Altered ovarian reserve in Ewe lambs exposed to a glyphosate-based herbicide.

Glyphosate-based herbicides (GBHs) are considered endocrine disruptors that affect the female reproductive tract of rats and ewe lambs. The present study aimed to investigate the impact of neonatal exposure to a low dose of a GBH on the ovarian follicular reserve of ewe lambs and the response to a gonadotropic stimulus with porcine FSH (pFSH). To this end, ewe lambs were orally exposed to an environmentally relevant GBH dose (1 mg/kg/day) or vehicle (Control) from postnatal day (PND) 1 to PND14, and then some received pFSH (50 mg/day) between PND41 and 43. The ovaries were dissected, and follicular types and gene expression were assessed via RT-PCR. The treatments did not affect the body weight of animals, but pFSH increased ovarian weight, not observed in GBH-exposed lambs. GBH-exposed lambs showed decreased Estrogen receptor-alpha (56%), Progesterone receptor (75%), Activin receptor II (ACVRII) (85%), and Bone morphogenetic protein 15 (BMP15) (88%) mRNA levels. Control lambs treated with pFSH exhibited downregulation of Follistatin (81%), ACVRII (77%), BMP15 (93%), and FSH receptor (FSHr) (72%). GBH-exposed lambs treated with pFSH displayed reduced ACVRII (68%), BMP15 (81%), and FSHr (50%). GBH-exposed lambs also exhibited decreased Anti-Müllerian hormone expression in primordial and antral follicles (27%) and (54%) respectively) and reduced Bone morphogenetic protein 4 (31%) expression in primordial follicles. Results suggest that GBH disrupts key follicular development molecules and interferes with pFSH action in ovarian receptors, decreasing the ovarian reserve. Future studies should explore whether this decreased ovarian reserve impairs adult ovarian function and its response to superovulation stimuli.

Pediatric tuberculosis in Mexico: A retrospective analysis of 100 patients.

Background: Analyzing the epidemiology and clinical manifestations of pediatric tuberculosis in endemic regions is crucial to meet the goal of ending tuberculosis. The objective was to assess the various clinical scenarios of tuberculosis in a large pediatric cohort in Mexico. Methods: This retrospective study from a pediatric referral center in Mexico included patients diagnosed with tuberculosis from 2012 to 2021. We analyzed clinical data and diagnostic study results, including demographic characteristics, underlying medical conditions, BCG vaccination, clinical presentation, imaging findings, microbiologic data, treatment, and clinical outcomes. Basic descriptive statistics and Chi-squared analysis were performed to summarize the metadata of pediatric patients with different clinical presentations of tuberculosis and evaluate their association with mortality, respectively. Results: A total of 100 patients were included with a mean age of 7.76 years ± 1.49 years. The most prevalent clinical presentation was pulmonary tuberculosis (n = 51). Only 51 patients were immunized with Bacillus Calmette-Guérin vaccine. The most commons symptoms were fever, cough and weight loss. Among patients with meningeal tuberculosis (n = 14), the most common clinical signs were seizures, fever, and vomiting. Cure was achieved in 52 patients, 12 patients died, and 36 continue in treatment. Clinical presentation of tuberculosis (p-value = 0.009) and immunodeficiency (p-value = 0.015) were significantly associated with mortality. Conclusions: Increasing the visibility of tuberculosis is imperative to end this disease. We report relevant clinical data of a large pediatric tuberculosis cohort, stratified by the different forms of disease. A high index of suspicion of tuberculosis is required for a timely diagnosis and treatment initiation, particularly among immunocompromised individuals, in whom mortality is higher.

Technetium-99m-ubiquicidin 29-41 SPECT-CT to detect postsurgical spinal infection: A case report.

