MED12 and CDK8/19 Modulate Androgen Receptor Activity and Enzalutamide Response in Prostate Cancer.

Prostate cancer progression is driven by androgen receptor (AR) activity, which is a target for therapeutic approaches. Enzalutamide is an AR inhibitor that prolongs the survival of patients with advanced prostate cancer. However, resistance mechanisms arise and impair its efficacy. One of these mechanisms is the expression of AR-V7, a constitutively active AR splice variant. The Mediator complex is a multisubunit protein that modulates gene expression on a genome-wide scale. MED12 and cyclin-dependent kinase (CDK)8, or its paralog CDK19, are components of the kinase module that regulates the proliferation of prostate cancer cells. In this study, we investigated how MED12 and CDK8/19 influence cancer-driven processes in prostate cancer cell lines, focusing on AR activity and the enzalutamide response. We inhibited MED12 expression and CDK8/19 activity in LNCaP (AR+, enzalutamide-sensitive), 22Rv1 (AR-V7+, enzalutamide-resistant), and PC3 (AR-, enzalutamide-insensitive) cells. Both MED12 and CDK8/19 inhibition reduced cell proliferation in all cell lines, and MED12 inhibition reduced proliferation in the respective 3D spheroids. MED12 knockdown significantly inhibited c-Myc protein expression and signaling pathways. In 22Rv1 cells, it consistently inhibited the AR response, prostate-specific antigen (PSA) secretion, AR target genes, and AR-V7 expression. Combined with enzalutamide, MED12 inhibition additively decreased the AR activity in both LNCaP and 22Rv1 cells. CDK8/19 inhibition significantly decreased PSA secretion in LNCaP and 22Rv1 cells and, when combined with enzalutamide, additively reduced proliferation in 22Rv1 cells. Our study revealed that MED12 and CDK8/19 regulate AR activity and that their inhibition may modulate response to enzalutamide in prostate cancer.

Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression.

In advanced prostate cancer (PC), in particular after acquisition of resistance to androgen receptor (AR) signaling inhibitors (ARSI), upregulation of AR splice variants compromises endocrine therapy efficiency. Androgen receptor splice variant-7 (ARV7) is clinically the most relevant and has a distinct 3' untranslated region (3'UTR) compared to the AR full-length variant, suggesting a unique post-transcriptional regulation. Here, we set out to evaluate the applicability of the ARV7 3'UTR as a therapy target. A common single nucleotide polymorphism, rs5918762, was found to affect the splicing rate and thus the expression of ARV7 in cellular models and patient specimens. Serine/arginine-rich splicing factor 9 (SRSF9) was found to bind to and increase the inclusion of the cryptic exon 3 of ARV7 during the splicing process in the alternative C allele of rs5918762. The dual specificity protein kinase CLK2 interferes with the activity of SRSF9 by regulating its expression. Inhibition of the Cdc2-like kinase (CLK) family by the small molecules cirtuvivint or lorecivivint results in the decreased expression of ARV7. Both inhibitors show potent anti-proliferative effects in enzalutamide-treated or -naive PC models. Thus, targeting aberrant alternative splicing at the 3'UTR of ARV7 by disturbing the CLK2/SRSF9 axis might be a valuable therapeutic approach in late stage, ARSI-resistant PC.

Correction: Morales et al. Characterizing Biogenic MnOx Produced by Pseudomonas putida MnB1 and Its Catalytic Activity towards Water Oxidation. Life 2024, 14, 171.

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Characterizing Biogenic MnOx Produced by Pseudomonas putida MnB1 and Its Catalytic Activity towards Water Oxidation.

Mn-oxidizing microorganisms oxidize environmental Mn(II), producing Mn(IV) oxides. Pseudomonas putida MnB1 is a widely studied organism for the oxidation of manganese(II) to manganese(IV) by a multi-copper oxidase. The biogenic manganese oxides (BMOs) produced by MnB1 and similar organisms have unique properties compared to non-biological manganese oxides. Along with an amorphous, poorly crystalline structure, previous studies have indicated that BMOs have high surface areas and high reactivities. It is also known that abiotic Mn oxides promote oxidation of organics and have been studied for their water oxidation catalytic function. MnB1 was grown and maintained and subsequently transferred to culturing media containing manganese(II) salts to observe the oxidation of manganese(II) to manganese(IV). The structures and compositions of these manganese(IV) oxides were characterized using scanning electron microscopy, energy dispersive X-ray spectroscopy, inductively coupled plasma optical emission spectroscopy, and powder X-ray diffraction, and their properties were assessed regarding catalytic functionality towards water oxidation in comparison to abiotic acid birnessite. Water oxidation was accomplished through the whole-cell catalysis of MnB1, the results for which compare favorably to the water-oxidizing ability of abiotic Mn(IV) oxides.

Clinical Characteristics and Outcomes in Adults With Moderate-to-Severe Complexity Congenital Heart Disease Undergoing Palliation or Surgical Repair.

