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This longitudinal study examined the long-term effects of the COVID-19 pandemic on social media use and its impact on psychiatric symptoms and well-being of 3,697 Israeli children and adolescents aged 8 to 14. Data were collected from October 2019 to June 2023, covering four school years and five measurement points prior to, throughout and post- COVID-19. Social media usage, psychiatric symptoms (depression, anxiety, somatization, and general distress), as well as subjective well-being (positive and negative emotions, and life satisfaction) were assessed. The analysis also probed the extent to which social support and extracurricular activities moderated the associations between social media use and mental health outcomes. The results of the growth mixed-effects models indicated a significant increase in social media use and psychiatric symptoms, and a significant decrease in subjective well-being over time. Greater social media use was related to more psychiatric symptoms and negative emotions, but also to more positive emotions and life satisfaction. Social support buffered the negative effects of excessive social media use on mental health, whereas extracurricular activities increased positive emotions, but also psychiatric symptoms related to social media use. These findings highlight the need for targeted interventions to regulate social media usage, given its lasting consequences on the mental health of children and adolescents in the wake of the COVID-19 pandemic., Competing Interests: Declarations. Competing interests: The authors have no competing interests to declare that are relevant to the content of this article., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Caregivers of children with attention deficit-hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) experience more stress than caregivers of typically developing children but there is limited research evaluating caregivers' quality of life (QoL). This study aimed to describe the association of caregiver QoL in children with ASD and/or ADHD. This study included patients with ADHD and/or ASD seen in one pediatric specialty clinic between September 2018-August 2020. Caregivers were classified as those caring for children with ASD-only, ADHD-only, or youth with both conditions (ADHD + ASD). An adapted version of the PedsQL Family Impact Module was used to measure caregiver QoL. The sample included caregivers of 931 children. The majority of these children were male (74.7%), non-Hispanic white (63.3%), and aged 6 to 12 years (57.8%). Across the groups, significant differences were observed in patient age (p < 0.0001), preferred language (p = 0.005), and insurance (p = 0.001). Caregivers of non-Hispanic Black children had 4-times the odds of reporting feeling isolated from others (OR 4.36, 95% CI 1.19-16.00 p = 0.03). Those caring for children with ADHD-only had significantly lower odds of reporting helplessness or hopelessness (OR 0.45, 95% CI 0.26-0.80, p = 0.004), and difficulty talking about their child's health with others (OR 0.30, 95% CI 0.17-0.54, p < 0.0001). Similarly, caregivers of children who had ADHD + ASD reported higher odds of difficulty making decisions together as a family (OR 14.18, 95% CI 1.15-17.91, p=0.04) and difficulty solving family problems together (OR 45.12, 95% CI 2.70-752.87), p = 0.008). Caring for children with ADHD and/or ASD may affect caregiver QoL., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Before surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines., Objective: To evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery., Design, Setting, and Participants: Randomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France., Intervention: Patients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115)., Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery., Results: Of the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes., Conclusions and Relevance: Among patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy., Trial Registration: ClinicalTrials.gov Identifier: NCT03374449.

Microplastic pollution has a significant threat to marine ecosystems, yet its impact on spineless cuttlefish ( Sepiella inermis ) remains under-researched. This study aims to address this gap by analysing microplastic contamination in Sepiella inermis from the North-East Bay of Bengal. This species is widely consumed and transported globally as food, thus holding significant health concerns. A total of 40 adult female cuttlefish were collected from two sampling sites (18°36'31.35″N 87°48'10.63″E and 15°43'35.37″N 88°12'07.01″E) in the Bay of Bengal. Tissue samples from tentacles, gut, and nidamental glands were analysed for microplastic content, alongside sediment and surface water samples. Parameters such as microplastic abundance, size, shape, and colour were recorded. The average abundance of microplastic particles was measured at 2.003 particles per gram in tentacle tissue, 2.31 particles per gram in gut tissue, and 0.99 particles per gram in nidamental gland tissue. The gut tissue exhibited the highest abundance of microplastics per gram. Chemical characterization using FT-IR and confocal Raman spectroscopy identified 11 types of microplastic polymers. Of the 11 types of plastic polymers identified, PVC was the most prevalent, accounting for 17.64 % of the microplastics found across all tissues. PVC microplastics can cause significant harm to marine life and human health by accumulating in the food chain and releasing harmful chemicals like phthalates, which can lead to endocrine disruption. ABS, PET, PP, PE, and PA microplastic polymers are highly persistent in environment, leading to long-term pollution in oceans. When ingested by marine organisms, they can disrupt entire ecosystems. In humans, the accumulation of these microplastics can impair the immune system and contribute to chronic diseases. The Pollution Load Index (PLI) was calculated for each tissue type, revealing that gut tissue is more prone to microplastic pollution compared to the nidamental gland and tentacles. The average PLI per gram of gut tissue was 2.26, which was significantly higher than 1, indicating substantial pollution. This research highlights the urgent need for comprehensive strategies to mitigate microplastic pollution, given the potential health risks associated with the consumption of contaminated marine species., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:SOURAV BAR reports financial support was provided by 10.13039/501100001501University Grants Commission. SOURAV BAR reports a relationship with University Grants Commission that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for the management of acute postoperative pain as part of a multimodal strategy to reduce opioid use, relieve pain, and reduce chronic pain in non-cardiac surgery. However, significant concerns arise in cardiac surgery due to the potential adverse effects of NSAID including increased bleeding and acute kidney injury (AKI). We hypothesized that NSAIDs are effective against pain and safe in the early postoperative period following cardiac surgery, taking contraindications into account., Methods: The KETOPAIN trial is a prospective, double blind, 1:1 ratio, versus placebo multicentric trial, randomizing 238 patients scheduled for cardiac surgery. Written consent will be obtained for all participants. The inclusion criterion is patients more than 18 years old undergoing for elective cardiac surgery under cardiopulmonary bypass (CPB). Patients will be allocated to the intervention (ketoprofen) group (n = 119) or the control (placebo) group (n = 119). In the intervention group, in addition to the standard treatment, patients will receive NSAIDs (ketoprofen) at a dose of 100 mg each 12 h 48 h after. The control group, in addition to the standard treatment, will receive a placebo of NSAIDs every 12 h for 48 h after surgery. An intention-to-treat analysis will be performed. The primary endpoint will be the intensity of acute postoperative pain at rest at 24 h from the end of surgery. Pain will be assessed using the numerous rating scale. The secondary endpoints will be postoperative pain on coughing during chest physiotherapy, postoperative pain until day 7, the pain trajectory between day 3 and day 7, cumulative opioid consumption within 48 h after surgery, nausea and vomiting, the occurrence of postoperative pulmonary complications within the first 7 days after surgery, neuropathic pain at 3 months, and quality of life at 3 months., Discussion: NSAIDs function as non-selective, reversible inhibitors of the cyclooxygenase enzyme and play a role in a multimodal pain management approach. While there are recommendations supporting the use of NSAIDs in major non-cardiac surgery, recent guidelines do not favor their use in cardiac surgery. However, this is based on low-quality evidence. Major concerns regarding NSAID use in cardiac surgery patients are potential increase in postoperative bleeding or AKI. However, few studies support the possible use of NSAIDs without the risk of bleeding and/or AKI. Also, in a recent French survey, many anesthesiologists reported using NSAIDs in cardiac surgery. To date, no large randomized study has been conducted to evaluate the efficacy of NSAIDs in the management of postoperative pain in cardiac surgery. The expected outcome of this study is an improvement in the management of acute postoperative pain in cardiac surgery with a multimodal strategy including the use of NSAIDs., Trial Registration: ClinicalTrials.gov NCT06381063. Registered on April 24, 2024., (© 2024. The Author(s).)

