Vitamin D status and incidence of tuberculosis infection conversion in contacts of pulmonary tuberculosis patients: a prospective cohort study.

The objective of this study was to estimate the relationship between serum vitamin D (VitD) status and tuberculosis (TB) infection conversion (TBIC), measured by the tuberculin skin test (TST) and an interferon-gamma release assay, the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in the contacts of pulmonary TB patients in Castellon (Spain) in a prospective cohort study from 2010 to 2012. Initially, the participants were negative to latent TB infection after a screening that included TST and QFT-GIT tests, and other examinations. A baseline determination of 25-hydroxyvitamin D [25(OH)D] was obtained by chemiluminescence immunoassay. After 8-10 weeks, participants were screened for a second time to determine TB infection conversion (TBIC). Poisson regression models were used in the statistical analysis. Of the 247 participants in the cohort, 198 (80·2%) were screened twice and 18 (9·1%) were TBIC cases. The means of VitD concentration in the TBIC cases and the non-cases were 20·7±11·9 and 27·2±11·4 ng/ml (P = 0·028), respectively. Adjusted for high exposure and TB sputum acid-fast bacilli (AFB)-positive index case, higher serum VitD concentration was associated with low incidence of TBIC (P trend = 0·005), and an increase of 1 ng/ml VitD concentration decreased the incidence of TBIC by 6% (relative risk 0·94, 95% confidence interval 0·90-0·99, P = 0·015). The results suggest that sufficient VitD level could be a protective factor of TBIC.

Epidemiological evolution and economic impact of the COVID-19 pandemic in the European Union and worldwide and effects of control strategies on them: An ecological study.

OBJECTIVE: To evaluate the epidemiological evolution and economic impact of COVID-19 pandemic in the European Union (EU) and worldwide, and the effects of control strategies on them. MATERIAL AND METHODS: We collected incidence, mortality, and gross domestic product (GDP) data between the first quarter of 2020 and of 2023. Then, we reviewed the effectiveness of the mitigation and zero-COVID control strategies. The statistical analysis was done calculating the incidence rate ratio (IRR) of two rates and its 95% confidence interval (CI). RESULTS: In the EU, COVID-19 presented six epidemic waves. The sixth one at the beginning of 2022 was the biggest. Globally, the biggest wave occurred at the beginning of 2023. Highest mortality rates were observed in the EU during 2020-2021 and globally at the beginning of 2021. In mitigation countries, mortality was much higher than in zero-COVID countries (IRR=6.82 [95% CI: 6.14-7.60]; p<0.001). A GDP reduction was observed worldwide, except in Asia. None of the eight zero-COVID countries presented a GDP growth percentage lower than the EU percentage in 2020, and 3/8 in 2022 (p=0.054). COVID-19 pandemic caused epidemic waves with high mortality rates and a negative impact on GDP. CONCLUSION: The zero-COVID strategy was more effective in avoiding mortality and potentially had a lower impact on GDP in the first pandemic year.

Factors associated with referrals for directly observed treatment and unsuccessful treatment.

To describe the characteristics of people indicated for directly observed treatment (DOT) in Spain, and the factors associated with unsuccessful treatment.This was a multicentre observational study based on a prospective follow-up of patients over 18 years old diagnosed with TB between 2006 and 2019 from the registry of the Programa Integrado de Investigación en Tuberculosis (PII-TB). Sociodemographic and clinical variables were collected. Adjusted odds ratios (aORs) were calculated for the indication of DOT and for having an unsuccessful treatment.A total of 7,883 patients were included. The indication of DOT was associated with being homeless (aOR 5.93, 95% CI 3.03-11.59), inactivity status (aOR 2.55, 95% CI 2.02-3.23), alcohol consumption (aOR 1.94, 95% CI 1.51-2.48), parenteral drug use (aOR 1.77, 95% CI 1.06-2.95) and HIV diagnosis (aOR 1.96, 95% CI 1.16-3.29). Unsuccessful treatment was associated with having an HIV diagnosis (aPR 2.31, 95% CI 1.31-4.08), having a worse clinical and radiological evolution (clinical progression: APR 15.59, 95% CI 8.21-29.60; radiological progression: aPR 12.84, 95% CI 6.46-25.52), need for hospitalisation (aPR 1.73, 95% CI 1.10-2.73), unsatisfactory tolerability (aPR 2.82, 95% CI 1.49-5.29), the existence of difficulties in understanding the prescribed treatment (aPR 1.92, 95% CI 1.21-3.06), as well as worse treatment satisfaction (aPR 7.27, 95% CI 4.32-12.24).The prioritisation of vulnerable populations is a key aspect to carry out the new Global Plan to End TB 2023-2030. In these groups DOT indication should be increased to ensure adherence and patient follow-up and outcomes..

