Down-Regulation-Resistant STAT4 Risk Haplotype Contributes to Lupus Nephritis Through CD4+ T Cell Interferon-γ Production.

OBJECTIVE: Variants in STAT4 are associated with systemic lupus erythematosus (SLE) and other autoimmune diseases. We undertook this study to investigate how disease-associated variants affect STAT4 expression, in particular in CD4+ T cells where STAT4 plays an essential role. METHODS: We compared Th1 differentiation between naive CD4+ T cells from healthy donors homozygous for the risk (R/R) or nonrisk (NR/NR) alleles. We analyzed epigenetic marks in STAT4 and evaluated the relevance of its third intron, assessed the consequences of Stat4 overexpression in vivo in mice, and analyzed the effects of the STAT4 genotype in patients with lupus nephritis. RESULTS: Naive CD4+ T cells from NR/NR healthy donors down-regulated STAT4 in response to interleukin-12 (IL-12). In contrast, cells from R/R healthy donors maintained high levels. R/R cells exhibited a higher abundance of transcriptionally active STAT4 and increased interferon-γ production. Accordingly, R/R healthy donors exhibited a stronger induction of local active enhancer marks. Genetic editing confirmed the presence of a negative regulatory region in the STAT4 third intron, where most of the SLE-associated STAT4 single-nucleotide polymorphisms (SNPs) are located. In vivo forced expression demonstrated that increases in Stat4 levels in T cells enhanced glomerulonephritis in mice. Accordingly, the R/R genotype was associated with suboptimal response to treatment and with worse clinical outcomes in patients with proliferative lupus nephritis. CONCLUSION: The SLE-associated STAT4 haplotype correlates with an abnormal IL-12-mediated STAT4 transcriptional regulation. Carriers of the risk variant exhibit exaggerated CD4+ proinflammatory capacities that, in the context of SLE, contribute to more severe disease. R/R patients may benefit from blockade of the IL-12/STAT4 pathway.

Sequential delay and probability discounting tasks in mice reveal anchoring effects partially attributable to decision noise.

Delay discounting and probability discounting decision making tasks in rodent models have high translational potential. However, it is unclear whether the discounted value of the large reward option is the main contributor to variability in animals' choices in either task, which may limit translation to humans. Male and female mice underwent sessions of delay and probability discounting in sequence to assess how choice behavior adapts over experience with each task. To control for "anchoring" (persistent choices based on the initial delay or probability), mice experienced "Worsening" schedules where the large reward was offered under initially favorable conditions that became less favorable during testing, followed by "Improving" schedules where the large reward was offered under initially unfavorable conditions that improved over a session. During delay discounting, both male and female mice showed elimination of anchoring effects over training. In probability discounting, both sexes of mice continued to show some anchoring even after months of training. One possibility is that "noisy", exploratory choices could contribute to these persistent anchoring effects, rather than constant fluctuations in value discounting. We fit choice behavior in individual animals using models that included both a value-based discounting parameter and a decision noise parameter that captured variability in choices deviating from value maximization. Changes in anchoring behavior over time were tracked by changes in both the value and decision noise parameters in delay discounting, but by the decision noise parameter in probability discounting. Exploratory decision making was also reflected in choice response times that tracked the degree of conflict caused by both uncertainty and temporal cost, but was not linked with differences in locomotor activity reflecting chamber exploration. Thus, variable discounting behavior in mice can result from changes in exploration of the decision options rather than changes in reward valuation.

Dysregulated protein kinase/phosphatase networks in SLE T cells.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with multiple phenotypic and functional aberrations in T lymphocytes. Among these, altered expression and/or activity of several protein kinases and phosphatases has been consistently documented in T cells obtained from patients with SLE. In this review, we describe and contextualize some of the kinase and phosphatase defects reported in T cells from patients with SLE, highlighting their relevance and possible consequences. Additionally, we discuss the origin of the defects and its significance for disease development and expression.

