decreases hippocampal glucocorticoid receptor expression, leading to decreased negative regulation of the hypothalamus-pituitary-adrenal axis. This can increase cortisol production which has been shown to increase Th2 cytokine production. Therefore, the link between PMPS and a Th2 offspring cytokine profile, mediated through epigenetic changes, may explain the positive relationship between PMPS and asthma in the offspring.Quaternary climate oscillations are a well-known driver of animal diversification, but their effects are most well studied in areas where glaciations lead to habitat fragmentation. In large areas of the planet, however, glaciations have had the opposite effect, but here their impacts are much less well understood. This is especially true in Southeast Asia, where cyclical changes in land distribution have generated enormous land expansions during glacial periods. In this study, we selected a panel of five songbird species complexes covering a range of ecological specificities to investigate the effects Quaternary land bridges have had on the connectivity of Southeast Asian forest biota. Specifically, we combined morphological and bioacoustic analysis with an arsenal of population genomic and modelling approaches applied to thousands of genome-wide DNA markers across a total of hundreds of individuals. Our analyses show that species dependent on forest understorey exhibit deep differentiation between Borneo and western Sundaland, with no evidence of gene flow during the land bridges accompanying the last 1-2 ice ages. In contrast, dispersive canopy species and habitat generalists have experienced more recent gene flow. Our results argue that there remains much cryptic species-level diversity to be discovered in Southeast Asia even in well-known animal groups such as birds, especially in nondispersive forest understorey inhabitants. We also demonstrate that Quaternary land bridges have not been equally suitable conduits of gene flow for all species complexes and that life history is a major factor in predicting relative population divergence time across Quaternary climate fluctuations.Objective We aimed to evaluate the validity of a MARSIPAN-guidance-adapted Early Warning System (MARSI MEWS) and compare it to the National Early Warning Score (NEWS) and an adapted version of the Physical Risk in Eating Disorders Index (PREDIX), to ascertain whether current practice is comparable to best-practice standards. Methods We collated 3,937 observations from 36 inpatients from Addenbrookes Hospital over 2017-2018 and used three independent raters to create a "gold standard" of deteriorating cases. We ascertained performance metrics (Receiver Operating Characteristic Area Under the curve) for MARSI MEWS, NEWS and PREDIX; we also tested the proof of concept of a machine-learning-based early-warning-system (ML-EWS) using cross-validation and out-of-sample prediction of cases. Results The MARSI MEWS system showed higher ROC AUC (0.916) compared to NEWS (0.828) or PREDIX (0.865). ML-EWS (random forest) performed well at independent samples analysis (0.980) and multilevel analysis (0.922). Conclusion MARSI MEWS seems most suitable for identifying critically deteriorating cases in anorexia nervosa inpatient population. We did not examine community practice in which the PREDIX arguably remains the best to ascertain deteriorating cases. Our results also provide a first proof of concept for the development of artificial-intelligence-based early warning systems in anorexia nervosa. Implications for inpatient clinical practice in eating disorders are discussed.Background Canine packed red blood cells (pRBCs) can be stored under refrigeration for several days; however, cellular metabolism remains active inside the units, thus producing substances that affect their quality. Objectives We aimed to evaluate hematologic, biochemical, and blood gas variable alterations that occur in canine pRBCs during storage, and their effects on recipient clinicopathologic parameters. Methods The study was conducted in two phases. In phase I, 15 pRBC units containing CPDA-1 were stored for 28 days; samples were collected weekly from the units of days 0 to 28 to measure the packed cell volume (PCV), pH, partial pressure carbon dioxide (PCO2 ), partial pressure oxygen (PO2 ), concentrations of lactate and potassium, and the percent hemolysis. In phase II, another 22 canine pRBC units stored for different time periods (maximum of 21 days) were transfused, and the recipients were evaluated before and after transfusion for changes in clinical parameters (heart rate, respiratory rate, systolic arterial pressure, and rectal temperature) and hematologic variables (PCV, lactate and potassium concentrations, pH, PCO2 , the ratio of arterial oxygen