Assessment of the Interelectrode Distance Effect over the Omnipole with High Multielectrode Arrays.

The development of high-density multielectrode catheters has significantly advanced cardiac electrophysiology mapping. High-density grid catheters have enabled the creation of a novel technique for reconstructing electrogram (EGM) signals known as "omnipole," which is believed to be more reliable than other methods, especially in terms of orientation independence. This study aims to evaluate how distance affects the omnipolar reconstruction of EGMs by comparing different configurations. Using an animal set up of perfused isolated rabbit hearts, recordings were taken using an ad hoc high-density epicardial multielectrode catheter. Inter-electrode distances ranging from 1 to 4 mm were analysed for their effect on the quality of resulting EGMs. Two biomarkers were computed to evaluate the robustness of the reconstructions: the areas contained within the bipolar loops and the amplitudes of the omnipoles. We hypothesised that both bipolar and omnipolar electrograms would be more robust at shorter inter-electrode distances. The results showed that an increase in distance triggers an increase in loop areas and amplitudes, which supports the hypothesis. This finding provides a more reliable estimate of wavefront propagation for the cross-omnipolar reconstruction method. These results emphasise the importance of distance in cardiac electrophysiology mapping and provide valuable insights into the use of high-density multielectrode catheters for EGM reconstruction.Clinical Relevance- The results of this study have direct clinical relevance in the application of the described techniques to recording systems in the cardiac electrophysiology laboratory, enabling clinicians to obtain more precise characterisation of signals in the myocardium.

Development of a cell for in-situ/operando Mössbauer spectroscopy studies of Catalysts: Application to the characterization of iron nanoparticles used in Fischer-Tropsch reaction.

In this paper, we report the design of a stainless-steel cell with polyimide film windows for carrying out in situ Mossbauer spectroscopy studies with a horizontal x-ray beam. It allows recording spectra at pressures up to 0.2-0.3 MPa and temperatures up to 500 °C under a gas flow rate of up to 100 ml min-1. The catalyst is either directly deposited on the heating element or pressed into the form of a pellet for larger quantities. A wide range of heating or cooling rates can be used, and a very accurate sample temperature can be monitored for several days. An example of application to the study of a catalyst based on iron nanoparticles entrapped in silicalite-1 used for the Fischer-Tropsch reaction is presented to illustrate the use of the cell.

Spatial distribution and temporal dynamics of invasive and native mosquitoes in a large Mediterranean city.

Mosquitoes, including invasive species like the Asian tiger mosquito Aedes albopictus, alongside native species Culex pipiens s.l., pose a significant nuisance to humans and serve as vectors for mosquito-borne diseases in urban areas. Understanding the impact of water infrastructure characteristics, climatic conditions, and management strategies on mosquito occurrence and effectiveness of control measures to assess their implications on mosquito occurrence is crucial for effective vector control. In this study, we examined data collected during the local vector control program in Barcelona, Spain, focusing on 234,225 visits to 31,334 different sewers, as well as 1817 visits to 152 fountains between 2015 and 2019. We investigated both the colonization and recolonization processes of mosquito larvae within these water infrastructures. Our findings revealed higher larval presence in sandbox-sewers compared to siphonic or direct sewers, and the presence of vegetation and the use of naturalized water positively influenced larval occurrence in fountains. The application of larvicidal treatment significantly reduced larvae presence; however, recolonization rates were negatively affected by the time elapsed since treatment. Climatic conditions played a critical role in the colonization and recolonization of sewers and urban fountains, with mosquito occurrence exhibiting non-linear patterns and, generally, increasing at intermediate temperatures and accumulated rainfall levels. This study emphasizes the importance of considering sewers and fountains characteristics and climatic conditions when implementing vector control programs to optimize resources and effectively reduce mosquito populations.