Background: Postsurgical spinal infections are a severe complication and a challenge to the neurosurgeon due to their complex management. Revision surgeries and the removal of hardware are usually necessary. Recently, advances in nuclear medicine have made it possible to employ radiotracers to identify infections. The radiolabeled antimicrobial peptide technetium-99m-ubiquicidin (99mTc-UBI) (29-41) has been demonstrated to detect bacterial infections. UBI 29-41 is a peptide sequence with selective binding to the anionic cell membrane of bacteria, which has recently been used to differentiate between infection and inflammation. Here, we describe the clinical utility of 99mTc-UBI 29-41 single-photon emission computed tomography-computed tomography (SPECT-CT) in a patient suspected of a postoperative infection. Case description: A 54-year-old male who presented with conus medullaris syndrome secondary to T12 spondylodiscitis and multiple abscess collections was initially managed with debridement, corpectomy, and minimally invasive lateral instrumentation. The patient developed postsurgical empyema near the surgical site. The image study avoided the need for a second surgery and hardware removal. Conclusion: The use of 99mTc-UBI 29-41 SPECT-CT served as a tool to avoid a second invasive procedure; instead, conservative management with antibiotics was performed with an effective outcome after two weeks. This radiotracer has utility in cases in which infection is suspected, but the location is not entirely clear, and information is needed to guide the therapeutic approach.

Rickettsial Disease Outbreak, Mexico, 2022.

Beginning in 2022, Nuevo Leon, Mexico, experienced an outbreak of rickettsioses that is still ongoing despite multidisciplinary control efforts. A total of 57 cases have been confirmed, particularly affecting children. We report a high mortality rate among hospitalized persons in Nuevo Leon. Continuing efforts are required to control the outbreak.

Adequate Mentorship Program for Holmium Laser Enucleation of the Prostate (HoLEP) Leads to Satisfactory Short-Term Outcomes in the Early Learning Curve of Young Urologists: First-Year Outcomes of a Newly Established Mentorship Training in Mexico.

Introduction Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms in men. Holmium Laser Enucleation of the Prostate (HoLEP) has been recommended by international guidelines as an alternative to transurethral resection of the prostate (TURP). HoLEP's learning curve and the lack of adequate mentorship remains an obstacle for the worldwide adoption of this technique. Objective To report the first-year learning curve of a newly established mentorship program in young urologists without any previous HoLEP experience. Methods We report a cohort of patients with BPH, with prostate size ≥70 grams, treated with HoLEP, analyzed for perioperative data and complications, and short-term postoperative complications and functional outcomes, at three and six months after surgery. Results A total of 47 patients were managed with HoLEP. Mean total operative time was 149.8 ± 42.9 minutes. We experienced five (10.6%) intraoperative complications, including one intravesical resection of the prostate with bipolar energy, three conversions to TURP and one conversion to open prostatectomy. We experienced four postoperative complications, all of them Clavien-Dindo ≤2. Median International Prostate Symptom Score (IPSS) decrease at six months was -17 points from baseline. Mean post-void residual volume and prostate-specific antigen significantly decreased by the third postoperative month. Multiple linear regression showed that prostate size is directly related to increased surgical time during the early learning curve. Discussion Our experience adequately reflects the importance of HoLEP mentorship in young urologists seeking training in this technique. Both surgeons had perioperative and postoperative outcomes deemed satisfactory based on previously published learning curves. Conclusions HoLEP is a technically difficult procedure, however, adequate mentorship leads to satisfying short-term outcomes since the early stages of the learning curve in young urologists with no previous training on this technique.

Gut microbial composition and functionality of school-age Mexican population with metabolic syndrome and type-2 diabetes mellitus using shotgun metagenomic sequencing.

