FT-4202, a selective pyruvate kinase R activator for sickle cell disease.

Anemia in patients with sickle cell disease (SCD) increases 2,3-diphosphoglycerate (2,3-DPG), decreasing hemoglobin-oxygen (HbO) affinity to improve oxygen offloading and promote hemoglobin polymerization (sickling) of red blood cells (RBCs). We report the discovery of FT-4202, an investigational, selective pyruvate kinase type-R (PKR) activator with a multimodal mechanism of action and potential to increase ATP and decrease 2,3-DPG, resulting in increased HbO affinity, decreased Hb polymerization, and improved RBC health. FT-4202 was identified via structure-enabled lead optimization medicinal chemistry using X-ray crystallography, molecular modeling, and thermal shift assays.

Body Mass Index Is Associated with Post-Acute Elevations in Biomarkers of Platelet Activation and Inflammation in Unvaccinated Adults Diagnosed with COVID-19 in the Previous 8 Weeks.

Introduction: Obesity has arisen as a prominent risk factor for COVID-19 severity and long COVID, potentially owed in part to the obesity-induced proinflammatory state. This study aimed to examine relationships among circulating inflammatory biomarkers and body mass index in nonhospitalized adults recently diagnosed with COVID-19.

Methods: This analysis included participants who completed a randomized placebo-controlled trial conducted in October 2020-March 2021.

Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial.

Depressive disorders are the most prevalent mental health conditions in the world. The commonly prescribed antidepressant medications can have serious side effects, and their efficacy varies widely. Thus, simple, effective adjunct therapies are needed.

Discovery and Preclinical Characterization of XMT-1660, an Optimized B7-H4-Targeted Antibody-Drug Conjugate for the Treatment of Cancer.

Antibody-drug conjugates (ADC) achieve targeted drug delivery to a tumor and have demonstrated clinical success in many tumor types. The activity and safety profile of an ADC depends on its construction: antibody, payload, linker, and conjugation method, as well as the number of payload drugs per antibody [drug-to-antibody ratio (DAR)]. To allow for ADC optimization for a given target antigen, we developed Dolasynthen (DS), a novel ADC platform based on the payload auristatin hydroxypropylamide, that enables precise DAR-ranging and site-specific conjugation.

Curcumin Confers Anti-Inflammatory Effects in Adults Who Recovered from COVID-19 and Were Subsequently Vaccinated: A Randomized Controlled Trial.

COVID-19 infection and vaccination offer disparate levels of defense against reinfection and breakthrough infection. This study was designed to examine the effects of curcumin supplementation, specifically HydroCurc (CURC), versus placebo (CON) on circulating inflammatory biomarkers in adults who had previously been diagnosed with COVID-19 and subsequently received a primary series of monovalent vaccine doses. This study was conducted between June 2021 and May 2022.

Systematic review and meta-analysis of individual serum lipids and analysis of lipid ratios in ankylosing spondylitis and healthy control cohorts: significantly lower mean HDL-cholesterol level in ankylosing spondylitis cohorts.

Objectives: Ankylosing spondylitis (AS) is suspected to have increased risk of atherosclerosis and cardiovascular disease (CVD) mortality. This systematic review and meta-analysis aims to critically study serum lipids and lipoprotein ratios in AS compared to healthy control (HC) subjects and determine any significant difference.

Methods: English-language articles were systematically searched in PubMed, Ovid Medline, Embase (Medline records removed), and Scopus databases from 1970 to 2021.

Postvoid residual bladder volume after uncomplicated vaginal delivery.

Objective: To create a reference curve for postvoid residual volume (PVRV) in asymptomatic postpartum women who are at low risk of developing postpartum urinary retention (PUR), a well-known complication in the immediate postpartum period.

Methods: This is a prospective observational study measuring PVRV after uncomplicated vaginal delivery. PVRV was assessed by transabdominal ultrasound using a portable ultrasound scanner within the first 26 h after delivery (PVRV 1) and on the day of discharge (day 2 or 3 postpartum) (PVRV 2).

Palmitoylethanolamide Reduces Proinflammatory Markers in Unvaccinated Adults Recently Diagnosed with COVID-19: A Randomized Controlled Trial.

Background: Inflammation is at the core of many chronic conditions and exacerbates infectious conditions, including the severity of coronavirus disease 2019 (COVID-19) infections.

Objectives: This study aimed to examine the effects of a novel food supplement, palmitoylethanolamide (PEA), specifically Levagen+, as compared with a placebo on proinflammatory biomarkers in adults recently diagnosed with COVID-19 who were unvaccinated and nonhospitalized.

Methods: This study was a double-blind randomized placebo-controlled trial conducted October 2020-March 2021 (clinicaltrials.

Erythrocyte osmotic fragility is not linked to vitamin C nutriture in adults with well-controlled type 2 diabetes.

Erythrocyte fragility is amplified by oxidative stress and linked to diabetes-specific microvascular disease. Vitamin C supplementation improves glycemic indices in adults with type 2 diabetes (T2D) by improving antioxidant status. This cross-sectional study examined the relationships between vitamin C status and erythrocyte osmotic fragility in adults with or without T2D.

Lipopolysaccharide and the gut microbiota: considering structural variation.

Systemic inflammation is associated with chronic disease and is purported to be a main pathogenic mechanism underlying metabolic conditions. Microbes harbored in the host gastrointestinal tract release signaling byproducts from their cell wall, such as lipopolysaccharides (LPS), which can act locally and, after crossing the gut barrier and entering circulation, also systemically. Defined as metabolic endotoxemia, elevated concentrations of LPS in circulation are associated with metabolic conditions and chronic disease.

