In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg⁻¹∙d⁻¹ had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg⁻¹∙d⁻¹. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.     

Territorywide Study of Early Coronavirus Disease Outbreak,Hong Kong,China

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10⁻³ substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.     

Surveillance of COVID-19–Associated Multisystem Inflammatory Syndrome in Children,South Korea

A concerning development during the coronavirus disease pandemic has been multisystem inflammatory syndrome in children. Reports of this condition in East Asia have been limited. In South Korea, 3 cases were reported to the national surveillance system for multisystem inflammatory syndrome in children. All case-patients were hospitalized and survived with no major disease sequelae.     

Long-term mortality of living kidney donors: a systematic review and meta-analysis

International Urology and Nephrology - To date, several studies have reported inconsistent findings regarding the mortality risk faced by living kidney donors and controls. Our study assessed the...     

Bone Radiomics Score Derived From DXA Hip Images Enhances Hip Fracture Prediction in Older Women

Dual-energy X-ray absorptiometry (DXA)-based bone mineral density testing is standard to diagnose osteoporosis to detect individuals at high risk of fracture. A radiomics approach to extract quantifiable texture features from DXA hip images may improve hip fracture prediction without additional costs. Here, we investigated whether bone radiomics scores from DXA hip images could improve hip fracture prediction in a community-based cohort of older women. The derivation set (143 women who sustained hip fracture [mean age 73 years, time to fracture median 2.1 years] versus 290 age-matched women [mean age 73 years] who did not sustain hip fracture during follow-up [median 5.5 years]) were split into the train set (75%) and the test set (25% hold-out set). Among various models using 14 selected features out of 300 texture features mined from DXA hip images in the train set, random forest model was selected as the best model to build a bone radiomics score (range 0 to 100) based on the performance in the test set. In a community-based cohort (2029 women, mean age 71 years) as the clinical validation set, the bone radiomics score was calculated using a model fitted in the train set. A total of 34 participants (1.7%) sustained hip fracture during median follow-up of 5.4 years (mean bone radiomics score 40 ± 16 versus 28 ± 12 in non-fractured, p < 0.001). A one-point bone radiomics score increment was associated with a 4% elevated risk of incident hip fracture (adjusted hazard ratio [aHR] = 1.04, p = 0.001) after adjustment for age, body mass index (BMI), previous history of fracture, and femoral neck T-score, with improved model fit when added to covariates (likelihood ratio chi-square 10.74, p = 0.001). The association between bone radiomics score with incident hip fracture remained robust (aHR = 1.06, p < 0.001) after adjustment for FRAX hip fracture probability. Bone radiomics scores estimated from texture features of DXA hip images have the potential to improve hip fracture prediction. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Pulmonary contusions in patients with rib fractures: The need to better classify a common injury

BackgroundPulmonary contusions are common injuries. Computed tomography reveals vast contused lung volume spectrum, yet pulmonary contusions are defined dichotomously (unilateral vs bilateral). We assessed whether there is stepwise increased risk of pulmonary complications among patients without, with unilateral, and with bilateral pulmonary contusion.MethodsWe identified adults admitted with rib fractures using the largest US inpatient database. After propensity-score-matching patients without vs with unilateral vs bilateral pulmonary contusions and adjusting for residual confounders, we compared risk for pneumonia, ventilator-associated pneumonia (VAP), respiratory failure, intubation, and mortality.ResultsAmong 148,140 encounters of adults with multiple rib fractures, 19% had concomitant pulmonary contusions. Matched patients with pulmonary contusions had increased risk of pneumonia 19% [95%CI:16–33%], respiratory failure 40% [95%CI: 31–50%], and intubation 46% [95%CI: 33–61%]. Delineation showed bilateral contusions, not unilateral contusions, attributed to increased risk of complications.ConclusionsThere is likely a correlation between contused lung volume and risk of pulmonary complications; dichotomously classifying pulmonary contusions is insufficient. Better understanding this correlation requires establishing the clinically significant contusion volume and a correspondingly refined classification system.     

Central Regulation of Branched-Chain Amino Acids Is Mediated by AgRP Neurons

Circulating branched-chain amino acids (BCAAs) are elevated in obesity and diabetes, and recent studies support a causal role for BCAAs in insulin resistance and defective glycemic control. The physiological mechanisms underlying BCAA regulation are poorly understood. Here we show that insulin signaling in the mediobasal hypothalamus (MBH) of rats is mandatory for lowering plasma BCAAs, most probably by inducing hepatic BCAA catabolism. Insulin receptor deletion only in agouti-related protein (AgRP)–expressing neurons (AgRP neurons) in the MBH impaired hepatic BCAA breakdown and suppression of plasma BCAAs during hyperinsulinemic clamps in mice. In support of this, chemogenetic stimulation of AgRP neurons in the absence of food significantly raised plasma BCAAs and impaired hepatic BCAA degradation. A prolonged fasting or ghrelin treatment recapitulated designer receptors exclusively activated by designer drugs–induced activation of AgRP neurons and increased plasma BCAAs. Acute stimulation of vagal motor neurons in the dorsal motor nucleus was sufficient to decrease plasma BCAAs. Notably, elevated plasma BCAAs were associated with impaired glucose homeostasis. These findings suggest a critical role of insulin signaling in AgRP neurons for BCAA regulation and raise the possibility that this control may be mediated primarily via vagal outflow. Furthermore, our results provide an opportunity to closely examine the potential mechanistic link between central nervous system–driven BCAA control and glucose homeostasis.     

Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.