Impact of Early- and High-Dose Caffeine on the Cerebellum Development in Newborn Rats.

INTRODUCTION: Preterm newborns struggle with maintaining an adequate respiratory pattern; early caffeine administration is suggested to stimulate respiration and reduce bronchopulmonary dysplasia, however, its consequences on the immature cerebellum remains unknown. This study aimed to assess the impact of early caffeine administration, at standard and high doses, accompanied by supplemental oxygen on cerebellar development in an experimental model. METHODS: Five groups of Wistar pups were formed (n = 8 offspring/group): (a) negative control: no intervention; (b) placebo: pups remaining from birth until the 7th day of life (DOL) exposed to fractional inspired oxygen (FiO2) 45%, resembling preterm infant condition and as a placebo, 0.2 mL oral 5% dextrose, from the first DOL until the 14th DOL; (c) caffeine group: oral caffeine, 1st DOL 20 mg/kg, and from 2nd to 14th DOL, 5 mg/kg (standard dose); (d) caffeine at the standard dose, plus O2: during the first 7 DOLs (FiO2: 45%); (e) caffeine: 40 mg/kg in the first DOL, 10 mg/kg the next 14 DOLs, plus O2 in the first 7 DOLs (FiO2: 45%). Subjects were sacrificed on their 15th DOL; measurements were taken from the cerebellum, specifically the external granular layer (EGL) and molecular layer (ML), with quantification of cell migration. RESULTS: Caffeine administration in pups resulted in a delay in cerebellum development based on persistent transitional EGL cells; this finding was exacerbated in groups exposed to caffeine plus O2, as evident from the thicker EGL. The negative control group showed near-complete cell migration with a thicker ML and a significantly smaller EGL. CONCLUSIONS: Early caffeine administration in newborn rats disrupts cerebellar cortex cell processes and connectivity pathways, with exacerbated effects in groups receiving caffeine plus O2.

In Silico Identification of Dysregulated miRNAs Targeting KRAS Gene in Pancreatic Cancer.

Pancreatic cancer (PC) is highly lethal, with KRAS mutations in up to 95% of cases. miRNAs inversely correlate with KRAS expression, indicating potential as biomarkers. This study identified miRNAs targeting KRAS and their impact on PC characteristics using in silico methods. dbDEMC identified dysregulated miRNAs in PC; TargetScan, miRDB, and PolymiRTS 3.0 identified miRNAs specific for the KRAS gene; and OncomiR evaluated the association of miRNAs with clinical characteristics and survival in PC. The correlation between miRNAs and KRAS was analysed using ENCORI/starBase. A total of 210 deregulated miRNAs were identified in PC (116 overexpressed and 94 underexpressed). In total, 16 of them were involved in the regulation of KRAS expression and 9 of these (hsa-miR-222-3p, hsa-miR-30a-5p, hsa-miR-30b-5p, hsa-miR-30e-5p, hsa-miR-377-3p, hsa-miR-495-3p, hsa-miR-654-3p, hsa-miR-877-5p and hsa-miR-885-5p) were associated with the clinical characteristics of the PC. Specifically, the overexpression of hsa-miR-30a-5p was associated with PC mortality, and hsa-miR-30b-5p, hsa-miR-377-3p, hsa-miR-495-3p, and hsa-miR-885-5p were associated with survival. Correlation analysis revealed that the expression of 10 miRNAs is correlated with KRAS expression. The dysregulated miRNAs identified in PC may regulate KRAS and some are associated with clinically relevant features, highlighting their potential as biomarkers and therapeutic targets in PC treatment. However, experimental validation is required for confirmation.

Pregnant Women with Multiple Sclerosis: An Overview of Gene Expression and Molecular Interaction Using Bioinformatics Analysis.

Multiple sclerosis (MS) is a common disease in young women of reproductive age, characterized by demyelination of the central nervous system (CNS). Understanding how genes related to MS are expressed during pregnancy can provide insights into the potential mechanisms by which pregnancy affects the course of this disease. This review article presents evidence-based studies on these patients' gene expression patterns. In addition, it constructs interaction networks using bioinformatics tools, such as STRING and KEGG pathways, to understand the molecular role of each of these genes. Bioinformatics research identified 25 genes and 21 signaling pathways, which allows us to understand pregnancy patients' genetic and biological phenomena and formulate new questions about MS during pregnancy.

