Enhanced Stature in the Elderly: The Immediate Impact of Acute Postural Exercises.

This study investigates the immediate effects of acute postural exercises on the stature of seniors, focusing on changes in both upright and supine stature measurements. A within-subject design with repeated measures was applied, involving seniors participating in continuous exercises aimed at enhancing core musculature strength and promoting muscle relaxation. Stature measurements were recorded pre- and post-exercise in both upright and supine positions, alongside assessments of body mass index (BMI) category classifications. The results revealed a post-exercise increase in stature ranging from 0.9 to 6.0 cm and from 0.2 to 7.2 cm in upright and supine positions, respectively, with an average increase of approximately 3.5 cm in both upright and supine positions. Statistically significant and clinically relevant changes were observed (p < 0.05), including a modification of BMI by approximately two units, reclassifying 55% of participants from overweight or obese to normal weight or overweight. Furthermore, the similarity between post-exercise upright stature and pre-exercise supine stature suggested that the supine position might provide a more accurate measure of stature in seniors. Conclusively, acute postural exercises have an immediate positive impact on the stature of seniors, suggesting their potential utility in clinical settings for accurate stature measurement. However, BMI results should be interpreted with caution because they are only related to the acute change in stature and therefore may lead to the misinterpretation of the study findings, so future studies focused on evaluating the chronic effect of postural exercises integration on the health outcomes of older adults are needed to demonstrate their potential utility in clinical settings to improve postural health and general well-being.

N-acetylcysteine during critical neurodevelopmental periods prevents behavioral and neurochemical deficits in the Poly I:C rat model of schizophrenia.

Schizophrenia is a chronic neurodevelopmental disorder with an inflammatory/prooxidant component. N-acetylcysteine (NAC) has been evaluated in schizophrenia as an adjuvant to antipsychotics, but its role as a preventive strategy has not been sufficiently explored. We aimed to evaluate the potential of NAC administration in two-time windows before the onset of symptoms in a schizophrenia-like maternal immune stimulation (MIS) rat model. Pregnant Wistar rats were injected with Poly I:C or Saline on gestational day (GD) 15. Three different preventive approaches were evaluated: 1) NAC treatment during periadolescence in the offspring (from postnatal day [PND] 35 to 49); 2) NAC treatment during pregnancy after MIS challenge until delivery (GD15-21); and 3) NAC treatment throughout all pregnancy (GD1-21). At postnatal day (PND) 70, prepulse inhibition (PPI) and anxiety levels were evaluated. In vivo magnetic resonance (MR) imaging was acquired on PND100 to assess structural changes in gray and white matter, and brain metabolite concentrations. Additionally, inflammation and oxidative stress (IOS) markers were measured ex vivo in selected brain regions. MIS offspring showed behavioral, neuroanatomical, and biochemical alterations. Interestingly, NAC treatment during periadolescence prevented PPI deficits and partially counteracted some biochemical imbalances. Moreover, NAC treatments during pregnancy not only replicated the beneficial outcomes reported by the treatment in periadolescence, but also prevented some neuroanatomical deficits, including reductions in hippocampal and corpus callosum volumes. This study suggests that early reduction of inflammation and prooxidation could help prevent the onset of schizophrenia-like symptoms, supporting the importance of anti-IOS compounds in ameliorating this disorder.

Description of clinical and genetic features of 122 patients included in the Spanish Pompe registry.

Pompe disease is a rare genetic disorder with an estimated prevalence of 1:60.000. The two main phenotypes are Infantile Onset Pompe Disease (IOPD) and Late Onset Pompe Disease (LOPD). There is no published data from Spain regarding the existing number of cases, regional distribution, clinical features or, access and response to the treatment. We created a registry to collect all these data from patients with Pompe in Spain. Here, we report the data of the 122 patients registered including nine IOPD and 113 LOPD patients. There was a high variability in how the diagnosis was obtained and how the follow-up was performed among different centres. Seven IOPD patients were still alive being all treated with enzymatic replacement therapy (ERT) at last visit. Ninety four of the 113 LOPD patients had muscle weakness of which 81 were receiving ERT. We observed a progressive decline in the results of muscle function tests during follow-up. Overall, the Spanish Pompe Registry is a valuable resource for understanding the demographics, patient's journey and clinical characteristics of patients in Spain. Our data supports the development of agreed guidelines to ensure that the care provided to the patients is standardized across the country.

THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation.

Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance imaging, revealing cortical shrinkage in Saline- and enlargement in MIA-offspring after THC-exposure. Additionally, MIA-offspring displayed enlarged ventricles and decreased hippocampus, which were partially reverted by both cannabinoids. CBD prevented THC-induced reduction in the corpus callosum, despite affecting white matter structure. Post-mortem studies revealed detrimental effects of THC, including increased inflammation and oxidative stress. CBD partially reverted these pro-inflammatory alterations and modulated THC's effects on the endocannabinoid system. In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted. Further research is needed to elucidate the underlying mechanisms involved in the observed benefits of THC.

Solanum aethiopicum L. from the Basilicata region as a source of specialized metabolites with promising anti-obesity effects: phytochemical characterization and in vivo investigation in high fat diet-fed mice.

Introduction: Solanum aethiopicum L., commonly known as scarlet eggplant (Solanaceae family) is one of the most traditionally cultivated vegetables in Basilicata, a southern region of Italy. Although multiple uses have been given to this vegetable, data about its anti-obesogenic activity are still limited. Methods: This study focuses on testing two different extracts obtained either from the peel or from the whole fruit of the Lucanian Solanum aethiopicum. Their ability to inhibit certain enzymatic activities was tested in vitro and then, the one that showed the better outcomes was tested on an experimental model of High-Fat Diet (HFD) induced obesity. Results: Spectrophotometric assays demonstrated that the peel extract possessed the highest ability to inhibit the selected enzymatic activities and so, its phytochemical profile was obtained through LC-MS chromatography. The oral administration of this extract (25 mg/kg) to HFD-fed mice reduced body weight gain and improved glucose and lipid metabolism. Similarly, the extract ameliorated the obesity-induced inflammatory status by reducing the expression of pro-inflammatory cytokines in both adipose and hepatic tissues. Interestingly, these effects were associated with the improvement of vascular dysfunction. Discussion: Lucanian Solanum aethiopicum extract may represent a new strategic approach for managing obesity and its associated diseases.

Very long-term follow-up after aortic stenting for coarctation of the aorta.

INTRODUCTION AND OBJECTIVES: Stent implantation is the preferred treatment in older children and adults with aortic coarctation (CoA). We aimed to determine the incidence of very late events after CoA stenting. METHODS: We analyzed a cohort of CoA patients who underwent stent implantation at our center between 1993 and 2018. Patients were periodically followed up in outpatient clinics, including computed tomography (CT) and fluoroscopy assessment. RESULTS: A total of 167 patients with CT and fluoroscopy data were included: 83 (49.7%) were aged ≤ 12 years and 46 (28%) were female. The mean clinical follow-up time was 17±8 (range 4-30) years and the mean time to CT/fluoroscopy was 11±7 years. Aortic aneurysm was present in 13% and was associated with the PALMAZ stent (OR, 3.09; 95%CI, 1.11-9.49; P=.036) and the stented length (OR, 0.94; 95%CI, 0.89-0.99; P=.039). Stent fracture was frequent (34%), but was not related to the presence of aneurysm. Stent fracture was associated with young age (OR, 3.57; 95%CI, 1.54-8.33; P=.003), male sex (OR, 4.00; 95%CI, 1.51-12.5, P=.008) and inversely with the PALMAZ stent (OR, 0.29; 95%CI, 0.12-0.67, P=.005). Reintervention was lower in adults (10%), mainly related to aneurysms. Those treated when aged ≤ 12 years had higher reintervention rates (43%) due to recoarctation somatic growth. CONCLUSIONS: This long-term follow-up study of CoA patients treated with stenting revealed a significant incidence of late events. Reintervention rates were higher in patients treated at younger ages. Periodic imaging surveillance appears to be advisable.

Protective effect of microbiota-derived short chain fatty acids on vascular dysfunction in mice with systemic lupus erythematosus induced by toll like receptor 7 activation.

