In paired preference tests, domestic chicks innately choose the colour green over red, and the shape of a frog over a sphere when both stimuli are green.

Many animals express unlearned colour preferences that depend on the context in which signals are encountered. These colour biases may have evolved in response to the signalling system to which they relate. For example, many aposematic animals advertise their unprofitability with red warning signals. Predators' innate biases against these warning colours have been suggested as one of the potential explanations for the initial evolution of aposematism. It is unclear, however, whether unlearned colour preferences reported in a number of species is truly an innate behaviour or whether it is based on prior experience. We tested the spontaneous colour and shape preferences of dark-hatched, unfed, and visually naive domestic chicks (Gallus gallus). In four experiments, we presented chicks with a choice between either red (a colour typically associated with warning patterns) or green (a colour associated with palatable cryptic prey), volume-matched spheres (representing a generalised fruit shape) or frogs (representing an aposematic animal's shape). Chicks innately preferred green stimuli and avoided red. Chicks also preferred the shape of a frog over a sphere when both stimuli were green. However, no preference for frogs over spheres was present when stimuli were red. Male chicks that experienced a bitter taste of quinine immediately before the preference test showed a higher preference for green frog-shaped stimuli. Our results suggest that newly hatched chicks innately integrate colour and shape cues during decision making, and that this can be augmented by other sensory experiences. Innate and experience-based behaviour could confer a fitness advantage to novel aposematic prey, and favour the initial evolution of conspicuous colouration.

Comparison of three short-course rifamycin-based regimens for the prevention of tuberculosis in patients with end-stage kidney disease: Study protocol for a randomised clinical trial (RIFAKiD-TB trial).

BACKGROUND AND PURPOSE: Screening for and treatment of latent tuberculosis (TB) in patients with end-stage kidney disease (ESKD) are recommended. However, there is limited evidence on safety and treatment completion in this population. The objective of the study is to evaluate three short-course rifamycin-based regimens for the treatment of latent TB in ESKD patients. METHODS: Study design and setting. This is a prospective, open label, randomized clinical trial, that will be conducted at seven teaching hospitals in Spain. Study population, randomization, and interventions. Consecutive adult patients with ESKD requiring treatment for a latent TB infection will be randomly allocated (1:1:1) to receive one of the three treatment regimens of the study: three months of daily isoniazid plus rifampicin (3HR); three months of once-weekly isoniazid plus rifapentine (3HP); or four months of daily rifampicin (4R). Participants will be followed regularly through pre-established visits and a blood test schedule from enrolment to a month after finishing the assigned treatment. Outcomes. The primary outcome will be treatment completion, while the secondary outcomes will be discontinuation of the assigned treatment due to adverse events, related or unrelated to the study treatment; definitive discontinuation of the assigned treatment because of adverse events related to the treatment of the study, and death. Sample size. Two hundred and twenty-five subjects (75 per arm) will be enrolled, which will enable the demonstration, if it exists, of an increase of 0.16 in treatment completion rates either in the 3HP or 4R arm with respect to the 3HR arm. DISCUSSION: Results of this clinical trial will contribute to evidence-based recommendations on the management of latent TB infection in ESKD patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05021731.

Activation of the Nucleus Taeniae of the Amygdala by Umami Taste in Domestic Chicks (Gallus gallus).

In chickens, the sense of taste plays an important role in detecting nutrients and choosing feed. The molecular mechanisms underlying the taste-sensing system of chickens are well studied, but the neural mechanisms underlying taste reactivity have received less attention. Here we report the short-term taste behaviour of chickens towards umami and bitter (quinine) taste solutions and the associated neural activity in the nucleus taeniae of the amygdala, nucleus accumbens and lateral septum. We found that chickens had more contact with and drank greater volumes of umami than bitter or a water control, and that chicks displayed increased head shaking in response to bitter compared to the other tastes. We found that there was a higher neural activity, measured as c-Fos activation, in response to umami taste in the right hemisphere of the nucleus taeniae of the amygdala. In the left hemisphere, there was a higher c-Fos activation of the nucleus taeniae of the amygdala in response to bitter than in the right hemisphere. Our findings provide clear evidence that chickens respond differently to umami and bitter tastes, that there is a lateralised response to tastes at the neural level, and reveals a new function of the avian nucleus taeniae of the amygdala as a region processing reward information.

