Essential Oil of Fractionated Oregano as Motility Inhibitor of Bacteria Associated with Urinary Tract Infections.

In this research, several analyses were carried out on concentrated fractions of Mexican oregano essential oil (Poliomintha longiflora Gray) in order to determine its ability to inhibit the growth and the motility of Escherichia coli (swimming), Pseudomonas aeruginosa (swimming), and Proteus vulgaris (swarming); these Gram-negative bacteria associated with urinary tract infections are motile due to the presence of flagella, which is considered an important virulence factor that favors their motility when trying to reach the target organ and cause an infection. Also, the resistance pattern to antibiotics of each strain was determined. The results showed resistance pattern (8 out of 12 antibiotics tested) for P. aureginosa, while E. coli and P. vulgaris were resistant to 4 antibiotics out of the 12 tested. On the other hand, fractionated oregano caused an inhibition of growth and a reduction in motility, varying between fractions and among bacteria. Fraction 4 showed major growth reduction, with MBC values ranging from 0.002 to 23.7 mg/mL. Treatment with fractionated oregano (F1, F2, F3, F4) reduced the motility by 92-81% for P. vulgaris, 90-83% for E. coli, and 100-8.9% for P. aeruginosa. These results demonstrated a higher performance with a lower application dose due to its high content of Carvacrol and Thymol; unlike other concentrated fractions, this synergy of oxygenated monoterpenes may cause greater antimicrobial activity.

Episodes of acute methotrexate-related neurotoxicity linked to compromised long-term neurocognitive function.

Methotrexate is a critical component of curative chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but is associated with neurotoxicity. Information on long-term outcomes following an acute neurotoxic event is limited. Therefore, this report compares neurocognitive performance more than 12 months post diagnosis (mean = 4 years) between ALL patients with (n = 25) and without (n = 146) a history of acute neurotoxicity. Compared to children with no documented on-treatment neurotoxic event, children who experienced a neurotoxic event during treatment exhibited poorer performance on measures of fine motor function (p = .02) and attention (p = .02). Children with ALL who experience acute neurotoxicity may be candidates for early neuropsychological screening and intervention.

[Growth Hormone treatment in children with Growth Hormone deficiency, idiopathic short stature, SHOX gene mutation, small for gestational age and Turner syndrome]. / Tratamiento con Hormona de Crecimiento en pacientes con déficit de hormona de crecimiento, talla baja idiopática, mutación gen SHOX, pequeños para edad gestacional y síndrome de Turner.

Growth hormone (GH) is effective in improving height in several conditions. OBJECTIVE: To describe the evolution of a group of children who received GH in a tertiary center between 2012-2022. PATIENTS AND METHOD: Descriptive, retrospective study. We analyzed the impact on height after GH use with Z-score according to etiology, age at onset and bone age. Patients under 15 years old at baseline and receiving GH for at least 12 months, with diagnoses of GH deficiency (GHD), idiopathic short stature (ISS), small for gestational age (SGA), SHOX Haploinsufficiency (SHOX) and Turner syndrome (TS) were included. Height was expressed as Z-score for age and sex, according to NCHS curves. RESULTS: 145 children received GH. Sixty patients were excluded due to irregular administration, incomplete data, less than 12 months of GH, change of hospital, and associated comorbidities. Seventy-three patients were analyzed, 23 GHD, 15 ISS, 20 SGA, 9 SHOX and 6 TS patients. Significant improvement in height (Z-score for age and sex) was observed in SGA (1.4 ± 0.8 gain; p < 0.001), GHD (1.1 ± 1.0; p < 0.001), ISS (1.1 ± 0.8; p < 0.001) and SHOX (0.8 ± 0.7; p = 0.007) patients. In TS, a non-statistically significant improvement was observed (0.7 ± 0.8; p = 0.085). In GHD, onset before 3 years showed a gain of 1.9 ± 1.1, vs 0.7 ± 0.6 (p = 0.083) and in ISS onset with bone age less than 9 years increased it by 1.7 ± 0.5 vs 0.5 ± 0.5 (p < 0.001). ADVERSE EVENTS: 27/73 (37%) headache, 18/73 (24%) lower extremity pain, 1/73 (1.5%) dizziness, 1/73 (1.5%) scoliosis, 1/73 (1.5%) epiphysiolysis and 1/73 (1.5%) craniopharyngioma recurrence. CONCLUSIONS: Children with GHD, ISS, SHOX mutation and SGA significantly improved their height, highlighting in GHD and ISS the importance of early treatment. Treatment was well tolerated in the 5 groups analyzed.

