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Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long‐term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet‐induced obesity. Exposure to BAM15 in vitro enhanced mitochondrial respiratory kinetics, improved insulin action, and stimulated nutrient uptake by sustained activation of AMPK. C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15‐treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid‐rich tissues. We provide the first phenotypic characterization and demonstration of pre‐clinical efficacy for BAM15 as a pharmacological approach for the treatment of obesity and related diseases. Synopsis This study presents a novel therapy for treatment of obesity‐related diseases. Oral delivery of the mitochondrial protonophore BAM15 markedly reduced weight gain and fat accrual while improving glycemic control. BAM15 displays extended mitochondrial activity compared to previous generation protonophores. BAM15 protects against diet induced obesity. BAM15 modulates body composition and glycemic control independently of its weight‐reducing effects. AMPK is required to sustain the metabolic benefit of BAM15, which occurs primarily in adipose tissue. Graphical Abstract This study presents a novel therapy for treatment of obesity‐related diseases. Oral delivery of the mitochondrial protonophore BAM15 markedly reduced weight gain and fat accrual while improving glycemic control.

Dysregulation of gut microbiota and intestinal barrier function has emerged as potential mechanisms underlying digestive diseases, yet targeted therapies are lacking The purpose of this investigation was to assess the efficacy of UCC118, a characterized probiotic strain, on exercise‐induced GI permeability in healthy humans. In a randomized, double‐blind, placebo‐controlled crossover study, seven healthy adults received 4 weeks of daily UCC118 or placebo supplementation. GI hyperpermeability was induced by strenuous treadmill running performed before and after each supplementation period. While running, participants ingested 5 g of lactulose, rhamnose, and sucrose. Urine was collected before, immediately after, and every hour for 5 h after exercise to assess GI permeability. Metagenomic sequencing was performed on fecal homogenates collected prior to exercise to identify changes in microbial diversity and taxon abundances. Inflammatory biomarkers were assessed from blood and fecal homogenates collected prior to and immediately following the cessation of exercise. Exercise significantly induced intestinal permeability of lactulose, rhamnose, and sucrose (P < 0.001). UCC118 significantly reduced sucrose (Δ = −0.38 ± 0.13 vs. 1.69 ± 0.79; P < 0.05) recovery, with no substantial change in lactulose (Δ = −0.07 ± 0.23 vs. 0.35 ± 0.15; P = 0.16) or rhamnose (Δ = −0.06 ± 0.22 vs. 0.48 ± 0.28; P = 0.22). Taxonomic sequencing revealed 99 differentially regulated bacteria spanning 6 taxonomic ranks (P < 0.05) after UCC118 supplementation. No differences in plasma IL‐6 or fecal zonulin were observed after UCC118 supplementation. The results described herein provide proof of principle that 4 weeks of UCC118 supplementation attenuated exercise‐induced intestinal hyperpermeability. Further research is warranted to investigate the as‐yet‐to‐be defined molecular processes of intestinal hyperpermeability and the effects of probiotic supplementation. Dysregulation of gut microbiota and intestinal barrier function have emerged as potential mechanisms underlying digestive diseases, yet targeted therapies are lacking. In a randomized, double‐blind, placebo‐controlled crossover study, 7 healthy adults 30 received 4 weeks of daily UCC118 or placebo supplementation. UCC118 significantly reduced sucrose recovery. Taxonomic sequencing revealed 99 differentially regulated gut microbes by UCC118. The results herein provide proof of principle that UCC118 supplementation can reduce intestinal hyperpermeability.

Facial penetrating gunshot wounds (GSWs) are seen in an assault, suicide, and accidental injury. They often carry high mortality given the important anatomical structures located within the neck. The foundations of maxillofacial GSWs are rooted in data from military combat, specifically the last world war. This type of injury is complex for reconstructive surgery due to significant soft tissue and bone loss. Management of maxillofacial GSWs is often challenging and has trended from serial debridement, immediate reconstruction, local tissue flaps, and distant free flap transfers depending on bullet trajectory and wound intricacy. We present a case of a 51-year-old male with a 22-caliber GSW to the left side of his face. Hemodynamics were stable on arrival and history included alcohol use. A left mandibular wound measured approximately 8 cm in diameter with exposed bone. A small 0.5-1 cm wound was also present inferiorly. A maxillofacial CT scan was utilized, showing a left mandibular body fracture. The patient underwent exploration and debridement on the same day of injury. Open reduction with internal fixation of the left mandible fracture and Synthes 2.5 mm locking plate was done. Additionally, a left pectoralis major myocutaneous muscle flap was performed two days later. Regional pectoralis flap reconstruction of facial firearm injury is scarcely acknowledged in the literature. Due to the location of the wound, the functionality of the jaw can be maintained in addition to ample blood supply by performing mandibular fixation and pectoralis major myocutaneous flap.

JEWELLS Primary School is fortunate to have an opera singer as part of its staf

JEWELLS Primary School is fortunate to have an opera singer as part of its staf

Bright Fields is a comprehensive and deeply intimate exploration of the life and work of Mississippi-born artist Marie Hull (1890–1980). Her paintings reflect a nine-decade journey of search, thought, and growth. She produced some of the most memorable and iconic works ever created by a southern artist. This elegant and exquisitely detailed book contains over two hundred newly photographed reproductions of the artist's finest works, many never before seen by the public. Hull was born in a small town near Jackson at a time when women were not allowed to vote and were denied many career opportunities. This did not deter Hull from a constant \"search for quality\" both in her life and in her art. She studied with some of the most important artists of her day, including William Merritt Chase, in Philadelphia, New York, and Europe. She won major national competitions and awards and was exhibited in some of the world's most prestigious art exhibitions and shows in the United States, Europe, and East Asia. During the Depression, Hull created a series of paintings depicting African Americans and local sharecroppers that is considered one of the most significant contributions to regionalist art in the country's history. These important, deeply moving works place her among the forefront of the great American portraitists. Three decades later, in her seventies, Hull would reveal her remarkable ability to evolve again, this time into one of the most significant abstract painters of the South. In her powerful, brilliantly colorful late works, she combines her mastery of landscape painting with a unique, persuasive synthesis of ideas from such artists as Mark Rothko, Willem de Kooning, and Hans Hofmann. Today, Hull's works are exhibited in museums and prestigious private collections throughout the country. Bright Fields expands our knowledge of the painter's remarkable life and work, illustrating why Hull's unique vision and tremendous creativity had, and continues to have, such a profound impact on art in the South and beyond.