What do we know (and need to know) about the role of urban habitats as ecological traps? Systematic review and meta-analysis.

Urban areas represent a spectrum that goes from being safe habitats for biodiversity (i.e., habitats more or equally preferred, without costs to fitness) to being ecological traps (i.e., habitats more or equally preferred, but with costs to fitness). Given the imminent urban expansion, it is valuable to assess how biodiversity is responding to urbanization and thus generate timely conservation strategies. We systematically review the urban ecology literature to analyze how much do we know about the role of urban areas as ecological traps. Using a formal meta-analytical approach, we test whether urban areas are functioning as ecological traps or as safe habitats for different taxonomic groups. We generated a data set of 646 effect sizes of different measures of habitat preferences and fitness from 38 papers published between 1985 and 2020. The data set covered 15 countries and 47 urban areas from four continents, including 29 animal species. Studies from North America and Europe were best represented, and birds were the most studied taxa. Overall, the meta-analysis suggests that urbanized habitats are functioning more as safe sites than as ecological traps, mainly for certain species with characteristics that have allowed them to adapt well to urban areas. That is, many of the studied species prefer more urbanized habitats over other less urbanized sites, and their fitness is not modified, or it is even increased. However, there was high heterogeneity among studies. We also performed meta-regressions to identify variables accounting for this heterogeneity across studies and we demonstrate that outcomes may depend on methodological aspects of studies, such as study design or the approach used to measure habitat preference and fitness. More research is needed for poorly studied regions and on a wider range of species before generalizations can be made on the role of urban areas for biodiversity conservation.

Water Availability-Demand Balance under Climate Change Scenarios in an Overpopulated Region of Mexico.

Climate change scenarios show that water availability could be decreasing in the near future, adding to the increasing problem of the growing water demands in socioeconomic sectors. The aim of this work was to generate a geographically explicit water balance concerning availability vs. demand in an overpopulated region of Mexico. Water balance and water deficit models were made for three periods of time: 1970-2000, and two future periods of time (2041-2060 and 2061-2080). Three global climate models were used in addition to two different climate scenarios from each (Representative Concentration Pathways (RCP) RCP 4.6 and RCP 8.5). Water demand for socioeconomic sectors was calculated through the water footprint. Water availability was 197,644.58 hm3/year, while that the water demand was 59,187 hm3/year. The socioeconomic sectors with the highest demand were domestic services (48%), agriculture (27%), livestock agriculture (20%), and timber production (5%). The highest water availability areas were not the same as those with the highest demand and vice versa. However, 39% of municipalities had a higher water demand than its availability. A significant reduction in water availability was identified, considering an interval of -15% to 40%. This variation depends on climate models, scenarios, and period of time. Areas with overpopulated cities in the region would have higher pressure on water availability. These results could be used in the implementation of public policies by focusing on adaptation strategies to reduce water deficit in the immediate future.

Protein-conformational diseases in childhood: Naturally-occurring hIAPP amyloid-oligomers and early ß-cell damage in obesity and diabetes.

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.

Saproxylic Cetoniidae (Coleoptera: Scarabaeoidea): A 'Females' World' or a Question of Dependence on Deadwood?

