Is Nasal Dysbiosis a Required Component for Neuroinflammation in Major Depressive Disorder?

Human microbiota is known to influence immune and cerebral responses by direct and/or indirect mechanisms, including hypothalamic-pituitary-adrenal axis signaling, activation of neural afferent circuits to the brain, and by altering the peripheral immune responses (cellular and humoral immune function, circulatory inflammatory cells, and the production of several inflammatory mediators, such as cytokines, chemokines, and reactive oxygen species). The inflammatory responses in the nasal mucosa (rhinitis) or paranasal sinuses (chronic rhinosinusitis) are dual conditions related with a greater risk for developing depression. In the nasal cavity, anatomic components of the olfactive function are in direct contact with the CNS through the olfactory receptors, neurons, and axons that end in the olfactory bulb and the entorhinal cortex. Local microbiome alterations (dysbiosis) are linked to transepithelial translocation of microorganisms and their metabolites, which disrupts the epithelial barrier and favors vascular permeability, increasing the levels of several inflammatory molecules (both cytokines and non-cytokine mediators: extracellular vesicles (exosomes) and neuropeptides), triggering local inflammation (rhinitis) and the spread of these components into the central nervous system (neuroinflammation). In this review, we discuss the role of microbiota-related immunity in conditions affecting the nasal mucosa (chronic rhinosinusitis and allergic rhinitis) and their relevance in major depressive disorders, focusing on the few mechanisms known to be involved and providing some hypothetical proposals on the pathophysiology of depression.

Adipose Tissue Dysfunction and the Role of Adipocyte-Derived Extracellular Vesicles in Obesity and Metabolic Syndrome.

Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.

Attenuated mutants of Salmonella enterica Typhimurium mediate melanoma regression via an immune response.

The lack of effective treatment options for an increasing number of cancer cases highlights the need for new anticancer therapeutic strategies. Immunotherapy mediated by Salmonella enterica Typhimurium is a promising anticancer treatment. Candidate strains for anticancer therapy must be attenuated while retaining their antitumor activity. Here, we investigated the attenuation and antitumor efficacy of two S. enterica Typhimurium mutants, ΔtolRA and ΔihfABpmi, in a murine melanoma model. Results showed high attenuation of ΔtolRA in the Galleria mellonella model, and invasion and survival in tumor cells. However, it showed weak antitumor effects in vitro and in vivo. Contrastingly, lower attenuation of the attenuated ΔihfABpmi strain resulted in regression of tumor mass in all mice, approximately 6 days after the first treatment. The therapeutic response induced by ΔihfABpmi was accompanied with macrophage accumulation of antitumor phenotype (M1) and significant increase in the mRNAs of proinflammatory mediators (TNF-α, IL-6, and iNOS) and an apoptosis inducer (Bax). Our findings indicate that the attenuated ΔihfABpmi exerts its antitumor activity by inducing macrophage infiltration or reprogramming the immunosuppressed tumor microenvironment to an activated state, suggesting that attenuated S. enterica Typhimurium strains based on nucleoid-associated protein genes deletion could be immunotherapeutic against cancer.

Improvement of digital Gabor holographic microscopy using a lens in plankton studies.

This work utilizes a Gabor Holographic Optical Scheme integrated with a microscope objective and a thin convex plane lens. This bi-telecentric lens system corrects spherical aberration from the objective, maintains consistent magnification across various reconstruction distances, and ensures a plane incidence on CMOS. Depending on the focal lengths of the objective and lens, the final image can be enlarged or reduced compared to the classic Gabor system, resulting in high-quality reconstructed phase images without spherical aberration. This setup was employed to capture phase distribution and intensity images of planktonic objects, such as copepods, achieving superior image quality.

Combined effect of SAR-endolysin LysKpV475 with polymyxin B and Salmonella bacteriophage phSE-5.

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 µg ml-1 against Pseudomonas aeruginosa ATCC 27853, 16.25 µg ml-1 against S. enterica Typhimurium ATCC 13311, and 32.50 µg ml-1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 µg ml-1) and P. aeruginosa P2307 (65.00 µg ml-1) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S. enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S. enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant Salmonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.