Gut metagenome in pediatric subjects with metabolic syndrome (MetS) and type-2 diabetes mellitus (T2DM) has been poorly studied, despite an alarming worldwide increase in the prevalence and incidence of obesity and MetS within this population. The objective of this study was to characterize the gut microbiome taxonomic composition of Mexican pediatric subjects with MetS and T2DM using shotgun metagenomics and analyze the potential relationship with metabolic changes and proinflammatory effects. Paired-end reads of fecal DNA samples were obtained through the Illumina HiSeq X Platform. Statistical analyses and correlational studies were conducted using gut microbiome data and metadata from all individuals. Gut microbial dysbiosis was observed in MetS and T2DM children compared to healthy subjects, which was characterized by an increase in facultative anaerobes (i.e., enteric and lactic acid bacteria) and a decrease in strict anaerobes (i.e., Erysipelatoclostridium, Shaalia, and Actinomyces genera). This may cause a loss of gut hypoxic environment, increased gut microbial nitrogen metabolism, and higher production of pathogen-associated molecular patterns. These metabolic changes may trigger the activation of proinflammatory activity and impair the host's intermediate metabolism, leading to a possible progression of the characteristic risk factors of MetS and T2DM, such as insulin resistance, dyslipidemia, and an increased abdominal circumference. Furthermore, specific viruses (Jiaodavirus genus and Inoviridae family) showed positive correlations with proinflammatory cytokines involved in these metabolic diseases. This study provides novel evidence for the characterization of MetS and T2DM pediatric subjects in which the whole gut microbial composition has been characterized. Additionally, it describes specific gut microorganisms with functional changes that may influence the onset of relevant health risk factors.

Characterization of gut microbiota associated with metabolic syndrome and type-2 diabetes mellitus in Mexican pediatric subjects.

BACKGROUND: Childhood obesity is a serious public health concern that confers a greater risk of developing important comorbidities such as MetS and T2DM. Recent studies evidence that gut microbiota may be a contributing factor; however, only few studies exist in school-age children. Understanding the potential role of gut microbiota in MetS and T2DM pathophysiology from early stages of life might contribute to innovative gut microbiome-based interventions that may improve public health. The main objective of the present study was to characterize and compare gut bacteria of T2DM and MetS children against control subjects and determine which microorganisms might be potentially related with cardiometabolic risk factors to propose gut microbial biomarkers that characterize these conditions for future development of pre-diagnostic tools. RESULTS: Stool samples from 21 children with T2DM, 25 with MetS, and 20 controls (n = 66) were collected and processed to conduct 16S rDNA gene sequencing. α- and ß-diversity were studied to detect microbial differences among studied groups. Spearman correlation was used to analyze possible associations between gut microbiota and cardiometabolic risk factors, and linear discriminant analyses (LDA) were conducted to determine potential gut bacterial biomarkers. T2DM and MetS showed significant changes in their gut microbiota at genus and family level. Read relative abundance of Faecalibacterium and Oscillospora was significantly higher in MetS and an increasing trend of Prevotella and Dorea was observed from the control group towards T2DM. Positive correlations were found between Prevotella, Dorea, Faecalibacterium, and Lactobacillus with hypertension, abdominal obesity, high glucose levels, and high triglyceride levels. LDA demonstrated the relevance of studying least abundant microbial communities to find specific microbial communities that were characteristic of each studied health condition. CONCLUSIONS: Gut microbiota was different at family and genus taxonomic levels among controls, MetS, and T2DM study groups within children from 7 to 17 years old, and some communities seemed to be correlated with relevant subjects' metadata. LDA helped to find potential microbial biomarkers, providing new insights regarding pediatric gut microbiota and its possible use in the future development of gut microbiome-based predictive algorithms.

Inhibition of Tumor Growth and Metastasis by Newcastle Disease Virus Strain P05 in a Breast Cancer Mouse Model.

PURPOSE: Conventional therapies and surgery remain the standard treatment for breast cancer. However, combating the eventual development of metastasis is still a challenge. Newcastle disease virus (NDV) is one of the various species of viruses under clinical evaluation as a vector for oncolytic, gene-, and immune-stimulating therapies. The purpose of this study was to evaluate the antitumor activity of a recombinant NDV (rNDV-P05) in a breast cancer murine model. METHODS: Tumors were induced by injecting the cellular suspension (4T1 cell line) subcutaneously. The virus strain P05 was applied three times at intervals of seven days, starting seven days after tumor induction, and was completed 21 days later. Determination of tumor weight, spleen index, and lung metastasis were done after sacrificing the mice. Serum levels of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, and TNF-related apoptosis-inducing ligand (TRAIL) were quantified by enzyme-linked immunosorbent assay. CD8+ infiltrated cells were analyzed by immunofluorescence. RESULTS: rNDV-P05 showed a route-of-administration-dependent effect, demonstrating that the systemic administration of the virus significantly reduces the tumor mass and volume, spleen index, and abundance of metastatic clonogenic colonies in lung tissue, and increases the inhibition rate of the tumor. The intratumoral administration of rNDV-P05 was ineffective for all the parameters evaluated. Antitumor and antimetastatic capability of rNDV-P05 is mediated, at least partially, through its immune-stimulatory effect on the upregulation of TNF-α, TRAIL, IFN-α, and IFN-γ, and its ability to recruit CD8+ T cells into tumor tissue. CONCLUSION: Systemic treatment with rNDV-P05 decreases the tumoral parameters in the breast cancer murine model.

