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This study aimed to uncover novel genes associated with neurodevelopmental disorders (NDD) by leveraging recent large-scale de novo burden analysis studies to enhance a virtual gene panel used in a diagnostic setting. We re-analyzed historical trio-exome sequencing data from 745 individuals with NDD according to the most recent diagnostic standards, resulting in a cohort of 567 unsolved individuals. Next, we designed a virtual gene panel containing candidate genes from three large de novo burden analysis studies in NDD and prioritized candidate genes by stringent filtering for ultra-rare de novo variants with high pathogenicity scores. Our analysis revealed an increased burden of de novo variants in our selected candidate genes within the unsolved NDD cohort and identified qualifying de novo variants in seven candidate genes: RIF1, CAMK2D, RAB11FIP4, AGO3, PCBP2, LEO1, and VCP. Clinical data were collected from six new individuals with de novo or inherited LEO1 variants and three new individuals with de novo PCBP2 variants. Our findings add additional evidence for LEO1 as a risk gene for autism and intellectual disability. Furthermore, we prioritize PCBP2 as a candidate gene for NDD associated with motor and language delay. In summary, by leveraging de novo burden analysis studies, employing a stringent variant filtering pipeline, and engaging in targeted patient recruitment, our study contributes to the identification of novel genes implicated in NDDs.
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Tuberculosis (TB) is the leading infectious cause of morbidity and mortality globally. Despite available tools for preventing, finding, and treating TB, many people with TB remain undiagnosed. In high-incidence settings, TB transmission is ubiquitous within the community, affecting both high-risk groups and the general population. In fact, most people who develop TB come from the general population. To disrupt the chain of transmission that sustains the TB epidemic, we need to find and treat everyone with infectious TB as early as possible, including those with minimal symptoms or subclinical TB who are unlikely to present for care. Important elements of an effective active case-finding strategy include effective social mobilisation and community engagement, using sensitive screening tools that can be used at scale, and embracing population-wide screening in high-incidence ('hot spot') areas. We require a better description of feasible delivery models, 'real-life' impact and cost effectiveness to enable wider implementation.
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Up to 25% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit postacute cognitive sequelae. Although millions of cases of coronavirus disease 2019 (COVID-19)-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1 (IL-1), a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of individuals with COVID-19. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 Beta variant leads to central nervous system infiltration of Ly6Chi monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1ß and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes postacute cognitive deficits. Vaccination with a low dose of adenoviral-vectored spike protein prevents hippocampal production of IL-1ß during breakthrough SARS-CoV-2 infection, loss of neurogenesis and subsequent memory deficits. Our study identifies IL-1ß as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new mouse model that is prevented by vaccination.
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COVID-19 , Hipocampo , Interleucina-1beta , Transtornos da Memória , Camundongos Endogâmicos C57BL , Neurogênese , SARS-CoV-2 , Animais , Interleucina-1beta/metabolismo , Interleucina-1beta/imunologia , Camundongos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Hipocampo/imunologia , Hipocampo/metabolismo , Transtornos da Memória/imunologia , Neurogênese/imunologia , Vacinação , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas contra COVID-19/imunologia , Masculino , Humanos , Microglia/imunologia , Microglia/metabolismo , Modelos Animais de Doenças , Receptores Tipo I de Interleucina-1/metabolismo , Receptores Tipo I de Interleucina-1/genética , Monócitos/imunologia , Monócitos/metabolismo , FemininoRESUMO
BACKGROUND: Spinal stenosis and amyotrophic lateral sclerosis (ALS) can co-occur and both manifest as signs of dysfunction of lower and/or upper motor neurons. Few studies have identified factors that alert the diagnosis of ALS in patients with spinal stenosis, and the influence of spinal decompression surgery on ALS progression remains unclear. OBJECTIVE: The objective of this study is to describe factors that are suggestive of an ALS diagnosis in patients with spinal stenosis and influence of spinal decompression surgery on the progression of ALS Materials and methods: A retrospective review of the institutional ALS database and electronic medical records was performed to identify patients with coexisting diagnoses of ALS and moderate to severe cervical and/or lumbosacral spine stenosis. Identified patients were divided into two subgroups: those with spinal decompression surgery and those without. Comparisons of clinical features and progression of ALS were made between subgroups. RESULTS: A total of 77 patients with ALS and coexisting moderate to severe cervical or lumbosacral spine stenosis were included. Among them, 50 patients underwent spinal decompression surgery and 27 did not. In comparison to patients with spinal decompression, patients without spinal decompression surgery were seen more frequently by neurologists (74% versus 26%), had less prominent radicular pain (19% versus 50%), demonstrated more frequent bulbar signs (30% versus 8%), experienced more likely weight loss (41% versus 4%), and disclosed more noticeable axonal loss changes on electromyography. Spinal decompression surgery did not modify the progression of ALS based on ALSFRS-R score change and analysis of survival duration. CONCLUSION: Our study identified a number of useful features that are suggestive of an ALS diagnosis when evaluating patients with spinal stenosis and may support the performance of spinal decompression surgery in a subset of selected ALS patients with symptomatic spinal stenosis.
