ABSTRACT
Many attempts have been proposed to evaluate the linkage between the oral-gut-liver axis and the mechanisms related to the diseases' establishment. One of them is the oral microbiota translocation into the bloodstream, liver, and gut, promoting a host dysbiosis and triggering the presence of some metabolites such as trimethylamine N-oxide (TMAO), known as a risk marker for cardiovascular disease, and especially the myocardial infarction (MI). In the present pilot study, the involvement of oral dysbiosis related to the presence of TMAO has been considered an independent component of the standard risk factors (SRs) in the development of MI, which has not been previously described in human cohorts. A positive and significant correlation of TMAO levels with Porphyromonas was identified; likewise, the increase of the genus Peptidiphaga in patients without SRs was observed. We determined that the presence of SRs does not influence the TMAO concentration in these patients. This report is the first study where the relationship between oral dysbiosis and TMAO is specified in the Mexican population. Our findings provide information on the possible contribution of the oral pathogens associated with gut dysbiosis in the development of MI, although further analysis should be performed.
Subject(s)
Gastrointestinal Microbiome , Methylamines , Microbiota , Myocardial Infarction , Humans , Dysbiosis/complications , Pilot ProjectsABSTRACT
Depression is the leading cause of disability worldwide, contributing to the global disease burden. From above, it is a priority to investigate models that fully explain its physiopathology to develop new treatments. In the last decade, many studies have shown that gut microbiota (GM) dysbiosis influences brain functions and participate, in association with immunity, in the pathogenesis of depression. Thereby, GM modulation could be a novel therapeutic target for depression. This review aims to evidence how the GM and the immune system influence mental illness, particularly depression. Here, we focus on the communication mechanisms between the intestine and the brain and the impact on the development of neuroinflammation contributing to the development of Major Depressive Disorder (MDD). However, most of the current findings are in animal models, suggesting the need for studies in humans. In addition, more analysis of metabolites and cytokines are needed to identify new pathophysiological mechanisms improving anti-depression treatments.
Subject(s)
Depressive Disorder, Major , Gastrointestinal Microbiome , Animals , Humans , Depressive Disorder, Major/therapy , Brain-Gut Axis , Neuroinflammatory Diseases , BrainABSTRACT
OBJECTIVES: This study compared the relationships of social determinants with cardiometabolic risk in different socioeconomic contexts: sociopolitically unstable Venezuela (VE) and stable Czechia (CZ). DESIGN: cross-sectional analysis involving two population-based studies. SETTING: Brno, Czechia and 23 cities of Venezuela. PARTICIPANTS: 25-64 years old subjects from CZ (2013-2014, n=1579, 56% females) and VE (2014-2017, n=1652, 70% females). MAIN OUTCOME MEASURES: The composite cardiometabolic risk score (CMRS) (scaled 0-8) was calculated using eight biomarkers (body mass index, waist circumference, blood glucose, systolic and diastolic blood pressure, total and high-density lipoprotein-cholesterol, triglycerides). Social characteristics included education in both countries, income in CZ and a composite measure of social position (SP) in VE. Sex stratified ordinal regression examined the social gradient in having less favourable CMRS. RESULTS: In CZ, men and women with low education and women with low income had higher odds of higher CMRS compared with those with high education and income with OR 1.45 (95% CI 1.01 to 2.21), 2.29 (95% CI 1.62 to 3.24) and 1.69 (95% CI 1.23 to 2.35). In VE, women with low education and low SP had higher odds to have higher CMRS OR 1.47 (95% CI 1.09 to 1.97) and 1.51 (95% CI 1.16 to 1.97), while men with low education and low SP had lower odds to have higher CMRS OR 0.64 (95% CI 0.41 to 1.00) and 0.61 (95% CI 0.40 to 0.97), compared with those with high education and high SP. Independently of age, sex and socioeconomic characteristics, Venezuelans had higher odds to have higher CMRS than Czechs (OR 2.70; 95% CI 2.37 to 3.08). CONCLUSIONS: The results suggest that the associations of socioeconomic status indices and cardiometabolic risk differed between CZ and VE, likely reflecting differences in the social environment among countries. Further research is needed to confirm and quantify these differences.
