180 research outputs found

    Methodological Challenges in Studies Examining the Effects of Breakfast on Cognitive Performance and Appetite in Children and Adolescents

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    Breakfast is purported to confer a number of benefits on diet quality, health, appetite regulation, and cognitive performance. However, new evidence has challenged the long-held belief that breakfast is the most important meal of the day. This review aims to provide a comprehensive discussion of the key methodological challenges and considerations in studies assessing the effect of breakfast on cognitive performance and appetite control, along with recommendations for future research. This review focuses on the myriad challenges involved in studying children and adolescents specifically. Key methodological challenges and considerations include study design and location, sampling and sample section, choice of objective cognitive tests, choice of objective and subjective appetite measures, merits of providing a fixed breakfast compared with ad libitum, assessment and definition of habitual breakfast consumption, transparency of treatment condition, difficulty of isolating the direct effects of breakfast consumption, untangling acute and chronic effects, and influence of confounding variables. These methodological challenges have hampered a clear substantiation of the potential positive effects of breakfast on cognition and appetite control and contributed to the debate questioning the notion that breakfast is the most important meal of the day

    Склад повітря та стан здоров'я людини

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    В обзоре проанализированы сведения од эволюции газового состава атмосферы Земного шара от протопланетного до современного периода развития. Показана положительная роль биогенного накопления кислорода в воздухе и отрицательные последствия кислородного стресса для организма человека. Рассмотрена биологическая роль электрических свойств воздуха, возможные последствия антропогенных влияний на состояние газовой оболочки Земли и лечебно-профилактические возможности инструментальной оротерапии в реабилитации пациентов в санаторно-курортных учреждениях.In review are analysed data about evolution contents of atmosphere of Earth. It is shown positive role of biogene accumulating in air of oxygen and negative consequences of oxygen stress. It is considered the biologic role of electric properties of air, potential consequences of anthropogenic influences on state atmosphere of Earth and healing and prophylactic possibilities of instrumental orotherapy in rehabilitation of patients on spa and resorts

    Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

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    <p>Abstract</p> <p>Background</p> <p>Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities.</p> <p>Methods</p> <p>We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected.</p> <p>Results</p> <p>Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics.</p> <p>Conclusions</p> <p>The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.</p

    Bacillus subtilis MreB Orthologs Self-Organize into Filamentous Structures underneath the Cell Membrane in a Heterologous Cell System

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    Actin-like bacterial cytoskeletal element MreB has been shown to be essential for the maintenance of rod cell shape in many bacteria. MreB forms rapidly remodelling helical filaments underneath the cell membrane in Bacillus subtilis and in other bacterial cells, and co-localizes with its two paralogs, Mbl and MreBH. We show that MreB localizes as dynamic bundles of filaments underneath the cell membrane in Drosophila S2 Schneider cells, which become highly stable when the ATPase motif in MreB is modified. In agreement with ATP-dependent filament formation, the depletion of ATP in the cells lead to rapid dissociation of MreB filaments. Extended induction of MreB resulted in the formation of membrane protrusions, showing that like actin, MreB can exert force against the cell membrane. Mbl also formed membrane associated filaments, while MreBH formed filaments within the cytosol. When co-expressed, MreB, Mbl and MreBH built up mixed filaments underneath the cell membrane. Membrane protein RodZ localized to endosomes in S2 cells, but localized to the cell membrane when co-expressed with Mbl, showing that bacterial MreB/Mbl structures can recruit a protein to the cell membrane. Thus, MreB paralogs form a self-organizing and dynamic filamentous scaffold underneath the membrane that is able to recruit other proteins to the cell surface

    SARS-CoV-2 antibody dynamics in blood donors and COVID-19 epidemiology in eight Brazilian state capitals: A serial cross-sectional study

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    BACKGROUND: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. METHODS: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil's most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. RESULTS: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5-21.2%) in Curitiba to 75.0% (95% CrI 70.8-80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system's collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43-3.53). CONCLUSIONS: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. FUNDING: This work was supported by Itaú Unibanco 'Todos pela Saude' program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS - Fazer o bem faz bem

    "Before we used to get sick all the time": perceptions of malaria and use of long-lasting insecticide-treated bed nets (LLINs) in a rural Kenyan community

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    <p>Abstract</p> <p>Background</p> <p>Malaria is a leading global cause of preventable morbidity and mortality, especially in sub-Saharan Africa, despite recent advances in treatment and prevention technologies. Scale-up and wide distribution of long-lasting insecticide-treated nets (LLINs) could rapidly decrease malarial disease in endemic areas, if used properly and continuously. Studies have shown that effective use of LLINs depends, in part, upon understanding causal factors associated with malaria. This study examined malaria beliefs, attitudes, and practices toward LLINs assessed during a large-scale integrated prevention campaign (IPC) in rural Kenya.</p> <p>Methods</p> <p>Qualitative interviews were conducted with 34 IPC participants who received LLINs as part of a comprehensive prevention package of goods and services. One month after distribution, interviewers asked these individuals about their attitudes and beliefs regarding malaria, and about their use of LLINs.</p> <p>Results</p> <p>Virtually all participants noted that mosquitoes were involved in causing malaria, though a substantial proportion of participants (47 percent) also mentioned an incorrect cause in addition to mosquitoes. For example, participants commonly noted that the weather (rain, cold) or consumption of bad food and water caused malaria. Regardless, most participants used the LLINs they were given and most mentioned positive benefits from their use, namely reductions in malarial illness and in the costs associated with its diagnosis and treatment.</p> <p>Conclusions</p> <p>Attitudes toward LLINs were positive in this rural community in Western Kenya, and respondents noted benefits with LLIN use. With improved understanding and clarification of the direct (mosquitoes) and indirect (e.g., standing water) causes of malaria, it is likely that LLIN use can be sustained, offering effective household-level protection against malaria.</p

