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El presente trabajo se realizó con el objetivo de evaluar el comportamiento de la variedad holandesa de papa “Santana”, plantada en áreas de producción de la Empresa Cítrico “Arimao”, del municipio de Cumanayagua, Cienfuegos, Cuba. Se utilizó un diseño de bloques al azar con dos tratamientos (Tubérculos madre, Calibre II, 35-45 mm y Calibre III, 45-55 mm) y cinco réplicas, en parcelas 22.5 m2. Durante el ciclo del cultivo se evaluó la emergencia de los tubérculos semilla, número de tallos por plantón y su altura, momento de la floración. Fueron registradas las temperaturas máximas, mínimas y media y se determinó la amplitud de las mismas. La cosecha del experimento fue de forma manual a los 84 días después de la plantación. Se calculó el rendimiento total en t ha-1. Los resultados se procesaron estadísticamente mediante un ANOVA, y se empleó la prueba de Duncan mediante el uso del programa estadístico Statgrafphics Cent.16. La emergencia de los tubérculos semilla a los 21 días alcanzó el 95 %, el número de tallos por plantón mostró diferencias significativas entre los dos calibres y repercutió en la densidad real del cultivo. La temperatura media ambiental posterior a la plantación superó los 25 °C, con una amplitud durante todo el ciclo del cultivo por debajo de los 10 °C. La mayor cantidad de tubérculos fue cuantificada por plantón, mientras que disminuyó por tallos. El rendimiento alcanzado sobrepasó las 22 t ha-1, sin diferencias estadísticas entre los tratamientos

El Programa de Agricultura urbana que se lleva a cabo en Cuba considera como un aspecto fundamental el manejo y conservación de los recursos fitogenéticos para garantizar producciones locales y contribuir a satisfacer las necesidades alimentarias de la población. Dentro de ellos la producción de frutas ocupa un renglón importante. Para constatar, la diversidad de frutales y sus componentes, se realizó un inventario durante el período de septiembre del 2018 a abril del 2019 en 11 patios de los Consejos populares del casco urbano del municipio de Cumanayagua: Brisas, Rafaelito y Vila. El balance del área total utilizada en los patios de los tres Consejos populares ubica un 69,01% dedicada a la producción de frutales. El inventario reportó 33 familias botánicas y 69 especies. Las familias botánicas más representadas resultaron Rutaceae con diez especies, Annonaceae, Anacardiaceae y Sapotaceae con cinco cada una. La diversidad intraespecífica en las especies identificadas arrojó el mango con 17, aguacate con 11 y la guayaba con 7. La dominancia fue baja en los tres Consejos, sin embargo donde hubo mayor riqueza los valores de dominancia resultaron bajos al Índice de Simpson. Los Consejos Rafaelito y Vila fueron más diversos, y a su vez equitativos en cuanto a la presencia y distribución de las especies de frutales diagnosticadas

Interferon-gamma (IFN-gamma) is crucial for protection against Mycobacterium tuberculosis, and the transcription factor cAMP response element binding protein (CREB) increases IFN-gamma transcription. We determined whether the transmembrane receptor signaling lymphocyte activation molecule (SLAM) and interleukin-17 (IL-17) affect CREB phosphorylation and IFN-gamma production in persons with tuberculosis. When T cells from patients with tuberculosis were activated with M. tuberculosis, 80% of SLAM(+) T cells expressed phosphorylated CREB, and SLAM activation increased CREB phosphorylation and IFN-gamma production. In contrast, IL-17 down-regulated SLAM expression, CREB phosphorylation, and IFN-gamma production. Therefore, IL-17 and SLAM have opposing effects on IFN-gamma production through CREB activation in persons with tuberculosis. [ABSTRACT FROM AUTHOR]

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Nearly 80% of the world's population trusts traditional medicine and plant-based drug compounds to improve health, and more than 50% of women who participated in a study have used herbal remedies during pregnancy. Bocconia frutescens L. is a plant native to tropical America, where infusion of its leaves has been widely used for the treatment of several gastrointestinal disorders. We have already shown that orogastric consumption of B. frutescens L. during the organogenesis period at concentrations equivalent to human consumption produces teratogenic effects in rats, but effects on progeny development have not yet been studied. In this study, we aimed to investigate the possible association between the consumption of B. frutescens L. at a dose equivalent to that consumed by humans and the neurological development of rat progeny. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle via the orogastric route during the organogenesis period (gestation days 7-13). The physical development and sensory and motor maturation of their offspring during lactation were analyzed with a battery of reflex and physical tests. B. frutescens L. produced a significant delay in physical development and sensorimotor maturation, compared to the control group. Proton nuclear magnetic resonance spectroscopy analysis showed signals for both flavonoids and alkaloids in the B. frutescens L. extract. We conclude that the delay in physical and neurological development could be interpreted as alterations in the maturation of some neuronal circuitries induced by B. frutescens L.

Introduction: Mycobacterium tuberculosis , the etiologic agent of tuberculosis (TB), has killed nearly one billion people during the last two centuries. Nowadays, TB remains a major global health problem ranked among the top 10 causes of death worldwide. One of the main challenges in developing new strategies to fight TB is focused on reducing the duration and complexity of drug regimens. Cannabidiol (CBD) is the main nonpsychoactive ingredient extracted from the Cannabis sativa L . plant, which has been shown to be biologically active against bacteria. The purpose of this work was to investigate the antimicrobial effect of CBD on M. tuberculosis intracellular infection. Materials and Methods: To assess the minimum inhibitory concentration (MIC) of CBD on mycobacterial strains, the MTT assay was performed on Mycobacterium smegmatis , and the Colony-Forming Unit (CFU) assay was conducted on Mtb H37Rv. Additionally, the cytotoxic effect of CBD on THP-1 cells was assessed by MTT assay. Moreover, macrophages derived from the THP-1 cell were infected with Mtb H37Rv (multiplicity of infection 1:10) to evaluate the intracellular activity of CBD by determining the CFU/mL. Results: Antimicrobial activity against M. smegmatis (MIC=100 μM) and Mtb H37Rv (MIC=25 μM) cultures was exhibited by CBD. Furthermore, the effect of CBD was also evaluated on Mtb H37Rv infected macrophage cells. Interestingly, a reduction in viable intracellular Mtb H37Rv bacteria was observed after 24 h of treatment. Moreover, CBD exhibited a safe profile toward human THP-1 cells, since it showed no toxicity (CC 50 =1075 μM) at a concentration of antibacterial effect (selectivity index 43). Conclusion: These results extend the knowledge regarding the antimicrobial activity of CBD and demonstrate its ability to kill the human intracellular pathogen M. tuberculosis.