Background: Congenital heart disease (CHD) survival rate has improved dramatically due to advances in diagnostic and therapeutic techniques. However, concerning the unrepaired CHD population of moderate and severe complexity, the data regarding risk predictors and surgical outcomes are scarce. Our aim was to describe the surgical results and predictors of in-hospital outcomes in adult patients with moderate-to-severe complexity CHD that were not repaired in childhood. Methods: We conducted a retrospective cohort study that included 49 adult patients with moderate-to-complex CHD who were treated in a single medical centre. Clinical and echocardiographic variables were obtained on admission, after surgical procedures and during follow-up. Results: Most of the patients were female (66%). Left ventricular ejection fraction and right ventricular outflow tract fractional shortening were within the normal range. The median pulmonary artery systolic pressure was 37 (27-55) mm Hg. The median time was 118 (80-181) minutes for extracorporeal circulation and 76 (49-121) minutes for aortic cross-clamping. The most frequent complication was postoperative complete atrioventricular block (12.2%). In-hospital survival rate was 87.7%. The development of low cardiac output syndrome with predominant right ventricle failure in the postoperative period was the most important predictor of in-hospital death (P = 0.03). Conclusions: Deciding to treat adults with CHD is challenging in moderate and severe unrepaired cases. Adequate clinical, functional, and imaging evaluation is essential to determine each patient's suitability for surgical management and to achieve the best clinical outcome for this population.

Contexte: Grâce aux avancées réalisées en matière de techniques diagnostiques et thérapeutiques, la survie des patients atteints d'une cardiopathie congénitale s'est considérablement améliorée. Cependant, en ce qui concerne les personnes atteintes d'une cardiopathie congénitale non corrigée présentant une complexité modérée ou extrême, les données portant sur les facteurs de risque prédictifs ainsi que sur les résultats chirurgicaux sont rares. Notre objectif était de décrire les résultats chirurgicaux ainsi que les facteurs prédictifs des résultats obtenus en milieu hospitalier chez les patients adultes atteints d'une cardiopathie congénitale présentant une complexité modérée ou extrême qui n'a pas été corrigée pendant l'enfance. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant 49 patients adultes atteints d'une cardiopathie congénitale modérée ou complexe qui ont reçu leurs traitements dans un seul centre médical. Les variables cliniques et échocardiographiques ont été obtenues au moment de l'admission, après les interventions chirurgicales et pendant la période de suivi. Résultats: Les patients étaient en majorité des femmes (66 %). La fraction d'éjection du ventricule gauche ainsi que la fraction de raccourcissement de la voie d'éjection ventriculaire droite sont demeurées dans les limites de la normale. La pression systolique médiane de l'artère pulmonaire a été de 37 mmHg (27-55 mmHg). Le temps médian écoulé pour la circulation extracorporelle a été de 118 minutes (80-181 minutes) et pour le clampage de la crosse aortique, de 76 minutes (49-121 minutes). Le bloc auriculo-ventriculaire postopératoire complet a été la complication la plus fréquente (12,2 %). Le taux de survie en milieu hospitalier a été de 87,7 %. Le développement du syndrome du faible débit cardiaque accompagné d'une insuffisance prédominante du ventricule droit durant la période postopératoire a constitué le principal facteur prédictif de décès à l'hôpital (p = 0,03). Conclusion: Il est difficile de traiter les adultes qui présentent une cardiopathie congénitale modérée ou sévère non corrigée. Il est essentiel que les évaluations cliniques, fonctionnelles et par imagerie soient réalisées de façon adéquate pour déterminer si une prise en charge chirurgicale convient aux patients et pour garantir les meilleurs résultats cliniques chez ces derniers.

Effects of maternal toxic substance consumption during breastfeeding on lactic acid bacteria abundance and nutritional content.

Breast milk is widely recognized as the primary source of nourishment for newborns, making it an unparalleled and indispensable provider of essential nutrients, microbiological components, immunological factors, and energy content. To investigate this further, a cohort comprising 254 breastfeeding women participated in interviews, and milk samples were aseptically collected for subsequent analysis involving bromatological, microbiological, and clinical analysis. The investigation focused on the identification of specific microorganisms in breast milk and their susceptibility to the exposure of toxic substances and controlled medications. Notably, this study places particular emphasis on the significant decline in lactic acid bacteria observed in breast milk when influenced by substances such as cocaine, cannabis, crystal, and morphine. These detrimental agents have been found to adversely affect the growth of microorganisms within breast milk. On the contrary, the outcomes of this study indicate that the utilization of toxic substances does not exert a noteworthy impact on the nutritional quality of breast milk.

A temporal analysis and response to nitrate availability of 3D root system architecture in diverse pennycress (Thlaspi arvense L.) accessions.

