The impact of comorbidity status in COVID-19 vaccines effectiveness before and after SARS-CoV-2 omicron variant in northeastern Mexico: a retrospective multi-hospital study.

Introduction: The end of the coronavirus disease 2019 (COVID-19) pandemic has been declared by the World Health Organization on May 5, 2023. Several vaccines were developed, and new data is being published about their effectiveness. However, the clinical trials for the vaccines were performed before the Omicron variant appeared and there are population groups where vaccine effectiveness still needs to be tested. The overarching goal of the present study was to analyze the effects of COVID-19 vaccination before and after the Omicron variant in patients considering comorbidities in a population from Nuevo Leon, Mexico. Methods: Epidemiological COVID-19 data from the Mexican Social Security Institute were collected from 67 hospitals located in northeastern Mexico, from July 2020 to May 2023, and a total of 669,393 cases were compiled, 255,819 reported a SARS-CoV-2 positive reverse transcription quantitative polymerase chain reaction (RT-qPCR) test or a positive COVID-19 antigen rapid test. Results: Before Omicron (BO, 2020-2021), after 14 days of two doses of COVID-19 vaccine, BNT162b2 and ChAdOx1 vaccines were effective against infection in non-comorbid and all comorbid subgroups, whereas after Omicron (AO, 2022- 2023) there was no significant effectiveness against infection with none of the vaccines. Regarding hospitalization BO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 significantly protected non-comorbid patients whereas BNT162b2, ChAdOx1, and mRNA-1273, protected all comorbid subgroups against hospitalization. AO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 were effective against hospitalization in non-comorbid patients whereas for most comorbid subgroups BNT162b2, ChAdOx1 and CoronaVac were effective against hospitalization. Non-comorbid patients were protected against death as an outcome of COVID-19 during the BO period with most vaccines whereas a reduction in effectiveness was observed AO with mRNA-1273 vaccines in patients with hypertension, and diabetes mellitus. Discussion: BO, COVID-19 vaccines were effective against infection, hospitalization, and death whereas AO, COVID-19 vaccines failed to protect the population from COVID-19 infection. A varying effectiveness against hospitalization and death is observed AO.

Paxlovid™ reduces the incidence of pneumonia, hospitalization, and death in a cohort of COVID-19 patients from northeast Mexico.

BACKGROUND: Information on Paxlovid™ effectiveness must be monitored and updated in real world scenarios. Our research question was what is the effectiveness of Paxlovid™ in adult patients with COVID-19? Therefore, we investigated the effectiveness of Paxlovid™ on reducing the incidence of pneumonia, hospitalization, and mortality in a cohort of COVID-19 positive adult patients from northeast Mexico. METHODS: A retrospective cohort study of COVID-19 positive adult patients from Nuevo Leon, Mexico from December 2020 to May 2023 (after Omicron BA-5 circulation) was performed. Paxlovid™ use was authorized in September 2022. Therefore, we analyzed effectiveness in patients with confirmed diagnosis who met selection criteria between September 2022 and May 2023 (n = 20,799; 5,673 with and 15,126 without Paxlovid™). RESULTS: The pneumonia (0.1% vs. 0.4%, p < 0.0001), hospitalization (0.1% vs. 1.2%, p < 0.0001), and death rates (0.04% vs. 0.2%, p < 0.0001) were lower in patients with Paxlovid™ treatment independently of age, sex, comorbidity, and COVID-19 and pneumococcal vaccination history. Effectiveness was 88.2%, 95.9% y 91.9% for pneumonia, hospitalization, and death, respectively. CONCLUSIONS: Paxlovid™ reduces the presentation of pneumonia, hospitalization, and death secondary to COVID-19. It is recommended to continue monitoring Paxlovid™ effectiveness, as other SARS-CoV-2 variants continue to emerge.

Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced HCC include atezolizumab, bevacizumab, sorafenib, among others. Atezolizumab and bevacizumab are immunological options recently incorporated into first-line treatments, along with sorafenib, for which great treatment achievements have been reached. However, sorafenib resistance is developed in most patients, and therapeutical combinations targeting cancer hallmark mechanisms and intracellular signaling have been proposed. In this review, we compiled evidence of the mechanisms of cell death caused by sorafenib administered alone or in combination with valproic acid and metformin and discussed them from a molecular perspective.

ESX-3 secretion system in Mycobacterium: An overview.

Mycobacteria are microorganisms distributed in the environment worldwide, and some of them, such as Mycobacterium tuberculosis or M. leprae, are pathogenic. The hydrophobic mycobacterial cell envelope has low permeation and bacteria need to export products across their structure. Mycobacteria possess specialized protein secretion systems, such as the Early Secretory Antigenic Target 6 secretion (ESX) system. Five ESX loci have been described in M. tuberculosis, called ESX-1 to ESX-5. The ESX-3 secretion system has been associated with mycobacterial metabolism and growth. The locus of this system is highly conserved across mycobacterial species. Metallo-proteins regulate negative ESX-3 transcription in high conditions of iron and zinc. Moreover, this secretion system is part of an antioxidant regulatory pathway linked to Zinc. EccA3, EccB3, EccC3, EccD3, and EccE3 are components of the ESX-3 secretion machinery, whereas EsxG-EsxH, PE5-PPE4, and PE15-PPE20 are proteins secreted by this system. In addition, EspG3 and MycP3 are complementary proteins involved in transport and proteolysis respectively. This system is associated to mycobacterial virulence by releasing the bacteria from the phagosome and inhibiting endomembrane damage response. Furthermore, components of this system inhibit the host immune response by reducing the recognition of M. tuberculosis-infected cells. The components of the ESX-3 secretion system play a role in drug resistance and cell wall integrity. Moreover, the expression data of this system indicated that external and internal factors affect ESX-3 locus expression. This review provides an overview of new findings on the ESX-3 secretion system, its regulation, expression, and functions.

Side Effects of COVID-19 Vaccines in Pregnant and Lactating Mexican Women and Breastfed Infants: A Survey-Based Study.

COVID-19 vaccines' safety has been extensively studied; however, further analysis is required in pregnant women, nursing mothers, and breastfed infants. Our aim was to compare the extension and severity of self-reported COVID-19 vaccine side effects in pregnant and breastfeeding women, and breastfed infants. In this cross-sectional study, COVID-19-vaccinated subjects were enrolled using an online survey in Mexico. Women were classified by pregnancy and breastfeeding status at the time of vaccination (n = 3167). After the first or only dose, there was a trend toward fewer systemic effects in pregnant women (p = 0.06). BNT162b2 (Pfizer-BioNTech) had a higher frequency of local symptoms in pregnancy. Lactating women experienced fewer local symptoms after the first or single dose (p = 0.04) and the opposite occurred after the second dose (p = 0.001). ChAdOx1 (AstraZeneca) increased the chances of developing both local and systemic symptoms after the first dose but decreased them after the second dose. The severity was similar across groups, although the result of lack of association in pregnancy requires studies with a larger sample size. Irritability was the most reported symptom in breastfed infants. This study contributes to the knowledge about the side effects in pregnant and lactating women, and breastfed babies.

Biomimetic Dispersive Solid-Phase Microextraction: A Novel Concept for High-Throughput Estimation of Human Oral Absorption of Organic Compounds.