Our objective was to investigate whether short-chain fatty acids (SCFAs), specifically acetate and butyrate, could prevent vascular dysfunction and elevated blood pressure (BP) in mice with systemic lupus erythematosus (SLE) induced by TLR7 activation using imiquimod (IMQ). Treatment with both SCFAs and dietary fibers rich in resistant starch (RS) or inulin-type fructans (ITF) effectively prevented the development of hypertension and cardiac hypertrophy. Additionally, these treatments improved aortic relaxation induced by acetylcholine and mitigated vascular oxidative stress. Acetate and butyrate treatments also contributed to the maintenance of colonic integrity, reduced endotoxemia, and decreased the proportion of helper T (Th)17 cells in mesenteric lymph nodes (MLNs), blood, and aorta in TLR7-induced SLE mice. The observed changes in MLNs were correlated with increased levels of GPR43 mRNA in mice treated with acetate and increased GPR41 levels along with decreased histone deacetylase (HDAC)- 3 levels in mice treated with butyrate. Notably, the effects attributed to acetate, but not butyrate, were nullified when co-administered with the GPR43 antagonist GLPG-0974. T cell priming and differentiation into Th17 cells in MLNs, as well as increased Th17 cell infiltration, were linked to aortic endothelial dysfunction and hypertension subsequent to the transfer of faecal microbiota from IMQ-treated mice to germ-free (GF) mice. These effects were counteracted in GF mice through treatment with either acetate or butyrate. To conclude, these findings underscore the potential of SCFA consumption in averting hypertension by restoring balance to the interplay between the gut, immune system, and vascular wall in SLE induced by TLR7 activation.

From collective health to "personalized" medicine: bioethical challenges in preimplantation genetic testing from a North-South perspective. / De la salud colectiva a la medicina "personalizada": desafíos bioéticos de la evaluación genética preimplantatoria desde la perspectiva norte-sur.

This article examines the scope and limitations of the precision medicine paradigm and its relationship with the collective health approach. To that end, it takes preimplantation genetic testing (PGT) as a paradigmatic example of technologies aimed at the "individualization" of health processes. In this regard, we review the characteristics and scientific and regulatory foundations of PGT technologies in Argentina, and discuss the next steps for their bioethical analysis. More specifically, we shed light on some of the conditions for their implementation from a north-south perspective. We propose three themes or problematic aspects as a synthesis of our analysis, related to biases in the production of knowledge, the values and interests underlying its uses, and the underlying epistemological assumptions of these technologies. Throughout the article, we review these dilemmas and suggest some issues that should be taken into account in future research.

El artículo se interroga por los alcances y los límites del paradigma de la medicina de precisión y su relación con el enfoque de la salud colectiva. Para ello, se toma la evaluación genética preimplantatoria o PGT (preimplantation genetic testing) dado que constituye un ejemplo paradigmático de tecnologías que apuntan a la "individualización" de los procesos de salud. En esta dirección, se revisan las características y los fundamentos científico-normativos acerca de las tecnologías PGT en Argentina, y el camino que queda por recorrer para su análisis bioético. De manera más específica, se visibilizan algunas de las condiciones de posibilidad para su implementación desde la perspectiva norte-sur. Como síntesis del análisis, proponemos tres ejes o nudos problemáticos relacionados con los sesgos en la producción de conocimiento, los valores e intereses subyacentes a sus usos y los presupuestos epistemológicos que operan en la base de estas tecnologías. A lo largo de este trabajo, presentamos estos dilemas y sugerimos algunas recomendaciones para ser tenidas en cuenta en futuras investigaciones.

Probiotics and Prebiotics in Cardiovascular Diseases.

This Special Issue, titled "Probiotics and Prebiotics in Cardiovascular Diseases", encompasses two comprehensive review articles examining the potential of gut-microbiota-targeted reprogramming interventions designed to prevent the onset and progression of cardiovascular diseases [...].

Screening for late-onset Pompe disease in Internal Medicine departments in Spain.

