Burtontimmermann0996

Cystic fibrosis (CF) is characterized by chronic inflammation and excessive cytokines secretion in the lung. Isogenic human CF bronchial epithelial (CFBE41o-) cell lines stably expressing wt-CFTR (WTBE) or F508del mutant (CFBE) are widely used tools in understanding responses to stimuli or drugs and CF pathogenesis in vitro. However, the intrinsic cellular differences in culture are unknown.

We performed integrative analyses of these isogenic cells at the protein, mRNA, and chromatin levels in the submerged and air-liquid interface (ALI) conditions to determine cell intrinsic effects of mutant versus complemented CFTR expression.

CFBE and WTBE cells displayed different cytokine secretion patterns, including IL-6, IL-8, CXCL1, CXCL10, and CCL5. The ALI culture dramatically increased cytokine secretion in both cells. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) result showed different chromatin landscapes upon polarization and CFBE cells, compared to WTBE cells, exhibited higher genome-wide chromatin accessibility under both culture methods. At the transcriptome level, differentially expressed genes identified by mRNA sequencing between two cell lines were highly concentrated in immunity-related pathways.

This multilayered study shows that expression of wild-type CFTR has an epithelial cell intrinsic effect on the cell's epigenome and transcriptome particularly in immunity relevant activities. These data will serve as a resource for the CF community and may serve as epithelial biomarkers for CFTR mRNA therapy.

This multilayered study shows that expression of wild-type CFTR has an epithelial cell intrinsic effect on the cell's epigenome and transcriptome particularly in immunity relevant activities. Glutathione supplier These data will serve as a resource for the CF community and may serve as epithelial biomarkers for CFTR mRNA therapy.

We explored the impact of implementing structured interviews and associated interviewer education on interrater agreement within a large academic residency program.

Faculty and senior resident interviewers from a large academic residency program participated in a 3-hour structured interview course. Before and after the course, participants completed a 15-item assessment pertaining to the characteristics, logistics, and guidelines associated with structured interviews. Along with interviewer training, interview day logistics also changed from an unstructured format (no specific questions, one overall 1-9 rating scale) to a structured interview format, including incorporation of behavioral-based competency questions that would be asked of every applicant and behavioral anchored rating scales (1-10; 10 = highest). Interrater agreement was assessed via intraclass correlation coefficients (ICC1) for the 2 years before and 2 years after incorporation of the structured interview format.

A total of 45 faculty ation can help increase agreement in ratings between interviewers. However, these data suggest that ongoing refresher trainings may be needed to maintain acceptable levels of interrater agreement.Medication use in children represents 15-20% of total drug sales. More than 50% of children receive at least one prescription medication a year. Despite this, few drugs have a paediatric formulation available. Furthermore, 80% of paediatric prescriptions are considered off-label. Off-label use is defined as the use of products that differ in dose, indication or route of administration from the one established in the summary of product characteristics. Off-label use is associated with an increased risk of adverse drug reactions, including therapeutic failure. The US Food and Drug Administration and the European Medicines Agency have made changes to regulations to incentivize the development of paediatric formulations. Novel paediatric formulations can ease drug administration, reducing medication errors, increasing dosing acceptability, medication adherence and improve safety. Two routes for paediatric drug approval are available, the traditional, requiring clinical trials and the formulation bridging path, where these formulations need to demonstrate equivalence with the existing adult formulations. New formulations seeking regulatory approval require bioequivalence studies, but the regulatory framework, which states that bioequivalence data are obtained from adults and then extrapolated to children, may be disregarding important physiological differences between these two populations of patients. It is important to ensure that drugs for children have been appropriately studied and are properly manufactured for them. Adequately designed studies will provide data that will improve our understanding of how drug disposition differs between adults and children and will pave the way for children to get the best possible treatment.

Multiple screening methods for malnutrition are available, but a systematic review of evidence in patients with colorectal cancer (CRC) is lacking. The aim of this study is to systematically investigate which outcome variables of nutritional screening methods are associated with treatment tolerance in patients with CRC.

A systematic review was performed with respect to outcome variables of nutritional screening methods and their association with systemic treatment tolerance in patients with CRC. The Cochrane guidelines for systematic reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Two authors independently assessed the risk of bias and quality of each included study.

A total of sixteen studies were included. The following screening methods for malnutrition were assessed in the included studies serum albumin, body mass index, C-reactive protein/albumin ratio, modified version of the Glasgow prognostic score, mini nutritional assessmenttus and associated risk for treatment intolerance. This grants practitioners the flexibility to choose from a variety of different nutritional screening methods. Nutritional screening can thus be tailored to the individual patient. Importantly, nutritional screening may help identify those patients at risk for chemotoxicity thus allowing for the implementation of targeted prehabilitation programs in order to prevent (severe) chemotoxicity.