A laboratory and simulation platform to integrate individual life history traits and population dynamics.

Understanding populations is important because they are a fundamental level of biological organization. Individual traits such as aging and lifespan interact in complex ways to determine birth and death and thereby influence population dynamics. However, we lack a deep understanding of the relationships between individual traits and population dynamics. To address this challenge, we established a laboratory population using the model organism C. elegans and an individual-based computational simulation informed by measurements of real worms. The simulation realistically models individual worms and the behavior of the laboratory population. To elucidate the role of aging in population dynamics, we analyzed old age as a cause of death and showed, using computer simulations, that it was influenced by maximum lifespan, rate of adult culling, and progeny number/food stability. Notably, populations displayed a tipping point for aging as the primary cause of adult death. Our work establishes a conceptual framework that could be used for better understanding why certain animals die of old age in the wild.

A SNAI2-PEAK1-INHBA stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting subpopulations of tumor cells positive for antiapoptotic and stress signaling markers.

Intercellular mechanisms by which the stromal microenvironment contributes to solid tumor progression and targeted therapy resistance remain poorly understood, presenting significant clinical hurdles. PEAK1 (Pseudopodium-Enriched Atypical Kinase One) is an actin cytoskeleton- and focal adhesion-associated pseudokinase that promotes cell state plasticity and cancer metastasis by mediating growth factor-integrin signaling crosstalk. Here, we determined that stromal PEAK1 expression predicts poor outcomes in HER2-positive breast cancers high in SNAI2 expression and enriched for MSC content. Specifically, we identified that the fibroblastic stroma in HER2-positive breast cancer patient tissue stains positive for both nuclear SNAI2 and cytoplasmic PEAK1. Furthermore, mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) express high PEAK1 protein levels and potentiate tumorigenesis, lapatinib resistance and metastasis of HER2-positive breast cancer cells in a PEAK1-dependent manner. Analysis of PEAK1-dependent secreted factors from MSCs revealed INHBA/activin-A as a necessary factor in the conditioned media of PEAK1-expressing MSCs that promotes lapatinib resistance. Single-cell CycIF analysis of MSC-breast cancer cell co-cultures identified enrichment of p-Akthigh/p-gH2AXlow, MCL1high/p-gH2AXlow and GRP78high/VIMhigh breast cancer cell subpopulations by the presence of PEAK1-expressing MSCs and lapatinib treatment. Bioinformatic analyses on a PEAK1-centric stroma-tumor cell gene set and follow-up immunostaining of co-cultures predict targeting antiapoptotic and stress pathways as a means to improve targeted therapy responses and patient outcomes in HER2-positive breast cancer and other stroma-rich malignancies. These data provide the first evidence that PEAK1 promotes tumorigenic phenotypes through a previously unrecognized SNAI2-PEAK1-INHBA stromal cell axis.

Threats and Interventions During the Treatment of Tuberculosis in an Inner-city District / Factores de riesgo e intervenciones durante el tratamiento de la tuberculosis en un barrio marginal

Background: Since there are active drugs against tuberculosis (TB), the most effective control measures are to assure treatment adherence and to perform contact tracing. Given the long treatment duration and characteristics of some TB patients, threats that put at risk treatment adherence may appear. Identify and address them is essential to achieve the objectives of disease control.Objectives: To identify the epidemiological characteristics of TB patients and the incidents and threats occurring during treatment, to describe the interventions performed to enhance treatment adherence and to determine if there are differences among native and foreign-born patients in the TB clinical unit of a referral hospital in the inner city of Barcelona.Methods: A descriptive, observational, cross-sectional study was performed. We recorded information on sociodemographic and clinical characteristics, incidents and interventions during treatment in all patients with TB diagnosed between September 2013 and August 2016.Results: 172 patients were included, 62.2% were foreign-born. The most common incidents and threats were medication-related complications (43.0%), missed follow-up visits (34.3%), communication problems (25.6%), comorbidities complications (23.8%), trips (19.2%), fear of social rejection (16.9%) and change of address (14.5%). The adherence-promoting interventions were: follow-up calls, directly observed treatment, medical and humanitarian reports, extra visits and cultural mediation. Incidents and interventions were more frequent in foreign-born patients, however there were no differences in treatment success among Spanish and foreign-born. (AU)