There is a quest for a novel in vitro analytical methodology that is properly validated for the prediction of human oral absorption and bioaccumulation of organic compounds with no need of animal models. The traditional log P parameter might not serve to predict bioparameters accurately inasmuch as it merely accounts for the hydrophobicity of the compound, but the actual interaction with the components of eukaryotic cells is neglected. This contribution proposes for the first time a novel biomimetic microextraction approach capitalized on immobilized phosphatidylcholine as a plasma membrane surrogate onto organic polymeric sorptive phases for the estimation of human intestinal effective permeability of a number of pharmaceuticals that are also deemed contaminants of emerging concern in environmental settings. A comprehensive exploration of the conformation of the lipid structure onto the surfaces is undertaken so as to discriminate the generation of either lipid monolayers or bilayers or the attachment of lipid nanovesicles. The experimentally obtained biomimetic extraction data is proven to be a superb parameter against other molecular descriptors for the development of reliable prediction models of human jejunum permeability with R2 = 0.76, but the incorporation of log D and the number of aromatic rings in multiple linear regression equations enabled improved correlations up to R2 = 0.88. This work is expected to open new avenues for expeditious in vitro screening methods for oral absorption of organic contaminants of emerging concern in human exposomics.

Sex, Age, and Comorbidities Are Associated with SARS-CoV-2 Infection, COVID-19 Severity, and Fatal Outcome in a Mexican Population: A Retrospective Multi-Hospital Study.

People with comorbidities and the male sex are at a higher risk of developing severe COVID-19. In the present study, we aim to investigate the associated factors for infection, severity, and death due to COVID-19 in a population from Nuevo León, México. Epidemiological COVID-19 data were collected from 65 hospitals from December 2020 to May 2022. A total of 75,232 cases were compiled from which 25,722 cases were positive for SARS-CoV-2. Male sex, older age, diabetes, obesity, and hypertension were associated with infection. In addition to the above-mentioned factors, renal disease, cardiovascular disease, and immunosuppression were found to be associated with increased COVID-19 severity. These factors, as well as neurological diseases, are also associated with death due to COVID-19. When comparing the different variants of SARs-CoV-2, the variant B1.1.519 increased the probability of death by 2.23 times compared to the AY.20 variant. Male sex, older age, diabetes, obesity, and hypertension are associated with SARS-CoV-2 infection, severity, and death. Along with the aforementioned comorbidities, renal disease, cardiovascular disease, and immunosuppression are also associated with severity and death. Another factor associated with death is the presence of neurological disease. The SARS-CoV-2 B1.1.519 variant increases the odds of death compared to the SARS-CoV-2 AY.20 variant.

ABC-GOALScl score predicts admission to the intensive care unit and mortality of COVID-19 patients over 60 years of age.

BACKGROUND: One of the risk factors for getting seriously ill from COVID-19 and reaching high mortality rates is older age. Older age is also associated with comorbidities, which are risk factors for severe COVID-19 infection. Among the tools that have been evaluated to predict intensive care unit (ICU) admission and mortality is ABC-GOALScl. AIM: In the present study we validated the utility of ABC-GOALScl to predict in-hospital mortality in subjects over 60 years of age who were positive for SARS-CoV-2 virus at the moment of admission with the purpose of optimizing sanitary resources and offering personalized treatment for these patients. METHODS: This was an observational, descriptive, transversal, non-interventional and retrospective study of subjects (≥ 60 years of age), hospitalized due to COVID-19 infection at a general hospital in northeastern Mexico. A logistical regression model was used for data analysis. RESULTS: Two hundred forty-three subjects were included in the study, whom 145 (59.7%) passed away, while 98 (40.3%) were discharged. Average age was 71, and 57.6% were male. The prediction model ABC-GOALScl included sex, body mass index, Charlson comorbidity index, dyspnea, arterial pressure, respiratory frequency, SpFi coefficient (Saturation of oxygen/Fraction of inspired oxygen ratio), serum levels of glucose, albumin, and lactate dehydrogenase; all were measured at the moment of admission. The area under the curve for the scale with respect to the variable of discharge due to death was 0.73 (IC 95% = 0.662-0.792). CONCLUSION: The ABC-GOALScl scale to predict ICU admission in COVID-19 patients is also useful to predict in-hospital death in COVID-19 patients ≥ 60 years old.

Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine.

