Background The association between obesity and fracture risk may be skeletal site- and sex-specific but results among studies are inconsistent. Whilst several studies reported higher bone mineral density (BMD) in patients with obesity, altered bone quality could be a major determinant of bone fragility in this population. Objectives This systematic review and meta-analysis aimed to compare, in men, premenopausal women and postmenopausal women with obesity vs. individuals without obesity: 1) the incidence of fractures overall and by site; 2) BMD; and 3) bone quality parameters (circulating bone turnover markers and bone microarchitecture and strength by advanced imaging techniques). Data sources PubMed (MEDLINE), EMBASE, Cochrane Library and Web of Science were searched from inception of databases until the 13th of January 2021. Data synthesis Each outcome was stratified by sex and menopausal status in women. The meta-analysis was performed using a random-effect model with inverse-variance method. The risks of hip and wrist fracture were reduced by 25% (n = 8: RR = 0.75, 95% CI: 0.62, 0.91, P = 0.003, I2 = 95%) and 15% (n = 2 studies: RR = 0.85, 95% CI: 0.81, 0.88), respectively, while ankle fracture risk was increased by 60% (n = 2 studies: RR = 1.60, 95% CI: 1.52, 1.68) in postmenopausal women with obesity compared with those without obesity. In men with obesity, hip fracture risk was decreased by 41% (n = 5 studies: RR = 0.59, 95% CI: 0.44, 0.79). Obesity was associated with increased BMD, better bone microarchitecture and strength, and generally lower or unchanged circulating bone resorption, formation and osteocyte markers. However, heterogeneity among studies was high for most outcomes, and overall quality of evidence was very low to low for all outcomes. Conclusions This meta-analysis highlights areas for future research including the need for site-specific fracture studies, especially in men and premenopausal women, and studies comparing bone microarchitecture between individuals with and without obesity. Systematic review registration number CRD42020159189

Dairy product intake is inversely associated with the risk of type 2 diabetes (T2D) in numerous cohort studies; yet, the beneficial effects of increased dairy product intake on T2D risk factors such as fasting plasma glucose, fasting insulin, insulin resistance with the homeostasis model assessment, and glycated hemoglobin (HbA1c) remain inconclusive in clinical trials. The objective of this study was to systematically review clinical trials observing the effects of elevated compared with minimal intake of dairy products on T2D risk factors in subjects without diabetes. Five databases [Medline, EMBASE, Central, CINAHL, AMED (Allied and Complementary Medicine)] were searched to identify randomized controlled trials that used elevated quantities of dairy products from ruminant sources in comparison with a lower intake in control groups. The review outcomes were fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HbA1c. Risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development, and Evaluation were addressed. From the 10,627 citations screened, 44 studies (3016 participants) were included, 38 of which were used in the meta-analyses. Fasting glucose was positively associated with elevated dairy intake [34 studies, n = 2678; mean difference (MD): 0.

Osteocalcin (OCN) is a bone-derived hormone involved in the regulation of glucose metabolism. In serum, OCN exists in carboxylated and uncarboxylated forms (ucOCN), and studies in rodents suggest that ucOCN is the bioactive form of this hormone. Whether this is also the case in humans is unclear, because a reliable assay to measure ucOCN is not available. Here, we established and validated a new immunoassay (ELISA) measuring human ucOCN and used it to determine the level of bioactive OCN in two cohorts of overweight or obese subjects, with or without type 2 diabetes (T2D). The ELISA could specifically detect ucOCN concentrations ranging from 0.037 to 1.8 ng/mL. In a first cohort of overweight or obese postmenopausal women without diabetes ( n = 132), ucOCN correlated negatively with fasting glucose (r = −0.18, P = 0.042) and insulin resistance assessed by the homeostatic model assessment of insulin resistance (r = −0.18, P = 0.038) and positively with insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp (r = 0.18, P = 0.043) or insulin sensitivity index derived from an oral glucose tolerance test (r = 0.26, P = 0.003). In a second cohort of subjects with severe obesity ( n = 16), ucOCN was found to be lower in subjects with T2D compared with those without T2D (2.76 ± 0.38 versus 4.52 ± 0.06 ng/mL, P = 0.009) and to negatively correlate with fasting glucose (r = −0.50, P = 0.046) and glycated hemoglobin (r = −0.57, P = 0.021). Moreover, the subjects with ucOCN levels below 3 ng/mL had a reduced insulin secretion rate during a hyperglycemic clamp ( P = 0.03). In conclusion, ucOCN measured with this novel and specific assay is inversely associated with insulin resistance and β-cell dysfunction in humans.

