Radiological findings in young children investigated for tuberculosis in Mozambique

INTRODUCTION: Chest radiography remains a critical tool for diagnosing intrathoracic tuberculosis (TB) in young children who are unable to expectorate. We describe the radiological findings in children under 3 years of age investigated for TB in the district of Manhica, southern Mozambique, an area with a high prevalence of TB and HIV. METHODS: Digital antero-posterior and lateral projections were performed and reviewed by two independent readers, using a standardized template. Readers included a local pediatrician and a pediatric radiologist blinded to all clinical information. International consensus case definitions for intra-thoracic TB in children were applied. RESULTS: A total of 766 children were evaluated of whom 43 (5.6%) had TB. The most frequent lesion found in TB cases was air space consolidation (65.1%), followed by suggestive hilar lymphadenopathy (17.1%) and pleural effusion (7.0%). Air space consolidation was significantly more common in TB cases than in non-TB cases (odds ratio 8.9; 95% CI: 1.6-50.5), as were hilar lymphadenopathy (OR 17.2; 95% CI: 5.7-52.1). The only case with miliary infiltrates and 3 with pleural effusions occurred in HIV-infected children. CONCLUSION: Frequent air space consolidation complicates radiological distinction between TB and bacterial pneumonia in young children, underscoring the need for epidemiological contextualization and consideration of all relevant signs and symptoms

Membrane insertion of soluble CLIC1 into active chloride channels is triggered by specific divalent cations

The CLIC family of proteins display the unique feature of altering their structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, can be found in the cytoplasm or in nuclear, ER and plasma membranes, with membrane overexpression linked to tumour proliferation. The molecular switch promoting CLIC1 membrane insertion has been related to environmental factors, but still remains unclear. Here, we use solution NMR studies to confirm that both the soluble and membrane bound forms are in the same oxidation state. Our data from fluorescence assays and chloride efflux assays indicate that Ca2+ and Zn2+ trigger association to the membrane into active chloride channels. We use fluorescence microscopy to confirm that an increase of the intracellular Ca2+ leads to re-localisation of CLIC1 to both plasma and internal membranes. Finally, we show that soluble CLIC1 adopts an equilibrium of oligomeric species, and Ca2+/Zn2+ mediated membrane insertion promotes the formation of a tetrameric assembly. Thus, our results identify Ca2+ and Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion.SIGNIFICANCE STATEMENT CLIC1, a member of the CLIC family of proteins, is expressed as a soluble protein in cells but can insert in the membrane forming a chloride channel. This chloride channel form is upregulated in different types of cancers including glioblastoma and promote tumour invasiveness and metastasis. The factors promoting CLIC1 membrane insertion nor the mechanism of this process are yet understood. Here, we use a combination of solution NMR, biophysics and fluorescence microscopy to identify Ca2+ and Zn2+ binding as the switch to promote CLIC1 insertion into the membrane to form active chloride channels. We also provide a simple mechanism how such transition to the membrane occurs. Such understanding will enable subsequent studies on the structure of the chloride channel form and its inhibition

MATERIAIS REEMBASADORES DE USO EM PRÓTESES TOTAIS

O processo de reabsorção óssea alveolar é contínuo ao longo da vida dos pacientes edêntulos,podendo causar desadaptação das próteses durante a fala e a mastigação. Sempre que existe anecessidade de substituição dos dentes faltantes por próteses totais, o material de escolha paraser utilizado na confecção das bases das próteses totais é a resina acrílica, ativada quimicamenteou termicamente. Esse material apresenta várias características e propriedades desejáveis, comoestética satisfatória, boa resistência, baixo custo e facilidade de manipulação. Entretanto, porser rígido, pode causar desconforto e lesões aos tecidos bucais de alguns pacientes, em razão doatrito da base dura da prótese com a fibromucosa; dessa forma, pesquisadores desenvolverammateriais resilientes, também conhecidos como base macia. Visto como uma solução alternativapara essa desestabilização, o reembasamento das próteses totais com esses materiais resilientesvisa a readaptar a base da prótese ao rebordo alveolar por meio da adição de uma camada dematérias plásticas à superfície interna da prótese total. Os materiais resilientes ou macios parabase de próteses totais são utilizados na clínica odontológica com a finalidade de proporcionarmaior conforto e eficiência mastigatória aos pacientes que se utilizam dessas próteses. Contudo,a maioria das próteses totais reembasadas com materiais resilientes não possuem longevidadesatisfatória, por sofrerem diversos tipos de avarias, como a microinfiltração, impossibilitando,muitas vezes, a continuidade de seu uso em razão do deslocamento do material forrador.Assim, o objetivo do presente trabalho foi realizar uma revisão de literatura para comparar osdiversos materiais para reembasamento presentes no mercado e analisar as características decada material.Palavras-chave: Reembasadores de prótese dentária. Elasticidade. Resinas acrílicas. Resistênciaà Tração