The characteristics of the vegetation fire (VF) regime are strongly influenced by geographical variables such as regional physiographic settings, location, and climate. Understanding the VF regime is extremely important for managing and mitigating the impacts of fires on ecosystems, communities, and human activities in forest fire-prone regions. The present study thereby aimed to explore the potential effects of the confounding factors on VF in India to offer actionable and achievable solutions for mitigating this concurring environmental issue sustainably. A global burn area (250 m) data (Fire-CCIv5.1) and fire radiative power (FRP) were used to investigate the dynamics of VF across seven different divisions in India. The study also used the maximum and minimum temperatures, precipitation, population density, and intensity of human modification to model forest burn areas (including grassland). The Coupled Model Intercomparison Project-6 (CMIP6) was used to predict the burn area for 2030 and 2050 future climate scenarios. The present study accounted for a sizable increasing trend of VF during 2001-2019 period. The highest increasing trend was found in central India (513 and 343 km 2  year -1 in the forest and crop fire, respectively), followed by southern India (364 km 2  year -1 in forest fire), and upper Indo-Gangetic plain (128 km 2  year -1 in crop fire). The FRP has varied significantly across the divisions, with the north-eastern Himalayas exhibiting the highest FRP hotspot. The maximum and minimum temperatures have the greatest influence on forest fires, according to Random Forest (RF) modeling. The estimated pre-monsoonal burn area for 2050 and 2050 future scenarios suggested a more frequent forest fire occurrence across India, particularly in southern and central India. A comprehensive forest fire control policy is therefore essential to safeguard and conserve forest cover in the regions, affected by forest fire periodically., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Postoperative complications, particularly respiratory complications, are of significant clinical concern in patients undergoing elective thoracic surgery. Dexamethasone (DXM), commonly administered to prevent postoperative nausea and vomiting (PONV), has potential anti-inflammatory effects that might be beneficial in reducing these complications. We aimed to investigate whether intraoperative DXM administration could mitigate the occurrence of respiratory complications following elective thoracic surgery., Methods: We conducted a single-center observational study, including patients who underwent elective thoracic surgery from 2012 to 2020. The primary outcome was the onset of acute respiratory failure within 7 days post-surgery. Secondary outcomes encompassed other postoperative complications, duration of hospital stay, and mortality within 30 days post-surgery. An overlap propensity score analysis was employed to estimate the treatment effect., Results: We included 1,247 adult patients, 897 who received dexamethasone (DXM) and 350 who served as controls. Intraoperative dexamethasone administration was associated with a significant reduction in respiratory complications with an adjusted relative risk (RR) of 0.65 (95% CI: 0.43-0.97). There was also a significant decline in composite infectious criteria with an adjusted RR of 0.76 (95% CI: 0.63-0.93). Cardiac complications were also assessed as a composite criterion, and a significant reduction was observed (adjusted RR, 0.68; 95% CI, 0.51-0.9). However, there were no association with mechanical complications, mortality within 30 days (adjusted RR of 0.43, 95% CI: 0.17-1.09) or in the length of hospital stay (adjusted RR of 0.85, 95% CI: 0.71-1.02)., Conclusions: Dexamethasone administration was associated with a reduction in postoperative respiratory complications. Further prospective studies are needed to confirm these findings., (Copyright © 2024 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species. However, it is not yet known whether they are also at risk within aggregation sites, where up to 400 individuals can gather to feed on seasonal bursts of planktonic productivity. These "constellation" sites are of significant ecological, socio-economic and cultural value. Here, through expert elicitation, we gathered information from most known constellation sites for this species across the world (>50 constellations and >13,000 individual whale sharks). We defined the spatial boundaries of these sites and their overlap with shipping traffic. Sites were then ranked based on relative levels of potential collision danger posed to whale sharks in the area. Our results showed that researchers and resource managers may underestimate the threat posed by large ship collisions due to a lack of direct evidence, such as injuries or witness accounts, which are available for other, sub-lethal threat categories. We found that constellations in the Arabian Sea and adjacent waters, the Gulf of Mexico, the Gulf of California, and Southeast and East Asia, had the greatest level of collision threat. We also identified 39 sites where peaks in shipping activity coincided with peak seasonal occurrences of whale sharks, sometimes across several months. Simulated collision mitigation options estimated potentially minimal impact to industry, as most whale shark core habitat areas were small. Given the threat posed by vessel collisions, a coordinated, multi-national approach to mitigation is needed within priority whale shark habitats to ensure collision protection for the species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) is a prevalent metabolic disorder often accompanied by oxidative stress, which contributes to various diabetic complications. Investigating the antioxidant activity of linalool (LIN) is crucial as it may offer a natural therapeutic approach to mitigate oxidative damage in DM. The aim of the present study was to investigate the antioxidant activity of LIN in a DM rat model. A total of 40 male Wistar albino rats (age, 8 weeks; weight, 250-300 g) were used. CONTROL and DM groups were administered physiological saline solution by oral gavage for 21 days. In rats in the DM + LIN and LIN groups, 100 mg/kg LIN was administered intragastrically after streptozotocin injection (n=10 per group). In the first (48 h after STZ injection), second (1 week later), third (2 weeks later), and fourth (3 weeks later) blood glucose measurements, a statistically significant increase was found in the blood glucose values of the DM and DM + LIN groups compared with those of the CONTROL group. During the 21-day experimental period, there was no reduction in blood glucose levels of the DM + LIN group. Consequently, no discernible anti-hyperglycemic effect of LIN was observed. Catalase enzyme activity, superoxide dismutase (SOD) enzyme activity, malondialdehyde (MDA) levels and glutathione (GSH) levels were measured spectrophotometrically. All assays were conducted according to the protocols provided in the respective kits. The results were analyzed to assess the oxidative status and antioxidant capacity in the experimental groups. Catalase (CAT) activity was decreased in the DM group compared with that in the CONTROL group in both the serum and liver. However, LIN administration restored CAT activity in the DM + LIN group to the level of the CONTROL group. In the liver, the DM + LIN-treated group showed a notable reduction in malondialdehyde (MDA) levels compared with those in the DM group. In conclusion, the present results suggest that the antioxidant properties of LIN may have a regulatory effect on the oxidative status in diabetes-affected systems, potentially offering therapeutic benefits in managing oxidative stress associated with diabetes., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Background/objectives: The aim of this study was to evaluate the long-term outcomes of a cohort of ophthalmologically resolved female idiopathic intracranial hypertension (IIH) patients. Methods: Our cross-sectional study included adult females with at least 6 months of ophthalmologically resolved IIH. Patients with papilledema or who underwent IIH-targeted surgical intervention were excluded. Participants completed a questionnaire consisting of medical information, the Migraine Disability Assessment Scale (MIDAS) and the Headache Impact Test (HIT-6). Electronic medical records and the results of imaging upon diagnosis were retrospectively reviewed. Results : One-hundred-and-four participants (mean age 35.5 ± 11.9 years) were included (7.85 ± 7 years post-IIH diagnosis). Patients with moderate-severe disability according to the MIDAS scale (n = 68, 65.4%) were younger (32.4 ± 8.9 vs. 41.5 ± 14.4 year-old, p < 0.001), had a shorter time interval from IIH diagnosis (5.9 ± 5.3 vs. 11.7 ± 8.5 years, p < 0.001), and had lower FARB scores (indicating a more narrowed transverse-sigmoid junction; 1.28 ± 1.82 vs. 2.47 ± 2.3, p = 0.02) in comparison to patients with low-mild disability scores. In multivariate analysis, a lower FARB score (OR 1.28, 95% CI 0.89-1.75, p = 0.12) and younger age (OR 1.09, 95% CI 0.98-1.19, p = 0.13) showed a trend toward an association with a moderate-severe MIDAS score. Moreover, in the sub-analysis of patients with a moderate-severe MIDAS scale score, the 10 patients with the highest MIDAS scores had a low FARB score (1.6 ± 1.1 vs. 2.7 ± 2.4, p = 0.041). Conclusions: High numbers of patients with ophthalmologically resolved IIH continue to suffer from related symptoms. Symptoms may be associated with the length of time from the diagnosis of IIH and a lower FARB score.