Food wastes for bioproduct production and potential strategies for high feedstock variability.

Unavoidable food wastes could be an important feedstock for industrial biotechnology, while their valorization could provide added value for the food processor. However, despite their abundance and low costs, the heterogeneous/mixed nature of these food wastes produced by food processors and consumers leads to a high degree of variability in carbon and nitrogen content, as well as specific substrates, in food waste hydrolysate. This has limited their use for bioproduct synthesis. These wastes are often instead used in anaerobic digestion and mixed microbial culture, creating a significant knowledge gap in their use for higher value biochemical production via pure and single microbial culture. To directly investigate this knowledge gap, various waste streams produced by a single food processor were enzymatically hydrolyzed and characterized, and the degree of variability with regard to substrates, carbon, and nitrogen was quantified. The impact of hydrolysate variability on the viability and performance of polyhydroxyalkanoates biopolymers production using bacteria (Cupriavidus necator) and archaea (Haloferax mediterranei) as well as sophorolipids biosurfactants production with the yeast (Starmerella bombicola) was then elucidated at laboratory-scale. After which, strategies implemented during this experimental proof-of-concept study, and beyond, for improved industrial-scale valorization which addresses the high variability of food waste hydrolysate were discussed in-depth, including media standardization and high non-selective microbial organisms growth-associated product synthesis. The insights provided would be beneficial for future endeavors aiming to utilize food wastes as feedstocks for industrial biotechnology.

Venous Thromboembolism Risk and Adherence to Pharmacological Thromboprophylaxis in Hospitalized Patients in Uruguay: First Nationwide Study.

INTRODUCTION: Venous thromboembolism (VTE) is a serious, frequent, and preventable medical complication in hospitalized patients. Although the efficacy of prophylaxis (pharmacological and/or mechanical) has been demonstrated, compliance with prophylaxis is poor at international and national levels. AIM: To determine the indication and use of pharmacological thromboprophylaxis in hospitalized patients in Uruguay. METHODS: An observational, descriptive, cross-sectional, multicentre study involving 31 nationwide healthcare facilities was conducted. Baseline characteristics associated with hospital admission, the percentage of the population with an indication for thromboprophylaxis, and the percentage of patients receiving pharmacological thromboprophylaxis were assessed. The VTE risk was determined using the Padua score for medical patients; the Caprini score for surgical patients; the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines for pregnant-postpartum patients. RESULTS: 1925 patients were included, representing 26% of hospitalized patients in Uruguay. 71.9% of all patients were at risk of VTE. Of all patients at risk of VTE, 58.6% received pharmacological thromboprophylaxis. The reasons for not receiving thromboprophylaxis were prescribing omissions in 16.1% of cases, contraindication in 15.9% and 9.4% of patients were already anticoagulated for other reasons. Overall, just 68% of patients were "protected" against VTE. Recommendations of major thromboprophylaxis guidelines were followed in 70.1% of patients at risk. CONCLUSIONS: Despite the progress made in adherence to thromboprophylaxis indications, nonadherence remains a problem, affecting one in six patients at risk of VTE in Uruguay.

Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy.

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community.

Epidemiology of childhood acute leukemias in marginalized populations of the central-south region of Mexico: results from a population-based registry.

Introduction: Acute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca). Methods: A population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype. Results: A total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states. Conclusion: The incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation.

Blood parameters and parasite burden in cattle with chronic fascioliasis.

