The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Hierarchical control in microgrid

It is required to utilize several control loops together to increase reliability and performance of microgrids. The current and voltage magnitudes, frequency and angle information, active and reactive power data provide the involved feedback for normal and island mode operations of microgrid. The hierarchical control structure of microgrid is responsible for microgrid synchronization, optimizing the management costs, control of power share with neighbor grids and utility grid in normal mode while it is responsible for load sharing, distributed generation, and voltage/frequency regulation in both normal and islanding operation modes. The load control of microgrid is performed by using more sophisticated electronic devices as well as regular circuit breakers. This regulation capacity could be improved since the ESS decreases the dependency to primary power sources. Although several improvements have been experienced in microgrid control strategies, the most intensive research areas are listed as decreasing the structural instability, improving the system performance to increase reliability, monitoring the harmonic contents, scaling the control infrastructure, enhancing the operation characteristics in error states, and implementing new control algorithms for normal and islanding operation. The microgrid system has hierarchical control infrastructure in different levels similar to conventional grids. The microgrid requires enhanced control techniques to manage any level of system. Safe operation of microgrid in both operation modes and connection and disconnection between microgrid and utility grid are depended to microgrid control techniques. The controllers should ensure to operate the system regarding to predefined circumstances and efficiency requirements. The hierarchical control methods and applications of microgrid infrastructure are presented in the proposed chapter

Influence of COVID-19 on lifestyle behaviors in the Middle East and North Africa Region: a survey of 5896 individuals

Background: Coronavirus disease (COVID-19) pandemic has affected health and lifestyle behaviors of people globally. This project aims to identify the impact of COVID-19 on lifestyle behavior of individuals in the Middle East and North Africa (MENA) region during confinement. Methods: We conducted an online survey in 17 countries (Egypt, Jordan, United Arab Emirates, Kuwait, Bahrain, Saudi Arabia, Oman, Qatar, Yemen, Syria, Palestine, Algeria, Morocco, Libya, Tunisia, Iraq, and Sudan) from the MENA region on August and September 2020. The questionnaire included self-reported information on lifestyle behaviors, including physical activity, eating habits, smoking, watching television, social media use and sleep before and during the pandemic. Logistic regression was performed to analyze the impact of COVID-19 on lifestyle behaviors. Results: A total of 5896 participants were included in the final analysis and 62.8% were females. The BMI of the participants was 25.4 &plusmn; 5.8&nbsp;kg/m2. Around 38.4% of the participants stopped practicing any physical activities during the confinement (P &lt; 0.001), and 57.1% reported spending more than 2&nbsp;h on social media (P &lt; 0.001). There were no significant changes in smoking habits. Also, 30.9% reported an improvement in their eating habits compared with 24.8% reported worsening of their eating habits. Fast-food consumption decreased significantly in 48.8% of the study population. This direct/indirect exposure to COVID-19 was associated with an increased consumption of carbohydrates (OR = 1.09; 95% CI = 1.02&ndash;1.17; P = 0.01), egg (OR = 1.08; 95% CI = 1.02&ndash;1.16; P = 0.01), sugar (OR = 1.09; 95% CI = 1.02&ndash;1.16; P = 0.02), meat, and poultry (OR = 1.13; 95% CI = 1.06&ndash;1.20; P &lt; 0.01). There was also associated increase in hours spent on watching television (OR = 1.07; 95% CI = 1.02&ndash;1.12; P &lt; 0.01) and social media (OR = 1.09; 95% CI = 1.01&ndash;1.18; P = 0.03). However, our results showed a reduction in sleeping hours among those exposed to COVID-19 infection (OR = 0.85; 95% CI = 0.77&ndash;0.94; P &lt; 0.01). Conclusions: The COVID-19 pandemic was associated with an increase in food consumption and sedentary life. Being exposed to COVID-19 by direct infection or through an infected household is a significant predictor of amplifying these changes. Public health interventions are needed to address healthy lifestyle behaviors during and after the COVID-19 pandemic