Subject(s)
Cardiovascular Diseases , Male , Humans , Female , Adult , Middle Aged , Cross-Sectional Studies , Cardiovascular Diseases/epidemiology , Czech Republic/epidemiology , Venezuela/epidemiology , Risk Factors , Social Class , Body Mass IndexABSTRACT
Trimethylamine N-oxide (TMAO) is a metabolite produced by the gut microbiota and has been mainly associated with an increased incidence of cardiovascular diseases (CVDs) in humans. There are factors that affect one's TMAO level, such as diet, drugs, age, and hormones, among others. Gut dysbiosis in the host has been studied recently as a new approach to understanding chronic inflammatory and degenerative diseases, including cardiovascular diseases, metabolic diseases, and Alzheimer's disease. These disease types as well as COVID-19 are known to modulate host immunity. Diabetic and obese patients have been observed to have an increase in their level of TMAO, which has a direct correlation with CVDs. This metabolite is attributed to enhancing the inflammatory pathways through cholesterol and bile acid dysregulation, promoting foam cell formation. Additionally, TMAO activates the transcription factor NF-κB, which, in turn, triggers cytokine production. The result can be an exaggerated inflammatory response capable of inducing endoplasmic reticulum stress, which is responsible for various diseases. Due to the deleterious effects that this metabolite causes in its host, it is important to search for new therapeutic agents that allow a reduction in the TMAO levels of patients and that, thus, allow patients to be able to avoid a severe cardiovascular event. The present review discussed the synthesis of TMAO and its contribution to the pathogenesis of various inflammatory diseases.
ABSTRACT
OBJECTIVE: Acknowledging the rates of endophthalmitis after cataract surgery is very important to understand the seriousness of the disease. Until now, there is no data of this situation in Argentina. The aim of this study was to estimate the incidence of postoperative endophthalmitis after cataract surgery at a tertiary hospital, a medical facility which provides a high degree of subspecialty expertise, in Buenos Aires, Argentina. METHOD: Retrospective cohort study of adult patients who underwent cataract phacoemulsification surgery between 2006 and 2020 at Hospital Italiano de Buenos Aires, was performed. Patients with endophthalmitis diagnosis within the first 6 weeks after surgery were included. Those who underwent extracapsular surgery or combined surgeries were excluded. RESULTS: A total of 29 326 cataract surgeries were performed in ten years. The annual incidence of acute postoperative endophthalmitis after cataract surgery was 0.102% (95% CI 0.069-0.146). Thirty cases of endophthalmitis were diagnosed. The main microorganism was Pseudomonas aeruginosa (45.4%). Final visual acuity was higher than 0.3 (LogMAR) in 46.6% of the patients. CONCLUSION: The incidence of endophthalmitis after cataract surgery in this hospital is within the range reported globally. Knowing the regional incidence contributes to decide if new prophylaxis measures are necessary.
OBJETIVO: Conocer las tasas de endoftalmitis después de la cirugía de cataratas es muy importante para comprender la gravedad de la enfermedad. Hasta el momento, no hay datos de su situación en Argentina. El objetivo de este estudio fue estimar la incidencia de endoftalmitis postoperatoria tras cirugía de catarata en un hospital de tercer nivel o alta complejidad de Buenos Aires, Argentina. Método: Se realizó un estudio de cohorte retrospectivo de pacientes adultos operados de facoemulsificación de cataratas entre 2006 y 2020 en el Hospital Italiano de Buenos Aires. Se incluyeron pacientes con diagnóstico de endoftalmitis dentro de las primeras 6 semanas posteriores a la cirugía. Se excluyeron los pacientes que se sometieron a cirugía extracapsular o cirugías combinadas. RESULTADOS: En diez años se realizaron un total de 29.326 operaciones de cataratas. La incidencia anual de endoftalmitis postoperatoria aguda después de la cirugía de cataratas fue del 0.102% (IC del 95%: 0.069-0.146). Treinta casos de endoftalmitis fueron identificados. El principal microorganismo fue Pseudomonas aeruginosa (45.4%). La agudeza visual final fue superior a 0.3 (LogMAR) en el 46.6% de los pacientes. Conclusión: La incidencia de endoftalmitis después de la cirugía de cataratas en este hospital está dentro del rango reportado a nivel mundial. Conocer la incidencia regional contribuye a decidir si son necesarias nuevas medidas de profilaxis.
