Convalescent plasma for COVID-19 in hospitalised patients : an open-label, randomised clinical trial

Background: The effects of convalescent plasma (CP) therapy in hospitalised patients with coronavirus disease 2019 (COVID-19) remain uncertain. This study investigates the effect of CP on clinical improvement in these patients. Methods: This is an investigator-initiated, randomised, parallel arm, open-label, superiority clinical trial. Patients were randomly (1:1) assigned to two infusions of CP plus standard of care (SOC) or SOC alone. The primary outcome was the proportion of patients with clinical improvement 28 days after enrolment. Results: A total of 160 (80 in each arm) patients (66.3% critically ill, 33.7% severely ill) completed the trial. The median (interquartile range (IQR)) age was 60.5 (48–68) years; 58.1% were male and the median (IQR) time from symptom onset to randomisation was 10 (8–12) days. Neutralising antibody titres >1:80 were present in 133 (83.1%) patients at baseline. The proportion of patients with clinical improvement on day 28 was 61.3% in the CP+SOC group and 65.0% in the SOC group (difference −3.7%, 95% CI −18.8–11.3%). The results were similar in the severe and critically ill subgroups. There was no significant difference between CP+SOC and SOC groups in pre-specified secondary outcomes, including 28-day mortality, days alive and free of respiratory support and duration of invasive ventilatory support. Inflammatory and other laboratory marker values on days 3, 7 and 14 were similar between groups. Conclusions: CP+SOC did not result in a higher proportion of clinical improvement on day 28 in hospitalised patients with COVID-19 compared to SOC alone

Feeding Induced by Cannabinoids Is Mediated Independently of the Melanocortin System

Cannabinoids, the active components of marijuana, stimulate appetite, and cannabinoid receptor-1 (CB1-R) antagonists suppress appetite and promote weight loss. Little is known about how CB1-R antagonists affect the central neurocircuitry, specifically the melanocortin system that regulates energy balance

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

FLORESTA URBANA, SOLUÇÕES BASEADAS NA NATUREZA E PAISAGEM: PLANEJAMENTO E PROJETO NA CIDADE DE SÃO CARLOS (SP)

Urbanization and the conflicts generated with the environment are one of the most challenging issues of our times, generating the need to create new and different approaches to urban territory such as Urban Forest, Ecosystem Services, Open Space System and Green Infrastructure and, more recently, Nature-based Solutions. However, the incorporation of these concepts in normative instruments, bases for the implementation of public policies, is still a great challenge in Latin American cities. Given the above, the aim of this article was to discuss and present the case of the city of São Carlos (SP), as an experience of planning an Urban Forest based on SbN, which is structured from a System of Open Spaces, shaped by legal bases. The method used was divided into three parts, the first being a historical-temporal review of the creation of legislation and planning cartographies of the last decade, the second analyzes the articulation of these instruments and cartographies and the third part presents a process of Landscape planning and design, based on a System of Open Spaces and Green Infrastructure. The instruments that sequentially marked a history of achievements ranging from the creation of Protection and Recovery Areas of Water Sources - APREM; Areas of Environmental Interest – AIA; Complementary Green Strips – FVC; Urban Parks and a System of Municipal Parks - SIPAM. It is hoped that from this article, paths for a more systemic planning can be glimpsed, anchored in cultural construction processes that integrate different agents and that are based on the notion of public interest and on closer relations between man and nature.La urbanización y los conflictos generados con el medio ambiente son uno de los temas más desafiantes de nuestro tiempo, generando la necesidad de crear nuevos y diferentes enfoques del territorio urbano como Bosque Urbano, Servicios Ecosistémicos, Sistema de Espacio Abierto e Infraestructura Verde y, más recientemente, Soluciones basadas en la naturaleza. Sin embargo, la incorporación de estos conceptos en instrumentos normativos, bases para la implementación de políticas públicas, sigue siendo un gran desafío en las ciudades latinoamericanas. Dado lo anterior, el objetivo de este artículo fue discutir y presentar el caso de la ciudad de São Carlos (SP), como una experiencia de planificación de un Bosque Urbano basado en SbN, que se estructura a partir de un Sistema de Espacios Abiertos, conformado por bases legales. El método utilizado se dividió en tres partes, siendo la primera una revisión histórico-temporal de la creación de legislación y cartografías urbanísticas de la última década, la segunda analiza la articulación de estos instrumentos y cartografías y la tercera parte presenta un proceso de planificación del paisaje. y diseño, basado en un Sistema de Espacios Abiertos e Infraestructura Verde. Los instrumentos que marcaron secuencialmente una historia de logros que van desde la creación de Áreas de Protección y Recuperación de Fuentes de Agua - APREM; Áreas de interés ambiental - AIA; Tiras verdes complementarias - FVC; Parques Urbanos y Sistema de Parques Municipales - SIPAM. Se espera que a partir de este artículo se vislumbren caminos para una planificación más sistémica, anclada en procesos de construcción cultural que integran diferentes agentes y que se guían por la noción de interés público y relaciones más estrechas entre el hombre y la naturaleza.A urbanização e os conflitos gerados com o meio ambiente se apresentam como uma das mais desafiadoras questões dos nossos tempos, gerando a necessidade da criação de novas e diferentes abordagens sobre o território urbano como Floresta Urbana, Serviços Ecossistêmicos, Sistema de Espaços Livres e Infraestrutura Verde e, mais recentemente, Soluções baseadas na Natureza. Contudo, a incorporação desses conceitos em instrumentos normativos, bases para implantação de políticas públicas, ainda é um grande desafio nas cidades da América Latina. Diante do exposto, o objetivo desse artigo foi discutir e apresentar o caso do município de São Carlos (SP), como uma experiência de planejamento de Floresta Urbana com base em SbN, que se estrutura a partir de um Sistema de Espaços Livres, moldado por bases legais. O método utilizado dividiu-se em três partes, sendo a primeira um resgate histórico-temporal da criação das legislações e das cartografias de planejamento da última década, a segunda analisa a articulação desses instrumentos e dessas cartografias e na terceira parte apresenta-se um processo de planejamento e projeto de Paisagem, baseado em um Sistema de Espaços Livres e de Infraestrutura Verde. Os instrumentos marcaram, sequencialmente, um histórico de conquistas, como a criação de Áreas de Proteção e Recuperação de Mananciais - APREM; Áreas de Interesse Ambiental - AIA; Faixas Verdes Complementares - FVC; Parques Urbanos e a proposta de um Sistema de Parques Municipais - SIPAM. Contribui-se, assim, para a construção de caminhos para um planejamento mais sistêmico, ancorado em processos de construção cultural que integrem diferentes agentes e que sejam pautados na noção de interesse público e nas relações mais próximas entre homem e natureza

