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IUCrData Aug 2023In the title com-pound (systematic name: 2,3-di-hydro-1,4-dithiino[2,3-]furan-5,7-dione), CHOS, the observed geometry agrees well with those of its phthalamide, thieno...
In the title com-pound (systematic name: 2,3-di-hydro-1,4-dithiino[2,3-]furan-5,7-dione), CHOS, the observed geometry agrees well with those of its phthalamide, thieno and hy-droxy analogs, and with a calculated geometry obtained by density functional theory (DFT) calculations. Specific structural features are an S-C-C-S torsion angle of -70.39 (17)° and S-C bonds to -hybridized C atoms approximately 0.1 Å shorter than those to -hybridized C atoms. Unlike the extended structures of the analogs, there are no directed inter-molecular inter-actions and the head-to-tail rows of mol-ecules that are a prominent structural motif of the packing can be rationalized in terms of optimized dipole-dipole inter-actions.
PubMed: 37693786
DOI: 10.1107/S2414314623006478 -
Hepatology (Baltimore, Md.) Aug 2023ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).
APPROACH AND RESULTS
Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.
CONCLUSIONS
Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.
Topics: Humans; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid; Acetates; Alkaline Phosphatase; Pruritus; Cholagogues and Choleretics
PubMed: 37386786
DOI: 10.1097/HEP.0000000000000395 -
Nutrients Aug 2023The POUNDS Lost trial is a 2-year clinical trial testing the effects of dietary interventions on weight loss. This study included 811 adults with overweight or obesity... (Review)
Review
The POUNDS Lost trial is a 2-year clinical trial testing the effects of dietary interventions on weight loss. This study included 811 adults with overweight or obesity who were randomized to one of four diets that contained either 15% or 25% protein and 20% or 40% fat in a 2 × 2 factorial design. By 2 years, participants on average lost from 2.9 to 3.6 kg in body weight in the four intervention arms, while no significant difference was observed across the intervention arms. In POUNDS Lost, we performed a series of ancillary studies to detect intrinsic factors particular to genomic, epigenomic, and metabolomic markers that may modulate changes in weight and other cardiometabolic traits in response to the weight-loss dietary interventions. Genomic variants identified from genome-wide association studies (GWASs) on obesity, type 2 diabetes, glucose and lipid metabolisms, gut microbiome, and dietary intakes have been found to interact with dietary macronutrients (fat, protein, and carbohydrates) in relation to weight loss and changes of body composition and cardiometabolic traits. In addition, we recently investigated epigenomic modifications, particularly blood DNA methylation and circulating microRNAs (miRNAs). We reported DNA methylation levels at , , , and were related to weight loss or changes of glucose, lipids, and blood pressure; we also reported thrifty miRNA expression as a significant epigenomic marker related to changes in insulin sensitivity and adiposity. Our studies have also highlighted the importance of temporal changes in novel metabolomic signatures for gut microbiota, bile acids, and amino acids as predictors for achievement of successful weight loss outcomes. Moreover, our studies indicate that biochemical, behavioral, and psychosocial factors such as physical activity, sleep disturbance, and appetite may also modulate metabolic changes during dietary interventions. This review summarized our major findings in the POUNDS Lost trial, which provided preliminary evidence supporting the development of precision diet interventions for obesity management.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Diet; Obesity; Cardiovascular Diseases; Randomized Controlled Trials as Topic
PubMed: 37630855
DOI: 10.3390/nu15163665 -
Journal of Insect Science (Online) Nov 2023British Columbia beekeepers, like many beekeepers around the world, are currently facing declines in honey bee health and high overwinter colony losses. To better...
British Columbia beekeepers, like many beekeepers around the world, are currently facing declines in honey bee health and high overwinter colony losses. To better understand the economics and the cycle of yearly colony loss and replacement of this critical agricultural industry, we collected and analyzed survey data on beekeeping costs and returns. Forty British Columbia beekeepers provided details about revenue sources, variable costs, capital costs, and investments. Ten surveyed beekeepers managed between 1 and 9 colonies, 10 managed between 10 and 39 colonies, 9 managed between 40 and 100 colonies, 5 managed between 101 and 299 colonies, 3 managed between 300 and 699 colonies, and 3 managed 700 colonies or more. The data was used to calculate beekeeping profit and to parameterize a model that explores the economic impact of colony loss rates and replacement strategies. Survey results show that when the data is aggregated, revenues exceed costs for beekeeping operations in British Columbia with a per colony profit of $56.92 or $0.87 per pound of honey produced. Surveyed operations with fewer than 100 colonies have negative profits, while operations with 100-299 colonies have positive profits. Surveyed operations in the Cariboo, North Coast, and Okanagan regions have the highest profits while surveyed operations in the Peace region have the lowest profits. Profit modeling shows that replacing losses with packages generates lower profit than replacing losses with split colonies. Our modeling shows that operations that diversify their revenue to include bee sales and commercial pollination accrue higher profits and can withstand higher winter loss rates.
Topics: Bees; Animals; Beekeeping; British Columbia; Agriculture; Honey; Pollination
PubMed: 38055942
DOI: 10.1093/jisesa/iead070