Antecedentes: Dado que existen medicamentos activos contra la tuberculosis (TB), las medidas de control más efectivas son asegurar la adherencia al tratamiento y realizar un seguimiento cercano. Debido a la larga duración del tratamiento y las características de algunos pacientes con TB, pueden entrar en juego ciertos factores que hacen peligrar la adherencia al tratamiento. Identificar estos factores y abordarlos es esencial para lograr los objetivos de control de la enfermedad.Objetivos: Identificar las características epidemiológicas de los pacientes con TB y los incidentes y factores que tienen lugar durante el tratamiento, describir las intervenciones realizadas para mejorar la adherencia al tratamiento y determinar si existen diferencias entre los pacientes nativos y extranjeros en la Unidad Clínica de TB de un hospital de referencia en el centro de la ciudad de Barcelona.Métodos: Se realizó un estudio descriptivo, observacional y transversal. Registramos las características sociodemográficas y clínicas de todos los pacientes con TB diagnosticados entre septiembre de 2013 y agosto de 2016, así como los incidentes y las intervenciones realizadas durante el tratamiento.Resultados: Se incluyeron 172 pacientes, el 62,2% eran nacidos en el extranjero. Los incidentes y los factores de riesgo más comunes fueron: complicaciones relacionadas con la medicación (43,0%), visitas de seguimiento perdidas (34,3%), problemas de comunicación (25,6%), complicaciones de las comorbilidades (23,8%), viajes (19,2%), miedo al rechazo social (16,9%) y cambio de domicilio (14,5%). Las intervenciones para el fomento de la adherencia fueron: llamadas de seguimiento, tratamiento directamente observado, informes médicos y humanitarios, visitas adicionales y mediación cultural. Los incidentes e intervenciones fueron más frecuentes en pacientes nacidos en el extranjero; sin embargo, no hubo diferencias en el éxito del tratamiento entre españoles y nacidos en el extranjero. (AU)

Threats and Interventions During the Treatment of Tuberculosis in an Inner-city District.

BACKGROUND: Since there are active drugs against tuberculosis (TB), the most effective control measures are to assure treatment adherence and to perform contact tracing. Given the long treatment duration and characteristics of some TB patients, threats that put at risk treatment adherence may appear. Identify and address them is essential to achieve the objectives of disease control. OBJECTIVES: To identify the epidemiological characteristics of TB patients and the incidents and threats occurring during treatment, to describe the interventions performed to enhance treatment adherence and to determine if there are differences among native and foreign-born patients in the TB clinical unit of a referral hospital in the inner city of Barcelona. METHODS: A descriptive, observational, cross-sectional study was performed. We recorded information on sociodemographic and clinical characteristics, incidents and interventions during treatment in all patients with TB diagnosed between September 2013 and August 2016. RESULTS: 172 patients were included, 62.2% were foreign-born. The most common incidents and threats were medication-related complications (43.0%), missed follow-up visits (34.3%), communication problems (25.6%), comorbidities complications (23.8%), trips (19.2%), fear of social rejection (16.9%) and change of address (14.5%). The adherence-promoting interventions were: follow-up calls, directly observed treatment, medical and humanitarian reports, extra visits and cultural mediation. Incidents and interventions were more frequent in foreign-born patients, however there were no differences in treatment success among Spanish and foreign-born. CONCLUSION: In this inner city several incidents occurred during TB treatment that can threaten adherence and are more common among foreign-born patients. Coordination among professionals from different healthcare settings was able to overcome obstacles in most cases and achieve TB treatment completion.