Low Cortisone as a Novel Predictor of the Low-Renin Phenotype.

A large proportion of patients with low-renin hypertension (LRH) correspond to primary aldosteronism (PA). However, some of these subjects have low to normal aldosterone. Since low renin is driven by excessive mineralocorticoids or glucocorticoids acting on mineralocorticoid receptors (MRs), we hypothesize that a low-cortisone condition, associated classically with 11ßHSD2 deficiency, is a proxy of chronic MR activation by cortisol, which can also lead to low renin, elevated blood pressure, and renal and vascular alterations. Objective: To evaluate low cortisone as a predictor of low renin activity and its association with parameters of kidney and vascular damage. Methods: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low plasma renin activity (<1 ng/mL × hours) and low cortisone (<25th percentile). Results: Plasma renin activity was associated with aldosterone (r = 0.36; P < .001) and cortisone (r = 0.22; P = .001). A binary logistic regression analysis showed that serum cortisone per ug/dL increase predicted the low-renin phenotype (OR 0.4, 95% CI 0.21-0.78). The receiver operating characteristic curves for cortisone showed an area under the curve of 0.6 to discriminate subjects with low renin activity from controls. The low-cortisone subjects showed higher albuminuria and PAI-1 and lower sodium excretion. The association study also showed that urinary cortisone was correlated with blood pressure and serum potassium (P < .05). Conclusion: This is the first study showing that low cortisone is a predictor of a low-renin condition. Low cortisone also predicted surrogate markers of vascular and renal damage. Since the aldosterone to renin ratio is used in the screening of PA, low cortisone values should be considered additionally to avoid false positives in the aldosterone-renin ratio calculation.

Effects of vaccination with Brucella melitensis, strains Rev 1 ΔeryCD and Rev 1, on the reproductive system of young male goats.

The present study evaluates the effects of vaccination with Brucella melitensis strains Rev 1 ΔeryCD and Rev 1 on the reproductive system of male goats. Three groups, each of them consisting of 15 six-month-old brucellosis-free male goats, were studied. The first group was vaccinated with the Rev 1 ΔeryCD strain, the second group received Rev 1 and the third group was inoculated with sterile physiological saline solution. The dose of both strains was of 1×109CFU/ml. Over the course of the five months of this study, three males from each group were euthanized every month. Their reproductive tracts, spleens, and lymph nodes were collected to analyze serology, bacteriology PCR, histology, and immunohistochemistry. Results show that vaccination with B. melitensis strains Rev 1 ΔeryCD and Rev 1 does not harm the reproductive system of male goats. Strain B. melitensis Rev 1 ΔeryCD displayed a lower capacity to colonize the reproductive tract than strain Rev 1, which was attributed to its limited catabolic action toward erythritol.

Las misiones médicas al Policlínico PAMS en Chincha: evolución del modelo de misión / The medical missions to the PAMS Polyclinic in Chincha: evolution of the mission's model

RESUMEN Presentamos la experiencia del Policlínico de la Peruvian American Medical Society (PAMS) en Chincha, en la ejecución de misiones médico-educativas en la región Chincha. El Policlínico PAMS presta atención médica general y especializada a la población de la zona, seis días a la semana. Además, recibe misiones médicas que vienen generalmente de los EE. UU. Desde 2011, se han recibido 43 misiones médicas. La composición y la naturaleza de las misiones han cambiado con el tiempo. Los primeros años se atraía a especialistas con el énfasis de traer equipos e insumos para mejorar la infraestructura del Policlínico. Ahora estamos limitados por la renuencia de voluntarios de venir al Perú en parte debido a que el gobierno americano considera que viajes al Perú son de alto riesgo. Esta limitación nos ha brindado la oportunidad de hacer misiones médicas juntamente con dos excelentes universidades peruanas. La experiencia ha sido positiva.

ABSTRACT We present the experience of the Polyclinic of the Peruvian American Medical Society (PAMS) in Chincha, in the execution of medical educational missions in the Chincha region. The PAMS Polyclinic provides general and specialized medical care to the population of the area, six days a week. In addition, the Polyclinic receives medical missions generally coming from the EE.UU. Since 2011, we have received 43 medical missions. The composition and nature of the missions have changed over time. The first years attracted specialists with the emphasis on bringing equipment and supplies to improve the infrastructure of the Polyclinic. We are now limited by the reluctance of volunteers to come to Peru in part because the U.S. government considers travel to Peru to be high-risk. This limitation has given us the opportunity to do medical missions together with two excellent Peruvian universities. This experience has been positive.