BACKGROUND: The screening of high-risk populations using dried blood spots (DBS) has allowed the rapid identification of patients with Pompe disease, mostly in Neurology departments. The aim of the study was to determine the prevalence of late-onset Pompe disease (LOPD) among patients not previously diagnosed or tested for this entity despite presenting possible signs or symptoms of the disease in Internal Medicine departments in Spain. METHODS: This epidemiological, observational, cross-sectional, multicenter study included a single cohort of individuals with clinical suspicion of LOPD seen at Internal Medicine departments in Spain. The diagnosis of LOPD was initially established on the basis of the result of DBS. If decreased enzyme acid-alpha-1,4-glucosidase (GAA) activity was detected in DBS, additional confirmatory diagnostic measurements were conducted, including GAA activity in lymphocytes, fibroblasts, or muscle and/or genetic testing. RESULTS: The diagnosis of LOPD was confirmed in 2 out of 322 patients (0.6%). Reasons for suspecting LOPD diagnosis were polymyositis or any type of myopathy of unknown etiology (in one patient), and asymptomatic or pauci-symptomatic hyperCKemia (in the other). The time between symptom onset and LOPD diagnosis was 2.0 and 0.0 years. Both patients were asymptomatic, with no muscle weakness. Additionally, 19.7% of the non-LOPD cases received an alternative diagnosis. CONCLUSIONS: Our study highlights the existence of a hidden population of LOPD patients in Internal Medicine departments who might benefit from early diagnosis and early initiation of potential treatments.

Targeting the gut microbiota with dietary fibers: a novel approach to prevent the development cardiovascular complications linked to systemic lupus erythematosus in a preclinical study.

This study is to investigate whether dietary fiber intake prevents vascular and renal damage in a genetic mouse model of systemic lupus erythematosus (SLE), and the contribution of gut microbiota in the protective effects. Female NZBWF1 (SLE) mice were treated with resistant-starch (RS) or inulin-type fructans (ITF). In addition, inoculation of fecal microbiota from these experimental groups to recipient normotensive female C57Bl/6J germ-free (GF) mice was performed. Both fiber treatments, especially RS, prevented the development of hypertension, renal injury, improved the aortic relaxation induced by acetylcholine, and the vascular oxidative stress. RS and ITF treatments increased the proportion of acetate- and butyrate-producing bacteria, respectively, improved colonic inflammation and integrity, endotoxemia, and decreased helper T (Th)17 proportion in mesenteric lymph nodes (MLNs), blood, and aorta in SLE mice. However, disease activity (splenomegaly and anti-ds-DNA) was unaffected by both fibers. T cell priming and Th17 differentiation in MLNs and increased Th17 infiltration was linked to aortic endothelial dysfunction and hypertension after inoculation of fecal microbiota from SLE mice to GF mice, without changes in proteinuria and autoimmunity. All these effects were lower in GF mice after fecal inoculation from fiber-treated SLE mice. In conclusion, these findings support that fiber consumption prevented the development of hypertension by rebalancing of dysfunctional gut-immune system-vascular wall axis in SLE.

Effect of sitagliptin on down-regulation of KAT7 and SIRT1 gene expression in breast cancer cell line MCF7.

BACKGROUND: To date, the main clinical interest in DPP4 is focused on its inhibition in diabetic patients to prolong the half-life of incretins. Epigenetic alterations resulting from DPP4 inhibition have been poorly explored. OBJECTIVE: The objective of this study was to determine, whether sitagliptin, a DPP4 inhibitor, has effects on the expression of KAT7 and SIRT1 (genes encoding a histone acetyltransferase and a histone deacetylase, respectively) in MCF7 breast cancer cells, which play an essential role in modulating the epigenetic landscape of chromatin. MATERIAL AND METHODS: MCF7 cells were incubated for 20 h with sitagliptin at concentrations of 0.5, 1.0 and 2.0 µM. Total RNA was isolated and the relative mRNA expression of KAT7 and SIRT1 was determined by RT-qPCR. RESULTS: There was downregulation in the relative expression of both genes; for KAT7, downregulation reached up to 0.49 (p = 0.027) and for SIRT1, it reached up to 0.55 (p = 0.037). CONCLUSIONS: These results suggest that sitagliptin has effects on the histone epigenetic landscape. This topic deserves further study due to the current sample use of DPP4 inhibitors in diabetic patients.

