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42 mins ago


The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric used in prior efforts to track change in arthropod communities.
Differences in species composition among their arthropod communities confirm that ecoregions are a useful synoptic for biogeographic patterns and for structuring conservation efforts. The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric used in prior efforts to track change in arthropod communities.
Huanglongbing, a devastating disease of citrus, is caused by the obligate, intracellular bacterium "Candidatus Liberibacter asiaticus" (CLas). CLas is transmitted by Diaphorina citri, the Asian citrus psyllid. Development of transmission-blocking strategies to manage huanglongbing relies on knowledge of CLas and D. citri interactions at the molecular level. Prior transcriptome analyses of D. citri point to changes in psyllid biology due to CLas infection but have been hampered by incomplete versions of the D. citri genome, proper host plant controls, and/or a lack of a uniform data analysis approach. In this work, we present lessons learned from a quantitative transcriptome analysis of excised heads, salivary glands, midguts, and bacteriomes from CLas-positive and CLas-negative D. citri using the chromosomal length D. citri genome assembly.

Each organ had a unique transcriptome profile and response to CLas infection. Though most psyllids were infected with the bacterium, CLas-derived transcripts were not detected in all organs. By analyzing the midgut dataset using both the Diaci_v1.1 and v3.0 D. citri genomes, we showed that improved genome assembly led to significant and quantifiable differences in RNA-sequencing data interpretation.

Our results support the hypothesis that future transcriptome studies on circulative, vector-borne pathogens should be conducted at the tissue-specific level using complete, chromosomal-length genome assemblies for the most accurate understanding of pathogen-induced changes in vector gene expression.
Our results support the hypothesis that future transcriptome studies on circulative, vector-borne pathogens should be conducted at the tissue-specific level using complete, chromosomal-length genome assemblies for the most accurate understanding of pathogen-induced changes in vector gene expression.With capabilities of sequencing ancient DNA to high coverage often limited by sample quality or cost, imputation of missing genotypes presents a possibility to increase the power of inference as well as cost-effectiveness for the analysis of ancient data. However, the high degree of uncertainty often associated with ancient DNA poses several methodological challenges, and performance of imputation methods in this context has not been fully explored. To gain further insights, we performed a systematic evaluation of imputation of ancient data using Beagle v4.0 and reference data from phase 3 of the 1000 Genomes project, investigating the effects of coverage, phased reference, and study sample size. Making use of five ancient individuals with high-coverage data available, we evaluated imputed data for accuracy, reference bias, and genetic affinities as captured by principal component analysis. We obtained genotype concordance levels of over 99% for data with 1× coverage, and similar levels of accuracy and reference bias at levels as low as 0.75×. Our findings suggest that using imputed data can be a realistic option for various population genetic analyses even for data in coverage ranges below 1×. We also show that a large and varied phased reference panel as well as the inclusion of low- to moderate-coverage ancient individuals in the study sample can increase imputation performance, particularly for rare alleles. In-depth analysis of imputed data with respect to genetic variants and allele frequencies gave further insight into the nature of errors arising during imputation, and can provide practical guidelines for postprocessing and validation prior to downstream analysis.
To compare the performance of the rabbit monoclonal antihuman CD246 antibody (D5F3 clone) with the established ALK1 clone for immunohistochemical assessment of anaplastic large cell lymphoma (ALCL).

Archival cases of ALCL (n = 27) were assessed immunohistochemically by use of ALK1 and D5F3 clones under standard Clinical Laboratory Improvement Amendments-compliant conditions. The intensity of cytoplasmic staining (0 = none; 1 = faint; 2 = moderate; 3+ = strong) and proportion of neoplastic cells (0%, <5%, 5%-50%, >50%) were evaluated and compared with clinical ALK break-apart fluorescence in situ hybridization (FISH) assays.

Nine ALCL specimens were positive for ALK expression by ALK1 staining (33%; 1 = 1+; 0 = 2+; 8 = 3+), while 14 were positive by D5F3 staining (48%; 3 = 1+; 1 = 2+; 10 = 3+). Across the cohort, D5F3 staining showed a significantly greater proportion of cells staining positive (P = .02) and greater intensity (P = .03). Of 3 cases positive for D5F3 only with FISH results, none showed rearrangements, although 1 showed copy number gains at the ALK locus in a subset of cells.

Overall, D5F3 showed greater stain intensity and proportion staining than ALK1 in ALK-positive ALCL cases, which is especially helpful in limited samples. Caution and consideration of orthogonal ALK testing types is recommended, especially for cases with weak or focal staining.
Overall, D5F3 showed greater stain intensity and proportion staining than ALK1 in ALK-positive ALCL cases, which is especially helpful in limited samples. Caution and consideration of orthogonal ALK testing types is recommended, especially for cases with weak or focal staining.
Single-molecule localization microscopy allows studying the dynamics of biomolecules in cells and resolving the biophysical properties of the molecules and their environment underlying cellular function. With the continuously growing amount of data produced by individual experiments, the computational cost of quantifying these properties is increasingly becoming the bottleneck of single-molecule analysis. Mining these data requires an integrated and efficient analysis toolbox.

We introduce TRamWAy, a modular Python library that features (i) a conservative tracking procedure for localization data, (ii) a range of sampling techniques for meshing the spatio-temporal support of the data, (iii) computationally efficient solvers for inverse models, with the option of plugging in user-defined functions and (iv) a collection of analysis tools and a simple web-based interface.

TRamWAy is a Python library and can be installed with pip and conda. The source code is available at https//github.com/DecBayComp/TRamWAy.
TRamWAy is a Python library and can be installed with pip and conda. The source code is available at https//github.com/DecBayComp/TRamWAy.
The Patient Experienced Symptom State (PESS) is a single-question, patient-reported outcome which is validated to assess global disease impact in rheumatoid arthritis (RA). This study addresses its sensitivity to change and reliability.

Disease activity, disease impact in the 7 domains of RAID and PESS were assessed in patients with RA from the NOR-DMARD registry, at two visits, six-months apart. The PESS over the last week was scored in five levels, from "very bad" to "very good".Disease impact and disease activity were compared between patients who improved, maintained or worsened PESS over time, through one-way analysis of variance (ANOVA), with post-hoc Bonferroni correction. Correlations between changes in these parameters were assessed through SpearmaƄs correlation coefficient. Sensitivity to change was assessed by standardized response mean (SRM) between the two visits. Reliability was analyzed through intraclass correlation coefficient between the two visits in patients with stable disease activity and impact.

In 353 patients (76.8% females, 9.9(9.6) years disease duration), patients who improved their PESS level was associated with substantial improvements in mean impact in all domains as well as disease activity. (p< 0.02). PESS change was moderately to strongly correlated with RAID domains and disease activity (rho 0.4-0.7). https://www.selleckchem.com/products/LBH-589.html PESS was responsive to change (SRM 0.65, 95%CI 0.54-0.76), particularly among RAID responders (SRM 1.79, 95%CI 1.54-1.99). PESS was moderately reliable in patients with stable condition (ICC 0.72, 95%CI 0.52-0.83).

PESS is valid, feasible, reliable and responsive, representing an opportunity to improve the assessment of disease impact with minimal questionnaire burden.
PESS is valid, feasible, reliable and responsive, representing an opportunity to improve the assessment of disease impact with minimal questionnaire burden.
Patients with systemic lupus erythematosus (SLE) have increased prevalence of clinical cardiovascular disease (CVD) and subclinical atherosclerosis. Although 30-40% of patients with SLE have vascular plaque on ultrasound scanning, this study is the first to consider the relationship between total burden of plaque and subsequent CVD risk.

One hundred patients with SLE and without any previous clinical CVD underwent vascular ultrasound scans of both carotid and both common femoral bifurcations between 2011 and 2013. Clinical, serological, demographic and treatment data were collected at baseline. Patients were followed till 2020 to identify those who developed new onset coronary disease or stroke. Statistical analysis to identify factors associated with increased risk of developing CVD events was carried out.