Daily Vinegar Ingestion Improves Depression Scores and Alters the Metabolome in Healthy Adults: A Randomized Controlled Trial.

Daily vinegar ingestion has been linked to improved glycemic control, but recent data suggest a separate unexplored role for vinegar in mental health. Utilizing a placebo-controlled, parallel arm study design, this 4-week trial examined the impact of daily vinegar ingestion on mood states and urinary metabolites in healthy college students. Participants were randomized to the vinegar group (VIN: = 14; 1.

The deubiquitylase USP9X controls ribosomal stalling.

When a ribosome stalls during translation, it runs the risk of collision with a trailing ribosome. Such an encounter leads to the formation of a stable di-ribosome complex, which needs to be resolved by a dedicated machinery. The initial stalling and the subsequent resolution of di-ribosomal complexes requires activity of Makorin and ZNF598 ubiquitin E3 ligases, respectively, through ubiquitylation of the eS10 and uS10 subunits of the ribosome.

Minimally Invasive Laparoscopic Transabdominal Cerclage with a "Needle-Free" Technique: A Single-Center Experience.

Background: In high-risk patients with cervical incompetence, laparoscopic cerclage is a promising treatment option. However, the procedure exhibits relevant surgical risks.

Aims: The purpose of this study was to evaluate a surgical "needle-free" technique for minimally invasive, laparoscopically placed cervico-isthmic cerclage in high-risk patients.

Perception of Labial Size and Objective Measurements-Is There a Correlation? A Cross-Sectional Study in a Cohort Not Seeking Labiaplasty.

Introduction: Poor genital self-image is a common phenomenon leading to an increasing interest in female genital surgery over the last years.

Aim: The aim was to correlate objective measurements of the labia minora with the individual subjective perception of the labial size.

Methods: In a cross-sectional study with 200 premenopausal women (median age 33.

Recurrence of genitals warts in pre-HPV vaccine era after laser treatment.

Purpose: Human papillomavirus (HPV) can cause condylomata acuminata, also known as genital warts. Our aim was to evaluate the long-term recurrence of genital warts after primary carbon dioxide laser treatment before the introduction of the vaccination against HPV.

Methods: Recurrence rate and localization of genital warts were analysed in a retrospective study in 1798 women presenting with a new diagnosis of genital warts from 1992 to 2009 at a University hospital and had received laser treatment.

Discovery of novel biaryl sulfonamide based Mcl-1 inhibitors.

Mcl-1 is an anti-apoptotic protein overexpressed in hematological malignancies and several human solid tumors. Small molecule inhibition of Mcl-1 would offer an effective therapy to Mcl-1 mediated resistance. Subsequently, it has been the target of extensive research in the pharmaceutical industry.

Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN).

The discovery, structure-activity relationships, and optimization of a novel class of fatty acid synthase (FASN) inhibitors is reported. High throughput screening identified a series of substituted piperazines with structural features that enable interactions with many of the potency-driving regions of the FASN KR domain binding site. Derived from this series was FT113, a compound with potent biochemical and cellular activity, which translated into excellent activity in in vivo models.

A Qualitative Description of Nurses' Experiences With Incorporating Research Into Practice.

Background: Baccalaureate-prepared nurses should be competent in accessing, evaluating, and implementing research evidence into nursing practice. The purpose of this study was to gain insight into nurses' experiences in accessing, evaluating, and implementing research into practice.

Method: Researchers conducted a qualitative descriptive study.

Health-related quality of life in patients with polycystic ovary syndrome: validation of the German PCOSQ-G.

Purpose: Patients with polycystic ovary syndrome (PCOS) report a decreased health-related quality of life (HRQOL) and higher levels of psychological distress. Validated questionnaires are necessary to assess the impact of PCOS on patients' lives. The aim of the present study was to evaluate the German "Polycystic Ovary Syndrome Questionnaire" (PCOSQ-G).

L1CAM and HER2 Expression in Early Endometrioid Uterine Cancer.

Recently L1CAM was shown to be a promising biomarker for early-stage endometrial carcinoma (EC). As L1CAM expression was found to be related to serous ECs and areas of serous differentiation in endometrioid carcinomas, there is evidence that L1CAM-positive cancers more likely resemble type II carcinomas. Furthermore, expression of growth factor receptor HER2 has been found to be closely associated with serous ECs.

Impact of endometriosis on quality of life, anxiety, and depression: an Austrian perspective.

Purpose: Several studies on the quality of life in patients with endometriosis have been performed with conflicting results. This cross-section survey examines the influence of endometriosis on the psychological well-being and the quality of life and the incidence of anxiety and depression among these patients, recruited from a tertiary care center in Austria.

Methods: Three standardized questionnaires of 62 patients with endometriosis were evaluated: status of health questionnaire (SF-36), hospital anxiety and depression scale (HADS-D), and endometriosis health profile (EHP-30).

How well do General EMS 911 dispatch protocols predict ED resource utilization for pediatric patients?

Introduction: The use of Emergency Medical Services (EMS) for low-acuity pediatric problems is well documented. Attempts have been made to curb potentially unnecessary transports, including using EMS dispatch protocols, shown to predict acuity and needs of adults. However, there are limited data about this in children.

High prevalence of hearing loss at the special olympics: is this representative of people with intellectual disability?

Background: The Healthy Hearing (HH) programme at the Special Olympics (SO) revealed hearing disorders in between 16 and 40% of athletes. However, it is not clear whether these prevalence represents the entire population with intellectual disability. Therefore, this study compares the hearing status of SO athletes with an intellectual disability (ID) to students with ID at a special needs school.