partial pressure to fractional inspired oxygen [PO2 /FiO2 ] ratio, oxygen saturation [SaO2 ], base excess, and bicarbonate [HCO3 ]). Results In the pRBC units, the PCV increased from 70% to 78.33%, the lactate concentration increased 627%, the potassium concentration increased 183%, the percent hemolysis reached 0.69%, and the pH decreased 9% after 28 days. However, the dogs who received transfusions were not negatively affected. There was a significant increase in PCVs, and a significant decrease in heart rates. Conclusion Canine pRBCs undergo hematologic, blood gas, and biochemical alterations during storage; however, the transfusion of pRBCs stored for up to 21 days increased PCVs without causing harm to the dogs.Background Arterial spin labeling (ASL) is a useful tool for measuring cerebral blood flow (CBF). However, due to the low signal-to-noise ratio (SNR) of the technique, multiple repetitions are required, which results in prolonged scan times and increased susceptibility to artifacts. Purpose To develop a deep-learning-based algorithm for simultaneous denoising and suppression of transient artifacts in ASL images. Study type Retrospective. Subjects 131 pediatric neuro-oncology patients for model training and 11 healthy adult subjects for model evaluation. Field strength/sequence 3T / pseudo-continuous and pulsed ASL with 3D gradient-and-spin-echo readout. Assessment A denoising autoencoder (DAE) model was designed with stacked encoding/decoding convolutional layers. Reference standard images were generated by averaging 10 pairwise ASL subtraction images. The model was trained to produce perfusion images of a similar quality using a single subtraction image. Performance was compared against Gaussian and non-locaals in raw ASL images. Level of evidence 3 TECHNICAL EFFICACY STAGE 1.A trial was conducted to evaluate whether nitrate reductase (NR) participates in salicylic acid (SA)-improved water stress (WS) tolerance in pepper plants. Before starting WS treatment, 0.5 mM SA was applied to half of well-watered (WW) and WS-plants as a foliar spray once a day for a week. Soil water holding capacity was maintained at 40 and 80% of the full water storing capacity for WS and well-watered (WW) plants, respectively. Water stress caused substantial decreases in total plant dry weight, Fv/Fm, chlorophyll a and b, relative water content, leaf water potential (ΨI) by 53, 37, 49, 21, 36 and 33%, respectively relative to control, but significant increases in malondialdehyde (MDA), hydrogen peroxide (H2 O2 ), electrolyte leakage (EL), methylglyoxal (MG), proline, key antioxidant enzymes' activities, NO and NR activity. The SA reduced oxidative stress, but improved antioxidant defence system, ascorbate-glutathione (AsA-GSH) cycle enzymes, glyoxalase system-related enzymes, glyoxalase I (Gly I) and glyoxalase II (Gly II), plant growth, photosynthetic traits, NO, NR and proline. SA-induced WS tolerance was further improved by supplementation of sodium nitroprusside (SNP), a donor of NO. NR inhibitor, sodium tungstate (ST) was applied in conjunction with SA and SA+SNP to the WW and WS-plants to assess whether NR contributes to SA-improved WS tolerance. ST abolished the beneficial effects of SA by reducing NO and NR activity in WS-pepper, but the application of SNP along with SA+ST reversed negative effects of ST, showing that NO and NR are jointly needed for SA-induced WS tolerance of pepper plants. This article is protected by copyright. All rights reserved.Density-functional theory calculations of (TiO2 )n clusters (n = 1-5) in the gas phase and adsorbed on pristine graphene as well as graphene quantum dots are presented. The cluster adsorption is found to be dominated by van der Waals forces. The electronic structure and in particular the excitation energies of the bare clusters and the TiO2 /graphene composites are found to vary largely in dependence on the size of the respective constituents. This holds in particular for the energy and the spatial localization of the highest occupied and lowest unoccupied molecular orbitals. In addition to a substantial gap narrowing, a pronounced separation of photoexcited electrons and holes is predicted in some instances. This is expected to prolong the lifetime of photoexcited carriers. Altogether, TiO2 /graphene composites are predicted to be promising photocatalysts with improved electronic and photocatalytic properties compared to bulk TiO2 .Experimental and theoretical studies have highlighted the impact of gene flow on the probability of evolutionary rescue in structured habitats. Mathematical modeling and simulations of evolutionary rescue in spatially or otherwise structured populations showed that intermediate migration rates can often maximize the probability of rescue