Subject(s)
Cataract Extraction , Cataract , Endophthalmitis , Adult , Humans , Retrospective Studies , Tertiary Care Centers , Incidence , Cataract Extraction/adverse effects , Endophthalmitis/epidemiology , Endophthalmitis/etiology , Endophthalmitis/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/drug therapy , Cataract/drug therapy , Anti-Bacterial Agents/therapeutic useABSTRACT
Abstract Objective: Acknowledging the rates of endophthalmitis after cataract surgery is very important to understand the seriousness of the disease. Until now, there is no data of this situation in Argentina. The aim of this study was to estimate the incidence of postoperative endophthalmitis after cataract surgery at a tertiary hospital, a medical facility which provides a high degree of subspecialty expertise, in Buenos Aires, Argentina. Method: Retrospective cohort study of adult patients who underwent cataract phacoemulsification sur gery between 2006 and 2020 at Hospital Italiano de Buenos Aires, was performed. Patients with endophthalmitis diagnosis within the first 6 weeks after surgery were included. Those who underwent extracapsular surgery or combined surgeries were excluded. Results: A total of 29 326 cataract surgeries were performed in ten years. The annual incidence of acute postoperative endophthalmitis after cataract surgery was 0.102% (95% CI 0.069-0.146). Thirty cases of endophthalmitis were diagnosed. The main microorganism was Pseudomonas aeruginosa (45.4%). Final visual acuity was higher than 0.3 (LogMAR) in 46.6% of the patients. Conclusion: The incidence of endophthalmitis after cataract surgery in this hospital is within the range reported globally. Knowing the regional incidence contributes to decide if new prophylaxis measures are necessary.
Resumen Objetivo: Conocer las tasas de endoftalmitis después de la cirugía de cataratas es muy importante para comprender la gravedad de la enfermedad. Hasta el momento, no hay datos de su situación en Argentina. El objetivo de este estudio fue estimar la incidencia de endoftalmitis postoperatoria tras cirugía de catarata en un hospital de tercer nivel o alta complejidad de Buenos Aires, Argentina. Método: Se realizó un estudio de cohorte retrospectivo de pacientes adultos operados de facoemulsificación de cataratas entre 2006 y 2020 en el Hospital Italiano de Buenos Aires. Se incluyeron pacientes con diagnóstico de endoftalmitis dentro de las prime ras 6 semanas posteriores a la cirugía. Se excluyeron los pacientes que se sometieron a cirugía extracapsular o cirugías combinadas. Resultados: En diez años se realizaron un total de 29.326 operaciones de cataratas. La incidencia anual de endoftalmitis postoperatoria aguda después de la cirugía de cataratas fue del 0.102% (IC del 95%: 0.069-0.146). Treinta casos de endoftalmitis fueron identificados. El principal microorganismo fue Pseudomonas aeruginosa (45.4%). La agudeza visual final fue superior a 0.3 (LogMAR) en el 46.6% de los pacientes. Conclusión: La incidencia de endoftalmitis después de la cirugía de cataratas en este hospital está dentro del rango reportado a nivel mundial. Conocer la incidencia regional contribuye a decidir si son necesarias nuevas medidas de profilaxis.
ABSTRACT
BACKGROUND: The gut has been hypothesized to be a protagonist tissue in multiple organ dysfunction syndrome (MODS) for the past three decades. Gastric reactance (XL) is a potential perfusion marker derived from gastric impedance spectroscopy (GIS), which is an emerging tool through which living tissue can be continuously measured to determine its pathophysiological evolution. This study aimed to compare the performance of XL [positive predictive values (PPV), negative predictive values (NPV), and area under the curve (AUC)] against commonly used perfusion markers before and during hypovolemic shock in swine subjects. METHODS: Prospective, controlled animal trial with two groups, control group (CG) N = 5 and shock (MAP ≤ 48 mmHg) group (SG) N = 16. Comparison time points were defined as T-2 (2 h before shock), T-1 (1 h before shock), T0 (shock), T1 (1 h after shock), and T2 (2 h after shock). Shock severity was assessed through blood gases, systemic and hemodynamic variables, and via histological examination for assessing inflammation-edema and detachment in the gastric mucosa. Macroscopic assessment of the gastric mucosa was defined in five levels (0-normal mucosa, 1-stippling or epithelial hemorrhage, 2-pale mucosa, 3-violet mucosa, and 4-marmoreal mucosa). Receiver Operating Characteristic (ROC) curves of perfusion markers and XL were calculated to identify optimal cutoff values and their individual ability to predict hypovolemic shock. RESULTS: Comparison among the CG and the SG showed statistically significant differences in XL measurements at T-1, T0, T1, and T2, while lactate showed statistically significant differences until T1 and T2. Statistically significant differences were detected in mucosa class (p < 0.001) and in inflammation-edema in the gastric body and the fundus (p = 0.021 and p = 0.043). The performance of the minimum XL value per subject per event (XL_Min) was better (0.81 ≤ AUC ≤ 0.96, 0.93 ≤ PPV ≤ 1.00, 0.45 ≤ NPV ≤ 0.83) than maximum lactate value (Lac_Max) per subject per event (0.29 ≤ AUC ≤ 0.82, 0.82 ≤ PPV ≤ 0.91, 0.24 ≤ NPV ≤ 0.82). Cutoff values for XL_Min show progressive increases at each time point, while cutoff values for Lac_Max increase only at T2. CONCLUSIONS: XL proved to be an indirect and consistent marker of inadequate gastric mucosal perfusion, which shows significant and detectable changes before commonly used markers of global perfusion under the hypovolemic shock conditions outlined in this work.