Thirty-six patients had plaque at baseline. During follow-up five patients (all had baseline plaque) developed coronary disease and two, without baseline plaque, developed lacunar strokes. Mean (SD) age of these patients was 46.5 (4.5) years. Patients with three or more baseline bifurcations with plaque were 10 times more likely to develop CVD than those with 0-2 bifurcations with plaques (OR 9.9, p= 0.009). TPA > 16mm2 was associated with six-fold increased risk of CVD (OR = 6.44, p= 0.028). Patients with disease duration > 14 years were more likely than those with disease duration < 14 years to develop CVD (OR 8.3 p= 0.043).

The number of bifurcations with plaque and TPA in patients with SLE may be valuable in assessing risk of CVD and deciding on clinical measures to reduce this risk.
The number of bifurcations with plaque and TPA in patients with SLE may be valuable in assessing risk of CVD and deciding on clinical measures to reduce this risk.Advocacy organizations have played a significant role in the field of nutrition in recent years. However, why are some advocates viewed as more effective than others? This paper derives metrics for assessing advocacy efficacy by first drawing on key insights from the nutrition and public policy scholarship. A set of metrics is proposed to capture the constitutive elements of three concepts that often emerge as critical from that literature organizational capacity, strong networks and external outreach. Based on a survey of 66 nutrition stakeholders in Nigeria, including at the federal level and within the states of Kaduna and Kano, the metrics are then applied to a set of advocacy organizations within the country. We show that the metrics can provide insights into why some advocacy organizations are perceived as more effective than others by policymakers. Specifically, we find that geographical reach, the share of budget allocated to advocacy, action plans with clear objectives, large networks that include government and non-governmental policy champions, multiple media and dissemination outputs and numerous training events collectively increase nutrition advocates' visibility to, and influence on, policymakers.

52 mins ago


P2X7 receptor (P2X7R) is an ATP-gated nonselective cationic channel playing important roles in a variety of physiological functions, including inflammation, and apoptotic or necrotic cell death. An extracellular domain has ten cysteine residues forming five intrasubunit disulfide bonds, which are needed for the P2X7R trafficking to the cell surface and the recognition of surface epitopes of apoptotic cells and bacteria. However, the underlying mechanisms of redox/S-nitrosylation of cysteine residues on P2X7R and its role in P2X7R-mediated post-status epilepticus (SE, a prolonged seizure activity) events remain to be answered.

Rats were given pilocarpine (380 mg/kg i.p.) to induce SE. Animals were intracerebroventricularly infused N
-nitro-L-arginine methyl ester hydrochloride (L-NAME, a NOS inhibitor) 3 days before SE, or protein disulfide isomerase (PDI) siRNA 1 day after SE using an osmotic pump. Thereafter, we performed Western blot, co-immunoprecipitation, membrane fraction, measurement of S-nitrosylat PDI-mediated regulations of dynamic redox status and S-nitrosylation of P2X7R may be a critical mechanism in the neuroinflammation and astroglial death following SE.
Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.

Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.

Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. https://www.selleckchem.com/products/rki-1447.html Surgical spacer placement significantly ilocally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.
To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.

In the Surveillance, Epidemiology, and End Results database,pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or withoutradiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection.

Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men,and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49-0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19-24 LNs removed (aHR 0.78; 95% CI 0.73-1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with < 18 LNs. The protective effect was not seen in those with 18-24 LNs (aHR 1.07; 95% CI 0.59-1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed.

Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.
Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.
One strategy to address the high number of U.S. opioid-related deaths is to restrict high-risk or inappropriate opioid analgesic prescribing and dispensing. Federal and state laws and regulations have implemented restrictions but less is known about commercial and public payers' policies aside from clinician anecdotal reports that these policies are increasing. To assess the number and types of policies with temporal trends, we examined commercial and public (Medicaid) payer policies in one state, Michigan, that has high opioid-related deaths and implemented opioid analgesic prescribing laws.

Policies for seven large commercial payers and the public payer for 2012-2018 were reviewed and categorized by actions. Joinpoint regression was used to summarize temporal trends on number of policies for all payers and subgroups.

Across the 7 years, there were 529 action policies (75.57 (95% confidence intervals (CI) 35.93, 115.22) actions per year) with a range of 36 to 103 actions by payer. Limitations on numberbing with a steady increase in the number of such policies implemented from 2014 to 2018. This case study documented that at least in one state with high opioid-related deaths and multiple commercial payers, new and different policies were increasingly implemented creating barriers to patient care. The impact of these policies is understudied, complicating recommendation of best practices.
Ethnic Chinese mothers in Malaysia adhere to 30 days of traditional postpartum practices (the "confinement period") aimed at recuperation after delivery. Recently there has been an emergence of confinement centres (CCs) where mothers stay and receive traditional confinement care. Ethnic Chinese mothers have low breastfeeding rates. There are concerns that practices in CCs could contribute to this but no data exists. We described mothers' breastfeeding experiences at CCs and identified areas for potential improvement in breastfeeding support.

Ethnic Chinese mothers intending to breastfeed their healthy infants were recruited post-delivery between August and October 2017 then, at 1 and 6 months, they were telephone interviewed about their experience. For every participant going to a CC after the birth, another mother going home ("home") for her confinement was recruited. Chi-square test was used to compare groups and multiple logistic regression was used to assess the effect of confinement place on exclusivticipants sought help for breastfeeding problems mainly from CC staff and support groups while home participants obtained help from friends and healthcare professionals.

Breastfeeding rates appeared to be similar at CCs and at home during the confinement period, but there were gaps in how CCs supported breastfeeding. Targeted training to CC staff to support breastfeeding may result in better outcomes for mothers staying in CCs.
Breastfeeding rates appeared to be similar at CCs and at home during the confinement period, but there were gaps in how CCs supported breastfeeding. Targeted training to CC staff to support breastfeeding may result in better outcomes for mothers staying in CCs.
7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD).

We identified three rare variants of potential clinical relevance for ASD a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which disrupted IMMP2L (one Dup7-ASD, one Dup7-non-ASD). There were no significant differences in gene-set or pathway variant burden between the Dup7-ASD and Dup7-non-ASD groups. However, overall intellectual ability negatively correlated with the number of rare loss-of-function variants present in nervous system development and membrane component pathways, and adaptive behaviour standard scores negatively correlated with the number of low-frequency likely-damaging missense variants found in genes expressed in the prenatal human brain. ASD severity positively correlated with the number of low frequency loss-of-function variants impacting genes expressed at low levels in the brain, and genes with a low level of intolerance.

Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.
Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.
For most parents, getting pregnant means having a child. Generally, the couple outlines plans and has expectations regarding the baby. When these plans are interrupted because of a perinatal loss, it turns out to be a traumatic experience for the family. Validating the grief of these losses has been a challenge to Brazilian society, which is evident considering the childbirth care offered to bereaved families in maternity wards. Positively assessed care that brings physical and emotional memories about the baby has a positive impact on the bereavement process that family undergoes. Therefore, this study aims to assess the effects supportive guidelines have on mental health. They were designed to assist grieving parents and their families while undergoing perinatal loss in public maternities in Ribeirão Preto, São Paulo state, Brazil.

A mixed-methods (qualitative/quantitative), quasi-experimental (before/after) study. The intervention is the implementation of bereavement supportive guidelines for women whochers, policymakers or those interested in developing specific protocols for their maternity wards.
Misconceptions about the usefulness of condoms and other contraceptives still expose many unmarried adolescents to the risk of unwanted teenage pregnancies and sexually-transmitted infections (STIs). This study explored beliefs and misconceptions about condoms and other contraceptives among adolescents in Ebonyi state, south-east Nigeria.