Introduction: Current guidelines recommend cardiovascular risk assessment as a preventive measure for cardiovascular diseases, whose fundamental etiology is arteriosclerosis. One of the tools used to estimate risk in clinical practice are atherogenic indices (AI), ratios between lipid fractions with well-established reference ranges. Despite its widespread use, there is still limited information on its clinical utility. In recent years, some research has reinforced the role of inflammation in the etiology and chronicity of the atherosclerotic process. The inclusion of inflammatory parameters in the AI calculation could improve its diagnostic performance in the detection of arteriosclerosis. We sought to evaluate a new AI as a ratio between C-reactive protein (CRP) values and high-density lipoprotein cholesterol (HDL) values., Methods: A total of 282 asymptomatic patients with no history of cardiovascular disease were included in the study. Laboratory tests with lipid profile and CRP, and carotid ultrasound to assess the presence of atheromatosis were performed in all of them. The new AI is established as the ratio between non-ultrasensitive CRP value in mg/dL (multiplied by 100) and HDL value in mg/dL. It was compared with the Castelli I and II indices, and the plasma atherogenic index. The optimal cut-off point of the new AI was value=1 as determined by ROC curve, with an area under the curve of 0.678 (95% CI 0.60-0.75; p<0.001)., Results: Mean age of patients was 60.4±14.5 years. A total of 118 patients (41.8% of total) had carotid arteriosclerosis. When evaluating the diagnostic performance of different AIs, we found that CRP·100/HDL ratio showed the highest values of sensitivity and positive predictive value (0.73 and 0.68, respectively) compared to the Castelli I and II indices, and the plasma atherogenic index. It was also the only predictor of carotid atheromatosis both when considering its values quantitatively (with OR 1.4 [95% CI 1.1-1.7]; p=0.005), and qualitatively (with OR 2.9 [95% CI 1.5-5.5]; p<0.001) in patients with a CRP·100/HDL ratio>1., Conclusions: The new PCR·100/HDL index showed the best diagnostic performance in the detection of carotid atheromatosis compared to other classic AIs in this Spanish population of asymptomatic patients., (Copyright © 2023 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Mycobacterium tuberculosis ( Mtb ), the etiologic agent of tuberculosis (TB), has killed nearly one billion people in the last two centuries. Nowadays, TB remains a major global health problem, ranking among the thirteen leading causes of death worldwide. Human TB infection spans different levels of stages: incipient, subclinical, latent and active TB, all of them with varying symptoms, microbiological characteristics, immune responses and pathologies profiles. After infection, Mtb interacts with diverse cells of both innate and adaptive immune compartments, playing a crucial role in the modulation and development of the pathology. Underlying TB clinical manifestations, individual immunological profiles can be identified in patients with active TB according to the strength of their immune responses to Mtb infection, defining diverse endotypes. Those different endotypes are regulated by a complex interaction of the patient's cellular metabolism, genetic background, epigenetics, and gene transcriptional regulation. Here, we review immunological categorizations of TB patients based on the activation of different cellular populations (both myeloid and lymphocytic subsets) and humoral mediators (such as cytokines and lipid mediators). The analysis of the participating factors that operate during active Mtb infection shaping the immunological status or immune endotypes of TB patients could contribute to the development of Host Directed Therapy.

Aim: Assess the psychometric properties of reliability and validity of the Family Needs Assessment (FNA) questionnaire designed for adults in Colombia. Conducting research studies to validate the FNA questionnaire in other contexts and age groups is important., Methods: Five hundred fifty-four caregivers of adults with intellectual disabilities participated in the study (298 men and 256 women). The ages of the individuals with disabilities ranged from 18 to 76 years. The authors carried out the linguistic adaptation of the items and cognitive interviews to identify if the items evaluated what was intended. A pilot test with 20 participants was also conducted. An initial confirmatory factor analysis was carried out. Given that, this analysis did not show a good adjustment of the theoretical model initially proposed, an exploratory factor analysis was carried out to elucidate the most appropriate structure for the Colombian population.., Results: The factor analysis found five factors, each with a high ordinal alpha (Caregiving and family interaction, social interaction and future planning, Economy, and recreation, independent living skills or autonomy, and Services related to disability). Of the 76 items, 59 were preserved, which had a factorial load greater than 0.40; and 17 were left out because they did not meet this requirement.., Conclusion: Future research considers corroborating the five factors found and establishing their clinical applications. Concerning the concurrent validity, the families perceive that high need for social interaction and future planning and little support for the person with an intellectual disability., (Copyright © 2023 Colombia Medica.)

Introduction: Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription., Methods: We evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing., Results: Using a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals., Discussion: IFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Álvarez, Hernández Del Pino, Barbero, Estermann, Celano, Musella, Palmero, García and Pasquinelli.)

Objective: The purpose of this study was to determine in vitro the inhibitory activity of the ethanolic extract of Cyperus rotundus (Cajamarca - Contumazá) against a standardize strain of Streptococcus mutans (ATCC®25175™)., Materials and Methods: This study was an experimental in vitro study, which consisted of determining the inhibitory effect of three concentrations of the ethanolic extract of Cyperus rotundus : 250 mg/ml, 500 mg/ml, and 1000 mg/ml against a strains of Streptococcus mutans (ATCC®25175™). Ten tests were performed for each concentration, having 0.12% chlorhexidine as a positive control for Streptococcus mutans plates and 10% DMSO as a negative control. To evaluate the inhibitory effect, the disk diffusion method or Kirby-Bauer test was used, reading the results at 48 hours after initial sowing., Results: None of the three concentrations of the ethanolic extract of Cyperus rotundus demosntrated inhibitory effects on the Streptococcus mutans strain; however, the positive control, chlorhexidine, clearly showed inhibition halos of 14.43 mm ± 1.23 mm after 48 hours of incubation., Conclusions: The ethanolic extract of Cyperus rotundus did not inhibit the growth of Streptococcus mutans . It is recommended to deepen the chemical analysis of the components of this plant and explore other extraction methods to verify its bacteriostatic action versus other oral and non-oral microorganisms., Competing Interests: Conflictos de intereses: Los autores declaran no tener conflictos de intereses