Functional mathematical model of dual pathway AV nodal conduction.

Dual atrioventricular (AV) nodal pathway physiology is described as two different wave fronts that propagate from the atria to the His bundle: one with a longer effective refractory period [fast pathway (FP)] and a second with a shorter effective refractory period [slow pathway (SP)]. By using His electrogram alternance, we have developed a mathematical model of AV conduction that incorporates dual AV nodal pathway physiology. Experiments were performed on five rabbit atrial-AV nodal preparations to develop and test the presented model. His electrogram alternances from the inferior margin of the His bundle were used to identify fast and slow wave front propagations. The ability to predict AV conduction time and the interaction between FP and SP wave fronts have been analyzed during regular and irregular atrial rhythms (e.g., atrial fibrillation). In addition, the role of dual AV nodal pathway wave fronts in the generation of Wenckebach periodicities has been illustrated. Finally, AV node ablative modifications have been evaluated. The model accurately reproduced interactions between FP and SP during regular and irregular atrial pacing protocols. In all experiments, specificity and sensitivity higher than 85% were obtained in the prediction of the pathway responsible for conduction. It has been shown that, during atrial fibrillation, the SP ablation significantly increased the mean HH interval (204 ± 39 vs. 274 ± 50 ms, P < 0.05), whereas FP ablation did not produce significant slowing of ventricular rate. The presented mathematical model can help in understanding some of the intriguing AV node mechanisms and should be considered as a step forward in the studies of AV nodal conduction.

[Contact tracing in patients infected with SARS-CoV-2. The fundamental role of Primary Health Care and Public Health]. / Estudio de contactos en infectados por SARS-CoV-2. El papel fundamental de la Atención Primaria y de la Salud Pública.

The aim of this study was to promote the rapid identification of the contacts of patients infected with SARS-CoV-2 and therefore the control of the pandemic. Different methodologies and recommendations on contact tracing for Primary Health Care (PHC) and Public Health Services (PHS), like articles in Pubmed about COVID-19 and contact tracing, official contact definitions, the classic contact tracing model in tuberculosis (TB), information about apps for contact tracing and the role of the diagnostic tests, were reviewed. To establish efficient prevention and control measures, it is always necessary to implement contact tracing based on clinical suspicion, early diagnosis and isolation of cases and contacts and their follow-up. The classic contact tracing model in TB can be applied to this new infection, but accelerating the process given its acute nature and its potential severity. Good coordination between PHC and PHS and having sufficient resources is essential.

Diagnostic benefits of adding EspC, EspF and Rv2348-B to the QuantiFERON Gold In-tube antigen combination.

Interferon (IFN)-γ release assays (IGRAs) are used to diagnose latent tuberculosis (TB) infection (LTBI). To improve the accuracy of these tests, different approaches, such as alternative cytokine detection and using different antigens, are considered. Following this purpose, this study aims to evaluate the addition of EspC, EspF and Rv2348-B to those present in the QuantiFERON-TB Gold In-Tube (QFN-G-IT). We included 115 subjects: 74 active TB patients, 17 LTBI individuals and 24 healthy controls. Whole blood samples were collected in QFN-G-IT and in-house tubes containing different combinations of EspC, EspF and Rv2348-B, together with ESAT-6, CFP-10, and TB7.7. After overnight incubation at 37 ºC, plasma was harvested and IFN-γ quantified. IFN-γ levels in the QFN-G-IT and in-house tubes correlated very good (Spearman Rho(r) > 0.86). In-house antigen combinations distinguished healthy individuals from those with active TB and LTBI (specificities and sensitivities higher than 87.5% and 96.3%, respectively [AUC > 0.938]). Adding EspC, EspF and Rv2348-B, increased the sensitivity of the test, being the addition of EspC and Rv2348-B the combination that yielded a higher sensitivity with no specificity loss. Addition of these antigens could improve diagnosis in patients with impaired or immature immune response who are at high risk of developing TB.