ABSTRACT
Breast cancer ranks first in terms of mortality and incidence rates worldwide among women. The HER2+ molecular subtype is one of the most aggressive subtypes; its treatment includes neoadjuvant chemotherapy and the use of a HER2 antibody. Some patients develop resistance despite positive results obtained using this therapeutic strategy. OBJECTIVE: To identify prognostic markers for treatment and survival in HER2+ patients. METHODS: Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). RESULTS: A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). CONCLUSION: We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.
ABSTRACT
Effective preventive care programs are urgently needed during humanitarian crises, as has been especially obvious during the COVID-19 pandemic. A pragmatic trial was designed: hybridized intervention (Diabetes Prevention Program [DPP] + medical nutrition therapy + liquid diet [LD]; LD group) vs. DPP only (DPP group). The participants were adults who were overweight/obese and at high risk of type 2 diabetes mellitus (T2DM). The LD consisted of a "homemade" milk- and fruit-juice-based beverage. Pandemic restrictions delayed the program by nine months, tripled the amount of time required for screening, and reduced the total sample to 60%. Eventually, 127 participants were randomized, and 94/127 participants (74.0%) completed the first phase. Participant dropout was influenced by migration, COVID-19 symptoms, education level, and socioeconomic status. In two months, the LD group lost 2.9 kg (p < 0.001) and the DPP group, 2.2 kg (p < 0.001) (between-group p = 0.170), with improvements in their cardiometabolic risk factors. At this stage, the DPP was shown to be feasible and effective, demonstrating weight loss with the improvement of cardiometabolic risk factors in a primary setting in Venezuela, a middle-income country with a chronic humanitarian crisis, during the COVID-19 pandemic.
Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Adult , COVID-19/epidemiology , COVID-19/prevention & control , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/prevention & control , Feasibility Studies , Humans , Pandemics/prevention & control , SARS-CoV-2 , Venezuela/epidemiologyABSTRACT
Abstract Objective: Waist circumference (WC) value reflects abdominal adiposity, but the amount abdominal fat that is associated to cardiometabolic risk factors varies among ethnicities. Determination of metabolic abnormalities has not undergone a WC adaptation process in Venezuela. The aim of the study was (1) to determine the optimal WC cutoff value associated with ≥2 cardiometabolic alterations and (2) incorporating this new WC cutoff, to determine the prevalence of abdominal obesity and cardiometabolic risk factors related in Venezuela. Methods: The study was national population-based, cross-sectional, and randomized sample, from 2014 to 2017. To assess performance of WC for identifying cardiometabolic alterations, receiver operating characteristics curves, area under the curve (AUC), sensitivity, specificity, and positive likelihood ratios were calculated. Results: Three thousand three hundred eighty-seven adults were evaluated with mean age of 41.2 ± 15.8 years. Using the best tradeoff between sensitivity and specificity, WC cutoffs of 90 cm in men (sensitivity = 72.4% and specificity = 66.1%) and 86 cm in women (sensitivity = 76.2% and specificity = 61.4%) were optimal for aggregation of ≥2 cardiometabolic alterations. AUC was 0.75 in men and 0.73 in women using these new cutoffs. Prevalence of abdominal obesity and metabolic syndrome was 59.6% (95 CI; 57.5-61.7) and 47.6% (95 CI; 45.2-50.0), respectively. Cardiometabolic risk factors were associated with being men, higher age, adiposity, and living in northern or western regions. Conclusion: The optimal WC values associated with cardiometabolic alterations were 90 cm in men and 86 cm in women. More than half of the Venezuelan population had abdominal obesity incorporating this new WC cutoff.