A qualitative study was undertaken in six local government areas in Ebonyi state, southeast Nigeria. Data were collected within a period of one month from in and out-of-school adolescents aged 13-18years using twelve focus group discussions (FGD). The data were analyzed using the thematic framework approach.

Majority of the adolescents were knowledgeable about methods of contraception, how they are used and their modes of action. They were also knowledgeable about the dual effects of condoms in prevention of pregnancy and STIs. However, some misconceptions that were expressed by some adolescents were that pregnancy could be prevented by the use of (i) hard drugs, (ii) t 'flesh to flesh' contact during sex. There was a general belief that contraceptive use in early age reduces fertility prospects for boys and girls. Mistaken beliefs about methods of preventing pregnancy persist among adolescents, and this raises concerns about the quality of information they receive. Concerted efforts should be made to debunk these wrong beliefs and properly educate adolescents on safe sex practices.

1 hr ago


terial for wound dressing in biomedical applications.The ssrA degron is commonly used in fusion proteins to control protein stability in bacteria or as an interaction module. These applications often rely on the modular activities of the ssrA tag in binding to the SspB adaptor and in engaging the ClpXP protease. However, a comparison of these activities for a substantial standard set of degron variants has not been conducted previously, which may hinder the development of new variants optimized exclusively for one application. Here, we strive to establish a benchmark that will facilitate the comparison of ssrA variants under uniform conditions. In our workflow, we included methods for expression and purification of ClpX, ClpP, SspB and eGFP-degrons, assays of ClpX ATPase activity, of eGFP-degron binding to SspB and for measuring eGFP-degron degradation in vitro and in vivo. Using uniform, precise and sensitive methods under the same conditions on a range of eGFP-degrons allowed us to determine subtle differences in their properties that can affect their potential applications. Our findings can serve as a reference and a resource for developing targeted protein degradation approaches.The use of selenium nanoparticles (SeNPs) in the biomedical area has been increasing as an alternative to the growing bacterial resistance to antibiotics. In this research, SeNPs were synthesized by green synthesis using ascorbic acid (AsAc) as a reducing agent and methanolic extract of Calendula officinalis L. flowers as a stabilizer. https://www.selleckchem.com/products/mv1035.html Characterization of SeNPs was performed by UV-vis spectrophotometry, infrared spectrophotometry (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) techniques. SeNPs of 40-60 nm and spherical morphologies were obtained. The antibacterial activity of marigold extracts and fractions was evaluated by disk diffusion methodology. The evaluation of SeNPs at different incubation times was performed through the colony-forming unit (CFU) count, in both cases against Serratia marcescens, Enterobacter cloacae, and Alcaligenes faecalis bacteria. Partial antibacterial activity was observed with methanolic extracts of marigold leaves and flowers and total inhibition with SeNPs from 2 h for S. marcescens, 1 h for E. cloacae, and 30 min for A. faecalis. In addition, SeNPs were found to exhibit antioxidant activity. The results indicate that SeNPs present a potentiated effect of both antimicrobial and antioxidant activity compared to the individual use of marigold extracts or sodium selenite (Na2SeO3). Their application emerges as an alternative for the control of clinical pathogens.Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17-45 Veratrum spp., Veratrum californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. californicum root and rhizome via liquid chromatography-mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.
The toxicity of chemotherapeutic anticancer drugs is a serious issue in clinics. Drug discovery from edible and medicinal plants represents a promising approach towards finding safer anticancer therapeutics.
T. Anderson (Acanthaceae) is an edible and medicinal plant in Nigeria. This study aims to discover cytotoxic compounds from this rarely explored
and investigate their underlying mechanism of action.

The cytotoxicity of the plant extract was evaluated in human ovarian cancer cell lines and normal human ovarian surface epithelia (HOE) cells using a sulforhodamine B assay. Bioassay-guided isolation was carried out using column chromatography including HPLC, and the isolated natural products were characterized using GC-MS, LC-HRMS, and 1D/2D NMR techniques. Induction of apoptosis was evaluated using Caspase 3/7, 8, and 9, and Annexin V and PI based flow cytometry assays. SwissADME and SwissTargetPrediction web tools were used to predict the molecular properties and possible protein targets of identithe treatment of ovarian cancer.
Clerodane diterpenoids (1 and 2) in J. insularis were identified as cytotoxic to ovarian cancer cells via the induction of apoptosis, providing an abundant and valuable source of hit compounds for the treatment of ovarian cancer.Many strategies have been developed to modulate the biological or biotechnical properties of oligonucleotides by introducing new chemical functionalities or by enhancing their affinity and specificity while restricting their conformational space. Among them, we review our approach consisting of modifications of the 5'-C-position of the nucleoside sugar. This allows the introduction of an additional chemical handle at any position on the nucleotide chain without disturbing the Watson-Crick base-pairing. We show that 5'-C bromo or propargyl convertible nucleotides (CvN) are accessible in pure diastereoisomeric form, either for nucleophilic displacement or for CuAAC conjugation. Alternatively, the 5'-carbon can be connected in a stereo-controlled manner to the phosphate moiety of the nucleotide chain to generate conformationally constrained nucleotides (CNA). These allow the precise control of the sugar/phosphate backbone torsional angles. The consequent modulation of the nucleic acid shape induces outstanding stabilization properties of duplex or hairpin structures in accordance with the preorganization concept. Some biological applications of these distorted oligonucleotides are also described. Effectively, the convertible and the constrained approaches have been merged to create constrained and convertible nucleotides (C2NA) providing unique tools to functionalize and stabilize nucleic acids.Using citric acid (CA) and ethylenediamine (EDA) as precursors, stable nitrogen-doped carbon dots (CD) nanosols were prepared by microwave procedure and characterized in detail. It was found that CDNs catalyze ethanol (Et)-HAuCl4 to generate gold nanoparticles (AuNPs), which have strong surface plasmon resonance, Rayleigh scattering, (RRS) and a surface plasmon resonance (SPR) absorption (Abs) effect at 370 nm and 575 nm, respectively. Compled the new catalytic amplification indicator reaction with the specific As3+ aptamer reaction, a new RRS/Abs dual-mode aptamer sensor for the assay of trace As3+ was developed, based on the RRS/Abs signals increasing linearly with As3+ increasing in the ranges of 5-250 nmol/L and 50-250 nmol/L, whose detection limits were 0.8 nmol/L and 3.4 nmol/L As3+, respectively. This analytical method has the advantages of high selectivity, simplicity, and rapidity, and it has been successfully applied to the detection of practical samples.In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (-11.265, -10.532, -10.422, -10.827, -10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors.Acute kidney injury (AKI) is a dose-limiting side effect of cisplatin therapy in cancer patients. However, effective therapies for cisplatin-induced AKI are not available. Oxidative stress, tubular cell death, and inflammation are known to be the major pathological processes of the disease. 6-Shogaol is a major component of ginger and exhibits anti-oxidative and anti-inflammatory effects. Accumulating evidence suggest that 6-shogaol may serve as a potential therapeutic agent for various inflammatory diseases. However, whether 6-shogaol exerts a protective effect on cisplatin-induced renal side effect has not yet been determined. The aim of this study was to evaluate the effect of 6-shogaol on cisplatin-induced AKI and to investigate its underlying mechanisms. An administration of 6-shogaol after cisplatin treatment ameliorated renal dysfunction and tubular injury, as shown by a reduction in serum levels of creatinine and blood urea nitrogen and an improvement in histological abnormalities. Mechanistically, 6-shogaol attenuated cisplatin-induced oxidative stress and modulated the renal expression of prooxidant and antioxidant enzymes. Apoptosis and necroptosis induced by cisplatin were also suppressed by 6-shogaol. Moreover, 6-shogaol inhibited cisplatin-induced cytokine production and immune cell infiltration. These results suggest that 6-shogaol exhibits therapeutic effects against cisplatin-induced AKI via the suppression of oxidative stress, tubular cell death, and inflammation.Orange peel by-products generated in the food industry are an important source of value-added compounds that can be potentially reused. In the current research, the effect of oven-drying (50-70 °C) and freeze-drying on the bioactive compounds and antioxidant potential from Navelina, Salustriana, and Sanguina peel waste was investigated using pressurized extraction (ASE). Sixty volatile components were identified by ASE-GC-MS. The levels of terpene derivatives (sesquitenenes, alcohols, aldehydes, hydrocarbons, and esters) remained practically unaffected among fresh and freeze-dried orange peels, whereas drying at 70 °C caused significative decreases in Navelina, Salustriana, and Sanguina peels. Hesperidin and narirutin were the main flavonoids quantified by HPLC-MS. Freeze-dried Sanguina peels showed the highest levels of total-polyphenols (113.3 mg GAE·g-1), total flavonoids (39.0 mg QE·g-1), outstanding values of hesperedin (187.6 µg·g-1), phenol acids (16.54 mg·g-1 DW), and the greatest antioxidant values (DPPH•, FRAP, and ABTS•+ assays) in comparison with oven-dried samples and the other varieties.