Vitamin D status and latent tuberculosis infection: conversion in nursing homes, Spain.

OBJECTIVE: To examine the potential association between vitamin D (VitD) deficiency and latent tuberculosis infection (LTBI) and its effect on TB infection conversion (TBIC) incidence.MATERIAL AND METHODS: We carried out a cross-sectional and prospective cohort study of nine pulmonary TB cases that occurred in 2015-2016 in five nursing homes and one mental disability institution in Castellon, Spain. QuantiFERON®-TB Gold and the tuberculin skin test were used to detect LTBI and TBIC, respectively. Serum 25-hydroxyvitamin D was measured using chemiluminescence immunoassay. Poisson regression and inverse probability weighting were used for statistical analyses.RESULTS: The study included 448 residents, 341 staff members with 48 relatives of TB cases (participation rate 82%): of these, respectively 122 (27.2%), 37 (10.9%) and 7 (14.6%) were LTBI-positive; and respectively 22 (7.7%), 10 (3.8%) and 1 (3.7%) were TBIC-positive. LTBI was not associated with VitD status. Severe VitD deficiency (SVDD; defined as VitD level < 10 ng/ml), found in 45.1% of residents, as well as VitD levels of <30 ng/ml (aRR 10.41 95% CI 1.48-73.26), were associated with increased TBIC risk (adjusted relative risk [aRR] 12.1, 95% CI 1.51-97.10), suggesting SVDD as a threshold effect. CONCLUSION: Severe VitD deficiency is a TBIC risk factor.

Impact of socio-economic inequities on tuberculosis in a Southern European city: what is the effect of the recession?

INTRODUCTION: Economic crises affect a population's health, particularly among the most deprived. The increase in health inequalities in the latest recession may have influenced the incidence of tuberculosis (TB). We analysed the effect of socio-economic inequities and recession on TB incidence in Barcelona, Spain. METHODS: We conducted a population-based incidence study of TB cases in Barcelona of patients who started treatment between 2003 and 2015. A multilevel interrupted time-series analysis was performed to analyse differences in incidence trends between the pre-recession (until 2008) and recession periods. RESULTS: We found differences in TB incidence according to deprivation and immigration status. TB incidence among the most deprived neighbourhoods was 2.72 times higher than the least deprived neighbourhoods. Compared with native-born persons, incidence was nine times higher among those born in Africa, and six times higher among those born in Asia and Oceania. The previous decreasing trend in incidence (4%) was accentuated during the recession (7%). CONCLUSIONS: TB incidence decreased during the recession, probably due to a reduction in the number of new immigrants and the TB programme. However, incidence was highly unequal between districts with different levels of deprivation, and between foreign-born persons from different geographic regions. Social measures are important to reduce inequalities and TB incidence in Barcelona.

Use of IP-10 detection in dried plasma spots for latent tuberculosis infection diagnosis in contacts via mail.

The aim of this study was to test the use of IP-10 detection in dried plasma from contact studies individuals (contacts of smear positive patients), by comparing it with IP-10 and IFN-γ detection in direct plasma, to establish IP-10 detection in DPS as a useful assay for LTBI diagnosis. Whole blood samples were collected from 80 subjects: 12 with active tuberculosis (TB), and 68 from contact studies. The amount of IFN-γ produced by sensitized T cells was determined in direct plasma by QuantiFERON Gold In-Tube test. IP-10 levels were determined in direct and dried plasma by an in-house ELISA. For dried plasma IP-10 determination, two 25 µl plasma drops were dried in Whatman903 filter paper and sent by mail to the laboratory. Regarding TB patients, 100.0%, 91.7% and 75.0% were positive for IFN-γ detection and IP-10 detection in direct and dried plasma, respectively. In contacts, 69.1%, 60.3% and 48.5% had positive results after IFN-γ and IP-10 in direct and dried plasma, respectively. The agreement among in vitro tests was substantial and IP-10 levels in direct and dried plasma were strongly correlated (r = 0.897). In conclusion, IP-10 detection in dried plasma is a simple and safe method that would help improve LTBI management.