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In recognition of the high rates of undetected tuberculosis in the community, the World Health Organization (WHO) encourages targeted active case finding (ACF) among "high-risk" populations. While this strategy has led to increased case detection in these populations, the epidemic impact of these interventions has not been demonstrated. Historical data suggest that population-wide (untargeted) ACF can interrupt transmission in high-incidence settings, but implementation remains lacking, despite recent advances in screening tools. The reservoir of latent infection-affecting up to a quarter of the global population -complicates elimination efforts by acting as a pool from which future tuberculosis cases may emerge, even after all active cases have been treated. A holistic case finding strategy that addresses both active disease and latent infection is likely to be the optimal approach for rapidly achieving sustainable progress toward TB elimination in a durable way, but safety and cost effectiveness have not been demonstrated. Sensitive, symptom-agnostic community screening, combined with effective tuberculosis treatment and prevention, should eliminate all infectious cases in the community, whilst identifying and treating people with latent infection will also eliminate tomorrow's tuberculosis cases. If real strides toward global tuberculosis elimination are to be made, bold strategies are required using the best available tools and a long horizon for cost-benefit assessment.
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OBJECTIVES: Treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is increasingly transitioning from hospital-centred to community-based care. A national policy for decentralised programmatic MDR/RR-TB care was adopted in South Africa in 2011. We explored variations in the implementation of care models in response to this change in policy, and the implications of these variations for people affected by MDR/RR-TB. DESIGN: A mixed methods study was done of patient movements between healthcare facilities, reconstructed from laboratory records. Facility visits and staff interviews were used to determine reasons for movements. PARTICIPANTS AND SETTING: People identified with MDR/RR-TB from 13 high-burden districts within South Africa. OUTCOME MEASURES: Geospatial movement patterns were used to identify organisational models. Reasons for patient movement and implications of different organisational models for people affected by MDR/RR-TB and the health system were determined. RESULTS: Among 191 participants, six dominant geospatial movement patterns were identified, which varied in average hospital stay (0-281 days), average patient distance travelled (12-198 km) and number of health facilities involved in care (1-5 facilities). More centralised models were associated with longer delays to treatment initiation and lengthy hospitalisation. Decentralised models facilitated family-centred care and were associated with reduced time to treatment and hospitalisation duration. Responsiveness to the needs of people affected by MDR/RR-TB and health system constraints was achieved through implementation of flexible models, or the implementation of multiple models in a district. CONCLUSIONS: Understanding how models for organising care have evolved may assist policy implementers to tailor implementation to promote particular patterns of care organisation or encourage flexibility, based on patient needs and local health system resources. Our approach can contribute towards the development of a health systems typology for understanding how policy-driven models of service delivery are implemented in the context of variable resources.
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Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , África do Sul , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Rifampina , HospitalizaçãoRESUMO
Up to 25% of SARS-CoV-2 patients exhibit post-acute cognitive sequelae. Although millions of cases of COVID-19-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1, a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of COVID-19 patients. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 beta variant, leads to CNS infiltration of Ly6Chi monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1ß and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes post-acute cognitive deficits. Breakthrough infection after vaccination with a low dose of adenoviral vectored Spike protein prevents hippocampal production of IL-1ß during breakthrough SARS-CoV-2 infection, loss of neurogenesis, and subsequent memory deficits. Our study identifies IL-1ß as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new murine model that is prevented by vaccination.