Single-molecule fluorescence resonance energy transfer (smFRET) methods employed to quantify time-dependent compositional and conformational changes within biomolecules require elevated illumination intensities to recover robust photon emission streams from individual fluorophores. Here we show that outside the weak-excitation limit, and in regimes where fluorophores must undergo many rapid cycles of excitation and relaxation, non-fluorescing, excitation-induced triplet states with lifetimes orders of magnitude longer lived than photon-emitting singlet states degrade photon emission streams from both donor and acceptor fluorophores resulting in illumination-intensity-dependent changes in FRET efficiency. These changes are not commonly taken into consideration; therefore, robust strategies to suppress excited state accumulations are required to recover accurate and precise FRET efficiency, and thus distance, estimates. We propose both robust triplet state suppression and data correction strategies that enable the recovery of FRET efficiencies more closely approximating true values, thereby extending the spatial and temporal resolution of smFRET., (© 2024. The Author(s).)

Study Objective: This post-hoc analysis of a randomized controlled trial was undertaken to establish the determinants of postoperative complications and acute kidney injury in high-risk noncardiac surgery patients supported with hemodynamic treatment strategies., Design: We conducted a post-hoc analysis of patients enrolled in the OPtimization Hemodynamic Individualized by the respiratory QUotiEnt (OPHIQUE) trial., Setting: Operating rooms in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021., Patients: We enrolled 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia., Interventions: All patients were treated according to hemodynamic treatment strategies which included cardiac output optimization by titration of fluid challenge and targeted systolic blood pressure to remain within ±10% of the reference value., Measurements: We assessed the association between pre-operative and intra-operative exposure of interest with a composite primary outcome of major complications or death within seven days following surgery using a multivariable logistic regression model. We also assessed the association between these exposures of interest and acute kidney injury., Main Results: The data of 341 patients were analyzed. In multivariate analysis, the factors independently associated with the primary outcome were age (OR = 1.04 (1.01-1.06), P = 0.002), preoperative hemoglobin concentration (OR = 0.85 (0.75-0.96), P = 0.012), non-vascular surgery (OR = 0.30 (0.17-0.53), P < 0.0001), and intraoperative surgical complications (OR = 2.08 (1.02-4.24), P = 0.046). The factors independently associated with postoperative acute kidney injury were age (OR = 1.04 (1.01-1.08), P = 0.008), preoperative creatinine concentration (OR = 1.01 (1.00-1.01), P = 0.049), non-vascular surgery (OR = 0.36 (0.20-0.66), P = 0.001), and intraoperative surgical complications (OR = 3.36 (1.50-7.55), P = 0.031)., Conclusions: Surgical complications, a lower preoperative hemoglobin concentration, age, and vascular surgery were associated with postoperative complications in a high-risk noncardiac surgery population supported with hemodynamic treatment strategies., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Post-induction anaesthesia often promotes intraoperative hypotension (IOH) that can worsen postoperative outcomes. This study aims to assess the benefit of norepinephrine versus ephedrine at the induction of anaesthesia to prevent postoperative complications following major abdominal surgery by preventing IOH., Methods and Analysis: The EPON STUDY is a prospective single-centre randomised controlled trial with the planned inclusion of 500 patients scheduled for major abdominal surgery at the Amiens University Hospital. The inclusion criteria are patients aged over 50 years weighing more than 50 kg with an American Society of Anesthesiologists physical status score of ≥2 undergoing major abdominal surgery under general anaesthesia. Patients are allocated either to the intervention group (n=250) or the standard group (n=250). In the intervention group, the prevention of post-induction IOH is performed with norepinephrine (dilution to 0.016 mg/mL) using an electric syringe pump at a rate of 0.48 mg/h (30 mL/h) from the start of anaesthesia and then titrated to achieve the haemodynamic target. In the control group, the prevention of post-induction IOH is performed with manual titration of ephedrine, with a maximal dose of 30 mg, followed by perfusion with norepinephrine. In both groups, the haemodynamic target to maintain is a mean arterial pressure (MAP) of 65 mm Hg or 70 mm Hg for patients with a medical history of hypertension. An intention-to-treat analysis will be performed. The primary outcome is the Clavien-Dindo score assessed up to 30 days postoperatively. The secondary endpoints are the length of hospital stay and length of stay in an intensive care unit/postoperative care unit; postoperative renal function; postoperative cardiovascular, respiratory, neurological, haematological and infectious complications at 1 month; and volume of intraoperative vascular filling and mortality at 1 month., Ethics and Dissemination: Ethical approval was obtained from the committee of protection of the persons of Ile de France in May 2021 (number 21 05 41). The authors will be involved in disseminating the research findings (through attending conferences and co-authoring papers). The results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences., Trial Registration Number: NCT05276596., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Serratus anterior plane block (SAPB) and paravertebral block (PVB) are well known to reduce pain levels after video-assisted thoracoscopic surgery (VATS). However, the relative efficacies of each block and a combination of the 2 have not been fully characterized. The objective of the present study was to assess the efficacy of PVB alone, SAPB alone and the combination of PVB and SAPB with regard to the occurrence and intensity of pain after VATS., Methods: We conducted the THORACOSOPIC single-centre, double-blind, randomized trial in adult patients due to undergo elective VATS lung resection. The participants were randomized to PVB only, SAPB only and PVB + SAPB groups. The primary end-point was pain on coughing on admission to the postanaesthesia care unit. The secondary end-points were postoperative pain at rest and on coughing at other time points and the cumulative opioid consumption. Pain was scored on a visual analogue scale., Results: One-hundred and fifty-six patients (52 in each group) were included. On admission to the postanaesthesia