Postnatal exposure to a glyphosate-based herbicide interferes with the development and growth of the mammary gland of pre-pubertal Ewe lambs.

The aim of the present study was to evaluate whether early postnatal exposure to a glyphosate-based herbicide (GBH) alters pre-pubertal mammary development in Friesian lambs. To this end, from postnatal day 1-14, ewe lambs were exposed subcutaneously or orally to GBH (2 mg/kg bw/day) or vehicle (control) and mammary gland biopsies were obtained at 45 days of age. GBH-exposed lambs exhibited larger mammary ducts and less area occupied by terminal duct lobular units than controls, accompanied by an increase in the area of adipocytes in the mammary stroma. Lambs subcutaneously exposed to GBH showed increased protein expression of estrogen receptor alpha; however, both GBH-exposed groups had decreased mRNA expression of this receptor. Control lambs showed nuclear progesterone receptor (PR) protein expression, whereas GBH-exposed animals showed cytoplasmic PR expression; both GBH-exposed groups exhibited decreased mRNA expression of PR. GBH-exposed lambs also had decreased epithelial cell proliferation. Regarding insulin-like growth factors, both groups showed similar IGF-1 mRNA and protein expression but decreased expression of its receptor, and increased IGFBP5 expression. In addition, phosphorylated AKT was only observed in the mammary gland of control lambs. Our results show that early postnatal exposure to GBH, regardless of the exposure route, affects the IGF-1 system and the AKT/protein kinase B pathway, interfering with steroid hormone receptor expression and cell proliferation. This consequently modifies the growth and development of the pre-pubertal mammary gland of Frisian lambs.

Effect of Mixed Particulate Emulsifiers on Spray-Dried Avocado Oil-in-Water Pickering Emulsions.

Avocado oil is a very valuable agro-industrial product which can be perishable in a short time if it is not stored in the right conditions. The encapsulation of the oils through the spray drying technique protects them from oxidation and facilitates their incorporation into different pharmaceutical products and food matrices; however, the selection of environmentally friendly emulsifiers is a great challenge. Four formulations of the following solid particles: Gum Arabic, HI-CAP®100 starch, and phosphorylated waxy maize starch, were selected to prepare avocado oil Pickering emulsions. Two of the formulations have the same composition, but one of them was emulsified by rotor-stator homogenization. The rest of the emulsions were emulsified by combining rotor-stator plus ultrasound methods. The protective effect of mixed particle emulsifiers in avocado oil encapsulated by spray drying was based on the efficiency of encapsulation. The best results were achieved when avocado oil was emulsified with a mixture of phosphorylated starch/HI-CAP®100, where it presented the highest encapsulation efficiency.

Direct and indirect effects of roads on space use by jaguars in Brazil.

Roads pose an imminent threat to wildlife directly through mortality and changes in individual behavior, and also indirectly through modification of the amount and configuration of wildlife habitat. However, few studies have addressed how these mechanisms interact to determine species response to roads. We used structural equation modeling to assess direct and indirect effects (via landscape modification) of roads on space use by jaguars in Brazil, using radio-tracking data available from the literature. We fit path models that directly link jaguars' space use to roads and to land cover, and indirectly link jaguars' space use to roads through the same land cover categories. Our findings show that space use by jaguars was not directly affected by roads, but indirect effects occurred through reductions in natural areas on which jaguars depend, and through urban sprawl. Males´ space use, however, was not negatively influenced by urban areas. Since jaguars seem to ignore roads, mitigation should be directed to road fencing and promoting safe crossings. We argue that planners and managers need to much more seriously take into account the deforestation and the unbridled urban expansion from roads to ensure jaguar conservation in Brazil.

