Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy.

The number of approved or investigational late phase viral vector gene therapies (GTx) has been rapidly growing. The adeno-associated virus vector (AAV) technology continues to be the most used GTx platform of choice. The presence of pre-existing anti-AAV immunity has been firmly established and is broadly viewed as a potential deterrent for successful AAV transduction with a possibility of negative impact on clinical efficacy and a connection to adverse events.

Condition-Dependent and Dynamic Impacts of Indoor Masking Policies for Coronavirus Disease 2019 Mitigation: A Nationwide, Interrupted Time-Series Analysis.

Background: The effectiveness and sustainability of masking policies as a pandemic control measure remain uncertain. Our aim was to evaluate different masking policy types on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and to identify factors and conditions impacting effectiveness.

Methods: Nationwide, retrospective cohort study of US counties from 4/4/2020-28/6/2021.

Therapeutic Development in Polyarticular Course Juvenile Idiopathic Arthritis: Extrapolation, Dose Selection, and Clinical Trial Design.

Objective: Stakeholders met to address persistent challenges facing the development of therapeutics for polyarticular juvenile idiopathic arthritis (pJIA), which result in fewer approved therapies for children with pJIA than adults with rheumatoid arthritis (RA) and long lag times from adult RA approval to pediatric labeling. Ensuring that new medications are authorized in a timely manner to meet the needs of JIA patients worldwide is critically important to multiple stakeholders.

Methods: The Food and Drug Administration in collaboration with the University of Maryland Center for Regulatory Science and Innovation held a public workshop entitled "Accelerating Drug Development for pJIA" on October 2, 2019, to address challenges surrounding access to new medications for children and adolescents with pJIA.

Cardiac rehabilitation utilization, barriers, and outcomes among patients with heart failure.

Exercise-based cardiac rehabilitation (CR) is effective for improving both primary (i.e., mortality and hospitalizations) and secondary (i.

Change in Homeless and Health Services Use Following Migration Among Veterans with Experience of Homelessness.

Background: Homelessness is associated with poor health outcomes, including lack of access to care. Homelessness experienced in rural areas is understudied but likely associated with difficulty accessing needed services. Prior studies have assessed the extent to which Veterans experiencing homelessness in rural areas "migrate" to urban areas, but have not focused on changes in services utilization following migration.

The role of daylight exposure on body mass in male mice.

Physiology and behavior are synchronized to the external environment by endogenous circadian rhythms that are set to precisely 24 h by exposure to bright light early in the day. Exposure to artificial light outside of the typical solar day, such as during the night, may impair aspects of physiology and behavior in human and non-human animals. Both the intensity and the wavelength of light are important in mediating these effects.

Association of hemoglobin A1c stability with mortality and diabetes complications in older adults with diabetes.

Introduction: Hemoglobin A1c (A1c) treatment goals in older adults should be individualized to balance risks and benefits. It is unclear if A1c stability over time within unique target ranges also affects adverse outcomes.

Research Design And Methods: We conducted a retrospective observational cohort study from 2004 to 2016 of veterans with diabetes and at least four A1c tests during a 3-year baseline.

Caregiver survey in glioblastoma focused on cognitive dysfunction: development and results from a multicenter study.

To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD.

Communicating risk and the landscape of cancer prevention - an exploratory study that examines perceptions of cancer-related genetic counseling and testing among African Americans and Latinos in the Midwest.

African American (AA) and Latino populations are impacted disproportionately by cancer incidence and mortality compared to the general US population. Contributing to these rates are multiple inheritable cancers that impact both men and women. Some of these diseases may be detected through genetic counseling and germline DNA testing; however, AA and Latinos are unaware and have limited knowledge and thus significantly underutilize these services and technologies.

Glucarpidase for Treating Adults with Delayed Methotrexate Elimination Due to Impaired Renal Function: An Economic Simulation Analysis.

Background: Glucarpidase is indicated for treating delayed methotrexate (MTX) elimination due to impaired renal function. Although glucarpidase is capable of rapidly eliminating MTX independent of renal clearance, its cost can be perceived as a barrier to use. However, no published economic analyses have evaluated glucarpidase relative to comparable treatments.

The disruptive relationship among circadian rhythms, pain, and opioids.

Pain behavior and the systems that mediate opioid analgesia and opioid reward processing display circadian rhythms. Moreover, the pain system and opioid processing systems, including the mesolimbic reward circuitry, reciprocally interact with the circadian system. Recent work has demonstrated the disruptive relationship among these three systems.

Extent of safety database in pediatric drug development: types of assessment, analytical precision, and pathway for extrapolation through on-target effects.

Pediatric patients should have access to medicines that have been appropriately evaluated for safety and efficacy through revised labelling. Given this goal, the adequacy of the pediatric clinical development plan and resulting safety database are critical factors to inform a favorable benefit-risk assessment for the intended use of the medicinal product. While extrapolation from adults can be used to support efficacy of drugs in children, there may be a reluctance to use the same approach in safety assessments, wiping out potential gains in trial efficiency through a reduction of sample size.

