Linzagolix rapidly reduces heavy menstrual bleeding in women with uterine fibroids: An analysis of the PRIMROSE 1 & 2 trials.

Objective: To study the timing of the effect of linzagolix, an oral GnRH antagonist, on significant reduction in heavy menstrual bleeding (HMB) in women with uterine fibroids.

Design: The study used pooled data from PRIMROSE1 and PRIMROSE2, two double-blind, similar placebo-controlled trials of linzagolix in US and Europe, respectively. Eligible participants were randomized equally across four treatment arms (linzagolix 100mg and 200mg, with and without concomitant hormonal add-back therapy [ABT] consisting of 1 mg estradiol and 0.

Complete genome sequence of singleton phage Magritte.

Actinobacteriophage Magritte was isolated from soil in Columbia, TN using as a host. Magritte is a singleton with a siphovirus morphology and a large genome of 133,228 bp encoding 250 predicted genes, including 26 tRNA genes.

Hierarchical selection of genetic and gene by environment interaction effects in high-dimensional mixed models.

Interactions between genes and environmental factors may play a key role in the etiology of many common disorders. Several regularized generalized linear models have been proposed for hierarchical selection of gene by environment interaction effects, where a gene-environment interaction effect is selected only if the corresponding genetic main effect is also selected in the model. However, none of these methods allow to include random effects to account for population structure, subject relatedness and shared environmental exposure.

An Examination of Underlying Domains in Childhood Adversity: A Scoping Review of Studies Conducting Factor Analyses on Adverse Childhood Experiences.

There is an abundance of research linking experiences of childhood adversity to negative physical and mental health outcomes. Areas that remain to be explored and expanded upon include the ideal set of events for inclusion in measures of childhood adversity and testing the models of risk (e.g.

Efficacy and Safety of GLP-1 Agonists on Metabolic Parameters in Non-diabetic Patients with Inflammatory Bowel Disease.

Background: Obesity in patients with IBD is increasing, accompanied by an increase in metabolic comorbidities. Although GLP-1 agonists have shown promise in weight reduction, their efficacy and safety in patients with IBD are underexplored. This study evaluated the impact of GLP-1-based therapies on weight loss and metabolic parameters in non-diabetic patients with IBD.

Endoscopy in Inflammatory Bowel Disease: Indications, Timing, and Biopsy Protocol.

The management of inflammatory bowel disease has seen significant advancements with the introduction of endoscopic examinations, allowing for diagnosis, assessment of inflammation severity, and monitoring of treatment response. The frequency of follow-up endoscopies is personalized based on the factors such as the disease course and treatment response. Endoscopic findings should be well described, and biopsies should be acquired in a thoughtful, protocolized manner.

Dramatic Changes in Thiopurine Metabolite Levels in a Patient With Inflammatory Bowel Disease Treated With Tirzepatide for Weight Loss.

Thiopurines can be used to maintain remission in patients with inflammatory bowel disease. Thiopurines require regular blood count monitoring and, in specific patients, thiopurine metabolites for assessment of optimization and safety. We present the case of a 42-year-old woman with ulcerative colitis postcolectomy and ileal pouch-anal anastomosis with subsequent antibiotic-resistant diffuse pouchitis and prepouch ileitis.

Mitochondrial elongation impairs breast cancer metastasis.

Mitochondrial dynamics orchestrate many essential cellular functions, including metabolism, which is instrumental in promoting cancer growth and metastatic progression. However, how mitochondrial dynamics influences metastatic progression remains poorly understood. Here, we show that breast cancer cells with low metastatic potential exhibit a more fused mitochondrial network compared to highly metastatic cells.

Successful Treatment of Severe Pyoderma Gangrenosum and Ulcerative Colitis With Upadacitinib.

Pyoderma gangrenosum (PG) is a rare inflammatory and ulcerative skin disorder that is often associated with an underlying systemic disease, including inflammatory bowel disease. Many treatments used to treat inflammatory bowel disease are also used for the treatment of PG, including systemic therapies, immunomodulators, and tumor necrosis factor-α inhibitors; however, their efficacy in PG is limited. Novel treatments of PG are needed.

Finite Element Simulation of Opening Angle Response of Porcine Aortas Using Layer Specific GAG Distributions in One and Two Layered Solid Matrices.

Purpose: Recent studies have identified an effect of glycosaminoglycans (GAG) on residual stresses in the aorta, underscoring the need to better understand their biomechanical roles.

Methods: Aortic ring models for each of the ascending, arch and descending thoracic regions of the porcine thoracic aorta were created in FEBioStudio, using a framework that incorporates the Donnan osmotic swelling in a porous solid matrix. The distribution of fixed charge densities (FCD) through the thickness of the tissue was prescribed as calculated from experimentally quantified sulfated GAG mural distributions.

Effectiveness of pharmacological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

Objective: To summarize the literature on pharmacotherapy for managing paediatric obesity.

Methods: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence.