We explored the dependence of some Cetoniidae species on saproxylic environments and microhabitats in a Mediterranean oak forest by analyzing species collected using different kinds of traps-log emergence, hollow emergence, and interception traps-and the sex ratio of the species in each trap. Comparing the sex ratio of the species collected via emergence versus interception was useful to unravel the degree of dependence on saproxylic microhabitats. Among the species studied, Cetonia aurataeformis Curti, 1913 (Coleoptera: Cetoniidae) was the only obligate tree hollow inhabitant. Special attention should thus be paid to the maintenance of tree hollows for the species' conservation in Mediterranean forests. A gradient of dependence on tree hollows was established from the more dependent Protaetia (Potosia) cuprea (Fabricius, 1775) (Coleoptera: Cetoniidae) and Protaetia (Potosia) opaca (Fabricius, 1787) (Coleoptera: Cetoniidae) to the less dependent Protaetia (Netocia) morio (Fabricius, 1781) (Coleoptera: Cetoniidae). All the latter species can be considered facultatively dependent, to varying degrees, on tree hollows. By contrast, the saproxylic affinity of Protaetia (Netocia) oblonga (Gory and Percheron, 1833) (Coleoptera: Cetoniidae), Tropinota squalida (Scopoli, 1783) (Coleoptera: Cetoniidae) and Oxythyrea funesta (Poda, 1761) (Coleoptera: Cetoniidae) was doubtful. Generally, the sex ratio of the studied species was female-biased. A possible explanation may be local male competition for females, suggesting the Cetoniinae is a female world. However, the range of difference in the female-biased sex ratio among species suggests it is important to explore other possible causes, such as differences in dispersal abilities.

Unpacking the aggregation-oligomerization-fibrillization process of naturally-occurring hIAPP amyloid oligomers isolated directly from sera of children with obesity or diabetes mellitus.

The formation of amyloid oligomers and fibrils of the human islet amyloid polypeptide (hIAPP) has been linked with ß- cell failure and death which causes the onset, progression, and comorbidities of diabetes. We begin to unpack the aggregation-oligomerization-fibrillization process of these oligomers taken from sera of pediatric patients. The naturally occurring or real hIAPP (not synthetic) amyloid oligomers (RIAO) were successfully isolated, we demonstrated the presence of homo (dodecamers, hexamers, and trimers) and hetero-RIAO, as well as several biophysical characterizations which allow us to learn from the real phenomenon taking place. We found that the aggregation/oligomerization process is active in the sera and showed that it happens very fast. The RIAO can form fibers and react with anti-hIAPP and anti-amyloid oligomers antibodies. Our results opens the epistemic horizon and reveal real differences between the four groups (Controls vs obesity, T1DM or T2DM) accelerating the process of understanding and discovering novel and more efficient prevention, diagnostic, transmission and therapeutic pathways.

Ventral pallidum is essential for cocaine relapse after voluntary abstinence in rats.

Addiction is a chronic relapsing disorder, and during recovery many people experience several relapse events as they attempt to voluntarily abstain from drug. New preclinical relapse models have emerged that capture this common human experience, and mounting evidence indicates that resumption of drug seeking after voluntary abstinence recruits neural circuits distinct from those recruited during reinstatement after experimenter-imposed abstinence, or abstinence due to extinction training. Ventral pallidum (VP), a key limbic node involved in drug seeking, has well-established roles in conventional reinstatement models tested following extinction training, but it is unclear whether this region also participates in more translationally relevant models of relapse. Here we show that chemogenetic inhibition of VP neurons decreased cocaine-, context-, and cue-induced relapse tested after voluntary, punishment-induced abstinence. This effect was strongest in the most compulsive, punishment-resistant rats, and reinstatement was associated with neural activity in anatomically defined VP subregions. VP inhibition also attenuated the propensity of rats to display "abortive lever pressing," a species-typical risk assessment behavior seen here during punished drug taking, likely resulting from concurrent approach and avoidance motivations. These results indicate that VP, unlike other connected limbic brain regions, is essential for resumption of drug seeking after voluntary abstinence. Since VP inhibition effects were strongest in the most compulsively cocaine-seeking individuals, this may also indicate that VP plays a particularly important role in the most pathological, addiction-like behavior, making it an attractive target for future therapeutic interventions.

Reduced thermal variability in cities and its impact on honey bee thermal tolerance.