Resumen Objetivo: El valor de la circunferencia abdominal (CA) refleja la adiposidad abdominal, pero la cantidad de grasa abdominal asociada a factores de riesgo cardiometabólicos varía según la etnia. La determinación de anomalías metabólicas no se ha adaptado a la CA en Venezuela. 1) Detrerminar el valor de corte óptimo de CA asociados a ≥ 2 alteraciones cardiometabólicas. 2) Incorporando este nuevo límite de CA, determinar la prevalencia de obesidad abdominal y factores de riesgo cardiometabólicos relacionados en Venezuela. Métodos: Fue un estudio poblacional, transversal, de muestreo aleatorio de 2014 a 2017. Para evaluar el valor de CA para identificar alteraciones cardiometabólicas, se realizaron curvas características operativa del receptor y se calculó área bajo la curva (ABC), sensibilidad, especificidad y razón de similitud. Resultados: se evaluaron 3387 adultos con una edad promedio de 41.2 ± 15.8 años. Utilizando la mejor relación entre sensibilidad y especificidad, se determinó que los valores de corte de 90 cm en hombres (sensibilidad = 72.4% y especificidad = 66.1%) y 86 cm en mujeres (sensibilidad = 76.2% y especificidad = 61.4%) fueron óptimos para la agregación de ≥ 2 alteraciones cardiometabólicas. El ABC fue de 0,75 en hombres y de 0,73 en mujeres usando estos nuevos puntos de corte. La prevalencia de obesidad abdominal y síndrome metabólico fue 59.6% (95IC; 57.5 - 61.7) y 47.6% (95CI; 45.2 - 50.0), respectivamente. La presencia de factores de riesgo cardiometabólicos se asoció con ser hombre, mayor edad, adiposidad y vivir en regiones del norte o del oeste. Conclusión: Los valores óptimos de CA asociados con alteraciones cardiometabólicas fueron 90 cm en hombres y 86 cm en mujeres. Más de la mitad de la población venezolana tenía obesidad abdominal al incorporar este nuevo corte de CA.
ABSTRACT
BACKGROUND: Waist circumference (WC) value reflects abdominal adiposity, but the amount abdominal fat that is associated to cardiometabolic risk factors varies among ethnicities. Determination of metabolic abnormalities has not undergone a WC adaptation process in Venezuela. AIMS: The aim of the study was (1) to determine the optimal WC cutoff value associated with ≥2 cardiometabolic alterations and (2) incorporating this new WC cutoff, to determine the prevalence of abdominal obesity and cardiometabolic risk factors related in Venezuela. METHODS: The study was national population-based, cross-sectional, and randomized sample, from 2014 to 2017. To assess performance of WC for identifying cardiometabolic alterations, receiver operating characteristics curves, area under the curve (AUC), sensitivity, specificity, and positive likelihood ratios were calculated. RESULTS: Three thousand three hundred eighty-seven adults were evaluated with mean age of 41.2 ± 15.8 years. Using the best tradeoff between sensitivity and specificity, WC cutoffs of 90 cm in men (sensitivity = 72.4% and specificity = 66.1%) and 86 cm in women (sensitivity = 76.2% and specificity = 61.4%) were optimal for aggregation of ≥2 cardiometabolic alterations. AUC was 0.75 in men and 0.73 in women using these new cutoffs. Prevalence of abdominal obesity and metabolic syndrome was 59.6% (95 CI; 57.5-61.7) and 47.6% (95 CI; 45.2-50.0), respectively. Cardiometabolic risk factors were associated with being men, higher age, adiposity, and living in northern or western regions. CONCLUSION: The optimal WC values associated with cardiometabolic alterations were 90 cm in men and 86 cm in women. More than half of the Venezuelan population had abdominal obesity incorporating this new WC cutoff.
ABSTRACT
Small ruminant lentiviruses (SRLVs) belong to the genus Lentivirus in the Retroviridae family. There are five genotypes (A, B, C, D, and E), where genotypes A and B have a global distribution and genotypes C, D, and E are limited to Europe. The presence of SRLV has been confirmed in Mexico, with genotype B detected in the central region of the country. We examined the presence of SRLVs and genotype prevalence in 1014 sheep and 1383 goats from 12 Mexican states. Using a commercial competitive ELISA (cELISA) test, we detected SRLV antibodies in 107 sheep (10.55%) and 466 goats (33.69%). We used an endpoint PCR to amplify the LTR region on seropositive animals. A total of 50 sheep and 75 goats tested positive via PCR. Positive amplicons from 11 sheep and 17 goats from ten Mexican States were cloned and sequenced. With the LTR sequence data obtained in this study, a phylogenetic analysis was performed; we also constructed a phylogenetic tree using the obtained sequences and GenBank's available sequences. All studied sequences were associated with genotype B, specifically with the FESC-752 isolate previously identified in Mexico. Highly conserved transcription factor binding sites were observed in analyzed alignments, such as AML (vis), AP-4, and TATA box. However, we identified nucleotide differences at site AP-1 that suggest function loss. Our study found that ovine and caprine genotype B SRLVs are widely distributed in Mexico; a highly conserved LTR region among the sequences evaluated in this study was also found.