Metastatic breast cancer cells are metabolically reprogrammed to maintain redox homeostasis during metastasis.

Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little is known regarding how cancer cells modify their acquired metabolic programs in response to different metastatic microenvironments. We have previously shown that liver-metastatic breast cancer cells adopt an intrinsic metabolic program characterized by increased HIF-1α activity and dependence on glycolysis. Here, we confirm by in vivo stable isotope tracing analysis (SITA) that liver-metastatic breast cancer cells retain a glycolytic profile when grown as mammary tumors or liver metastases.

Total body irradiation: A transition from a Co-60 treatment unit to an IMRT lateral-field extended-SAD technique.

Purpose: The purpose of this work was to detail our center's experience in transitioning from a Co-60 treatment technique to an intensity modulated radiation therapy (IMRT) based lateral-field extended source-to-axis distance (e-SAD) technique for total body irradiation (TBI).

Materials And Methods: An existing beam model in RayStation v.10A was validated for the use of e-SAD TBI treatments.

Single-Step 3D Bioprinting of Alginate-Collagen Type I Hydrogel Fiber Rings to Promote Angiogenic Network Formation.

In the advent of tissue engineering and regenerative medicine, the demand for innovative approaches to biofabricate complex vascular structures is increasing. We describe a single-step 3D bioprinting method leveraging Aspect Biosystems RX1 technology, which integrates the crosslinking step at a flow-focusing junction, to biofabricate immortalized adult rat brain endothelial cell (SV-ARBEC)-encapsulated alginate-collagen type I hydrogel rings. This single-step biofabrication process involves the strategic layer-by-layer assembly of hydrogel rings, encapsulating SV-ARBECs in a spatially controlled manner while optimizing access to media and nutrients.

Commentary: importance of considering sex and gender when designing cancer care programs.

Due to perceived methodological complications, scientific studies have often excluded females. As a result, male-based findings have been generalized to females, despite physiological and biological differences between sexes. Gender has been even less considered in the literature, with little exploration specifically beyond traditional man/woman representation.

Reduced exercise capacity for muscle mass in adolescents living with obesity.

Background: Adolescents living with obesity (AlwO) can have limited exercise capacity. Exercise capacity can be predicted by a 2-factor model comprising lung function and leg muscle function, but no study has looked at cycling leg muscle function and its contribution to cycling exercise capacity in AlwO.

Methods: Twenty-two nonobese adolescents and 22 AlwO (BMI > 95 percentile) were studied.

Clinical Application of Intestinal Ultrasound in Inflammatory Bowel Disease.

Purpose Of Review: Intestinal ultrasound (IUS) is a non-invasive, accurate, and well-tolerated tool that provides real-time assessment of inflammatory bowel disease (IBD) activity and is therefore an ideal monitoring tool. This review describes the evolving role of IUS in each phase of clinical management of IBD.

Recent Findings: Accumulating evidence has demonstrated that IUS is an excellent tool for the assessment of suspected IBD, with a very high negative predictive value.

p66ShcA promotes malignant breast cancer phenotypes by alleviating energetic and oxidative stress.

Significant efforts have focused on identifying targetable genetic drivers that support the growth of solid tumors and/or increase metastatic ability. During tumor development and progression to metastatic disease, physiological and pharmacological selective pressures influence parallel adaptive strategies within cancer cell sub-populations. Such adaptations allow cancer cells to withstand these stressful microenvironments.

Multimodal Prehabilitation for Patients Undergoing Endovascular Aortic Aneurysm Repair Surgery: A Feasibility Study.

Background: Elective treatment options for aortic abdominal aneurysms include open repair or the less-invasive endovascular aortic aneurysm repair (EVAR). Recovery from EVAR is generally considered easier and faster than open repair. Despite this, EVAR remains a major procedure, and average return to preoperative quality of life is at least 3 months.

Construction of an arrayed CRISPRi library as a resource for essential gene function studies in .

The construction of arrayed mutant libraries has advanced the field of bacterial genetics by allowing researchers to more efficiently study the exact function and importance of encoded genes. In this study, we constructed an arrayed clustered regularly interspaced short palindromic repeats interference (CRISPRi) library, known as rrayed CRISRi (SNAP), as a resource to study >250 essential and growth-supporting genes in . SNAP will be made available to the research community, and we anticipate that its distribution will lead to high-quality, high-throughput, and reproducible studies of essential genes.

Evolocumab in paediatric heterozygous familial hypercholesterolaemia: cognitive function during 80 weeks of open-label extension treatment.

Aims: PCSK9 inhibition intensively lowers low density lipoprotein cholesterol and is well tolerated in adults and paediatric patients with familial hypercholesterolaemia (FH). HAUSER-RCT showed that 24 weeks of treatment with evolocumab in paediatric patients did not affect cognitive function. This study determined the effects of 80 additional weeks of evolocumab treatment on cognitive function in paediatric patients with heterozygous FH.