Introduction: Roots have a central role in plant resource capture and are the interface between the plant and the soil that affect multiple ecosystem processes. Field pennycress (Thlaspi arvense L.) is a diploid annual cover crop species that has potential utility for reducing soil erosion and nutrient losses; and has rich seeds (30-35% oil) amenable to biofuel production and as a protein animal feed. The objective of this research was to (1) precisely characterize root system architecture and development, (2) understand plastic responses of pennycress roots to nitrate nutrition, (3) and determine genotypic variance available in root development and nitrate plasticity. Methods: Using a root imaging and analysis pipeline, the 4D architecture of the pennycress root system was characterized under four nitrate regimes, ranging from zero to high nitrate concentrations. These measurements were taken at four time points (days 5, 9, 13, and 17 after sowing). Results: Significant nitrate condition response and genotype interactions were identified for many root traits, with the greatest impact observed on lateral root traits. In trace nitrate conditions, a greater lateral root count, length, density, and a steeper lateral root angle was observed compared to high nitrate conditions. Additionally, genotype-by-nitrate condition interaction was observed for root width, width:depth ratio, mean lateral root length, and lateral root density. Discussion: These findings illustrate root trait variance among pennycress accessions. These traits could serve as targets for breeding programs aimed at developing improved cover crops that are responsive to nitrate, leading to enhanced productivity, resilience, and ecosystem service.

Helios+ and RORγt+ Treg populations are differentially regulated by MHCII, CD28, and ICOS to shape the intestinal Treg pool.

Foxp3+ regulatory T cells (Tregs) are essential for intestinal homeostasis. Tregs in the small intestine include Helios+ thymus-derived Tregs (tTregs) and RORγt+ Tregs that differentiate in the periphery after antigenic stimulation (pTregs). TCR and costimulatory signals sustain Tregs with effector phenotypes, including those in the intestine, but it is unknown if tTregs and pTregs have similar requirements for these pathways. We previously used mice lacking peripheral expression of MHCII to demonstrate that the small intestine sustains tTregs independently of peripheral antigen. Here, we show that the effector phenotype and tissue-resident signature of tTregs are also MHCII-independent. Using this model, we define the distinct costimulatory requirements of intestinal tTregs and pTregs. Helios+ effector tTregs proliferate through CD28 and require neither ICOS nor MHCII for maintenance. In contrast, RORγt+ pTregs use CD28 and ICOS. Notably, the differential costimulatory utilization allows tTregs and pTregs to dynamically respond to perturbations to support a fixed number of intestinal Tregs. This suggests that the environmental regulation of costimulatory ligands might shape the subpopulations of intestinal Tregs and promote effective homeostasis and defense. Our data reveal new complexity in effector Treg biology and costimulatory signaling of tTregs and pTregs and highlight the importance of analyzing both subpopulations.

Management of copy number variants associated with incomplete penetrance and variable expressivity-Results of a French survey.

Increasing interest regarding neurodevelopmental disorders and democratization of chromosomal microarray analysis have led to growing identification of neuro-susceptibility copy number variations (CNVs). These CNVs have incomplete penetrance and variable expressivity (PIEV), which makes phenotypic features hard to predict. The French Consortium "AchroPuce" has provided a list of 17 CNVs that should be considered as PIEV CNVs. This list led to consensual French practices of healthcare professionals in postnatal diagnosis. However, no consensus was established in prenatal diagnosis and fetal pathology. 121 French health professionals were surveyed their opinions and practices regarding reporting of PIEV CNVs to patients, in order to identify key points so as to establish French recommendations. The survey showed that professionals in favor of reporting PIEV CNVs to patients in prenatal diagnosis and fetal pathology (respectively, 76% and 84% of respondents) considered highlighted that multidisciplinary consultation is the main point-of-care management before family survey. This statement is close to recommendations published worldwide. As a consequence, multidisciplinary expertise should be the basis of French recommendations concerning the reporting of PIEV CNVs and genetic counseling in prenatal diagnosis and fetal pathology.

Cardiometabolic Risk Factors in Mexican Adults With Congenital Heart Disease.

Background: In recent decades, adults living with congenital heart disease (ACHD) have improved their survival, thus increasing their predisposition to the onset of cardiometabolic risk factors and chronic health conditions. Objectives: The purpose of this study was to describe cardiometabolic risk profiles in the ACHD population and their relationship to congenital heart disease (CHD) lesion complexity. Methods: We performed a cross-sectional study from ACHD in a third-tier referral center in Mexico City. The association between cardiometabolic risk factors and CHD complexity was estimated using logistic regression models. Results: Our study cohort included 1,171 ACHD patients (median age: 31 [IQR: 23.2-42.7] years, male 63.6%). Cardiac diagnosis was classified as mild (44.9%), moderate (37.8%), and severe (17.2%) CHD complexity. Low high-density lipoprotein cholesterol (55%) was the most common cardiometabolic risk factor; followed by insulin resistance (54.5%) and prediabetes (52.4%). Patients with mild and moderate CHD had a higher prevalence of obesity and metabolic syndrome, while patients with severe CHD had a higher prevalence of hyperuricemia and subclinical hypothyroidism. In the logistic regression analysis, the severity of CHD was associated with higher odds of hyperuricemia (moderate CHD, OR: 1.87; 95% CI: 1.20-2.93; P = 0.010; severe CHD, OR: 2.75; 95% CI: 1.64-4.62; P < 0.001) and lower risks of metabolic syndrome (OR: 0.61; 95% CI: 0.41-0.91; P = 0.010), prediabetes (OR: 0.58; 95% CI: 0.42-0.81; P < 0.001), and arterial hypertension (OR: 0.49; 95% CI: 0.33-0.74; P < 0.001) compared with mild CHD complexity. Conclusions: We observed high rates of cardiometabolic risk factors in Mexican ACHD patients and these risk profiles varied by CHD lesion complexity. These results highlight the need for ongoing metabolic health surveillance in the ACHD population.