ANTECEDENTES: Hasta la fecha, el principal interés clínico de la DPP4 se centra en su inhibición en pacientes diabéticos para prolongar la vida media de las incretinas. Las alteraciones epigenéticas resultantes de la inhibición de DPP4 han sido poco exploradas. OBJETIVO: Determinar si la sitagliptina, un inhibidor de DPP4, tiene efectos sobre la expresión de KAT7 y SIRT1 (genes que codifican una histona acetiltransferasa y una histona desacetilasa, respectivamente) en células de cáncer de mama MCF7, que desempeñan un papel esencial en la modulación del paisaje epigenético de la cromatina. MÉTODO: Las células MCF7 se incubaron durante 20 h con sitagliptina a concentraciones de 0.5, 1.0 y 2.0 µM. Se aisló el ARN total y se determinó la expresión relativa de ARNm de KAT7 y SIRT1 mediante RT-qPCR. RESULTADOS: Hubo una regulación a la baja en la expresión relativa de ambos genes; para KAT7, la regulación negativa alcanzó hasta 0.49 (p = 0.027) y para SIRT1 alcanzó hasta 0.55 (p = 0.037). CONCLUSIONES: Estos resultados sugieren que la sitagliptina tiene efectos sobre el paisaje epigenético de las histonas. Este tema merece más estudios debido al uso actual de inhibidores de DPP4 en pacientes diabéticos.

Guía de presión encarcelada en el tratamiento percutáneo de las bifurcaciones coronarias: daño estructural y resultados clínicos / Jailed pressure wire technique for coronary bifurcation lesions: structural damage and clinical outcomes

Introducción y objetivos: El uso de una guía de presión encarcelada para evaluar los resultados de la rama lateral durante la técnica del stent provisional parece factible. Sin embargo, existen dudas sobre su seguridad por el daño mecánico de la guía y son escasos los datos referentes al pronóstico de los pacientes. El objetivo de este estudio fue evaluar el daño estructural de la guía de presión en la técnica de la guía encarcelada y examinar los resultados clínicos a medio plazo. Métodos: Se incluyó a 99 pacientes con lesiones bifurcadas tratadas mediante la técnica de guía de presión encarcelada y, como control histórico, a 114 pacientes tratados mediante la técnica de la guía encarcelada con guías no poliméricas. Se evaluó el daño de la guía mediante microscopía estereoscópica. El objetivo primario fue localizar la presencia de daño microscópico significativo. Se examinaron eventos cardiovasculares adversos mayores a los dos años de seguimiento. Resultados: El daño microscópico significativo fue más frecuente en las guías de presión que en las no poliméricas (53,5% vs 22,8%, p <0,001). No hubo fracturas en ningún grupo. Hubo menos intervenciones de la rama lateral en el grupo de la guía de presión (posdilatación 32,3% vs 56,1%, p=0,001; stent, 0,0% vs 2,6%, p=0,104). El riesgo de eventos cardiovasculares a los 2 años fue similar en ambos grupos (HRadj=0,42; IC95%, 0,10-1,73; p=0,229). Conclusiones: La guía de presión fue menos resistente al encarcelamiento que la guía no polimérica. Los pacientes tratados con guía de presión requirieron menos intervenciones de la rama lateral, pero tuvieron similar riesgo de eventos a los 2 años de seguimiento. (AU)

Introduction and objectives: The use of a pressure wire as a jailed wire to evaluate side branch results during provisional stenting seems feasible. However, safety concerns exist due to the mechanical damage of the wire and the lack of prospective data evaluating the prognosis of patients treated using this technique. This study sought to evaluate the structural damage of the pressure wire in patients treated using the jailed pressure wire technique and to assess mid-term clinical outcomes. Methods: We enrolled 99 patients with single bifurcation lesions and provisional stenting as the strategy of choice. A jailed pressure wire was used to guide side branch intervention according to the instantaneous wave-free ratio (iFR). A total of 114 patients and the respective nonpolymer-coated jailed wires were used as historical controls. Guidewire damage was evaluated by stereomicroscopy. The primary endpoint was significant microscopic damage. Major adverse cardiac events were evaluated at 2-year follow-up. Results: Significant microscopic damage was more frequent in pressure wires than in nonpolymer-coated wires (53.5% vs 22.8%, P<.001). There were no fractures in either group. There were fewer side branch interventions in the pressure wire group (postdilation/kissing balloon, 32.3% vs 56.1%, P=.001; stenting, 0.0% vs 2.6%, P=.104). The 2-year rate of major adverse cardiac events was similar between the 2 groups (HRadj, 0.42; 95%CI, 0.10-1.73; P=.229). Conclusions: Pressure wires were less resistant to jailing than conventional nonpolymer-coated wires. Patients treated with iFR-guided provisional stenting required fewer side branch interventions but had similar 2-year clinical outcomes than patients treated with the angiography-guided technique. (AU)