Alterations of myeloid cell populations have been reported in patients with tuberculosis (TB). In this work, we studied the relationship between myeloid-derived suppressor cells (MDSC) and monocytes subsets with the immunological responsiveness of TB patients. Individuals with active TB were classified as low responders (LR-TB) or high responders (HR-TB) according to their T cell responses against a cell lysate of Mycobacterium tuberculosis ( Mtb -Ag). Thus, LR-TB, individuals with severe disease, display a weaker immune response to Mtb compare to HR-TB, subjects with strong immunity against the bacteria. We observed that LR-TB presented higher percentages of CD16 positive monocytes as compared to HR-TB and healthy donors. Moreover, monocyte-like (M-MDSC) and polymorphonuclear-like (PMN-MDSC) MDSC were increased in patients and the proportion of M-MDSC inversely correlated with IFN-γ levels released after Mtb -Ag stimulation in HR-TB. We also found that LR-TB displayed the highest percentages of circulating M-MDSC. These results demonstrate that CD16 positive monocytes and M-MDSC frequencies could be used as another immunological classification parameter. Interestingly, in LR-TB, frequencies of CD16 positive monocytes and M-MDSC were restored after only three weeks of anti-TB treatment. Together, our findings show a link between the immunological status of TB patients and the levels of different circulating myeloid cell populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Amiano, Pellegrini, Morelli, Martinena, Rolandelli, Castello, Casco, Ciallella, de Casado, Armitano, Stupka, Gallego, Palmero, García and Tateosian.)

Immunity against Mycobacterium tuberculosis ( Mtb ) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb . Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb . Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb . Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pellegrini, Tateosian, Morelli and García.)

Neutrophils infected with Mycobacterium tuberculosis ( Mtb ) predominate in tuberculosis patients' lungs. Neutrophils phagocytose the pathogen, but the mechanism of pathogen elimination is controversial. Macroautophagy/autophagy, a crucial mechanism for several neutrophil functions, can be modulated by immunological mediators. The costimulatory molecule SLAMF1 can act as a microbial sensor in macrophages being also able to interact with autophagy-related proteins. Here, we demonstrate for the first time that human neutrophils express SLAMF1 upon Mtb -stimulation. Furthermore, SLAMF1 was found colocalizing with LC3B + vesicles, and activation of SLAMF1 increased neutrophil autophagy induced by Mtb . Finally, tuberculosis patients' neutrophils displayed reduced levels of SLAMF1 and lower levels of autophagy against Mtb as compared to healthy controls. Altogether, these results indicate that SLAMF1 participates in neutrophil autophagy during active tuberculosis. Abbreviations: AFB: acid-fast bacilli; BafA1: bafilomycin A 1 ; CLL: chronic lymphocytic leukemia; DPI: diphenyleneiodonium; EVs: extracellular vesicles; FBS: fetal bovine serum; HD: healthy donors; HR: high responder (tuberculosis patient); IFNG: interferon gamma; IL1B: interleukin 1 beta; IL17A: interleukin 17A; IL8: interleukin 8; LR: low responder (tuberculosis patient); mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MAPK1/ERK2: mitogen-activated protein kinase 1; MAPK14/p38: mitogen-activated protein kinase 14; Mtb: Mycobacterium tuberculosis; Mtb- Ag: Mycobacterium tuberculosis , Strain H37Rv, whole cell lysate; NETs: neutrophils extracellular traps; PPD: purified protein derivative; ROS: reactive oxygen species; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; SLAMF1: signaling lymphocytic activation molecule family member 1; TB: tuberculosis; TLR: toll like receptor.

The environmental context during gestation may modulate the postpartum variations in maternal behaviors observed within different animal species. Most of our experimental knowledge on this phenomenon and its physiological effects have been gained by confronting the pregnant mother with stressful situations, with the consensual results indicating a reduced maternal behavior and a hyper reactivity of stress-related neural paths. Here, in contrast, by exposing nulliparous rats strictly during pregnancy to a standard laboratory environment (STD) or a highly stimulating sensory and social environment (EE), we investigated the hypothesis that subjects frequently exposed to social stimuli and novel situations during pregnancy will show postpartum changes in subcortical brain areas' activity related to the processing of social stimuli and novelty, such that there will be modifications in maternal behavior. We found that EE mothers doubled the levels of licking and grooming, and active hovering over pups during the first postpartum week than STD dams, without a difference in the time of contact with the pups. Associated with these behaviors, EE dams showed increased c-Fos immunoreaction in hypothalamic nuclei and distinct responses in amygdalar nuclei, than STD dams. In the maternal defensive test, EE dams tripled the levels of aggressive behaviors of the STD rats. Additionally, in two different tests, EE mothers showed lower levels of postpartum anxiety-like behaviors when confronted with novel situations. Our results demonstrate that the activity of brain areas related to social behavior is adaptable by environmental circumstances experienced during gestation, presumably to prepare the progeny for these particular conditions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Prostaglandin E2 (PGE2), an active lipid compound derived from arachidonic acid, regulates different stages of the immune response of the host during several pathologies such as chronic infections or cancer. In fact, manipulation of PGE2 levels was proposed as an approach for countering the Type I IFN signature of tuberculosis (TB). However, very limited information regarding the PGE2 pathway in patients with active TB is currently available. In the present work, we demonstrated that PGE2 exerts a potent immunosuppressive action during the immune response of the human host against Mycobacterium tuberculosis (Mtb) infection. Actually, we showed that PGE2 significantly reduced the surface expression of several immunological receptors, the lymphoproliferation and the production of proinflammatory cytokines. In addition, PGE2 promoted autophagy in monocytes and neutrophils cultured with Mtb antigens. These results suggest that PGE2 might be attenuating the excessive inflammatory immune response caused by Mtb, emerging as an attractive therapeutic target. Taken together, our findings contribute to the knowledge of the role of PGE2 in the human host resistance to Mtb and highlight the potential of this lipid mediator as a tool to improve anti-TB treatment.

Tuberculosis dates back to ancient times but it is not a problem of the past. Each year, millions of people die from tuberculosis. After inhalation of infectious droplet nuclei, Mycobacterium tuberculosis reaches the lungs where it can manipulate the immune system and survive within host macrophages, establishing a persistent infection. The signaling lymphocytic activation molecule family member 1 (SLAMF1) is a self-ligand receptor that can internalize gram-negative bacteria and regulate macrophages' phagosomal functions. In tuberculosis, SLAMF1 promotes Th1-protective responses. In this work, we studied the role of SLAMF1 on macrophages' functions during M. tuberculosis infection. Our results showed that both M. tuberculosis and IFN-γ stimulation induce SLAMF1 expression in macrophages from healthy donor and Tohoku Hospital Pediatrcs-1 cells. Costimulation through SLAMF1 with an agonistic antibody resulted in an enhanced internalization of M. tuberculosis by macrophages. Interestingly, we found that SLAMF1 interacts with M. tuberculosis and colocalizes with the bacteria and with early and late endosomes/lysosomes markers (EEA1 and LAMP2), suggesting that SLAMF1 recognize M. tuberculosis and participate in the endolysosomal maturation process. Notably, increased levels of SLAMF1 were detected in CD14 cells from pleural effusions of tuberculosis patients, indicating that SLAMF1 might have an active function at the site of infection. Taken together, our results provide evidence that SLAMF1 improves the uptake of M. tuberculosis by human monocyte-derived macrophages., (©2020 Society for Leukocyte Biology.)