Acute Combined Cerebrolysin and Nicotinamide Administration Promote Cognitive Recovery Through Neuronal Changes in the Hippocampus of Rats with Permanent Middle Cerebral Artery Occlusion.

Stroke is one of the leading causes of disability worldwide, where the Hippocampus (HPC) is affected. HPC organizes memory, which is a cognitive domain compromised after a stroke, where cerebrolysin (CBL) and Nicotinamide (NAM) have been recognized as potentially therapeutic. In this study, we aimed to evaluate the efficacy of a combined administration of CBL and NAM in a rat stroke model. Male Sprague-Dawley rats (n = 36) were divided into four groups: saline (pMCAO - Saline), CBL (pMCAO + CBL), NAM (pMCAO + NAM), and experimental (pMCAO + CBL-NAM) (n = 9 per group). A permanent middle cerebral artery occlusion (pMCAO) was induced through electrocauterization of the middle cerebral artery, followed by the administration of CBL (2.5 ml/kg), NAM (500 mg/kg) or combined immediately after skin suture, as well as at 24, 48, and 72 h post-surgery. The rats were evaluated in the novel object recognition test; hippocampal infarct area measurement; reconstruction of neurons from CA1 for Sholl analysis; and, measurement of brain-derived neurotrophic factor (BDNF) levels near the infarct zone. Our findings revealed that the administration of CBL or NAM induced infarct reduction, improved cognition, and increased BDNF levels. Moreover, a combination of CBL and NAM increased dendritic intersection in CA1 pyramidal neurons. Thus, the combined administration of CBL and NAM can promote cognitive recovery after a stroke, with infarct reduction, cytoarchitectural changes in HPC CA1 neurons, and BDNF increase. Our findings suggest that this combination therapy could be a promising intervention strategy for stroke.

Cultural context and self-care impact on medical students' quality of life. A mixed-methods approach.

BACKGROUND: Medical education can make it difficult for students to take actions to improve their health. OBJECTIVE: To evaluate the influence of the university context on self-care behaviors and quality of life. MATERIAL AND METHODS: A mixed-methods approach was used, with surveys being combined to assess self-care and quality of life, with in-depth interviews to explore cultural influences and perceptions. Statistical analysis and qualitative data coding were carried out, with methods being integrated through network analysis. RESULTS: Self-care scores exceeded 50 points, and quality of life scores exceeded 60 points. Medical students' context is shaped by motivations, expectations, skills, and goals that influence identity formation and contribute to the medical profession. CONCLUSIONS: There is a positive connection between self-care practices and quality of life. However, academic stress can potentially disrupt self-care routines. Furthermore, an association between obesity and a decrease in quality of life stands out, which emphasizes the need for health promotion actions.

ANTECEDENTES: La educación médica puede dificultar que los estudiantes realicen acciones para mejorar su salud. OBJETIVO: Evaluar la influencia del contexto universitario en los comportamientos de autocuidado y la calidad de vida. ­. MATERIAL Y MÉTODOS: Se empleó un enfoque de métodos mixtos, combinando encuestas para evaluar el autocuidado y la calidad de vida, con entrevistas en profundidad para explorar influencias culturales y percepciones. Se llevaron a cabo análisis estadísticos y codificación de datos cualitativos; los métodos se integraron a través del análisis de redes. RESULTADOS: Las puntuaciones de autocuidado superaron los 50 puntos y las de calidad de vida, los 60 puntos. El contexto de los estudiantes de medicina está moldeado por motivaciones, expectativas, habilidades y metas que influyen en la formación de la identidad y contribuyen a la profesión médica. CONCLUSIONES: Existe una conexión positiva entre prácticas de autocuidado y la calidad de vida; sin embargo, el estrés académico pueden interrumpir potencialmente las rutinas de autocuidado. Además, se destaca la asociación entre la obesidad y la afectación en la calidad de vida, lo que enfatiza la necesidad de acciones de promoción de la salud.

Modulation of the Circadian Rhythm and Oxidative Stress as Molecular Targets to Improve Vascular Dementia: A Pharmacological Perspective.