Abnormal Nailfold Capillaroscopy in a Patient With Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) is an emerging entity during the coronavirus disease 2019 pandemic. Medium- and large-vessel changes are present in MIS-C; however, microcirculatory impairment has not been documented. We report a case of MIS-C in a toddler that presented with persistent fever, gastrointestinal symptoms and rash. Nailfold videocapillaroscopy was abnormal, suggesting microcirculatory disease in the setting of MIS-C.

Producción de leche real vs la calculada a partir de la ENL estimada por el algoritmo de análisis de imágenes red-green-blue de gramíneas / Produção real de leite vs produção de leite calculada a partir da energía líquida de lactação estimada pelo algoritmo para análise de imagens vermelho-verde-azul de gramíneas

Knowledge about the net lactation energy (NLE) contained in the dry matter of grasses is necessary to make decisions about forage and the balance of diets for grazing cattle. Its determination is made in laboratories using wet or dry chemistry methods, which are costly, delayed, and sometimes present sampling- or process-related reliability problems. An algorithm, which analyzes the red-green-blue (RGB) images of grasses taken by drone, has been developed as a technological alternative. This has allowed us estimating the NLE level, reducing costs, and changing the sampling system and analysis method. The objective of the present study was to compare the milk production, which was calculated from the NLE and estimated using the algorithm for analysis of RGB images of grasses (included in the TaurusWebs® software), vs the actual milk production. The study was conducted in 15 dairy farms belonging to the dairy control system of the Colácteos dairy cooperative, which are located in the upper tropical region (Department of Nariño, Colombia). The prairies evaluated were composed of mixtures of Kikuyo (Pennisetum clandestinum), Raigrás (Lolium spp), and False Poa (Holcus lanatus). The result was analyzed using a linear regression model (R²=0.86; R=0.93). In the Student´s t-test, the actual and estimated milk production averages were equal (P>0.05). In conclusion, the NLE calculated using the algorithm satisfactorily explains the study livestock production, and the information generated by the algorithm can be used to calculate the NLE of grasses.(AU)

O conhecimento sobre a energia líquida de lactação (NLE) contida na matéria seca das gramíneas é necessário para a tomada de decisões sobre forragem e o equilíbrio das dietas para pastagem. Sua determinação é feita em laboratórios usando métodos de química úmida ou seca, que são dispendiosos, atrasados e às vezes apresentam problemas de confiabilidade relacionados a amostras ou processos. Um algoritmo, que avalia as imagens vermelho-verde-azul (RGB) de gramíneas tiradas por drone, foi desenvolvido como uma alternativa tecnológica. Isso nos permitiu estimar o nível de NLE, reduzir custos e alterar o sistema de amostragem e o método de análise. O objetivo do presente estudo foi comparar a produção de leite, calculada a partir do NLE e estimada usando o algoritmo para análise de imagens RGB de gramíneas (incluídas no software TaurusWebs®) versus a produção real de leite. O estudo foi realizado em 15 fazendas leiteiras pertencentes ao sistema de controle de laticínios da cooperativa de laticínios Colácteos, localizada na região tropical superior (Departamento de Nariño, Colômbia). As pradarias avaliadas foram compostas por misturas de Kikuyo (Pennisetum clandestinum), Raigrás (Lolium spp) e False Poa (Holcus lanatus). O resultado foi analisado usando um modelo de regressão linear (R² = 0,86; R = 0,93). No teste t de Student, as médias reais e estimadas de produção de leite foram iguais (P> 0,05). Em conclusão, o NLE calculado usando o algoritmo explica satisfatoriamente a produção animal estudada, e as informações geradas pelo algoritmo podem ser usadas para calcular o NLE das gramíneas.(AU)

Producción de leche real vs la calculada a partir de la ENL estimada por el algoritmo de análisis de imágenes red-green-blue de gramíneas / Produção real de leite vs produção de leite calculada a partir da energía líquida de lactação estimada pelo algoritmo para análise de imagens vermelho-verde-azul de gramíneas