Mycobacterium tuberculosis ( Mtb ) infection is one of the leading causes of death worldwide. The Modified Vaccinia Ankara (MVA) vaccine vector expressing the mycobacterial antigen 85A (MVA85A) was demonstrated to be safe, although it did not improve BCG efficacy, denoting the need to search for improved tuberculosis vaccines. In this work, we investigated the effect of IL-12 DNA -as an adjuvant- on an Ag85A DNA prime/MVA85A boost vaccination regimen. We evaluated the immune response profile elicited in mice and the protection conferred against intratracheal Mtb H37Rv challenge. We observed that the immunization scheme including DNA-A85A+DNA-IL-12/MVA85A induced a strong IFN-γ production to Ag85A in vitro , with a significant expansion of IFN-γ + CD4 + and IFN-γ + CD8 + anti-Ag85A lymphocytes. Furthermore, we also detected a significant increase in the proportion of specific CD8 + CD107 + T cells against Ag85A. Additionally, inclusion of IL-12 DNA in the DNA-A85A/MVA85A vaccine scheme induced a marked augment in anti-Ag85A IgG levels. Interestingly, after 30 days of infection with Mtb H37Rv, DNA-A85A+DNA-IL-12/MVA85A vaccinated mice displayed a significant reduction in lung bacterial burden. Together, our findings suggest that IL-12 DNA might be useful as a molecular adjuvant in an Ag85A DNA/MVA prime-boost vaccine against Mtb infection., (Copyright © 2020 Morelli, Del Medico Zajac, Pellegrini, Amiano, Tateosian, Calamante, Gherardi and García.)

Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and IFN-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c, whereas 43% of HW QFT negative people produced elevated IFN-γ amounts against Rv2626c. Conversely, 69% of CC QFT positive subjects didn´t produce IFN-γ to Rv2626c. Interestingly, a similar pattern of IgG anti-Rv2626c plasma levels was observed. Therefore, determination of IFN-γ and IgG levels against the dormancy antigen Rv2626c allows to identify established LTBI.

It is estimated that 80% of the world population trusts traditional medicine. A large number of Americans use infusions of Bocconia frutescens L. leaves to treat cough and gastrointestinal disorders. However, phytochemical studies reveal that this plant contains alkaloids and other potentially harmful substances. This study aimed to evaluate the teratogenic effects of B. frutescens L. in an experimental model. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle by orogastric route during the organogenesis period (gestation days 7-13), and external and internal congenital malformations were analyzed on the progeny on gestational day 20. Bocconia frutescens L. produced a significant increase in the number of different malformations, relative to the control group. We conclude that the consumption of B. frutescens L. during pregnancy at a dose equivalent to that consumed by humans increases the risk of teratogenic effects.

Targeting the apoptosis machinery is a promising therapeutic approach in myeloid malignancies. BCL2L1 is a well-known glucocorticoid-responsive gene and a key apoptosis regulator that, when over-expressed, can contribute to tumor development, progression and therapeutic resistance. Moreover, synthetic glucocorticoids, like dexamethasone, are frequently used in the treatment of hematopoietic diseases due to its pro-apoptotic properties. We report here that the trithorax protein ASH2L, considered one of the core subunits of H3K4-specific MLL/SET methyltransferase complexes, contributes to anti-apoptotic BCL-X L over-expression and cell survival in patient-derived myeloid leukemia cells. We find that the unliganded glucocorticoid receptor (uGR) and ASH2L interact in a common protein complex through a chromatin looping determined by uGR and ASH2L binding to BCL2L1 specific +58 HRE and promoter region, respectively. Upon addition of dexamethasone, GR and ASH2L recruitment is reduced, BCL-X L expression diminishes and apoptosis is induced consequently. Overall, our findings indicate that uGR and ASH2L may act as key regulatory players of BCL- X L upregulation in AML cells., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Th17 lymphocytes, that produce IL17A, IL17F, and IL22, play a crucial role during the immune response against Mycobacterium tuberculosis ( Mtb ) infection. Whereas, the contribution of IL17A in immunity to tuberculosis is usually accepted, the role of IL17F has been scarcely studied so far. The aim of this work was to evaluate the existence of a potential association of the non-synonymous variant rs763780 SNP of the IL17F gene with human tuberculosis. Accordingly, by comparing healthy donors (HD) and tuberculosis patients (TB) populations we demonstrated an association between the C allele of the SNP and the susceptibility to tuberculosis disease in Argentina. Furthermore, we found that peripheral blood mononuclear cells (PBMCs) from individuals with a more effective immune response against Mtb secreted the highest levels of IL17F when stimulated with a lysate of Mtb ( Mtb -Ag). Besides, we evidenced that Mtb -Ag-stimulated PBMCs from HD carrying the C variant of the SNP displayed the lowest IFNG secretion, proliferation index, and SLAM expression as compared to TT carriers. Moreover, Mtb -Ag-stimulated PBMCs from TB carrying the C allele produced the lowest levels of IFNG, the highest level of IL17A, and the minimum proliferation indexes as compared to TT TB, suggesting a relationship between the C allele and tuberculosis severity. In fact, TB carrying the C allele presented a more severe disease, with the highest bacilli burden in sputum. Together, our findings identify the IL17F rs763780 SNP as a biomarker of tuberculosis susceptibility and advanced disease severity in Argentina, suggesting that IL17F could be a critical cytokine in tuberculosis immunity., (Copyright © 2019 Rolandelli, Pellegrini, Hernández Del Pino, Tateosian, Amiano, Morelli, Castello, Casco, Levi, Palmero and García.)

Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis ( Mtb ) infection, and several polymorphisms located in its gene are associated with risk of tuberculosis in diverse populations. Nevertheless, the genetic resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG rs1861494 polymorphism (G→A) was reported to alter the binding of transcription factors to this region, influencing IFNG production. Using a case-control study, we found an association between the AA and AG genotypes and tuberculosis resistance (AA vs. GG: odds ratio (OR) = 0.235, p -value = 0.012; AG vs. GG: OR = 0.303, p -value = 0.044; AA vs. AG: OR = 0.776, p -value = 0.427; AA + AG vs. GG: OR = 0.270, p -value = 0.022). Moreover, Mtb -antigen stimulated peripheral blood mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the highest amounts of IFNG in culture supernatants ( p -value = 0.034) and presented the greatest percentage of CD4⁺IFNG⁺ lymphocytes ( p -value = 0.035), in comparison with GG carriers. No association between the polymorphism and clinical parameters of tuberculosis severity was detected. However, our findings indicate that the rs1861494 single nucleotide polymorphism (SNP) could be considered as a biomarker of tuberculosis resistance in the Argentinean population., Competing Interests: The authors declare no conflict of interest.

