Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia.

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges.

Perspectives of Emergency Medicine Physicians on Hidradenitis Suppurativa Care.

Introduction: Hidradenitis suppurativa (HS) is a chronic skin condition that often requires acute care during periods of flares, with many patients visiting the emergency department over 5 times before receiving a proper diagnosis. However, little is known about emergency medicine (EM) providers' experiences and knowledge of HS management.

Methods: In this study, an anonymous survey was distributed to EM providers to identify knowledge and practice gaps in HS care.

Factors Contributing to Non-Concordance Between End-of-Life Care and Advance Care Planning.

Context: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life.

Objectives: To examine factors contributing to nonconcordance between end-of-life care and advance care planning.

Methods: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention.

Anti-tau intrabodies: From anti-tau immunoglobulins to the development of functional scFv intrabodies.

Over the last decade, there has been a growing interest in intrabodies and their therapeutic potential. Intrabodies are antibody fragments that are expressed inside a cell to target intracellular antigens. In the context of intracellular protein misfolding and aggregation, such as tau pathology in Alzheimer's disease, intrabodies have become an interesting approach as there is the possibility to target early stages of aggregation.

Optimizing point-of-care testing strategies for diagnosis and treatment of hepatitis C virus infection in Australia: a model-based cost-effectiveness analysis.

Background: Timely diagnosis and treatment of hepatitis C virus (HCV) is critical to achieve elimination goals. This study evaluated the cost-effectiveness of point-of-care testing strategies for HCV compared to laboratory-based testing in standard-of-care.

Methods: Cost-effectiveness analyses were undertaken from the perspective of Australian Governments as funders by modelling point-of-care testing strategies compared to standard-of-care in needle and syringe programs, drug treatment clinics, and prisons.

Patient Perspectives on Hidradenitis Suppurativa and Infertility: A Survey Study.

Background: Hidradenitis suppurativa (HS) is an inflammatory skin condition which predominantly affects women of childbearing age in the USA. There is a lack of research on the association between HS and fertility.

Objectives: The aim of this study was to understand the perspectives of females with HS regarding the impact of their disease on reproductive health, the impact of fertility treatments on HS, and the impact of HS treatments on fertility.

pH Dependence of a GPR4 Selective Antagonist Hampers Its Therapeutic Potential.

Inflammatory bowel disease (IBD) is characterized by chronic mucosal inflammation of the gastrointestinal tract and is associated with extracellular acidification of mucosal tissue. Several extracellular pH-sensing receptors, including G protein-coupled receptor 4 (GPR4), play an important role in the regulation of inflammatory and immune responses, and GPR4 deficiency has been shown to be protective in IBD animal models. To confirm the therapeutic potential of GPR4 antagonism in IBD, we tested Compound 13, a selective GPR4 antagonist, in the interleukin 10-/- mouse model of colitis.

Guidance on COVID-19 Vaccination in Hidradenitis Suppurativa Patients: A Modified Delphi Consensus of Experts.

Introduction: Hidradenitis suppurativa (HS) patients may be at increased risk of COVID-19 infection and complications from their medications and comorbidities. There is a lack of expert consensus on recommendations for the COVID-19 vaccine for HS patients. Herein, we aim to provide expert-driven consensus recommendations regarding COVID-19 vaccinations in HS patients.

Allergen Composition, Marketing Claims, and Affordability of Pediatric Sunscreens.

Background: Childhood sun exposure is associated with development of future skin cancers. Sunscreens are an important tool to prevent harmful ultraviolet rays.

Objectives: The aims of the study are to evaluate sunscreens targeted to children and to analyze cost, marketing claims, ingredients, and allergens to help consumers select products.

Management Landscape of Pediatric Hidradenitis Suppurativa.

Introduction: Pediatric hidradenitis suppurativa (HS) is an understudied condition, and the literature describing the provider landscape for this disease is limited. We aim to characterize healthcare utilization in a cohort of pediatric HS patients at an academic institution.

Methods: Patients diagnosed with HS before age 18 were identified via retrospective chart review using ICD-9/10 codes for HS.

Variants in impair LSM complexes assembly, neurodevelopment in zebrafish and may be associated with an ultra-rare neurological disease.

Leukodystrophies, genetic neurodevelopmental and/or neurodegenerative disorders of cerebral white matter, result from impaired myelin homeostasis and metabolism. Numerous genes have been implicated in these heterogeneous disorders; however, many individuals remain without a molecular diagnosis. Using whole-exome sequencing, biallelic variants in were uncovered in two unrelated individuals, one with a leukodystrophy and the other who died .

Primary Tumors of the Pituitary Gland: Radiologic-Pathologic Correlation.

Primary tumors of the pituitary gland are the second most common histologic category of primary central nervous system tumors across all age groups and are the most common in adolescents to young adults, despite originating from a diminutive endocrine gland that is often described as "about the size of a pea." The vast majority of these represent primary tumors of the adenohypophysis, specifically pituitary adenomas, which can be either functional or silent with regard to hormone hypersecretion. According to the fourth edition of the World Health Organization classification of endocrine tumors, published in 2017, cellular lineage and immunohistochemical stains for pituitary hormones and/or transcription factors help with making the correct pathologic diagnosis.

Readability, Quality, and Timeliness of Patient Online Health Resources for Contact Dermatitis and Patch Testing.

Background: Contact dermatitis (CD) causes significant impact on patient quality of life. It is the most common occupational skin disease, accounting for more than US $1 billion of medical costs. Patch testing (PT) is the criterion standard for diagnosis of allergic CD.

Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma.

Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features.

Incorporating Baseline Breast Density When Screening Women at Average Risk for Breast Cancer : A Cost-Effectiveness Analysis.

Background: Breast density classification is largely determined by mammography, making the timing of the first screening mammogram clinically important.

Objective: To evaluate the cost-effectiveness of breast cancer screening strategies that are stratified by breast density.

Design: Microsimulation model to generate the natural history of breast cancer for women with and those without dense breasts and assessment of the cost-effectiveness of strategies tailored to breast density and nontailored strategies.

BPRDP056, a novel small molecule drug conjugate specifically targeting phosphatidylserine for cancer therapy.

Zinc(II)-dipicolylamine (Zn-DPA) has been shown to specifically identify and bind to phosphatidylserine (PS), which exists in bulk in the tumor microenvironment. BPRDP056, a Zn-DPA-SN38 conjugate was designed to provide PS-targeted drug delivery of a cytotoxic SN38 to the tumor microenvironment, thereby allowing a lower dosage of SN38 that induces apoptosis in cancer cells. Micro-Western assay showed that BPRDP056 exhibited apoptotic signal levels similar to those of CPT-11 in the treated tumors growing in mice.

Intramedullary Masses of the Spinal Cord: Radiologic-Pathologic Correlation.

Spinal cord tumors are a challenge for patients and neurosurgeons because of the high risk of neurologic deficits from the disease process and surgical interventions. Spinal cord tumors are uncommon, and approximately 2%-3% of primary intra-axial tumors of the central nervous system occur in the spinal cord. Primary intra-axial tumors are usually derived from neuroepithelial tissue, especially glial cells.