Riesgo de desarrollar diabetes mellitus tipo 2 según escala Finnish Diabetes Risk Score en atención primaria / Risk of Developing Type 2 Diabetes Mellitus According to the Finnish Diabetes Risk Score in Primary care

Introducción: La diabetes mellitus tipo 2, representa 90-95 por ciento de todas las diabetes, es una enfermedad crónica potencialmente prevenible, la escala Finnish Diabetes Risk Score es uno de los instrumentos más utilizados a nivel mundial para evaluar el riesgo de presentar diabetes en 10 años con enfoque fácil y económico. Objetivo: Determinar el riesgo de desarrollar diabetes en los próximos 10 años según escala Finnish Diabetes Risk Score en pacientes en una Unidad Médica Familiar de México. Métodos: Estudio transversal analítico, se aplicó la escala Finnish Diabetes Risk Score a 383 pacientes y se analizaron las variables implicadas en dicha escala, las variables edad e índice de masa corporal se describieron con medidas de tendencia central, las variables sexo, escolaridad, así como aquellas dicotómicas y de intervalo, mediante razones y proporciones. Se midió asociación mediante Odds Ratio para dicotómicas y coeficiente de Spearman para numéricas. Resultados: La mediana de edad fue de 47 años, predominó el sexo femenino, el 71,5 por ciento reportó sedentarismo, el 51,9 por ciento refirió un familiar de primer grado con diabetes, se determinó probabilidad del 67 por ciento de tener peso normal al realizar actividad física diaria; se determinó una probabilidad del 65 por ciento de presentar prediabetes si se tiene sobrepeso u obesidad, se determinó asociación lineal entre índice de masa corporal y edad, el riesgo predominante para desarrollar diabetes mellitus tipo 2 en 10 años fue alto. Conclusiones: El riesgo de desarrollar diabetes en 10 años en la población estudiada fue elevado y se relacionó con falta de actividad física, antecedentes familiares y sobrepeso(AU)

Introduction: Type 2 diabetes mellitus, accounts for 90-95 percent of all diabetes. It is a potentially preventable chronic disease. The Finnish Diabetes Risk Score is one of the most widely used instruments worldwide to assess the risk of developing diabetes in 10 years with an easy and inexpensive approach. Objective: To determine the risk of developing diabetes in the next 10 years according to the Finnish Diabetes Risk Score in patients in a Family Medical Unit in Mexico. Methods: Analytical cross-sectional study. The Finnish Diabetes Risk Score was applied to 383 patients and the variables involved in this scale were analyzed. The variables age and body mass index were described with measures of central tendency, while the variables gender, schooling, as well as dichotomous and interval variables, were described by ratios and proportions. Association was measured by Odds Ratio for dichotomous variables and Spearman's coefficient for numerical variables. Results: The average age was 47 years and female gender predominated. Sedentary lifestyle was reported by 71.5 percent and 51.9 percent reported a first-degree relative with diabetes. A 67percent probability of having a normal weight was determined when performing daily physical activity. In addition, a 65percent probability of having prediabetes was established if overweight or obese, and a linear association was found between body mass index and age. The predominant risk for developing type 2 diabetes mellitus in 10 years was high. Conclusions: The risk of developing diabetes in 10 years in the studied population was high and was related to lack of physical activity, family history and overweight(AU)

Maternal Supplementation with N-Acetylcysteine Modulates the Microbiota-Gut-Brain Axis in Offspring of the Poly I:C Rat Model of Schizophrenia.