care unit, the 3 groups did not differ significantly with regard to the pain on coughing: the visual analogue scale score was 3 (0-6), 4 (0-8) and 2 (0-6) in the PVB, SAPB and PVB + SAPB groups, respectively (P = 0.204). During postoperative care, the overall pain score was significantly lower in the SABP + PVP group at rest and on cough., Conclusions: The combination of SABP + PVB could be beneficial for pain management in VATS in comparison to SABP or PVB alone., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Introduction: Voice therapy (VT), a cornerstone in dysphonia treatment, relies on patient adherence for efficacy. Despite its positive outcomes, adherence rates remain consistently low. This study investigates the impact of cultural background on adherence to VT., Methods: This is a retrospective cohort study that included all adult patients referred to our institution's Speech and Hearing unit, in 2018 for VT related to dysphonia. The study group included a distinct adult minority group (Bedouin Arabs) which was compared to a control group. Adherence rates, demographic factors, and therapy outcomes were analyzed., Results: A total of 137 adult patients with dysphonia (20 in the study group and 117 in the control group) were included. There were no significant differences in adherence rates between the study and control groups (75% vs 74.3%, P = 1), with an overall nonadherence rate of 74.4%. The median leg of time for VT was 239days, and the median number of visits was 3.0. Logistic regression analysis, adjusting for age and visits, indicated lower odds of dysphonia improvement in the study group (odds ratios [OR]: 0.12, P = 0.05). However, visits showed a significant positive impact on improvement (OR: 2.58, P < 0.001)., Conclusion: While cultural background does not impact adherence rate, it is associated with different attendance patterns and lower voice outcomes following VT. Future efforts should concentrate on investigating aspects of adherence such as home exercises, accessibility of treatment, and the frequency of follow-up sessions to facilitate customized interventions for specific populations., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Despite advancements in using multi-temporal satellite data to assess long-term changes in Northeast India's tea plantations, a research gap exists in understanding the intricate interplay between biophysical and biochemical characteristics. Further exploration is crucial for precise, sustainable monitoring and management. In this study, satellite-derived vegetation indices and near-proximal sensor data were deployed to deduce various physico-chemical characteristics and to evaluate the health conditions of tea plantations in northeast India. The districts, such as Sonitpur, Jorhat, Sibsagar, Dibrugarh, and Tinsukia in Assam were selected, which are the major contributors to the tea industry in India. The Sentinel-2A (2022) data was processed in the Google Earth Engine (GEE) cloud platform and utilized for analyzing tea plantations biochemical and biophysical properties. Leaf chlorophyll (C ab ) and nitrogen contents are determined using the Normalized Area Over Reflectance Curve (NAOC) index and flavanol contents, respectively. Biophysical and biochemical parameters of the tea assessed during the spring season (March-April) 2022 revealed that tea plantations located in Tinsukia and Dibrugarh were much healthier than the other districts in Assam which are evident from satellite-derived Enhanced Vegetation Index (EVI), Modified Soil Adjusted Vegetation Index (MSAVI), Leaf Area Index (LAI), and Fraction of Absorbed Photosynthetically Active Radiation (fPAR), including the C ab and nitrogen contents. The C ab of healthy tea plants varied from 25 to 35 µg/cm 2 . Pearson correlation among satellite-derived C ab and nitrogen with field measurements showed R 2 of 0.61-0.62 (p-value < 0.001). This study offered vital information about land alternations and tea health conditions, which can be crucial for conservation, monitoring, and management practices., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity., (© 2024. The Author(s).)

Background: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience., Methods: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement., Discussion: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Norepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors' distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion., Methods: A prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion., Results: Thirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [- 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p < 0.001) with norepinephrine infusion, being classified as VW responders. The VW responders improved cardiac index (from 1.8 (0.6) L min -1 m -2 to 2.2 (0.5) L min -1 m -2 , p = 0.002), capillary refill time (from to 4.2 (1.1) s to 3.1 (1) s, p = 0.006), and pCO 2 gap (from 9 [7;10] mmHg to 6 [4;8] mmHg, p = 0.04). No baseline parameters were able to predict the VW response to norepinephrine. In comparison, VW non-responders did not significantly change the VW (from 5 [-5;16] mmHg to -2 [-12;15] mmHg, p = 0.17), cardiac index (from 1.6 (0.3) L min -1 m -2 to 1.8 (0.4) L min -1 m -2 , p = 0.09) and capillary refill time (from 4.1 (1) s to 3.7 (1.4), p = 0.44)., Conclusions: In post-cardiac surgery patients with vasoplegic arterial hypotension, the vascular waterfall is low. Norepinephrine did not systematically restore the vascular waterfall. Increase of the vascular waterfall was associated with an improvement of laboratory and clinical parameters of tissue perfusion., (© 2023. European Society of Intensive Care Medicine and Springer Nature Switzerland AG.)

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide and Inflammation plays a critical role in the development of CVD. Despite considerable progress in understanding the underlying mechanisms and various treatment options available, significant gaps in therapy necessitate the identification of novel therapeutic targets. Sphingolipids are a family of lipids that have gained attention in recent years as important players in CVDs and the inflammatory processes that underlie their development. As preclinical studies have shown that targeting sphingolipids can modulate inflammation and ameliorate CVDs, targeting sphingolipids has emerged as a promising therapeutic strategy. This review discusses the current understanding of sphingolipids' involvement in inflammation and cardiovascular diseases, the existing therapeutic approaches and gaps in therapy, and explores the potential of sphingolipids-based drugs as a future avenue for CVD treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ya'ar Bar, Pintel, Abd Alghne, Khattib and Avni.)