Fascioliasis is a trematodiasis that affects domestic and wild animals as well as humans worldwide. It is a well-recognized disease in livestock, were it produces serious economic losses. Yet in cattle, there is limited information about the burden of liver flukes and its relation to the eggs per gram shed to the environment. There is also lack of knowledge on the effect of parasite load in blood parameters of infected animals, which is important to evaluate the severity and progression of the disease. The objective of this work was to gain insight in these aspects. Cattle from Mendoza province, Argentina, were inspected at a farm and at the abattoir determining the presence or absence of Fasciola hepatica. Each animal was sampled for blood and feces and in the slaughterhouse the livers were inspected. Hematology and blood chemistry parameters were determined, feces were examined for F. hepatica eggs by a quantitative sedimentation technique and livers were thoroughly inspected to determine the number of flukes. Infected cattle presented a mild burden of liver flukes per animal, strongly correlated (r = 0.72) to the number of eggs per gram of feces. The total number of eggs (X̄=35,100) shed per animal to the environment and the type of livestock management techniques in the region exacerbate the role of cattle as efficient reservoirs of this disease. Statistically significant lower red blood cell, lymphocyte and neutrophil counts were observed in infected compared to uninfected animals. All hepatic parameters tested showed highly statistically significant differences (p < 0.001) as well as proteins by cause of rise of globulins in infected cattle. The correlation between the amount of flukes in the liver and the number of eggs per gram of faces indicates coprology as a reliable and cost-effective method to infer parasite burden. The impact of fascioliasis on blood parameters can be of aid for the veterinary practitioner on the assessment of this disease on cattle.

Nanoceria Anti-inflammatory and Antimicrobial Nanodrug: Cellular and Molecular Mechanism of Action.

INTRODUCTION: Nanoceria is a well-known nanomaterial with various properties, including antioxidant, proangiogenic, and therapeutic effects. Despite its potential, there are still aspects that require further exploration, particularly its anti-inflammatory and antimicrobial activities. METHOD: The global demand for novel anti-inflammatory and antimicrobial drugs underscores the significance of understanding nanoceria in both contexts. In this study, we evaluated the effect of nanoceria on macrophage polarization to better understand its anti-inflammatory effects. Additionally, we investigated the mechanism of action of nanoceria against Cryptococcus neoformans (ATCC 32045), Candida parapsilosis (ATCC 22019), Candida krusei (ATCC 6258), and Candida albicans. RESULT: The results demonstrated that nanoceria can polarize macrophages toward an anti-inflammatory profile, revealing the cellular mechanisms involved in the anti-inflammatory response. Concerning the antimicrobial effect, it was observed that nanoceria have a more pronounced impact on Candida parapsilosis, leading to the formation of pronounced pores on the surface of this species. CONCLUSION: Finally, biochemical analysis revealed transitory alterations, mainly in liver enzymes. The data support the use of nanoceria as a potential anti-inflammatory and antimicrobial drug and elucidate some of the mechanisms involved, shedding light on the properties of this nanodrug.

Laceración vaginal poscoital: Revisión de casos y propuesta de atención médica / Postcoital vaginal laceration: Review of cases and proposed approach

Resumen OBJETIVO: Describir la caracterización clínica, atención médica y quirúrgica de los casos de laceración poscoital y proponer un protocolo de atención para mejorar la calidad del diagnóstico y tratamiento. MATERIALES Y MÉTODOS: Estudio retrospectivo de serie de casos de pacientes con diagnóstico de laceración vaginal poscoital atendidas en dos hospitales rurales entre 2017 y 2022. RESULTADOS: Se encontraron 6 pacientes que ingresaron al servicio de Urgencias con diagnóstico de laceración vaginal poscoital. Todas fueron intervenidas quirúrgicamente después de la lesión. La mediana de edad de las pacientes fue de 29.5 años (límites 19 y 68 años). Tres de las pacientes eran nuligestas e igual cantidad refirió coito por primera vez, 2 pacientes tenían una pareja estable y 2 nueva pareja. El tiempo transcurrido desde el coito hasta el momento de la atención tuvo una mediana de 2 horas (límites 1 y 3 horas). Solo 2 pacientes requirieron trasfusión de un paquete globular. El sitio de la laceración fue el fondo de saco vaginal posterior en 3 de los 6 casos; no se registraron decesos. CONCLUSIONES: La laceración poscoital es una urgencia rara que puede complicarse por la excesiva pérdida sanguínea, que es mayor si existe retraso en la búsqueda de atención y diagnóstico. Para obtener desenlaces favorables su tratamiento debe ser quirúrgico inmediato, basado en un protocolo estandarizado.