Vascular senescence in progeria: role of endothelial dysfunction.

Aims: Hutchinson-Gilford progeria syndrome (HGPS) is a pre-mature aging disorder caused by the mutation of the LMNA gene leading to an irreversibly farnesylated lamin A protein: progerin. The major causes of death in HGPS are coronary and arterial occlusive disease. In the murine model of HGPS, vascular smooth muscle cell (VSMC) loss is the primary vascular manifestation, which is different from the arterial occlusive disease seen in older patients. Methods and results: To identify the mechanisms of HGPS vascular disease in humans, we differentiated isogenic endothelial cells (ECs) and VSMCs from HGPS-induced pluripotent stem cells (iPSCs) and control-iPSCs. Both HGPS-ECs and HGPS-VSMCs manifested cellular hallmarks of aging, including dysmorphic nuclei, impaired proliferation, increased ß-galactosidase staining, shortened telomeres, up-regulated secretion of inflammatory cytokines, increased DNA damage, loss of heterochromatin, and altered shelterin protein complex (SPC) expression. However, at similar days after differentiation, even with lower levels of progerin, HGPS-ECs manifested more severe signs of senescence, as indicated in part by a higher percentage of ß-galactosidase positive cells, shorter telomere length, and more DNA damage signals. We observed increased γH2A.X binding to RAP1 and reduced TRF2 binding to lamin A in HGPS-ECs but not in HGPS-VSMCs. The expression of γH2A.X was greater in HGPS-ECs than in HGPS-VSMCs and is associated with greater telomere shortening, impaired SPC interactions, and loss of heterochromatin. Conclusion: Although progerin expression has a deleterious effect on both ECs and VSMCs, the dysfunction is greater in HGPS-ECs compared with HGPS-VSMCs. This study suggests that an endothelial-targeted therapy may be useful for HGPS patients.

Telomerase therapy reverses vascular senescence and extends lifespan in progeria mice.

AIMS: Hutchinson-Gilford progeria syndrome (HGPS) is an accelerated ageing syndrome associated with premature vascular disease and death due to heart attack and stroke. In HGPS a mutation in lamin A (progerin) alters nuclear morphology and gene expression. Current therapy increases the lifespan of these children only modestly. Thus, greater understanding of the underlying mechanisms of HGPS is required to improve therapy. Endothelial cells (ECs) differentiated from induced pluripotent stem cells (iPSCs) derived from these patients exhibit hallmarks of senescence including replication arrest, increased expression of inflammatory markers, DNA damage, and telomere erosion. We hypothesized that correction of shortened telomeres may reverse these measures of vascular ageing. METHODS AND RESULTS: We generated ECs from iPSCs belonging to children with HGPS and their unaffected parents. Telomerase mRNA (hTERT) was used to treat HGPS ECs. Endothelial morphology and functions were assessed, as well as proteomic and transcriptional profiles with attention to inflammatory markers, DNA damage, and EC identity genes. In a mouse model of HGPS, we assessed the effects of lentiviral transfection of mTERT on measures of senescence, focusing on the EC phenotype in various organs. hTERT treatment of human HGPS ECs improved replicative capacity; restored endothelial functions such as nitric oxide generation, acetylated low-density lipoprotein uptake and angiogenesis; and reduced the elaboration of inflammatory cytokines. In addition, hTERT treatment improved cellular and nuclear morphology, in association with a normalization of the transcriptional profile, effects that may be mediated in part by a reduction in progerin expression and an increase in sirtuin 1 (SIRT1). Progeria mice treated with mTERT lentivirus manifested similar improvements, with a reduction in inflammatory and DNA damage markers and increased SIRT1 in their vasculature and other organs. Furthermore, mTERT therapy increased the lifespan of HGPS mice. CONCLUSION: Vascular rejuvenation using telomerase mRNA is a promising approach for progeria and other age-related diseases.

In vivo assessment and characterization of lactic acid bacteria with probiotic profile isolated from human milk powder / Evaluación y caracterización in vivo de bacterias acidolácticas con perfil probiótico aisladas a partir de leche materna en polvo