The GST domain of GDAP1 is a frequent target of mutations in the dominant form of axonal Charcot Marie Tooth type 2K

International audienceBackground: Mutations in GDAP1 associate with both demyelinating (CMT4A) and axonal (CMT2K) forms of CMT. While CMT4A shows recessive inheritance, CMT2K can present with either recessive (AR-CMT2K) or dominant segregation pattern (AD-CMT2K), the latter being characterized by milder phenotypes and later onset. The majority of the GDAP1 mutations are associated with CMT4A and AR-CMT2K, with only 4 heterozygous mutations identified in AD-CMT2K. Methods: We screened GDAP1 gene in a series of 43 index patients, 39 with CMT2 and 4 with intermediate CMT, with both sporadic and familial occurrence of the disease. Results: Three novel mutations were identified in three families with dominant segregation of the disease: two missense changes, p.Arg226Ser and p.Ser34Cys, affecting the GST domain of the GDAP1 protein and a novel deletion (c.23delAG) leading to early truncation of the protein upstream the GST domain. Wide variability in clinical presentation is shared by all three families mostly in terms of age at onset and disease severity. A rare variant p.Gly269Arg, located within the GST domain, apparently acts as phenotype modulator in the family carrying the deletion. Conclusion: The results obtained reveal a GDAP1 mutation frequency of 27% in the dominant families analyzed, a figure still unreported for this gene, thus suggesting that GDAP1 involvement in dominant CMT2 might be higher than expected

Elderly caregivers profile and oral health perception

The aim of this study was to evaluate the profile and the oral health perception of elderly caregivers who in charge of giving assistance to three benefiting institutions in the city of Araçatuba, Brazil. A form was filled in by the interviewers according to the caregivers' answers. In relation to schooling level, 83.3% have a nurse aid's technician course and 16.7% don't present any type of technical formation. More than half of the interviewed caregivers (61.11%) reported that they started working for necessity, not for affinity. It was detected lack of oral health perception which showed that most of the caregivers need more knowledge of the most prevalent oral diseases. Most of them (55.56%) believe that tooth loosing is part of aging. According to the obtained results, it was proved that caregivers need more information about oral health related to elderly