Abstract OBJECTIVE: To describe the clinical characterization, medical and surgical management of cases of postcoital laceration and to propose a management protocol to improve the quality of diagnosis and treatment. MATERIALS AND METHODS: Retrospective case series study of patients diagnosed with post-coital vaginal laceration seen in two rural hospitals between 2017 and 2022. RESULTS: We found 6 patients admitted to the emergency department with a diagnosis of postcoital vaginal laceration. All underwent surgical intervention following the injury. The median age of the patients was 29.5 years (range 19 to 68 years). Three of the patients were nulligestas and the same number reported having sexual intercourse for the first time, 2 patients had a regular partner and 2 had a new partner. The median time from intercourse to treatment was 2 hours (range 1 and 3 hours). Only 2 patients required a globule pack transfusion. The site of laceration was the posterior vaginal fornix in 3 of 6 cases; no deaths were recorded. CONCLUSIONS: Postcoital laceration is a rare emergency that may be complicated by excessive blood loss, which is increased if there is a delay in seeking care and diagnosis. For a favourable outcome, treatment should be immediate surgery based on a standardised protocol.

Cognitive flexibility impairment in temporal lobe epilepsy: The impact of epileptic foci lateralization on executive functions.

INTRODUCTION: Temporal Lobe Epilepsy (TLE) has been associated with memory impairments, which are typically linked to hippocampal and mesial temporal cortex lesions. Considering the presence of extensive bidirectional frontotemporal connections, it can be hypothesized that executive dysfunction in TLE is modulated by the lateralization of the epileptic foci. MATERIAL AND METHODS: A comprehensive neuropsychological executive functions protocol was administered to 63 participants, including 42 individuals with temporal lobe epilepsy (20 with right-TLE and 22 with left-TLE) and 21 healthy controls aged 20-49. RESULTS: The results indicate that TLE patients exhibit poorer executive performance compared to healthy controls in working memory (F(2,60) = 4.18, p <.01), planning (F(2,60) = 4.71, p <.05), set shifting (F(2,60) = 10.1, p <.001), phonetic verbal fluency (F(2,60) = 11.71, p <.01) and semantic verbal fluency (F(2,60) = 9.61, p <.001. No significant differences were found in cognitive inhibition. Furthermore, right-TLE patients showed lower performance than left-TLE in set shifting (F(1,61) = 6.45, p <.05), while no significant differences were observed in working memory, planning, inhibition, and verbal fluency. CONCLUSIONS: This research emphasize the importance of considering the lateralization of the temporal lobe focus to achieve a more accurate neuropsychological characterization. The cognitive differences between left and right TLE patients highlight the need for individualized approaches in their treatment and care.

Unveiling Hidden Risks: Intentional Molecular Screening for Sexually Transmitted Infections and Vaginosis Pathogens in Patients Who Have Been Exclusively Tested for Human Papillomavirus Genotyping.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection (STI) worldwide, with popular screening methods including the Papanicolaou test and HPV genotyping. However, in clinical practice, coinfections with other pathogens are often underestimated. Therefore, our study aims to describe the prevalence of STIs and vaginosis in urogenital samples from patients who had been tested exclusively for HPV genotyping. METHODS: This analytical, prospective, cross-sectional study included 408 males and females. Eligible participants had positive and negative HPV genotyping test results and agreed to early detection or had HPV antecedents. They provided the same urogenital samples used for HPV detection and, through our multiplex in-house PCR assay, we screened for Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2 (HSV), Mycoplasma spp., molluscum contagiosum virus (MCV), Treponema pallidum, Haemophilus spp., Staphylococcus aureus, and Klebsiella spp. The subsequent statistical analysis aimed to reveal correlations between HPV genotypes and the identified pathogens. RESULTS: Of the participants, 72.1% (n = 294) tested positive for HPV genotypes. HR-HPV (high-risk HPV) genotypes comprised 51 (8.1%), 66 (7.1%), and 58 (6.1%). Haemophilus spp., Ureaplasma spp., Candida spp., Staphylococcus aureus, and Mycoplasma spp. frequently co-occurred with HPV infection (p < 0.05). Gender-based variations were notorious for Ureaplasma spp., Mycoplasma spp., and MCV (p < 0.05). Coinfections were prevalent (43.9%), with a positive HPV result elevating the risk for Trichomonas vaginalis, Mycoplasma spp., Staphylococcus aureus, HSV, and MCV (OR > 1, p < 0.05). HPV 16 correlated with HSV and Ureaplasma spp., while HPV 6 was linked with HSV and MCV (p < 0.05). CONCLUSIONS: This screening strategy uncovered significant coinfections and associations between HPV genotypes and pathogens, underscoring the importance of routine screening to explore clinical implications in urogenital health.