INTRODUCTION: breast milk (MH) contains nutrients and bioactive compounds for child development, including probiotic bacteria, which contribute to intestinal maturation. This benefit accompanies the individual until adulthood. There are new methods such as spray drying that give this compound a good conservation without loss of microbiota. OBJECTIVE: the aim of this study was to analyze the viability of lactic acid bacteria isolated from human milk with probiotic potential after the spray drying process, as well as to evaluate the possible adhesion in the colon of mice of the Balb/C strain after feeding them powdered human milk and a commercial formula milk. METHOD: we isolated and identified the presence of lactic acid bacteria with possible probiotic potential in powdered human milk using the MALDI-TOF MS technique. Powdered human milk and a commercial formula milk were fed to mice of the Bald/C strain for 14 weeks. Glucose level and weight were measured in the mice. The feces were collected to verify the presence of lactic bacteria. The mice were sacrificed and their intestines were weighed, isolating the lactic acid bacteria both from the intestines and from the feces. The strains isolated from mice fed human milk were evaluated for their probiotic potential, analyzing their ability to inhibit pathogens, resistance to pH, temperature, adhesion, and hydrophobicity. RESULTS: the presence of Lactobacillus fermentum LH01, Lactobacillus rhamnosus LH02, Lactobacullis reuteri LH03, and Lactobacillus plantarum LH05 in powdered human milk was identified. All strains showed a possible probiotic profile due to the ability of bacteria to resist low pH, bile salts, and exposure to gastric enzymes, as well as their hydrophobicity and self-aggregation capacity, and their failure to show hemagglutination or hemolysis activity in a culture medium rich in erythrocytes. We observed that the consumption of powdered human milk prevented weight gain and constipation in mice. CONCLUSIONS: after spray drying, strains with possible probiotic potential may be preserved in human milk. The consumption of powdered human milk with probiotic bacteria prevents constipation and weight gain in mice, when compared to those fed a commercial formula milk

INTRODUCCIÓN: la leche materna (HM) contiene los nutrientes y compuestos bioactivos necesarios para el desarrollo infantil, incluidas bacterias probióticas, que contribuyen a la maduración intestinal. OBJETIVO: el objetivo de este estudio fue analizar la viabilidad de las bacterias acidolácticas aisladas de la leche humana con potencial probiótico, después del proceso de secado, así como evaluar su posible adhesión en el colón de ratones (BAlb/C) alimentados con leche humana en polvo y leche de una fórmula comercial. MÉTODO: se aislaron e identificaron mediante la técnica de Maldi-Tof-MS las bacterias acidolácticas con posible potencial probiótico en la leche humana en polvo. Se alimentó con leche humana en polvo y leche de una fórmula comercial a ratones de la cepa Bald/C durante 14 semanas. Se midieron el nivel de glucosa y el peso. Las heces se recolectaron para verificar la presencia de bacterias lácticas. Los ratones se sacrificaron y se pesaron los intestinos, aislando las bacterias lácticas tanto de los intestinos como de las heces. En las cepas aisladas de la leche humana se evaluó el potencial probiótico analizando su capacidad para inhibir patógenos, resistir distintos pH y temperaturas, adherirse y mostrar hidrofobicidad. RESULTADOS: se identificó la presencia de Lactobacillus fermentum LH01, Lactobacillus rhamnosus LH02, Lactobacullis reuteri LH03 y L. plantarum LH05 en la leche humana en polvo. Todas las cepas mostraron resistencia a los pH bajos, a las sales biliares y a la exposición a enzimas gástricas, así como una buena hidrofobicidad y capacidad de autoagregación. Además, no presentaron actividad de hemaglutinación o hemólisis en un medio de cultivo rico en eritrocitos. Observamos que el consumo de leche humana en polvo evita en los ratones el aumento de peso y el estreñimiento. CONCLUSIONES: después del secado por aspersión, las cepas con posible potencial probiótico pueden conservarse en la leche materna. El consumo de leche humana en polvo con bacterias probióticas evita el estreñimiento y el aumento de peso en los ratones, en comparación con los alimentados con leche de una formula comercial

In vivo assessment and characterization of lactic acid bacteria with probiotic profile isolated from human milk powder.

INTRODUCTION: Introduction: breast milk (MH) contains nutrients and bioactive compounds for child development, including probiotic bacteria, which contribute to intestinal maturation. This benefit accompanies the individual until adulthood. There are new methods such as spray drying that give this compound a good conservation without loss of microbiota. Objective: the aim of this study was to analyze the viability of lactic acid bacteria isolated from human milk with probiotic potential after the spray drying process, as well as to evaluate the possible adhesion in the colon of mice of the Balb/C strain after feeding them powdered human milk and a commercial formula milk. Method: we isolated and identified the presence of lactic acid bacteria with possible probiotic potential in powdered human milk using the MALDI-TOF MS technique. Powdered human milk and a commercial formula milk were fed to mice of the Bald/C strain for 14 weeks. Glucose level and weight were measured in the mice. The feces were collected to verify the presence of lactic bacteria. The mice were sacrificed and their intestines were weighed, isolating the lactic acid bacteria both from the intestines and from the feces. The strains isolated from mice fed human milk were evaluated for their probiotic potential, analyzing their ability to inhibit pathogens, resistance to pH, temperature, adhesion, and hydrophobicity. Results: the presence of Lactobacillus fermentum LH01, Lactobacillus rhamnosus LH02, Lactobacullis reuteri LH03, and Lactobacillus plantarum LH05 in powdered human milk was identified. All strains showed a possible probiotic profile due to the ability of bacteria to resist low pH, bile salts, and exposure to gastric enzymes, as well as their hydrophobicity and self-aggregation capacity, and their failure to show hemagglutination or hemolysis activity in a culture medium rich in erythrocytes. We observed that the consumption of powdered human milk prevented weight gain and constipation in mice. Conclusions: after spray drying, strains with possible probiotic potential may be preserved in human milk. The consumption of powdered human milk with probiotic bacteria prevents constipation and weight gain in mice, when compared to those fed a commercial formula milk.

