Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent.

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery.

Current global status of male reproductive health.

Background: The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts.

Trans-vaccenic acid reprograms CD8 T cells and anti-tumour immunity.

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8 T cell function and anti-tumour immunity in vivo.

Seq-ing the mechanisms of migraine.

The trigeminal ganglia (TG) play a crucial role in migraine pathophysiology. In this issue of Neuron, Yang et al. developed a single-cell atlas profiling the transcriptome and epigenome of mouse and human TG, thus providing a roadmap for therapeutic targeting.

Designing Policy Solutions to Build a Healthier Rural America.

Disparities exist in the health, livelihood, and opportunities for the 46-60 million people living in America's rural communities. Rural communities across the United States need a new energy and focus concentrated around health and health care that allows for the designing capturing, and spreading of existing and new innovations. This paper aims to provide a framework for policy solutions to build a healthier rural America describing both the current state of rural health policy and the policies and practices in states that could be used as a national model for positive change.

Pain, Motivation, Migraine, and the Microbiome: New Frontiers for Opioid Systems and Disease.

For decades the broad role of opioids in addiction, neuropsychiatric disorders, and pain states has been somewhat well established. However, in recent years, with the rise of technological advances, not only is the existing dogma being challenged, but we are identifying new disease areas in which opioids play a critical role. This review highlights four new areas of exploration in the opioid field.

Model Informed Dosing Regimen and Phase I Results of the Anti-PD-1 Antibody Budigalimab (ABBV-181).

Budigalimab is a humanized, recombinant, Fc mutated IgG1 monoclonal antibody targeting programmed cell death 1 (PD-1) receptor, currently in phase I clinical trials. The safety, efficacy, pharmacokinetics (PKs), pharmacodynamics (PDs), and budigalimab dose selection from monotherapy dose escalation and multihistology expansion cohorts were evaluated in patients with previously treated advanced solid tumors who received budigalimab at 1, 3, or 10 mg/kg intravenously every 2 weeks (Q2W) in dose escalation, including Japanese patients that received 3 and 10 mg/kg Q2W. PK modeling and PK/PD assessments informed the dosing regimen in expansion phase using data from body-weight-based dosing in the escalation phase, based on which patients in the multihistology expansion cohort received flat doses of 250 mg Q2W or 500 mg every four weeks (Q4W).

The Role of Community Health Needs Assessments in Medicalizing Poverty.

The Patient Protection and Affordable Care Act (ACA), passed in 2010, is considered by many to be the most significant healthcare overhaul since the 1960s, but part of its promise - improvement of population health through requirements for non-profit hospitals to provide "community benefit" - has not been met. This paper examines the history of community benefit legislation, how community benefit dollars are allocated, and innovative practices by a few hospitals and communities that are addressing primarily non-medical factors that influence health such as social disadvantage, attitudes, beliefs, risk exposure, and social inequalities.

Connecting older grandmothers raising grandchildren with community resources improves family resiliency, social support, and caregiver self-efficacy.

Custodial grandparenting can be especially challenging for older grandmothers facing age specific issues. Kinship navigator programs are social service delivery programs intended to inform grandparents and other relatives raising children about available resources and services, provide information specific to their individual needs, and help families navigate service systems. Our study utilizes self-report data from one kinship navigator federal demonstration project, which used a randomized control trial, to examine demographic characteristics for grandmothers under and over 55 years of age, whether grandmother caregivers (≥55 years) improve family resilience, social support, and caregiver self-efficacy, and which interventions improved outcomes for grandmothers (≥55 years).

Novel single nucleotide polymorphism in CYP2C9 is associated with changes in warfarin clearance and CYP2C9 expression levels in African Americans.

Warfarin is a widely used anticoagulant whose active S-enantiomer is primarily metabolized by the CYP2C9 enzyme. The CYP2C9*2 and CYP2C9*3 alleles are associated with lower warfarin dose requirement and decreased enzyme activity. In contrast, we previously identified a novel single-nucleotide polymorphism (SNP) (rs7089580A > T) in CYP2C9 that is associated with higher warfarin dose requirement in African Americans (AAs).

Effects of saturation and esterification of fat sources on site and extent of digestion in steers: ruminal fermentation and digestion of organic matter, fiber, and nitrogen.

Five steers (average 526 kg) fitted with ruminal, duodenal, and ileal cannulas were used in a 5 x 6 Youden square design with 14-d periods. Diets contained chopped alfalfa hay, corn silage, and concentrate (25:35:40, DM basis). Treatments were 1) control (no added fat), 2) tallow (T), 3) partially hydrogenated tallow (PHT), 4) hydrogenated tallow (HT), 5) blend (1:1) of HT and hydrogenated free fatty acids (HTHFA), and 6) hydrogenated free fatty acids (HFA).