KLK7 expression in human tumors: a tissue microarray study on 13,447 tumors.

BACKGROUND: Kallikrein-related peptidase 7 (KLK7) is a chymotrypsin-like serine protease which is essential for the desquamation of corneocytes and thus plays a pivotal role in maintaining skin homeostasis. In cancer, KLK7 overexpression was suggested to represent a route for metastasis through cleavage of cell junction and extracellular matrix proteins of cancer cells. METHODS: To comprehensively determine KLK7 protein expression in normal and neoplastic tissues, a tissue microarray containing 13,447 samples from 147 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. RESULTS: KLK7 positivity was found in 64 of 147 tumor categories, including 17 tumor categories with at least one strongly positive case. The highest rate of KLK7 positivity was found in squamous cell carcinomas from various sites of origin (positive in 18.1%-63.8%), ovarian and endometrium cancers (4.8%-56.2%), salivary gland tumors (4.8%-13.7%), bilio-pancreatic adenocarcinomas (20.0%-40.4%), and adenocarcinomas of the upper gastrointestinal tract (3.3%-12.5%). KLK7 positivity was linked to nodal metastasis (p = 0.0005), blood vessel infiltration (p = 0.0037), and lymph vessel infiltration (p < 0.0001) in colorectal adenocarcinoma, nodal metastasis in hepatocellular carcinoma (p = 0.0382), advanced pathological tumor stage in papillary thyroid cancer (p = 0.0132), and low grade of malignancy in a cohort of 719 squamous cell carcinomas from 11 different sites of origin (p < 0.0001). CONCLUSIONS: These data provide a comprehensive overview on KLK7 expression in normal and neoplastic human tissues. The prognostic relevance of KLK7 expression and the possible role of KLK7 as a drug target need to be further investigated.

Hypoxia effects on glioblastoma progression through YAP/TAZ pathway regulation.

The resistance of glioblastomas (GBM) to standard therapies poses a clinical challenge with limited survival despite interventions. The tumor microenvironment (TME) orchestrates GBM progression, comprising stromal and immune cells and is characterized by extensive hypoxic regions. Hypoxia activates the hypoxia-inducible factor 1 alpha (HIF-1α) pathway, interacting with the Hippo pathway (YAP/TAZ) in crucial cellular processes. We discuss here the related signaling crosstalk between YAP/TAZ and regions of hypoxia in the TME with particular attention on the MST1/2 and LATS1/2-regulated YAP/TAZ activation, impacting cell proliferation, invasion, and stemness. Moreover, the hypoxia-YAP/TAZ axis influence on angiogenesis, stem cells, and metabolic regulators is defined. By reviewing extracellular matrix alterations activation of YAP/TAZ, modulation of signaling pathways we also discuss the significance of spatial constraints and epigenetic modifications contribution to GBM progression, with potential therapeutic targets in YAP/TAZ-mediated gene regulation. Comprehensive understanding of the hypoxia-Hippo pathway-TME interplay offers insights for novel therapeutic strategies, aiming to provide new directions for treatment.

Design and functional characterization of Salmo salar TLR5 agonist peptides derived from high mobility group B1 acidic tail.

Toll-like receptor 5 (TLR5) responds to the monomeric form of flagellin and induces the MyD88-depending signaling pathway, activating proinflammatory transcription factors such as NF-κB and the consequent induction of cytokines. On the other hand, HMGB1 is a highly conserved non-histone chromosomal protein shown to interact with and activate TLR5. The present work aimed to design and characterize TLR5 agonist peptides derived from the acidic tail of Salmo salar HMGB1 based on the structural knowledge of the TLR5 surface using global molecular docking platforms. Peptide binding poses complexed on TLR5 ectodomain model from each algorithm were filtrated based on docking scoring functions and predicted theoretical binding affinity of the complex. Circular dichroism spectra were recorded for each peptide selected for synthesis. Only intrinsically disordered peptides (6W, 11W, and SsOri) were selected for experimental functional assay. The functional characterization of the peptides was performed by NF-κB activation assays, RT-qPCR gene expression assays, and Piscirickettsia salmonis challenge in SHK-1 cells. The 6W and 11W peptides increased the nuclear translation of p65 and phosphorylation. In addition, the peptides induced the expression of genes related to the TLR5 pathway activation, pro- and anti-inflammatory response, and differentiation and activation of T lymphocytes towards phenotypes such as TH1, TH17, and TH2. Finally, it was shown that the 11W peptide protects immune cells against infection with P. salmonis bacteria. Overall, the results indicate the usefulness of novel peptides as potential immunostimulants in salmonids.