ABSTRACT: Knowledge about the net lactation energy (NLE) contained in the dry matter of grasses is necessary to make decisions about forage and the balance of diets for grazing cattle. Its determination is made in laboratories using wet or dry chemistry methods, which are costly, delayed, and sometimes present sampling- or process-related reliability problems. An algorithm, which analyzes the red-green-blue (RGB) images of grasses taken by drone, has been developed as a technological alternative. This has allowed us estimating the NLE level, reducing costs, and changing the sampling system and analysis method. The objective of the present study was to compare the milk production, which was calculated from the NLE and estimated using the algorithm for analysis of RGB images of grasses (included in the TaurusWebs® software), vs the actual milk production. The study was conducted in 15 dairy farms belonging to the dairy control system of the Colácteos dairy cooperative, which are located in the upper tropical region (Department of Nariño, Colombia). The prairies evaluated were composed of mixtures of Kikuyo (Pennisetum clandestinum), Raigrás (Lolium spp), and False Poa (Holcus lanatus). The result was analyzed using a linear regression model (R²=0.86; R=0.93). In the Student´s t-test, the actual and estimated milk production averages were equal (P>0.05). In conclusion, the NLE calculated using the algorithm satisfactorily explains the study livestock production, and the information generated by the algorithm can be used to calculate the NLE of grasses.

RESUMO: O conhecimento sobre a energia líquida de lactação (NLE) contida na matéria seca das gramíneas é necessário para a tomada de decisões sobre forragem e o equilíbrio das dietas para pastagem. Sua determinação é feita em laboratórios usando métodos de química úmida ou seca, que são dispendiosos, atrasados e às vezes apresentam problemas de confiabilidade relacionados a amostras ou processos. Um algoritmo, que avalia as imagens vermelho-verde-azul (RGB) de gramíneas tiradas por drone, foi desenvolvido como uma alternativa tecnológica. Isso nos permitiu estimar o nível de NLE, reduzir custos e alterar o sistema de amostragem e o método de análise. O objetivo do presente estudo foi comparar a produção de leite, calculada a partir do NLE e estimada usando o algoritmo para análise de imagens RGB de gramíneas (incluídas no software TaurusWebs®) versus a produção real de leite. O estudo foi realizado em 15 fazendas leiteiras pertencentes ao sistema de controle de laticínios da cooperativa de laticínios Colácteos, localizada na região tropical superior (Departamento de Nariño, Colômbia). As pradarias avaliadas foram compostas por misturas de Kikuyo (Pennisetum clandestinum), Raigrás (Lolium spp) e False Poa (Holcus lanatus). O resultado foi analisado usando um modelo de regressão linear (R² = 0,86; R = 0,93). No teste t de Student, as médias reais e estimadas de produção de leite foram iguais (P> 0,05). Em conclusão, o NLE calculado usando o algoritmo explica satisfatoriamente a produção animal estudada, e as informações geradas pelo algoritmo podem ser usadas para calcular o NLE das gramíneas.

Los Disability Studies y el Acompañamiento a Estudiantes con Discapacidad en la Universidad Española / Disability Studies and Accompanying Students with Disabilities in Spanish University

RESUMEN: El artículo presenta una investigación centrada en los programas de acompañamiento a estudiantes con discapacidad a partir del giro conceptual de los Disability studies. El objetivo de la investigación ha sido buscar aquellos elementos clave que han configurado este cambio en el acceso de los estudiantes con discapacidad a la Universidad y de los programas de acompañamiento que se han creado. El análisis se ha centrado en tres categorías: evolución del número de estudiantes, innovaciones en la universidad y en personalización. La investigación concluye admitiendo que el cambio generalizado de la mirada sobre las personas con discapacidad ha supuesto que las universidades hayan normalizado la presencia de personas con discapacidad en los diferentes estudios. Los datos revelan la importancia de la consolidación de proyectos de apoyo para hacer posible su incorporación a las universidades. Pero los estudiantes con discapacidad todavía relatan el gran esfuerzo que deben realizar para cursar sus estudios, hecho que demuestra que todavía no se ha conseguido plenamente la igualdad de oportunidades. El horizonte se plantea con universidades tan accesibles como para ir reduciendo los apoyos específicos porque ya no sean necesarios.

