Starrprater0788

Immunotherapy, targeting programmed death-1 (PD-1) enhances antitumor T-cell activity in patients with malignancies. Blocking PD-1 or its ligand may lead to fulminant colitis as serious adverse event in these patients. Since little is known of the presence and role of PD-1

T cells in colitis of different etiologies, we determined PD-1

T cells in mucosal specimens of patients with inflammatory bowel disease, infectious colitis (InfC), immunotherapy-related colitis (ImC) and healthy controls (HC).

Newly diagnosed patients with ulcerative colitis (UC,

 = 73), Crohn's disease (CD,

 = 50), InfC (

 = 5), ImC (

 = 8) and HC (

 = 8) were included. Baseline inflamed colonic biopsies were studied with immunohistochemistry and flowcytometry.

Using immunohistochemistry, PD-1 was not present on lymphocytes in the epithelium of all patients, nor in HC. The percentage PD-1

of all lymphocytes in the lamina propria was 40% in UC, 5% in InfC, 3% in ImC and 0% in HC. Flowcytometry showed significant higher percentages of PD-1

T cells in inflamed biopsy specimens of UC patients (22%) compared to all other groups CD patients (13%), InfC (12%), ImC (5%) and HC (6%).

There are relevant differences in distribution and frequencies of mucosal PD-1

T-cell subsets in patients with UC, CD, InfC and ImC, supporting the hypothesis that these types of colitis are driven by different immunological pathways. The increased numbers of PD-1

and PD-L1

lymphocytes in the colonic mucosa of UC patients suggest that the PD-1/PD-L1 pathway might be more activated in UC than in CD.

There are relevant differences in distribution and frequencies of mucosal PD-1+ T-cell subsets in patients with UC, CD, InfC and ImC, supporting the hypothesis that these types of colitis are driven by different immunological pathways. The increased numbers of PD-1+ and PD-L1+ lymphocytes in the colonic mucosa of UC patients suggest that the PD-1/PD-L1 pathway might be more activated in UC than in CD.To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo. Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro, and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet-visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 μg ± 12.508 and 127.438 μg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs (p=.006) and closed to 150 μg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro. SCLs were safe in vitro and in vivo, PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.This study describes the research and healthcare priorities of individuals living with COPD. On an online survey, individuals living with COPD assigned a percentage of funding to 22 research priorities and a percentage of time spent communicating with a healthcare provider to 24 healthcare priorities, indicating which topics were most important. For each research and healthcare priority, we examined the selection frequency of the priority and used chi-square analyses to examine differences in priority selection by quartiles of airflow obstruction (percent predicted forced expiratory volume in 1-sec (FEV1%predicted)) and breathlessness burden and exacerbation risk. Based on participants' responses (N = 148, 47% women; Mean ± Standard Deviation age = 68 ± 9 yrs) relief of breathlessness was the most often selected research (76% of respondents) and healthcare priority (61% of respondents). It was selected most often, regardless of disease severity or breathlessness burden and exacerbation risk. We found differences for disease severity and breathlessness burden and exacerbation risk in some research priorities (e.g., to improve the maximal amount of exercise of adults living with COPD in and out of the home (χ2(3) = 9.97, Cramer's V =.28) and healthcare priorities (e.g., increase your ability to exercise (χ2(3) = 9.72, Cramer's V =.27)). This study provides empirical evidence that relief of breathlessness is a top research and healthcare priority for individuals living with COPD. Future healthcare and research activities should align with the priorities of individuals with COPD to improve their care by minimizing disease/symptom burden and optimizing health-related quality of life.Introduction Artificial intelligence (AI) has inspired computer-aided drug discovery. The widespread adoption of machine learning, in particular deep learning, in multiple scientific disciplines, and the advances in computing hardware and software, among other factors, continue to fuel this development. Much of the initial skepticism regarding applications of AI in pharmaceutical discovery has started to vanish, consequently benefitting medicinal chemistry.Areas covered The current status of AI in chemoinformatics is reviewed. The topics discussed herein include quantitative structure-activity/property relationship and structure-based modeling, de novo molecular design, and chemical synthesis prediction. Advantages and limitations of current deep learning applications are highlighted, together with a perspective on next-generation AI for drug discovery.Expert opinion Deep learning-based approaches have only begun to address some fundamental problems in drug discovery. Certain methodological advances, such as message-passing models, spatial-symmetry-preserving networks, hybrid de novo design, and other innovative machine learning paradigms, will likely become commonplace and help address some of the most challenging questions. Open data sharing and model development will play a central role in the advancement of drug discovery with AI.Glomerular filtration rate (GFR) measured by urinary clearance of inulin is considered the gold standard for assessment of kidney function in both adults and children. Because the procedure is cumbersome, GFR is estimated (eGFR) using algorithms based on the observed relationship between measured GFR (mGFR) and more accessible biomarkers such as creatinine and cystatin C. In children, most of the data on this relationship is retrieved from patients with reduced kidney function. Nonetheless, eGFR equations are widely in use in healthy children to evaluate kidney status and diagnose kidney disease. The aim of the present study was to compare the distribution of eGFR using two established pediatric eGFR equations incorporating age, height and serum creatinine (Schwartz-Lyon and Full Age Spectrum-height) and two recently published equations restricted to age and serum creatinine (Lund-Malmö Revised 18 and European Kidney Function Consortium equation) in 1200 healthy schoolchildren age 6-12 years. In addition, we present 2.5th, median and 97.5th percentiles for serum creatinine stratified by age and gender. Depending on the equation used, mean eGFR ranged from 101.6 to 115.4 mL/min/1.73 m2. The lower 2.5th percentile ranged from 83.3 to 89.0 mL/min/1.73 m2 and the fraction of children with eGFR less then 90 mL/min/1.73 m2 ranged from 2.9% to 9.8%. In conclusion, expected values of eGFR in healthy children are significantly dependent on the equation used. When decision limits for diagnosis or classification are applied to eGFR results, the related equation should be clearly stated.