in gradually or abruptly deteriorating habitats. These theoretical results corroborate the positive effect of gene flow on evolutionary rescue that has been identified in experimental yeast populations. The observations that gene flow can facilitate adaptation are in seeming conflict with traditional population genetics results that show that gene flow usually hampers (local) adaptation. Identifying conditions for when gene flow facilitates survival chances of populations rather than reducing them remains a key unresolved theoretical question. We here present a simple analytically tractable model for evolutionary rescue in a two-deme model with gene flow. Our main result is a simple condition for when migration facilitates evolutionary rescue, as opposed as no migration. We further investigate the roles of asymmetries in gene flow and/or carrying capacities, and the effects of density regulation and local growth rates on evolutionary rescue.Background Cytology appears to be a viable option to histological samples for proper storage and maintenance of autopsy material for DNA extraction and analysis. In the present study, we tested the feasibility of using archived air-dried smears produced at the time of the autopsy for simple molecular analysis, comparing quantity and quality of the DNA extracted from the smears to that of correspondent histological specimens. Methods Air-dried cytological smears were obtained from scrapings of exactly the same areas collected for histological study. DNA was extracted using a commercially available protocol from all samples, with calculation of purity ratio and overall concentration. The integrity of the extracted DNA was also verified through conventional PCR. Results Five cases of lung tumors (2 small cell carcinomas and 3 adenocarcinomas) were collected. Percentage of tumor cells and necrosis ranged from 30 to 90% and from 10 to 40%, respectively, in the cytological preparations and from 50 to 90% and from 10 to 80%, respectively, in the histological preparations. 260/280 purity ratio had a median of 1.87 in cytology versus 1.94 in histology. Mean DNA concentration for cytological preparations was 2653 ng / ml versus 757,2 ng/ml for histological preparations. DNA from all five cases of cytology were successfully amplified by conventional PCR, in contrast to none from the histology specimens. Conclusions Archived air-dried smears scraped from tumoral lesions in autopsies have proven to yield a good concentration of quality DNA for conventional PCR, with better results than formalin fixed paraffin embedded material.Background and aim We investigated the relationship of BMI and waist circumference with the risk of colorectal cancer (CRC) using a population-based cohort database and to explore the relationship of CRC with diabetes status. Methods Retrospective data (age >20 years) on anthropometric variables, blood parameters of fasting sugar, lipid levels, and blood pressure were collected from the National Health Insurance Corporation database between 2009 and 2012. Cox regression models were used to estimate hazard ratio (HR) and corresponding 95% confidence intervals (95% CI). Results Of the 23 121 360 people studied, 120 579 were diagnosed with CRC after a median follow-up period of 5.4 years. Both waist circumference and BMI were positively associated with increased risk of CRC, regardless of age or sex. After mutual adjustment, only waist circumference was significantly associated with increased risk of CRC (HR 1.275, 95% CI 1.205-1.349). When the risk of CRC was compared according to diabetes status among people with the same waist circumference range, risk of CRC was higher for those with worse diabetes status. Conclusion When waist circumference and BMI were mutually adjusted, only waist circumference was associated with CRC risk. In addition, the risk of CRC is gradually higher in those with worsening diabetes, even if their waist circumferences are within the same range.Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening debilitating lung disease necessitating long-term oral antifungal treatment. However, development of antifungal-resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single-case reports and case series reporting less then 10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n = 143) or an echinocandin (n = 237) and were included in the meta-analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI) 52%-70%; I2 = 73.3%; P less then .001), to amphotericin B was 58% (95% CI 36%-80%; I2 = 86.6%; P less then .001) and to echinocandins was 62% (95% CI 53%-72%; I2 = 63.6%; P less then .001). Amphotericin B courses were usually doses at slightly less then 1 mg/Kg (deoxycholate) or 3 mg/Kg (liposomal) for 2-3 weeks. Micafungin doses varied from 