Primary vs. Secondary Heart Failure Diagnosis: Differences in Clinical Outcomes, Healthcare Resource Utilization and Cost.

There is scarce information on patients with secondary heart failure diagnosis (sHF). We aimed to compare the characteristics, burden, and outcomes of sHF with those with primary HF diagnosis (pHF). Retrospective, observational study on patients ≥18 years with emergency department (ED) visits during 2018 with pHF and sHF in ED or hospital (ICD-10-CM) diagnostic codes. Baseline characteristics, 30-day and 1-year mortality, readmission and re-ED visit rates, and costs were compared between sHF and pHF. Out of the 797 patients discharged home from the ED, 45.5% had sHF, and these presented lower 1-year hospitalization, re-ED visit rates, and costs. In contrast, out of the 2,286 hospitalized patients, 55% had sHF and 45% pHF. Hospitalized sHF patients had significantly (p < 0.01) greater comorbidity, lower use of recommended HF therapies, longer length of stay (10.8 ± 10.1 vs. 9.7 ± 7.9 days), and higher in-hospital and 1-year mortality (32 vs. 25.8%) with no significant differences in readmission rates and lower 1-year re-ED visit rate. Hospitalized sHF patients had higher total costs (€12,262,422 vs. €9,144,952, p < 0.001), mean cost per patient-year (€9,755 ± 13,395 vs. €8,887 ± 12,059), and average daily cost per patient. Hospitalized sHF patients have a worse initial prognosis, greater use of healthcare resources, and higher costs.This study was an investigator-initiated initiative sponsored and supported by the grant from AstraZeneca Spain. LV receives research funding from the Instituto de Salud Carlos III, Spain (CM20/00104). GM is supported by a pre-doctoral grant by the Spanish Ministry of Education (FPU18/03606).S

Incidence of Tuberculosis Among Young Children in Rural Mozambique

BACKGROUND: Tuberculosis (TB) contributes significantly to child morbidity and mortality. This study aimed to estimate the minimum community-based incidence rate of TB among children <3 years of age in Southern Mozambique. METHODS: Between October 2011 and October 2012, in the Manhica District Health and Demographic Surveillance System, we enrolled prospectively all presumptive TB cases younger than 3 years of age through passive and active case finding. Participants included all children who were either symptomatic or were close contacts of a notified adult smear-positive pulmonary TB. Children were clinically evaluated at baseline and follow-up visits. Investigation for TB disease included chest radiography, HIV and tuberculin skin testing as well as gastric aspirate and induced sputum sampling, which were processed for smear, culture and mycobacterial molecular identification. RESULTS: During the study period, 13,764 children <3 years contributed to a total of 9575 person-year. Out of the 789 presumptive TB cases enrolled, 13 had TB culture confirmation and 32 were probable TB cases. The minimum community-based incidence rate of TB (confirmed plus probable cases) was 470 of 100,000 person-year (95% confidence interval: 343-629 of 100,000). HIV co-infection was present in 44% of the TB cases. CONCLUSION: These data highlight the huge burden of pediatric TB. This study provides one of the first prospective population-based incidence data of childhood tuberculosis and adds valuable information to the global effort of producing better estimates, a critical step to inform public health policy

