NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

Guidelines for the standardization of pre-analytical variables for salivary biomarker studies in Alzheimer's disease research: An updated review and consensus of the Salivary Biomarkers for Dementia Research Working Group.

There is a pressing need for accessible biomarkers with high diagnostic accuracy for Alzheimer's disease (AD) diagnosis to facilitate widespread screening, particularly in underserved groups. Saliva is an emerging specimen for measuring AD biomarkers, with distinct contexts of use that could complement blood and cerebrospinal fluid and detect various analytes. An interdisciplinary, international group of AD and related dementias (ADRD) researchers convened and performed a narrative review of published studies on salivary AD biomarkers.

Comparison of Physical Frailty Assessments in Heart Failure With Preserved Ejection Fraction.

Background: Frailty is a known determinant of poor clinical outcomes in heart failure with preserved ejection fraction (HFpEF). However, prevalence estimates and effect sizes vary in part due to multiple tools available to measure frailty.

Objectives: This study aimed to compare the prevalence and prognostic value of six commonly used frailty assessments in adults with HFpEF.

Acute Decompensated Valvular Disease in the Intensive Care Unit.

Acute decompensated valvular disease encompasses a group of complex and challenging conditions, which are often the primary reason for admission to the cardiac intensive care unit and can also complicate the management of other primary cardiac disorders. Critically ill patients with valvular disease also present unique diagnostic and management challenges. Historically, medical and percutaneous interventional therapies have been limited and surgery was the only definitive treatment; however, surgical risk can at times be prohibitive.

Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy.

Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5-30 mg every 2 weeks or 2-10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines.

Pulmonary Embolism: Webcast June 13 2024.

This 61-minute webcast features a conversation about "Pulmonary Embolism"-the focus of Issue 20.3. Hosted by the issue's editors, the discussion engages the authors on emerging themes and lessons learned while researching and writing the articles.

Transition symptom management careers: Historical patterns of mental health symptoms and service use among young adults experiencing a psychiatric crisis.

Young adults access mental health services at lower rates than both older and younger age groups despite high levels of need. Mental health service use is known to be influenced by prior experiences with treatment, with episodes of symptoms and treatment producing patterns of service use over time, or what we call a "symptom management career". This qualitative study examined the symptom management careers of 55 young adults (ages 18-25) who were admitted to an inpatient, short term, crisis stabilization unit.

Do Risk Factors for HCC Impact the Association of CT/MRI LIRADS Major Features With HCC? An Individual Participant Data Meta-Analysis.

Guidelines suggest the Liver Imaging Reporting and Data System (LI-RADS) may not be applicable for some populations at risk for hepatocellular carcinoma (HCC). However, data assessing the association of HCC risk factors with LI-RADS major features are lacking. To evaluate whether the association between HCC risk factors and each CT/MRI LI-RADS major feature differs among individuals at-risk for HCC.

Updates on the Pathogenesis of Canine and Feline Atopic Dermatitis: Part 1, History, Breed Prevalence, Genetics, Allergens, and the Environment.

Canine atopic dermatitis (cAD) and feline atopic skin syndrome are inflammatory and pruritic skin diseases with both environmental and genetic factors. Genetic factors may include barrier defects and a predisposition to mount T helper 2 lymphocyte immune response when allergens are encountered. These diseases have repeatable patterns of skin and ear inflammation and commonly lead to Staphylococcal and Malassezia skin and ear infections.

Updates on the Pathogenesis of Canine Atopic Dermatitis and Feline Atopic Skin Syndrome: Part 2, the Skin Barrier, the Microbiome, and Immune System Dysfunction.

Alterations in the lipid layer and intercellular corneocyte connections can lead to increased allergen penetration through the skin surface. A normal cutaneous microbiome keeps the opportunistic pathogen Staphylococcus pseudintermedius levels low, but allergic inflammation leads to decreased diversity and increase in S pseudintermedius. Keratinocytes sound the initial allergen alarm via cytokine signaling and promote T-helper 2 (Th-2) inflammation.

The Impact of Sleep and Exercise on Brain Atrophy in Mild Cognitive Impairment.

Chronic sleep deprivation and lack of physical exercise may have detrimental effects on overall health, particularly in terms of brain health, with significant implications for cognitive function and well-being. This review explores the impact of chronic sleep deprivation and physical exercise on brain atrophy in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Drawing insights from 40 selected studies, the review synthesizes evidence on these lifestyle factors' correlations with neurodegenerative changes.

Exposure therapy consortium: Outcomes of the proof-of-principle study.

Background: This paper reports on the outcomes of a proof-of-principle study for the Exposure Therapy Consortium, a global network of researchers and clinicians who work to improve the effectiveness and uptake of exposure therapy. The study aimed to test the feasibility of the consortium's big-team science approach and test the hypothesis that adding post-exposure processing focused on enhancing threat reappraisal would enhance the efficacy of a one-session large-group interoceptive exposure therapy protocol for reducing anxiety sensitivity.

Methods: The study involved a multi-site cluster-randomized controlled trial comparing exposure with post-processing (ENHANCED), exposure without post-processing (STANDARD), and a stress management intervention (CONTROL) in students with elevated anxiety sensitivity.

An Exploratory Analysis of Child Characteristics Predicting Clinical Outcomes in Parent-Led Cognitive Behavioral Teletherapy for Anxiety in Autistic Children.