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04/27/2024

Join host Manila Chan as she discusses the Christmas Massacre in Nigeria and the plight of Christians in central Nigeria with author and human rights activist Jason Jones, providing valuable insight into the challenges faced by Christians in areas affected by terrorist groups like Boko Haram.

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04/27/2024

Join host Manila Chan as she discusses the Christmas Massacre in Nigeria and the plight of Christians in central Nigeria with author and human rights activist Jason Jones, providing valuable insight into the challenges faced by Christians in areas affected by terrorist groups like Boko Haram.

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42 mins ago


The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric used in prior efforts to track change in arthropod communities.
Differences in species composition among their arthropod communities confirm that ecoregions are a useful synoptic for biogeographic patterns and for structuring conservation efforts. The present results also demonstrate that metabarcoding enables large-scale monitoring of shifts in species composition, making it possible to move beyond the biomass measurements that have been the key metric used in prior efforts to track change in arthropod communities.
Huanglongbing, a devastating disease of citrus, is caused by the obligate, intracellular bacterium "Candidatus Liberibacter asiaticus" (CLas). CLas is transmitted by Diaphorina citri, the Asian citrus psyllid. Development of transmission-blocking strategies to manage huanglongbing relies on knowledge of CLas and D. citri interactions at the molecular level. Prior transcriptome analyses of D. citri point to changes in psyllid biology due to CLas infection but have been hampered by incomplete versions of the D. citri genome, proper host plant controls, and/or a lack of a uniform data analysis approach. In this work, we present lessons learned from a quantitative transcriptome analysis of excised heads, salivary glands, midguts, and bacteriomes from CLas-positive and CLas-negative D. citri using the chromosomal length D. citri genome assembly.

Each organ had a unique transcriptome profile and response to CLas infection. Though most psyllids were infected with the bacterium, CLas-derived transcripts were not detected in all organs. By analyzing the midgut dataset using both the Diaci_v1.1 and v3.0 D. citri genomes, we showed that improved genome assembly led to significant and quantifiable differences in RNA-sequencing data interpretation.

Our results support the hypothesis that future transcriptome studies on circulative, vector-borne pathogens should be conducted at the tissue-specific level using complete, chromosomal-length genome assemblies for the most accurate understanding of pathogen-induced changes in vector gene expression.
Our results support the hypothesis that future transcriptome studies on circulative, vector-borne pathogens should be conducted at the tissue-specific level using complete, chromosomal-length genome assemblies for the most accurate understanding of pathogen-induced changes in vector gene expression.With capabilities of sequencing ancient DNA to high coverage often limited by sample quality or cost, imputation of missing genotypes presents a possibility to increase the power of inference as well as cost-effectiveness for the analysis of ancient data. However, the high degree of uncertainty often associated with ancient DNA poses several methodological challenges, and performance of imputation methods in this context has not been fully explored. To gain further insights, we performed a systematic evaluation of imputation of ancient data using Beagle v4.0 and reference data from phase 3 of the 1000 Genomes project, investigating the effects of coverage, phased reference, and study sample size. Making use of five ancient individuals with high-coverage data available, we evaluated imputed data for accuracy, reference bias, and genetic affinities as captured by principal component analysis. We obtained genotype concordance levels of over 99% for data with 1× coverage, and similar levels of accuracy and reference bias at levels as low as 0.75×. Our findings suggest that using imputed data can be a realistic option for various population genetic analyses even for data in coverage ranges below 1×. We also show that a large and varied phased reference panel as well as the inclusion of low- to moderate-coverage ancient individuals in the study sample can increase imputation performance, particularly for rare alleles. In-depth analysis of imputed data with respect to genetic variants and allele frequencies gave further insight into the nature of errors arising during imputation, and can provide practical guidelines for postprocessing and validation prior to downstream analysis.
To compare the performance of the rabbit monoclonal antihuman CD246 antibody (D5F3 clone) with the established ALK1 clone for immunohistochemical assessment of anaplastic large cell lymphoma (ALCL).

Archival cases of ALCL (n = 27) were assessed immunohistochemically by use of ALK1 and D5F3 clones under standard Clinical Laboratory Improvement Amendments-compliant conditions. The intensity of cytoplasmic staining (0 = none; 1 = faint; 2 = moderate; 3+ = strong) and proportion of neoplastic cells (0%, <5%, 5%-50%, >50%) were evaluated and compared with clinical ALK break-apart fluorescence in situ hybridization (FISH) assays.

Nine ALCL specimens were positive for ALK expression by ALK1 staining (33%; 1 = 1+; 0 = 2+; 8 = 3+), while 14 were positive by D5F3 staining (48%; 3 = 1+; 1 = 2+; 10 = 3+). Across the cohort, D5F3 staining showed a significantly greater proportion of cells staining positive (P = .02) and greater intensity (P = .03). Of 3 cases positive for D5F3 only with FISH results, none showed rearrangements, although 1 showed copy number gains at the ALK locus in a subset of cells.

Overall, D5F3 showed greater stain intensity and proportion staining than ALK1 in ALK-positive ALCL cases, which is especially helpful in limited samples. Caution and consideration of orthogonal ALK testing types is recommended, especially for cases with weak or focal staining.
Overall, D5F3 showed greater stain intensity and proportion staining than ALK1 in ALK-positive ALCL cases, which is especially helpful in limited samples. Caution and consideration of orthogonal ALK testing types is recommended, especially for cases with weak or focal staining.
Single-molecule localization microscopy allows studying the dynamics of biomolecules in cells and resolving the biophysical properties of the molecules and their environment underlying cellular function. With the continuously growing amount of data produced by individual experiments, the computational cost of quantifying these properties is increasingly becoming the bottleneck of single-molecule analysis. Mining these data requires an integrated and efficient analysis toolbox.

We introduce TRamWAy, a modular Python library that features (i) a conservative tracking procedure for localization data, (ii) a range of sampling techniques for meshing the spatio-temporal support of the data, (iii) computationally efficient solvers for inverse models, with the option of plugging in user-defined functions and (iv) a collection of analysis tools and a simple web-based interface.

TRamWAy is a Python library and can be installed with pip and conda. The source code is available at https//github.com/DecBayComp/TRamWAy.
TRamWAy is a Python library and can be installed with pip and conda. The source code is available at https//github.com/DecBayComp/TRamWAy.
The Patient Experienced Symptom State (PESS) is a single-question, patient-reported outcome which is validated to assess global disease impact in rheumatoid arthritis (RA). This study addresses its sensitivity to change and reliability.