12.5 to 300 mg (frequently, 150 mg) daily for at least 3 weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5-35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head-to-head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short- and longer-term outcomes of these agents.Monarch butterflies are known for their spectacular annual migration in eastern North America, with millions of monarchs flying up to 4,500 kilometers to overwintering sites in central Mexico. Monarchs also live west of the Rocky Mountains, where they travel shorter distances to overwinter along the Pacific Coast. It is often assumed that eastern and western monarchs form distinct evolutionary units, but genomic studies to support this notion are lacking. We used a tethered flight mill to show that migratory eastern monarchs have greater flight performance than western monarchs, consistent with their greater migratory distances. However, analyzing more than 20 million SNPs in 43 monarch genomes, we found no evidence for genomic differentiation between eastern and western monarchs. Genomic analysis also showed identical and low levels of genetic diversity, and demographic analyses indicated similar effective population sizes and ongoing gene flow between eastern and western monarchs. Gene expression analysis of a subset of candidate genes during active flight revealed differential gene expression related to non-muscular motor activity. Our results demonstrate that eastern and western monarchs maintain migratory differences despite ongoing gene flow, and suggest that migratory differences between eastern and western monarchs are not driven by select major-effects alleles. Instead, variation in migratory distance and destination may be driven by environmentally induced differential gene expression, or by many alleles of small effect.Artemisinin (ART) has been shown to suppress B cell activation and plasma cell formation. However, its effect on splenic marginal zone (MZ) B cells is unknown. Splenic MZ B cells play a critical role in rapidly induced Ab production against blood-borne foreign Ags. Dysfunction of MZ B cells, due to inhibition of its proliferation or displacement of its homing, results in an attenuated adaptive humoral response. Here, we investigate the effect of ART on splenic MZ B (CD19+ CD21high CD23low ) and B10 (CD19+ CD1dhigh CD5+ ) B cells to explore the mechanisms of ART-induced immunosuppression in T cell-deficient nude mice challenged with hamster xenoantigens. In this study, we demonstrate that ART decreases T cell-independent xenogeneic IgM Ab production and, this is associated with a strong suppression of MZ B cell proliferation and a relative increase of CD21low CD23+ follicular and B10 B cells. In addition, this suppression impairs IL-10 production. Taken together, our data indicate that ART suppresses B cell immune responses through a distinctive effect on splenic MZ B and other B cells. This represents a new mechanism of ART-induced immunosuppression.Anti-double-stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti-dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti-dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti-dsDNA IgG. The results revealed that TWEAK dose-dependently enhanced cellular internalization of anti-dsDNA IgG and the expression of high-mobility group box 1 (HMGB1). In addition, TWEAK and anti-dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti-dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor-κB and phosphatidylinositide 3-kinase/protein kinase B pathways. Therefore, TWEAK/Fn14 signaling contributes to the penetration of anti-dsDNA IgG and relevant fibrotic processes in mesangial cells.Topical timolol has been shown to be effective on treatment of Kaposi sarcoma. We present the case of a 72-year-old man with classic Kaposi sarcoma on upper limbs, treated with topical timolol 0.5% twice a day with a pruritic eruption on areas of application.Members of the NLR family pyrin domain containing (NLRPs) are pattern recognition receptors that participate in innate immunity. They form inflammasomes, which are platforms for caspase-1 recruitment and activation. The NLRP pyrin domain (PYD) is critical for the assembly of inflammasomes due to its ability to mediate protein interactions. Despite intensive structural studies on inflammasomes with PYDs, the structure of the PYD of NLRP9-the least studied member of the family-remains unknown. Herein, we report the crystal structure of the human NLRP9 PYD at 2.1 Å resolution, which reveals a kinked N-terminal loop oriented toward the interior of the helical bundle. Based on our findings, we propose a regulatory role for the kinked N-terminal loop of NLRP9 PYD in inflammasome assembly.The degradation of red clover isoflavones was studied