The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

Association of the rs1966265 and rs351855 FGFR4 Variants with Colorectal Cancer in a Mexican Population and Their Analysis In Silico.

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors (p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group (p < 0.05). Associations were observed between the rs1966265 GA genotype and patients with rectal cancer and stage III-IV disease. The rs351855 AA genotype was a risk factor for partial chemotherapy response, and the GA + AA genotype for age ≥ 50 years at diagnosis and rectal cancer was associated with a partial response to chemotherapy (p < 0.05). The AA haplotype was associated with increased susceptibility to CRC. In silico analysis indicated that the rs351855 variant is likely pathogenic (score = 0.998). Genotypic expression analysis in blood samples showed statistically significant differences (p < 0.05). EFNA4, SLC3A2, and HNF1A share signaling pathways with FGFR4. Therefore, rs1966265 and rs351855 may be potential CRC risk factors.

Contexto cultural e impacto del autocuidado en la calidad de vida de los estudiantes de medicina. Enfoque de métodos mixtos / Cultural context and self-care impact on medical students’ quality of life. A mixed-methods approach

Resumen Antecedentes: La educación médica puede dificultar que los estudiantes realicen acciones para mejorar su salud. Objetivo: Evaluar la influencia del contexto universitario en los comportamientos de autocuidado y la calidad de vida. Material y métodos: Se empleó un enfoque de métodos mixtos, combinando encuestas para evaluar el autocuidado y la calidad de vida, con entrevistas en profundidad para explorar influencias culturales y percepciones. Se llevaron a cabo análisis estadísticos y codificación de datos cualitativos; los métodos se integraron a través del análisis de redes. Resultados: Las puntuaciones de autocuidado superaron los 50 puntos y las de calidad de vida, los 60 puntos. El contexto de los estudiantes de medicina está moldeado por motivaciones, expectativas, habilidades y metas que influyen en la formación de la identidad y contribuyen a la profesión médica. Conclusiones: Existe una conexión positiva entre prácticas de autocuidado y la calidad de vida; sin embargo, el estrés académico pueden interrumpir potencialmente las rutinas de autocuidado. Además, se destaca la asociación entre la obesidad y la afectación en la calidad de vida, lo que enfatiza la necesidad de acciones de promoción de la salud.

Abstract Background: Medical education can make it difficult for students to take actions to improve their health. Objective: To evaluate the influence of the university context on self-care behaviors and quality of life. Material and methods: A mixed-methods approach was used, with surveys being combined to assess self-care and quality of life, with in-depth interviews to explore cultural influences and perceptions. Statistical analysis and qualitative data coding were carried out, with methods being integrated through network analysis. Results: Self-care scores exceeded 50 points, and quality of life scores exceeded 60 points. Medical students’ context is shaped by motivations, expectations, skills, and goals that influence identity formation and contribute to the medical profession. Conclusions: There is a positive connection between self-care practices and quality of life. However, academic stress can potentially disrupt self-care routines. Furthermore, an association between obesity and a decrease in quality of life stands out, which emphasizes the need for health promotion actions.

Environmental enrichment and cerebrolysin improve motor and cognitive performance in a rat model of stroke, in conjunction with an increase in hippocampal AMPA but not NMDA receptor subunits.

Stroke is a pathology related to the vascular system in the brain and it is one of the main causes of disability, representing a burden on public health. This lesion provokes a disorganization of sensory-motor and cognitive systems, the latter associated with hippocampal activity, a structure in which α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA N-methyl-D-aspartate (NMDA) receptors are important for the integration of information. Several molecules have been studied for their capacity to enhance recovery from a stroke, including cerebrolysin that could potentially be reinforced by environmental enrichment. Here, stroke was induced in 40 male rats and 24 h later, they were administered cerebrolysin (2.5 ml/kg), put in an environmentally enriched arena or given both treatments, for 10 days. Subsequently, motor functioning was assessed with the Bederson test and the cognitive domain was assessed through novel object recognition. Hematoxylin/eosin staining was then used to assess the infarct size, and AMPA-GRIA1 and NMDA-R1 subunits in the hippocampus were measured by ELISA. In motor and cognitive performance, the administration of cerebrolysin and environmental enrichment enhanced recovery. Moreover, the infarct size decreased in all the groups that received a treatment, but an increase occurred in AMPA-GRIA1 only in experimental group regarding to control group, while NMDA-R1 had no differences. These results suggest that cerebrolysin and environmental enrichment could act in synergy to recover after a stroke, leading to a smaller infarct area and the presence of more AMPA-GRIA1 subunits in the hippocampus of experimental group. These data encourage further studies in which neurorehabilitation approaches can be combined with cerebrolysin administration to treat the motor and cognitive symptoms of stroke.