Anesthesia with propofol slows atrial fibrillation dominant frequencies.

The mechanisms responsible for the maintenance of atrial fibrillation (AF) are not completely understood yet. It has been demonstrated that AF can be modulated by several cardiac diseases, the autonomic nervous system and even drugs with purportedly no antiarrhythmic properties. We evaluated the effects of a widely used anaesthetic agent (propofol) in the fibrillation patterns. Spectral analysis was performed over atrial electrograms at baseline and immediately after a propofol bolus. Only after performing principal component analysis (PCA), we were able to significantly detect that propofol slows AF.

In vitro antimicrobial activity of the leaf extract of Harungana madagascariensis Lam. Ex Poir. (Hypericaceae) against strains causing otitis externa in dogs and cats.

Otitis externa in dogs and cats is always caused by a combination of yeasts and bacteria, among which the most important are Malassezia pachydermatis, Staphylococcus intermedius and Pseudomonas species. These organisms often develop resistance to classical antimicrobial agents. Therefore, the aim of this study was to investigate the antimicrobial activities of an ethyl acetate leaf extract of Harungana madagascariensis against the organisms cited, to carry out the phytochemical investigation of this extract and to determine its bioactive chemical class using dilution techniques, the bioautography method and the standard phytochemical method described by Harborne (1973). Phytochemical analysis revealed the presence of saponins, tannins, flavonoids, alkaloids and anthracenic derivatives. The bioassay showed that the antimicrobial properties may be attributed to astilbin, a flavanone derivative identified on the basis of its spectroscopic data. The results suggest that the extract could be used in an antimicrobial preparation effective against the whole range of organisms incriminated in otitis externa in dogs and cats, with a minimal inhibitory concentration (MIC) of 250 microg/ml.

Isolation and in vitro antibacterial activity of astilbin, the bioactive flavanone from the leaves of Harungana madagascariensis Lam. ex Poir. (Hypericaceae).

Harungana madagascariensis is well known for its topical antibacterial properties used in the elaboration of a lot of skin hygiene products. The aim of this study was, on the one hand, to evaluate the in vitro antibacterial activities of aqueous, ethanolic and ethyl acetate crude extracts of Harungana madagascariensis leaves against bacterial strains representative of skin microflora and, on the other hand, to determine the chemical structure of the active compound. Only the ethyl acetate leaf extract presented important antibacterial activity. Its fractionation was carried out by column chromatography using silica gel 60 and it yielded 11 fractions. A bioautographic method, revealed in these fractions the presence of a flavanone as the active compound astilbin or 3-O-alpha-L-rhamnoside-5,7,3',4'-tetrahydroxydihydroflavonol which was identified on the basis of its spectroscopic data. Concerning the antibacterial activity against the representative skin microflora of the armpit and feet, MIC and MBC ranged from 25 to 250 and 100 to 750 microg ml-1, respectively. The results showed that some bacteria considered to be responsible for bad odours at the armpit and feet levels, were destroyed at 200 microg ml-1 (MBC), a concentration sparing most of the useful saprophytic microflora. The minimal inhibitory quantity (MIQs) of astilbin ranged from 50 to 100 microg.

Tuberculosis clinical units improve contact tracing.

INTRODUCTION: The Barcelona Tuberculosis Programme was established in 1987, and in 2007 five tuberculosis (TB) clinical units were created to improve the follow-up of cases and contacts. This included the designation of a nurse for case management. OBJECTIVE: To assess the impact of the TB clinical units on the screening programme for TB contacts. METHODS: Before-after population-based study before (2003-2007) and after (2008-2013) the creation of the clinical units. To determine which factors were related to contact tracing, we fitted a multivariate logistic regression model to estimate odds ratios (OR) with their 95% confidence intervals (CIs). RESULTS: Following the creation of the clinical units, the proportion of prescriptions for latent tuberculous infection among contacts in the clinical units increased from 40.7% to 57.4% (P < 0.001), and treatment adherence from 75.9% to 80.3% (P = 0.035). One factor associated with contact tracing was receiving care after the creation of the clinical units (2008-2013) (OR 1.2, 95%CI 1.0-1.3). During the second period, receiving care outside the clinical units reduced the probability of contact tracing (OR 0.7, 95%CI 0.5-0.9). CONCLUSION: The creation of the TB clinical units represents an organisational improvement for the study and management of contacts of patients with TB.