Background: There is a need to develop non-invasive markers to identify the occurrence of anaerobic metabolism in high-risk surgery. Our objective was to demonstrate that a goal-directed therapy algorithm incorporating the respiratory exchange ratio (ratio between CO 2 production and O 2 consumption) can reduce postoperative complications., Methods: We conducted a randomized, multicenter, controlled clinical trial in four university medical centers and one non-university hospital from December 26, 2018, to September 9, 2021. 350 patients with a high risk of postoperative complications undergoing high-risk noncardiac surgery lasting 2 h or longer under general anesthesia were enrolled. The control group was treated according to current hemodynamic guidelines. The interventional group was treated according to an algorithm based on the measurement of the respiratory exchange ratio. The primary outcome was a composite of major complications or death within seven days of surgery. The secondary outcomes were the length of hospital stay, 30-day mortality, and the total intraoperative volume of fluids administered., Results: The primary outcome occurred for 78 patients (45.6%) in the interventional group and 83 patients (48.8%) in the control group (relative risk: 0.93, 95% confidence interval [CI]: 0.75-1.17; p = 0.55). There were no clinically relevant differences between the two groups for secondary outcomes., Conclusions: In high-risk surgery, a goal-directed therapy algorithm integrating the measurement of the respiratory-exchange ratio did not reduce a composite outcome of major postoperative complications or death within seven days after surgery compared to routine care., Trial Registration: ClinicalTrials.gov, NCT03852147., (Copyright © 2023 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

The vulnerabilities of cancer cells constitute a promising strategy for drug therapeutics. This paper integrates proteomics, bioinformatics, and cell genotype together with in vitro cell proliferation assays to identify key biological processes and potential novel kinases that could account, at least in part, for the clinical differences observed in colorectal cancer (CRC) patients. This study started by focusing on CRC cell lines stratified by their microsatellite ( MS ) state and p53 genotype. It shows that cell-cycle checkpoint, metabolism of proteins and RNA, signal transduction, and WNT signaling processes are significantly more active in MSI-High p53-WT cell lines. Conversely, MSI-High cell lines with a mutant (Mut) p53 gene showed hyperactivation of cell signaling, DNA repair, and immune-system processes. Several kinases were linked to these phenotypes, from which RIOK1 was selected for additional exploration. We also included the KRAS genotype in our analysis. Our results showed that RIOK1's inhibition in CRC MSI-High cell lines was dependent on both the p53 and KRAS genotypes. Explicitly, Nintedanib showed relatively low cytotoxicity in MSI-High with both mutant p53 and KRAS (HCT-15) but no inhibition in p53 and KRAS WT (SW48) MSI-High cells. This trend was flipped in CRC MSI-High bearing opposite p53-KRAS genotypes (e.g., p53-Mut KRAS-WT or p53-WT KRAS-Mut), where observed cytotoxicity was more extensive compared to the p53-KRAS WT-WT or Mut-Mut cells, with HCT 116 (KRAS-Mut and p53-WT) being the most sensitive to RIOK1 inhibition. These results highlight the potential of our in silico computational approach to identify novel kinases in CRC sub-MSI-High populations as well as the importance of clinical genomics in determining drug potency.

The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, and transgenes without prior exposure to its targets. Here, we show that endogenous targets of the HUSH complex fall into two distinct classes based on the presence or absence of H3K9me3. These classes are further distinguished by their transposon content and differential response to the loss of HUSH. A de novo genomic rearrangement at the Sox2 locus induces a switch from H3K9me3-independent to H3K9me3-associated HUSH targeting, resulting in silencing. We further demonstrate that HUSH interacts with the termination factor WDR82 and-via its component MPP8-with nascent RNA. HUSH accumulates at sites of high RNAPII occupancy including long exons and transcription termination sites in a manner dependent on WDR82 and CPSF. Together, our results uncover the functional diversity of HUSH targets and show that this vertebrate-specific complex exploits evolutionarily ancient transcription termination machinery for co-transcriptional chromatin targeting and genome surveillance., Competing Interests: Declaration of interests J.W. is a paid member of Camp4 and Paratus scientific advisory boards. J.W. is an advisory board member at Cell Press journals including Cell, Molecular Cell, and Developmental Cell., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Genomic imprinting underlies the mammalian requirement for sexual reproduction. Nonetheless, the relative contribution of the two parental genomes during human development is not fully understood. Specifically, a fascinating question is whether the formation of the gonad, which holds the ability to reproduce, depends on equal contribution from both parental genomes. Here, we differentiated androgenetic and parthenogenetic human pluripotent stem cells (hPSCs) into ovarian granulosa-like cells (GLCs). We show that in contrast to biparental and androgenetic cells, parthenogenetic hPSCs present a reduced capacity to differentiate into GLCs. We further identify the paternally expressed gene IGF2 as the most upregulated imprinted gene upon differentiation. Remarkably, while IGF2 knockout androgenetic cells fail to differentiate into GLCs, the differentiation of parthenogenetic cells supplemented with IGF2 is partly rescued. Thus, our findings unravel a surprising essentiality of genes that are only expressed from the paternal genome to the development of the female reproductive system., Competing Interests: Conflict of interests N.B. is CSO of NewStem Ltd., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest S.C.B. and R.B.A. have an equity interest in Lumidyne Technologies.

Magnetic Particle imaging (MPI) allows to measure and quantify background-free tracer distribution with a high temporal resolution. Anatomical structures are not displayed in MPI, rendering orientation within a sample error-prone and necessitating co-registration with other imaging modalities such as MRI. To support this challenge, defined external landmarks (fiducials) made from materials visible in each of the imaging modalities respectively were used in this work. Resulting signals can be aligned with the merged image containing both anatomical data and information about the tracer distribution. Defining the optimal fiducial placement is demanding and can drastically impact the 3D MPI-MRI image presentation. Here we present an adaptable 3D-printed fiducial system for preclinical co-registration of MRI and MPI data designed for easy visualisation. Clinical relevance- MPI is a promising imaging modality with many conceivable clinical applications. Simple and reliable co-registration with other imaging modalities will be crucial for a seamless transition into the clinic.