ABSTRACT: This paper presents a research focused on accompanying programs for students with disabilities based on the conceptual shift of Disability Studies. The objective of the research was to look for those key elements that have configured this change in the access to the University for students with disabilities and the accompanying programs that have been created. The analysis has focused on three categories: student evolution, university innovations, and personalization. The research concludes by admitting that the widespread change of gaze on people with disabilities has meant that universities have standardized the presence of people with disabilities in different studies. The data reveal the importance of consolidating support projects to make possible that people with disabilities join the university. However, students with disabilities still recount the great effort they must make to keep on their studies, demonstrating that equal opportunities have not yet been fully achieved. The horizon is raised with universities so accessible that allow to reduce specific supports because they are no longer needed.

Serum Irisin Levels, Endothelial Dysfunction, and Inflammation in Pediatric Patients with Type 2 Diabetes Mellitus and Metabolic Syndrome.

The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the pediatric population. Irisin, an adipomyokine, is involved in white adipose tissue browning, energy expenditure, insulin sensitivity, and anti-inflammatory pathways. Data on the associations among circulating irisin levels, soluble cell adhesion molecules (sCAMs), and inflammatory cytokines is scarce in children and adolescents with MetS and T2DM. Subjects aged 6-16 years were grouped into T2DM, MetS, and healthy controls. Serum irisin levels were significantly lower in the MetS (6.6 [2.8-18.0] ng/mL) and T2DM (6.8 [2.2-23.2] ng/mL) groups compared with controls (30.3 [24.6-57.1] ng/mL). Negative correlations between irisin and the BMI percentile (R = -0.358), WC percentile (R = -0.308), and triglycerides (R = -0.284) were identified, while positive associations with TC (R = 0.287), HDL-c (R = 0.488), and LDL-c (R = 0.414) were observed. Significant negative correlations were found between irisin and sNCAM (R = -0.382), sICAM-2 (R = -0.300), sVCAM-1 (R = -0.292), MCP-1 (R = -0.308), and IFN-α2 (R = -0.406). Of note, lower concentrations of most sCAMs (sICAM-1, sPSGL-1, sP-selectin, sEpCAM, sICAM-2, sALCAM, sPECAM-1, sCD44, sVCAM-1, sICAM-3, sL-selectin, and sNCAM) were shown in T2DM subjects compared with MetS patients. Lower irisin levels induce a lack of inhibition of oxidative stress and inflammation. In T2DM, higher ROS, AGEs, glucotoxicity, and inflammation trigger endothelial cell apoptosis, which downregulates the sCAM expression as a compensatory mechanism to prevent further vascular damage. In opposition, in subjects with MetS that have not yet developed T2DM and its accompanying stressors, the upregulation of the sCAM expression is ensued.

Re-sensitizing Ampicillin and Kanamycin-Resistant E. coli and S. aureus Using Synergistic Metal Micronutrients-Antibiotic Combinations.

Due to the recent emergence of multi-drug resistant strains, the development of novel antimicrobial agents has become a critical issue. The use of micronutrient transition metals is a promising approach to overcome this problem since these compounds exhibit significant toxicity at low concentrations in prokaryotic cells. In this work, we demonstrate that at concentrations lower than their minimal inhibitory concentrations and in combination with different antibiotics, it is possible to mitigate the barriers to employ metallic micronutrients as therapeutic agents. Here, we show that when administered as a combinatorial treatment, Cu2+, Zn2+, Co2+, Cd2+, and Ni2+ increase susceptibility of Escherichia coli and Staphylococcus aureus to ampicillin and kanamycin. Furthermore, ampicillin-resistant E. coli is re-sensitized to ampicillin when the ampicillin is administered in combination with Cu2+, Cd2+, or Ni2. Similarly, Cu2+, Zn2+, or Cd2+ re-sensitize kanamycin-resistant E. coli and S. aureus to kanamycin when administered in a combinatorial treatment with those transition metals. Here, we demonstrate that for both susceptible and resistant bacteria, transition-metal micronutrients, and antibiotics interact synergistically in combinatorial treatments and exhibit increased effects when compared to the treatment with the antibiotic alone. Moreover, in vitro and in vivo assays, using a murine topical infection model, showed no toxicological effects of either treatment at the administered concentrations. Lastly, we show that combinatorial treatments can clear a murine topical infection caused by an antibiotic-resistant strain. Altogether, these results suggest that antibiotic-metallic micronutrient combinatorial treatments will play an important role in future developments of antimicrobial agents and treatments against infections caused by both susceptible and resistant strains.