The fibrin clot penetration and in vivo bactericidal activity of RP 59500, a new semisynthetic streptogramin, for two Staphylococcus aureus strains (one methicillin resistant and the other methicillin susceptible), two Staphylococcus epidermidis strains (one methicillin resistant and the other methicillin susceptible), and one Enterococcusfaecalis strain were evaluated. The clots, inserted subcutaneously, were infected with a mean of 108 CFU of the pathogen per g. For each strain, groups of four rabbits received a single intravenous injection of 50 mg of RP 59500 per kg of body weight over 30 min. The mean peak level of RP 59500 in serum in the infected rabbits was 61.9 + 6.3 ,ug/ml. The drug was detectable in serum at a level of 0.8 ,ug/ml up to 4 h after administration. The mean peak fibrin clot drug level at 1 h was 3.3 ± 0.1 ,ug/g. At 6 h, the level in clots was 1.2 + 0.1 ,ug/g. The mean half-life in serum in infected rabbits was 0.34 ± 0.01 h, while in clots the drug exhibited a longer half-life of 3.8 ± 0.4 h. In vivo, this new streptogramin sterilized the clots infected with the two S. aureus strains studied in less than 1 h and induced a marked reduction in colony counts of the two S. epidermidis strains studied for up to 24 h. The activity of the streptogramin against E. faecalis was limited.These results suggest that RP 59500 should be further evaluated for the treatment of infection with methicillin-resistant staphylococci.RP 59500 belongs to the streptogramin class of antibiotics. It is a mixture of two soluble semisynthetic derivatives of the purified natural pristinamycin produced by fermentation of the Streptomycespristinaespiralis compounds PI (RP 57669) and PII (RP 54476), which are present in a proportion of 30:70 (wt/wt), respectively (1, 7). The antibiotics of the streptogramin family are inhibitors of protein biosynthesis through their irreversible blocking action on the ribosome. RP 59500 is active against a range of gram-positive pathogenic bacteria. Included in this group are methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, erythromycin-resistant Streptococcus pneumoniae, other streptococci, and clostridia. It also has activity against Neisseria spp., Moraxella catarrhalis, Haemophilus influenzae, Legionella spp., Mycoplasma spp., and chlamydiae (7). As it is the first formulation of an injectable streptogramin, it may, if proven effective, have great clinical importance for the treatment of serious infections caused by gram-positive organisms.The present investigation was undertaken to study the efficacy and penetration of RP 59500 in fibrin clots. Fibrin is one of the main constituents of the inflammatory process, and bacteria located within the core of fibrin clots are protected from host defenses and the action of the antibiotics, as they often interact with and adhere to major constituents of clots. Moreover, penetration of antimicrobial agents within the clots is quite variable. New antibiotics that can penetrate fibrin and sterilize gram-...

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The association between obesity and fracture risk is complex and may vary by definition of obesity, skeletal site, and sex. We aimed to evaluate the relationships between obesity, defined using body mass index (BMI) or waist circumference (WC), and fracture incidence at any site and by skeletal site (i.e., major osteoporotic fractures [MOFs], distal lower limb fractures [tibia, ankle, feet], and distal upper limb fractures [forearm/elbow, wrist]). The secondary aim was to assess the aforementioned relationships by sex. We used CARTaGENE, a large population‐based cohort of individuals aged 40–70 years from Quebec, Canada, who were assessed in 2009–2010. Incident fractures were identified via linkage with healthcare administrative databases over a 7‐year period. Cox proportional hazard models adjusted for several potential confounders were used to estimate the relationships, with exposures treated as continuous variables. Results are reported as adjusted hazard ratios (aHRs) and 95% confidence intervals. We identified 19 357 individuals (mean ± standard deviation: age 54 ± 8 years, BMI 27 ± 5 kg/m2, WC 94 ± 14 cm; 51.6% women). During follow‐up, 497 women and 323 men sustained a fracture. There was a linear relationship between fracture incidence and WC, while cubic splines best fitted the relationship for BMI. Greater WC was associated with an increased risk of fracture at the distal lower limbs in the whole cohort and in the subgroup of women: aHR for each 10 cm increased in WC of 1.12 (1.03, 1.21) and 1.12 (1.01, 1.24), respectively. In men, WC was not significantly associated with any fracture outcome. Higher BMI was also significantly associated with distal lower limb fracture risk in the whole cohort (p = 0.018). No significant relationships were found between either WC or BMI and the risk of any fracture, MOFs, and distal upper limb fractures. In middle‐aged individuals, obesity, and mainly abdominal obesity, was associated with distal lower limb fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The differential tissue distributions of aztreonam and ceftazidime within fibrin clots infected with Pseudomonas aeruginosa, Enterobacter cloacae, and Serratia marcescens, their efficacies, and the in vivo bacterial morphological changes induced by these drugs were evaluated. Rabbits were given intravenously a single dose of 100 mg of either agents/kg of body weight. In the cores of the clots, the peak levels of both drugs were much lower than those observed in the peripheries and in serum. Aztreonam's half-lives within the peripheries and in the cores of the fibrin clots were up to six times higher than that observed in serum, while ceftazidime's half-lives in clots were twice that observed in serum. This resulted in a much greater penetration ratio for aztreonam than for ceftazidime. Both drugs controlled the growth of P. aeruginosa in vivo, but E. cloacae and S. marcescens responded better to ceftazidime. Morphological changes were more abundant in the peripheries than in the cores of the clots. In the control group, P. aeruginosa's morphology in the cores was different than that in the peripheries of the clots. Against P. aeruginosa, aztreonam did induce morphological changes in the cores while ceftazidime did not. Electron microscopic studies revealed that morphological changes associated with aztreonam seemed different than those of ceftazidime. Along with elongation of bacteria, more bow tie and herniated bacteria were observed with aztreonam. Though both agents selectively affect PBP 3, as manifested by elongated bacteria, they induce in the peripheries of the clots thickening, breaks, and detachment in bacterial cell walls, alterations which are generally associated with antibiotics affecting PBP 1a and 1b.