Forest fires impact on soil, water, and biota resources. The current forest fires in the West Coast of the United States (US) profoundly impacted the atmosphere and air quality across the ecosystems and have caused severe environmental and public health burdens. Forest fire led emissions could significantly exacerbate the air pollution level and, therefore, would play a critical role if the same occurs together with any epidemic and pandemic health crisis. Limited research is done so far to examine its impact in connection to the current pandemic. As of October 21, nearly 8.2 million acres of forest area were burned, with more than 25 casualties reported so far. In-situ air pollution data were utilized to examine the effects of the 2020 forest fire on atmosphere and coronavirus (COVID-19) casualties. The spatial-temporal concentrations of particulate matter (PM 2.5 and PM 10 ) and Nitrogen Dioxide (NO 2 ) were collected from August 1 to October 30 for 2020 (the fire year) and 2019 (the reference year). Both spatial (Multiscale Geographically Weighted Regression) and non-spatial (Negative Binomial Regression) analyses were performed to assess the adverse effects of fire emission on human health. The in-situ data-led measurements showed that the maximum increases in PM 2.5 , PM 10 , and NO 2 concentrations (μg/m 3 ) were clustered in the West Coastal fire-prone states during August 1 - October 30, 2020. The average concentration (μg/m 3 ) of particulate matter (PM 2.5 and PM 10 ) and NO 2 was increased in all the fire states severely affected by forest fires. The average PM 2.5 concentrations (μg/m 3 ) over the period were recorded as 7.9, 6.3, 5.5, and 5.2 for California, Colorado, Oregon, and Washington in 2019, increasing up to 24.9, 13.4, 25.0, and 17.0 in 2020. Both spatial and non-spatial regression models exhibited a statistically significant association between fire emission and COVID-19 incidents. Such association has been demonstrated robust and stable by a total of 30 models developed for analyzing the spatial non-stationary and local association. More in-depth research is needed to better understand the complex relationship between forest fire emission and human health., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Mucopolysaccharidosis type VII (MPS VII) is a recessively inherited lysosomal storage disorder caused due to β-glucuronidase (β-GUS) enzyme deficiency. Prominent clinical symptoms include hydrops fetalis, musculoskeletal deformities, neurodegeneration and hepatosplenomegaly leading to premature death in most cases. Apart from these, MPS VII is also characterized as adipose storage deficiency disorder although the underlying mechanism of this lean phenotype in the patients or β-GUS-deficient mice still remains a mystery. We addressed this issue using our recently developed Drosophila model of MPS VII (the CG2135 -/- fly), which also exhibited a significant loss of body fat. We report here that the lean phenotype of the CG2135 -/- larvae is due to fewer number of adipocytes, smaller lipid droplets and reduced adipogenesis. Our data further revealed that there is an abnormal accumulation of autophagosomes in the CG2135 -/- larvae due to autophagosome-lysosome fusion defect. Decreased lysosome-mediated turnover also led to attenuated mTOR activity in the CG2135 -/- larvae. Interestingly, treatment of the CG2135 -/- larvae with mTOR stimulators, 3BDO or glucose, led to the restoration of mTOR activity with simultaneous correction of the autophagy defect and adipose storage deficiency. Our finding thus established a hitherto unknown mechanistic link between autophagy dysfunction, mTOR downregulation and reduced adiposity in MPS VII., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Many vital processes in the eye are under circadian regulation, and circadian dysfunction has emerged as a potential driver of eye aging. Dietary restriction is one of the most robust lifespan-extending therapies and amplifies circadian rhythms with age. Herein, we demonstrate that dietary restriction extends lifespan in Drosophila melanogaster by promoting circadian homeostatic processes that protect the visual system from age- and light-associated damage. Altering the positive limb core molecular clock transcription factor, CLOCK, or CLOCK-output genes, accelerates visual senescence, induces a systemic immune response, and shortens lifespan. Flies subjected to dietary restriction are protected from the lifespan-shortening effects of photoreceptor activation. Inversely, photoreceptor inactivation, achieved via mutating rhodopsin or housing flies in constant darkness, primarily extends the lifespan of flies reared on a high-nutrient diet. Our findings establish the eye as a diet-sensitive modulator of lifespan and indicates that vision is an antagonistically pleiotropic process that contributes to organismal aging., (© 2022. The Author(s).)

A fluid challenge can generate an infraclinical interstitial syndrome that may be detected by the appearance of B-lines by lung ultrasound. Our objective was to evaluate the appearance of B-lines as a diagnostic marker of preload unresponsiveness and postoperative complications in the operating theater. We conducted a prospective, bicentric, observational study. Adult patients undergoing abdominal surgery were included. Stroke volume (SV) was determined before and after a fluid challenge with 250 mL crystalloids (Delta-SV) using esophageal Doppler monitoring. Responders were defined by an increase of Delta-SV > 10% after fluid challenge. B-lines were collected at four bilateral predefined zones (right and left anterior and lateral). Delta-B-line was defined as the number of newly appearing B-lines after a fluid challenge. Postoperative pulmonary complications were prospectively recorded according to European guidelines. In total, 197 patients were analyzed. After a first fluid challenge, 67% of patients were responders and 33% were non-responders. Delta-B-line was significantly higher in non-responders than responders [4 (2-7) vs 1 (0-3), p < 0.0001]. Delta-B-line was able to diagnose fluid non-responders with an area under the curve of 0.74 (95% CI 0.67-0.80, p < 0.0001). The best threshold was two B-lines with a sensitivity of 80% and a specificity of 57%. The final Delta-B-line could predict postoperative pulmonary complications with an area under the curve of 0.74 (95% CI 0.67-0.80, p = 0.0004). Delta-B-line of two or more detected in four lung ultrasound zones can be considered to be a marker of preload unresponsiveness after a fluid challenge in abdominal surgery.The objectives and procedures of the study were registered at Clinicaltrials.gov (NCT03502460; Principal investigator: Stéphane BAR, date of registration: April 18, 2018)., (© 2022. The Author(s).)

The outbreak of SARS CoV-2 (COVID-19) has posed a serious threat to human beings, society, and economic activities all over the world. Worldwide rigorous containment measures for limiting the spread of the virus have several beneficial environmental implications due to decreased anthropogenic emissions and air pollutants, which provide a unique opportunity to understand and quantify the human impact on atmospheric environment. In the present study, the associated changes in Land Surface Temperature (LST), aerosol, and atmospheric water vapor content were investigated over highly COVID-19 impacted areas, namely, Europe and North America. The key findings revealed a large-scale negative standardized LST anomaly during nighttime across Europe (-0.11 °C to -2.6 °C), USA (-0.70 °C) and Canada (-0.27 °C) in March-May of the pandemic year 2020 compared to the mean of 2015-2019, which can be partly ascribed to the lockdown effect. The reduced LST was corroborated with the negative anomaly of air temperature measured at meteorological stations (i.e. -0.46 °C to -0.96 °C). A larger decrease in nighttime LST was also seen in urban areas (by ∼1-2 °C) compared to rural landscapes, which suggests a weakness of the urban heat island effect during the lockdown period due to large decrease in absorbing aerosols and air pollutants. On the contrary, daytime LST increased over most parts of Europe due to less attenuation of solar radiation by atmospheric aerosols. Synoptic meteorological variability and several surface-related factors may mask these changes and significantly affect the variations in LST, aerosols and water vapor content. The changes in LST may be a temporary phenomenon during the lockdown but provides an excellent opportunity to investigate the effects of various forcing controlling factors in urban microclimate and a strong evidence base for potential environmental benefits through urban planning and policy implementation., Competing Interests: The authors declare no conflict of interest., (© 2021 Elsevier Ltd. All rights reserved.)