Disease activity, disease impact in the 7 domains of RAID and PESS were assessed in patients with RA from the NOR-DMARD registry, at two visits, six-months apart. The PESS over the last week was scored in five levels, from "very bad" to "very good".Disease impact and disease activity were compared between patients who improved, maintained or worsened PESS over time, through one-way analysis of variance (ANOVA), with post-hoc Bonferroni correction. Correlations between changes in these parameters were assessed through SpearmaƄs correlation coefficient. Sensitivity to change was assessed by standardized response mean (SRM) between the two visits. Reliability was analyzed through intraclass correlation coefficient between the two visits in patients with stable disease activity and impact.

In 353 patients (76.8% females, 9.9(9.6) years disease duration), patients who improved their PESS level was associated with substantial improvements in mean impact in all domains as well as disease activity. (p< 0.02). PESS change was moderately to strongly correlated with RAID domains and disease activity (rho 0.4-0.7). https://www.selleckchem.com/products/LBH-589.html PESS was responsive to change (SRM 0.65, 95%CI 0.54-0.76), particularly among RAID responders (SRM 1.79, 95%CI 1.54-1.99). PESS was moderately reliable in patients with stable condition (ICC 0.72, 95%CI 0.52-0.83).

PESS is valid, feasible, reliable and responsive, representing an opportunity to improve the assessment of disease impact with minimal questionnaire burden.
PESS is valid, feasible, reliable and responsive, representing an opportunity to improve the assessment of disease impact with minimal questionnaire burden.
Patients with systemic lupus erythematosus (SLE) have increased prevalence of clinical cardiovascular disease (CVD) and subclinical atherosclerosis. Although 30-40% of patients with SLE have vascular plaque on ultrasound scanning, this study is the first to consider the relationship between total burden of plaque and subsequent CVD risk.

One hundred patients with SLE and without any previous clinical CVD underwent vascular ultrasound scans of both carotid and both common femoral bifurcations between 2011 and 2013. Clinical, serological, demographic and treatment data were collected at baseline. Patients were followed till 2020 to identify those who developed new onset coronary disease or stroke. Statistical analysis to identify factors associated with increased risk of developing CVD events was carried out.

Thirty-six patients had plaque at baseline. During follow-up five patients (all had baseline plaque) developed coronary disease and two, without baseline plaque, developed lacunar strokes. Mean (SD) age of these patients was 46.5 (4.5) years. Patients with three or more baseline bifurcations with plaque were 10 times more likely to develop CVD than those with 0-2 bifurcations with plaques (OR 9.9, p= 0.009). TPA > 16mm2 was associated with six-fold increased risk of CVD (OR = 6.44, p= 0.028). Patients with disease duration > 14 years were more likely than those with disease duration < 14 years to develop CVD (OR 8.3 p= 0.043).

The number of bifurcations with plaque and TPA in patients with SLE may be valuable in assessing risk of CVD and deciding on clinical measures to reduce this risk.
The number of bifurcations with plaque and TPA in patients with SLE may be valuable in assessing risk of CVD and deciding on clinical measures to reduce this risk.Advocacy organizations have played a significant role in the field of nutrition in recent years. However, why are some advocates viewed as more effective than others? This paper derives metrics for assessing advocacy efficacy by first drawing on key insights from the nutrition and public policy scholarship. A set of metrics is proposed to capture the constitutive elements of three concepts that often emerge as critical from that literature organizational capacity, strong networks and external outreach. Based on a survey of 66 nutrition stakeholders in Nigeria, including at the federal level and within the states of Kaduna and Kano, the metrics are then applied to a set of advocacy organizations within the country. We show that the metrics can provide insights into why some advocacy organizations are perceived as more effective than others by policymakers. Specifically, we find that geographical reach, the share of budget allocated to advocacy, action plans with clear objectives, large networks that include government and non-governmental policy champions, multiple media and dissemination outputs and numerous training events collectively increase nutrition advocates' visibility to, and influence on, policymakers.

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P2X7 receptor (P2X7R) is an ATP-gated nonselective cationic channel playing important roles in a variety of physiological functions, including inflammation, and apoptotic or necrotic cell death. An extracellular domain has ten cysteine residues forming five intrasubunit disulfide bonds, which are needed for the P2X7R trafficking to the cell surface and the recognition of surface epitopes of apoptotic cells and bacteria. However, the underlying mechanisms of redox/S-nitrosylation of cysteine residues on P2X7R and its role in P2X7R-mediated post-status epilepticus (SE, a prolonged seizure activity) events remain to be answered.

Rats were given pilocarpine (380 mg/kg i.p.) to induce SE. Animals were intracerebroventricularly infused N
-nitro-L-arginine methyl ester hydrochloride (L-NAME, a NOS inhibitor) 3 days before SE, or protein disulfide isomerase (PDI) siRNA 1 day after SE using an osmotic pump. Thereafter, we performed Western blot, co-immunoprecipitation, membrane fraction, measurement of S-nitrosylat PDI-mediated regulations of dynamic redox status and S-nitrosylation of P2X7R may be a critical mechanism in the neuroinflammation and astroglial death following SE.
Particle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.

Data from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.

Surgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. https://www.selleckchem.com/products/rki-1447.html Surgical spacer placement significantly ilocally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.
To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection.

In the Surveillance, Epidemiology, and End Results database,pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or withoutradiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection.

Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men,and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49-0.84) in those with < 18 lymph nodes (LNs) removed, but not in those with 19-24 LNs removed (aHR 0.78; 95% CI 0.73-1.13), and in those with ≥ 25 LNs removed (aHR 0.96; 95% CI 0.75-1.24). For 5-year DSS, similar effect was observed. The adjusted hazard ratio was 0.66 (95% confidence interval, 0.45-0.97) in those with < 18 LNs. The protective effect was not seen in those with 18-24 LNs (aHR 1.07; 95% CI 0.59-1.96), and in those with ≥ 25 LNs (aHR 1.12; 95% CI 0.81-1.56). Sensitivity testing also showed a robust protective effect of postoperative radiotherapy in patients with < 18 LNs removed.

Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.
Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.
One strategy to address the high number of U.S. opioid-related deaths is to restrict high-risk or inappropriate opioid analgesic prescribing and dispensing. Federal and state laws and regulations have implemented restrictions but less is known about commercial and public payers' policies aside from clinician anecdotal reports that these policies are increasing. To assess the number and types of policies with temporal trends, we examined commercial and public (Medicaid) payer policies in one state, Michigan, that has high opioid-related deaths and implemented opioid analgesic prescribing laws.

Policies for seven large commercial payers and the public payer for 2012-2018 were reviewed and categorized by actions. Joinpoint regression was used to summarize temporal trends on number of policies for all payers and subgroups.

Across the 7 years, there were 529 action policies (75.57 (95% confidence intervals (CI) 35.93, 115.22) actions per year) with a range of 36 to 103 actions by payer. Limitations on numberbing with a steady increase in the number of such policies implemented from 2014 to 2018. This case study documented that at least in one state with high opioid-related deaths and multiple commercial payers, new and different policies were increasingly implemented creating barriers to patient care. The impact of these policies is understudied, complicating recommendation of best practices.
Ethnic Chinese mothers in Malaysia adhere to 30 days of traditional postpartum practices (the "confinement period") aimed at recuperation after delivery. Recently there has been an emergence of confinement centres (CCs) where mothers stay and receive traditional confinement care. Ethnic Chinese mothers have low breastfeeding rates. There are concerns that practices in CCs could contribute to this but no data exists. We described mothers' breastfeeding experiences at CCs and identified areas for potential improvement in breastfeeding support.

Ethnic Chinese mothers intending to breastfeed their healthy infants were recruited post-delivery between August and October 2017 then, at 1 and 6 months, they were telephone interviewed about their experience. For every participant going to a CC after the birth, another mother going home ("home") for her confinement was recruited. Chi-square test was used to compare groups and multiple logistic regression was used to assess the effect of confinement place on exclusivticipants sought help for breastfeeding problems mainly from CC staff and support groups while home participants obtained help from friends and healthcare professionals.