INTRODUCCIÓN: Introducción: la leche materna (HM) contiene los nutrientes y compuestos bioactivos necesarios para el desarrollo infantil, incluidas bacterias probióticas, que contribuyen a la maduración intestinal. Objetivo: el objetivo de este estudio fue analizar la viabilidad de las bacterias acidolácticas aisladas de la leche humana con potencial probiótico, después del proceso de secado, así como evaluar su posible adhesión en el colón de ratones (BAlb/C) alimentados con leche humana en polvo y leche de una fórmula comercial. Método: se aislaron e identificaron mediante la técnica de Maldi-Tof-MS las bacterias acidolácticas con posible potencial probiótico en la leche humana en polvo. Se alimentó con leche humana en polvo y leche de una fórmula comercial a ratones de la cepa Bald/C durante 14 semanas. Se midieron el nivel de glucosa y el peso. Las heces se recolectaron para verificar la presencia de bacterias lácticas. Los ratones se sacrificaron y se pesaron los intestinos, aislando las bacterias lácticas tanto de los intestinos como de las heces. En las cepas aisladas de la leche humana se evaluó el potencial probiótico analizando su capacidad para inhibir patógenos, resistir distintos pH y temperaturas, adherirse y mostrar hidrofobicidad. Resultados: se identificó la presencia de Lactobacillus fermentum LH01, Lactobacillus rhamnosus LH02, Lactobacullis reuteri LH03 y L. plantarum LH05 en la leche humana en polvo. Todas las cepas mostraron resistencia a los pH bajos, a las sales biliares y a la exposición a enzimas gástricas, así como una buena hidrofobicidad y capacidad de autoagregación. Además, no presentaron actividad de hemaglutinación o hemólisis en un medio de cultivo rico en eritrocitos. Observamos que el consumo de leche humana en polvo evita en los ratones el aumento de peso y el estreñimiento. Conclusiones: después del secado por aspersión, las cepas con posible potencial probiótico pueden conservarse en la leche materna. El consumo de leche humana en polvo con bacterias probióticas evita el estreñimiento y el aumento de peso en los ratones, en comparación con los alimentados con leche de una formula comercial.

Influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana / Influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk

Introducción: la leche materna es el primer alimento fundamental de los neonatos y proporciona todas las fuentes de energía, nutrientes y protección inmunológica que necesitan durante sus primeros meses de vida. Lamentablemente, existen circunstancias específicas que implican que la madre no pueda alimentar correctamente a su bebé, ya que las necesidades nutricionales de la madre difieren en cierta medida durante los diversos periodos de la vida, especialmente en la lactancia, ya que se aumentan las necesidades nutricionales debido a la pérdida de nutrientes, primero por el calostro y luego a través de la leche materna. Objetivo: demostrar la influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana. Métodos: se llevaron a cabo 70 encuestas descriptivas de nutrición y toma de muestras de leche a mujeres en estado lactante. Las leches fueron sometidas a diversos análisis bromatológicos y microbiológicos para evaluar su calidad nutricional y posible actividad probiótica. Resultados: se demostró que la ingesta de alimentos de la madre influye en la calidad nutricional de la leche. Asimismo, afecta el desarrollo y crecimiento de las bacterias lácticas. Se aislaron e identificaron diversas cepas en leche humana del género Lactobacillus, además de bacterias patógenas como el caso de Lodderomyces elongisporus, entre otros. Conclusiones: la alimentación de las madres se refleja directamente en la calidad nutricional de la leche. Se observó que la cantidad de nutrientes esenciales de la leche, como son los hidratos de carbono, lípidos y proteínas, varían conforme a la alimentación y el ritmo de vida de las madres, así como la disminución significativa de bacterias lácticas con potencial probiótico

Introduction: breast milk is the first fundamental food of newborns and it provides all the sources of energy, nutrients and the immunological protection they need during their first months of life. Unfortunately, there are specific circumstances that imply that the mother cannot feed her baby correctly, since the mother's nutritional needs differ to a certain extent during different periods of life. Especially in breastfeeding, since nutritional needs are increased, due to the loss of nutrients, first by colostrum and then by breast milk. Objective: to demonstrate the influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk. Methods: seventy descriptive surveys of nutrition and sampling of milk to women in nursing state were carried out. The milks were subjected to various bromatological and microbiological analyzes to evaluate their nutritional quality and possible probiotic activity. Results: it was shown that the mother's food intake influences the nutritional quality of the milk. Likewise, it affects the development and growth of lactic acid bacteria. Several strains were isolated and identified in human milk of the genus Lactobacillus, as well as pathogenic bacteria such as Lodderomyces elongisporus among others. Conclusions: the mothers' nutrition is directly reflected in the nutritional quality of the milk. It was observed that the amount of essential nutrients of milk such as carbohydrates, lipids and proteins vary according to the diet and life rhythm of the mothers, as well as the significant decrease of lactic bacteria with probiotic potential

[Influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk]. / Influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana.