The microbiota-gut-brain axis is a complex interconnected system altered in schizophrenia. The antioxidant N-acetylcysteine (NAC) has been proposed as an adjunctive therapy to antipsychotics in clinical trials, but its role in the microbiota-gut-brain axis has not been sufficiently explored. We aimed to describe the effect of NAC administration during pregnancy on the gut-brain axis in the offspring from the maternal immune stimulation (MIS) animal model of schizophrenia. Pregnant Wistar rats were treated with PolyI:C/Saline. Six groups of animals were studied according to the study factors: phenotype (Saline, MIS) and treatment (no NAC, NAC 7 days, NAC 21 days). Offspring were subjected to the novel object recognition test and were scanned using MRI. Caecum contents were used for metagenomics 16S rRNA sequencing. NAC treatment prevented hippocampal volume reduction and long-term memory deficits in MIS-offspring. In addition, MIS-animals showed lower bacterial richness, which was prevented by NAC. Moreover, NAC7/NAC21 treatments resulted in a reduction of proinflammatory taxons in MIS-animals and an increase in taxa known to produce anti-inflammatory metabolites. Early approaches, like this one, with anti-inflammatory/anti-oxidative compounds, especially in neurodevelopmental disorders with an inflammatory/oxidative basis, may be useful in modulating bacterial microbiota, hippocampal size, as well as hippocampal-based memory impairments.

The Prebiotic Effects of an Extract with Antioxidant Properties from Morus alba L. Contribute to Ameliorate High-Fat Diet-Induced Obesity in Mice.

Obesity is a global health issue, in which modifications in gut microbiota composition have a key role. Different therapeutic strategies are being developed in combination with diet and exercise, including the use of plant extracts, such as those obtained from Morus alba L. leaves. Recent studies have revealed their anti-inflammatory and antioxidant properties. The aim of the present work was to evaluate whether the beneficial effects of M. alba L. leaf extract in high-fat diet-induced obesity in mice is correlated with its impact on gut microbiota. The extract reduced body weight gain and attenuated lipid accumulation, as well as increased glucose sensitivity. These effects were associated with an amelioration of the obesity-associated inflammatory status, most probably due to the described antioxidant properties of the extract. Moreover, M. alba L. leaf extract mitigated gut dysbiosis, which was evidenced by the restoration of the Firmicutes/Bacteroidota ratio and the decrease in plasma lipopolysaccharide (LPS) levels. Specifically, the extract administration reduced Alistipes and increased Faecalibaculum abundance, these effects being correlated with the beneficial effects exerted by the extract on the obesity-associated inflammation. In conclusion, anti-obesogenic effects of M. alba L. leaf extract may be mediated through the amelioration of gut dysbiosis.

Targeting M2 Macrophages with a Novel NADPH Oxidase Inhibitor.

ROS in cancer cells play a key role in pathways regulating cell death, stemness maintenance, and metabolic reprogramming, all of which have been implicated in resistance to chemo/ immunotherapy. Adjusting ROS levels to reverse the resistance of cancer cells without impairing normal cell functions is a new therapeutic avenue. In this paper, we describe new inhibitors of NADPH oxidase (NOX), a key enzyme in many cells of the tumor microenvironment. The first inhibitor, called Nanoshutter-1, NS1, decreased the level of tumor-promoting "M2" macrophages differentiated from human blood monocytes. NS1 disrupted the active NADPH oxidase-2 (NOX2) complex at the membrane and in the mitochondria of the macrophages, as shown by confocal microscopy. As one of the characteristics of tumor invasion is hypoxia, we tested whether NS1 would affect vascular reactivity by reducing ROS or NO levels in wire and pressure myograph experiments on isolated blood vessels. The results show that NS1 vasodilated blood vessels and would likely reduce hypoxia. Finally, as both NOX2 and NOX4 are key proteins in tumors and their microenvironment, we investigated whether NS1 would probe these proteins differently. Models of NOX2 and NOX4 were generated by homology modeling, showing structural differences at their C-terminal NADPH site, in particular in their last Phe. Thus, the NADPH site presents an unexploited chemical space for addressing ligand specificity, which we exploited to design a novel NOX2-specific inhibitor targeting variable NOX2 residues. With the proper smart vehicle to target specific cells of the microenvironment as TAMs, NOX2-specific inhibitors could open the way to new precision therapies.

