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1.
Nat Immunol ; 25(7): 1158-1171, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38902519

RESUMO

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.


Assuntos
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 , Feminino
2.
J Nutr ; 151(10): 3253-3261, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34195827

RESUMO

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.


Assuntos
Nutrientes , Estado Nutricional , Animais , Dieta , Ingestão de Alimentos , Micronutrientes , Necessidades Nutricionais , Valor Nutritivo
3.
J Neuroophthalmol ; 41(4): e619-e621, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32868571

RESUMO

BACKGROUND: Occurrence of comitant ocular deviation in myasthenia gravis (MG) is not well described. METHODS: A retrospective analysis of patients with ocular or generalized MG evaluated at a neuro-ophthalmology clinic for a 6-year period. Comitant ocular deviation was defined as magnitude of deviations in all planes varying by <20% from the measurement in the primary position. RESULTS: Among the 120 patients included, 89 patients had ocular and 31 patients generalized MG. At the initial strabismus testing, comitant ocular deviation was present in 27 (22.5%) patients. Among the 16 patients who had a follow-up, ocular deviation remained comitant in 6 patients and converted to incomitant or no ocular deviation in 10 patients. An additional 7 patients demonstrated comitant ocular deviation at follow-up. Brain MRI was performed in 18 patients with comitant ocular deviation, and none showed abnormalities in the brainstem or cerebellum. CONCLUSION: Comitant ocular deviation can be an ocular manifestation of MG. Its presence does not necessarily indicate a central etiology in patients with MG neither excluding a MG diagnosis.


Assuntos
Miastenia Gravis , Estrabismo , Humanos , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Estudos Retrospectivos , Estrabismo/diagnóstico , Estrabismo/etiologia
4.
Brain Behav Immun ; 76: 165-181, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30465881

RESUMO

New neurons are continuously produced by neural stem cells (NSCs) within the adult hippocampus. Numerous diseases, including major depressive disorder and HIV-1 associated neurocognitive disorder, are associated with decreased rates of adult neurogenesis. A hallmark of these conditions is a chronic release of neuroinflammatory mediators by activated resident glia. Recent studies have shown a neuroprotective role on NSCs of cannabinoid receptor activation. Yet, little is known about the effects of GPR55, a candidate cannabinoid receptor, activation on reductions of neurogenesis in response to inflammatory insult. In the present study, we examined NSCs exposed to IL-1ß in vitro to assess inflammation-caused effects on NSC differentiation and the ability of GPR55 agonists to attenuate NSC injury. NSC differentiation and neurogenesis was determined via immunofluorescence and flow cytometric analysis of NSC markers (Nestin, Sox2, DCX, S100ß, ßIII Tubulin, GFAP). GPR55 agonist treatment protected against IL-1ß induced reductions in neurogenesis rates. Moreover, inflammatory cytokine receptor mRNA expression was down regulated by GPR55 activation in a neuroprotective manner. To determine inflammatory responses in vivo, we treated C57BL/6 and GPR55-/- mice with LPS (0.2 mg/kg/day) continuously for 14 days via osmotic mini-pump. Reductions in NSC survival (as determined by BrdU incorporation), immature neurons, and neuroblast formation due to LPS were attenuated by concurrent direct intrahippocampal administration of the GPR55 agonist, O-1602 (4 µg/kg/day). Molecular analysis of the hippocampal region showed a suppressed ability to regulate immune responses by GPR55-/- animals manifesting in a prolonged inflammatory response (IL-1ß, IL-6, TNFα) after chronic, systemic inflammation as compared to C57BL/6 animals. Taken together, these results suggest a neuroprotective role of GPR55 activation on NSCs in vitro and in vivo and that GPR55 provides a novel therapeutic target against negative regulation of hippocampal neurogenesis by inflammatory insult.


Assuntos
Hipocampo/metabolismo , Inflamação/metabolismo , Células-Tronco Neurais/imunologia , Neurogênese/fisiologia , Receptores de Canabinoides/metabolismo , Animais , Canabidiol/análogos & derivados , Canabidiol/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proteína Duplacortina , Feminino , Hipocampo/imunologia , Hipocampo/patologia , Imunidade Ativa , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células-Tronco Neurais/patologia , Neurônios/metabolismo , Neurônios/patologia , Neuroproteção/efeitos dos fármacos , Neuroproteção/imunologia , Receptores de Canabinoides/genética , Receptores de Canabinoides/imunologia
5.
J Surg Res ; 213: 84-89, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28601337