Urbanization is one of the most significant land cover transformations, and while climate alteration is one of its most cited ecological consequences we have very limited knowledge on its effect on species' thermal responses. We investigated whether changes in environmental thermal variability caused by urbanization influence thermal tolerance in honey bees (Apis mellifera) in a semi-arid city in central Mexico. Ambient environmental temperature and honey bee thermal tolerance were compared in urban and rural sites. Ambient temperature variability decreased with urbanization due to significantly higher nighttime temperatures in urban compared to rural sites and not from differences in maximum daily temperatures. Honey bee thermal tolerance breadth [critical thermal maxima (CTmax)-critical thermal minima (CTmin)] was narrower for urban bees as a result of differences in cold tolerance, with urban individuals having significantly higher CTmin than rural individuals, and CTmax not differing among urban and rural individuals. Honey bee body size was not correlated to thermal tolerance, and body size did not differ between urban and rural individuals. We found that honey bees' cold tolerance is modified through acclimation. Our results show that differences in thermal variability along small spatial scales such as urban-rural gradients can influence species' thermal tolerance breadths.

Pavlovian Extinction and Recovery Effects in Aversive Pavlovian to Instrumental Transfer.

Three studies explored the sensitivity of aversive Pavlovian to instrumental transfer (PIT) to Pavlovian extinction in rodents. Rats underwent Pavlovian conditioning prior to avoidance training. The PIT test then involved assessment of the effects of the Pavlovian conditioned stimulus (CS) on the performance of the avoidance response (AR). Conducting extinction prior to avoidance training and transfer testing, allowed spontaneous recovery and shock reinstatement of extinguished motivation, whereas conducting extinction following avoidance training and just prior to PIT testing successfully reduced transfer effects. This was also the case in a design that compared responding to an extinguished CS against a non-extinguished CS rather than comparing extinguished and non-extinguished groups to one another. While extinction treatments in many appetitive PIT studies do not successfully reduce transfer, and can sometimes enhance the effect, the current findings show that an extinction treatment temporally close to transfer testing can reduce the motivational impact of the aversive Pavlovian CS on instrumental avoidance responding.

Beta Diversity in a Highly Heterogeneous Area: Disentangling Species and Taxonomic Dissimilarity for Terrestrial Vertebrates.

Quantifying differences in species composition among communities provides important information related to the distribution, conservation and management of biodiversity, especially when two components are recognized: dissimilarity due to turnover, and dissimilarity due to richness differences. The ecoregions in central Mexico, within the Mexican Transition Zone, have outstanding environmental heterogeneity and harbor huge biological richness, besides differences in the origin of the biota. Therefore, biodiversity studies in this area require the use of complementary measures to achieve appropriate information that may help in the design of conservation strategies. In this work we analyze the dissimilarity of terrestrial vertebrates, and the components of turnover and richness differences, among six ecoregions in the state of Hidalgo, central Mexico. We follow two approaches: one based on species level dissimilarity, and the second on taxonomic dissimilarity. We used databases from the project "Biodiversity in the state of Hidalgo". Our results indicate that species dissimilarity is higher than taxonomic dissimilarity, and that turnover contributes more than richness differences, both for species and taxonomic total dissimilarity. Moreover, total dissimilarity, turnover dissimilarity and the dissimilarity due to richness differences were positively related in the four vertebrate groups. Reptiles had the highest values of dissimilarity, followed by mammals, amphibians and birds. For reptiles, birds, and mammals, species turnover was the most important component, while richness differences had a higher contribution for amphibians. The highest values of dissimilarity occurred between environmentally contrasting ecoregions (i.e., tropical and temperate forests), which suggests that environmental heterogeneity and differences in the origin of biotas are key factors driving beta diversity of terrestrial vertebrates among ecoregions in this complex area.