Subject(s)
Genotype , Goat Diseases , Goats/virology , Lentivirus Infections/genetics , Lentivirus/genetics , Sheep Diseases , Sheep/virology , Terminal Repeat Sequences , Animals , Female , Goat Diseases/genetics , Goat Diseases/virology , Male , Mexico , Sheep Diseases/genetics , Sheep Diseases/virologyABSTRACT
The transmission frequency of small ruminant lentiviruses (SRLVs) through the placenta is controversial and may be associated with breed susceptibility. In Mexico, SRLV infections in sheep have been poorly studied. This work explores the presence of antibodies and proviral DNA in Mexican Pelibuey sheep. Enzyme-linked immunosorbent assays (ELISAs; three commercial kits and two on the basis of synthetic peptides) and polymerase chain reaction (PCR; amplifying the long terminal repeat and gag segments) were performed to diagnose SRLV infection in 25 adult Pelibuey ewes with an average age of 2.5 years and 32 fetuses with gestational ages ranging from 40 to 90 days without clinical signs of SRLV. Two of the three commercial ELISAs and the synthetic peptide-based ones were positive for SRLV antibody detection in 28% and 24% of the ewes, respectively, whereas none of the fetuses were positive by any of the ELISAs. By PCR, 31% of the ewes and, interestingly, two fetuses were positive. Characteristic SRLV lesions were not found in the fetal and/or ewe tissues, including those with positive PCR results. These findings demonstrate the susceptibility of Pelibuey sheep to SRLV infection and the low transmission frequency through the placenta.
Subject(s)
Lentivirus Infections/veterinary , Lentiviruses, Ovine-Caprine/isolation & purification , Sheep Diseases/virology , Animals , Enzyme-Linked Immunosorbent Assay/veterinary , Female , Lentivirus Infections/epidemiology , Lentivirus Infections/virology , Lentiviruses, Ovine-Caprine/classification , Mexico/epidemiology , Sheep , Sheep Diseases/epidemiologyABSTRACT
Lianas are a common plant growth form in tropical forests, where they compete intensely with trees, decreasing tree recruitment, growth, and survival. If the detrimental effects of lianas vary significantly with tree species identity, as is often assumed, then lianas may influence tree species diversity and community composition. Furthermore, recent studies have shown that liana abundance and biomass are increasing relative to trees in neotropical forests, which will likely magnify the detrimental effects of lianas and may ultimately alter tree species diversity, relative abundances, and community composition. Few studies, however, have tested the responses of multiple tree species to the presence of lianas in robust, well-replicated experiments. We tested the hypotheses that lianas reduce tree seedling growth and survival, and that the effect of lianas varies with tree species identity. We used a large-scale liana removal experiment in Central Panama in which we planted 14 replicate seedlings of 14 different tree species that varied in shade tolerance in each of 16 80 x 80 m plots (eight liana-removal and eight unmanipulated controls; 3136 total seedlings). Over a nearly two-yr period, we found that tree seedlings survived 75% more, grew 300% taller, and had twice the aboveground biomass in liana-removal plots than seedlings in control plots, consistent with strong competition between lianas and tree seedlings. There were no significant differences in the response of tree species to liana competition (i.e., there was no species by treatment interaction), indicating that lianas had a similar negative effect on all 14 tree species. Furthermore, the effect of lianas did not vary with tree species shade tolerance classification, suggesting that the liana effect was not solely based on light. Based on these findings, recently observed increases in liana abundance in neotropical forests will substantially reduce tree regeneration, but will not significantly alter tropical tree species diversity, relative abundance, or community composition.
