Anterior-enriched filopodia create appearance of asymmetric membrane microdomains in polarizing C. elegans zygotes

The association of molecules within membrane microdomains is critical for the intracellular organization of cells. During polarization of the C. elegans zygote, both polarity proteins and actomyosin regulators associate within dynamic membrane-associated foci. Recently, a novel class of asymmetric PIP2 membrane-associated structures was described, suggesting that PIP2 domains could constitute signaling hubs to promote cell polarization and actin nucleation. Here we probe the nature of these domains using a variety of membrane- and actin cortex-associated probes. These data demonstrate that these domains are filopodia, which are stimulated transiently during polarity establishment and accumulate in the zygote anterior. The resulting membrane protrusions create local membrane topology that quantitatively accounts for observed local increases in fluorescence signal of membrane-associated molecules, suggesting molecules are not selectively enriched in these domains relative to bulk membrane and that the PIP2 pool as revealed by PHPLCδ1 simply reflects plasma membrane localization. Given the ubiquity of 3D membrane structures in cells, including filopodia, microvilli, and membrane folds, similar caveats are likely to apply to analysis of membrane-associated molecules in a broad range of systems

Impact of melatonin on driving performance

BACKGROUND Because millions of people are self-prescribing melatonin for various indications, the safety aspects of this substance have become very important. The aim of our study was to determine whether or not melatonin impairs driving-related performance. METHODS Twenty healthy men and women aged 21-57 years volunteered for this randomized, placebo-controlled, double-blind, crossover study. The crossover arms were separated by an interval of at least 4 weeks. On each testing day, melatonin 5 mg or placebo was taken at 1630 h; 60 minutes later a test series was performed, consisting of a medical examination, body sway measurement, and a standardized driving computer test battery to assess attention, reaction time, power of concentration, and sensomotor coordination. Subjective sleepiness was measured on three occasions during the test session using the Stanford Sleepiness Scale questionnaire. RESULTS Just one of the 16 main variables of the driving computer test battery, the selective attention tested by signal-detection, was significantly affected by melatonin (p < .05). However, even those values were still within the normal range. Subjective sleepiness was increased by melatonin, although the result was significant only after the prolonged concentration task (p < .05). Neither the clinical examination nor the body sway test showed signs of any drug influence. CONCLUSIONS The overall result of the computer test battery showed no objective adverse impact of melatonin on driving performance. However, due to the increased subjective sleepiness after administration of this hormone, caution should be exercised when driving under the influence of melatonin

Conservation and restoration of Nardus grasslands in the Swiss northern Alps

Aim: Species‐rich Nardus grasslands are high nature‐value habitats. In Switzerland, many of these grasslands are degraded even though they have been under protection since the 1980s. Degradation shows two divergent trends: Nardus grasslands are either dominated by Nardus stricta or by eutrophic plants, both trends leading to the disappearance of typical Nardus grassland species. With this study, we aim to identify the factors that could be adjusted to conserve the integrity of this habitat. Location: Bernese Alps, Switzerland. Methods: In 2016, we investigated the underlying causes of this degradation process by assessing vegetation composition in 48 Nardus grasslands located in the Swiss northern Alps of canton Bern and linking it to soil, management and environmental variables. To explore the effect of the degradation on higher trophic levels, orthopteran species richness and densities were assessed. Results: Results show that Nardus meadows (mown) are rarely degraded compared to Nardus pastures (grazed). Within pastures, eutrophic plants are most abundant on small pastures with low soil carbon/nitrogen ratio, indicating high nutrient availability. Nardus stricta dominance is most problematic on north‐exposed slopes and in summer pastures. A plausible driver of both degradation trends is the grazing management regime: within small pastures at low elevation where the grazing periods are short but intense, soil carbon/nitrogen ratio is low because of high dung deposition, thus the eutrophic species become dominant. Contrastingly, on large summer pastures with low‐intensity and long‐term grazing, N. stricta becomes dominant due to selective grazing. Both degradation trends show a negative impact on the orthopteran density. Conclusion: Species‐rich Nardus grasslands are a precious alpine habitat for specialised plant species and orthopterans. With an extensive mowing regime or a more controlled grazing regime that homogenises intensity in time and space, species‐rich Nardus grasslands can be conserved in Switzerland