Salud comunitaria confinada: reflexiones y experiencias desde la salud pública local / Confined community health: reflections and experiences from the local public health

Este artículo pretende compartir las reflexiones sobre la acción comunitaria en que la Agència de Salut Pública de Barcelona ha estado involucrada en la emergencia de COVID-19. El trabajo realizado puede ordenarse en tres etapas, frecuentemente solapadas: detectar necesidades o problemas, e informar; contactar con las personas participantes y agentes territoriales para valorar qué hacer y cómo hacerlo; y adaptar las intervenciones a la "nueva normalidad" y generar respuestas con los activos comunitarios a las necesidades detectadas. Los problemas emergentes incluyeron: no poder realizar el confinamiento (por falta de casa, condiciones materiales, vivir en situación de violencia); brecha digital (falta de conocimientos, dispositivos, acceso a Wifi); mayor exposición al COVID-19 en los trabajos esenciales pero precarizados, feminizados y racializados (cuidados, limpieza, alimentación), frecuentes en los barrios en que trabajamos; barreras idiomáticas y culturales para seguir las recomendaciones; pérdida de empleo; ingresos insuficientes para cubrir necesidades básicas; dificultades de conciliación; aislamiento social; y deterioro de la salud emocional provocado por la situación. Durante el proceso, algunas intervenciones se adaptaron para continuar de forma telemática, y se intentaron cubrir las necesidades primarias sobre conocimientos y dispositivos de algunas personas participantes a través de las redes solidarias y recursos existentes. La acción comunitaria en salud, desde una mirada crítica, interseccional y local, mediante trabajo intersectorial y la participación de la comunidad, puede contribuir a: facilitar una respuesta adaptada al contexto en caso de crisis sanitaria y mitigar los efectos derivados de esta crisis económica y social

This paper aims to share the reflections related to the community actions in which the Agència de Salut Pública de Barcelona has been involved during the emergency of COVID-19. The tasks carried out can be arranged in three stages, frequently overlapping: detection of needs and problems; contact with key stakeholders to assess what to do and how to do it; adaptation of the interventions to the "new normal" and generation of new responses. The emerging problems included: not being able to do the confinement (due to homelessness, material conditions, living in a situation of violence); digital gap (lack of knowledge, devices, access to Wifi); greater exposure to COVID-19 in the essential but precarious, feminized and racialized jobs (care, cleaning, food shops) that are the most frequent in the neighborhoods in where we work; language and cultural barriers that preclude to follow recommendations; to lose employment; insufficient income to cover basic needs; social isolation; and the deterioration of emotional health caused by the situation. During the process, some interventions were adapted to be delivered on-line. Solidarity networks and local resources were key to meet basic needs, but also other needs related to lack of digital knowledge or device. Community action in health, from a critical, intersectional and local perspective, and with intersectoral work and community participation, can contribute to: facilitate a contextualized response in the event of a health crisis; mitigate the effects derived from its economic and social crisis

Toxicity and Alkaloid Profiling of the Skin of the Golfo Dulcean Poison Frog Phyllobates vittatus (Dendrobatidae).

Frogs in the genus Phyllobates are known for the presence of batrachotoxin, a highly toxic alkaloid, in their skin. Nevertheless, Phyllobates frogs from Costa Rica and Panama (P. lugubris and P. vittatus) are considered non-toxic, as they have been reported to harbor low concentrations of this alkaloid. However, the potential toxicity of Central American Phyllobates has not been assessed experimentally. Our goal was to determine the toxicity of the whole skin of P. vittatus, an endemic species from the Southeastern Pacific region of Costa Rica. We performed median lethal dose (LD50) tests in mice to determine general toxicity, and an irritant assay based on the behavioral responses of mice to subcutaneous injection, to determine differences in irritability, as a measure of toxicity, among three study localities. Using UPLC-ESI-QTOF, we obtained chemical profiles of the methanolic extract of frog skins. Due to the absence of mortality at the studied doses, we were unable to estimate LD50. However, we recorded a list of toxicity symptoms in mice that are consistent with cardiotoxic effects, and found that mice presented more symptoms at higher concentrations of skin extracts during the first hour of the LD50 assays, recovering completely at all doses by the end of the assay. On the other hand, we did not detect differences in irritability among studied localities. Additionally, we putatively identified three toxic alkaloids (Batrachotoxinin A, DHQ 251A and Lehm 275A). This study provides the first experimental data on the toxicity and associated symptoms in mice, as well as the chemical profile of the skin of P. vittatus. We suggest that the skin alkaloids of P. vitattus may confer a chemical defense towards predators.