Coupling remote sensing and eDNA to monitor environmental impact: A pilot to quantify the environmental benefits of sustainable agriculture in the Brazilian Amazon.

Monitoring is essential to ensure that environmental goals are being achieved, including those of sustainable agriculture. Growing interest in environmental monitoring provides an opportunity to improve monitoring practices. Approaches that directly monitor land cover change and biodiversity annually by coupling the wall-to-wall coverage from remote sensing and the site-specific community composition from environmental DNA (eDNA) can provide timely, relevant results for parties interested in the success of sustainable agricultural practices. To ensure that the measured impacts are due to the environmental projects and not exogenous factors, sites where projects have been implemented should be benchmarked against counterfactuals (no project) and control (natural habitat) sites. Results can then be used to calculate diverse sets of indicators customized to monitor different projects. Here, we report on our experience developing and applying one such approach to assess the impact of shaded cocoa projects implemented by the Instituto de Manejo e Certificação Florestal e Agrícola (IMAFLORA) near São Félix do Xingu, in Pará, Brazil. We used the Continuous Degradation Detection (CODED) and LandTrendr algorithms to create a remote sensing-based assessment of forest disturbance and regeneration, estimate carbon sequestration, and changes in essential habitats. We coupled these remote sensing methods with eDNA analyses using arthropod-targeted primers by collecting soil samples from intervention and counterfactual pasture field sites and a control secondary forest. We used a custom set of indicators from the pilot application of a coupled monitoring framework called TerraBio. Our results suggest that, due to IMAFLORA's shaded cocoa projects, over 400 acres were restored in the intervention area and the community composition of arthropods in shaded cocoa is closer to second-growth forests than that of pastures. In reviewing the coupled approach, we found multiple aspects worked well, and we conclude by presenting multiple lessons learned.

Effectiveness of an intervention to improve ART adherence among men who have sex with men living with HIV: a randomized controlled trial in three public HIV clinics in Mexico.

We conducted a parallel-group randomized controlled trial in three HIV clinics in Mexico to evaluate a user-centred habit-formation intervention to improve ART adherence among MSM living with HIV. We randomized 74 participants to the intervention group and 77 to the control group. We measured adherence at one, four, and ten months through medication possession ratio and self-reported adherence. Additionally, we measured viral load, CD4 cell count, major depression disorder symptoms, and alcohol and substance use disorder at baseline, fourth and tenth months. We found no statistically significant effect on adherence between groups. However, the intervention demonstrated positive results in major depression disorder symptoms (21% vs. 6%, p = 0.008) and substance use disorder (11% vs. 1%, p = 0.018) in the fourth month. The latter is relevant because, in addition to its direct benefit, it might also improve the chances of maintaining adequate adherence in the long term. This trial was retrospectively registered at ClinicalTrials.gov (trial number NCT03410680) on 8 January 2018.Trial registration: ClinicalTrials.gov identifier: NCT03410680.

Analysis and Bayesian estimation of a model for Chikungunya dynamics with relapse: An outbreak in Acapulco, Mexico.

Chikungunya is a vector-borne viral disease transmitted by Aedes aegypti and Aedes albopictus mosquitoes. It does not have any specific treatment, and there is no vaccine. Recent epidemiological data have indicated that a relapse of the infection can occur within three months of the initial infection; however, until now, mathematical models for the spread of the disease have not considered this factor. We propose a mathematical model for the transmission of the Chikungunya virus that considers relapse. We calculated the basic reproductive number $ (R_0) $ of the disease by using the next-generation operator method. We proved the existence of a forward bifurcation. We determined the existence and the global stability of the equilibrium points by using the Lyapunov function method. We fitted the model to data from an outbreak in 2015 in Acapulco, Mexico to estimate the model parameters and $ R_0 $ with the Bayesian approach via a Hamiltonian Monte Carlo method. In the local sensitivity analysis, we found that the fraction of infected individuals who become asymptomatic has a strong impact on the basic reproductive number and makes some control measures insufficient. The impact of the fraction of infected individuals who become asymptomatic should be considered in Chikungunya control strategies.

