Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Barrier immune effectors are maintained during transition from nurse to forager in the honey bee.

Foragers facilitate horizontal pathogen transmission in honey bee colonies, yet their systemic immune function wanes during transition to this life stage. In general, the insect immune system can be categorized into mechanisms operating at both the barrier epithelial surfaces and at the systemic level. As proposed by the intergenerational transfer theory of aging, such immunosenescence may result from changes in group resource allocation. Yet, the relative influence of pathogen transmission and resource allocation on immune function in bees from different stages has not been examined in the context of barrier immunity. We find that expression levels of antimicrobial peptides (AMPs) in honey bee barrier epithelia of the digestive tract do not follow a life stage-dependent decrease. In addition, correlation of AMP transcript abundance with microbe levels reveals a number of microbe-associated changes in AMPs levels that are equivalent between nurses and foragers. These results favor a model in which barrier effectors are maintained in foragers as a first line of defense, while systemic immune effectors are dismantled to optimize hive-level resources. These findings have important implications for our understanding of immunosenescence in honey bees and other social insects

Similar midgut barrier AMP expression in nurse and forager stages.

<p>Individual levels of the six honey bee AMPs relative to <i>β-actin</i> in midgut tissue for Nurses (n = 46) and Foragers (n = 45), as assessed by behavior and location cues, for <i>Abaecin</i> (A), <i>Hymenoptaecin</i> (B), <i>Defensin 1</i> (C), <i>Defensin 2</i> (D), <i>Apidaecin</i> (E), and <i>Apisimin</i> (F) from the six trials. Boxes show 1st and 3rd interquartile range with line denoting medians. Whiskers encompass 95% of the individuals. Outliers are denoted with filled circles.</p

NFκB-family transcriptional activators of the Toll and Imd pathways are similar in nurses and foragers.

<p>Individual levels of <i>Relish</i> (A) and <i>Dorsal-like 1a</i> (B) relative to <i>β-actin</i> in midgut tissue from Nurses (n = 23) and Foragers (n = 22) from trials 1, 3, and 5. Boxes show 1st and 3rd interquartile range with line denoting medians. Whiskers encompass 95% of the individuals. Outliers are denoted with filled circles.</p

Nurse and forager AMP expression in fatbody tissue.

<p>Individual levels of the six honey bee AMPs relative to <i>β-actin</i> in abdominal tissue for Nurse and Foragers, as assessed by behavior and location cues, for <i>Abaecin</i> (A), <i>Hymenoptaecin</i> (B), <i>Defensin 1</i> (C), <i>Defensin 2</i> (D), <i>Apidaecin</i> (E), and <i>Apisimin</i> (F) from trials 3 and 4. Boxes show 1st and 3rd interquartile range with line denoting medians. Whiskers encompass 95% of the individuals. Outliers are denoted with filled circles.</p

Differences in AMP expression based on level s of DWV and of all bacteria are similar in nurse and foragers.

<p>Correlation of levels of <i>Apidaecin</i> (n = 92), with levels of DWV (A) and <i>Defensin 1</i> (B) and <i>Apidaecin</i> (C), with levels of all bacteria (16S RNA).</p

Broad range of AMP production in midgut barrier epithelium.

<p>Individual levels of the six honey bee AMPs (<i>Abaecin (n = 91), Hymenoptaecin (n = 91), Defensin 1 (n = 92)</i>, <i>Defensin 2 (n = 91), Apidaecin</i> (<i>n = 92)</i>, and <i>Apisimin</i> (<i>n = 92)</i>) and the immune signaling protein <i>Relish</i> (<i>n = 91)</i> relative to <i>β-actin</i> in midgut tissue from both nurses and foragers from multiple hives. Boxes show 1st and 3rd interquartile range with line denoting medians. Whiskers encompass 95% of the individuals. Outliers are denoted with filled circles.</p

Differences in AMP expression between <i>Nosema</i> infected and non-infected bees are similar in nurse and foragers.

<p>Levels of the six honey bee AMPs (<i>Abaecin</i> (n = 91), <i>Hymenoptaecin</i> (n = 91), <i>Defensin 1</i> (n = 92), <i>Defensin 2</i> (n = 91), <i>Apidaecin</i> (n = 92), and <i>Apisimin</i> (n = 92) relative to <i>β-actin</i> in midgut tissue from bees that were positive (+) or negative (−) for <i>Nosema ceranae</i> (A). Levels of <i>Abaecin</i> (B) and <i>Apidaecin</i> (C) relative to <i>β-actin</i> in midgut tissue from bees that were positive (+) or negative (−) for <i>Nosema ceranae</i> for all bees and split into nurses and foragers. Boxes show 1st and 3rd interquartile range with line denoting medians. Whiskers encompass 95% of the individuals. Outliers are denoted with filled circles.</p

Splenic infarction in sickle cell trait: A comprehensive systematic review of case studies

Abstract Sickle cell trait (SCT), a commonly asymptomatic condition, has many associated clinical complications that upon presentation, can be very difficult to attribute to SCT. The effects of SCT on the spleen, for example, are not completely understood, though there have been a number of case reports detailing related complications in diverse populations. Our objective was to perform the first comprehensive case report review of splenic infarction in SCT patients to highlight the relevance of this seemingly rare condition. We conducted an extensive literature search reviewing case reports and case series of acute splenic infarctions from 1970 to 2020. This comprehensive search resulted in 54 articles with a total of 85 individuals. The ages ranged from 7 to 65, 12% were female. Individuals were of African‐American (26%), European (16%), South Asian (13%), Middle Eastern (7%), Latin American (7%), North or East African (4%), Mediterranean (4%), West African (1%), and unknown (22%) origins. Although splenic infarct in SCT patients has been associated with high altitudes, 39% of cases reporting altitude occurred below 3000 m. Among cases where HbS values were recorded, 88% occurred in individuals with HbS levels higher than 35%, suggesting that high HbS values may be a risk factor for splenic infarction. Our findings indicate that splenic infarct occurs across a wide range of demographic populations and environmental settings. While our understanding of SCT evolves, the findings here suggest that future advances in research and healthcare could benefit more from real‐time surveillance and registry initiation for various SCT outcomes such as splenic infarct