Secretomes from metastatic breast cancer cells, enriched for a prognostically unfavorable LCN2 axis, induce anti-inflammatory MSC actions and a tumor-supportive premetastatic lung.

Cancer metastasis is responsible for the clear majority of cancer-related deaths. Survival and expansion of cancer cells at secondary sites requires that these premetastatic microenvironments be primed by primary tumor cells and their secreted factors. Efforts to date have been limited by immune-deficient in vivo models and/or the need for finely-tuned analysis time points that reduce contributions from early-disseminating cancer cells. In this regard, we developed a tumor cell-free syngeneic breast cancer model for characterizing tumor cell secretome-mediated reprogramming of premetastatic tissues. We demonstrate that secretomes from metastatic breast cancer cells differentially regulate the lung and brain, promoting a tumor-supportive lung microenvironment with both elevated CD73 expression and decreased TNFα expression. Using in vitro models of CD73-positive mesenchymal stem cells (MSCs) and macrophages/monocytes, we tested whether MSCs can mediate anti-inflammatory effects of metastatic breast cancer cells. Notably, conditioned media from metastatic Py230 cells reprogrammed the secretomes of MSCs toward an anti-inflammatory state. Mining transcriptome data from Py8119 and Py230 cells revealed a lipocalin 2 (LCN2) axis that is selectively expressed in the metastatic Py230 cells, predicts poor breast cancer patient survival and is elevated in circulating serum of mice chronically treated with conditioned media from Py230 cells. Taken together, these results establish the utility of an immune-competent tumor cell-free model for characterizing the mechanisms of breast cancer cell priming of the premetastatic niche, demonstrate that MSCs can mediate the anti-inflammatory effects of metastatic breast cancer cells and substantiate LCN2 as a promising therapeutic target for blocking breast cancer progression.

Changes in nesting sites abundance and their use by woodpeckers along an urban gradient: a ten-year comparison

Woodpeckers nesting substrate abundance may be reduced by urban expansion, negatively affecting their reproduction. Long-term studies in the tropics are rare but valuable to estimate how urban development has affected ecological communities. We present a ten-year comparison on nesting substrate abundance and their use by Melanerpes rubricapillus and M. chrysauchen woodpeckers along an urban gradient in Golfito, Costa Rica; which include three habitats and three substrates (snags, palms, and posts). Conditions remained unchanged in non-urban areas. In semi-urban areas, snag, posts, and nests on them, have decreased. In urban areas, despite snags and posts remaining constant, their use also decreased. In semi-urban and urban areas, palms and palm nests increased. This long term comparison indicates that woodpeckers took advantage of the increased presence of ornamental palms in gardens.

La abundancia de sustratos para anidación de pájaras carpinteros puede reducirse debido a la expansión urbana, afectando negativamente su reproducción. Los estudios a largo plazo en los trópicos son escazos, pero valiosos para estimar cómo el desarrollo urbano ha afectado las comunidades ecológicas. Presentamos una comparación de diez años sobre la abundancia y uso de sustratos de anidación de los carpinteros Melanerpes rubricapillus y M. chrysauchen en un gradiente urbano en Golfito, Costa Rica; que incluye tres hábitats y tres sustratos (tocones, palmas y postes). Las condiciones permanecieron similares en áreas no urbanas. En las áreas semi urbanas, los postes y tocones, así como los nidos en ellos disminuyeron. En áreas urbanas, a pesar de que los postes permanecieron constantes, su uso disminuyó. En las áreas semi urbanas y urbanas, la cantidad de palmas y de nidos en estas aumentó. Esta comparación a largo plazo indica que los carpinteros tomaron ventaja del aumento en la presencia de palmas ornamentales en los jardines.

Community health workers improve contact tracing among immigrants with tuberculosis in Barcelona.