Subject(s)
Forests , Seedlings/growth & development , Trees/classification , Trees/physiology , Panama , Seasons , Species Specificity , Trees/growth & development , Tropical ClimateABSTRACT
MAPKs such as ERK1/2 are dephosphorylated, and consequently inactivated, by dual specificity phosphatases (MKPs). In Leydig cells, LH triggers ERK1/2 phosphorylation through the action of protein kinase A. We demonstrate that, in MA-10 Leydig cells, LH receptor activation by human chorionic gonadotropin (hCG) up-regulates MKP-2, a phosphatase that dephosphorylates ERK1/2, among other MAPKs. After 2 hours, hCG and 8-bromo-cAMP (8Br-cAMP) significantly increased MKP-2 mRNA levels (3-fold), which declined to basal levels after 6 hours. MKP-2 protein accumulation exhibited a similar kinetic profile. In cells transiently expressing flag-MKP-2 protein, hCG/8Br-cAMP stimulation promoted the accumulation of the chimera (2.5-fold after 3 h of stimulation). Pharmacologic and biochemical approaches showed that the accumulation of flag-MKP-2 involves a posttranslational modification that increases MKP-2 half-life. MKP-2 down-regulation by a short hairpin RNA (MKP-2 shRNA) raised the levels of phosphorylated ERK1/2 reached by 8Br-cAMP stimulation. This effect was evident after 180 min of stimulation, which suggests that MKP-2 down-regulates the late phase of cAMP-induced ERK1/2 activity. Also, MKP-2 down-regulation by MKP-2 shRNA increased the stimulatory effect of 8Br-cAMP on both promoter activity and messenger levels of CYP11A1, which encodes for the steroidogenic enzyme P450scc and is induced by LH/hCG through protein kinase A and ERK1/2 activities. Our findings demonstrate, for the first time, that LH/hCG tightly regulates MKP-2 expression, which modulates the induction of CYP11A1 by 8Br-cAMP. MKP-2 up-regulation might control ERK1/2 activity in a specific temporal frame to modulate the expression of a finite repertory of ERK-dependent genes.
Subject(s)
Cholesterol Side-Chain Cleavage Enzyme/metabolism , Chorionic Gonadotropin/metabolism , Leydig Cells/enzymology , Protein Tyrosine Phosphatases/metabolism , RNA, Messenger/metabolism , Receptors, LH/metabolism , 8-Bromo Cyclic Adenosine Monophosphate/metabolism , Animals , Cell Line, Tumor , Male , Mice , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Phosphorylation , RNA, Messenger/analysis , Real-Time Polymerase Chain Reaction , Up-RegulationABSTRACT
Se diseñó el programa de un curso sobre temas de cultura general integral con el objetivo de desarrollar una mayor y mejor interacción social entre los estudiantes. Fue impartido como tiempo electivo a alumnos de segundo año de la carrera de Medicina y al primer año de la licenciatura en Tecnología de la Salud, en cinco de sus perfiles, con resultados satisfactorios en las encuestas y evaluaciones realizadas. Se concluye que la aplicación de este programa contribuye a incrementar el interés y motivación de los estudiantes por estos temas, influye en sus relaciones humanas al incrementarse la comunicación e intercambio de conocimientos y experiencias, y les permite una mejor interpretación de los procesos naturales y sociales que acontecen(AU)
Subject(s)
Education, Medical , Training Support , CultureABSTRACT
MAP kinases (MAPKs), such as ERK1/2, exert profound effects on a variety of physiological processes. In steroidogenic cells, ERK1/2 are involved in the expression and activation of steroidogenic acute regulatory protein, which plays a central role in the regulation of steroidogenesis. In MA-10 Leydig cells, LH and chorionic gonadotropin (CG) trigger transient ERK1/2 activation via protein kinase A, although the events that lead to ERK1/2 inactivation are not fully described. Here, we describe the hormonal regulation of MAPK phosphatase-1 (MKP-1), an enzyme that inactivates MAPKs, in MA-10 cells. In our experiments, human CG (hCG)/cAMP stimulation rapidly and transiently increased MKP-1 mRNA levels by a transcriptional action. This effect was accompanied by an increase in protein levels in both nuclear and mitochondrial compartments. In cells transiently expressing flag-MKP-1 protein, hCG/cAMP promoted the accumulation of the recombinant protein in a time-dependent manner (10-fold at 1 h). Moreover, hCG/cAMP triggered ERK1/2-dependent MKP-1 phosphorylation. The blockade of cAMP-induced MAPK kinase/ERK activation abated MKP-1 phosphorylation but only partially reduced flag-MKP-1 protein accumulation. Together, these results suggest that hCG regulates MKP-1 at transcriptional and posttranslational level, protein phosphorylation being one of the mechanisms involved in this regulation. Our study also demonstrates that MKP-1 overexpression reduces the effects of cAMP on ERK1/2 phosphorylation, steroidogenic acute regulatory gene promoter activity, mRNA levels, and steroidogenesis, whereas MKP-1 down-regulation by small interfering RNA produces opposite effects. In summary, our data demonstrate that hCG regulates MKP-1 expression at multiple stages as a negative feedback regulatory mechanism to modulate the hormonal action on ERK1/2 activity and steroidogenesis.