Salmonella enterica and outer membrane vesicles are current and future options for cancer treatment.

Conventional cancer therapies have many limitations. In the last decade, it has been suggested that bacteria-mediated immunotherapy may circumvent the restrictions of traditional treatments. For example, Salmonella enterica is the most promising bacteria for treating cancer due to its intrinsic abilities, such as killing tumor cells, targeting, penetrating, and proliferating into the tumor. S. enterica has been genetically modified to ensure safety and increase its intrinsic antitumor efficacy. This bacterium has been used as a vector for delivering anticancer agents and as a combination therapy with chemotherapy, radiotherapy, or photothermic. Recent studies have reported the antitumor efficacy of outer membrane vesicles (OMVs) derived from S. enterica. OMVs are considered safer than attenuated bacteria and can stimulate the immune system as they comprise most of the immunogens found on the surface of their parent bacteria. Furthermore, OMVs can also be used as nanocarriers for antitumor agents. This review describes the advances in S. enterica as immunotherapy against cancer and the mechanisms by which Salmonella fights cancer. We also highlight the use of OMVs as immunotherapy and nanocarriers of anticancer agents. OMVs derived from S. enterica are innovative and promising strategies requiring further investigation.

Resistencia a los azoles en cepas de Aspergilus fumigatus sensu stricto aislados de muestras clínicas respiratorias

Introducción. La aspergilosis invasiva presenta alta mortalidad en pacientes con enfermedades crónicas e inmunocomprometidos. Aspergillus fumigatus sensu stricto (AFSS) es el principal agente etiológico y su tipificación requiere de métodos moleculares. La incidencia incrementada de AI resistentes a los antifúngicos demanda un diagnóstico certero y oportuno. Métodos. Se estudiaron 20 cepas de la micoteca del Instituto de Medicina Tropical - Universidad Nacional Mayor de San Marcos, aisladas de muestras respiratorias e identificadas como Aspergillus fumigatus sensu lato mediante el estudio macroscópico y microscópico. Las cepas fueron referidas a la Universidad Nacional del Litoral para su tipificación mediante una PCR screening para AFSS basada en secuencias del gen CYP51A y el estudio de sensibilidad antifúngica para voriconazol (VOR), itraconazol (ITC), posaconazol (POS), isavuconazol (ISA), anidulafungina (ANF), caspofungina (CSF) y anfotericina B (AMB) obteniendo la concentración inhibitoria mínima (CIM) mediante el protocolo de CLSI M38M51S-Ed3. Resultados. Las 20 cepas fueron identificadas como AFSS. Ninguna de las cepas tuvo una CIM por encima del punto de corte clínico (VOR), ni epidemiológico (ITC, ISA, AMB y CSF). POS fue la droga más potente frente a la colección de cepas evaluadas (media geométrica (GM) de CIM de 0,042 µg/ml). Conclusiones. Todos los aislamientos fueron tipificados como AFSS sensibles a los azoles según los puntos de corte clínico, posaconazol tuvo la mayor actividad antifúngica. Nuestros hallazgos aportan a incrementar la escasa información sobre la etiología y sensibilidad a los antifúngicos de uso clínico de las aspergilosis invasiva en nuestro país.