Gene expression in multiple sclerosis during pregnancy based on integrated bioinformatics analysis.

BACKGROUND: The modulation of the activity disease in patients with Multiple Sclerosis (MS) that occurs during pregnancy is a helpful model which could provide insight into central disease mechanisms and facilitate treatment. Therefore, the aim of the study was to identify differentially expressed genes in-silico to perform biological function pathway enrichment analysis and protein-protein interaction from pregnant women with MS. METHODS: Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. We selected the microarray dataset GSE17449. The gene expression dataset contains the data of mononuclear cells from four different groups sought, including seven healthy women (H), four healthy pregnant women (HP), eight women with multiple sclerosis (WMS), and nine women nine months pregnant with multiple sclerosis (PMS). The GSEA software was employed for enrichment analysis, and the REACTOME database was used for biological pathways. The protein-protein interaction (PPI) network was plotted with STRING. The databases used to identify the connection of DEGs with different signaling pathways were KEGG and WIKIPATHWAYS. RESULTS: We identified 42 differentially expressed genes in pregnant women with MS. The significant pathways included IL-10 signaling pathway, ErbB2 activates, the hemoglobin complex (HBD, HBB, HBA1, AHSP, and HBA2), IL-17 signaling pathway (LCN2 and MMP9), antigen processing and presentation, and Th17 cell differentiation (HLA-DQA1), Rap1 signaling pathway (ID1), NOD-Like receptor signaling pathway (CAMP and DEFA4), PD-L1 Signaling, Interferon gamma signaling (MMP9 and ARG1), Neutrophil degranulation (CAMP, DEFA4, ELANE, CEACAM8, S100P, CHI3L1, AZU1, OLFM4, CRISP3, LTF, ARG1, PGLYRP1, and TCN1). In the WIKIPATHWAYS set, significance was found Vitamin B12 metabolism (TCN1, HBB, and HBA2), and IL-18 signaling pathway (S100P). CONCLUSION: This study can be used to understand several essential target genes and pathways identified in the present study, which may serve as feasible targets for MS therapies.

HIV-1 Tat Induces Dysregulation of PGC1-Alpha and Sirtuin 3 Expression in Neurons: The Role of Mitochondrial Biogenesis in HIV-Associated Neurocognitive Disorder (HAND).

During the antiretroviral era, individuals living with HIV continue to experience milder forms of HIV-associated neurocognitive disorder (HAND). Viral proteins, including Tat, play a pivotal role in the observed alterations within the central nervous system (CNS), with mitochondrial dysfunction emerging as a prominent hallmark. As a result, our objective was to examine the expression of genes associated with mitophagy and mitochondrial biogenesis in the brain exposed to the HIV-1 Tat protein. We achieved this by performing bilateral stereotaxic injections of 100 ng of HIV-1 Tat into the hippocampus of Sprague-Dawley rats, followed by immunoneuromagnetic cell isolation. Subsequently, we assessed the gene expression of Ppargc1a, Pink1, and Sirt1-3 in neurons using RT-qPCR. Additionally, to understand the role of Tert in telomeric dysfunction, we quantified the activity and expression of Tert. Our results revealed that only Ppargc1a, Pink1, and mitochondrial Sirt3 were downregulated in response to the presence of HIV-1 Tat in hippocampal neurons. Interestingly, we observed a reduction in the activity of Tert in the experimental group, while mRNA levels remained relatively stable. These findings support the compelling evidence of dysregulation in both mitophagy and mitochondrial biogenesis in neurons exposed to HIV-1 Tat, which in turn induces telomeric dysfunction.

