Impact of obstructive sleep apnea on the levels of placental growth factor (PlGF) and their value for predicting short-term adverse outcomes in patients with acute coronary syndrome

Background Placental growth factor (PlGF) induces angiogenesis and promotes tissue repair, and plasma PlGF levels change markedly during acute myocardial infarction (AMI). Currently, the impact of obstructive sleep apnea (OSA) in patients with AMI is a subject of debate. Our objective was to evaluate the relationships between PlGF levels and both the severity of acute coronary syndrome (ACS) and short-term outcomes after ACS in patients with and without OSA. Methods A total of 538 consecutive patients (312 OSA patients and 226 controls) admitted for ACS were included in this study. All patients underwent polygraphy in the first 72 hours after hospital admission. The severity of disease and short-term prognoses were evaluated during the hospitalization period. Plasma PlGF levels were measured using an electrochemiluminescence immunoassay. Results Patients with OSA were significantly older and more frequently hypertensive and had higher BMIs than those without OSA. After adjusting for age, smoking status, BMI and hypertension, PlGF levels were significantly elevated in patients with OSA compared with patients without OSA (19.9 pg/mL, interquartile range: 16.6–24.5 pg/mL; 18.5 pg/mL, interquartile range: 14.7–22.7 pg/mL; p<0.001), and a higher apnea-hypopnea index (AHI) was associated with higher PlGF concentrations (p<0.003). Patients with higher levels of PlGF had also an increased odds ratio for the presence of 3 or more diseased vessels and for a Killip score>1, even after adjustment. Conclusions The results of this study show that in patients with ACS, elevated plasma levels of PlGF are associated with the presence of OSA and with adverse outcomes during short-term followup. Trial Registration ClinicalTrials.gov NCT0133508

Catalysis over zinc-incorporated berlinite (ZnAlPO4) of the methoxycarbonylation of 1,6-hexanediamine with dimethyl carbonate to form dimethylhexane-1,6-dicarbamate

<p>Abstract</p> <p>Background</p> <p>The alkoxycarbonylation of diamines with dialkyl carbonates presents promising route for the synthesis of dicarbamates, one that is potentially 'greener' owing to the lack of a reliance on phosgene. While a few homogeneous catalysts have been reported, no heterogeneous catalyst could be found in the literature for use in the synthesis of dicarbamates from diamines and dialkyl carbonates. Because heterogeneous catalysts are more manageable than homogeneous catalysts as regards separation and recycling, in our study, we hydrothermally synthesized and used pure berlinite (AlPO₄) and zinc-incorporated berlinite (ZnAlPO₄) as heterogeneous catalysts in the production of dimethylhexane-1,6-dicarbamate from 1,6-hexanediamine (HDA) and dimethyl carbonate (DMC). The catalysts were characterized by means of XRD, FT-IR and XPS. Various influencing factors, such as the HDA/DMC molar ratio, reaction temperature, reaction time, and ZnAlPO₄/HDA ratio, were investigated systematically.</p> <p>Results</p> <p>The XRD characterization identified a berlinite structure associated with both the AlPO₄and ZnAlPO₄catalysts. The FT-IR result confirmed the incorporation of zinc into the berlinite framework for ZnAlPO₄. The XPS measurement revealed that the zinc ions in the ZnAlPO₄structure possessed a higher binding energy than those in ZnO, and as a result, a greater electron-attracting ability. It was found that ZnAlPO₄catalyzed the formation of dimethylhexane-1,6-dicarbamate from the methoxycarbonylation of HDA with DMC, while no activity was detected on using AlPO₄. Under optimum reaction conditions (i.e. a DMC/HDA molar ratio of 8:1, reaction temperature of 349 K, reaction time of 8 h, and ZnAlPO₄/HDA ratio of 5 (mg/mmol)), a yield of up to 92.5% of dimethylhexane-1,6-dicarbamate (with almost 100% conversion of HDA) was obtained. Based on these results, a possible mechanism for the methoxycarbonylation over ZnAlPO₄was also proposed.</p> <p>Conclusion</p> <p>As a heterogeneous catalyst ZnAlPO₄berlinite is highly active and selective for the methoxycarbonylation of HDA with DMC. We propose that dimethylhexane-1,6-dicarbamate is formed <it>via </it>a catalytic cycle, which involves activation of the DMC by a key active intermediate species, formed from the coordination of the carbonyl oxygen with Zn(II), as well as a reaction intermediate formed from the nucleophilic attack of the amino group on the carbonyl carbon.</p