Introduction. Invasive Aspergillosis (IA) poses a significant threat to patients with chronic diseases and compromised immune systems, with Aspergillus fumigatus sensu stricto (AFSS) being the primary etiological agent. Accurate and timely diagnosis is crucial, particularly given the rising incidence of IA strains resistant to antifungals, necessitating molecular methods for typing. Methods. Twenty strains from Instituto de Medicina Tropical - Universidad Nacional Mayor de San Marcos, mycological collection, previously identified as Aspergillus fumigatus sensu lato through macroscopic and microscopic analysis, were studied. These strains were forwarded to the Universidad Nacional del Litoral for AFSS typing using a PCR screening based on CYP51A gene sequences. Antifungal susceptibility testing was performed for Voriconazole (VOR), Itraconazole (ITC), Posaconazole (POS), Isavuconazole (ISA), Anidulafungin (ANF), Caspofungin (CSF), and Amphotericin B (AMB), obtaining Minimum Inhibitory Concentrations (MICs) according to CLSI M38M51S-Ed3. Results. All 20 strains were identified as AFSS. None of the strains exhibited MICs above the clinical breakpoint (VOR) or the epidemiological cutoffs (ITC, ISA, AMB, and CSF). POS demonstrated the highest potency against the strain collection, with a geometric mean MIC of 0,042 µg/ml. Conclusions. All isolates were classified as azole-sensitive Aspergillus fumigatus sensu stricto (AFSS) based on clinical cutoff points, particularly posaconazole, which exhibited superior antifungal activity. Our findings contribute to augmenting the limited information on the etiology and clinical antifungal sensitivity of IA in our country.

Milk Composition of Creole Goats Raised at Different Altitudes in an Extensive Production System in Northeast Mexico.

Goat milk composition is affected by feeding, and in semiarid rangeland, information on Creole goat milk physicochemical composition is lacking. For the fulfillment of this objective, three agroecological regions (AR) considering altitude (lowland 87, highland 779, and mountain 1309 m above sea level) with different botanical compositions were chosen. Every AR analyzed accounted for 30 goat herds, with a total of 90 herds. The results demonstrated that altitude had an influence mainly on density and protein. Milk density increases as altitude increases; conversely, milk protein increases as altitude decreases. On the other hand, in the mountain and lowland ARs, the salts and solids not fat (SNF) percentages were higher compared to that of the highland AR (p < 0.05). The freezing point (FP) was higher at highland altitudes compared to that of mountain and lowland ARs (p < 0.01). In the milk fatty acids (FA) profile, only the C14:1 value was affected by altitude, whereas goat milk at lowland and mountain altitudes had higher values compared to that at highland altitudes (p < 0.05). Additionally, late lactation stage fat, FP, and pH values were higher compared to early lactation values. The opposite effect was observed for salts and SNF. In the FA profile, late lactation values were higher for C10:0 and C8:0 compared to early lactation values. The opposite trend was observed for C18:2n6t. The thrombogenic index was significantly higher at lowland altitudes compared to highland altitudes, and similar to the mountain AR. These goat milk characteristics could be explained as a consequence of animal nutrition, as well as the goat's meat-type phenotype.

Green Synthesis of Mesquite-Gum-Stabilized Gold Nanoparticles for Biomedical Applications: Physicochemical Properties and Biocompatibility Assessment.

Using cytotoxic reducing and stabilizing agents in the synthesis of gold nanoparticles (AuNPs) limits their use in biomedical applications. One strategy to overcome this problem is using "green" synthesis methodologies using polysaccharides. In the present study, we propose a green methodology for synthetizing AuNPs with mesquite gum (MG) as a reducing agent and steric stabilizer in Gold(III) chloride trihydrate aqueous solutions to obtain biocompatible nanoparticles that can be used for biomedical applications. Through this method, AuNPs can be produced without using elevated temperatures or pressures. For synthetizing gold nanoparticles coated with mesquite gum (AuNPs@MG), Gold(III) chloride trihydrate was used as a precursor, and mesquite gum was used as a stabilizing and reducing agent. The AuNPs obtained were characterized using UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, scanning transmission electron microscopy, and FT-IR spectroscopy. The stability in biological media (phosphate buffer solution), cytotoxicity (MTT assay, hematoxylin, and eosin staining), and hemocompatibility (Hemolysis assay) were measured at different concentrations and exposure times. The results showed the successful synthesis of AuNPs@MG with sizes ranging from 3 to 30 nm and a zeta potential of -31 mV. The AuNPs@MG showed good colloidal stability in PBS (pH 7.4) for up to 24 h. Finally, cytotoxicity assays showed no changes in cell metabolism or cell morphology. These results suggest that these gold nanoparticles have potential biomedical applications because of their low cytotoxicity and hemotoxicity and improved stability at a physiological pH.