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ß-Casomorphin-7 (BCM-7) is a peptide released through the proteolysis of ß-casein (ß-CN), which is considered a bioactive peptide displaying evidence of promoting the binding and activation of the µ-opioid receptor located in various body parts, such as the gastrointestinal tract, the immune system and potentially the central nervous system. The possible effects of BCM-7 on health are a theme rising in popularity due to evidence found in several studies on the modulation of gastrointestinal proinflammatory responses that can trigger digestive symptoms, such as abdominal discomfort. With the advancement of studies, the hypothesis that there is a correlation of the possible effects of BCM-7 with the microbiota-gut-brain axis has been established. However, some studies have suggested the possibility that these adverse effects are restricted to a portion of the population, and the topic is controversial due to the small number of in vivo studies, which makes it difficult to obtain more conclusive results. In addition, a threshold of exposure to BCM-7 has not yet been established to clarify the potential of this peptide to trigger physiological responses at gastrointestinal and systemic levels. The proportion of the population that can be considered more susceptible to the effects of BCM-7 are evidenced in the literature review. The challenges of establishing the adverse effects of BCM-7 are discussed, including the importance of quantifying the BCM-7 release in the different ß-CN genotypes. In summary, the reviewed literature provides plausible indications of the hypothesis of a relationship between ß-CN A1/BCM-7 and adverse health effects; however, there is need for further, especially in vivo studies, to better understand and confirm the physiological effects of this peptide.
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Neurologic complications of Zika virus (ZIKV) infection across the lifespan have been described during outbreaks in Southeast Asia, South America, and Central America since 2016. In the adult CNS ZIKV tropism for neurons is tightly linked to its effects, with neuronal loss within the hippocampus during acute infection and protracted synapse loss during recovery, which is associated with cognitive deficits. The effects of ZIKV on cortical networks have not been evaluated. Although animal behavior assays have been used previously to model cognitive impairment, in vivo brain imaging can provide orthogonal information regarding the health of brain networks in real time, providing a tool to translate findings in animal models to humans. In this study, we use widefield optical imaging to measure cortical functional connectivity (FC) in mice during acute infection with, and recovery from, intracranial infection with a mouse-adapted strain of ZIKV. Acute ZIKV infection leads to high levels of myeloid cell activation, with loss of neurons and presynaptic termini in the cerebral cortex and associated loss of FC primarily within the somatosensory cortex. During recovery, neuron numbers, synapses and FC recover to levels near those of healthy mice. However, hippocampal injury and impaired spatial cognition persist. The magnitude of activated myeloid cells during acute infection predicted both recovery of synapses and the degree of FC recovery after recovery from ZIKV infection. These findings suggest that a robust inflammatory response may contribute to the health of functional brain networks after recovery from infection.
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The scale-up of rifampicin-based prevention regimens is an essential part of the global leprosy strategy. Daily rifampicin may reduce the effectiveness of the oral contraceptive pill (OCP), but little is known about the effects of rifampicin at the less frequent dosing intervals used for leprosy prophylaxis. As many women of reproductive age rely on OCP for family planning, evaluating the interaction with less-than-daily rifampicin regimens would enhance the scalability and acceptability of leprosy prophylaxis. Using a semi-mechanistic pharmacokinetic model of rifampicin induction, we simulated predicted changes in OCP clearance when coadministered with varying rifampicin dosing schedules. Rifampicin given as a single dose (600 or 1200 mg) or 600 mg every 4 weeks was not predicted to result in a clinically relevant interaction with OCP, defined as a >25% increase in clearance. Simulations of daily rifampicin were predicted to increase OCP clearance within the range of observed changes previously reported in the literature. Therefore, our findings suggest that OCP efficacy will be maintained when coadministered with rifampicin-based leprosy prophylaxis regimens of 600 mg once, 1200 mg once, and 600 mg every 4 weeks. This work provides reassurance to stakeholders that leprosy prophylaxis can be used with OCP without any additional recommendations for contraception prevention.