Abundancia relativa, estructura poblacional, preferencia de hábitat y patrones de actividad del tapir centroamericano Tapirus bairdii (Perissodactyla: Tapiridae), en la Selva de Los Chimalapas, Oaxaca, México / Relative abundance, population structure, habitat preferences and activity patterns of Tapirus bairdii (Perissodactyla: Tapiridae), in Chimalapas forest, Oaxaca, Mexico

Baird’s tapir (Tapirus bairdii) is endangered primarily because of habitat loss and fragmentation, and overhunting throughout its distribution range. One of the priority land areas for the conservation of this species is the Northern part of its range in the Chimalapas forest, Oaxaca. The aim of this research was to determine the relative abundance, population structure, habitat preferences and activity patterns of Baird´s tapir (Tapirus bairdii) in the Chimalapas forest, Oaxaca, Mexico, through the non-invasive technique of camera-trap sampling. A total of five sampling sessions were undertaken among 2009-2013, and used a total of 30 camera-traps in each period. The determinant factor of the sampling design was the hunting between two study areas. A total sampling effort of 9 000 trap-days allowed to estimate an index of relative abundance (IRA) of 6.77 tapir photographs/1 000 trap-days (n=61). IRA varied significantly between sampling stations (Mann-Whitney, p<0.01). The frequency of Baird´s tapir photos was higher in the dry season in tropical rain forest without hunting (x², p<0.5). In the rainy season, the tropical rain forest and secondary vegetation habitats showed higher photo frequency than expected from random (x², p<0.5). Considering population structure, a 95.08% of adult animals was obtained in photographic records (n=58). Three types of activity pattern were observed, with more nocturnal records (88.33%; Kruskal-Wallis, p<0.05). The Chimalapas forest appears to be the second most important terrestrial priority ecoregion, just after the Mayan Forest (Campeche, Chiapas, Quintana Roo), for the conservation of tapir populations, not only for Mexico but also for Central America. Rev. Biol. Trop. 62 (4): 1407-1419. Epub 2014 December 01.

El tapir centroamericano (Tapirus bairdii) está en peligro de extinción debido principalmente a la pérdida y fragmentación de su hábitat, y a la cacería sin control en toda su área de distribución. Una de las regiones terrestres prioritarias para la conservación de esta especie en la zona norte de su distribución se encuentra en la Selva de los Chimalapas, Oaxaca. Por lo que el objetivo de la presente investigación fue determinar la abundancia relativa, estructura poblacional, preferencia de hábitat y patrones de actividad del tapir centroamericano (Tapirus bairdii) en la Selva de los Chimalapas, Oaxaca, México, mediante el uso de cámaras trampa. Se realizaron cinco periodos de muestreo fotográfico entre 2009 y 2013 con un total de 30 cámaras trampa en cada periodo. El factor de diseño fue la intensidad de caza entre dos sitios. Con un esfuerzo total de muestreo de 9 000 días/trampa se estimó un índice de abundancia relativa (IAR) de 6.77/1 000 trampas-noche (n=61), variando significativamente entre estaciones de muestreo (Mann-Whitney, p<0.01). Durante la temporada de secas, los tapires fueron más abundantes y utilizaron con mayor intensidad el bosque tropical perennifolio sin cacería (x², p<0.5). Mientras que en la temporada de lluvia, el bosque tropical perennifolio con cacería y la vegetación secundaria con cacería fueron los hábitat significativamente más utilizados que lo esperado (x², p<0.5). Con respecto a la estructura poblacional se obtuvo un 95.08% de registros fotográficos de animales adultos (n=58). Se registraron tres tipos de patrones de actividad para la especie, siendo el patrón nocturno el que presentó mayor porcentaje de registros; 88.33% (Kruskal-Wallis, p<0.05). Finalmente, con base al número de registros fotográficos y a los resultados obtenidos es posible considerar a la Selva de los Chimalapas como la segunda eco-región terrestre prioritaria en importancia; después de la Selva Maya (Campeche, Chiapas, Quintana Roo), en la conservación de las poblaciones de tapir centroamericano, no sólo de México, sino de Centroamérica.

[Relative abundance, population structure, habitat preferences and activity patterns of Tapirus bairdii (Perissodactyla: Tapiridae), in Chimalapas forest, Oaxaca, Mexico]. / Abundancia relativa, estructura poblacional, preferencia de hábitat y patrones de actividad del tapir centroamericano Tapirus bairdii (Perissodactyla: Tapiridae), en la Selva de Los Chimalapas, Oaxaca, México.