in vitro using a rumen fluid buffer system. Various amounts of red clover extract (5-75 mg) together with hay or concentrate-rich diet were added to 40 ml of rumen fluid obtained from non-lactating and lactating dairy cows, respectively, and incubated for 0, 3, 6, 12 or 24 hr. Following incubation, concentrations of daidzein, genistein, formononetin, biochanin A and equol were determined in the samples. After 3 hr of incubation, isoflavone metabolism and equol production could be observed. The results obtained indicate that hay diet provides better conditions for isoflavone metabolism, as concentrations of daidzein, formononetin and biochanin A were higher in incubations based on the concentrate-rich diet and the production of equol was higher in incubations based on the hay diet. Furthermore, in incubations with higher amounts of added clover extract, a decrease in equol production was observed. Further studies are needed to clarify the role of adaptation of rumen microflora on isoflavone degradation kinetics and to clarify the interrelationship between various dietary factors, rumen microbiota and isoflavones. The knowledge of isoflavone metabolism kinetics in dependence on studied factors will be useful for the optimization of feeding dose.Human T cell leukemia virus type 1 (HTLV-1) as the first human retrovirus is currently a serious endemic health challenge. Despite the use of assorted molecular or serological assays for HTLV-1 detection, there are several limitations due to the lack of a confirmatory test that may affect the accuracy of the results. Herein, a novel label-free biosensor for the detection of HTLV-1 Tax gene has been reported. An electrochemical facile ecofriendly synthesis method has been demonstrated based on a synthesis of nanocomposite of reduced graphene oxide, polypyrrole, and gold nanoparticles (rGO-PPy-(l-Cys)-AuNPs) deposited on the surface of screen-printed carbon electrode. Electrochemical techniques were used to characterize and study the electrochemical behavior of the rGO-PPy-(l-Cys)-AuNPs, which exhibited a stable reference peak at 0.21 V associated with hybridization forms by applying the differential pulse voltammetry. The designed DNA biosensor presented a wide linear range from 0.1 fM to 100 µM and a low detection limit of 20 atto-molar. The proposed biosensor presented in this study provides outstanding selectivity, sensitivity, repeatability, and reproducibility.Background The purpose of the study was to examine the associations among cardiorespiratory fitness (CRF), weight status and academic achievement in youth, and to determine if these relationships are moderated by poverty status. Methods The sample included 5th (N = 27,791) and 8th grade (N = 16,047) South Carolina students. Academic achievement was assessed using a state-wide assessment and classified into 2 categories (ie, does not meet/approaches standards vs meets/exceeds standards). CRF was assessed and expressed as Healthy Fitness Zone (HFZ) or Needs Improvement/Needs-Improvement-Health Risk. Students' demographics and poverty status were reported. Multilevel logistic regression analyses were used to examine the association between CRF, weight status and academic achievement. Interaction terms were introduced into the final models. Analyses were performed separately by grade level and academic subject. Results The CRF was significantly associated with the odds of meeting/exceeding academic standards after controlling for covariates and adjusting for weight status. The relationship between CRF and academic achievement varied significantly by poverty status. After adjustment for CRF, weight status was not significantly associated with academic achievement. Conclusions The odds of achieving academic standards were significantly higher among students achieving CRF HFZ regardless of poverty status. CRF may partially mitigate the adverse effect of poverty on academic achievement.Background and objective COPD is the third most common cause of death worldwide and fourth most common in the United States. In hospitalized patients with COPD, mortality, morbidity and healthcare resource utilization are high. Skeletal muscle loss is frequent in patients with COPD. However, the impact of muscle loss on adverse outcomes has not been systematically evaluated. We tested the hypothesis that patients hospitalized for COPD exacerbation with, compared to those without, a secondary diagnosis of muscle loss phenotype (all ICD-9 codes associated with muscle loss including cachexia) will have higher mortality and cost of care. Methods The NIS database of hospitalized patients in 2011 (1 January-31 December) in the United States was used. The impact of a muscle loss phenotype on in-hospital mortality, LOS and cost of care for each