Neonatal exposure to a glyphosate-based herbicide alters the uterine differentiation of prepubertal ewe lambs.

The exposure to endocrine-disrupting compounds (EDCs), such as glyphosate-based herbicides (GBHs), during early life might alter female fertility. The aim of the present study was to evaluate the effects of neonatal exposure to a GBH on sheep uterine development. To achieve this, Friesian ewe lambs were exposed to GBH (2 mg/kg of body weight/day; n = 12) or vehicle (controls; n = 10) through s.c. injections, from postnatal day (PND) 1 to PND14; on PND45, the uteri were obtained to evaluate histomorphological and molecular parameters. Morphological parameters were determined by picrosirius-hematoxylin staining. Protein expression of Ki67 (as a cell proliferation marker), p27, and molecules involved in uterine organogenetic differentiation was measured by immunohistochemistry. We also determined the mRNA expression of the IGF molecular pathway by RT-PCR. Although histomorphology was not modified, the uteri of GBH-exposed ewe lambs showed lower cell proliferation, together with higher p27 protein expression. In addition, the uteri of GBH-exposed ewe lambs showed increased gene expression of insulin-like growth factor binding protein 3 (IGFBP-3), decreased expression of ERα in the luminal (LE) and glandular (GE) epithelia and in the subepithelial stroma (SS), and lower PR expression in the LE but higher in the GE and SS. In addition, GBH treatment decreased the uterine expression of Wnt5a in the GE, of Wnt7a in the SS, of ß-catenin in the LE and GE, of Hoxa10 in the SS, and of Foxa2 in the GE as compared with controls. In conclusion, neonatal exposure to GBH decreased cell proliferation and altered the expression of molecules that control proliferation and development in the uterus. All these changes might have adverse consequences on uterine differentiation and functionality, affecting the female reproductive health of sheep. GBH may be responsible for uterine subfertility, acting as an EDC.

Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus.

Proinflammatory cytokines and the novel myokine irisin, a cleavage product of FNDC5, have been found to play a role in obesity and type 2 diabetes mellitus (T2DM). Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity, yet its association with inflammatory markers is still limited. Circulating irisin has been found to be increased in obesity, while in adult subjects with T2DM decreased levels have been found. However, data establishing the association of circulating irisin in children and adolescents with T2DM has not been described in the literature. The objective of this study was to determine irisin plasma concentration and its association with metabolic and adiposity markers and with hs-CRP, a surrogate marker of inflammation used in clinical practice, in a pediatric population with T2DM. A cross-sample of 40 Mexican children and adolescents aged 7-17 were recruited, 20 diagnosed with T2DM and 20 healthy controls. Plasma irisin levels were found to be lower in the T2DM group compared with controls, which could be attributed to a reduced PGC-1α activity in muscle tissue with a consequent decrease in FNDC5 and irisin expression. Irisin concentration was found to be positively correlated with HDL-c, LDL-c, and total cholesterol, while negatively correlated with BMI, waist circumference, and triglycerides. However, after multiple regression analysis, only HDL-c correlation remained significant. hs-CRP was higher in the T2DM group and positively associated with adiposity markers, unfavorable lipid profile, insulin levels, and HOMA-IR, but no association with irisin was found. Given the favorable metabolic effects attributed to irisin, the low plasma levels found in children and adolescents with T2DM could exacerbate the inflammatory and metabolic imbalances and the intrinsic cardiovascular risk of this disease. We propose an "irisin-proinflammatory/anti-inflammatory axis" to explain the role of irisin as a metabolic regulator in obesity and T2DM.