BACKGROUND: The generation of induced pluripotent stem cells has opened the field of study for stem cell research, disease modeling and drug development. However, the epigenetic signatures present in somatic cells make cell reprogramming still an inefficient process. This epigenetic memory constitutes an obstacle in cellular reprogramming. Here, we report the effect of hydralazine (HYD) and valproic acid (VPA), two small molecules with proven epigenetic activity, on the expression of pluripotency genes in adult (aHF) and neonatal (nbHF) human fibroblasts. METHODS: aHF and nbHF were treated with HYD and/or VPA, and viability and gene expression assays for OCT4, NANOG, c-MYC, KLF4, DNMT1, TET3, ARID1A and ARID2 by quantitative PCR were performed. aHF and nbHF were transfected with episomal plasmid bearing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and exposed to HYD and VPA to determine the reprogramming efficiency. Methylation sensitive restriction enzyme (MSRE) qPCR assays were performed on OCT4 and NANOG promoter regions. Immunofluorescence assays were carried out for pluripotency genes on iPSC derived from aHF and nbHF. RESULTS: HYD upregulated the expression of OCT4 (2.5-fold) and NANOG (fourfold) genes but not c-Myc or KLF4 in aHF and had no significant effect on the expression of all these genes in nbHF. VPA upregulated the expression of NANOG (twofold) in aHF and c-MYC in nbHF, while it downregulated the expression of NANOG in nbHF. The combination of HYD and VPA canceled the OCT4 and NANOG overexpression induced by HYD in aHF, while it reinforced the effects of VPA on c-Myc expression in nbHF. The HYD-induced overexpression of OCT4 and NANOG in aHDF was not dependent on demethylation of gene promoters, and no changes in the reprogramming efficiency were observed in both cell populations despite the downregulation of epigenetic genes DNMT1, ARID1A, and ARID2 in nbHF. CONCLUSIONS: Our data provide evidence that HYD regulates the expression of OCT4 and NANOG pluripotency genes as well as ARID1A and ARID2 genes, two members of the SWI/SNF chromatin remodeling complex family, in normal human dermal fibroblasts.

Expression of Intermediate Filaments in the Developing Testis and Testicular Germ Cell Cancer.

Cytokeratin and desmin expression have been associated with Sertoli cell maturity and the development of testicular germ cell cancer (TGCC). Thus, the present study aimed to characterize the expression of these intermediate filaments in normal testis development and TGCC. Cytokeratin and desmin were determined by immunohistochemistry and immunofluorescence in human fetal, and adult testis and tissue from patients with pre-invasive germ cell neoplasia in-situ (GCNIS) or invasive TGCC. Desmin was expressed in Sertoli cells of the human fetal testis, and the proportion of desmin expressing Sertoli cells was significantly reduced in the second trimester, compared with the first trimester (31.14% vs. 6.74%, p = 0.0016). Additionally, Desmin was expressed in the majority of Sertoli cells in the adult testis and TGCC samples. Cytokeratin was detected in Sertoli cells of human fetal testis but was not expressed in Sertoli cells of human adult testis. In patients with TGCC, cytokeratin was not expressed in Sertoli cells in tubules with active spermatogenesis but was detected in Sertoli cells in tubules containing GCNIS cells in patients with both pre-invasive and invasive TGCC. In conclusion, desmin was not associated with Sertoli cell maturation or progression to TGCC. However, cytokeratin appeared to be an indicator of impaired Sertoli cell maturation.

Extension and Severity of Self-Reported Side Effects of Seven COVID-19 Vaccines in Mexican Population.

