Determinants of low bone turnover in type 2 diabetes-the role of PTH

Determinants of low bone turnover in type 2 diabetes (T2DM) are poorly understood. To investigate the relationship between markers of bone turnover, glycaemic control, disease duration and calciotropic hormones in T2DM we assessed baseline biochemical data from the DiabOS Study, a prospective multicenter observational cohort study. In a cross-sectional study-design data from 110 postmenopausal women and men aged 50-75 years diagnosed with T2DM for at least 3 years and 92 non-diabetic controls were evaluated. Biochemical markers of bone formation (N-terminal propeptide of type I procollagen [PINP]), bone-specific alkaline phosphatase [BAP]) and resorption (C-terminal cross-linking telopeptide of type I collagen [CTX]), measures of calcium homeostasis (intact parathormone [iPTH], 25-Hydroxyvitamin D, calcium, magnesium) and glycaemic control were assessed. After adjustment for age, gender and body mass index (BMI), patients with T2DM had lower serum levels of PINP (p < 0.001), CTX (p < 0.001), iPTH (p = 0.03) and magnesium (p < 0.001) compared to controls. Serum calcium, creatinine, 25-Hydroxyvitamin D and sclerostin did not differ between both groups. In multivariate linear regression analyses only serum iPTH remained an independent determinant of bone turnover markers in T2DM (PINP: p = 0.02; CTX: p < 0.001 and BAP: p < 0.01), whereas glycated haemoglobin (HbA1c), disease duration, age and BMI were not associated with bone turnover. In conclusion low bone turnover in T2DM is associated with low iPTH. The underlying mechanism remains to be elucidated

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally

Formation of Pb(III) Intermediates in the Electrochemically Controlled Pb(II)/PbO 2

The formation of lead dioxide PbO(2), an important corrosion product in drinking water distribution systems with lead-bearing plumbing materials, has been hypothesized to involve Pb(III) intermediates, but their nature and formation mechanisms remain unexplored. This study employed the electrochemical (EC) method of rotating ring disk electrode (RRDE) and quantum chemical (QC) simulations to examine the generation of intermediates produced during the oxidation of Pb(II) to PbO(2). RRDE data demonstrate that PbO(2) deposition and reduction involves at least two intermediates. One of them is a soluble Pb(III) species that undergoes further transformations to yield immobilized PbO(2) nanoparticles. The formation of this intermediate in EC system is mediated by hydroxyl radicals (OH(•)), as was evidenced by the suppression of intermediates formation in the presence of the OH(•) scavenger para-chlorobenzoic acid. QC simulations confirmed that the oxidation of Pb(II) by OH(•) proceeds via Pb(III) species. These results show that Pb(III) intermediates play an important role in the reactions determining transitions between Pb(II) and Pb(IV) species and could impact lead release in drinking water

Capsule endoscopy in the investigation of patients with portal hypertension and anemia

Introduction: Data on small bowel abnormalities in patients with portal hypertension (PHT) are limited. Bleeding from the gastrointestinal tract and anemia are common complications in these patients. Capsule endoscopy (CE) was used to evaluate small bowel (SB) pathology in patients with PHT and anemia, and possible associations with various parameters were examined. Methods: Thirty-five patients with PHT referred for CE investigation of the SB for anemia were prospectively enrolled in the study, as well as 70 age- and sex-matched control patients with anemia, normal liver function and no evidence of PHT who underwent CE. Results: Findings compatible with portal hypertensive enteropathy (PHE) were detected in 65.7% of the patients and in 15.7% of the controls (χ2=26.641, P=0.000). Abnormalities in PHT patients included varices in 25.7%, diffuse changes of mucosa with inflammatory-like appearance in 42.9%, and angiodysplasias and/or spider angiomas in 22.9% of cases. The presence of PHE was significantly associated only with the presence of severe portal hypertensive gastropathy, while the presence of SB varices alone was significantly associated with the presence of severe portal hypertensive gastropathy, larger esophageal varices and the presence of colonic varices. Conclusions: Varices, diffuse changes of mucosa with infiammatory-like appearance, and angiodysplasias and/or spider angiomas are detected more often in patients with PHT than in controls, and probably constitute the endoscopic characteristics of PHE. CE of the SB added a significant number of likely important findings to those detected by conventional endoscopic techniques for the clinical management of patients with PHT and anemia. © 2008 Pulsus Group Inc. All rights reserved

The addition of clomiphene citrate to ovarian stimulation protocols for poor responders

Poor ovarian response (POR) is one of the most challenging problems in assisted reproduction. Several strategies have been used to improve pregnancy rates. The use of Clomiphene Citrate (CC) has been shown to improve ovarian stimulation outcomes and decrease gonadotropin requirements in women of advanced reproductive age. However, the combination of CC and gonadotropins to improve pregnancy rates after in IVF in poor responders is still unexplored due to the small number of trials with few participants. This is a prospective cohort trial involving 12 patients diagnosed with poor ovarian response who underwent ovarian stimulation during the period between June 2015 and September of 2017. All patients were treated with the maximum dose of gonadotropins (hMG, 300 IU/day, hMG group) according to a short gonadotropin/GnRH antagonist protocol. In a subsequent cycle those patients underwent the same stimulation protocol with the addition of 100 mg of CC from day 3 to day 7 (CC-hMG group). Supplementation with 100 mg of CC resulted in a statistically significant increase in estradiol levels, number of follicles and number of oocytes retrieved, as well as an increase in the number of total embryos available for transfer. Furthermore, a significant reduction was observed in cancellation rates in the CC-hMG group. Two clinical pregnancies, which resulted in two live births and 3 biochemical pregnancies were achieved in the CC/hMG group. Furthermore, by employing open-source, biological data we identified a common gene (Estrogen Receptor 1, ESR1) between genetic targets of clomiphene treatment and POR which could explain the benefits of clomiphene in this group of patients. In conclusion, the addition of CC 100 mg to the stimulation regimen in women diagnosed with POR and previous failed IVF cycles could improve stimulation results, but this study could not demonstrate any benefit in terms of clinical pregnancies and live births. The effectiveness of this treatment requires further investigation. © 2020 Elsevier B.V