Subject(s)
Chorionic Gonadotropin/metabolism , Cyclic AMP/metabolism , Dual Specificity Phosphatase 1/metabolism , Leydig Cells/metabolism , Transcriptional Activation , Animals , Cell Line , Cell Nucleus/metabolism , Dual Specificity Phosphatase 1/antagonists & inhibitors , Dual Specificity Phosphatase 1/genetics , Genes, Reporter , Leydig Cells/cytology , MAP Kinase Signaling System/drug effects , Male , Mice , Mitochondria/metabolism , Phosphoproteins/genetics , Phosphoproteins/metabolism , Phosphorylation/drug effects , Promoter Regions, Genetic , Protein Kinase Inhibitors/pharmacology , Protein Processing, Post-Translational/drug effects , RNA, Messenger/metabolism , RNA, Small Interfering , Recombinant Fusion Proteins/metabolism , Transcriptional Activation/drug effectsABSTRACT
Gastric impedance spectroscopy has been proposed as a method of monitoring mucosal injury due to hypoperfusion and ischemia in the critically ill. During validation tests for this procedure, it was found that 60% of the measurements had errors by factors inherent to the clinical setting, indicating that some kind of automatic error detection should be incorporated to potentially avoid the loss of measurements. This paper presents an algorithm developed to detect errors due to bad connection, bad location or bad contact of the electrode probe. A labeled database with 20,908 sets of 92 spectral measurements each, obtained from critically ill patients was used as training/testing data. To reduce the dimensionality, the database was resized by dividing the spectral range into four bands, and then by computing mean and standard deviation in magnitude, phase, resistance and reactance for each band and measurement. Initial exploration into the data space was performed by k-means clustering, establishing the number of classes. Sequential Forward Selection was performed to determine best features from the reduced data set. Finally, Support Vector Machine classifiers were designed in a one-vs-rest hierarchical scheme to classify the quality of the spectra. Each classifier gave a hit rate greater than 95% and an area under the relative operating characteristic curve of 0.99. In a validation run with cardiac surgery and intensive care unit patient spectra, the error rates were 2.3% and 8.4% respectively.
Subject(s)
Algorithms , Artifacts , Artificial Intelligence , Diagnosis, Computer-Assisted/methods , Dielectric Spectroscopy/methods , Pattern Recognition, Automated/methods , Stomach/physiology , Humans , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Leishmania mexicana is an intracellular protozoan parasite that infects macrophages and dendritic cells and causes a chronic cutaneous disease. Although many enzymatic activities have been reported in this parasite, the presence of kinases and phosphatases has been poorly studied. These enzymes control the phosphorylation and dephosphorylation of proteins. Specifically, protein tyrosine kinases phosphorylate tyrosine residues and protein tyrosine phosphatases (PTPases) dephosphorylate tyrosine residues. PTPase activities have been reported as pathogenic factors in various infectious microorganisms such as viruses, bacteria, and parasites. Also, it has been shown that the induction of one or more PTPase activities in macrophages represents an important pathogenicity factor in Leishmania. Recently, we reported a membrane-bound PTPase activity in promastigotes of Leishmania major. In the present work, we give evidence that promastigotes of L. mexicana are able to secrete a PTPase into the culture medium. Two antibodies: one monoclonal against the catalytic domains of the human placental PTPase 1B and a polyclonal rabbit anti-recombinant protein Petase7 from Trypanosoma brucei cross-reacted with a 50-kDa molecule. The anti-human PTPase 1B antibody depleted the enzymatic activity present in the conditioned medium. The pattern of sensitivity and resistance to specific PTPase and serine/threonine inhibitors showed that this enzyme is a protein tyrosine phosphatase.
Subject(s)
Leishmania mexicana/enzymology , Protein Tyrosine Phosphatases/metabolism , Protozoan Proteins/metabolism , Antibodies, Monoclonal/immunology , Antibodies, Protozoan/immunology , Culture Media/chemistry , Protein Tyrosine Phosphatases/immunology , Protozoan Proteins/immunology , Virulence Factors/immunology , Virulence Factors/metabolismABSTRACT
Se ha encontrado una variante en el cayodo aórtico, la cual es única por su poca frecuencia, 0,11 por ciento. La formación normal de la mencionada porción de la aorta ampliamente revisada y comparada con la variante hallada, consistente en la dislocación del arco derecho y anterior, ausencia del troco braquicefálico, la arteria subclavia derecha naciendo de la aorta descendiente y con trayectoria a la derecha y pre-traqueal