Molecular Investigation of SNAC as an Oral Peptide Permeation Enhancer in Lipid Membranes via Solid-State NMR.

Oral peptide therapeutics are increasingly favored in the pharmaceutical industry for their ease of use and better patient adherence. However, they face challenges with poor oral bioavailability due to their high molecular weight and surface polarity. Permeation enhancers (PEs) like salcaprozate sodium (SNAC) have shown promise in clinical trials, achieving about 1% bioavailability.

Molecular mechanisms for stabilizing biologics in the solid state.

Protein drugs exhibit challenges of biophysical and biochemical instability due to their structural complexity and rich dynamics. Solid-state biologics aim to enhance stability by increasing molecular rigidity within the formulation matrix, representing a primary category of drug products alongside sterile liquid formulations. Understanding the molecular mechanisms behind the stabilization and destabilization of protein drugs, influenced by formulation composition and drying processes, provides scientific rationale for drug product design.

Examining PTSD Prevalence Among Underserved Populations in the Integrated Community Mental Health Setting 2019 to 2022.

Background: The prevalence of Post Traumatic Stress Disorder (PTSD) has been rising since the start of the COVID-19 pandemic, and affects females, sexual and gender minorities, and individuals with social risks at higher rates.

Objective: This study examines if the prevalence of PTSD increased from 2019 to 2022 among patients who received care in a national network of safety-net, community-based health centers with integrated behavioral health programs that serve patients at high risk for PTSD.

Methods: We analyzed electronic health record data from patients with 1 or more behavioral health visits during 2019 to 2022 using repeated cross-sectional data to visualize trends.

Implementation strategies to improve adoption of unmet social needs screening and referrals in care management using enabling technologies: study protocol for a cluster randomized trial.

Background: Adverse social determinants of health contribute to health inequities. Practice guidelines now recommend incorporating patient unmet social needs into patient care, and payors increasingly reimburse for screening and providing related referrals to community organizations. Emergent electronic health record (EHR)-based tools can enable clinical-community linkages, but their adoption commonly faces workflow and infrastructure barriers.

Glycine synthesis from nitrate and glyoxylate mediated by ferroan brucite: An integrated pathway for prebiotic amine synthesis.

Amino acids are present in all known life, so identifying the environmental conditions under which they can be synthesized constrains where life on Earth might have formed and where life might be found on other planetary bodies. All known abiotic amino acid syntheses require ammonia, which is only produced in reducing and neutral atmospheres. Here, we demonstrate that the Fe-bearing hydroxide mineral ferroan brucite [Fe,Mg(OH)] can mediate the reaction of nitrate and glyoxylate to form glycine, the simplest amino acid used in life.

Genotyping Error Detection and Customised Filtration for SNP Datasets.

A major challenge in analysing single-nucleotide polymorphism (SNP) genotype datasets is detecting and filtering errors that bias analyses and misinterpret ecological and evolutionary processes. Here, we present a comprehensive method to estimate and minimise genotyping error rates (deviations from the 'true' genotype) in any SNP datasets using triplicates (three repeats of the same sample) in a four-step filtration pipeline. The approach involves: (1) SNP filtering by missing data; (2) SNP filtering by error rates; (3) sample filtering by missing data and (4) detection of recaptured individuals by using estimated SNP error rates.

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review.

Purpose: Optimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols.

Methods: A systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted.

Cut-offs for relapse detection in men with stage I testicular germ cell tumors during active surveillance within a prospective multicentre cohort study using either raw or housekeeper normalized miR-371a-3p serum levels.

Purpose: MiR-371a-3p represents a novel liquid biomarker that detects all histologies of germ-cell tumors (GCT) except teratoma. However, it is currently unclear whether miR-371a-3p results obtained directly from RT-PCR (raw Cq) or normalized for housekeeper genes and transformed into the relative quantity (RQ) value should be used and at what cut-off level. The purpose of this research was to evaluate, which values should be used, and a potential cut-off level for relapse-detection to inform subsequent studies.

Capturing the care of complex community-based health center patients: A comparison of multimorbidity indices and clinical classification software.

Objective: To compare morbidity burden captured from multimorbidity indices and aggregated measures of clinically meaningful categories captured in primary care community-based health center (CBHC) patients.

Data Sources And Study Setting: Electronic health records of patients seen in 2019 in OCHIN's national network of CBHCs serving patients in rural and underserved communities.

Study Design: Age-stratified analyses comparing the most common conditions captured by the Charlson, Elixhauser, and Multimorbidity Weighted (MWI) indices, and Classification Software Refined (CCSR) and Chronic Condition Indicator (CCI) algorithms.

Molecular Mechanism of P53 Peptide Permeation through Lipid Membranes from Solid-State NMR Spectroscopy and Molecular Dynamics Simulations.