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INTRODUCTION: Progress towards leprosy elimination is threatened by increasing incidence in 'hot-spot' areas where more effective control strategies are urgently required. In these areas, active case finding and leprosy prevention limited to known contacts is insufficient for control. Population-wide active case-finding together with universal prevention through mass drug administration (MDA) has been shown to be effective in 'hot-spot' areas, but is logistically challenging and expensive. Combining leprosy screening and MDA with other population-wide screening activities such as for tuberculosis may increase programme efficiency. There has been limited evaluation of the feasibility and effectiveness of combined screening and MDA interventions. The COMBINE study aims to bridge this knowledge gap. METHODS AND ANALYSIS: This implementation study will assess the feasibility and effectiveness of active leprosy case-finding and treatment, combined with MDA using either single-dose rifampicin or rifamycin-containing tuberculosis preventive or curative treatment, for reducing leprosy incidence in Kiribati. The leprosy programme will run over 2022-2025 in concert with population-wide tuberculosis screening-and-treatment in South Tarawa. The primary research question is to what extent the intervention reduces the annual leprosy new case detection rate (NCDR) in adults and children compared with routine screening and postexposure prophylaxis (PEP) among close contacts (baseline leprosy control activities). Comparisons will be made with (1) the preintervention NCDR separably among adults and children in South Tarawa (before-after study) and (2) the corresponding NCDRs in the rest of the country. Additionally, the postintervention prevalence of leprosy obtained from a survey of a 'hot-spot' sub-population will be compared with prevalence documented during the intervention. The intervention will be implemented in collaboration with the Kiribati National Leprosy Programme. ETHICS AND DISSEMINATION: Approval has been obtained from the Kiribati Ministry of Health and Medical Services (MHMS), the University of Otago (H22/111) and the University of Sydney (2021/127) Human Research Ethics Committees. Findings will be shared with the MHMS, local communities and internationally through publication.
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Dermatite , Hanseníase , Adulto , Criança , Humanos , Administração Massiva de Medicamentos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Rifampina/uso terapêutico , MicronésiaRESUMO
Electron tubes continue to provide the highest speeds possible for recording dynamics of hot high-energy density plasmas. Standard streak camera drive electronics and CCD readout are not compatible with the radiation environment associated with high DT fusion yield inertial confinement fusion experiments >1013 14 MeV DT neutrons or >109 n cm-2 ns-1. We describe a hardened x-ray streak camera developed for the National Ignition Facility and present preliminary results from the first experiment on which it has participated, recording the time-resolved bremsstrahlung spectrum from the core of an inertial confinement fusion implosion at more than 40× the operational neutron yield limit of the previous National Ignition Facility x-ray streak cameras.
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Plant-based beverages (PBB) are often marketed and used by consumers as alternatives to ruminant milks, particularly bovine milk (hereafter referred to as milk). However, much research has established that there is variation in nutritional composition among these products, as well as demonstrating that they are largely not nutritional replacements for milk. A survey of the prices and nutrition labels of PBB available in New Zealand supermarkets was undertaken. Selected almond, coconut, oat, rice, and soy PBB products were then analyzed for nutritional content, including energy, fat, protein, amino acid, bioavailable amino acid, and trace element contents. Finally, the protein and calcium contents of well-mixed and unshaken products were analyzed to ascertain the impact of colloidal stability on nutrient content. All PBB groups were more expensive than milk on average, while their declared nutrient contents on package labels was highly variable within and between groups. Analyses of selected PBB revealed that soy products had the most similar proximate composition to milk, while all other PBB groups contained less than 1.1 g protein per 100 mL on average. Many PBB were fortified with calcium to a similar concentration as that in milk. Shaken and unshaken samples showed divergent protein and calcium content for several PBB products but had no effect on the composition of milk, indicating that the nutrient content of PBB at the point of consumption will be dependent on whether the product has been shaken. Only the soy PBB had comparable amino acid content and bioavailability to milk. Overall, our results demonstrate the diversity in composition and nutritional properties of PBB available in New Zealand. While the existent environmental footprint data on PBB shows that they generally have lower carbon emissions than milk, milk currently accounts for approximately 1% of the average New Zealand resident's consumption-based emissions. Except for calcium-fortified soy PBB, none of the commercially available PBB had nutritional compositions that were broadly comparable to milk.
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BACKGROUND/IMPORTANCE: There is heterogeneity among the outcomes used in regional anesthesia research. OBJECTIVE: We aimed to produce a core outcome set for regional anesthesia research. METHODS: We conducted a systematic review and Delphi study to develop this core outcome set. A systematic review of the literature from January 2015 to December 2019 was undertaken to generate a long list of potential outcomes to be included in the core outcome set. For each outcome found, the parameters such as the measurement scale, timing and definitions, were compiled. Regional anesthesia experts were then recruited to participate in a three-round electronic modified Delphi process with incremental thresholds to generate a core outcome set. Once the core outcomes were decided, a final Delphi survey and video conference vote was used to reach a consensus on the outcome parameters. RESULTS: Two hundred and six papers were generated following the systematic review, producing a long list of 224 unique outcomes. Twenty-one international regional anesthesia experts participated in the study. Ten core outcomes were selected after three Delphi survey rounds with 13 outcome parameters reaching consensus after a final Delphi survey and video conference. CONCLUSIONS: We present the first core outcome set for regional anesthesia derived by international expert consensus. These are proposed not to limit the outcomes examined in future studies, but rather to serve as a minimum core set. If adopted, this may increase the relevance of outcomes being studied, reduce selective reporting bias and increase the availability and suitability of data for meta-analysis in this area.