Does the COVID-19 vaccination affect endometrial receptivity after single euploid embryo transfer, measured by sustained implantation rate?

A retrospective cohort study analysing two groups of single euploid embryo transfers using own oocytes one historical cohort of 3272 transfers 1 year before the pandemic; and one comprising 890 transfers in women previously vaccinated with mRNA vaccines against severe acute respiratory syndrome coronavirus 2. The main outcomes were clinical pregnancy rate (CPR) and sustained implantation rate (SIR) per embryo transfer. These outcomes were compared between non-vaccinated and vaccinated women, and women who had received one and two doses. Lastly, vaccinated women were divided into quartiles according to the time from last dose to embryo transfer.

Similar CPR and SIR were found between non-vaccinated and vaccinated women, and the odds ratio for both outcomes was not statistically significant after being controlled for potential confounders (OR 0.937, 95% CI 0.695 to 1.d reproductive treatment.Possible applicability of controlled temperature chain (CTC) for selected antisera and vaccines was evaluated. Bivalent oral polio vaccine (OPV), hepatitis B vaccine (HepB vaccine; monovalent and combined) and antisera (lyophilized and liquid scorpion-antivenom and liquid snake-antivenom) were tested. Samples were stored at accelerated (35 ± 5 °C) and freezing (-25 ± 5 °C) conditions for 24 h, one week and one month in addition to recommended storage condition (2-8 °C), except OPV samples that were tested at accelerated and refrigerated (2-8 °C) conditions compared to recommended storage conditions (-25 ± 5 °C). All samples were tested for potency. Protein content and composition were determined for antisera samples. All vaccine vial-monitors were evaluated. HepB vaccine was subjected to aluminum-content assay, shake test and microscopical examination. No significant change in antisera potency was detectable under accelerated condition for a week. OPV stored in refrigerator for a month and at accelerated condition for 48 h maintained acceptable potency. Monovalent and combined HepB vaccine maintained acceptable potency under accelerated condition for a month and a week, respectively. Freezing adversely affected HepB vaccine. In conclusion, reevaluation of storage conditions of tested products is urgently required; this can reduce storage costs and improves their availability. Other products should be tested for possible CTC applicability.

To assess a clearing protocol using ethyl cinnamate, an organic substance which is non-toxic for humans, and its value in light-sheet microscopy study of post-implantation cochlear damage in the Mongolian gerbil.

The animals underwent right cochlear implantation in the round window by a retroauricular approach. They were then euthanized 10 weeks after implantation (electrode array in place). The cochleae were prepared according to a 29-day protocol including steps of fixation, microdissection, decalcification, permeabilization, blocking, fluorescent immunolabeling, dehydration and finally clearing in ethyl cinnamate solution. Acquisition of transparent cochleae was performed by light-sheet microscopy. Imaris software was then used for 3D analysis.

The transparent cochleae had not undergone any shrinkage or any significant architectural changes. Six cochleae were acquired by light-sheet microscopy, allowing good visibility of the whole cochlea. 3D immunofluorescence analysis of the cochlea provided sufficient image resolution for analysis of the spiral ganglion neurons and assessment of the fibrotic tissue reaction surrounding the electrode array.

The ethyl cinnamate clearing protocol was effective for light-sheet microscopy analysis of the whole Mongolian gerbil cochlea with the implant left in situ. This technique is suitable for the study of post-implantation cell and tissue damage in the same sample, without the potential toxicity of other methods described to date.

The ethyl cinnamate clearing protocol was effective for light-sheet microscopy analysis of the whole Mongolian gerbil cochlea with the implant left in situ. This technique is suitable for the study of post-implantation cell and tissue damage in the same sample, without the potential toxicity of other methods described to date.

To evaluate the impact of the first three waves of COVID-19 on the academic and surgical training of ENT and Head and Neck Surgery residents in France.

Observational, retrospective study. A 55-item survey of academic education and surgical training was sent to ENT residents in five major French regions (Île-de-France, Rhône-Alpes Auvergne, Occitanie, Grand Est, Grand Ouest) from August to October 2021.

Eighty-nine out of 135 residents (66%) responded. Two-thirds considered that surgical training was more affected than academic education, with reductions evaluated of 50-75%, 25-50% and 0-25% for the first three waves, respectively. Residents in Île-de-France, Rhône-Alpes Auvergne and Grand Est were the most affected by the first wave (75-100% reduction in surgical activity, in parallel to increased admissions). Otology, rhinology and functional exploration were the most affected, whereas pediatrics and oncology were spared. Seventy-one of the 89 residents (79.7%) felt that the first wave impacted their career, while this proportion decreased to 39.