INTRODUCTION: Introduction: breast milk is the first fundamental food of newborns and it provides all the sources of energy, nutrients and the immunological protection they need during their first months of life. Unfortunately, there are specific circumstances that imply that the mother cannot feed her baby correctly, since the mother's nutritional needs differ to a certain extent during different periods of life. Especially in breastfeeding, since nutritional needs are increased, due to the loss of nutrients, first by colostrum and then by breast milk. Objective: to demonstrate the influence of the diet of Mexican women on the nutritional quality and the presence of beneficial microorganisms in human milk. Methods: seventy descriptive surveys of nutrition and sampling of milk to women in nursing state were carried out. The milks were subjected to various bromatological and microbiological analyzes to evaluate their nutritional quality and possible probiotic activity. Results: it was shown that the mother's food intake influences the nutritional quality of the milk. Likewise, it affects the development and growth of lactic acid bacteria. Several strains were isolated and identified in human milk of the genus Lactobacillus, as well as pathogenic bacteria such as Lodderomyces elongisporus among others. Conclusions: the mothers' nutrition is directly reflected in the nutritional quality of the milk. It was observed that the amount of essential nutrients of milk such as carbohydrates, lipids and proteins vary according to the diet and life rhythm of the mothers, as well as the significant decrease of lactic bacteria with probiotic potential.

INTRODUCCIÓN: Introducción: la leche materna es el primer alimento fundamental de los neonatos y proporciona todas las fuentes de energía, nutrientes y protección inmunológica que necesitan durante sus primeros meses de vida. Lamentablemente, existen circunstancias específicas que implican que la madre no pueda alimentar correctamente a su bebé, ya que las necesidades nutricionales de la madre difieren en cierta medida durante los diversos periodos de la vida, especialmente en la lactancia, ya que se aumentan las necesidades nutricionales debido a la pérdida de nutrientes, primero por el calostro y luego a través de la leche materna. Objetivo: demostrar la influencia de la dieta de mujeres mexicanas sobre la calidad nutricional y la presencia de microorganismos benéficos en la leche humana. Métodos: se llevaron a cabo 70 encuestas descriptivas de nutrición y toma de muestras de leche a mujeres en estado lactante. Las leches fueron sometidas a diversos análisis bromatológicos y microbiológicos para evaluar su calidad nutricional y posible actividad probiótica. Resultados: se demostró que la ingesta de alimentos de la madre influye en la calidad nutricional de la leche. Asimismo, afecta el desarrollo y crecimiento de las bacterias lácticas. Se aislaron e identificaron diversas cepas en leche humana del género Lactobacillus, además de bacterias patógenas como el caso de Lodderomyces elongisporus, entre otros. Conclusiones: la alimentación de las madres se refleja directamente en la calidad nutricional de la leche. Se observó que la cantidad de nutrientes esenciales de la leche, como son los hidratos de carbono, lípidos y proteínas, varían conforme a la alimentación y el ritmo de vida de las madres, así como la disminución significativa de bacterias lácticas con potencial probiótico.

Manejo de la Hiperuricemia en Pacientes en Argentina. Una Encuesta Mediante Cuestionario / Hyperuricemia Management in Patients from Argentina. A Questionnaire Survey

Resumen Introducción: Durante muchos años el ácido úrico se ha considerado como un producto metabólico inerte del metabolismo de las purinas, sin embargo, ha sido recientemente asociado a una serie de estados de enfermedad crónica. No hay hallazgos concluyentes disponibles en la actualidad para tomar una conducta activa clara respecto al tratamiento de ácido úrico sérico, y cuál sería su objetivo terapéutico. Material y métodos: Debido a esta controversia, se decidió llevar a cabo una encuesta para evaluar cuáles son las decisiones que se toman en este contexto, en el ámbito médico de la Argentina. Se consultó en qué pacientes se evaluaba en forma rutinaria el ácido úrico sérico, resultando en un 53.2% de todos los pacientes, sin diferenciar patologías, y un 11.5% refirió que no lo realiza rutinariamente. Con respecto al tratamiento sólo refirieron tratarlo con enfermedad renal un 62.5%; con diabetes 61.7%; con síndrome metabólico 60.4%; con enfermedad cardiovascular un 50.3%; con gota, cálculos renales o dolor articular, un 91.3%, 74% y 36.1% respectivamente. Resultados: Los datos de la encuesta confirman la falta de evidencia en el criterio para la selección de pacientes, a los fines de evaluar los niveles de ácido úrico sérico y su tratamiento. Conclusiones: De esta forma, se concluye que prima la necesidad de realizar estudios prospectivos y randomizados de las patologías con alta incidencia de uricemia elevada, para poder determinar normativas que orienten una conducta a los especialistas según los resultados obtenidos, y que dicha decisión no esté basada solo en la opinión de los expertos.