Production of IFN-γ contributes to host defense against Mycobacterium tuberculosis (Mtb) infection. We previously demonstrated that Signaling lymphocytic activation molecule-associated protein (SAP) expression on cells from tuberculosis (TB) patients was inversely correlated with IFN-γ production. Here we first investigated the role of NK, T- and B-cell antigen (NTB-A)/SAP pathway in the regulation of Th1 response against Mtb. Upon antigen stimulation, NTB-A phosphorylation rapidly increases and afterwards modulates IFN-γ and IL-17 secretion. To sustain a healthy immune system, controlled expansion and contraction of lymphocytes, both during and after an adaptive immune response, is essential. Besides, restimulation-induced cell death (RICD) results in an essential homeostatic mechanism for precluding excess T-cell accumulation and associated immunopathology during the course of certain infections. Accordingly, we found that the NTB-A/SAP pathway was required for RICD during active tuberculosis. In low responder (LR) TB patients, impaired RICD was associated with diminished FASL levels, IL-2 production and CD25 high expression after cell-restimulation. Interestingly, we next observed that SAP mediated the recruitment of the Src-related kinase FYNT, only in T cells from LR TB patients that were resistant to RICD. Together, we showed that the NTB-A/SAP pathway regulates T-cell activation and RICD during human TB. Moreover, the NTB-A/SAP/FYNT axis promotes polarization to an unfavorable Th2-phenotype.

During mycobacterial infection, macroautophagy/autophagy, a process modulated by cytokines, is essential for mounting successful host responses. Autophagy collaborates with human immune responses against Mycobacterium tuberculosis (Mt) in association with specific IFNG secreted against the pathogen. However, IFNG alone is not sufficient to the complete bacterial eradication, and other cytokines might be required. Actually, induction of Th1 and Th17 immune responses are required for protection against Mt. Accordingly, we showed that IL17A and IFNG expression in lymphocytes from tuberculosis patients correlates with disease severity. Here we investigate the role of IFNG and IL17A during autophagy in monocytes infected with Mt H37Rv or the mutant MtΔRD1. Patients with active disease were classified as high responder (HR) or low responder (LR) according to their T cell responses against Mt. IL17A augmented autophagy in infected monocytes from HR patients through a mechanism that activated MAPK1/ERK2-MAPK3/ERK1 but, during infection of monocytes from LR patients, IL17A had no effect on the autophagic response. In contrast, addition of IFNG to infected monocytes, increased autophagy by activating MAPK14/p38 α both in HR and LR patients. Interestingly, proteins codified in the RD1 region did not interfere with IFNG and IL17A autophagy induction. Therefore, in severe tuberculosis patients' monocytes, IL17A was unable to augment autophagy because of a defect in the MAPK1/3 signaling pathway. In contrast, both IFNG and IL17A increased autophagy levels in patients with strong immunity to Mt, promoting mycobacterial killing. Our findings might contribute to recognize new targets for the development of novel therapeutic tools to fight the pathogen.

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.

IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette-Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens. BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited. QuantiFERON-TB Gold In-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6, Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly, whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people.

Protective immunity against Mycobacterium tuberculosis (Mtb) requires IFNG. Besides, IFNG-mediated induction of autophagy suppresses survival of virulent Mtb in macrophage cell lines. We investigated the contribution of autophagy to the defense against Mtb antigen (Mtb-Ag) in cells from tuberculosis patients and healthy donors (HD). Patients were classified as high responders (HR) if their T cells produced significant IFNG against Mtb-Ag; and low responders (LR) when patients showed weak or no T cell responses to Mtb-Ag. The highest autophagy levels were detected in HD cells whereas the lowest quantities were observed in LR patients. Interestingly, upon Mtb-Ag stimulation, we detected a positive correlation between IFNG and MAP1LC3B-II/LC3-II levels. Actually, blockage of Mtb-Ag-induced IFNG markedly reduced autophagy in HR patients whereas addition of limited amounts of IFNG significantly increased autophagy in LR patients. Therefore, autophagy collaborates with human immune responses against Mtb in close association with specific IFNG secreted against the pathogen.

Immune control of Mycobacterium tuberculosis depends on interferon γ (IFN-γ)-producing CD4(+) lymphocytes. Previous studies have shown that T cells from patients with tuberculosis produce less IFN-γ, compared with healthy donors, in response to mycobacterial antigens, although IFN-γ responses to mitogens are preserved. In this work, we found that M. tuberculosis-induced IFN-γ production by human T cells correlated with phosphorylation of the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), and p38. Moreover, the majority of IFN-γ-producing T cells expressed signaling lymphocyte activation molecule (SLAM), and SLAM activation further increased ERK phosphorylation. Interestingly, patients with tuberculosis had delayed activation of ERK and p38, and this was most marked in patients with the poorest IFN-γ responses (ie, low responders). Besides, SLAM signaling failed to phosphorylate ERK in low responders. Our findings suggest that activation of p38 and ERK, in part through SLAM, mediates T-cell IFN-γ production in response to M. tuberculosis, a pathway that is defective in patients with tuberculosis.

Background: Vertical position is an option to delivery to which several advantages have been attributed. This research exposes its related findings., Objective: To compare obstetric and perinatal outcomes between supine and vertical position at delivery., Patients and Method: We performed a randomized double-blind study including healthy women assigned to the supine or upright posture (vertical) during labor with complications following the delivery in the puerperium stage. The variables evaluated were: blood loss, pain in the second period of labor and immediate postpartum, duration of the second period of labor, perineal and vaginal tears, need to forceps implement, accommodation in position and perinatal outcome., Results: 164 patients were randomized into two groups, the vertical position (I) and the supine position (II). The losses were 5.4%, and the Caesarean rate was of 4.6%. Difference was found only for vaginal tears in the vertical posture, with a relative risk of 1.4 (CI 1.1-3.2), and shortening of the second period with a significant difference of 10 minutes on average (p < 0.05)., Conclusions: The upright posture during childbirth provides no improvement in perinatal outcomes and fewer obstetric conditions. It shortens the second period of labor, but it is a risk factor for vaginal tears. The best position for birth is which offers more comfort to the patient.

