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.