    Upregulation of Barrel GABAergic Neurons Is Associated with Cross-Modal Plasticity in Olfactory Deficit

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    Background: Loss of a sensory function is often followed by the hypersensitivity of other modalities in mammals, which secures them well-awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain to be documented. Methodology/Principal Findings: Multidisciplinary approaches, such as electrophysiology, behavioral task and immunohistochemistry, were used to examine the involvement of specific types of neurons in cross-modal plasticity. We have established a mouse model that olfactory deficit leads to a whisking upregulation, and studied how GABAergic neurons are involved in this cross-modal plasticity. In the meantime of inducing whisker tactile hypersensitivity, the olfactory injury recruits more GABAergic neurons and their fine processes in the barrel cortex, as well as upregulates their capacity of encoding action potentials. The hyperpolarization driven by inhibitory inputs strengthens the encoding ability of their target cells. Conclusion/Significance: The upregulation of GABAergic neurons and the functional enhancement of neuronal networks may play an important role in cross-modal sensory plasticity. This finding provides the clues for developing therapeuti

    Decelerating Spread of West Nile Virus by Percolation in a Heterogeneous Urban Landscape

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    Vector-borne diseases are emerging and re-emerging in urban environments throughout the world, presenting an increasing challenge to human health and a major obstacle to development. Currently, more than half of the global population is concentrated in urban environments, which are highly heterogeneous in the extent, degree, and distribution of environmental modifications. Because the prevalence of vector-borne pathogens is so closely coupled to the ecologies of vector and host species, this heterogeneity has the potential to significantly alter the dynamical systems through which pathogens propagate, and also thereby affect the epidemiological patterns of disease at multiple spatial scales. One such pattern is the speed of spread. Whereas standard models hold that pathogens spread as waves with constant or increasing speed, we hypothesized that heterogeneity in urban environments would cause decelerating travelling waves in incipient epidemics. To test this hypothesis, we analysed data on the spread of West Nile virus (WNV) in New York City (NYC), the 1999 epicentre of the North American pandemic, during annual epizootics from 2000–2008. These data show evidence of deceleration in all years studied, consistent with our hypothesis. To further explain these patterns, we developed a spatial model for vector-borne disease transmission in a heterogeneous environment. An emergent property of this model is that deceleration occurs only in the vicinity of a critical point. Geostatistical analysis suggests that NYC may be on the edge of this criticality. Together, these analyses provide the first evidence for the endogenous generation of decelerating travelling waves in an emerging infectious disease. Since the reported deceleration results from the heterogeneity of the environment through which the pathogen percolates, our findings suggest that targeting control at key sites could efficiently prevent pathogen spread to remote susceptible areas or even halt epidemics

    Novel Escape Mutants Suggest an Extensive TRIM5α Binding Site Spanning the Entire Outer Surface of the Murine Leukemia Virus Capsid Protein

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    After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5α and CA, we selected a panel of novel N-tropic murine leukaemia virus (N-MLV) escape mutants by a serial passage of replication competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using a small percentage of unrestricted cells to allow multiple rounds of virus replication. The newly identified mutations, many of which involve changes in charge, are distributed over the outer ‘top’ surface of N-MLV CA, including the N-terminal β-hairpin, and map up to 29 Ao apart. Biological characterisation with a number of restriction factors revealed that only one of the new mutations affects restriction by human TRIM5α, indicating significant differences in the binding interaction between N-MLV and the two TRIM5αs, whereas three of the mutations result in dual sensitivity to Fv1n and Fv1b. Structural studies of two mutants show that no major changes in the overall CA conformation are associated with escape from restriction. We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5α binding

    Identification of Novel Mt-Guab2 Inhibitor Series Active against M. tuberculosis

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    Tuberculosis (TB) remains a leading cause of mortality worldwide. With the emergence of multidrug resistant TB, extensively drug resistant TB and HIV-associated TB it is imperative that new drug targets be identified. The potential of Mycobacterium tuberculosis inosine monophosphate dehydrogenase (IMPDH) as a novel drug target was explored in the present study. IMPDH exclusively catalyzes the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) in the presence of the cofactor nicotinamide adenine dinucleotide (NAD+). Although the enzyme is a dehydrogenase, the enzyme does not catalyze the reverse reaction i.e. the conversion of XMP to IMP. Unlike other bacteria, M. tuberculosis harbors three IMPDH-like genes, designated as Mt-guaB1, Mt-guaB2 and Mt-guaB3 respectively. Of the three putative IMPDH's, we previously confirmed that Mt-GuaB2 was the only functional ortholog by characterizing the enzyme kinetically. Using an in silico approach based on designed scaffolds, a series of novel classes of inhibitors was identified. The inhibitors possess good activity against M. tuberculosis with MIC values in the range of 0.4 to 11.4 µg mL−1. Among the identified ligands, two inhibitors have nanomolar Kis against the Mt-GuaB2 enzyme
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