An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models.

Huntington's disease (HD) is a fatal, dominantly inherited neurodegenerative disorder caused by CAG trinucleotide expansion in exon 1 of the huntingtin (HTT) gene. Since the reduction of pathogenic mutant HTT messenger RNA is therapeutic, we developed a mutant allele-sensitive CAG RNA-targeting CRISPR-Cas13d system (Cas13d-CAG) that eliminates toxic CAG RNA in fibroblasts derived from patients with HD and induced pluripotent stem cell-derived neurons. We show that intrastriatal delivery of Cas13d-CAG via an adeno-associated viral vector selectively reduces mutant HTT mRNA and protein levels in the striatum of heterozygous zQ175 mice, a model of HD.

Differential expression of a brain aging biomarker across discrete chronic pain disorders.

Chronic pain has widespread, detrimental effects on the human nervous system and its prevalence and burden increase with age. Machine learning techniques have been applied on brain images to produce statistical models of brain aging. Specifically, the Gaussian process regression is particularly effective at predicting chronological age from neuroimaging data which permits the calculation of a brain age gap estimate (brain-AGE).

Involvement of the ACE2/Ang-(1-7)/MasR Axis in Pulmonary Fibrosis: Implications for COVID-19.

Pulmonary fibrosis is a chronic, fibrotic lung disease affecting 3 million people worldwide. The ACE2/Ang-(1-7)/MasR axis is of interest in pulmonary fibrosis due to evidence of its anti-fibrotic action. Current scientific evidence supports that inhibition of ACE2 causes enhanced fibrosis.

Maternal Dietary Diversity and Growth of Children Under 24 Months of Age in Rural Dodoma, Tanzania.

Objective: To identify predictors of maternal dietary diversity in rural Dodoma, Tanzania and assess its association with child growth outcomes.

Methods: A cross-sectional survey of 361 mothers with children under 24 months of age was conducted in 5 villages in rural Dodoma, Tanzania. Maternal diets were assessed using food frequency questionnaires, and dietary diversity was categorized using Minimum Dietary Diversity for Women (MDD-W) guidelines.

Rich Food Biodiversity Amid Low Consumption of Food Items in Kilosa District, Tanzania.

Background: Indigenous foods, which contribute largely to the majority of the households' food basket in rural Tanzanian communities, have not been fully characterized or documented.

Objectives: The study aimed to document foods available and consumed in Kilosa District, Tanzania, in an attempt to promote, revive use, and build evidence for sustainable utilization of the rich local biodiversity.

Methods: Data were collected from 307 households in 3 agroecological zones in Kilosa District during the beginning of the rainy season (February-May) and immediately after harvest (September-October).

Socio-economic and spatial correlates of subclinical iodine deficiency among pregnant women age 15-49 years in Tanzania.

Background: Iodine deficiency is a widespread global health problem that affects about 2 billion people each year. Pregnant women are particularly vulnerable to iodine deficiency due to increased iodine requirement leading to death, miscarriage, and stillbirth. Iodine deficiency also has significant negative effects on newborns including impaired cognitive development, impaired learning capabilities, and stunting.

Prognostic Value of Noninvasive Cardiovascular Testing in Patients With Stable Chest Pain: Insights From the PROMISE Trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain).

Background: Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing.

Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal.

Changes in Medical Therapy and Lifestyle After Anatomical or Functional Testing for Coronary Artery Disease.

Background: Diagnostic testing in the care of patients newly presenting with symptoms suggestive of coronary artery disease may influence risk factor management, independent of test type or test results. However, little is known about changes in medications and lifestyle after anatomical or functional testing.

Methods And Results: We examined what factors influenced preventive medical therapy and lifestyle practices at 60 days among 10 003 symptomatic patients (53% women; mean age 61 years) randomly assigned to anatomical testing with coronary computed tomographic angiography or functional testing (NCT01174550).

Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans.

Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR.

Metabolic reprogramming through fatty acid transport protein 1 (FATP1) regulates macrophage inflammatory potential and adipose inflammation.

Objective: A novel approach to regulate obesity-associated adipose inflammation may be through metabolic reprogramming of macrophages (MΦs). Broadly speaking, MΦs dependent on glucose are pro-inflammatory, classically activated MΦs (CAM), which contribute to adipose inflammation and insulin resistance. In contrast, MΦs that primarily metabolize fatty acids are alternatively activated MΦs (AAM) and maintain tissue insulin sensitivity.

Outcomes of anatomical versus functional testing for coronary artery disease.

Background: Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care.

Methods: We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication.

Weight Loss Reversed Obesity-Induced HGF/c-Met Pathway and Basal-Like Breast Cancer Progression.

Epidemiologic studies demonstrate that obesity is associated with an aggressive subtype of breast cancer called basal-like breast cancer (BBC). Using the C3(1)-TAg murine model of BBC, we previously demonstrated that mice displayed an early onset of tumors when fed obesogenic diets in the adult window of susceptibility. Obesity was also shown to elevate mammary gland expression and activation of hepatocyte growth factor (HGF)/c-Met compared to lean controls, a pro-tumorigenic pathway associated with BBC in patients.