Terapia medico nutricional en pacientes que reciben terapia de oxigenación por membrana extracorpórea: conocimiento en progreso / Medical nutrition therapy in patients receiving extracorporeal membrane oxygenation: knowledge in progress

Resumen El soporte nutricional (SN) en pacientes adultos que reciben terapia de oxigenación por membrana extracorpórea (ECMO, extracorporeal membrane oxygenation) es controvertido. Si bien existen guías para el SN en pacientes pediátricos con ECMO, en adultos no se cuenta con estos lineamientos para el uso, tipo, ruta y momento de la terapia nutricional. En pacientes críticamente enfermos es bien sabido que la nutrición enteral (NE) temprana es beneficiosa, no obstante existe la posibilidad de que en pacientes con ECMO la NE temprana condicione complicaciones gastrointestinales. Asimismo, no se han establecido metas calóricas, proteicas y dosis o tipos de micronutrimentos que usar para esta población en específico, siendo un reto para el clínico encargado de brindar el SN. Aunado a esto los pacientes con ECMO son algunos de los más gravemente enfermos en las unidades de cuidados intensivos, donde la desnutrición se asocia con una mayor morbilidad y mortalidad. En cuanto al uso de nutrición parenteral (NP), no se tiene descrito si implica riesgo de falla en el circuito al momento de introducir lípidos al oxigenador. Por lo anterior es imperativa una correcta evaluación e intervención nutricional específica, realizada por expertos en el tema para mejorar el pronóstico y la calidad de vida en esta población, siendo un objetivo primordial en los cuidados de los pacientes adultos que reciben terapia de ECMO.

Abstract Nutritional support in adult patients receiving extracorporeal membrane oxygenation (ECMO) therapy is controversial. Although there are guidelines for the NS (Nutritional support) in pediatric patients with ECMO, in adults these guidelines are not available for the use, type, route and timing of nutritional therapy. In critically ill patients it is well known that early enteral nutrition is beneficial, however there is the possibility that in patients with ECMO early enteral nutrition leads to gastrointestinal complications. Likewise, there have not been established caloric targets, proteins and doses or types of micronutrients to use for this specific population being a challenge for the clinician. In addition, patients with ECMO are some of the most seriously ill in intensive care units, where malnutrition is associated with increased morbidity and mortality. Regarding the use of parenteral nutrition (NP) it has not been described if it implies a risk of circuit failure at the time of introducing lipids to the oxygenator. Therefore, a correct evaluation and specific nutritional intervention by experts in the field is imperative to improve the prognosis and quality of life in this population, which is a primary goal in the care of adult patients receiving extracorporeal membrane oxygen.

Micronuclei and nuclear buds in amniotic tissue of rats treated with cyclophosphamide.

Fetal development can be altered by DNA damage caused by maternal exposure to chemical, physical, or biological agents during gestation. One method of assessing genotoxicity is to detect micronuclei (MNs) and/or nuclear abnormalities. This can be performed in vivo and requires only frequently dividing tissues, such as amniotic tissue (AT), which is in contact with the fetal environment and is composed of very thin layers of cells. This study evaluated the presence of MNs, nucleoplasmic bridges, and nuclear buds (NBs) in the fetal AT following maternal exposure to cyclophosphamide (CP) during pregnancy. Pregnant Wistar rats were divided into a negative control group and an experimental group that was orally administered CP (10 mg/kg). Daily blood smears were obtained from pregnant rats on days 14-19 of gestation. The rats were dissected, and fetal ATs were obtained on the 19th day of gestation. The MN and NB frequencies in AT cells were analyzed using a fluorescence microscope (100 ×). Micronucleated erythrocytes in the peripheral blood of the control rats were also assessed. Micronucleated polychromatic erythrocyte frequencies were significantly higher than those in the controls. Polychromatic erythrocyte frequencies were lower in CP-treated rats than in controls at 48-120 h. Fetuses in the CP-treated group also showed a significant increase in MNs and NBs in AT cells. In conclusion, AT could be used for analyzing MNs and NBs in rats following maternal exposure to a genotoxic agent and as a viable alternative for analyzing the integrity of fetal DNA during gestation.

Medical nutrition therapy in patients receiving extracorporeal membrane oxygenation: knowledge in progress.