Immune responses are qualitatively and quantitatively influenced by a complex network of receptor-ligand interactions. Among them, the CD137:CD137L pathway is known to modulate innate and adaptive human responses against Mycobacterium tuberculosis. However, the underlying mechanisms of this regulation remain unclear. In this work, we developed a Bayesian Computational Model (BCM) of in vitro CD137 signaling, devised to fit previously gathered experimental data. The BCM is fed with the data and the prior distribution of the model parameters and it returns their posterior distribution and the model evidence, which allows comparing alternative signaling mechanisms. The BCM uses a coupled system of non-linear differential equations to describe the dynamics of Antigen Presenting Cells, Natural Killer and T Cells together with the interpheron (IFN)-γ and tumor necrosis factor (TNF)-α levels in the media culture. Fast and complete mixing of the media is assumed. The prior distribution of the parameters that describe the dynamics of the immunological response was obtained from the literature and theoretical considerations Our BCM applies successively the Levenberg-Marquardt algorithm to find the maximum a posteriori likelihood (MAP); the Metropolis Markov Chain Monte Carlo method to approximate the posterior distribution of the parameters and Thermodynamic Integration to calculate the evidence of alternative hypothesis. Bayes factors provided decisive evidence favoring direct CD137 signaling on T cells. Moreover, the posterior distribution of the parameters that describe the CD137 signaling showed that the regulation of IFN-γ levels is based more on T cells survival than on direct induction. Furthermore, the mechanisms that account for the effect of CD137 signaling on TNF-α production were based on a decrease of TNF-α production by APC and, perhaps, on the increase in APC apoptosis. BCM proved to be a useful tool to gain insight on the mechanisms of CD137 signaling during human response against Mycobacterium tuberculosis.

Th1 lymphocytes are crucial in the immune response against Mycobacterium tuberculosis. Nevertheless, IFN-γ alone is not sufficient in the complete eradication of the bacteria, suggesting that other cytokines might be required for pathogen removal. Th17 cells have been associated with M. tuberculosis infection, but the role of IL-17-producing cells in human TB remains to be understood. Therefore, we investigated the induction and regulation of IFN-γ and IL-17 during the active disease. TB patients were classified as High and Low Responder individuals according to their T cell responses against the antigen, and cytokine expression upon M. tuberculosis stimulation was investigated in peripheral blood and pleural fluid. Afterwards, the potential correlation among the proportions of cytokine-producing cells and clinical parameters was analyzed. In TB patients, M. tuberculosis induced IFN-γ and IL-17, but in comparison with BCG-vaccinated healthy donors, IFN-γ results were reduced significantly, and IL-17 was markedly augmented. Moreover, the main source of IL-17 was represented by CD4(+)IFN-γ(+)IL-17(+) lymphocytes, a Th1/Th17 subset regulated by IFN-γ. Interestingly, the ratio of antigen-expanded CD4(+)IFN-γ(+)IL-17(+) lymphocytes, in peripheral blood and pleural fluid from TB patients, was correlated directly with clinical parameters associated with disease severity. Indeed, the highest proportion of CD4(+)IFN-γ(+)IL-17(+) cells was detected in Low Responder TB patients, individuals displaying severe pulmonary lesions, and longest length of disease evolution. Taken together, the present findings suggest that analysis of the expansion of CD4(+)IFN-γ(+)IL-17(+) T lymphocytes in peripheral blood of TB patients might be used as an indicator of the clinical outcome in active TB.

Protective immunity against Mycobacterium tuberculosis is primarily mediated by the interaction of antigen-specific T cells and antigen presenting cells, which often depends on the interplay of cytokines produced by these cells. Costimulatory signals represent a complex network of receptor-ligand interactions that qualitatively and quantitatively influence immune responses. Thus, here we investigated the function of CD137 and CD137L, molecules known to have a central role in immune regulation, during human tuberculosis (TB). We demonstrated that M. tuberculosis antigen stimulation increased both CD137 and CD137L expression on monocytes and NK cells from TB patients and healthy donors, but only up-regulated CD137 on T lymphocytes. Blockage of the CD137 pathway enhanced the levels of interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by monocytes and NK against M. tuberculosis. In contrast, CD137 blockage significantly decreased the specific degranulation of CD8(+) T cells and the percentage of specific IFN-γ and TNF-α producing lymphocytes against the pathogen. Furthermore, inhibition of the CD137 pathway markedly increased T-cell apoptosis. Taken together, our results demonstrate that CD137:CD137L interactions regulate the innate and adaptive immune response of the host against M. tuberculosis.

Background: Obstetric Morbidity Extreme (OME) is a promising addition to the investigation of maternal deaths and is used for the evaluation and improvement of maternal health services is defined as a severe obstetric complication that threatens the life of the pregnant woman and requires urgent medical intervention to prevent death of the mother., Objective: To identify association between diseases and obstetric morbidity Extreme., Material and Method: Transversal review analytical records. We searched for codes related to conditions that could cause extreme obstetric morbidity and the indirect causes that might cause it., Results: The prevalence of OME 21 per 1000 newborns, diseases with greater association were eclampsia, liver failure and preeclampsia yielded the highest OR and statistical significance, the association of OME derived from surgery despite having a high prevalence in the analysis showed no association, in the same way if other variables showed association but had no significance and confidence intervals are below the unit that is the case of renal failure, metabolic failure and blood transfusion., Conclusions: The OME is caused by group entities specific disease (FLASOG) in most cases such as preeclampsia, eclampsia and obstetric hemorrhage.

Tuberculous pleurisy allows the study of specific cells at the site of Mycobacterium tuberculosis infection. Among pleural lymphocytes, natural killer (NK) cells are a major source of interferon gamma (IFN-gamma), and their functions are regulated by activating and inhibitory receptors. Programmed death-1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are recognized inhibitory receptors in adaptive immunity, but their role during innate immunity remains poorly understood. We investigated the PD-1:PD-L1/PD-L2 pathway on NK cell effector functions in peripheral blood and pleural fluid from patients with tuberculosis. M. tuberculosis stimulation significantly up-regulated PD-1, PD-L1, and PD-L2 levels on NK cells. Interestingly, a direct correlation between PD-1 and IFN-gamma expression on NK cells was observed. Moreover, blockade of the PD-1 pathway markedly augmented lytic degranulation and IFN-gamma production of NK cells against M. tuberculosis. Furthermore, PD-1(+) NK cells displayed a diminished IFN-gamma mean fluorescence intensity, denoting the relevance of PD-1 on IFN-gamma regulation. Together, we described a novel inhibitory role played by PD-1:PD-L interactions in innate immunity in tuberculosis.