BACKGROUND: The important increase in immigration during recent years has changed the epidemiology and control strategies for tuberculosis (TB) in many places. This study evaluates the effectiveness of intervention with community health workers (CHW) to improve contact tracing among immigrants. METHODS: The study included all TB cases detected by the Barcelona TB Program from 2000 to 2005 and compared a period without CHW intervention (2000-2002) to a period with CHW intervention (2003-2005). The influence on contact tracing of sex, age, hospital of diagnosis, district of residence, birthplace, HIV, homeless and CHW intervention was analysed by logistic regression. Odds ratio (OR) and 95% confidence intervals (CI) were calculated. RESULTS: 960 foreign born TB cases were detected, 388 in the intervention period. Contact tracing was performed on 65,7% of 201 smear-positive cases during the pre-intervention period compared to 81.6% of 152 smear-positive TB cases during the intervention period (p < 0.001). Risk factors associated with incomplete contact tracing of smear-positive index cases included being diagnosed in two hospitals without contact tracing TB unit (OR = 3.5; CI:1.4-8.9) and (OR = 4.6; CI:1.6-13.5) respectively, birth place in India-Pakistan (OR = 4.4; CI:1.9-10.3) or North Africa (OR = 4.3; CI:1.8-10.5), having an unknown residence (OR = 5.4; CI:1.6-18.0), being HIV-infected (OR = 6.1; CI:2.5-14.8) or homeless (OR = 3.3; CI:1.3-8.2), and the absence of CHW intervention (OR = 2.4; CI:1.3-4.3). CONCLUSIONS: The effectiveness of contact tracing for TB control in areas with high immigration can be improved by incorporating CHWs who act as translators, cultural mediators and facilitators who accompany cases and contacts through treatment and follow-up.

New drugs for tuberculosis treatment.

Available data on anti-tuberculosis drug research reveal different properties of the agents and provoke speculation about future directions. Higher doses of the rifamycins are promising and are currently being evaluated in regimens of shorter duration that the isoniazid plus rifampin-based, six-to-nine month-course therapy. Moxifloxacin and gatifloxacin might shorten tuberculosis treatment as well, possibly in combination with rifapentine, while SQ109 could enhance the activity of rifampin-containing regimens. On the other hand, co-administration of moxifloxacin and PA-824 could be active against latent tuberculosis, whereas linezolid, PA-824 and TMC207 are candidates for a rifampin-free regimen in multidrug-resistant and extensively-resistant tuberculosis. Unfortunately, shorter than existent treatment regimens based on the new agents discussed here are likely to take at least another decade to be fully developed and implemented in clinical practice.

New drugs for tuberculosis treatment

Los datos disponibles en el proceso de investigación de nuevos fármacos antituberculosos han descubiertodiferentes propiedades de los compuestos que permiten crear expectativas acerca de sus futuras indicaciones.Modelos terapéuticos que incluyan altas dosis de rifamicinas y pautas que asocien rifapentina conmoxifloxacino o gatifloxacino podrían acortar el tratamiento de la tuberculosis, mientras que SQ109 incrementaríala actividad de las combinaciones basadas en esta rifamicina. Por otra parte, la tuberculosis latentepodría tratarse adecuadamente con la asociación de moxifloxacino y PA-824, y la tuberculosis multirresistentey extensamente resistente con linezolid, PA-824 y TMC207, en pautas sin rifampicina.Desgraciadamente, tratamientos más cortos que los existentes, basados en asociaciones de los fármacosque se comentan en este trabajo, llevarán al menos otra década para ser completamente desarrollados eintroducidos en la práctica clínica (AU)

AbstractAvailable data on anti-tuberculosis drug research reveal different properties of the agents and provoke speculation about future directions. Higher doses of the rifamycins are promising and are currently being evaluated in regimens of shorter duration that the isoniazid plus rifampin-based, six-to-nine month-course therapy. Moxifloxacin and gatifloxacin might shorten tuberculosis treatment as well, possibly in combination with rifapentine, while SQ109 could enhance the activity of rifampin-containing regimens. On the other hand, co-administration of moxifloxacin and PA-824 could be active against latent tuberculosis, whereas linezolid, PA-824 and TMC207 are candidates for a rifampin-free regimen in multidrug-resistant and extensively-resistant tuberculosis. Unfortunately, shorter than existent treatment regimens based on the new agents discussed here are likely to take at least another decade to be fully developed and implemented in clinical practice (AU)

[On the way to shortening tuberculosis treatments: clinical trials of the Unitat d' Investagació en Tuberculosi de Barcelona supported by the Centers for Disease Control and Prevention]. / En el camino para acortar los tratamientos de la tuberculosis: los ensayos clínicos de la Unitat d'Investigació en la Tuberculosi de Barcelona impulsados por los Centres for Disease Control and Prevention.