Nutritional support in adult patients receiving extracorporeal membrane oxygenation (ECMO) therapy is controversial. Although there are guidelines for the NS (Nutritional support) in pediatric patients with ECMO, in adults these guidelines are not available for the use, type, route and timing of nutritional therapy. In critically ill patients it is well known that early enteral nutrition is beneficial, however there is the possibility that in patients with ECMO early enteral nutrition leads to gastrointestinal complications. Likewise, there have not been established caloric targets, proteins and doses or types of micronutrients to use for this specific population being a challenge for the clinician. In addition, patients with ECMO are some of the most seriously ill in intensive care units, where malnutrition is associated with increased morbidity and mortality. Regarding the use of parenteral nutrition (NP) it has not been described if it implies a risk of circuit failure at the time of introducing lipids to the oxygenator. Therefore, a correct evaluation and specific nutritional intervention by experts in the field is imperative to improve the prognosis and quality of life in this population, which is a primary goal in the care of adult patients receiving extracorporeal membrane oxygen.

El soporte nutricional (SN) en pacientes adultos que reciben terapia de oxigenación por membrana extracorpórea (ECMO, extracorporeal membrane oxygenation) es controvertido. Si bien existen guías para el SN en pacientes pediátricos con ECMO, en adultos no se cuenta con estos lineamientos para el uso, tipo, ruta y momento de la terapia nutricional. En pacientes críticamente enfermos es bien sabido que la nutrición enteral (NE) temprana es beneficiosa, no obstante existe la posibilidad de que en pacientes con ECMO la NE temprana condicione complicaciones gastrointestinales. Asimismo, no se han establecido metas calóricas, proteicas y dosis o tipos de micronutrimentos que usar para esta población en específico, siendo un reto para el clínico encargado de brindar el SN. Aunado a esto los pacientes con ECMO son algunos de los más gravemente enfermos en las unidades de cuidados intensivos, donde la desnutrición se asocia con una mayor morbilidad y mortalidad. En cuanto al uso de nutrición parenteral (NP), no se tiene descrito si implica riesgo de falla en el circuito al momento de introducir lípidos al oxigenador. Por lo anterior es imperativa una correcta evaluación e intervención nutricional específica, realizada por expertos en el tema para mejorar el pronóstico y la calidad de vida en esta población, siendo un objetivo primordial en los cuidados de los pacientes adultos que reciben terapia de ECMO.

Genetic Basis of Inflammatory Demyelinating Diseases of the Central Nervous System: Multiple Sclerosis and Neuromyelitis Optica Spectrum.

Demyelinating diseases alter myelin or the coating surrounding most nerve fibers in the central and peripheral nervous systems. The grouping of human central nervous system demyelinating disorders today includes multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) as distinct disease categories. Each disease is caused by a complex combination of genetic and environmental variables, many involving an autoimmune response. Even though these conditions are fundamentally similar, research into genetic factors, their unique clinical manifestations, and lesion pathology has helped with differential diagnosis and disease pathogenesis knowledge. This review aims to synthesize the genetic approaches that explain the differential susceptibility between these diseases, explore the overlapping clinical features, and pathological findings, discuss existing and emerging hypotheses on the etiology of demyelination, and assess recent pathogenicity studies and their implications for human demyelination. This review presents critical information from previous studies on the disease, which asks several questions to understand the gaps in research in this field.

Neurocognitive Psychiatric and Neuropsychological Alterations in Parkinson's Disease: A Basic and Clinical Approach.

The main histopathological hallmarks of Parkinson's disease (PD) are the degeneration of the dopaminergic neurons of the substantia nigra pars compacta and the loss of neuromelanin as a consequence of decreased dopamine synthesis. The destruction of the striatal dopaminergic pathway and blocking of striatal dopamine receptors cause motor deficits in humans and experimental animal models induced by some environmental agents. In addition, neuropsychiatric symptoms such as mood and anxiety disorders, hallucinations, psychosis, cognitive impairment, and dementia are common in PD. These alterations may precede the appearance of motor symptoms and are correlated with neurochemical and structural changes in the brain. This paper reviews the most crucial pathophysiology of neuropsychiatric alterations in PD. It is worth noting that PD patients have global task learning deficits, and cognitive functions are compromised in a way is associated with hypoactivation within the striatum, anterior cingulate cortex, and inferior frontal sulcus regions. An appropriate and extensive neuropsychological screening battery in PD must accurately assess at least five cognitive domains with some tests for each cognitive domain. This neuropsychological screening should consider the pathophysiological and clinical heterogeneity of cognitive dysfunction in PD.