RESUMO

BACKGROUND: Studies on medicine wards have shown that numeric pages can be disruptive of workflow and patient care. We created a quality improvement program among surgical ward nurses and residents and hypothesized that a text-based, urgency-stratified initiative would improve communication at no detriment to patient care. METHODS: Surgery residents recorded preintervention data for 1 mo including number of total pages, text pages, and numeric pages received from surgical floors. Nurses and residents completed surveys to assess preintervention satisfaction with communication, responsiveness, and workflow. Nurses were then instructed to use text paging for nonurgent issues. Paging data were again recorded for 1 mo, surveys repeated, and patient safety and satisfaction data collected. Primary endpoints evaluated included patient safety and satisfaction data. Secondary endpoints included communication satisfaction of nurses and residents. RESULTS: After text paging implementation, 40.1% of nonurgent pages sent from nurses to resident physicians were alphanumeric texts versus only 17.9% before implementation (P < 0.0001). There was a 19.5% reduction in the number of nonurgent numeric pages sent (P < 0.0001). Overall, 70% of nurses responded postintervention that text paging was the preferred method of contacting a physician and that the text paging initiative improved efficiency. After implementation, 62% of nurses thought that overall communication with clinicians improved. In addition, there was no change in patient safety issues or patient satisfaction. CONCLUSIONS: Our text paging initiative for all nonurgent pages from nurses to residents improved physician-nurse workflow and communication on the surgical ward with no decrease in patient satisfaction or safety.


Assuntos
Relações Interprofissionais , Melhoria de Qualidade/organização & administração , Centro Cirúrgico Hospitalar/organização & administração , Envio de Mensagens de Texto , Atitude do Pessoal de Saúde , Eficiência Organizacional , Humanos , Internato e Residência , Enfermeiras e Enfermeiros , Ohio , Segurança do Paciente , Satisfação do Paciente , Fluxo de Trabalho
6.
Eur J Nucl Med Mol Imaging ; 42(7): 1032-42, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25820674

RESUMO

PURPOSE: (82)Rb is an ultra-short-lived positron emitter used for myocardial blood flow quantification with PET imaging. The aim of this study was to quantify the biodistribution and radiation dosimetry in patients with coronary disease and in healthy normal volunteers. METHODS: A total of 30 subjects, 26 patients with known or suspected coronary artery disease (CAD) and four healthy volunteers were injected with (82)Rb chloride at 10 MBq/kg followed by a 10-min dynamic PET scan. Chest scans at rest were acquired in all subjects, as well as one additional biodistribution scan of the head, neck, abdomen, pelvis or thighs. Chest scans under stress were acquired in 25 of the CAD patients. (82)Rb time-integrated activity coefficients were determined in 22 source organs using volume of interest analysis, including corrections for partial-volume losses. The mean time-integrated activity coefficients were used to calculate the whole-body effective dose using tissue weighting factors from the International Commission on Radiological Protection (ICRP) Publications 60 and 103. RESULTS: A total of 283 organ time-integrated activity coefficients were calculated, with a minimum of four values per source organ. The rest and stress mean effective dose was 0.8 mSv/GBq, according to the most recent ICRP definition. Using 10 MBq/kg for 3D PET imaging, the effective dose to a gender-averaged reference person (60 kg female and 73 kg male) is 1.1 mSv for a complete rest and stress perfusion study. For 2D PET using a typical injected activity of 1.1 to 2.2 GBq each for rest and stress, the effective dose for a complete study is 1.8 to 3.5 mSv. CONCLUSION: The current effective dose estimate in CAD patients is four times lower than the values reported previously by the ICRP, and about 35% lower than previous in vivo studies in young healthy subjects.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Imagem de Perfusão do Miocárdio , Tomografia por Emissão de Pósitrons , Doses de Radiação , Compostos Radiofarmacêuticos/farmacocinética , Radioisótopos de Rubídio/farmacocinética , Adulto , Idoso , Estudos de Casos e Controles , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Tecidual
7.
Cureus ; 16(1): e51587, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38313873

RESUMO

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.

8.
Lancet Reg Health West Pac ; 46: 101047, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38827931

RESUMO

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.

9.
Eur J Hum Genet ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965372

RESUMO

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.

10.
J Dairy Sci ; 101(11): 9623-9624, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30342696
11.
Foods ; 12(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37685085

RESUMO

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.

12.
bioRxiv ; 2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37461558

RESUMO

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.

13.
Res Sq ; 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37790551

RESUMO

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.

14.
Front Med (Lausanne) ; 10: 1275140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37908846

RESUMO

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.

15.
J Clin Pharmacol ; 63(11): 1283-1289, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37409982

RESUMO

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.

16.
BMJ Open ; 13(6): e065369, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37385746

RESUMO

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.


Assuntos
Dermatite , Hanseníase , Adulto , Criança , Humanos , Administração Massiva de Medicamentos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Hanseníase/epidemiologia , Rifampina/uso terapêutico , Micronésia
17.
BMJ Open ; 13(11): e067121, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37977868

RESUMO

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.


Assuntos
Antituberculosos , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Antituberculosos/uso terapêutico , África do Sul , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Rifampina , Hospitalização
18.
J Neurol Sci ; 436: 120252, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405618

RESUMO

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.


Assuntos
Legionella , Rabdomiólise , Creatina Quinase , Humanos , Incidência , Estudos Retrospectivos , Rabdomiólise/diagnóstico , Rabdomiólise/epidemiologia
19.
Front Nutr ; 9: 766796, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35187029

RESUMO

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.

20.
Front Nutr ; 9: 957486, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003838

RESUMO

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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