A few studies examined the comparative side effects of Coronavirus Disease-19 (COVID-19) vaccines. We compared the extension and severity of self-reported side effects of seven COVID-19 vaccines [BNT162b2 (Pfizer-BioNTech), ChAdOx1 (AstraZeneca), mRNA-1273 (Moderna), CoronaVac (Sinovac Life Sciences), Gam-COVID-Vac (Gamaleya's Sputnik V), Ad5-nCoV (CanSinoBIO), and Ad26.CoV2.S (Johnson & Johnson/Janssen)] in the Mexican population. We also evaluated the association of type of vaccine, sex, age, comorbidity, and history of allergies to the extent and severity of side effects. This was a cross-sectional study carried out online between August 12 and September 3, 2021 in Mexico. The first inclusion criterion was to receive a COVID-19 vaccine and the second, being at least 18 years old. The survey link was distributed via multiple social media platforms. We questioned about the type of vaccine and symptoms based on short-term side effects reported in the literature. Side effect extension was classified as local, systemic, or both. We asked about the need to take medicine, stop activities/miss work, or seek medical attention. Then, a severity index was constructed based on responses. Descriptive and stepwise multivariate logistic ordinal regression analyses were used to calculate odds ratio (OR) and 95% CI for each outcome adjusted by potential confounders. The mean age was 38.9 ± 11.0 years (n = 4,024). Prevalence of at least one side effect varied between vaccines and by a number of doses. At dose 1, ChAdOx1 was the vaccine with the highest rate of at least one side effect (85%) followed by Gam-COVID-Vac (80%). Both were associated to greater extension (adjusted OR 2.53, 95% CI 2.16, 2.96 and adjusted OR 2.41, 95% CI 1.76, 3.29, respectively) and severity of side effects (adjusted OR 4.32, 95% CI 3.73, 5.00 and adjusted OR 3.00, 95% CI 2.28, 3.94, respectively). Young age (<50 years), female sex, comorbidity, and history of allergies were associated with greater extension and severity, independent of the type of vaccine and potential confounders. At dose 2, mRNA-1273 was the vaccine with the highest rate of side effects (88%) and the only vaccine associated to greater extension (adjusted OR 2.88, 95% CI 1.59, 5.21) and severity of symptoms (adjusted OR 3.14, 95% CI 1.82, 5.43). Continuous studies are necessary to acknowledge more post-vaccine symptoms in different populations.

Prevalence of VOYAGER PAD trial exclusion criteria in unselected patients undergoing lower limb revascularization.

BACKGROUND: The VOYAGER PAD trial investigated data on dual pathway inhibition after lower limb revascularization for peripheral arterial disease (PAD). Multiple exclusion criteria were applied. However, neither data on the prevalence of exclusion criteria nor on the total number of patients screened for inclusion was discussed. METHODS: We performed a single-center prospective observational study in unselected PAD patients undergoing lower limb revascularization. Demographic and disease-specific data was collected. RESULTS: One hundred fifty patients were included with only 29 patients (19.3%) as potential candidates for the VOYAGER PAD study medication. Poorly controlled diabetes or severe uncontrolled hypertension (33.3%), major tissue loss (18.7%), acute limb ischaemia within prior 2 weeks (17.3%) and a history of intracranial hemorrhage, stroke or TIA (16%) were amongst the exclusion criteria most frequently met. Compared to VOYAGER PAD study patients, significant differences regarding sex (36.7% female vs. 25.8%), renal insufficiency (29.0% vs. 20.1%), previous myocardial infarction (16.7% vs. 11.1%) and known carotid artery disease (18.7% vs. 8.6%) revealed. Patients presented significantly more frequently with critical limb ischemia (56.7% vs. 30.4%) and a history of previous peripheral revascularization (72.0% vs. 35.9%). Fewer endovascular interventions (52% vs. 65.5%) and more surgeries (58% vs. 34.5%) were performed. CONCLUSIONS: In unselected patients undergoing revascularization for peripheral arterial disease, the majority presents with characteristics that, at present, preclude prescription of rivaroxaban in addition to aspirin. This patient cohort represents a population with higher rates of comorbidities and more complex vascular interventions, but might also benefit from dual pathway inhibition strategy.

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.

Selenite Downregulates STAT3 Expression and Provokes Lymphocytosis in the Liver of Chronically Exposed Syrian Golden Hamsters.