Age of the onset of menarche and its complications: a literature review.

BACKGROUND: The menarche plays an important role in a woman's life, as its onset may generate the development of certain pathologies in the future. OBJECTIVES: To review the updated bibliography about risk factors related to the age of onset of menarche. SEARCH STRATEGY: A systematic search review of PubMed, Scopus, EMBASE, EBSCO-Host, Springer Link, and Clinical Key from November 2021 to May 2022. DATA COLLECTION AND ANALYSIS: From each article a descriptive summary organized by first author, year of publication, type of article, characteristics of the study, and results was extracted. The results of the different articles were compared before using them in the current literature review. MAIN RESULTS: A total of 15 824 articles were collected, from which 33 articles were used following the inclusion and exclusion criteria. It was found that an early estrogen stimulus triggers a predisposing factor for pathologies such as insulin resistance, asthma and short stature. In contrast, a late estrogenic stimulus generates low bone mineral density. CONCLUSIONS: The importance of menarche as a protective or triggering factor of pathologies helps us to implement preventive measures to avoid these future pathologies.

Dietary fish oil increases catalase activity in patients with probable Alzheimer's disease.

Introduction: Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the presence of neuritic plaques and neurofibrillary tangles that finally result in synaptic and neuronal loss. Oxidative stress accompanies pathological changes in AD. Objective: to assess the efficacy of dietary omega 3 polyunsaturated fatty acids supplementation on the levels of proteins oxidation, hydroperoxides and enzymatic activities of catalase and superoxide dismutase in AD patients. Methods: clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or placebo for one year. Oxidative stress markers were assessed in plasma using spectrophotometric methods. Results: carbonyl groups in proteins and hydroperoxides in plasma have similar values in both treatment groups at the beginning of the study. At six and 12 months of treatment, these values decreased significantly in the fish oil group, while in the placebo group no changes were observed in both oxidative stress markers. Catalase activity increased significantly at six and twelve months after treatment in patients treated with fish oil. While the superoxide dismutase activity was not modified in both study groups. Conclusions: patients who consume omega 3 polyunsaturated fatty acids at a stable dose of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) show decreased oxidation of proteins and lipids in plasma. In addition, an increase in catalase activity was detected. Thus, the presented data warrants further studies evaluating the antioxidant effect of omega 3 polyunsaturated fatty acids.

Introducción: Antecedentes: la enfermedad de Alzheimer (EA) es un trastorno neurodegenerativo caracterizado por la presencia de placas neuríticas y ovillos neurofibrilares que finalmente resultan en pérdida sináptica y neuronal. El estrés oxidativo acompaña los cambios patológicos en la EA. Objetivo: evaluar la eficacia de la suplementación dietética con ácidos grasos poliinsaturados omega 3 sobre los niveles de oxidación de proteínas, hidroperóxidos y actividades enzimáticas de catalasa y superóxido dismutasa en pacientes con EA. Métodos: ensayo clínico, controlado, aleatorizado, doble ciego. Los pacientes consumieron aceite de pescado o placebo durante un año. Los marcadores de estrés oxidativo se evaluaron en plasma mediante métodos espectrofotométricos. Resultados: los grupos carbonilo en proteínas e hidroperóxidos en plasma tuvieron valores similares en ambos grupos de tratamiento al inicio del estudio. A los seis y 12 meses de tratamiento estos valores disminuyeron significativamente en el grupo de aceite de pescado, mientras que en el grupo placebo no se observaron cambios en ambos marcadores. La actividad de catalasa aumentó significativamente a los seis y doce meses después del tratamiento en pacientes tratados con aceite de pescado; sin embargo, la actividad superóxido dismutasa no se modificó en ambos grupos de estudio. Conclusiones: los pacientes que consumieron los ácidos grasos poliinsaturados omega 3 a una dosis estable de ácido docosahexaenoico (DHA) y ácido eicosapentaenoico (EPA) muestran una oxidación reducida de proteínas y lípidos en plasma. Además, se detectó un aumento en la actividad de la catalasa. Por tanto, los datos presentados justifican más estudios que evalúen el efecto antioxidante de dichos ácidos grasos.