Expression of ERG11, ERG3, MDR1 and CDR1 genes in Candida tropicalis / Expresión de los genes ERG11, ERG3, MDR1 y CDR1 en Candida tropicalis

INTRODUCTION: Drug resistance to azoles is a growing problem in the Candida genus. OBJECTIVE: To analyze molecularly the genes responsible for fluconazole resistance in Candida tropicalis strains. MATERIALS AND METHODS: Nineteen strains, with and without exposure to fluconazole, were selected for this study. The expression of MDR1, CDR1, ERG11, and ERG3 genes was analyzed in sensitive, dose-dependent sensitive, and resistant strains exposed to different concentrations of the antifungal drug. RESULTS: MDR1, ERG11 and ERG3 genes were significantly overexpressed in the different sensitivity groups. CDR1 gene expression was not statistically significant among the studied groups. Seven of the eight fluconazole-resistant strains showed overexpression of one or more of the analyzed genes. In some dose-dependent sensitive strains, we found overexpression of CDR1, ERG11, and ERG3. CONCLUSION: The frequency of overexpression of ERG11 and ERG3 genes indicates that they are related to resistance. However, the finding of dose-dependent resistant/sensitive strains without overexpression of these genes suggests that they are not exclusive to this phenomenon. More basic research is needed to study other potentially involved genes in the resistance mechanism to fluconazole.

Introducción: La farmacorresistencia a los azoles es un problema creciente en el género Candida. Objetivo: Analizar molecularmente los genes responsables de la resistencia a fluconazol en cepas de Candida tropicalis. Materiales y métodos: Para este estudio, se seleccionaron 19 cepas, con exposición a fluconazol y sin ella. Se analizó la expresión de los genes MDR1, CDR1, ERG11 y ERG3 en cepas sensibles, sensibles dependiente de la dosis, y resistentes, previamente expuestas a diferentes concentraciones del fármaco antifúngico. Resultados: Se encontró que los genes MDR1, ERG11 y ERG3 estaban significativamente sobreexpresados en los diferentes grupos de sensibilidad. La expresión del gen CDR1 no fue estadísticamente significativa entre los grupos estudiados. Siete de las ocho cepas resistentes a fluconazol mostraron sobreexpresión de uno o más de los genes analizados. En algunas cepas sensibles dependientes de la dosis, se encontró sobreexpresión de CDR1, ERG11 y ERG3. Conclusión: La sobreexpresión de los genes ERG11 y ERG3 indica que están relacionados con la resistencia de las cepas de Candida. Sin embargo, el hallazgo de cepas resistentes o sensibles según la dosis, sin sobreexpresión de estos genes, sugiere que pueden existir otros genes involucrados en este fenómeno. Se necesitan más investigaciones básicas que contribuyan al estudio de otros genes potencialmente involucrados en el mecanismo de resistencia al fluconazol.

[Meckel's diverticulitis, an uncommon cause of acute abdomen]. / Diverticulitis de Meckel, una causa poco frecuente de abdomen agudo.

Meckel's diverticulum corresponds to the aberrant involution of the omphalo-mesenteric canal or vitelline duct, which is located at the level of the antimesenteric border of the terminal ileum. It is the most common structural anomaly of the gastrointestinal tract, it is almost always asymptomatic and its diagnosis is usually incidental, however the complication with diverticulitis is an unusual condition. We describe the case of a 65-year-oldman, who was admitted from another institution with a diagnosis of acute abdomen. On physical examination, he presented signs of peritoneal irritation with evidence of leukocytosis and neutrophilia in the admission blood count. Computerized tomography of the abdomen with intra venous contrast was performed, which was interpreted as complicated Meckel's diverticulitis, being corroborated during the surgical act and confirmed by pathological anatomy. Meckel's diverticulitis is a rare entity, however it is important to recognize it within the differential diagnoses of acute abdomen, which will allow prompt intervention and a favorable outcome.