Ecological and human exposure assessment to PBDEs in Adige River

The interest for environmental issues and the concern resulting from the potential exposure to contaminants were the starting point to develop methodologies in order to evaluate the consequences that those might have over both the environment and human health. Considering the feature of POPs, including PBDEs, such as bioaccumulation, biomagnification, long-range transport and adverse effects even long time after exposure, risk assessment of POPs requires specific approaches and tools. In this particular context, the MERLIN-Expo tool was used to assess the aquatic environmental exposure of Adige River to PBDEs and the accumulation of PBDEs in humans through the consumption of possible contaminated local aquatic food. The aquatic food web models provided as output of the deterministic simulation the time trend of concentrations for twenty years of BDE-47 and total PBDEs, expressed using the physico-chemical properties of BDE-47, in aquatic organisms of the food web of Adige River. For BDE-47, the highest accumulated concentrations were detected for two benthic species: Thymallus thymallus and Squalius cephalus whereas the lowest concentrations were obtained for the pelagic specie Salmo trutta marmoratus. The trend obtained for the total PBDEs, calculated using the physico-chemical properties of BDE-47, follows the one of BDE-47. For human exposure, different BDE-47 and total PBDEs concentration trends between children, adolescent, adults and elderly were observed, probably correlated with the human intake of fish products in the daily diet and the ability to metabolize these contaminants. In detail, for the adolescents, adults and elderly a continuous accumulation of the target contaminants during the simulation's years was observed, whereas for children a plateau at the end of the simulation period was perceived

Multivariate adjusted odds ratios for ≥3 diseased vessels.

<p>Multivariate adjusted odds ratios for ≥3 diseased vessels.</p

Levels of PlGF according to AHI groups.

<p>Error bars represent 95% confidence intervals. The Kruskal-Wallis test was used for comparisons among groups.</p

Anthropometric, clinical and biochemical variables for patients with obstructive sleep apnea (OSA) and controls.

<p>Anthropometric, clinical and biochemical variables for patients with obstructive sleep apnea (OSA) and controls.</p

Baseline patient characteristics and variables related to the severity of acute coronary syndrome according to PlGF status.

<p>Baseline patient characteristics and variables related to the severity of acute coronary syndrome according to PlGF status.</p

Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial

Background: Shorter treatments are needed for drug-susceptible tuberculosis. Adjunctive statins increase bactericidal activity in preclinical tuberculosis models. We investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis. We tested the hypothesis that adjunctive rosuvastatin accelerates sputum culture conversion within the first 8 weeks of treatment of rifampicin-susceptible tuberculosis. Methods: This phase 2b, randomised, open-label, multicentre trial conducted in five hospitals or clinics in three countries with high tuberculosis burden (ie, the Philippines, Viet Nam, and Uganda) enrolled adult participants aged 18–75 years with sputum smear or Xpert MTB/RIF positive, rifampicin-susceptible tuberculosis who had received less than 7 days of previous tuberculosis treatment. Participants were randomly assigned via a web-based system to receive either 10 mg rosuvastatin once per day for 8 weeks plus standard tuberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol; rosuvastatin group) or standard tuberculosis therapy alone (control group). Randomisation was stratified by trial site, history of diabetes, and HIV co-infection. Laboratory staff and central investigators involved in data cleaning and analysis were masked to treatment allocation, but study participants and site investigators were not. Both groups continued standard treatment to week 24. Sputum samples were collected once per week for the first 8 weeks after randomisation, and then at weeks 10, 12, and 24. The primary efficacy outcome was time to culture conversion (TTCC; days) in liquid culture by week 8, assessed in randomised participants who had microbiological confirmation of tuberculosis, took at least one dose of rosuvastatin, and who did not show resistance to rifampicin (modified intention-to-treat population), for which groups were compared with the Cox proportional hazards model. The main safety outcome was grade 3–5 adverse events by week 24, assessed in the intention-to-treat population, for which groups were compared with Fisher\u27s exact test. All participants completed 24 weeks of follow-up. This trial is registered with ClinicalTrials.gov (NCT04504851). Findings: Between Sept 2, 2020, and Jan 14, 2021, 174 participants were screened and 137 were randomly assigned to the rosuvastatin group (70 participants) or control group (67 participants). In the modified intention-to-treat population of 135 participants, 102 (76%) were men and 33 (24%) were women. Median TTCC in liquid media was 42 days (95% CI 35–49) in the rosuvastatin group (68 participants) and 42 days (36–53) in the control group (67 participants; hazard ratio 1·30 [0·88–1·91], p=0·19). Grade 3–5 adverse events occurred in six (9%) of 70 in the rosuvastatin group (none were considered related to rosuvastatin) and four (6%) of 67 in the control group (p=0·75). There were no serious adverse events that were considered to be related to rosuvastatin. Interpretation: Adjunctive rosuvastatin at 10 mg once per day was safe but did not produce substantive benefits on culture conversion in the overall study population. Future trials could explore the safety and efficacy of higher doses of adjunctive rosuvastatin. Funding: National Medical Research Council, Singapore