Breastfeeding rates appeared to be similar at CCs and at home during the confinement period, but there were gaps in how CCs supported breastfeeding. Targeted training to CC staff to support breastfeeding may result in better outcomes for mothers staying in CCs.
Breastfeeding rates appeared to be similar at CCs and at home during the confinement period, but there were gaps in how CCs supported breastfeeding. Targeted training to CC staff to support breastfeeding may result in better outcomes for mothers staying in CCs.
7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD).

We identified three rare variants of potential clinical relevance for ASD a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which disrupted IMMP2L (one Dup7-ASD, one Dup7-non-ASD). There were no significant differences in gene-set or pathway variant burden between the Dup7-ASD and Dup7-non-ASD groups. However, overall intellectual ability negatively correlated with the number of rare loss-of-function variants present in nervous system development and membrane component pathways, and adaptive behaviour standard scores negatively correlated with the number of low-frequency likely-damaging missense variants found in genes expressed in the prenatal human brain. ASD severity positively correlated with the number of low frequency loss-of-function variants impacting genes expressed at low levels in the brain, and genes with a low level of intolerance.

Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.
Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.
For most parents, getting pregnant means having a child. Generally, the couple outlines plans and has expectations regarding the baby. When these plans are interrupted because of a perinatal loss, it turns out to be a traumatic experience for the family. Validating the grief of these losses has been a challenge to Brazilian society, which is evident considering the childbirth care offered to bereaved families in maternity wards. Positively assessed care that brings physical and emotional memories about the baby has a positive impact on the bereavement process that family undergoes. Therefore, this study aims to assess the effects supportive guidelines have on mental health. They were designed to assist grieving parents and their families while undergoing perinatal loss in public maternities in Ribeirão Preto, São Paulo state, Brazil.

A mixed-methods (qualitative/quantitative), quasi-experimental (before/after) study. The intervention is the implementation of bereavement supportive guidelines for women whochers, policymakers or those interested in developing specific protocols for their maternity wards.
Misconceptions about the usefulness of condoms and other contraceptives still expose many unmarried adolescents to the risk of unwanted teenage pregnancies and sexually-transmitted infections (STIs). This study explored beliefs and misconceptions about condoms and other contraceptives among adolescents in Ebonyi state, south-east Nigeria.

A qualitative study was undertaken in six local government areas in Ebonyi state, southeast Nigeria. Data were collected within a period of one month from in and out-of-school adolescents aged 13-18years using twelve focus group discussions (FGD). The data were analyzed using the thematic framework approach.

Majority of the adolescents were knowledgeable about methods of contraception, how they are used and their modes of action. They were also knowledgeable about the dual effects of condoms in prevention of pregnancy and STIs. However, some misconceptions that were expressed by some adolescents were that pregnancy could be prevented by the use of (i) hard drugs, (ii) t 'flesh to flesh' contact during sex. There was a general belief that contraceptive use in early age reduces fertility prospects for boys and girls. Mistaken beliefs about methods of preventing pregnancy persist among adolescents, and this raises concerns about the quality of information they receive. Concerted efforts should be made to debunk these wrong beliefs and properly educate adolescents on safe sex practices.

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terial for wound dressing in biomedical applications.The ssrA degron is commonly used in fusion proteins to control protein stability in bacteria or as an interaction module. These applications often rely on the modular activities of the ssrA tag in binding to the SspB adaptor and in engaging the ClpXP protease. However, a comparison of these activities for a substantial standard set of degron variants has not been conducted previously, which may hinder the development of new variants optimized exclusively for one application. Here, we strive to establish a benchmark that will facilitate the comparison of ssrA variants under uniform conditions. In our workflow, we included methods for expression and purification of ClpX, ClpP, SspB and eGFP-degrons, assays of ClpX ATPase activity, of eGFP-degron binding to SspB and for measuring eGFP-degron degradation in vitro and in vivo. Using uniform, precise and sensitive methods under the same conditions on a range of eGFP-degrons allowed us to determine subtle differences in their properties that can affect their potential applications. Our findings can serve as a reference and a resource for developing targeted protein degradation approaches.The use of selenium nanoparticles (SeNPs) in the biomedical area has been increasing as an alternative to the growing bacterial resistance to antibiotics. In this research, SeNPs were synthesized by green synthesis using ascorbic acid (AsAc) as a reducing agent and methanolic extract of Calendula officinalis L. flowers as a stabilizer. https://www.selleckchem.com/products/mv1035.html Characterization of SeNPs was performed by UV-vis spectrophotometry, infrared spectrophotometry (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) techniques. SeNPs of 40-60 nm and spherical morphologies were obtained. The antibacterial activity of marigold extracts and fractions was evaluated by disk diffusion methodology. The evaluation of SeNPs at different incubation times was performed through the colony-forming unit (CFU) count, in both cases against Serratia marcescens, Enterobacter cloacae, and Alcaligenes faecalis bacteria. Partial antibacterial activity was observed with methanolic extracts of marigold leaves and flowers and total inhibition with SeNPs from 2 h for S. marcescens, 1 h for E. cloacae, and 30 min for A. faecalis. In addition, SeNPs were found to exhibit antioxidant activity. The results indicate that SeNPs present a potentiated effect of both antimicrobial and antioxidant activity compared to the individual use of marigold extracts or sodium selenite (Na2SeO3). Their application emerges as an alternative for the control of clinical pathogens.Veratrum spp. grow throughout the world and are especially prevalent in high mountain meadows of North America. All parts of Veratrum plants have been used for the treatment of ailments including injuries, hypertension, and rheumatic pain since as far back as the 1600s. Of the 17-45 Veratrum spp., Veratrum californicum alkaloids have been proven to possess favorable medicinal properties associated with inhibition of hedgehog (Hh) pathway signaling. Aberrant Hh signaling leads to proliferation of over 20 cancers, including basal cell carcinoma, prostate and colon among others. Six of the most well-studied V. californicum alkaloids are cyclopamine (1), veratramine (2), isorubijervine (3), muldamine (4), cycloposine (5), and veratrosine (6). Recent inspection of the ethanolic extract from V. californicum root and rhizome via liquid chromatography-mass spectrometry has detected up to five additional alkaloids that are proposed to be verazine (7), etioline (8), tetrahydrojervine (9), dihydrojervine (10), 22-keto-26-aminocholesterol (11). For each alkaloid identified or proposed in V. californicum, this review surveys literature precedents for extraction methods, isolation, identification, characterization and bioactivity to guide natural product drug discovery associated with this medicinal plant.
The toxicity of chemotherapeutic anticancer drugs is a serious issue in clinics. Drug discovery from edible and medicinal plants represents a promising approach towards finding safer anticancer therapeutics.
T. Anderson (Acanthaceae) is an edible and medicinal plant in Nigeria. This study aims to discover cytotoxic compounds from this rarely explored
and investigate their underlying mechanism of action.