of the 174 808 hospitalizations for COPD exacerbations was analysed. Results Of the subjects admitted for a COPD exacerbation, 12 977 (7.4%) had a secondary diagnosis of muscle loss phenotype. A diagnosis of muscle loss phenotype was associated with significantly higher in-hospital mortality (14.6% vs 5.7%, P less then 0.001), LOS (13.3 + 17.1 vs 5.7 + 7.6, P less then 0.001) and median hospital charge per patient ($13 947 vs $6610, P less then 0.001). Multivariate regression analysis showed that muscle loss phenotype increased mortality by 111% (95% CI 2.0-2.2, P less then 0.001), LOS by 68.4% (P less then 0.001) and the direct cost of care by 83.7% (P less then 0.001) compared to those without muscle loss. Conclusion In-hospital mortality, LOS and healthcare costs are higher in patients with COPD exacerbations and a muscle loss phenotype.The Plumbaginaceae (non-core Caryophyllales) is a family well known for species adapted to a wide range of arid and saline habitats. Of its salt-tolerant species, at least 45 are in the genus Limonium; two in each of Aegialitis, Limoniastrum and Myriolimon, and one each in Psylliostachys, Armeria, Ceratostigma, Goniolimon and Plumbago. All the halophytic members of the family have salt glands and salt glands are also common in the closely related Tamaricaceae and Frankeniaceae. The halophytic species of the three families can secrete a range of ions (Na+ , K+ , Ca2+ , Mg2+ , Cl- , HCO3 - , SO4 2 ) and other elements (As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn). Salt glands are, however, absent in salt-tolerant members of the sister family Polygonaceae. We describe the structure of the salt glands in the three families and consider whether glands might have arisen as a means to avoid the toxicity of Na+ and/or Cl- or to regulate Ca2+ concentrations with the leaves. We conclude that the establishment of lineages with salt glands took place after the split between the Polygonaceae and its sister group the Plumbaginaceae. This article is protected by copyright. All rights reserved.Aims Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by a mutation in the TSC1 or TSC2 gene with a broad spectrum of physical and psychological manifestations. The aim of the study was to examine incontinence, psychological problems, and adaptive behavior skills in patients with TSC. Methods Through a worldwide TSC support group, 26 children (4-17 years) and 15 adults (18-50 years) with TSC were recruited (38.1% male, mean age 16.4 years). Parents or care-givers completed the Developmental Behavior Checklist (DBC), the Parental Questionnaire Enuresis/urinary Incontinence, and the Vineland Adaptive Behavior Scales (3rd edition). Results A total of 60.0% of the participants had nocturnal enuresis (NE), 51.3% daytime urinary incontinence (DUI) and 52.4% fecal incontinence (FI). 65.4% of children and 50.0% of adults had a clinically relevant DBC score. Psychological symptoms were associated with at least one subtype of incontinence. The mean adaptive behavior composite (ABC) score of the patients was 57.2 (SD = 26.1), with 38.1% in the average or below-average range (IQ >70), 26.2% with a mild, 11.9% with a moderate and 23.8% with a severe/profound intellectual disability. The incontinence rate was significantly higher in the groups with a lower ABC score. Conclusion A substantial proportion of patients with TSC are affected by incontinence and psychological symptoms. Incontinence was higher in persons with lower adaptive skills and those with at least one type of incontinence showed a significantly higher DBC score. As incontinence and psychological problems affect daily functioning and well-being, assessment, and treatment are recommended.Purpose High-Dose-Rate (HDR) brachytherapy is one of the most effective ways to treat the prostate cancer, which is the second most common cancer in men worldwide. This treatment delivers highly conformal dose through the transperineal needle implants and is guided by a real time ultrasound (US) imaging system. Currently, the brachytherapy needles in the US images are manually segmented by physicists during the treatment, which is time-consuming and error-prone. In this study, we propose a set of deep learning based algorithms to accurately segment the brachytherapy needles and locate the needle tips from the US images. Methods Two deep neural networks are developed to address this problem. First, a modified deep U-Net is used to segment the pixels belonging to the brachytherapy needles from the US images. Second, an additional VGG-16 based deep convolutional network is combined with the segmentation network to predict the locations of the needle tips. The networks are trained and evaluated on a clinical US images dataset with labeled needle trajectories collected in our hospital (Institutional Review Board approval (IRB 41755)). Results The evaluation results show that our method can accurately extract the trajectories of the needles with a resolution of 0.668 mm and 0.319 mm in x and y direction respectively. 