Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Complete mitochondrial genome of nearly threatened freshwater ornamental fish, Microphis deocata and its phylogenetic relationship within Syngnathidae

Microphis deocata (deocata pipefish), belonging to family Syngnathidae, is one of the important indigenous ornamental fish species listed as near threatened in the IUCN red list. Here, we first report the complete mitochondrial genome of deocata pipefish using Illumina next-generation sequencing platform. The total length of the mitogenome is 16,526 bp. It encompasses 13 protein coding genes, 2 ribosomal rRNAs, and 22 tRNAs. The WANCY region (a cluster of five tRNA genes) contains the 50 bp OL light strand origin of replication. Phylogenetic analysis of Syngnathidae revealed M. deocata to cluster with Oostethus manadensis, forming a sister group with Doryrhamphus japonicas and Dunckerocampus dactyliophorus. The mitochondrial genome sequence data generated in the present study will play an important role in population genetic analysis and developing conservation strategies for this species

Raman spectroscopy with a 1064-nm wavelength laser as a potential molecular tool for prostate cancer diagnosis : a pilot study.

Raman spectroscopy is widely used to investigate the structure and property of the molecules from their vibrational transitions and may allow for the diagnosis of cancer in a fast, objective, and nondestructive manner. This experimental study aims to propose the use of the 1064-nm wavelength laser in a Raman spectroscopy and to evaluate its discrimination capability in prostate cancer diagnosis. Seventy-four spectra from patients who underwent radical prostatectomy were evaluated. The acquired signals were filtered, normalized, and corrected for possible oscillations in the laser intensity and fluorescence effects. Wilcoxon tests revealed significant differences between the benign and malign samples associated with the deformation vibration characteristic of nucleic acids, proteins, and lipids. A classifier based on support vector machines was able to predict the Gleason scores of the samples with 95% of accuracy, opening a perspective for the use of the 1064-nm excitatory wavelength in prostatic cancer diagnosis

Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus.

Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus

Fluorescence-based <i>in vitro</i> assays.

<p>Values are expressed as the mean ± SEM (n = 4). No significant differences were registered for the different SWCNT-PEG concentrations (<i>p</i>>0.05).</p><p>Fluorescence-based <i>in vitro</i> assays.</p

Effect of SWCNT-PEG dispersions on lipid peroxidation (LPO) in the hippocampus (A) 1 and (B) 7 days after infusion.

<p>Values are expressed as the mean ± SEM, n = 4–6. No significant difference in LPO levels was observed between the groups (<i>p</i>>0.05).</p

Effect of SWCNT-PEG dispersions on (A) acquisition and (B) persistence of contextual fear memory.

<p>Schematics of the procedures used in the experiments are presented above the graphs. Values are expressed as the mean ± SEM, n = 10–12. No significant difference in time spent in freezing was observed between the groups (<i>p</i>>0.05).</p

Effect of SWCNT-PEG dispersions on total antioxidant capacity against peroxyl radicals (ACAP) in the hippocampus (A) 1 and (B) 7 days after infusion.

<p>Values are expressed as the mean ± SEM, n = 4–6. ^#<i>p</i><0.05 vs. 2.1 mg/mL SWCNT-PEG and vs. the control group; *<i>p</i> <0.05 vs. the control group.</p

Raman spectroscopy of rat hippocampal homogenates 1 and 7 days after SWCNT-PEG dispersions infusion.

<p>(A) Raman spectrum acquired from SWCNT-PEG dispersion at 2.1 mg/mL. (B) Detection curve of SWCNT-PEG based on radial breath mode (RBM). Raman spectra in hippocampal homogenates (C) 1 and (D) 7 days after infusion. Dotted squares indicate the RBM region. Ct+: positive control; Ct-: negative control.</p

Effect of SWCNT-PEG on the number of crossings in open field task.

<p>Values expressed as the mean ± SEM (n = 6). Animals tested at 30 min were subjected to another test-session at 1 day. No significant differences were observed between the groups (<i>p</i>>0.05).</p><p>Effect of SWCNT-PEG on the number of crossings in open field task.</p