Arsenic is considered a worldwide pollutant that can be present in drinking water. Arsenic exposure is associated with various diseases, including cancer. Antioxidants as selenite and α-tocopherol-succinate have been shown to modulate arsenic toxic effects. Since changes in STAT3 and PSMD10 gene expression have been associated with carcinogenesis, the aim of this study was to evaluate the effect of arsenic exposure and co-treatments with selenite or α-tocopherol-succinate on the expression of these genes, in the livers of chronically exposed Syrian golden hamsters. Animals were divided into six groups: (i) control, (ii) chronically treated with 100 ppm arsenic, (iii) treated with 6 ppm α-tocopherol-succinate (α-TOS), (iv) treated with 8.5 ppm selenite, (v) treated with arsenic + α-TOS, and (vi) treated with arsenic + selenite. Urine samples and livers were collected after 20 weeks of continuous exposure. The urine samples were analyzed for arsenic species by atomic absorption spectrophotometry, and real-time RT-qPCR analysis was performed for gene expression evaluation. A reduction in STAT3 expression was observed in the selenite-treated group. No differences in PSMD10 expression were found among groups. Histopathological analysis revealed hepatic lymphocytosis in selenite-treated animals. As a conclusion, long-term exposure to arsenic does not significantly alter the expression of STAT3 and PSMD10 oncogenes in the livers of hamsters; however, selenite down-regulates STAT3 expression and provokes lymphocytosis.

5-Aza-2'-Deoxycytidine and Valproic Acid in Combination with CHIR99021 and A83-01 Induce Pluripotency Genes Expression in Human Adult Somatic Cells.

A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripotency genes reactivation that might preclude their clinical application. During the reprogramming process, a somatic cell must undergo several epigenetic modifications to induce groups of genes capable of reactivating the endogenous pluripotency core. Here, looking to increase the reprograming efficiency in somatic cells, we evaluated the effect of epigenetic molecules 5-aza-2'-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain. The addition of this cocktail to culture medium increased the expression of OCT4, SOX2, and KLF4 expression by 2.1-fold, 8.5-fold, and 2-fold, respectively, with respect to controls; concomitantly, a reduction in methylated CpG sites in OCT4 promoter region was observed. The epigenetic cocktail also induced the expression of the metastasis-associated gene S100A4. However, the epigenetic cocktail did not induce the morphological changes characteristic of the reprogramming process. In summary, 5AZ, VPA, CHIR99021, and A83-01 induced the expression of OCT4 and SOX2, two critical genes for iPSC. Future studies will allow us to precise the mechanisms by which these compounds exert their reprogramming effects.

High Prevalence of Avian Influenza Virus Among Wild Waterbirds and Land Birds of Mexico.

Aquatic wild birds, especially waterfowl, have been long considered the main reservoirs of the avian influenza A virus; however, recent surveys have found an important prevalence of these viruses among land birds as well. Migration has been suggested as an important factor in the avian influenza virus dissemination. We aimed to estimate the prevalence of influenza A viruses in wild birds (waterbirds and land birds; resident and migratory) in eastern Mexico, where the three main North American migration flyways converge and where there was no previous information on this subject. We detected influenza with reverse transcription coupled with a PCR approach. Of the 534 birds sampled between 2010 and 2012, we detected the influenza A virus in a high proportion of birds (39%). Prevalence was particularly high in land birds (49%) when compared to aquatic birds (26%); there was no difference in overall prevalence between resident (39%) and migratory birds (39%). The high prevalence of the avian influenza virus in land birds was noteworthy in the innermost sampling areas in northern Mexico (Coahuila [82%] and Nuevo Leon [43%]).