First Optimization of Novel, Potent, Selective PDE11A4 Inhibitors for Age-Related Cognitive Decline.

Phosphodiesterase 11A4 (PDE11A4) is a dual-acting cyclic nucleotide hydrolase expressed in neurons in the CA1, subiculum, amygdalostriatal transition area and amygdalohippocampal area of the extended hippocampal formation. PDE11A4 is the only PDE enzyme to emanate solely from hippocampal formation, a key brain region for the formation of long-term memory. PDE11A4 expression increases in the hippocampal formation of both humans and rodents as they age. Interestingly, PDE11A knockout mice do not show age-related deficits in associative memory and show no gross histopathology. This suggests that inhibition of PDE11A4 might serve as a therapeutic option for age-related cognitive decline. A novel, yeast-based high throughput screen previously identified moderately potent, selective PDE11A4 inhibitors, and this work describes initial efforts that improved potency more than 10-fold and improved some pharmaceutical properties of one of these scaffolds, leading to selective, cell-penetrant PDE11A4 inhibitors, one of which is 10-fold more potent compared to tadalafil in cell-based activity.

Continuous bioreactor production of polyhydroxyalkanoates in Haloferax mediterranei.

In this work, the viability of continuous poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production with controlled composition in Haloferax mediterranei when fed volatile fatty acids is demonstrated. Continuous fermentations showed to greatly outperform batch fermentations with continuous feeding. Operating the bioreactor continuously allowed for PHBV productivity normalised by cell density to increase from 0.29 to 0.38 mg L-1 h-1, in previous continuously fed-fed batch fermentations, to 0.87 and 1.43 mg L-1 h-1 in a continuous mode of operation for 0.1 and 0.25 M carbon concentrations in the media respectively. Continuous bioreactor experiments were carried out for 100 h, maintaining control over the copolymer composition at around 30 mol% 3-hydroxyvalerate 3HV. This work presents the first continuous production of PHBV in Haloferax mediterranei which continuously delivers polymer at a higher productivity, compared to fed-batch modes of operation. Operating bioreactors continuously whilst maintaining control over copolymer composition brings new processing opportunities for increasing biopolymer production capacity, a crucial step towards the wider industrialisation of polyhydroxyalkanoates (PHAs).

Ultrasonographic Screening of Dairy Cows with Normal Uterine Involution or Developing Postpartum Uterine Disease Using B-Mode, Color, and Spectral Doppler.