Perioperative Fully Closed-Loop Insulin Delivery in Patients Undergoing Elective Surgery: An Open-Label, Randomized Controlled Trial

OBJECTIVE Perioperative management of glucose levels remains challenging. We aimed to assess whether fully closed-loop subcutaneous insulin delivery would improve glycemic control compared with standard insulin therapy in insulin-requiring patients undergoing elective surgery. RESEARCH DESIGN AND METHODS We performed a single-center, open-label, randomized controlled trial. Patients with diabetes (other than type 1) undergoing elective surgery were recruited from various surgical units and randomly assigned using a minimization schedule (stratified by HbA1c and daily insulin dose) to fully closed-loop insulin delivery with fast-acting insulin aspart (closed-loop group) or standard insulin therapy ac-cording to local clinical practice (control group). Study treatment was adminis-tered from hospital admission to discharge (for a maximum of 20 days). The primary end point was the proportion of time with sensor glucose in the target range (5.6–10.0 mmol/L). RESULTS Forty-five patients were enrolled and assigned to the closed-loop (n 5 23) or the control (n 5 22) group. One patient (closed-loop group) withdrew from the study before surgery and was not analyzed. Participants underwent abdominal (57%), vascular (23%), orthopedic (9%), neuro (9%), or thoracic (2%) surgery. The mean proportion of time that sensor glucose was in the target range was 76.7 ± 10.1% in the closed-loop and 54.7 ± 20.8% in the control group (mean difference 22.0 percentage points [95% CI 11.9; 32.0%]; P < 0.001). No episodes of severe hypoglycemia (<3.0 mmol/L) or hyperglycemia with ketonemia or any study-related adverse events occurred in either group. CONCLUSIONS In the context of mixed elective surgery, the use of fully closed-loop subcutaneous insulin delivery improves glucose control without a higher risk of hypoglycemia. © 2022 by the American Diabetes Association.

Risk of venous thromboembolism in ovarian cancer patients receiving neoadjuvant chemotherapy

To determine the incidence of venous thromboembolism (VTE) and define clinical risk factors associated with the development of new-onset VTE in patients receiving neoadjuvant chemotherapy (NACT) for ovarian cancer (OC). An institutional ovarian cancer database was used to identify all OC patients receiving NACT from 04/2015–09/2018. VTE events were recorded and included clinically diagnosed deep venous thrombosis (DVT) and/or pulmonary embolism (PE). The incidence of VTE events was categorized according to treatment phases (P): P0) First visit/prior to induction of NACT; P1) during NACT before interval debulking surgery (IDS); P2) intraoperative through day 28 post-IDS; P3) during adjuvant chemotherapy. A total of 290 patients were identified during the study period. Seventy-five (25.9%) developed a VTE at some point from time of presentation through the peri-operative period. Forty (13.8%) presented with VTE prior to initiation of NACT. An additional 27 (11.6%) developed a VTE during NACT (P1); 6 (3.9%) during the intraoperative and 28-day post-operative period (P2); and 2 (1.3%) during the adjuvant period (P3). The overall VTE rate was 25.9% (n = 75). FIGO stage IV disease was the only factor associated with increased risk for a new-onset VTE [Odds Ratio (OR): 3.9 (95% Confidence Interval [CI] = 1.2–13.6; p = 0.03]. Patients receiving NACT for advanced OC are at extremely high risk for developing thromboembolic events, either at initial presentation or during induction of NACT, a treatment phase that is traditionally without use of prophylactic anticoagulation. Since Khorana scoring is not predictive in this population, clinicians might need to consider increased screening or use of prophylactic anticoagulation in patients receiving NACT for OC, particularly in advanced metastatic disease. •The overall risk of venous thromboembolism (VTE) in ovarian cancer (OC) patients receiving NACT was >25%.•The highest rate was observed at initial presentation and during the induction of NACT.•FIGO stage IV disease was the only risk factor associated with an increased risk for VTE.•Prophylactic anticoagulation should be considered in OC patients receiving NACT, especially those with metastatic disease