In mammals, imprinted genes are regulated by differentially methylated regions (DMRs) that are inherited from germ cells, leading to monoallelic expression in accordance with parent-of-origin. Yet, it is largely unknown how imprinted DMRs are maintained in human embryos despite global DNA demethylation following fertilization. Here, we explored the mechanisms involved in imprinting regulation by employing human parthenogenetic embryonic stem cells (hpESCs), which lack paternal alleles. We show that although global loss of DNA methylation in hpESCs affects most imprinted DMRs, many paternally-expressed genes (PEGs) remain repressed. To search for factors regulating PEGs, we performed a genome-wide CRISPR/Cas9 screen in haploid hpESCs. This revealed ATF7IP as an essential repressor of a set of PEGs, which we further show is also required for silencing sperm-specific genes. Our study reinforces an important role for histone modifications in regulating imprinted genes and suggests a link between parental imprinting and germ cell identity., (© 2021. The Author(s).)

Objective: Angiopoietins (Angs) regulate endothelial permeability. Ang-1 and 2 (Ang-1 and Ang-2) are implied in endothelial stability through an antagonism effect. The objectives of the present study were to describe and compare changes in Ang levels after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR)., Design: A prospective, single-center study., Participants: Adult patients with aortic stenosis scheduled for SAVR or TAVR., Interventions: None., Measurements and Main Results: Ang-1 and Ang-2 were measured using an enzyme-linked immunosorbent assay right before surgery (T0), at the end of surgery (T1), and at day one (T2). Sixty consecutive patients (SAVR group [n = 30] and TAVR group [n = 30]) were included between January and June 2017. Ang-1 decreased significantly after both TAVR (T0: 3,663 [2,602-4,262]; T1: 1,611 [981-2,409]; T2: 1,082 [652-1,589] ng/mL; p < 0.0001) and SAVR (T0: 1,603 [975-2,849]; T1: 783 [547-1,024]; T2: 828 [460-1,227] ng/mL; p = 0.0001). Ang-2 increased significantly after SAVR (T0: 2,472 [1,502-3,622]; T1: 2,997 [1,759-3,839]; T2: 5,421 [3,557-7,087] ng/mL; p < 0.0001) but did not change markedly after TAVR (T0: 3,343 [2,661-6,272]; T1: 3,788 [2,574-5,016]; T2: 3,446 [3,029-6,313] ng/mL; p = 0.066). Among patients with paravalvular leakage, the changes in the plasma Ang-2 level and the Ang-2/Ang-1 ratio were greater., Conclusion: SAVR induces greater alterations of Ang homeostasis than TAVR, confirming a role for the use of cardiopulmonary bypass. Paravalvular leakage after TAVR is associated with Ang changes similar to those observed with SAVR., Competing Interests: Conflict of Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

SARS CoV-2 (COVID-19) coronavirus has been causing enormous suffering, death, and economic losses worldwide. There are rigorous containment measures on industries, non-essential business, transportation, and citizen mobility to check the spread. The lockdowns may have an advantageous impact on reducing the atmospheric pollutants. This study has analyzed the change in atmospheric pollutants, based on the Sentinel-5Ps and ground-station observed data during partial to complete lockdown period in 2020. Results revealed that the mean tropospheric NO 2 concentration substantially dropped in 2020 due to lockdown against the same period in 2019 by 18-40% over the major urban areas located in Europe (i.e. Madrid, Milan, Paris) and the USA (i.e. New York, Boston, and Springfield). Conversely, urban areas with partial to no lockdown measures (i.e. Warsaw, Pierre, Bismarck, and Lincoln) exhibited a relatively lower dropdown in mean NO 2 concentration (3 to 7.5%). The role of meteorological variability was found to be negligible. Nevertheless, the reduced levels of atmospheric pollutants were primarily attributed to the shutdown of vehicles, power plants, and industrial emissions. Improvement in air quality during COVID-19 may be temporary, but regulatory bodies should learn to reduce air pollution on a long-term basis concerning the trade-offs between the environment, society, and economic growth. The intersection of urban design, health, and environment should be addressed by policy-makers to protect public health and sustainable urban policies could be adopted to build urban resilience against any future emergencies., Competing Interests: The authors declare no conflict of interest., (© 2021 Elsevier Ltd. All rights reserved.)

We highlight Martinez-Miguel et al. (2021), which demonstrates that an amino acid substitution in RPS23 found in thermophilic archaea contributes to increased translation fidelity, lifespan, and stress response but slows development and reproduction in other organisms., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Intra-cellular active transport by native cargos is ubiquitous. We investigate the motion of spherical nano-particles (NPs) grafted with flexible polymers that end with a nuclear localization signal peptide. This peptide allows the recruitment of several mammalian dynein motors from cytoplasmic extracts. To determine how motor-motor interactions influenced motility on the single microtubule level, we conducted bead-motility assays incorporating surface adsorbed microtubules and combined them with model simulations that were based on the properties of a single dynein. The experimental and simulation results revealed long time trajectories: when the number of NP-ligated motors N m increased, run-times and run-lengths were enhanced and mean velocities were somewhat decreased. Moreover, the dependence of the velocity on run-time followed a universal curve, regardless of the system composition. Model simulations also demonstrated left- and right-handed helical motion and revealed self-regulation of the number of microtubule-bound, actively transporting dynein motors. This number was stochastic along trajectories and was distributed mainly between one, two, and three motors, regardless of N m . We propose that this self-regulation allows our synthetic NPs to achieve persistent motion that is associated with major helicity. Such a helical motion might affect obstacle bypassing, which can influence active transport efficiency when facing the crowded environment of the cell.

Indirect measurement of the respiratory exchange ratio (RER) has been shown to predict the occurrence of postoperative complications after major open non-cardiac surgery. Our main objective was to demonstrate the ability of the RER, indirectly measured by the anaesthesia respirator, to predict the occurrence of postoperative complications following laparoscopic surgery. We performed an observational, prospective and monocentric study. Haemodynamic and respiratory parameters were collected at several timepoints to calculate the RER by a non-volumetric method: RER = (FetCO 2 -FiCO 2 )/(FiO 2 -FetO 2 ). Fifty patients were prospectively included. Nine patients (18%) had at least one postoperative complication. The mean RER was significantly higher for the subgroup of patients with complications than the subgroup without (1.04 ± 0.27 vs 0.88 ± 0.13, p < 0.05). The RER could predict the occurrence of post-operative complications with an area under the ROC curve of 0.73 (95% CI 0.59-0.85, p = 0.021). The best cut off was 0.98, with a sensitivity of 56% and a specificity of 88%. One hour after insufflation, the FiO 2 -FetO 2 difference was significantly lower and the RER was significantly higher in the complications subgroup than in the subgroup without complications (4.4/- 1.6% vs 5.8/- 1.2%, p = 0.001 and 0.95 [0.85-1.04] vs 0.83 [0.75-0.92], p = 0.04, respectively). The RER measured during laparoscopic surgery can predict the occurrence of postoperative complications.Trial registration The objectives and procedures of the study was registered at Clinicaltrials.gov (NCT03751579); date: November 23, 2018., (© 2020. Springer Nature B.V.)