The cytotoxicity of the plant extract was evaluated in human ovarian cancer cell lines and normal human ovarian surface epithelia (HOE) cells using a sulforhodamine B assay. Bioassay-guided isolation was carried out using column chromatography including HPLC, and the isolated natural products were characterized using GC-MS, LC-HRMS, and 1D/2D NMR techniques. Induction of apoptosis was evaluated using Caspase 3/7, 8, and 9, and Annexin V and PI based flow cytometry assays. SwissADME and SwissTargetPrediction web tools were used to predict the molecular properties and possible protein targets of identithe treatment of ovarian cancer.
Clerodane diterpenoids (1 and 2) in J. insularis were identified as cytotoxic to ovarian cancer cells via the induction of apoptosis, providing an abundant and valuable source of hit compounds for the treatment of ovarian cancer.Many strategies have been developed to modulate the biological or biotechnical properties of oligonucleotides by introducing new chemical functionalities or by enhancing their affinity and specificity while restricting their conformational space. Among them, we review our approach consisting of modifications of the 5'-C-position of the nucleoside sugar. This allows the introduction of an additional chemical handle at any position on the nucleotide chain without disturbing the Watson-Crick base-pairing. We show that 5'-C bromo or propargyl convertible nucleotides (CvN) are accessible in pure diastereoisomeric form, either for nucleophilic displacement or for CuAAC conjugation. Alternatively, the 5'-carbon can be connected in a stereo-controlled manner to the phosphate moiety of the nucleotide chain to generate conformationally constrained nucleotides (CNA). These allow the precise control of the sugar/phosphate backbone torsional angles. The consequent modulation of the nucleic acid shape induces outstanding stabilization properties of duplex or hairpin structures in accordance with the preorganization concept. Some biological applications of these distorted oligonucleotides are also described. Effectively, the convertible and the constrained approaches have been merged to create constrained and convertible nucleotides (C2NA) providing unique tools to functionalize and stabilize nucleic acids.Using citric acid (CA) and ethylenediamine (EDA) as precursors, stable nitrogen-doped carbon dots (CD) nanosols were prepared by microwave procedure and characterized in detail. It was found that CDNs catalyze ethanol (Et)-HAuCl4 to generate gold nanoparticles (AuNPs), which have strong surface plasmon resonance, Rayleigh scattering, (RRS) and a surface plasmon resonance (SPR) absorption (Abs) effect at 370 nm and 575 nm, respectively. Compled the new catalytic amplification indicator reaction with the specific As3+ aptamer reaction, a new RRS/Abs dual-mode aptamer sensor for the assay of trace As3+ was developed, based on the RRS/Abs signals increasing linearly with As3+ increasing in the ranges of 5-250 nmol/L and 50-250 nmol/L, whose detection limits were 0.8 nmol/L and 3.4 nmol/L As3+, respectively. This analytical method has the advantages of high selectivity, simplicity, and rapidity, and it has been successfully applied to the detection of practical samples.In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (-11.265, -10.532, -10.422, -10.827, -10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors.Acute kidney injury (AKI) is a dose-limiting side effect of cisplatin therapy in cancer patients. However, effective therapies for cisplatin-induced AKI are not available. Oxidative stress, tubular cell death, and inflammation are known to be the major pathological processes of the disease. 6-Shogaol is a major component of ginger and exhibits anti-oxidative and anti-inflammatory effects. Accumulating evidence suggest that 6-shogaol may serve as a potential therapeutic agent for various inflammatory diseases. However, whether 6-shogaol exerts a protective effect on cisplatin-induced renal side effect has not yet been determined. The aim of this study was to evaluate the effect of 6-shogaol on cisplatin-induced AKI and to investigate its underlying mechanisms. An administration of 6-shogaol after cisplatin treatment ameliorated renal dysfunction and tubular injury, as shown by a reduction in serum levels of creatinine and blood urea nitrogen and an improvement in histological abnormalities. Mechanistically, 6-shogaol attenuated cisplatin-induced oxidative stress and modulated the renal expression of prooxidant and antioxidant enzymes. Apoptosis and necroptosis induced by cisplatin were also suppressed by 6-shogaol. Moreover, 6-shogaol inhibited cisplatin-induced cytokine production and immune cell infiltration. These results suggest that 6-shogaol exhibits therapeutic effects against cisplatin-induced AKI via the suppression of oxidative stress, tubular cell death, and inflammation.Orange peel by-products generated in the food industry are an important source of value-added compounds that can be potentially reused. In the current research, the effect of oven-drying (50-70 °C) and freeze-drying on the bioactive compounds and antioxidant potential from Navelina, Salustriana, and Sanguina peel waste was investigated using pressurized extraction (ASE). Sixty volatile components were identified by ASE-GC-MS. The levels of terpene derivatives (sesquitenenes, alcohols, aldehydes, hydrocarbons, and esters) remained practically unaffected among fresh and freeze-dried orange peels, whereas drying at 70 °C caused significative decreases in Navelina, Salustriana, and Sanguina peels. Hesperidin and narirutin were the main flavonoids quantified by HPLC-MS. Freeze-dried Sanguina peels showed the highest levels of total-polyphenols (113.3 mg GAE·g-1), total flavonoids (39.0 mg QE·g-1), outstanding values of hesperedin (187.6 µg·g-1), phenol acids (16.54 mg·g-1 DW), and the greatest antioxidant values (DPPH•, FRAP, and ABTS•+ assays) in comparison with oven-dried samples and the other varieties.


The XPC PAT -/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT -/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.Ultraviolet (UV) exposure has been linked to skin damage and carcinogenesis, but recently UVB has been proposed as a therapeutic approach for cancer. Herein, we investigated the cellular and molecular effects of UVB in immortal and tumorigenic HPV positive and negative cells. Cells were irradiated with 220.5 to 1102.5 J/m2 of UVB and cell proliferation was evaluated by crystal violet, while cell cycle arrest and apoptosis analysis were performed through flow cytometry. UVB effect on cells was recorded at 661.5 J/m2 and it was exacerbated at 1102.5 J/m2. All cell lines were affected by proliferation inhibition, cell cycle ablation and apoptosis induction, with different degrees depending on tumorigenesis level or HPV type. Analysis of the well-known UV-responsive p53, E2F1 and microtubules system proteins was performed in SiHa cells in response to UVB through Western-blotting assays. E2F1 and the Microtubule-associated protein 2 (MAP2) expression decrease correlated with cellular processes alteration while p53 and Microtubule-associated Protein 1S (MAP1S) expression switch was observed since 882 J/m2, suggesting they were required under more severe cellular damage. However, expression transition of α-Tubulin3C and β-Tubulin was abruptly noticed until 1102.5 J/m2 and particularly, γ-Tubulin protein expression remained without alteration. This study provides insights into the effect of UVB in cervical cancer cell lines.The prevalence of overweight/obesity is high among Black women in England, who also face high risks of pregnancy and childbirth complications. This study explored African migrant women's perceptions of pre- and post-migration influences on their weight-related behaviours and weight management support during pregnancy. Interviews were conducted with women of child-bearing age from Ghana, Nigeria, and Cameroon (n = 23). Data were analysed using thematic analysis. Four themes were identified changing dietary behaviours after migration, changing physical activity (PA) behaviours after migration, increased discourse on obesity, and weight management advice and support received. Navigating a new food environment, interactions with other populations in England, and the need to socialise influenced changes in dietary behaviours. Participants considered that living in England 'makes you lazy' due to its obesogenic environment, while increased discourses on obesity heightened weight awareness. Women struggled to relate to dietary advice from midwives but found PA advice useful. Relatives provided valuable support but could influence unhealthy weight-related practices. There is a need for interventions addressing gaps in weight management support for these women, especially considering their migrant backgrounds and multicultural identities. Further research is needed to understand their unique challenges, and collaborations with relatives could inform the development of effective weight management interventions.In order to deliver an aerosolized drug in a breath-triggered manner, the initiation of the patient's inspiration needs to be detected. The best-known systems monitoring breathing patterns are based on flow sensors. However, due to their large dead space volume, flow sensors are not advisable for monitoring the breathing of (preterm) neonates. Newly-developed respiratory sensors, especially when contact-based (invasive), can be tested on (preterm) neonates only with great effort due to clinical and ethical hurdles. Therefore, a physiological model is highly desirable to validate these sensors. For developing such a system, abdominal movement data of (preterm) neonates are required. We recorded time sequences of five preterm neonates' abdominal movements with a time-of-flight camera and successfully extracted various breathing patterns and respiratory parameters. Several characteristic breathing patterns, such as forced breathing, sighing, apnea and crying, were identified from the movement data. Respiratory parameters, such as duration of inspiration and expiration, as well as respiratory rate and breathing movement over time, were also extracted. This work demonstrated that respiratory parameters of preterm neonates can be determined without contact. Therefore, such a system can be used for breathing detection to provide a trigger signal for breath-triggered drug release systems. Furthermore, based on the recorded data, a physiological abdominal movement model of preterm neonates can now be developed.
A subgroup of patients with acute kidney injury (AKI) do not fulfil the functional criteria for AKI diagnosis but show elevated levels of new biomarkers reflecting tubular injury, suggesting that these patients suffer "subclinical AKI". We investigated the incidence and possible implications of "subclinical AKI", compared to no and clinical AKI among ST elevation myocardial infarction patients (STEMI) treated with primary coronary intervention (PCI).