Circadian Rhythms Disrupted by Light at Night and Mistimed Food Intake Alter Hormonal Rhythms and Metabolism.

Availability of artificial light and light-emitting devices have altered human temporal life, allowing 24-hour healthcare, commerce and production, and expanding social life around the clock. However, physiology and behavior that evolved in the context of 24 h solar days are frequently perturbed by exposure to artificial light at night. This is particularly salient in the context of circadian rhythms, the result of endogenous biological clocks with a rhythm of ~24 h.

A generalized covariate-adjusted top-scoring pair algorithm with applications to diabetic kidney disease stage classification in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Background: The growing amount of high dimensional biomolecular data has spawned new statistical and computational models for risk prediction and disease classification. Yet, many of these methods do not yield biologically interpretable models, despite offering high classification accuracy. An exception, the top-scoring pair (TSP) algorithm derives parameter-free, biologically interpretable single pair decision rules that are accurate and robust in disease classification.

Host Determinants of Fungal Species Composition and Symptom Manifestation in the Sorghum Grain Mold Disease Complex.

Sorghum grain mold (SGM) is an important multifungal disease complex affecting sorghum () production systems worldwide. SGM-affected sorghum grain can be contaminated with potent fumonisin mycotoxins produced by , a prevalent SGM-associated taxon. Historically, efforts to improve resistance to SGM have achieved only limited success.

Structural violence and the uncertainty of viral undetectability for African, Caribbean and Black people living with HIV in Canada: an institutional ethnography.

Biomedical advances in healthcare and antiretroviral treatment or therapy (ART) have transformed HIV/AIDS from a death sentence to a manageable chronic disease. Studies demonstrate that people living with HIV who adhere to antiretroviral therapy can achieve viral suppression or undetectability, which is fundamental for optimizing health outcomes, decreasing HIV-related mortality and morbidity, and preventing HIV transmission. African, Caribbean, and Black (ACB) communities in Canada remain structurally disadvantaged and bear a disproportionate burden of HIV despite biomedical advancements in HIV treatment and prevention.

The deacylase sirtuin 5 reduces malonylation in nonmitochondrial metabolic pathways in diabetic kidney disease.

Early diabetic kidney disease (DKD) is marked by dramatic metabolic reprogramming due to nutrient excess, mitochondrial dysfunction, and increased renal energy requirements from hyperfiltration. We hypothesized that changes in metabolism in DKD may be regulated by Sirtuin 5 (SIRT5), a deacylase that removes posttranslational modifications derived from acyl-coenzyme A and has been demonstrated to regulate numerous metabolic pathways. We found decreased malonylation in the kidney cortex (∼80% proximal tubules) of type 2 diabetic BKS db/db mice, associated with increased SIRT5 expression.

Pyostomatitis Vegetans With Orofacial and Vulvar Granulomatosis in a Pediatric Patient.

Pyostomatitis vegetans (PSV) is a rare disorder strongly associated with inflammatory bowel disease (IBD), most commonly ulcerative colitis, but has infrequently been found in patients with Crohn disease (CD). We present the case of a 7-year-old girl with PSV and extraintestinal findings suggestive of CD-chelitis granulomatosa, perianal and vulvar edema with biopsies revealing noncaseating granulomas, and anal skin tags-and an elevated calprotectin noted during a cutaneous flare. She did not have clinical or endoscopically identified underlying gastrointestinal involvement for 4 years after symptom onset.

Integrating Real-World Evidence in Economic Evaluation of Oral Anticoagulants for Stroke Prevention in Non-valvular Atrial Fibrillation in a Developing Country.

Objective: This study aimed to estimate the cost effectiveness of non-vitamin K oral anticoagulants (NOACs) compared with warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) in Thailand where suboptimal anticoagulation control is common.

Materials And Methods: A hypothetical cohort of 65-year-old patients with NVAF and their disease progression was simulated in the Markov model. The following anticoagulant agents were used: warfarin, dabigatran, rivaroxaban, and apixaban.

Long-Term Health Care Costs for Service Members Injured in Iraq and Afghanistan.

Introduction: Over the last two decades, the conflicts in Iraq and Afghanistan have cost the United States significantly in terms of lives lost, disabling injuries, and budgetary expenditures. This manuscript calculates the differences in costs between veterans with combat injuries vs veterans without combat injuries. This work could be used to project future costs in subsequent studies.

Hypothermia or Machine Perfusion in Kidney Donors.

Background: Therapeutic hypothermia in brain-dead organ donors has been shown to reduce delayed graft function in kidney recipients after transplantation. Data are needed on the effect of hypothermia as compared with machine perfusion on outcomes after kidney transplantation.

Methods: At six organ-procurement facilities in the United States, we randomly assigned brain-dead kidney donors to undergo therapeutic hypothermia (hypothermia group), ex situ kidney hypothermic machine perfusion (machine-perfusion group), or both (combination-therapy group).