Factors Associated with Fatality during the Intensive Phase of Anti-Tuberculosis Treatment.

OBJECTIVE: To determine the case-fatality rate (CFR) at the end of the intensive phase of tuberculosis (TB) treatment, and factors associated with fatality. METHODS: TB patients diagnosed between 2006 and 2013 were followed-up during treatment. We computed the CFR at the end of the intensive phase of TB treatment, and the incidence of death per 100 person-days (pd) of follow-up. We performed survival analysis using the Kaplan-Meier method and Cox regression, and calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: A total of 5,182 patients were included, of whom 180 (3.5%) died; 87 of these deaths (48.3%) occurred during the intensive phase of treatment, with a CFR of 1.7%. The incidence of death was 0.028/100 pd. The following factors were associated with death during the intensive phase: being >50 years (HR = 36.9;CI:4.8-283.4); being retired (HR = 2.4;CI:1.1-5.1); having visited the emergency department (HR = 3.1;CI:1.2-7.7); HIV infection (HR = 3.4;CI:1.6-7.2); initial standard treatment with 3 drugs (HR = 2.0;CI:1.2-3.3) or non-standard treatments (HR = 2.68;CI:1.36-5.25); comprehension difficulties (HR = 2.8;CI:1.3-6.1); and smear-positive sputum (HR = 2.3-CI:1.0-4.8). CONCLUSION: There is a non-negligible CFR during the intensive phase of TB, whose reduction should be prioritised. The CFR could be a useful indicator for evaluating TB programs.

Crystallization and preliminary X-ray diffraction study of an endoglucanase from Clostridium thermocellum.

Endoglucanase D, a cellulose degradation enzyme from Clostridium thermocellum has been cloned in Escherichia coli, purified and crystallized. The crystals are trigonal, space group P3(1)12 (or P3(2)12) with a = 57.7 (+/- 0.1) A, c = 192.1 (+/- 0.2) A, and diffract X-rays to a resolution of 2.8 A. They are suitable for a high-resolution X-ray diffraction analysis.

Spatiotemporal blind source separation approach to atrial activity estimation in atrial tachyarrhythmias.

The analysis and characterization of atrial tachyarrhythmias requires, in a previous step, the extraction of the atrial activity (AA) free from ventricular activity and other artefacts. This contribution adopts the blind source separation (BSS) approach to AA estimation from multilead electrocardiograms (ECGs). Previously proposed BSS methods for AA extraction--e.g., independent component analysis (ICA)--exploit only the spatial diversity introduced by the multiple spatially-separated electrodes. However, AA typically shows certain degree of temporal correlation, with a narrowband spectrum featuring a main frequency peak around 3.5-9 Hz. Taking advantage of this observation, we put forward a novel two-step BSS-based technique which exploits both spatial and temporal information contained in the recorded ECG signals. The spatiotemporal BSS algorithm is validated on simulated and real ECGs from a significant number of atrial fibrillation (AF) and atrial flutter (AFL) episodes, and proves consistently superior to a spatial-only ICA method. In simulated ECGs, a new methodology for the synthetic generation of realistic AF episodes is proposed, which includes a judicious comparison between the known AA content and the estimated AA sources. Using this methodology, the ICA technique obtains correlation indexes of 0.751, whereas the proposed approach obtains a correlation of 0.830 and an error in the estimated signal reduced by a factor of 40%. In real ECG recordings, we propose to measure performance by the spectral concentration (SC) around the main frequency peak. The spatiotemporal algorithm outperforms the ICA method, obtaining a SC of 58.8% and 44.7%, respectively.