Uterine involution, ovarian activity, and incidence of postpartum uterine disease (PUD) were assessed in forty-eight dairy cows from calving until the 10th postpartum week. Postpartum follow-up included evaluation of uterine involution and ovarian structures by B-mode, Doppler color, and Doppler spectral ultrasound of the right uterine artery in cows with no calving or postpartum uterine problems (healthy cows). Data from cows that developed PUD (PUD cows) were compared with healthy cows matched by herd and days in milk (DIM). Data were analyzed by descriptive statistics, simple regression, one-way ANOVA, or repeated ANOVA measures, and in data analysis of healthy cows, uterine horn diameter assessed by B-mode ultrasound ranged from 22.9 ± 2.4 to 19.4 ± 1.4 mm and 19.9 ± 2.2 to 20.5 ± 2.3 mm from the fourth to the seventh postpartum week in the left and right uterine horns, respectively (P > 0.05). During the study, 15 and 7 cows had corpus luteum in the left and right ovaries, respectively. The mean time for the first postpartum CL was 30.1 ± 3.2 DIM (min 8, max 67 DIM). In data analysis of PUD cows, uterine blood flow assessed by color Doppler ranged from 7.4 ± 4.0 to 43.75 ± 10.3% in cows that developed PUD compared to 16.7 ± 11.0% in healthy cows (P > 0.05). No statistically significant changes were found in resistance index, pulsatility index, time-averaged maximum velocity, time-averaged mean velocity, or diastole/systole ratio (D/S) in cows that developed PUD compared to healthy cows (P > 0.05). Finally, no correlation was found between Doppler spectral parameters and uterine involution (P > 0.05). Our data suggest that cows receiving transition diets and exhibiting normal calving undergo a rapid macroscopic uterine involution and ovarian follicular dynamics resumption. Complete ultrasound evaluation provides valuable data for assessing uterine involution in postpartum dairy cows.

Diagnóstico micológico de histoplasmosis en Uruguay, reporte de una serie de casos de la última década / Mycological diagnosis of histoplasmosis in Uruguay, report of a series of cases of the last decade

Introducción: La histoplasmosis es una micosis sistémica que afecta a humanos, su agente Histoplasma capsulatum, hongo dimorfo, es ubicuo en la naturaleza. Frecuentemente se presenta como reactivación en personas con infección por VIH/SIDA, con manifestaciones polimórficas y diseminadas. Las lesiones mucocutáneas son una importante llave diagnóstica. Objetivo: Contribuir al conocimiento de esta patología a través del reporte de los diagnósticos de laboratorio de histoplasmosis realizados en Uruguay en los últimos 10 años. Materiales y Métodos: Se realizó un estudio observacional, retrospectivo de las histoplasmosis diagnosticadas en el laboratorio de referencia de Micología de Facultad de Medicina y dos laboratorios clínicos. Se enrolaron los registros clínicos y analíticos asociados. Resultados: Fueron 69 los diagnósticos de histoplasmosis. Más de 80% correspondió a personas con infección por VIH/SIDA. El 62,3% del total presentó lesiones de piel y/o mucosas y en 58% el diagnóstico se realizó mediante el estudio de estas. El 62,3% de los diagnósticos se realizaron mediante la visualización al microscopio óptico de frotis coloreados. Conclusiones: La mayoría de las histoplasmosis se vinculan a la infección por VIH/SIDA. El estudio micológico de las lesiones de piel y/o de mucosas, es accesible, mínimamente invasivo, rápido y presenta una excelente performance diagnóstica.

Background: Histoplasmosis is a systemic mycosis that affects humans, its agent Histoplasma capsulatum, a dimorphic fungus, is ubiquitous in nature. It frequently presents as reactivation in people with HIV/AIDS infection, with polymorphic and disseminated manifestations. Mucocutaneous lesions are characteristic and an important diagnostic key. Aim: To contribute to the knowledge of this pathology through the report of histoplasmosis laboratory diagnosis made in Uruguay in the last 10 years. Methods: We conducted an observational, retrospective study of diagnosed histoplasmosis in the Mycology reference laboratory of the Faculty of Medicine and two clinical laboratories. Associated clinical and analytical records were obtained. Results: There were 69 histoplasmosis diagnoses. More than 80% corresponded to people with HIV/AIDS infection. 62.3% of the total presented skin and/or mucosal lesions and in 58% the diagnosis was made by studying them. 62.3% of the diagnoses were initially made by viewing colored smears under an optical microscope. Conclusions: Most histoplasmosis is linked to HIV/AIDS infection. Exposure to a high fungal load is a constant in cases of immunocompetent individuals. The mycological study of skin and/or mucosal lesions is accessible, minimally invasive, fast and has excellent diagnostic performance.

Inflammation- and cancer-related microRNAs in rat renal cortex after subchronic exposure to fluoride.