Differences in Tridimensional Shoulder Kinematics between Asymptomatic Subjects and Subjects Suffering from Rotator Cuff Tears by Means of Inertial Sensors: A Cross-Sectional Study.

Background: The aim of this study was to analyze differences in three-dimensional shoulder kinematics between asymptomatic subjects and patients who were diagnosed with rotator cuff tears. Methods: This cross-sectional study recruited 13 symptomatic subjects and 14 asymptomatic subjects. Data were obtained from three inertial sensors placed on the humerus, scapula and sternum. Kinematic data from the glenohumeral, scapulothoracic and thoracohumeral joints were also calculated. The participants performed shoulder abductions and flexions. The principal angles of movements and resultant vectors in each axis were studied. Results: The glenohumeral joint showed differences in abduction (p = 0.001) and flexion (p = 0.000), while differences in the scapulothoracic joint were only significant during flexion (p = 0.001). The asymptomatic group showed higher velocity values in all sensors for both movements, with the differences being significant (p < 0.007). Acceleration differences were found in the scapula during abduction (p = 0.001) and flexion (p = 0.014), as well as in the sternum only during shoulder abduction (p = 0.022). Conclusion: The results showed kinematic differences between the patients and asymptomatic subjects in terms of the mobility, velocity and acceleration variables, with lower values for the patients.

Partial Two-Stage Exchange for Infected Total Hip Arthroplasty: A Treatment to Take into Account.

INTRODUCTION: Two-stage revision is the gold standard for chronic periprosthetic joint infection (PJI). The removal of well-fixed implants, especially the femoral component, can be extremely difficult and additional osteotomies may be needed, which is time-consuming and results in bone stock loss. When the femoral stem is osseointegrated, there is no clear indication for the use of partial two-stage revision. The primary objective was to assess infection eradication after surgery. METHODS: Retrospective study of specific case series. A total of eight patients with a chronic uncemented PJI, in the setting of complex revision surgeries, were treated with partial two-stage revision, which included selective retention of the well-fixed femoral component and complete acetabular removal. Stem retention was carried out regardless of the bacteria or associated comorbidities. RESULTS: All patients were re-revision cases with at least two previous surgeries (range, 2-4). Complex revisions were performed in five cases (non-articulated spacer) and simple revisions in three cases (articulated spacer). The minimum follow-up time was 24 months (range, 24-132 months). The infection eradication rate at final follow-up was 100%. CONCLUSION: Partial two-stage reconstruction is a promising technique for the treatment of chronic PJI in patients with a well-fixed stem and complex re-revision acetabular procedures. Further prospective studies and prolonged follow-ups are required to confirm our results.

Oxidative Damage by 3-nitrotyrosine in Young Adults with Obesity: Its Implication in Chronic and Contagious Diseases.

INTRODUCTION: Cellular damage by oxidation occurs in numerous chronic diseases, such as obesity, type II diabetes, cardiovascular disease, nonalcoholic fatty liver, etc. The oxidized compound 3-nitrotyrosine is a marker of oxidative stress and protein oxidation damage. OBJECTIVE: The article aims to assess whether 3-nitrotyrosine levels are higher in young people with obesity than in the same population without obesity. METHODS: Anthropometry and blood chemistry analyses were performed on 24 young Mexican participants (18-30 years old), categorized into two groups based on their waist circumference: Withobesity (≥ 80 cm women; ≥ 90 cm men) and without-obesity (<80 cm women; <90 cm men). Additionally, 3-nitrotyrosine blood values were quantified by ELISA. RESULTS: Except for HDL-cholesterol, the mean values of lipids increased in women and men with obesity (p<0.05), and 3-nitrotyrosine concentration (nM/µg total protein) was higher by 60% in the group with-obesity compared to the group without-obesity, both for women (66.21 ± 23.85 vs. 40.69 ± 16.25, p<0.05) and men (51.72 ± 20.56 vs. 30.52 ± 5.21, p<0.05). CONCLUSION: Oxidative damage measured by compound 3-nitrotyrosine was higher in the group with obesity than in the group without obesity, which, if not controlled, could lead to a chronic oxidative condition and thereby to a degree of cellular aging with adverse health effects.