Alta prevalencia del virus de la influenza aviar entre aves acuáticas silvestres y aves terrestres de México. Las aves silvestres acuáticas, especialmente las aves anseriformes, han sido consideradas durante mucho tiempo los principales reservorios del virus de la influenza aviar A; sin embargo, muestreos recientes también han encontrado una importante prevalencia de estos virus entre las aves terrestres. Se ha sugerido que la migración es un factor importante en la diseminación del virus de la influenza aviar. El objetivo de este estudio fue estimar la prevalencia de los virus de la influenza A en aves silvestres (aves acuáticas y terrestres; residentes y migratorias) en el este de México, donde convergen las tres rutas migratorias principales de América del Norte y donde no había información previa sobre este tema. Se detectó al virus de influenza mediante transcripción reversa acoplada a PCR. De las 534 aves muestreadas entre los años 2010 y 2012, se detectó al virus de la influenza A en una alta proporción de aves (39%). La prevalencia fue particularmente alta en las aves terrestres (49%) en comparación con las aves acuáticas (26%); no se observó diferencia en la prevalencia general entre las aves residentes (39%) y las migratorias (39%). La alta prevalencia del virus de la influenza aviar en las aves terrestres fue notable en las áreas de muestreo hacia el interior del norte de México (Coahuila [82%] y Nuevo León [43%]).

The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells.

BACKGROUND: Testicular germ cell cancer (TGCC) develops from pre-malignant germ neoplasia in situ (GCNIS) cells. GCNIS originates from fetal gonocytes (POU5F1+/MAGE-A4-), which fail to differentiate to pre-spermatogonia (POU5F1-/MAGE-A4+) and undergo malignant transformation. Gankyrin is an oncogene which has been shown to prevent POU5F1 degradation and specifically interact with MAGE-A4 in hepatocellular carcinoma (HCC) cells. We aimed to investigate the role of Gankyrin in progression from gonocyte to pre-invasive GCNIS and subsequent invasive TGCC. METHODS: We determined Gankyrin expression in human fetal testicular tissue (gestational weeks 9-20; n = 38), human adult testicular tissue with active spermatogenesis (n = 9), human testicular tissue with germ cell maturation delay (n = 4), testicular tissue from patients with pre-invasive GCNIS (n = 6), and invasive TGCC including seminoma (n = 6) and teratoma (n = 7). Functional analysis was performed in-vitro by siRNA knock-down of Gankyrin in the NTera2 cells (derived from embryonal carcinoma). RESULTS: Germ cell expression of Gankyrin was restricted to a sub-population of prespermatogonia in human fetal testes. Nuclear Gankyrin was also expressed in GCNIS cells of childhood and adult pre-invasive TGCC patients, and in GCNIS from seminoma and non-seminoma patients. Cytoplasmic expression was observed in seminoma tumour cells and NTera2 cells. Gankyrin knock-down in NTera2 cells resulted in an increase in apoptosis mediated via the TP53 pathway, whilst POU5F1 expression was unaffected. Furthermore, Gankyrin knock-down in NTera2 cells increased cisplatin sensitivity with an increase in cell death (13%, p < 0.05) following Gankyrin knock-down, when compared to cisplatin treatment alone, likely via BAX and FAS. Our results demonstrate that Gankyrin expression changes in germ cells during normal transition from gonocyte to prespermatogonia. In addition, changes in Gankyrin localisation are associated with progression of pre-invasive GCNIS to invasive TGCC. Furthermore, we found that Gankyrin is involved in the regulation of NTera2 cell survival and that a reduction in Gankyrin expression can modulate cisplatin sensitivity. CONCLUSIONS: These results suggest that manipulation of Gankyrin expression may reduce the cisplatin dose required for the treatment of TGCC, with benefits in reducing dose-dependent side effects of chemotherapy. Further studies are required in order to assess the effects of modulating Gankyrin on GCNIS/TGCC using in vivo models.

Electroconvulsive therapy clinical database: Influence of age and gender on the electrical charge. / Base de datos clínica de terapia electroconvulsiva: influencia de edad y género en la carga eléctrica.