The proximal tubule is a target of subchronic exposure to fluoride (F) in the kidney. Early markers are used to classify kidney damage, stage, and prognosis. MicroRNAs (miRNAs) are small sequences of non-coding single-stranded RNA that regulate gene expression and play an essential role in developing many pathologies, including renal diseases. This study aimed to evaluate the expression of Cytokine-Chemokine molecules (IL-1α/1ß/4/6/10, INF-γ, MIP-1α, MCP-1, RANTES, and TGF ß1/2/3) and inflammation-related miRNAs to evidence the possible renal mechanisms involved in subchronic exposure to F. Total protein and miRNAs were obtained from the renal cortex of male Wistar rats exposed to 0, 15 and 50 mg NaF/L through drinking water during 40 and 80 days. In addition, cytokines-chemokines were analyzed by multiplexing assay, and a panel of 77 sequences of inflammatory-related miRNAs was analyzed by qPCR. The results show that cytokines-chemokines expression was concentration- and time-dependent with F, where the 50 mg NaF/L were the main altered groups. The miRNAs expression resulted in statistically significant differences in thirty-four miRNAs in the 50 mg NaF/L groups at 40 and 80 days. Furthermore, a molecular interaction network analysis was performed. The relevant pathways modified by subchronic exposure to fluoride were related to extracellular matrix-receptor interaction, Mucin type O-glycan biosynthesis, Gap junction, and miRNAs involved with renal cell carcinoma. Thus, F-induced cytokines-chemokines suggest subchronic inflammation; detecting miRNAs related to cancer and proliferation indicates a transition from renal epithelium to pathologic tissue after fluoride exposure.

Study on manipulation of ruminal fermentation using a bioelectrochemical system.

The purpose of this work was to develop a two-chamber bioelectrochemical cell to modify the metabolic activity of rumen microorganisms by applying an electric potential to the ruminal liquid. Carbohydrate fermentation changes were evaluated along with a molecular characterization by DNA sequencing of the ruminal microbial community. We observed that an electrochemical stimulation potential of 0.75 V enhanced basal acetate, propionate, and butyrate production by 71%, 86%, and 63%, respectively, with no detectable effects on grass substrate disappearance. The applied electric potential also led to changes in the volatile fatty acids production but not on the core microbiome.

Subclassification of B-acute lymphoblastic leukemia according to age, immunophenotype and microenvironment, predicts MRD risk in Mexican children from vulnerable regions.

Introduction: The decisive key to disease-free survival in B-cell precursor acute lymphoblastic leukemia in children, is the combination of diagnostic timeliness and treatment efficacy, guided by accurate patient risk stratification. Implementation of standardized and high-precision diagnostic/prognostic systems is particularly important in the most marginalized geographic areas in Mexico, where high numbers of the pediatric population resides and the highest relapse and early death rates due to acute leukemias are recorded even in those cases diagnosed as standard risk. Methods: By using a multidimensional and integrated analysis of the immunophenotype of leukemic cells, the immunological context and the tumor microenvironment, this study aim to capture the snapshot of acute leukemia at disease debut of a cohort of Mexican children from vulnerable regions in Puebla, Oaxaca and Tlaxcala and its potential use in risk stratification. Results and discussion: Our findings highlight the existence of a distinct profile of ProB-ALL in children older than 10 years, which is associated with a six-fold increase in the risk of developing measurable residual disease (MRD). Along with the absence of CD34+ seminal cells for normal hematopoiesis, this ProB-ALL subtype exhibited several characteristics related to poor prognosis, including the high expression level of myeloid lineage markers such as MPO and CD33, as well as upregulation of CD19, CD34, CD24, CD20 and nuTdT. In contrast, it showed a trend towards decreased expression of CD9, CD81, CD123, CD13, CD15 and CD21. Of note, the mesenchymal stromal cell compartment constituting their leukemic niche in the bone marrow, displayed characteristics of potential suppressive microenvironment, such as the expression of Gal9 and IDO1, and the absence of the chemokine CXCL11. Accordingly, adaptive immunity components were poorly represented. Taken together, our results suggest, for the first time, that a biologically distinct subtype of ProB-ALL emerges in vulnerable adolescents, with a high risk of developing MRD. Rigorous research on potential enhancing factors, environmental or lifestyle, is crucial for its detection and prevention. The use of the reported profile for early risk stratification is suggested.