New treatment guidelines are required to improve the tuberculosis control strategies that have been used for 30 years. Seven centers of the Barcelona Tuberculosis Research Unit (BTRU) (Unitat d'Investigació en Tuberculosi de Barcelona) are collaborating with the Division of Tuberculosis Elimination of the United States Centers for Disease Control and Prevention in a series of clinical trials on latent tuberculosis infection and tuberculosis disease. BTRU participation began in 2004 with Study 26, an evaluation of the efficacy and tolerability of rifapentine plus isoniazid administered once weekly for 3 months compared with the standard treatment for latent tuberculosis infection. The BTRU centers together enrolled 246 patients (3% of the total). General enrollment was completed in February, 2008. HIV-infected patient and child enrollment continues. Treatment with 12 doses instead of 270 doses is expected to be a clear success. However, the analysis will be completed in 2010. Study 28 (started in 2006), designed for the treatment of pulmonary tuberculosis, compared standard treatment with an experimental regimen substituting moxifloxacin for isoniazid. BTRU centers together enrolled 15 patients (3.5% of the total). The provisional results (presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, 2007) showed no difference between the sputum conversion rate of each regimen at week 8 of treatment. Study 29 is currently underway, in which rifapentine was introduced in the experimental regimen for active tuberculosis treatment.

Factors associated with differences between conventional contact tracing and molecular epidemiology in study of tuberculosis transmission and analysis in the city of Barcelona, Spain.

The aim of this study was to analyze the factors associated with conventional contact tracing (CCT) and molecular epidemiology (ME) methods in assessing tuberculosis (TB) transmission, comparing the populations studied and the epidemiological links established by both methods. Data were obtained from TB case and CCT registries, and ME was performed using IS6110-based restriction fragment length polymorphism (RFLP) analysis and mycobacterial interspersed repetitive unit 12 (MIRU12) typing as a secondary typing method. During two years (2003 and 2004), 892 cases of TB were reported, of which 687 (77%) were confirmed by culture. RFLP analysis was performed with 463 (67.4%) of the 687 isolated strains, and MIRU12 types in 75 strains were evaluated; 280 strains (60.5%) had a unique RFLP pattern, and 183 (39.5%) shared patterns, grouping into 65 clusters. CCT of 613 (68.7%) of 892 cases detected 44 clusters involving 101 patients. The results of both CCT and ME methods yielded 96 clusters involving 255 patients. The household link was the one most frequently identified by CCT (corresponding to 80.7% of the cases clustered by this method), whereas nonhousehold and unknown links were associated with 94.1% of the strains clustered by ME. When both methods were used in 351 cases (39.3%), they showed the same results in 214 cases (61%). Of the remainder, 106 (30.2%) were clustered only by ME, 19 (5.5%) were clustered only by CCT, and 12 (3.4%) were clustered by both methods but into different clusters. Patients with factors potentially associated with social problems were less frequently studied by CCT (P = 0.002), whereas patients of <15 years of age, most with negative cultures, were less frequently studied by ME (P = 0.005). Significant differences in the populations studied by ME versus CCT were observed, possibly explaining the scarce correlation found between the results of these methods. Moreover, ME allowed the detection of nonhousehold contact relationships, whereas CCT was more useful for tracing transmission chains involving patients of <15 years of age. In conclusion, the two methods are complementary, suggesting the need to improve the methodology of contact study protocols.

Fatal liver failure: molecular evidence for chronic active Epstein-Barr virus infection.

Epstein-Barr virus (EBV) infection is a benign disease, which may occasionally be fatal, particularly in children and immunocompromised patients. Epstein-Barr virus infection is rare in elderly subjects and seems to have a self-limited course. A case of fatal liver failure due to chronic active EBV infection in a 75-year-old man is described. The etiology was established postmortem by cellular expression of EBV-DNA in liver and lymphatic tissue. This patient meets the diagnostic criteria of a case definition for a highly probable "severe chronic active EBV syndrome." Either suspected or unsuspected, the long-term prognosis of this syndrome is poor and its mortality high.