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INTRODUCTION: Population-wide interventions offer a pathway to tuberculosis (TB) and leprosy elimination, but 'real-world' implementation in a high-burden setting using a combined approach has not been demonstrated. This implementation study aims to demonstrate the feasibility and evaluate the effect of population-wide screening, treatment and prevention on TB and leprosy incidence rates, as well as TB transmission. METHODS AND ANALYSIS: A non-randomised 'screen-and-treat' intervention conducted in the Pacific atoll of South Tarawa, Kiribati. Households are enumerated and all residents ≥3 years, as well as children <3 years with recent household exposure to TB or leprosy, invited for screening. Participants are screened using tuberculin skin testing, signs and symptoms of TB or leprosy, digital chest X-ray with computer-aided detection and sputum testing (Xpert MTB/RIF Ultra). Those diagnosed with disease are referred to the National TB and Leprosy Programme for management. Participants with TB infection are offered TB preventive treatment and those without TB disease or infection, or leprosy, are offered leprosy prophylaxis. The primary study outcome is the difference in the annual TB case notification rate before and after the intervention; a similar outcome is included for leprosy. The effect on TB transmission will be measured by comparing the estimated annual risk of TB infection in primary school children before and after the intervention, as a co-primary outcome used for power calculations. Comparison of TB and leprosy case notification rates in South Tarawa (the intervention group) and the rest of Kiribati (the control group) before, during and after the intervention is a secondary outcome. ETHICS AND DISSEMINATION: Approval was obtained from the University of Sydney Human Research Ethics Committee (project no. 2021/127) and the Kiribati Ministry of Health and Medical Services (MHMS). Findings will be shared with the MHMS and local communities, published in peer-reviewed journals and presented at international conferences.
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Hanseníase , Mycobacterium tuberculosis , Tuberculose , Criança , Humanos , Hanseníase/diagnóstico , Hanseníase/epidemiologia , Hanseníase/prevenção & controle , Micronésia/epidemiologia , Tuberculose/epidemiologiaRESUMO
INTRODUCTION: A number of case and case series descriptions established an association between Legionella infection and hyperCKemia, but the frequency and severity of hyperCKemia in Legionella infection remain unknown. This study aims to investigate the incidence, extent, and consequences of hyperCKemia in a large group of patients with Legionella infection. METHODS: This retrospective study included patients with confirmed Legionella infection during a ten-year period who received creatine kinase (CK) testing. Comparisons were performed between groups of Legionella patients with and without hyperCKemia. RESULTS: A total of 267 patients were included. HyperCKemia was present in 144 (53.9%) patients. The mean peak CK value was 9598 IU/L (range: 226 to 462,000 IU/L) while peak CK exceeded 1000 IU/L in 82 (56.9%) patients and 5000 IU/L in 33 (22.9%). When compared to patients without hyperCKemia, patients with hyperCKemia had higher incidences of neurologic symptoms (p = 0.036), acute renal failure (p = 0.028), dialysis requirement (p = 0.009), and need for ICU care (p = 0.016). HyperCKemia resolved in most Legionella patients by 7 days from CK peaking. DISCUSSION: Legionella infection requiring hospitalization appears to be associated with increased incidence of hyperCKemia and rhabdomyolysis. Greater awareness of the high incidence and the possible severity of hyperCKemia is needed when treating patients with Legionella infection.