Galaxy clusters and groups in the ALHAMBRA Survey

We present a catalogue of 348 galaxy clusters and groups with $0.2<z<1.2$ selected in the 2.78 $deg^2$ ALHAMBRA Survey. The high precision of our photometric redshifts, close to $1\%$, and the wide spread of the seven ALHAMBRA pointings ensure that this catalogue has better mass sensitivity and is less affected by cosmic variance than comparable samples. The detection has been carried out with the Bayesian Cluster Finder (BCF), whose performance has been checked in ALHAMBRA-like light-cone mock catalogues. Great care has been taken to ensure that the observable properties of the mocks photometry accurately correspond to those of real catalogues. From our simulations, we expect to detect galaxy clusters and groups with both $70\%$ completeness and purity down to dark matter halo masses of $M_h\sim3\times10^{13}\rm M_{\odot}$ for $z<0.85$. Cluster redshifts are expected to be recovered with $\sim0.6\%$ precision for $z<1$. We also expect to measure cluster masses with $\sigma_{M_h|M^*_{CL}}\sim0.25-0.35\, dex$ precision down to $\sim3\times10^{13}\rm M_{\odot}$, masses which are $50\%$ smaller than those reached by similar work. We have compared these detections with previous optical, spectroscopic and X-rays work, finding an excellent agreement with the rates reported from the simulations. We have also explored the overall properties of these detections such as the presence of a colour-magnitude relation, the evolution of the photometric blue fraction and the clustering of these sources in the different ALHAMBRA fields. Despite the small numbers, we observe tentative evidence that, for a fixed stellar mass, the environment is playing a crucial role at lower redshifts (z$<$0.5).Comment: Accepted for publication in MNRAS. Catalogues and figures available online and under the following link: http://bascaso.net46.net/ALHAMBRA_clusters.htm

A Zn2+-triggered two-step mechanism of CLIC1 membrane insertion and activation into chloride channels

The chloride intracellular channel (CLIC) protein family displays the unique feature of altering its structure from a soluble form to a membrane-bound chloride channel. CLIC1, a member of this family, is found in the cytoplasm or in internal and plasma membranes, with membrane relocalisation linked to endothelial disfunction, tumour proliferation and metastasis. The molecular switch promoting CLIC1 activation remains under investigation. Here, cellular Cl− efflux assays and immunofluorescence microscopy studies have identified intracellular Zn2+ release as the trigger for CLIC1 activation and membrane insertion. Biophysical assays confirmed specific binding to Zn2+, inducing membrane association and enhancing Cl− efflux in a pH-dependent manner. Together, our results identify a two- step mechanism with Zn2+ binding as the molecular switch promoting CLIC1 membrane insertion, followed by pH-mediated activation of Cl− efflux

How should performance in EBUS mediastinal staging in lung cancer be measured?

There has been a paradigm shift in mediastinal staging algorithms in non-small cell lung cancer over the last decade in the United Kingdom (UK). This has seen endoscopic nodal staging (predominantly endobronchial ultrasound, EBUS) almost replace surgical staging (predominantly mediastinoscopy) as the pathological staging procedure of first choic

Obstáculos e desafios atuais da saúde pública no Brasil

The present work proposes a critical reflection concerning the process of implementation of the Brazilian Unified Health System (SUS), by analyzing the difficulties, dilemmas, weaknesses and challenges faced by the system. In addition, we discuss the positive aspects of the SUS, its future prospects and possible directions and problem-solving strategies, having as a reference the consolidation of a democratic societyO presente trabalho desenvolve uma reflexão crítica sobre o processo de implementação do Sistema Único de Saúde (SUS) no Brasil, analisando as dificuldades, dilemas, debilidades e desafios a que tem de fazer frente este sistema. Além disso, o artigo discute seus pontos fortes, assinalando as perspectivas de futuro e possíveis vias e estratégias de solução dos problemas, tendo como referência a consolidação de uma sociedade democrática

J-PAS: Forecasts for dark matter - dark energy elastic couplings

We consider a cosmological model where dark matter and dark energy feature a coupling that only affects their momentum transfer in the corresponding Euler equations. We perform a fit to cosmological observables and confirm previous findings within these scenarios that favour the presence of a coupling at more than $3\sigma$. This improvement is driven by the Sunyaev-Zeldovich data. We subsequently perform a forecast for future J-PAS data and find that clustering measurements will permit to clearly discern the presence of an interaction within a few percent level with the uncoupled case at more than $10\sigma$ when the complete survey, covering $8500$ sq. deg., is considered. We found that the inclusion of weak lensing measurements will not help to further constrain the coupling parameter. For completeness, we compare to forecasts for DESI and Euclid, which provide similar discriminating power.Comment: 34 pages, 17 figures, added some clarifications and discussions, matches published versio