The SARS CoV-2 (COVID-19) pandemic and the enforced lockdown have reduced the use of surface and air transportation. This study investigates the impact of the lockdown restrictions in India on atmospheric composition, using Sentinel-5Ps retrievals of tropospheric NO 2 concentration and ground-station measurements of NO 2 and PM 2.5 between March-May in 2019 and 2020. Detailed analysis of the changes to atmospheric composition are carried out over six major urban areas (i.e. Delhi, Mumbai, Kolkata, Chennai, Bangalore, and Hyderabad) by comparing Moderate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth (AOD) and land surface temperature (LST) measurements in the lockdown year 2020 and pre-lockdown (2015-2019). Satellite-based data showed that NO 2 concentration reduced by 18% (Kolkata), 29% (Hyderabad), 32-34% (Chennai, Mumbai, and Bangalore), and 43% (Delhi). Surface-based concentrations of NO 2 , PM 2.5 , and AOD also substantially dropped by 32-74%, 10-42%, and 8-34%, respectively over these major cities during the lockdown period and co-located with the intensity of anthropogenic activity. Only a smaller fraction of the reduction of pollutants was associated with meteorological variability. A substantial negative anomaly was found for LST both in the day (-0.16 °C to -1 °C) and night (-0.63 °C to -2.1 °C) across select all cities, which was also consistent with air temperature measurements. The decreases in LST could be associated with a reduction in pollutants, greenhouse gases and water vapor content. Improvement in air quality with lower urban temperatures due to lockdown may be a temporary effect, but it provides a crucial connection among human activities, air pollution, aerosols, radiative flux, and temperature. The lockdown for a shorter-period showed a significant improvement in environmental quality and provides a strong evidence base for larger scale policy implementation to improve air quality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Dietary restriction (DR) extends healthy lifespan in diverse species. Age and nutrient-related changes in the abundance of microRNAs (miRNAs) and their processing factors have been linked to organismal longevity. However, the mechanisms by which they modulate lifespan and the tissue-specific role of miRNA-mediated networks in DR-dependent enhancement of lifespan remains largely unexplored. We show that two neuronally enriched and highly conserved microRNAs, miR-125 and let-7 mediate the DR response in Drosophila melanogaster . Functional characterization of miR-125 demonstrates its role in neurons while its target chinmo acts both in neurons and the fat body to modulate fat metabolism and longevity. Proteomic analysis revealed that Chinmo exerts its DR effects by regulating the expression of FATP, CG2017, CG9577, CG17554, CG5009, CG8778, CG9527 , and FASN1 . Our findings identify miR-125 as a conserved effector of the DR pathway and open the avenue for this small RNA molecule and its downstream effectors to be considered as potential drug candidates for the treatment of late-onset diseases and biomarkers for healthy aging in humans., Competing Interests: MP, SB, SB, AY, NS, JT, PK, GC No competing interests declared, (© 2021, Pandey et al.)

Quorum quenching (QQ) is the ability to interfere with bacterial cell to cell communication, known as quorum sensing (QS). QQ enzymes that degrade or modify acyl homoserine lactones (AHLs) have been attracting increasing interest as promising agents for inhibiting QS-mediated bacterial pathogenicity. Plant pathogens from the genus Erwinia cause diseases in several economically important crops. Fire blight is a devastating plant disease caused by Erwinia amylovora , affecting a wide range of host species within the Rosaceae and posing a major global threat for commercial apple and pear production. While QS has been described in Erwinia species, no AHL-degrading enzymes were identified and characterized. Here, phylogenetic analysis and structural modeling were applied to identify an AHL lactonase in E. amylovora (dubbed EaAiiA). Following recombinant expression and purification, the enzyme was biochemically characterized. EaAiiA lactonase activity was dependent on metal ions and effectively degraded AHLs with high catalytic efficiency. Its highest specific activity ( k cat /K M value) was observed against one of the AHLs (3-oxo-C6 - homoserine lactone) secreted from E. amylovora . Exogenous addition of the purified enzyme to cultures of E. amylovora reduced the formation of levan, a QS-regulated virulence factor, by 40% and the transcription level of the levansucrase-encoding gene by 55%. Furthermore, preincubation of E. amylovora cultures with EaAiiA inhibited the progress of fire blight symptoms in immature Pyrus communis fruits. These results demonstrate the ability of the identified enzyme from E. amylovora to act as a quorum-quenching lactonase.

Introduction: It has been suggested that dynamic arterial elastance (Ea dyn ) can predict decreases in arterial pressure in response to changing norepinephrine levels. The objective of this study was to determine whether Ea dyn is correlated with determinants of the vascular waterfall [critical closing pressure (CCP) and systemic arterial resistance (SARi)] in patients treated with norepinephrine. Materials and Methods: Patients treated with norepinephrine for vasoplegia following cardiac surgery were studied. Vascular and flow parameters were recorded immediately before the norepinephrine infusion and then again once hemodynamic parameters had been stable for 15 min. The primary outcomes were Ea dyn and its associations with CCP and SARi. The secondary outcomes were the associations between Ea dyn and vascular/flow parameters. Results: At baseline, all patients were hypotensive with Ea dyn of 0.93 [0.47;1.27]. Norepinephrine increased the arterial blood pressure, cardiac index, CCP, total peripheral resistance (TPRi), arterial elastance, and ventricular elastance and decreased Ea dyn [0.40 (0.30;0.60)] and SARi. Ea dyn was significantly associated with arterial compliance (C A ), CCP, and TPRi ( p < 0.05). Conclusion: In patients with vasoplegic syndrome, Ea dyn was correlated with determinants of the vascular waterfall. Ea dyn is an easy-to-read functional index of arterial load that can be used to assess the patient's macro/microcirculatory status. Clinical Trial Registration: ClinicalTrials.gov #NCT03478709., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bar, Nguyen, Abou-Arab, Dupont, Bouhemad and Guinot.)

Background: Preschool-age children with developmental disabilities (DD) have higher prevalence of obesity than children without DD. This study aimed to explore the relationship between parent perception of their children's anthropometric phenotype and child body mass index (BMI) z score change over one school year among preschoolers with DD., Methods: The analysis consisted of a subsample (N  =  64) of children with DD from a larger randomized controlled trial to test an obesity prevention program in the childcare center setting. Parents ranks their child's anthropometric phenotype on a visual silhouette chart on a scale from 1 (underweight) to 7 (obese) and that rank score is compared to their BMI z score change over one school year., Results: The majority (75%) of parents with an obese child underestimated their child's anthropometric phenotype while 7% parents with a non-obese child overestimated. Parent overestimation of child anthropometric phenotype status is associated with increased BMI z score change over 1 school year among preschool-age children with disabilities., Conclusion: Parental overestimation of child anthropometric phenotype status was associated with weight gain in preschool children with DD after one school year.