Baird's tapir (Tapirus bairdii) is endangered primarily because of habitat loss and fragmentation, and overhunting throughout its distribution range. One of the priority land areas for the conservation of this species is the Northern part of its range in the Chimalapas forest, Oaxaca. The aim of this research was to determine the relative abundance, population struc- ture, habitat preferences and activity patterns of Baird's tapir (Tapirus bairdii) in the Chimalapas forest, Oaxaca, Mexico, through the non-invasive technique of camera-trap sampling. A total of five sampling sessions were undertaken among 2009-2013, and used a total of 30 camera-traps in each period. The determinant factor of the sampling design was the hunting between two study areas. A total sampling effort of 9000 trap-days allowed to estimate an index of relative abundance (IRA) of 6.77 tapir photographs/1,000 trap-days (n = 61). IRA varied significantly between sampling stations (Mann-Whitney, p < 0.01). The frequency of Baird's tapir photos was higher in the dry season in tropical rain forest without hunting (χ2, p < 0.5). In the rainy season, the tropical rain forest and secondary vegetation habitats showed higher photo frequency than expected from random (χ2, p < 0.5). Considering population structure, a 95.08% of adult animals was obtained in photographic records (n = 58). Three types of activity pattern were observed, with more nocturnal records (88.33%; Kruskal-Wallis, p < 0.05). The Chimalapas forest appears to be the second most important terrestrial priority ecoregion, just after the Mayan Forest (Campeche, Chiapas, Quintana Roo), for the conservation of tapir populations, not only for Mexico but also for Central America.

Vertebrate dissimilarity due to turnover and richness differences in a highly beta-diverse region: the role of spatial grain size, dispersal ability and distance.

We explore the influence of spatial grain size, dispersal ability, and geographic distance on the patterns of species dissimilarity of terrestrial vertebrates, separating the dissimilarity explained by species replacement (turnover) from that resulting from richness differences. With data for 905 species of terrestrial vertebrates distributed in the Isthmus of Tehuantepec, classified into five groups according to their taxonomy and dispersal ability, we calculated total dissimilarity and its additive partitioning as two components: dissimilarity derived from turnover and dissimilarity derived from richness differences. These indices were compared using fine (10 x 10 km), intermediate (20 x 20 km) and coarse (40 x 40 km) grain grids, and were tested for any correlations with geographic distance. The results showed that total dissimilarity is high for the terrestrial vertebrates in this region. Total dissimilarity, and dissimilarity due to turnover are correlated with geographic distance, and the patterns are clearer when the grain is fine, which is consistent with the distance-decay pattern of similarity. For all terrestrial vertebrates tested on the Isthmus of Tehuantepec both the dissimilarity derived from turnover and the dissimilarity resulting from richness differences make important contributions to total dissimilarity, and dispersal ability does not seem to influence the dissimilarity patterns. These findings support the idea that conservation efforts in this region require a system of interconnected protected areas that embrace the environmental, climatic and biogeographic heterogeneity of the area.

Occupational exposure to organophosphate and carbamate pesticides affects sperm chromatin integrity and reproductive hormone levels among Venezuelan farm workers.

OBJECTIVES: Several reports suggest that chronic pesticide exposure may affect semen quality and male fertility in humans. The objective of this study was to evaluate the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality, as well as levels of reproductive and thyroid hormones of Venezuelan farm workers. METHODS: Thirty-five healthy men (unexposed group) and 64 male agricultural workers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH) and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. RESULTS: Evidence of pesticide exposure was found in 87.5% of farmers based on AChE and BuChE inhibition. Significant increments were observed in sperm DFI with significant decreases in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology and vitality in these workers. The levels of Tt, PRL, FT4 and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. CONCLUSIONS: Our results confirm the potential impact of chronic occupational exposure to OP/CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.