INTRODUCTION: The influence of age and gender in the electrical charge delivered in a given population was analysed using an electroconvulsive therapy (ECT) clinical database. MATERIAL AND METHOD: An observational, prospective, longitudinal study with descriptive analysis was performed using data from a database that included total bilateral frontotemporal ECT carried out with a Mecta spECTrum 5000Q® in our hospital over 6 years. From 2006 to 2012, a total of 4,337 ECT were performed on 187 patients. Linear regression using mixed effects analysis was weighted by the inverse of the number of ECT performed on each patient per year of treatment. RESULTS: The results indicate that age is related with changes in the required charge (P=.031), as such that the older the age a higher charge is needed. Gender is also associated with changes in charge (P=.014), with women requiring less charge than men, a mean of 87.3mC less. When the effects of age and gender are included in the same model, both are significant (P=.0080 and P=.0041). Thus, for the same age, women require 99.0mC less charge than men, and in both genders the charge increases by 2.3mC per year. CONCLUSIONS: From our study, it is concluded that the effect of age on the dosage of the electrical charge is even more significant when related to gender. It would be of interest to promote the systematic collection of data for a better understanding and application of the technique.

Topical Treatment of Leishmania tropica Infection Using (-)-α-Bisabolol Ointment in a Hamster Model: Effectiveness and Safety Assessment.

There is currently no reliable treatment for the management of cutaneous leishmaniasis, and intralesional antimonial injections remain the main treatment. The present work aims at evaluating the antileishmanial effectiveness and safety of (-)-α-bisabolol (1) in a novel topical formulation on a cutaneous leishmaniasis model involving Leishmania tropica-infected Syrian hamsters. The topical treatment with 1 reduced lesion thickness to 56% at 2.5%, showing a higher efficacy than the reference control, meglumine antimoniate. Other regimens (ointment at 1% and 5% and oral treatment at 200 mg/kg) reduced the footpad thickness as well. The skin parasite load decreased after the experiment in all treatment groups, particularly in those animals treated with the 2.5% formulation (83.2%). Treatment with (-)-α-bisabolol at different concentrations or through an oral route did not lead to the appearance of toxicity or side effects in healthy hamsters or infected animals. Therefore, topical (-)-α-bisabolol was more effective than meglumine antimoniate in this cutaneous leishmaniasis model without showing toxicity effects on the hamsters. These results are of great interest and might be used for the development of alternatives for the treatment of cutaneous leishmaniasis, either in monotherapy or in combination with other drugs whose skin permeability could be enhanced by this sesquiterpene.

E-Waste Informal Recycling: An Emerging Source of Lead Exposure in South America.

BACKGROUND: Primitive electronic waste (e-waste) recycling creates exposures to several hazardous substances including lead. In Uruguay, primitive recycling procedures are a significant source of lead exposure. OBJECTIVES: The aim of this study was to examine lead exposure in blood lead levels (BLLs) in low-income children exposed to lead through burning cables. METHODS: A sample of children and adolescents exposed to lead through burning cable activities were assessed at the Department of Toxicology in Montevideo, Uruguay, between 2010 and 2014. Soil lead levels of residences were taken shortly after their assessment. FINDINGS: The final sample included 69 children and adolescents (mean age 7.89 years). More than 66% of participants had an additional source of lead exposure-manual gathering of metals-and <5% were exposed to lead through landfills or paint. Average BLLs at first consultation were 9.19 ug/dL and lower at the second measurement (5.86 µg/dL). Data from soil lead levels ranged from 650 to 19,000 mg of lead/kg of soil. The interventions conducted after the assessment included family education in the clinic and at home, indoor and outdoor remediation. We found a decrease in BLLs of 6.96 µg/dL. Older children had lower BLLs (r = -0.24; P = 0.05). Statistical analyses also showed that children living in areas with higher soil lead levels had significantly higher BLLs (r = 0.50; P < 0.01). Additionally, we found greater BLLs from burning cable activities when children had been exposed to lead-based paint (r = 0.23; P < 0.1). CONCLUSION: Among children exposed to e-waste recycling, the most common additional source of lead exposure was the manual gathering of metals. The average BLL among children and adolescents in this study is higher than the BLLs currently suggested in medical intervention. Future research should focus on exploring effective interventions to reduce lead exposure among this vulnerable group.