Parent-led cognitive behavioral therapy (CBT) is an efficient, promising form of therapy that may be well suited for autistic youth with anxiety disorders. A recent clinical trial found that parent-led CBT - in which parents led their child through a guided CBT workbook with varying degrees of therapist support - was efficacious for reducing anxiety and associated functional impairment. While such findings demonstrate promise for future intervention development and dissemination efforts with this population, more work is needed to elucidate clinical factors that impact response to treatment as well as drop-out.

Ecological and anthropogenic effects on the genomic diversity of lemurs in Madagascar.

Ecological variation and anthropogenic landscape modification have had key roles in the diversification and extinction of mammals in Madagascar. Lemurs represent a radiation with more than 100 species, constituting roughly one-fifth of the primate order. Almost all species of lemurs are threatened with extinction, but little is known about their genetic diversity and demographic history.

BCMA-directed CAR T-cell Therapy in patients with multiple myeloma and CNS involvement.

We investigated BCMA-directed CART in patients with relapsed or refractory multiple myeloma (RRMM) and CNS involvement. Ten patients who received either ide-cel (n=6) or cilta-cel (n=4) were included in this analysis. Patients had brain/cranial nerve and/or spinal cord involvement/leptomeningeal disease evident on either MRI (100%) and/or CSF (40%).

Safety and Phosphate-Binding Capacity of Oxylanthanum Carbonate in Healthy Volunteers.

Despite the widespread use of currently available serum phosphate management options, elevated serum phosphate is common in patients with end-stage kidney disease on dialysis. Characteristics of currently available phosphate binders that lead to poor patient experiences such as large drug volume size of required daily medication (e.g.

Preventative treatment of tuberous sclerosis complex with sirolimus: Phase I safety and efficacy results.

Objective: Tuberous sclerosis complex (TSC) results from overactivity of the mechanistic target of rapamycin (mTOR). Sirolimus and everolimus are mTOR inhibitors that treat most facets of TSC but are understudied in infants. We sought to understand the safety and potential efficacy of preventative sirolimus in infants with TSC.

Enhanced Maturity and Functionality of Vascular Human Liver Organoids through 3D Bioprinting and Pillar Plate Culture.

Liver tissues, composed of hepatocytes, cholangiocytes, stellate cells, Kupffer cells, and sinusoidal endothelial cells, are differentiated from endodermal and mesodermal germ layers. By mimicking the developmental process of the liver, various differentiation protocols have been published to generate human liver organoids (HLOs) in vitro using induced pluripotent stem cells (iPSCs). However, HLOs derived solely from the endodermal germ layer often encounter technical hurdles such as insufficient maturity and functionality, limiting their utility for disease modeling and hepatotoxicity assays.

Building Research Capacity (BRC): Purposes, Components, and Activities to Date.

The Building Research Capacity (BRC) initiative was founded in 2015 as a collaboration between the Association of Departments of Family Medicine (ADFM) and the North American Primary Care Research Group (NAPCRG). It aims to enhance family medicine research engagement by helping develop researchers, research educators, and research leaders. Through consultations, a fellowship, tailored presentations at national conferences, and ongoing assessment, BRC addresses the dynamic needs of various stakeholders in family medicine research.

Mentoring for the Diverse Range of Family Physicians' Engagement in Research.

Primary care researchers are increasingly at the forefront of developing innovations and new research methods to address complex issues in health care, including multi-morbidity, social determinants of health, health equity, managing population health in clinical practice, patient satisfaction, and provider burnout. Research demonstrates that "primary care is the only health care component where an increased supply is associated with better population health and more equitable outcomes." As a primary care specialty, family medicine has evolved beyond its initial focus on clinical practice and education to realizing the imperative for the discipline to robustly engage in research and embrace the responsibility to generate the evidence that drives changes in primary care practice and policy.

EXPOSURE TO THE POLYCHLORINATED BIPHENYL MIXTURE AROCLOR 1254 ELICITS NEUROLOGICAL AND CARDIAC DEVELOPMENTAL EFFECTS IN EARLY LIFE STAGE ZEBRAFISH (Danio rerio).

The goal of this study was to compare the bioaccumulation of the PCB mixture Aroclor 1254 in zebrafish to cardiac and neurologic outcomes. The establishment of effect concentrations (ECs) for cardiac and neurotoxic effects of PCBs in early life stage fish is challenging due to a lack of measured PCB concentrations in test media (e.g.

Quantitative pupillometry as a potential biomarker in early concussion assessment.

Background: There are limited objective methods when it comes to identifying and diagnosing concussion. Pupil assessment is performed routinely as a standard-of-care following traumatic brain injury (TBI). Unlike the highly subjective and limited reliability of pupil assessment using penlights and flashlights, Quantitative pupillometry (QP) is an established, valid, and reliable method of pupillary assessment.

Assessing intrinsic capacity for person-centred HIV care: a cross-sectional study in ageing populations in Malaysia and Hong Kong.

Introduction: WHO's Integrated Care for Older People (ICOPE) proposes we measure the functional construct of intrinsic capacity (IC) to monitor and identify individuals with age-associated vulnerabilities. Assessments of IC may be useful to address the evolving, non-HV care needs of ageing people with HIV (PWH). However, to date, its utility within the context of HIV has not been assessed.

Molecular Testing for the World Health Organization Classification of Central Nervous System Tumors: A Review.

Importance: Molecular techniques, including next-generation sequencing, genomic copy number profiling, fusion transcript detection, and genomic DNA methylation arrays, are now indispensable tools for the workup of central nervous system (CNS) tumors. Yet there remains a great deal of heterogeneity in using such biomarker testing across institutions and hospital systems. This is in large part because there is a persistent reluctance among third-party payers to cover molecular testing.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.