We included 223 patients with STEMI treated with PCI. Neutrophil gelatinase-associated lipocalin (NGAL) was used as a marker of renal tubular damage in the absence of functional AKI, with NGAL levels ≥100 ng/mL suggesting subclinical AKI. Patients were assessed for the occurrence of in-hospital adverse outcomes.

Of the study patients, 45 (25%) had subclinical AKI. These patients were more likely to have left ventricular ejection fraction ≤45% (33% vs. 23%.
= 0.01), in-hospital adverse outcomes (73% vs. 48%;
= 0.005), and a combination of the two. https://www.selleckchem.com/products/e-7386.html The multivariate regression model demonstrated that subclinical AKI was independently associated with in-hospital adverse outcomes (OR 3.71, 95% CI 1.30-10.62,
= 0.02).

Subclinical AKI is common among STEMI patients and is independently associated with adverse outcomes, even in the absence of functional AKI.
Subclinical AKI is common among STEMI patients and is independently associated with adverse outcomes, even in the absence of functional AKI.

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Results Survivors of childhood ALL demonstrated significant differences in amplitude of accommodation, PCT, and TBUT compared to age-matched controls. Survivors had a lower median (interquartile range [IQR]) amplitude of accommodation compared to controls (11.0 D [9.0-13.0] vs. 12.0 D [10.5-15]; p = 0.045). Survivors also showed a longer median (IQR) PCT in comparison to controls (931.00 mseconds (857.00-1063.00) vs. 875.50 mseconds (825.75-966.00); p = 0.024). In addition, median (IQR) TBUT was worse in survivors in comparison to the control group (9 seconds [6-13] vs. 11 seconds [10-15]; p = 0.001). Conclusion Survivors of childhood ALL demonstrate premature ocular aging features compared to age-matched controls. Thus, survivors may benefit from having ocular examinations as part of their routine late-effects screening to detect age-related ocular morbidities early in its course.Depression is a common mental health disease with a high risk of relapse in people with a mental health condition. Mindfulness-based cognitive therapy (MBCT) showed higher efficacy in reducing depressive symptoms and prevent relapse for depressed patients. The study examined the effectiveness of MBCT versus the control group (CG) for the depression symptom reduction. A controlled trial was used to examine the effectiveness of MBCT or CG on depressive patients in Nigeria. Out of 357 screened subjects, 101 patients were randomized to receive either MBCT (n = 50) or CG (n = 51) and prospectively followed for 2 months. The intervention delivered according to the published manuals, and Beck Depression Inventory (BDI) was used to assess MDD severity among the patients. All assessments were conducted at three levels (baseline, 2 and 4 months). At the end of the 8 weeks of MBCT intervention, MBCT participants did not have significantly fewer depressive symptoms compared to those in the CG. However, the MBCT group had a significant depressive symptom reduction after 2 month follow up. The findings are in line with other studies, which show MBCT significantly decreased depression severity and improved treatment response rates after 2 months follow up, confirmed MBCT viability in the management of MDD.
To determine the real-world short-term efficacy and safety of apremilast for Behçet's disease (BD).

The study included patients who received apremilast for refractory oral ulcers in addition to meeting International Study Group criteria for BD or the revised International Criteria for Behçet's Disease. To assess the efficacy of apremilast, Behçet's disease current activity form (BDCAF) and patients' self-perception of their disease activity were monitored for three months. The disease phenotypes, laboratory data, concomitant medication use, and adverse events were also investigated.

Fourteen BD patients were included in the study. Concomitant drug use were as follows colchicine 92.9%, prednisolone 21.4%, immunosuppressants 28.6%, and tumor-necrosis inhibitor 14.3%. Oral ulcers and BDCAF scores at 3 months showed significant improvement compared to baseline. Adverse events during the study were diarrhea (
 = 3, 21.4%), nausea (
 = 3, 21.4%), music hallucination (
 = 1, 7.1%), and branch retinal vein occlusion (
 = 1, 7.1%). Apremilast was discontinued in 1 patient (7.1%) due to nausea.

Significant improvement in oral ulcer and BDCAF with apremilast was confirmed in real-world BD patients after 3 months. The combination of colchicine and apremilast appears to be well tolerated in BD in the short-term.
Significant improvement in oral ulcer and BDCAF with apremilast was confirmed in real-world BD patients after 3 months. The combination of colchicine and apremilast appears to be well tolerated in BD in the short-term.Purpose This study describes the prevalence trends of electronic cigarette (e-cigarette) use in young adult cancer survivors and compares these to the prevalence among young adults without a cancer history. It also examines the association between conventional cigarette use, binge drinking, depression, and other sociodemographic factors, and e-cigarette use in young adult cancer survivors. Methods Cross-sectional analyses, using the Behavioral Risk Factor Surveillance System, 2016-2018, were done. Multivariable logistic regression was used to examine the associations between conventional cigarette use, binge drinking, and depression as well as other factors associated with e-cigarette use in young adult cancer survivors. Results Lifetime e-cigarette use increased from 40.1% in 2016 to 47.4% in 2018. Former smokers were 5.47 times (95% confidence interval [CI] 3.48-8.61) more likely to be lifetime e-cigarette users and 1.9 times (95% CI 1.12-3.23) more likely to be current e-cigarette users compared to never smokers. Current smokers were over sixteen folds more likely (adjusted odds ratio 16.50, 95% CI 11.59-23.57) to be lifetime e-cigarette users and 2.1 times (95% CI 1.24-3.57) more likely to be current e-cigarette users relative to never smokers. Furthermore, binge drinking and depression were associated with higher odds of lifetime e-cigarette use, while increasing age was associated with lower odds of e-cigarette use. Compared to females, males were significantly more likely to be current users of e-cigarettes relative to former users. Conclusion Conventional cigarette use, binge drinking, depression, age, and gender were found to be associated with e-cigarette use among young adult cancer survivors. https://www.selleckchem.com/ Policies targeted at e-cigarette control among young adult cancer survivors need to be multipronged, simultaneously addressing other harmful practices such as binge drinking and the use of conventional cigarettes.
To explore the ability of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI)/ultrasound (US) fusion imaging (FI) to improve the prognosis of radiofrequency ablation (RFA) by ablating the characteristic findings of hepatocellular carcinoma (HCC) in hepatobiliary phase (HBP) imaging.

We retrospectively recruited 115 solitary HCC lesions with size of (15.9 ± 4.6) mm. They were all treated by RFA and preoperative EOB-MRI. According to the modalities guiding RFA performance, the lesions were grouped into contrast enhanced US (CEUS)/US guidance group and EOB-MRI/US FI guidance group. For the latter group, the ablation scope was set to cover the HBP findings (peritumoral hypointensity and irregular protruding margin). The presence of HBP findings, the modalities guided RFA, the recurrence rate were observed.

After an average follow-up of 377 days, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) were 14.8% and 38.4%, respectively. The lesions having HBP findings exhibited a higher recurrence rate (73.