Children and adolescents with cerebral palsy have diverse needs and often engage with healthcare services, including paediatric rehabilitation. Partnering with these children and adolescents on research projects to inform practice has the potential to ensure services continue to remain relevant and appropriate. This study aimed to identify what children and adolescents with cerebral palsy suggest are effective ways for researchers to involve them as partners in research.

This qualitative study was guided by interpretive description. Children and adolescents with cerebral palsy between 8 and 18 years participated in semi-structured, activity-based focus groups or interviews. Verbatim transcripts were coded and analysed using thematic analysis. One member of the research team was a young woman with cerebral palsy.

Seventeen children and adolescents with cerebral palsy from NSW and Victoria (Australia) were involved. mTOR inhibitor Participants were between 8 and 18 years (mean = 12 years), male (

 = 11) and female (

 , and considerations for researchers to facilitate involvement of children and adolescents with cerebral palsy as partners in research.IMPLICATIONS FOR REHABILITATIONThe commitment in healthcare to client-centred practice requires that consumers, including children and young people with cerebral palsy, have opportunities to influence the direction of research which impacts them.Children and young people with cerebral palsy are interested in research partnerships and motivated to be involved in various areas of research.Effective research partnerships with younger populations can be facilitated by researchers acknowledging a child or young person's expertise, and employing strategies relating to open communication, flexibility and support.Chronic obstructive pulmonary disease (COPD) is characterized by high cardiovascular risk, which is further amplified during acute COPD exacerbations (AECOPD). Endothelial dysfunction has been previously suggested as one of the potential pathogenetic mechanisms. In order to study the effects of AECOPD on endothelial function assessed by available functional methods, we performed a literature search involving Pubmed and Scopus databases. Eligible studies were those that included adult patients with COPD and evaluated endothelial damage via semi-invasive or noninvasive functional methods, during AECOPD and after recovery or in stable condition. Newcastle-Ottawa Scale was applied to evaluate the quality of retrieved studies. Endothelial function was significantly impaired during AECOPD compared to recovery/stable condition (SMD -0.87, 95%CI [-1.19, -0.55]). Patients during AECOPD presented a significantly worse response in endothelium-dependent (flow-mediated dilatation WMD -2.59, 95%CI [-3.75, -1.42]) and independent vasodilation (nitroglycerine-mediated dilatation WMD -3.13, 95%CI [-5.18, -1.09]) compared to recovery. Sensitivity analyses confirmed the above results. In conclusion, endothelium-dependent and independent vasodilation is worse during AECOPD compared to the stable condition. Endothelial dysfunction could play a role in the high cardiovascular risk during AECOPD.