Laringitis crónica asociada a reflujo gastroesofágico: La perspectiva del gastroenterólogo / Reflux laryngitis: a Gastroenterologist's perspective

La enfermedad por reflujo gastroesofágico (ERGE) es una causa frecuente de consulta en gastroenterología. La ERGE tiene manifestaciones digestivas y extradigestivas. Las manifestaciones extradigestivas que con mayor frecuencia se asocian a ERGE son la tos crónica, laringitis crónica y dolor torácico. La laringitis crónica, definida como la inflamación de la laringe que persiste por más de unas semanas, se asocia de manera frecuente a ERGE en la práctica clínica. Sin embargo, en varios estudios donde se utilizó la monitoría de pH esofágico como herramienta diagnóstica, no se encontró una clara asociación entre laringitis crónica y reflujo. Además, estudios en los que se manejaron inhibidores de bomba de protones en pacientes con sospecha de laringitis crónica por reflujo, mostraron una alta tasa de fracaso terapéutico, ya que en la gran mayoría de los casos, los síntomas persistían a pesar de una adecuada inhibición de la secreción ácida. Consideramos que aunque la ERGE puede ser la responsable de algunos episodios de laringitis crónica, no es la enfermedad que está asociada con mayor frecuencia, y en muchos de los casos en los que se ha descartado razonablemente la ERGE como responsable de los síntomas, deben investigarse de manera exhaustiva otras causas.

Gastroesophageal reflux disease (GERD) is a frequent cause of consultations with gastroenterologists. Extra-digestive symptoms such as chronic coughing, laryngitis and chest pain are frequently associated with GERD. Chronic laryngitis is one of the symptoms most often associated with GERD, yet various studies which have used monitoring esophageal pH as a diagnostic tool have not found any clear association between chronic laryngitis and reflux. Moreover, studies which have treated patients suspected of having chronic laryngitis caused by reflux with proton pump inhibitors (PPIs) have had had rates of therapeutic failures. Symptoms continue to persist in these patients despite adequate inhibition of acid secretion. To date, no evidence exists of the association between chronic laryngitis and GERD, much less evidence of a causal relation. We consider that, although GERD may be responsible for some episodes of chronic laryngitis, it is not the illness most frequently associated with it, and in the many cases in which GERD has been reasonably ruled out, other potential causes must be investigated.

Efectos de exposición ocupacional a plaguicidas sobre la integridad de la cromatina espermática

Objetivo: Evaluar los efectos de la exposición a plaguicidas organofosforados y carbamatos sobre la integridad de cromatina espermática en trabajadores agrícolas. Métodos: Se evaluaron 64 trabajadores del campo, con edades entre 18 y 55 años, de la comunidad rural de Bailadores, Municipio Rivas Dávila, Estado Mérida, Venezuela, expuestos directamente a plaguicidas. Para el diagnóstico de exposición a plaguicidas, fueron determinados los niveles de las colinesterasas eritrocitaria (AChE) y plasmática (PChE). Para evaluar la fertilidad masculina, a cada trabajador se le realizó seminograma y se les evaluó la integridad de la estructura de cromatina espermática mediante la técnica "Sperm Chromatin Structure Assay" (SCSA). Resultados: El 25% de los trabajadores agrícolas presentó niveles deprimidos de AChE y el 83% con niveles anormales de PChE, con una reducción <75% del nivel normal. El grupo con edades entre 18 y 28 años fue el más afectado. Diferencias significativas fueron obtenidas en los promedios de los niveles de colinesterasas entre los casos normales y alterados, tanto para AChE (3,95±0,42 vs. 2,72±0,16, ρ<0,0001) así como para PChE (2,08±0,25 vs. 1,43±0,32, ρ<0,0001). El 69,7% de los trabajadores con niveles anormales de PChE presentó alteración en el ADN espermático. Se encontró una correlación negativa significativa entre el Índice de Fragmentación de ADN (IDF) espermático y los niveles de PChE (ρ=0,02). Conclusiones: En trabajadores agrícolas expuestos directamente a plaguicidas organofosforados y carbamatos, un alto porcentaje presentó niveles anormalmente deprimidos de PChE, junto con alteración en el ADN espermático. Estos resultados demuestran que los trabajadores se encuentran con alto riesgo de exposición a los efectos tóxicos de plaguicidas, lo cual efectivamente se comprueba con los resultados de análisis de las enzimas colinesterasas y la aplicación de la técnica SCSA para determinar la integridad de la cromatina espermática.