Macrocyclic peptides show promise in targeting high-value therapeutically relevant binding sites due to their high affinity and specificity. However, their clinical application is often hindered by low membrane permeability, which limits their effectiveness against intracellular targets. Previous studies focused on peptide conformations in various solvents, leaving a gap in understanding their interactions with and translocation through lipid bilayers.

Developing and evaluating a brief, socially primed video intervention to enable bystander cardiopulmonary resuscitation: A randomised control trial.

Background: Over 30,000 people experience out-of-hospital cardiac arrest in the United Kingdom annually, with only 7-8% of patients surviving. One of the most effective methods of improving survival outcomes is bystander intervention in the form of calling the emergency services and initiating chest compressions. Additionally, the public must feel empowered to act and use this knowledge in an emergency.

Care Quality and Equity in Health Centers During and After the COVID-19 Pandemic.

Introduction: Federally Qualified Community Health Centers (FQHCs) are on the frontline of efforts to improve healthcare equity and reduce disparities exacerbated by the COVID-19 pandemic. This study assesses the provision and equity of preventive care and chronic disease management by FQHCs before, during, and after the pandemic.

Methods: Using electronic health record data from 210 FQHCs nationwide and employing segmented regression in an interrupted time series design, preventive screening and chronic disease management were assessed for 939,053 patients from 2019 to 2022.

Shared social identity and social norms shape risk-taking at mass gatherings.

Shared social identity and social norms are often un(der)recognized within mass gatherings health literature, yet they can increase infectious disease transmission by motivating people to engage in risk-taking behaviours. Across three experiments (N = 1551), we investigated how shared social identities, perceived norms of resource-sharing, and perceived riskiness of sharing interact to shape decisions that can lead to disease transmission. In Experiment 1 (N = 528), we examined how shared social identity and perceived descriptive norms affect the likelihood of crowd members sharing resources that may contribute to disease spread.

A low-cost phantom design for evaluating spine SABR calculations in the presence of prosthetic vertebral stabilization.

Dose-perturbation characteristics are important to consider during the calculation of radiation therapy protocols for patients who are going to receive high doses that would reach the tolerance limits of the spinal cord [1]. Several studies have investigated dose perturbations introduced by metal implants in close proximity to spine SABR treatments [2-7]. However, there is a lack of work assessing this effect using the RayStation TPS [8].

Variation in multimorbidity by sociodemographics and social drivers of health among patients seen at community-based health centers.

Purpose: Understanding variation in multimorbidity across sociodemographics and social drivers of health is critical to reducing health inequities.

Methods: From the multi-state OCHIN network of community-based health centers (CBHCs), we identified a cross-sectional cohort of adult (> 25 years old) patients who had a visit between 2019-2021. We used generalized linear models to examine the relationship between the Multimorbidity Weighted Index (MWI) and sociodemographics and social drivers of health (Area Deprivation Index [ADI] and social risks [e.

Dissolved silica affects the bulk iron redox state and recrystallization of minerals generated by photoferrotrophy in a simulated Archean ocean.

Chemical sedimentary deposits called Banded Iron Formations (BIFs) are one of the best surviving records of ancient marine (bio)geochemistry. Many BIF precursor sediments precipitated from ferruginous, silica-rich waters prior to the Great Oxidation Event at ~2.43 Ga.

Identity leadership and adherence to COVID-19 safety guidance in hospital settings.

COVID-19 presents unique and complex challenges to the Scottish National Health Service (NHS). As COVID-19 preventative measures are effective at reducing disease spread, promoting staff adherence in high-risk workplaces is vital. The present research explored the role of identity leadership on (a) staff's appraisals of leadership and (b) staff's adherence to and attitudes towards COVID-19 guidance.

Changing genomic epidemiology of COVID-19 in long-term care facilities during the 2020-2022 pandemic, Washington State.

Background: Long-term care facilities (LTCFs) are vulnerable to disease outbreaks. Here, we jointly analyze SARS-CoV-2 genomic and paired epidemiologic data from LTCFs and surrounding communities in Washington state (WA) to assess transmission patterns during 2020-2022, in a setting of changing policy. We describe sequencing efforts and genomic epidemiologic findings across LTCFs and perform in-depth analysis in a single county.

Early response monitoring during [Lu]Lu-PSMA I&T therapy with quantitated SPECT/CT predicts overall survival of mCRPC patients: subgroup analysis of a Swiss-wide prospective registry study.

Purpose: To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Lutetium-PSMA I&T therapy.

Methods: Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [Lu]Lu-PSMA I&T (EKNZ: 2021-01271) in mCRPC patients treated with at least two cycles of [Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss).

Intact polar lipidome and membrane adaptations of microbial communities inhabiting serpentinite-hosted fluids.

The generation of hydrogen and reduced carbon compounds during serpentinization provides sustained energy for microorganisms on Earth, and possibly on other extraterrestrial bodies (e.g., Mars, icy satellites).