Insights from the first global population estimate of Weddell seals in Antarctica

The Weddell seal is one of the best-studied marine mammals in the world, owing to a multidecadal demographic effort in the southernmost part of its range. Despite their occurrence around the Antarctic coastline, we know little about larger scale patterns in distribution, population size, or structure. We combined high-resolution satellite imagery from 2011, crowd-sourcing, and habitat modeling to report the first global population estimate for the species and environmental factors that influence its distribution. We estimated ~202,000 (95% confidence interval: 85,345 to 523,140) sub-adult and adult female seals, with proximate ocean depth and fast-ice variables as factors explaining spatial prevalence. Distances to penguin colonies were associated with seal presence, but only emperor penguin population size had a strong negative relationship. The small, estimated population size relative to previous estimates and the seals' nexus with trophic competitors indicates that a community ecology approach is required in efforts to monitor the Southern Ocean ecosystem

Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. Materials and methods: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. Results: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. Conclusions: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Synthesis of the Bipyridine-Type Ligand 3-(2-Pyridyl)-5,6-diphenyl-1,2,4-triazine and Structural Elucidation of Its Cu(I) and Ag(I) Complexes

The synthesis of a substituted diimine with a bipydirine-type backbone, (3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine, L) and its coordination towards Cu(I) and Ag(I) is studied in the presence of diphosphine ligand bis(diphenylphosphino)methane, dppm. The metal complexes are characterized by IR, 1H, and 13C NMR and single crystal X ray diffraction studies. They are dinuclear, as they are held by diphosphine bridges between the tetrahedral metal centers, forming eight-membered ring with the participation of the bridging diphosphinomethane ligands. Within each ring, the planar orientations of M2P2 and of all four P atoms are realized. Solid state excitation spectra are dominated by metal-to-ligand charge transfer bands (MLCT), while geometry relaxation permits only low-intensity emission for the copper compound