Abstract Introduction: For many years, uric acid was considered to be an inert product of purine metabolism; however, it has recently been associated with a number of chronic diseases. Nowadays, there are no conclusive findings available regarding a clear action plan to treat serum uric acid or which specific therapeutic goals it would have. Methods: Given this controversy, a survey was conducted in order to evaluate which decisions are taken regarding this situation within the Argentinian medical community. The question was in which cases serum uric acid was routinely assessed and the result was 53.2% no matter the pathology; 11,5% of physicians did not assess it routinely. Regarding its treatment, 62.5% of them reported to have treated it as part of kidney disease; 61.7 % as part of diabetes; 60.4% as part of metabolic syndrome; 50.3% as part of cardiovascular disease; 91.3 % as part of gout; 74% as part of renal stones, and 36.1% as part of joint pain. Results: The data collected by means of the survey show a lack of evidence for establishing the patient selection criteria when evaluating levels of serum uric acid and its treatment. Conclusions: Therefore, it is concluded that it is necessary to conduct prospective and randomized studies of conditions with a high incidence of elevated uricemia in order to develop guidelines for specialists according to results; this decision should not be based on experts' opinion alone.

Compositional Analysis of the Human Microbiome in Cancer Research.

Gut microbial composition has shown to be associated with obesity, diabetes mellitus, inflammatory bowel disease, colitis, autoimmune disorders, and cancer, among other diseases. Microbiome research has significantly evolved through the years and continues to advance as we develop new and better strategies to more accurately measure its composition and function. Careful selection of study design, inclusion and exclusion criteria of participants, and methodology are paramount to accurately analyze microbial structure. Here we present the most up-to-date available information on methods for gut microbial collection and analysis.

Embarazo ectópico abdominal de término con neonato vivo: caso clínico y revisión de la bibliografía / Advanced abdominal pregnancy with a living neonate: Case report and literature review

Resumen ANTECEDENTES: El embarazo ectópico abdominal es una alteración poco frecuente, pero con alta tasa de morbilidad y mortalidad materno-fetal-neonatal. Para establecer el diagnóstico se requiere un alto grado de sospecha y casi siempre se efectúa durante el procedimiento quirúrgico. Es el único tipo de embarazo ectópico que puede llegar a término. CASO CLÍNICO: Paciente de 35 años, con antecedente obstétrico de dos cesáreas, que acudió al servicio médico por dolor abdominal de larga evolución, con varios meses de amenorrea, sin control prenatal. El dolor fue inicialmente adjudicado a una hernia umbilical, pero ante su persistencia se reexaminó a la paciente y se encontró una masa abdominal, por lo que se sospechó embrazo ectópico. El ultrasonido abdominal y la resonancia magnética confirmaron el embarazo de término, que finalizó mediante laparotomía. Se decidió dejar la placenta in situ, debido al riesgo de hemorragia por su remoción. Tanto el neonato como la madre fueron dados de alta en buenas condiciones después de dos semanas de estancia hospitalaria, con posterior seguimiento. CONCLUSIONES: Aunque el embarazo ectópico abdominal es una alteración poco frecuente, es importante saber qué debe hacerse de acuerdo con las semanas de gestación, debido al incremento reciente en su incidencia y a la alta tasa de complicaciones, con la finalidad de preservar el bienestar materno-fetal y la fertilidad femenina.

Abstract BACKGROUND: Abdominal pregnancy is a rare clinical entity with a high risk for both the mother and the product. It's diagnosis requires a high level of suspicion, being usually made during the surgical management of the case. It is the only type of ectopic pregnancy that can reach term. CLINICAL CASE: A 35 year-old patient, with two previous cesarean deliveries, who presents with chronic abdominal pain, without prenatal consultations and with several months of amenorrhea. The pain is initially atributted to an umbilical hernia, but due to it's persistence she is re-examined, finding an abdominal mass and raising suspicion of a possible ectopic pregnancy. She's sent to a hospital in western Mexico, where she undergoes abdominal examination with ultrasound and magnetic resonance, which shows a full term abdominal pregnancy, for which a laparotomy is performed. The placenta is left in situ, due to the high risk of hemorrhage associated with it's removal. Both the newborn and the mother are released from the hospital in good conditions after two weeks of stay, with subsequent follow-up. CONCLUSIONS: Despite it being a rare condition, it's important to be acquainted with the proper management according to the gestational age of the pregnancy due to the recent rise in it's incidence, as well as it's particularly high rate of complicactions, in order to preserve the wellbeing of both patients when possible, as well as maternal fertility.

Dual-energy X-ray absorptiometry visceral adipose tissue estimates: reproducibility and impact of pre-assessment diet.

We examined the reproducibility of dual-energy x-ray absorptiometry (DXA) visceral adipose tissue (VAT) estimates as well as the impact of pre-assessment diet. In a counterbalanced design, 41 adults received 6 DXA scans, while consuming standardized high- and low-carbohydrate (LC) diets. The impact of pre-assessment diet was examined via repeated-measures analysis of variance and reproducibility of VAT estimates was evaluated by technical error of measurement (TEM) and s.e. of a single determination (SESD). VAT area, mass and volume were acutely decreased by ~ 6.5% after the LC diet (P ≤ 0.001), but not the high-carbohydrate diet (P > 0.3). Differences persisted after an overnight fast. TEMs for VAT area, mass and volume were < 5 cm2, ≤ 0.2 kg and < 25 cm3. SESDs for all VAT variables were ≤ 5.5%. In conclusion, DXA VAT estimates exhibit good reproducibility in controlled conditions, but may be impacted by pre-assessment diet.