Astrocytes: biology and pathology

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

The state of cardiac surgery in EthiopiaCentral MessagePerspective

Objectives: Six billion people globally do not have access to cardiac surgical care. In this study, we aimed to describe state of cardiac surgery in Ethiopia. Methods: Data on status of local cardiac surgery collected from surgeons and cardiac centers. Medical travel agents were interviewed about number of cardiac patients who were assisted to travel abroad for surgery. Historical data and number of patients treated by non-governmental organizations were collected via interviews and by accessing existing databases. Results: Patients access cardiac care via 3 avenues: mission-based, abroad referral, and care at local centers. Traditionally, the first 2 have been the main mode of access; however, since 2017, an entirely local team has begun performing heart surgery in the country. Currently, surgical cardiac care is provided at 4 local centers: a charity organization, a tertiary public hospital, and 2 for-profit centers. Procedures at the charity center are provided for free, whereas in others, patients mostly pay out of pocket. There are only 5 cardiac surgeons for 120 million people. More than 15,000 patients are on waitlist for surgery, mainly because of lack of consumables and limited numbers of centers and workforce. Conclusions: There is a change in the trend from non-governmental mission- and referral-based care toward care in local centers in Ethiopia. The local cardiac surgery workforce is growing but still insufficient. The number of procedures is limited with long wait lists due to limited workforce, infrastructure, and resources. All stakeholders should work on training more workforce, providing consumables, and creating feasible financing schemes

Clinical and biochemical profiles in response to treatment of uncomplicated severe acute malnutrition : preliminary results from the multi-centric optidiag study

Background: The use of mid-upper arm circumference (MUAC) as the sole assessment tool for identifying children with severe acute malnutrition (SAM) is based on the assumption that those with low weight-for-height z-scores (WHZ) are at lower risk for morbidity and mortality than those with low MUAC. However, the pathophysiology and functional severity associated with different anthropometric phenotypes of SAM have not been well-characterized. Objective: The aim of this study was to describe and compare the response to medico-nutritional care in children with uncomplicated SAM identified among three anthropometric phenotypes: both low MUAC and low WHZ, low MUAC only, and low WHZ only. Methods: A multicentric cohort study was conducted in uncomplicated, non-edematous children aged 6-59 months with SAM in Bangladesh, Burkina Faso and Liberia. Alongside routine anthropometric measurements, a wide range of critical indicators of clinical and nutritional status and viability was collected at admission, two weeks and eight weeks, including serum leptin, a marker of adipose tissue reserves associated with mortality risk in SAM. Results: A total of 282 patients were included in the study (n=103 low MUAC only, n=89 low WHZ only, n=90 both deficits). Leptin levels at baseline were lower in children with combined defects in WHZ and MUAC and those with low WHZ only than in children with low MUAC alone. During eight weeks of treatment, the weight gain velocity and plasma leptin levels rose more quickly in children with combined defects than in children in the other two groups. At eight weeks those with combined defects and with low WHZ only had higher prevalence of pneumonia than children with low MUAC only. Leptin concentrations correlated far more strongly with WHZ (r=0.41, p<0.001) than with MUAC (r=0.12, p=0.074) at two weeks and eight weeks (r=0.46, r=0.32, respectively). On the other hand, the increase in leptin levels after eight weeks correlated more strongly with MUAC change (r=0.41, p<0.001) than with WHZ change (r=0.29, p<0.001). Conclusion: The correlation indicates that leptin has prognostic value for tracking adipose tissue accretion during the recovery process. Our previous analysis at admission showed that children with low WHZ only had equally or more severe deficits in nutritional and health status than children with low MUAC. The present analyses throughout recovery suggest that these children respond similarly to treatment compared with those with both deficits. Therefore, we suggest retaining WHZ as an independent criterion for diagnosing SAM, in line with current WHO recommendations. Presented at: The 11th Belgian Nutrition Society Annual Symposium; April 24th, 2023, Paleis der Academiën, Brussels, Belgium; “Nutrition and Physical Activity: from Basic Scientific to Daily Practice.” Presenting Author: Lishi Deng, MSc, PhD Candidate, [email protected]

Effectiveness of Bubble Continuous Positive Airway Pressure (BCPAP) for Treatment of Children Aged 1–59 Months with Severe Pneumonia and Hypoxemia in Ethiopia: A <i>Pragmatic Cluster Randomized Controlled Clinical Trial</i>

Despite the beneficial effect of bubble continuous positive airway pressure (BCPAP) oxygen therapy for children with severe pneumonia under the supervision of physicians that has been shown in different studies, effectiveness trials in developing country settings where low-flow oxygen therapy is the standard of care are still needed. Thus, the aim of this study is to assess the effectiveness of bubble CPAP oxygen therapy compared to the WHO standard low-flow oxygen therapy among children hospitalized with severe pneumonia and hypoxemia in Ethiopia. This is a cluster randomized controlled trial where six district hospitals are randomized to BCPAP and six to standard WHO low-flow oxygen therapy. The total sample size is 620 per arm. Currently, recruitment of the patients is still ongoing where the management and follow-up of the enrolled patients are performed by general physicians and nurses under the supervision of pediatricians. The primary outcome is treatment failure and main secondary outcome is death. We anticipate to complete enrollment by September 2022 and data analysis followed by manuscript writing by December 2022. Findings will also be disseminated in December 2022. Our study will provide data on the effectiveness of BCPAP in treating childhood severe pneumonia and hypoxemia in a real-world setting