Fats are important nutrients in our diet, they have wide chemical properties that drive diverse metabolic effects. The trans fatty acids (TFA) are common compounds found in industrialized food, and recent research has shown they should be avoided due to their increased risk of cardiovascular disease (CVD). Some of the mechanisms involved include: reduction of c-HDL concentration, increase of low density lipoprotein, Lp (a), triglycerides; disturbance in prostaglandin balance and they may also promote insulin resistance. Obese subjects are prone to increased CVD risk associated with a state of chronic inflammation that can be worsened by TFA intake. The US population consumes approximately 5.3 g TFA per day (2.6% of their total energy intake and 7.4% of their fat energy). Recently, WHO recommendations suggest the intake of TFA should be lower than 1% of energy per day. Current fast food industry products have to decrease the amount of TFA content, and the experience from different countries shows that the elimination of trans fatty acids is a cost effective and feasible public health intervention.

Introduction: Early mortality in pediatric patients after liver transplantation (30 days) may be due to surgical and anesthetic perioperative factors., Objective: To identify anesthetic risk factors associated with early mortality in pediatric patients who undergo liver transplantation (OLT)., Materials and Methods: This retrospective study of all patients who underwent a deceased or living donor liver transplantation evaluated demographic variables of age, weight, gender, degree of malnutrition, and etiology, as well as qualitative variables of anesthesia time, bleeding, massive transfusion, acid-base balance, electrolyte and metabolic disorders, as well as graft prereperfusion postreperfusion characteristics. Chi-square tests with corresponding odds ratio (OR) and 95% confidence intervals as well as Interactions were tested among significant variables using multivariate logistic regression models. P < or =.05 was considered significant., Results: We performed 64 OLT among whom early death occurred in 20.3% (n = 13). There were deaths associated with malnutrition (84.6% vs 43.6%) in the control group (P < .01); massive bleeding, 76.9% (n = 10) versus 25.8% in the control group (P < .05) including transfusions in 84.6% (n = 11) versus 43.6% in the control group (P < .03); preperfusion metabolic acidosis in 84.6% (n = 11) versus 72.5% (n = 37; P < .05); posttransplant hyperglycemia in 69.2% (n = 9) versus 23.5% (n = 12; P < .01); and postreperfusion hyperlactatemia in 92.3% (n = 12) versus 68.6% (n = 35; P < .045)., Conclusion: Prereperfusion metabolic acidosis, postreperfusion hyperlactatemia, and hyperglycemia were significantly more prevalent among patients who died early. However, these factors were exacerbated by malnutrition, bleeding, and massive transfusions. Postreperfusion hypokalemia and hypernatremia showed high but not significant frequencies in both groups., (Copyright 2010. Published by Elsevier Inc.)

Objective: Determine if the Spanish version of the IWQOL (Impact of Weight on Quality of Life) questionnaire is reproducible and sensitive to detect differences among WHO's classification of obesity., Methods: The IWQOL was translated into Spanish and adapted to the Mexican context while maintaining a wide comprehensive vocabulary applicable to Latin American countries. We measured reproducibility using a test-retest method (n=82, BMI 37.8+/-8.4), sensitivity to detect differences between types of obesity (n=105, BMI 35.1+/-9.5), and sensitivity to detect differences after treatment for weight loss within groups (n=40, BMI 39.2+/-7)., Results: The IWQOL questionnaire was reliable and sensitive enough to detect differences among and within groups. All domains were highly reproducible (scores differed by less than 2 points) and had high internal validity (Cronbach alpha coefficient >0.92 for all scales). The IWQOL detected differences between groups stratfied by severity of obesity, the lowest score was for BMI >45. Subjects who underwent weight loss treatment and lost 6.4 kg (95% CI 4.6, 8.2) during a period of 2.70+/-1 month had an improvement in all scales except for the "Work" domain., Conclusions: The IWQOL questionnaire is a reliable and sensitive tool that can be used for research purposes in Mexico and the Latin America region. Our study validates the use of IWQOL among Mexican subjects.

Protective immunity against Mycobacterium tuberculosis requires the generation of cell-mediated immunity. We investigated the expression and role of programmed death 1 (PD-1) and its ligands, molecules known to modulate T cell activation, in the regulation of IFN-gamma production and lytic degranulation during human tuberculosis. We demonstrated that specific Ag-stimulation increased CD3+PD-1+ lymphocytes in peripheral blood and pleural fluid from tuberculosis patients in direct correlation with IFN-gamma production from these individuals. Moreover, M. tuberculosis-induced IFN-gamma participated in the up-regulation of PD-1 expression. Blockage of PD-1 or PD-1 and its ligands (PD-Ls: PD-L1, PD-L2) enhanced the specific degranulation of CD8+ T cells and the percentage of specific IFN-gamma-producing lymphocytes against the pathogen, demonstrating that the PD-1:PD-Ls pathway inhibits T cell effector functions during active M. tuberculosis infection. Furthermore, the simultaneous blockage of the inhibitory receptor PD-1 together with the activation of the costimulatory protein signaling lymphocytic activation molecule led to the promotion of protective IFN-gamma responses to M. tuberculosis, even in patients with weak cell-mediated immunity against the bacteria. Together, we demonstrated that PD-1 interferes with T cell effector functions against M. tuberculosis, suggesting that PD-1 has a key regulatory role during the immune response of the host to the pathogen.

Leptin is thought to signal energy stores, thus helping the body balance energy intake and expenditure. However, the strong relationship between leptin and adiposity in populations with adequate nutrition or common obesity is not universal across ecologic contexts, and leptin often correlates only weakly, or not at all, with adiposity in populations of lean or marginally-nourished males. To clarify whether the relationship between adiposity and leptin changes during development, this study examines leptin and body fat among children and adolescents of lowland Bolivia. Anthropometric measures of body composition and dried blood spot samples were collected from 487 Tsimane' ranging from 2 to 15 years of age. Leptin was assayed using an enzyme immunoassay protocol validated for use with blood spot samples. In this population, leptin concentrations were among the lowest reported in a human population (mean +/- SD: 1.26 +/- 0.5 and 0.57 +/- 0.3 in females and males). In addition, the relationship between leptin and adiposity follows distinct developmental trajectories in males and females. In males, leptin is weakly correlated with most measures of body composition at all ages investigated. However, in females, the level of body fat and the strength of the correlation between body fat and leptin (a measure of its strength as a signal of energy stores) both increase markedly with age. These findings suggest a more important role of leptin as a signal of energy stores among females as they approach reproductive maturity, while raising questions about the function of this hormone in lean males., (Copyright 2008 Wiley-Liss, Inc.)