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Legionella , Rabdomiólise , Creatina Quinase , Humanos , Incidência , Estudos Retrospectivos , Rabdomiólise/diagnóstico , Rabdomiólise/epidemiologiaRESUMO
An increasing global population requires increasing food and nutrient availability. Meat is recognized as a nutrient dense food, particularly notable for its high-quality protein content, B vitamin and mineral content. However, it is not known how important meat is currently in nourishing the global population. The DELTA Model was used to calculate the contribution of meat (defined as animal flesh, excluding fish and seafood) to the global availability of 29 nutrients. This model utilizes global food production and use data, coupled with data for food waste, food nutrient composition and nutrient bioavailability to calculate the total amount of each nutrient available for consumption by the global population. Around 333 million tons of meat were produced globally in 2018, 95% of which was available as food, constituting ~7% of total food mass. Meat's contribution to nutrient availability was disproportionately higher than this: meat provided 11% of global food energy availability, 29% of dietary fat and 21% of protein. For the micronutrients, meat provided high proportions of vitamins: A (24%), B1 and B2 (15% each), B5 (10%), B6 (13%), and B12 (56%). Meat also provided high proportions of several trace elements: zinc (19%), selenium (18%), iron (13%), phosphorous (11%), and copper (10%). Meat is a poor contributor to fiber, magnesium and vitamins C and E. Meat was responsible for 16% (cystine) to 32% (lysine) of global availability of the bioavailable indispensable amino acids included in the model, due partly to the high digestibility of these nutrients from meat (83-100%). Of the total meat mass available as food in 2018, 23% was ruminant meat, 34% poultry meat, 32% pig meat, 2% other meat, and 9% offal and fats. The disproportionate contribution of meat to the global availability of nutrients emphasizes its important place in delivering nutrition to the current global population.
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BACKGROUND: Increasing attention is being directed at the environmental, social, and economic sustainability of the global food system. However, a key aspect of a sustainable food system should be its ability to deliver nutrition to the global population. Quantifying nutrient adequacy with current tools is challenging. OBJECTIVE: To produce a computational model illustrating the nutrient adequacy of current and proposed global food systems. METHODS: The DELTA Model was constructed using global food commodity balance sheet data, alongside demographic and nutrient requirement data from UN and European Food Safety Authority sources. It also includes nutrient bioavailability considerations for protein, the indispensable amino acids, iron, and zinc, sourced from scientific literature. RESULTS: The DELTA Model calculates global per capita nutrient availability under conditions of equal distribution and identifies areas of nutrient deficiency for various food system scenarios. Modeling the 2018 global food system showed that it supplied insufficient calcium (64% of demographically weighted target intake) and vitamin E (69%), despite supplying sufficient macronutrients. Several future scenarios were modeled, including variations in waste; scaling up current food production for the 2030 global population; plant-based food production systems; and removing sugar crops from the global food system. Each of these scenarios fell short of meeting requirements for multiple nutrients. These results emphasize the need for a balanced approach in the design of future food systems. CONCLUSIONS: Nutrient adequacy must be at the forefront of the sustainable food system debate. The DELTA Model was designed for both experts and nonexperts to inform this debate as to what may be possible, practical, and optimal for our food system. The model results strongly suggest that both plant and animal foods are necessary to achieve global nutrition. The model is freely available for public use so that anyone can explore current and simulated global food systems.
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Nutrientes , Estado Nutricional , Animais , Dieta , Ingestão de Alimentos , Micronutrientes , Necessidades Nutricionais , Valor NutritivoRESUMO
In 2011, the South African National TB Programme launched a policy of decentralized management of drug-resistant tuberculosis (DR-TB) in order to expand the capacity of facilities to treat patients with DR-TB, minimize delays to access care and improve patient outcomes. This policy directive was implemented to varying degrees within a rapidly evolving diagnostic and treatment landscape for DR-TB, placing new demands on already-stressed health systems. The variable readiness of district-level systems to implement the policy prompted questions not only about differences in health systems resources but also front-line actors' capacity to implement change in resource-constrained facilities. Using a grounded theory approach, we analysed data from in-depth interviews and small group discussions conducted between 2016 and 2018 with managers (n = 9), co-ordinators (n = 15), doctors (n = 7) and nurses (n = 18) providing DR-TB care. Data were collected over two phases in district-level decentralized sites of three South African provinces. While health systems readiness assessments conventionally map the availability of 'hardware', i.e. resources and skills to deliver an intervention, a notable absence of systems 'hardware' meant that systems 'software', i.e. health care workers (HCWs) agency, behaviours and interactions provided the basis of locally relevant strategies for decentralized DR-TB care. 'Software readiness' was manifest in four areas of DR-TB care: re-organization of service delivery, redressal of resource shortages, creation of treatment adherence support systems and extension of care parameters for vulnerable patients. These strategies demonstrate adaptive capacity and everyday resilience among HCW to withstand the demands of policy change and innovation in stressed systems. Our work suggests that a useful extension of health systems 'readiness' assessments would include definition and evaluation of HCW 'software' and adaptive capacities in the face of systems hardware gaps.