Activity

Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacterial metabolite, stimulates mucus release from goblet cells via activation of G-protein-coupled receptor (GPCR) 5-HT4R. Germ-free mice colonized with engineered Bacteroides thetaiotaomicron optimized to produce tryptamine (Trp D+) exhibit decreased weight loss and increased mucus release following dextran sodium sulfate treatment when compared with mice colonized with control B. thetaiotaomicron (Trp D-). Additional beneficial effects in preventing barrier disruption and lower disease activity index were seen only in female mice, highlighting sex-specific effects of the bacterial metabolite. This study demonstrates potential for the precise modulation of mucus release by microbially produced 5-HT4 GPCR agonist as a therapeutic strategy to treat inflammatory conditions of the GI tract.PINK1 loss-of-function mutations cause early onset Parkinson disease. PINK1-Parkin mediated mitophagy has been well studied, but the relevance of the endogenous process in the brain is debated. Here, the absence of PINK1 in human dopaminergic neurons inhibits ionophore-induced mitophagy and reduces mitochondrial membrane potential. Compensatory, mitochondrial renewal maintains mitochondrial morphology and protects the respiratory chain. This is paralleled by metabolic changes, including inhibition of the TCA cycle enzyme mAconitase, accumulation of NAD+, and metabolite depletion. Loss of PINK1 disrupts dopamine metabolism by critically affecting its synthesis and uptake. The mechanism involves steering of key amino acids toward energy production rather than neurotransmitter metabolism and involves cofactors related to the vitamin B6 salvage pathway identified using unbiased multi-omics approaches. We propose that reduction of mitochondrial membrane potential that cannot be controlled by PINK1 signaling initiates metabolic compensation that has neurometabolic consequences relevant to Parkinson disease.

While age is associated with an increase in cognitive flexibility and executive functioning as a result of normal development during childhood, less is known about the effect of racial variation in children’s age-related cognitive development. The Marginalization-related Diminished Returns (MDRs) phenomenon suggests that, under racism, social stratification, segregation, and discrimination, individual-level economic and non-economic resources and assets show weaker effects on children’s development for marginalized, racialized, and minoritized families.

We conducted this study to compare racial groups of children for age-related changes in their card sorting abilities.

This cross-sectional study included 10,414 9-10-year-old American children. Data came from the Adolescent Brain Cognitive Development (ABCD) study. The independent variable was age, a continuous variable measured in months. The dependent variable was dimensional change card sort (DCCS) score, which reflected cognitive flexibility, and wasncome with high-income children. Conceptualizing race as a social factor that alters normal childhood development is a finding that is in line with MDRs. Marginalization due to social stratification and racism interfere with the normal age-related cognitive development of American children.Unicompartmental and total knee arthroplasty (UKA and TKA) have demonstrated excellent mid- and long-term outcomes and have been compared in clinical series for decades; however, to our knowledge, no study has sufficiently matched UKA and TKA cohorts on preoperative osteoarthritis severity. The purpose of this study was to evaluate patient-reported outcomes of radiographically and demographically matched UKA and TKA cohorts.

One hundred and thirty-five UKAs and 135 TKAs were matched by patient age, sex, body mass index, and American Society of Anesthesiologists Physical Status (ASA-PS) classification as well as preoperative osteoarthritis severity in medial and lateral tibiofemoral and patellofemoral compartments (Kellgren-Lawrence grading system). MDV3100 Patient-reported outcome measures for pain, function, activity level, and satisfaction were evaluated at minimum 1-year follow-up via components of the modern Knee Society Score, the University of California Los Angeles (UCLA) activity-level score, and a Likert satisfaction scale.

The patients in the UKA group reported significantly less pain, a higher activity level, and greater satisfaction while performing several functional activities and could walk for a longer amount of time before stopping due to knee discomfort compared with those in the TKA group (p ≤ 0.038). In addition, a greater proportion of patients in the UKA than in the TKA group were “satisfied or very satisfied” with their knee replacement surgery at minimum 1-year follow-up (90% versus 81%; p = 0.043).

With minimum 1-year follow-up, patients who underwent UKA reported significantly higher function, less pain, and a greater level of patient satisfaction than a radiographically and demographically matched TKA cohort.

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.[This corrects the article DOI 10.2106/JBJS.OA.18.00054.].There is a paucity of research regarding the relationship between anemia and postoperative morbidity and mortality among geriatric patients presenting with hip fracture. The objective of this study was to determine the effect of anemia at presentation on 30-day morbidity and mortality among geriatric patients with hip fracture.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for all hip fracture patients ≥60 years old from 2011 to 2016. Included were all emergency unilateral, nonpathological hip fractures (femoral neck, intertrochanteric, or subtrochanteric) treated with arthroplasty, intramedullary nailing, or open reduction and internal fixation. Anemia was classified as a hematocrit (HCT) level of <0.41 and <0.36 for male and female patients, respectively. Age, body mass index (BMI), race, comorbidities, smoking status, American Society of Anesthesiologists (ASA) class, baseline functional status, time to surgery, operative time, anesthesia type, need for transfusion, fixation method, length of stay (LOS), and discharge destination were collected.