We evaluated the role of regulatory T cells (CD4(+) CD25(+) Foxp3(+) cells, Tregs) in human Mycobacterium tuberculosis infection. Tregs were expanded in response to M. tuberculosis in healthy tuberculin reactors, but not in tuberculin-negative individuals. The M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) resulted in regulatory T cell expansion, whereas the M. tuberculosis 19-kDa protein and heat shock protein 65 had no effect. Anti-IL-10 and anti-TGF-beta alone or in combination, did not reduce expansion of Tregs. In contrast, the cyclooxygenase enzyme-2 inhibitor NS398 significantly inhibited expansion of Tregs, indicating that prostaglandin E2 (PGE2) contributes to Treg expansion. Monocytes produced PGE2 upon culturing with heat-killed M. tuberculosis or ManLAM, and T cells from healthy tuberculin reactors enhanced PGE2 production by monocytes. Expanded Tregs produced significant amounts of TGF-beta and IL-10 and depletion of Tregs from PBMC of these individuals increased the frequency of M. tuberculosis-responsive CD4(+) IFN-gamma cells. Culturing M. tuberculosis-expanded Tregs with autologous CD8(+) cells decreased the frequency of IFN-gamma(+)cells. Freshly isolated PBMC from tuberculosis patients had increased percentages of Tregs, compared to healthy tuberculin reactors. These findings demonstrate that Tregs expand in response to M. tuberculosis through mechanisms that depend on ManLAM and PGE2.

Objective: Programs aimed at obesity prevention among elementary school age children have failed. In the present study, we analyzed the association between parental and child food preferences and determined whether this is influenced by the parents' gender and socio-economic status., Material and Methods: We invited 300 children from a state elementary school (SES) and368 from a private middle class school (PMCS) to participate. A questionnaire was given to each parent to complete together with another questionnaire asking questions about their child. The questionnaire included items on consumption of specific foods. Canonical correlation coefficients (CC) were calculated to assess the association between children's food preferences and their parents' food preferences., Results: Mothers from the PMCS group had lower Body Mass Index (BMIs) than mothers from the SES (24 +/- 4 vs. 26 +/- 4, p < 0.001). Fathers and children from the PMCS group were taller and weighed more than those from the SES but their BMI's were similar. CC indicate that mothers influence their children's food preferences by 30%, and this association is stronger in the SES group. Preference for simple carbohydrates was observed among children without parental supervision. Regular soft drinks were preferred by children in both schools, but diet sodas were more common among PMCS. All families avoided giving their children diet soft drinks., Conclusions: Socio-economic status and gender diferentially influence children's meal preferences. Obsesity prevention programs should take into account parental food preferences as an important factor that determines obesity during childhood. We expect that our results will contribute to the design of more appropriate prevention programs.

Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)- gamma production during tuberculosis by investigating the role of CD31, a receptor that attenuates T cell receptor signals. After antigen stimulation, CD3(+)CD31(+) blood lymphocytes decreased in healthy donors and in tuberculosis patients with robust Th1 responses to Mycobacterium tuberculosis and IFN- gamma was secreted only by CD31(-) T cells. In contrast, in patients with weak Th1 cytokine responses to M. tuberculosis, the level of CD3(+)CD31(+) lymphocytes was increased and IFN- gamma production was low. Furthermore, the inverse relationship between CD31 expression and IFN- gamma production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN- gamma inducer in tuberculosis. Interestingly, CD31 bound to SLAM-associated protein (SAP), an IFN- gamma inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN- gamma response to M. tuberculosis. Thus, CD31, when binding to SAP, interferes with Th1 responses, suggesting that CD31 has a key regulatory role in the signaling pathway(s) leading to the IFN- gamma response to M. tuberculosis.

Obesity is associated with a complex systemic inflammatory reaction that has been associated with the development of atherosclerosis and insulin resistance. Obesity also induces macrophage accumulation in adipose tissue. Macrophages produce many of the pro inflammatory molecules released by adipose tissue and have been implicated in the development of obesity-induced adipose tissue inflammation. Monocyte chemoattractant proteins (MCPs) and their receptors play key roles in the development of inflammatory responses and are crucial for the recruitment of immune cells towards inflammation sites. Adipose tissue expression of at least 1 MCP, C-C motif chemokine ligand-2 (CCL2 or MCP1), increases in proportion to adiposity. The C-C motif chemokine receptor-2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Because CCR2 regulates monocyte and macrophage chemotaxis and local inflammatory responses, it has been hypothesized that monocyte chemoattractant molecules acting through CCR2 might regulate obesity-induced inflammation in adipose tissue. Our study focuses on the molecular and genetic mechanisms that recruit and retain macrophages in adipose tissue.

Immune cells are modulated through the crosslinking of receptors named "immunoreceptors". Ligation of immunoreceptors by their ligands induces a tyrosine-phosphorylation signal that is essential for cell activation or inhibition. Physiologically, immunoreceptor triggering is not enough for cell activation, and stimulation of co-receptors is necessary for antigen-evoked cytokine production. Thus, signal transduction pathways mediated by proteins that regulate cytokine secretion are critical to achieve an effective immune response of the host, where the balance between positive and negative signaling allows effective immune responses, preventing tolerance and autoimmunity. This review deals with recent studies based on the role of the receptor signaling lymphocytic activation molecule (SLAM), a signaling protein that modulates cytokine secretion by immune cells, and the transmembrane glycoprotein CD31, which plays multiple roles in cellular signaling events by modulating the balance between inhibitory and stimulatory signals to immune cells. Recent studies have shed light on the ability of these molecules to transmit different signals that regulate the ability of innate and adaptive immune cells to synthesize stimulatory and inhibitory cytokines.

Although the efficacy of laryngeal mask airway (LMA) has been demonstrated for securing patency of the airway in children, it has not yet been compared to endotracheal tube (ET) in this population. This study aimed to compare the safety and efficacy of LMA vs. ET in children undergoing elective diagnostic upper gastrointestinal endoscopies. Sixty ASA I-III patients were randomly allocated to ET (Group I) or LMA (Group II). A set of cardiovascular and respiratory parameters were obtained before, during and after the endoscopic procedure. The recovery time and the time to discharge were also registered. The cardiovascular and respiratory parameters evaluated in the study varied across the different evaluation periods. However, they remained within physiological ranges and were not different between groups. The median (range) recovery time was 4 (2-10) min and the time to discharge was 58 (36-88) min in the ET group and 3 (1-7) min and 50 (35-67) min in the LMA group (P > 0.10), respectively. In a 16 month-old, 80 cm and 10 kg girl, we failed to secure the patency of the airway with LMA. In conclusion, the LMA was as effective and safe as ET for securing the airway of children undergoing diagnostic upper endoscopies. However, the 3% failure rate occurred with LMA.