To examine putative sources of interindividual variation in calcium absorption efficiency, we studied 41 healthy premenopausal women (mean age, 36.4 yr). About half were randomized to pretreatment with supplemental 25-hydroxyvitamin D (25OHD; 20 micrograms/day [corrected] for approximately 34 days) before testing. We measured dietary factors, humoral regulators, intestinal motility, mucosal histology, mucosal vitamin D receptor levels, and calcium absorption efficiency. In winter tests, but not in summer tests, calcium absorption fraction was significantly higher in the pretreated group (mean, 0.465 vs. 0.387). Serum 25OHD, intestinal transit, and urinary calcium to creatinine ratio were all significantly and positively correlated to calcium absorption efficiency. However, neither the level of 1,25-dihydroxyvitamin D receptors in duodenal mucosa nor circulating 1,25-dihydroxyvitamin D was related to calcium absorption efficiency. These findings, which are consistent with other published human data, suggest that 25OHD plays a more prominent role in the regulation of calcium absorption than is generally believed. In a multiple regression model, serum 25OHD, mouth to cecum transit time, and fasting urinary calcium/creatinine ratio explained 44% of the observed variation in calcium absorption efficiency.

c Bacteria use a chemical communication process called quorum sensing to monitor cell density and to alter behavior in response to fluctuations in population numbers. Previous studies with Vibrio harveyi have shown that LuxR, the master quorum-sensing regulator, activates and represses >600 genes. These include six genes that encode homologs of the Escherichia coli Bet and ProU systems for synthesis and transport, respectively, of glycine betaine, an osmoprotectant used during osmotic stress. Here we show that LuxR activates expression of the glycine betaine operon betIBA-proXWV, which enhances growth recovery under osmotic stress conditions. BetI, an autorepressor of the V. harveyi betIBA-proXWV operon, activates the expression of genes encoding regulatory small RNAs that control quorum-sensing transitions. Connecting quorum-sensing and glycine betaine pathways presumably enables V. harveyi to tune its execution of collective behaviors to its tolerance to stress.

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss.

Quality assurance (QA) in surgical pathology has focused primarily on retrospective audits of randomly selected cases. The authors describe an effective method of prospective audit for a selected class of surgical specimens--diagnostic biopsies--and document the benefits, additional staff time required and impact on turnaround time. Additionally, these results were compared with a retrospective review. During a 6-month period, all diagnostic surgical pathology biopsies (n = 2,694, 55% of all cases) were reviewed by a second pathologist before release of the final report. Errors detected were subdivided into four categories: (1) major: errors in diagnosis that could directly affect patient care; (2) diagnostic discrepancies: errors in diagnosis that should not affect patient care; (3) minor: correct diagnosis rendered, but report correction required to add supportive information; (4) clerical: typographical and grammatical errors. Thirty-two major errors were found, involving 1.2% of cases reviewed. This manner of review caused an increase in overall turnaround time from 1.62 days to 1.79 days, and an increase in turnaround time for diagnostic biopsies from 1.44 days to 1.50 days. Time spent in performing prospective peer review averaged 4 hours per day. For comparison, results were included from a retrospective review performed on 480 of the 5,556 cases accessioned in a 6-month period before the institution of prospective quality assurance. This retrospective review revealed eight major errors (1.7%). In conclusion, the prospective peer review of diagnostic biopsies yields sufficient benefits in increased accuracy of diagnostic reports to justify the slight increase in additional work by pathologists.

Curcumin, a naturally occurring plant polyphenolic compound, may have beneficial effects in nonalcoholic steatohepatitis (NASH) development. We examined whether curcumin supplementation could be used in both prevention and treatment of NASH with fibrosis. Female Wistar rats were provided ad libitum access to a “western diet” (WD) high in fat (43% kcal), sucrose (29% kcal), and cholesterol (2% w/v), as well as 15% fructose drinking water. Intraperitoneal CC14 injections (0.5 mL/kg) were also administered at weeks 1, 2, 4, and 6 to accelerate development of a NASH with fibrosis phenotype. Rats were randomized to four groups (n = 9–12/group) and fed ad libitum: (1) WD for 8‐weeks (8WD), (2) WD enriched with curcumin for 8‐weeks (8WD+C; 0.2% curcumin, BCM‐95, DolCas Biotech) to assess prevention, (3) WD for 12‐weeks (12WD), (4) WD for 8‐weeks followed by 4‐weeks WD+C (12WD+C) to assess treatment. Curcumin prevention (8WD vs. 8WD+C) attenuated (P < 0.05) histological liver inflammation, molecular markers of fibrosis (Col1a1 mRNA) and a serum marker of liver injury (AST). Curcumin treatment (12WD vs. 12WD+C) reduced (P < 0.05) hepatocellular inflammation, steatosis, NAFLD Activity Scores, and serum markers of liver injury (AST, ALP). Moreover, curcumin treatment also increased hepatic pACC/ACC, ApoB100, and SOD1 protein, and decreased hepatic FGF‐21 levels; whereas, curcumin prevention increased hepatic glutathione levels. Both curcumin prevention and treatment reduced molecular markers of hepatic fibrosis (Col1a1 mRNA) and inflammation (TNF‐α, SPP1 mRNA). Curcumin supplementation beneficially altered the NASH phenotype in female Wistar rats, particularly the reversal of hepatocellular inflammation.