El divertículo de Meckel (DM) corresponde a la involución aberrante del canal onfalo-mesentérico o conducto vitelino, el cual se ubica a nivel del borde antimesentérico del íleon terminal. Es la anomalía estructural más común del tracto gastrointestinal, casi siempre es asintomático y su diagnóstico por lo general es incidental, sin embargo, la complicación con diverticulitis es una condición poco usual. Describimos el caso de un hombre de 65 años, que ingresó referido de otra institución con diagnóstico de abdomen agudo, al examen físico presentó signos de irritación peritoneal con evidencia de leucocitosis y neutrofilia en hemograma de ingreso. Se realizó tomografía computarizada de abdomen con contraste endovenoso, la cual se interpretó como diverticulitis de Meckel complicada, siendo corroborado durante el acto quirúrgico y confirmado mediante anatomía patológica. La diverticulitis de Meckel es una entidad rara, sin embargo, es importante reconocerla dentro de los diagnósticos diferenciales de abdomen agudo, lo cual permitirá una pronta intervención y un favorable desenlace.

Restorative methods as a strategy for the prevention of violence and bullying in primary and secondary schools in Mexico: An exploratory study.

School coexistence processes are mediated by conflict situations that are often not adequately, immediately and comprehensively resolved by schools, giving rise to violence. School violence has become a matter of global priority not only at the school or family level, but also socially due to its magnitude and scope. In the Program for International Student Assessment (PISA), reported in 2018 that 23% of students in Mexico had suffered bullying at least once a month, these data are worrying as they reveal high rate of violence. Considering the increase of violence in Mexican educational institutions, we wonder if students' awareness in the use of communication to resolve disagreements would be achieved after participating in a conflict prevention project applying restorative practices. The objective of this study was to test whether students acquired greater emotional self-regulation, self-determination, and peaceful strategies to resolve conflicts after participating in a project centred on the restorative paradigm. A total of 336 students from an elementary school and a high school located in Mexico participated in this study. An ad hoc questionnaire was administered to the students by a restorative justice specialist in the middle of the school year. Statistical analyses were performed with the Statistical Package for the Social Sciences V. 25. The results obtained showed that, after the implementation of this program for five months, students in both schools showed greater emotional self-regulation and self-determination. In conclusion, providing students with restorative strategies to resolve disputes favoured the use of peaceful conflict resolution strategies.

Diverticulitis de Meckel, una causa poco frecuente de abdomen agudo / Meckel's diverticulitis, an uncommon cause of acute abdomen

Resumen El divertículo de Meckel (DM) corresponde a la involución aberrante del canal onfalo-mesentérico o conducto vitelino, el cual se ubica a nivel del borde antimesentérico del íleon terminal. Es la anomalía estructural más común del tracto gastrointestinal, casi siempre es asintomático y su diagnóstico por lo general es incidental, sin embargo, la complica ción con diverticulitis es una condición poco usual. Describimos el caso de un hombre de 65 años, que ingresó referido de otra institución con diagnóstico de abdomen agudo, al examen físico presentó signos de irritación peritoneal con evidencia de leucocitosis y neutrofilia en hemograma de ingreso. Se realizó tomografía computarizada de abdomen con contraste endovenoso, la cual se interpretó como diverticulitis de Meckel complicada, siendo corroborado durante el acto quirúrgico y confirmado mediante anatomía patológica. La diverticulitis de Meckel es una entidad rara, sin embargo, es importante reconocerla dentro de los diagnósticos diferenciales de abdomen agudo, lo cual permitirá una pronta intervención y un favorable desenlace.

Abstract Meckel's diverticulum corresponds to the aberrant invo lution of the omphalo-mesenteric canal or vitelline duct, which is located at the level of the antimesenteric border of the terminal ileum. It is the most common structural anomaly of the gastrointestinal tract, it is almost always asymptomatic and its diagnosis is usually incidental, how ever the complication with diverticulitis is an unusual con dition. We describe the case of a 65-year-oldman, who was admitted from another institution with a diagnosis of acute abdomen. On physical examination, he presented signs of peritoneal irritation with evidence of leukocytosis and neutrophilia in the admission blood count. Computerized tomography of the abdomen with intra venous contrast was performed, which was interpreted as complicated Meckel's diverticulitis, being corroborated during the surgical act and confirmed by pathological anatomy. Meckel's diverticulitis is a rare entity, however it is important to recognize it within the differential diagnoses of acute abdomen, which will allow prompt intervention and a favorable outcome.