95.4% of the x direction and 99.2% of the y direction have error ≤ 2 mm. Moreover, The position resolutions of the tips are 0.721 mm, 0.369 mm and 1.877 mm in x, y and z directions respectively, while 94.2%, 98.3% and 67.5% of the data have error ≤ 2 mm. Conclusions This paper proposed a neural network based algorithm to segment the brachytherapy needles from the US images and locate the needle tip. It can be used in the HDR brachytherapy to help improve the efficiency and quality of the treatments.Purpose The study investigators hypothesized that Point of Care Ultrasound (POCUS) training through bolus didactic and workshop experiences may be sufficient for trainees to learn the cognitive aspects, while an extended period of exposure with formative feedback is responsible for developing the psychomotor skills critical for POCUS. Methods The investigators studied trainees over the course of an academic year. They compared trainees' performance on written (cognitive) and observed image acquisition (psychomotor) exams at baseline and at each subsequent quarter, using a stepped-wedge design. They performed linear regression analysis to determine which variables contributed to knowledge and psychomotor skill development. Results Twenty-six trainees met the study requirements and participated in the POCUS curriculum. Participating in a POCUS rotation was consistently associated with an increase in psychomotor scores. There was no consistent variable to predict an increase in trainee's score on written knowledge assessments. Conclusions Extended exposure to POCUS over a 4-week rotation with direct and indirect formative feedback can explain difference in scores on psychomotor skills assessments. Trainees scored similarly on the written assessment with or without a POCUS rotation. Training through didactic and workshop experiences may be sufficient to learn the cognitive aspects, but not psychomotor skills required for POCUS.Investigate the effect of flufenamic acid (FFA) on lung injury of sepsis rats. Rat sepsis model was established using cecal ligation and puncture (CLP). The pathomorphology of lung tissue was detected by Hematoxylin-eosin (H&E) staining. The expression levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and high mobility group box-1 (HMGB-1) in serum and TNF-α, IL-6, malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in lung tissues. The viability of RLE-6TN cells was detected by CCK-8 assay. The expression of carbonyl reductase 1 (CBR1) in RLE-6TN cells was analyzed by Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The inflammatory response was obviously enhanced in CLP-constructed sepsis rats and alleviated by FFA treatment. Sepsis induced the increase of W/D ratio, promoted the levels of TNF-α, IL-6, HMGBR1, and MDA and inhibited the levels of SOD and GSH. FFA could effectively alleviate the sepsis-induced lung injury. The viability of RLE-6TN cells induced by LPS was improved with the treatment of FFA. CBR1 expression in LPS-induced RLE-6TN cells was decreased and FFA could up-regulate the CBR1 expression. In addition, LPS-induced lung injury promoted the inflammatory response in lung tissues, increased the W/D ratio and levels of TNF-α, IL-6, HMGBR1, and MDA while inhibited the levels of SOD and GSH. FFA could effectively improve the LPS-induced lung injury while the effect of FFA on LPS-induced lung injury was alleviated by CBR1 interference. FFA may alleviate sepsis-induced lung injury by up-regulating CBR1.Aim Deliberate self-poisoning or overdose is a common presentation to the paediatric emergency departments (ED) due to a lack of emergency access to child and adolescent mental health services. We overview medical and psychiatric assessment of overdoses in youth with the most commonly implicated drug, paracetamol, as a case study. Methods A what, when and why framework is adopted to guide clinicians on what information should be ascertained, when overdose treatment should be initiated and how to explore why the overdose occurred. Results Presentations are often asymptomatic while gastrointestinal symptoms offer an alarm signal for severe hepatotoxicity. A worst-case exposure amount and time elapsed since ingestion should be calculated to determine whether N-acetylcysteine treatment is indicated. Establishing reasons why the young person took the overdose, along with assessing the degree of remorse or regret, is crucial for discharge planning. Conclusion Given the importance of timely assessment and treatment, paediatric