Objective: To evaluate the effects of exposure to organophosphate and carbamate pesticides on the integrity of sperm chromatin in farm workers. Methods: In this study, we evaluated 64 farm workers, aged between 18 and 55 years, from the rural community of Bailadores, Municipality of Rivas Dávila, Mérida State, Venezuela, directly exposed to pesticides. For the diagnosis of pesticide exposure, levels of erythrocyte (AChE) and plasma (PchE) cholinesterases. were determined. To evaluate male fertility, each worker underwent semen analysis and the integrity of sperm chromatin structure was assessed using the "Sperm Chromatin Structure Assay (SCSA) technique. Results: The results of this study showed that 25% of agricultural workers had depressed levels of AChE and a majority, 83%, was found with abnormal levels of PChE. The group with corresponding ages between 18 and 28 years was the most affected. Significant differences were obtained in the average cholinesterase levels between normal and altered cases for both AChE (3.95 ± 0.42 vs. 2.72 ± 0.16, p < 0.0001) and PChE (2.08 ± 0.25 vs. 1.43 ± 0.32, ρ < 0.0001). Among workers with abnormal PChE levels, 69.7% presented alterations of sperm chromatin structure. There was a significant negative correlation between sperm DNA Fragmentation Index (DFI) and the levels of PChE (ρ = 0.02). Conclusions: In agricultural workers directly exposed to organophosphate and carbamate pesticides, a high percentage showed abnormally depressed PChE, along with altered sperm chromatin structure. These results show that farm workers are at high risk of exposure to the toxic effects of pesticides, which were effectively demonstrated with the results of analysis of cholinesterase enzymes and the implementation of the SCSA technique for determining the status of the sperm chromatin structure.

[Kidney transplant program: Mexican Institute of Transplants. Model of synergy between private hospital and private assistance foundations]. / Programa de trasplante renal: Instituto Mexicano de Trasplantes. Modelo de sinergia entre hospital privado y fundaciones de asistencia privada.

INTRODUCTION: The Mexican Institute of Transplantation (IMT) was created in 1999 in response to the need to meet the demand for transplants in the south of the country for patients with limited resources. Thanks to the synergy with private assistance foundations this task has been accomplished. OBJECTIVE: To describe the IMT experience in kidney transplants. RESULTS: From November 1999 to May 23,2011, 754 kidney transplants were performed in the IMT, of which 733 were from living donors and only 21 from deceased donors. In our experience, the 10-year patient and graft survival were 84.4 and 72.4%, respectively. The average follow-up of patients was 44 months, it was during the first year after transplantation when most of patients were lost. More than 50% of patients have been supported by private assistance foundations. The IMT has participated in research protocols for phase II and phase III, for the development of new immunosuppressants. CONCLUSION: The synergy between our private medical institution and private assistance foundations has permitted to transplant low income patients, a similar association can be carried out in governmental health institutions that have overcharge in their transplant services.

[Medical reflections on a case of pulmonary thromboembolism in pregnancy]. / Reflexiones médicas a propósito de un caso de tromboembolia pulmonar en el embarazo.

Maternal mortality is still high in the world. Pulmonary thromboembolism as a cause of death is the second in developed countries. The frequency of reported events in Latin-American is 0.6%, which contrasts with that reported for developed countries (14.9%). This difference may be related to information bias. A review of the current information about this topic is presented, and we report a short case of a pregnant woman who presented pulmonary thromboembolism event at 30 weeks of pregnancy. Appropriate therapy allowed maternal and fetal survival.