emergency staff need to be familiar with the protocol for care. Attention needs to be focused on both the medical and psychological risk, and staff need to consider the reasons behind the overdose and following a biopsychosocial assessment, ensure that the young person and family are adequately signposted for future mental health care if needed.Background A pandemic of SARS-CoV-2 infection broke out all over the world, however, epidemiological data and viral shedding in pediatric patients are limited. Methods We conducted a retrospective, multi-center study, and followed up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with RT-PCR method, and epidemiological data between children and adults in the same families was compared. Effect of antiviral therapy was evaluated observationally and fecal viral excretion times among groups with different antiviral regiments were compared with Kaplan Meier plot. Results By February 29, 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had COVID-19 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Conclusion Children have lower susceptibility of SARS-CoV-2 infection, longer incubation and fecal viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine. This article is protected by copyright. All rights reserved.Objective To evaluate the effect of art therapy on cancer patients' quality of life and physical and psychological symptoms. Methods The databases PubMed, Embase, Web of Science, The Cochrane Library, Clinical Trial.gov, the China National Knowledge Infrastructure (CNKI), Wanfang and the Chinese Biomedical Literature Database (CBM) were searched from their inception up to 20 August 2019. Trials examining the effects of art therapy on physical and psychological symptoms and quality of life versus a control group were included. The methodological quality of the included randomised controlled trials was assessed using the risk of bias tool of Cochrane Handbook. Meanwhile, the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the methodological quality of the non-randomised studies. Results Twelve studies involving 587 cancer patients were included. The results revealed that art therapy significantly reduced anxiety symptoms (standard mean difference [SMD] = -0.46, 95% confidence interval [CI] [-0.90, 0.02], p = .04), depression symptoms (SMD = -0.47, 95% CI [-0.72, 0.21], p less then .01), and fatigue (SMD = -0.38, 95% CI [-0.68, -0.09], p = .01) in cancer patients. Art therapy also significantly improved the quality of life of cancer patients (SMD = 0.43, 95% CI [0.18, 0.68], p less then .01). Conclusions Art therapy had a positive effect on quality of life and symptoms in cancer patients and can be used as a complementary treatment for cancer patients.A quick, simple, and high-yield nucleic acid isolation process is crucial for high-quality DNA analysis. The ability of the MicroGEM PDQeX phytoGEM system and Omega Bio-tek E.Z.N.A.® Plant DS Mini kit to extract PCR-ready DNA was evaluated by extracting the forensically relevant "legal high" plant species Ipomoea purpurea, Artemisia absinthium, Mitragyna speciosa, Datura stramonium, and Papaver somniferum. The plant material was pulverized, processed using the manufacturer's plant protocol for the PDQeX Nucleic Acid Extraction or the manufacturer's protocol for the Omega extraction, quantified using the Invitrogen Qubit 2.0 Fluorometer, and analyzed for amplifiability by PCR using a Qiagen Rotor-Gene Q instrument and published assays. The DNA amplicons for the legal high species produced high-resolution melt curves concordant with the melts observed when DNA was isolated using the Qiagen DNeasy Plant Mini Kit in previous studies.Aims Intraductal carcinoma (IDC) is an adverse histopathological parameter for prostate cancer outcome, but not incorporated in current tumour grading. To account for its dismal prognosis and omit basal cell immunohistochemistry, it has been proposed to grade IDC based on its underlying architectural pattern. Our objective was to determine the impact of IDC grade assignment on prostate cancer biopsy and radical prostatectomy tumour grading. Methods and results A cohort of 1,031 prostate cancer biopsies and 835 radical prostatectomies was assigned a Grade Group according to the 2014 International Society of Urological Pathology (ISUP) guidelines, not incorporating IDC in grading. Tumour grading was compared with a Grade Group in which IDC was graded based on its underlying architecture. Out of 1,031 biopsies, 139 (13.5%) had IDC. Grade assignment to IDC led to a Grade Group change in 17 (1.6%) cases 4/486 (0.8%) Grade Group 1 were reclassified as Grade Group 2, 9/375 (2.4%) Grade Group 2 as 3, and 4/58 (6.9%) Grade Group 4 as 5.
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