Emotionally expressive interdependence in Latin America: Triangulating through a comparison of three cultural zones.

Evidence suggests that Latin Americans display elevated levels of emotional expressivity and positivity. Here, we tested whether Latin Americans possess a unique form of interdependence called expressive interdependence, characterized by the open expression of positive emotions related to social engagement (e.g., feelings of closeness to others). In Study 1, we compared Latin Americans from Chile and Mexico with European Americans in the United States, a group known to be highly independent. Latin Americans expressed positive socially engaging emotions, particularly in response to negative events affecting others, whereas European Americans favored positive socially disengaging emotions, such as pride, especially in response to personally favorable circumstances. Study 2 replicated these findings with another group of Latin Americans from Colombia and European Americans in the United States. Study 2 also included Japanese in Japan, who expressed positive emotions less than Latin and European Americans. However, Japanese displayed a higher tendency to express negative socially engaging emotions, such as guilt and shame, compared to both groups. Our data demonstrate that emotional expression patterns align with overarching ethos of interdependence in Latin America and Japan and independence among European Americans. However, Latin Americans and Japanese exhibited different styles of interdependence. Latin Americans were expressive of positive socially engaging emotions, whereas Japanese were less expressive overall. Moreover, when Japanese expressed emotions, they emphasized negative socially engaging emotions. Implications for theories of culture and emotion are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney.

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-ß-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-ß-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage.

Dietoterapia en artritis reumatoide: Revisión de la evidencia

La artritis reumatoide (RA), es una enfermedad crónica reumática, caracterizada por un daño articular progresivo y manifestaciones extraarticulares, que pueden desencadenar una discapacidad. La etiología de las patologías autoinmunes, incluyendo la RA, es compleja, abarcando factores de tipo genético, hormonal, dietarios y ambientales. Sin embargo, los mecanismos fisiológicos por los que estos agentes contribuyen a la patogenia aún no están definidos completamente. Estudios sugieren un impacto de la disbiosis del microbioma intestinal en la patogénesis de la artritis reumatoide sugiriendo también la alteración de la permeabilidad intestinal como una posible causa. Esta se puede relacionar con patrones dietarios influyentes en la prevención de esta patología así como una propuesta de tratamiento complementario al manejo farmacológico tradicional, considerando el riesgo aumentado de estos pacientes de desarrollar síndrome metabólico y "caquexia reumatoide", una acumulación de tejido adiposo acompañado de una disminución de tejido muscular debido a los cambios catabólicos debido a la inflamación crónica e inactividad física a consecuencia de las dificultades motoras. Ante evidencia reciente que propone patrones de alimentación e intervenciones dietarias como tratamiento complementario a la terapia farmacológica en el manejo de la RA, la siguiente revisión narrativa cualitativa se propone revisar la efectividad de intervenciones propuestas en términos de dolor y actividad de enfermedad, encontrando dentro de la amplia heterogeneidad de intervenciones propuestas, aquellos patrones dietéticos con efecto modulador de la microbiota intestinal como la dieta mediterránea y sus variaciones en contexto de la promoción de un estilo de vida serían positivas como terapia complementaria a esta patología.

Rheumatoid arthritis (RA) is a chronic rheumatic disease characterised by progressive joint damage and extra-articular manifestations that can lead to disability. The aetiology of autoimmune diseases, including RA, is complex, involving genetic, hormonal, dietary, and environmental factors. However, the physiological mechanisms by which these agents contribute to pathogenesis have not yet been fully defined. More recent studies suggest an impact of gut microbiome dysbiosis on the pathogenesis of autoimmune diseases in both animal and human models, including rheumatoid arthritis, also suggesting altered intestinal permeability as a possible cause. This modification of the gut microbiome may be related to influential diet patterns in the prevention of this pathology, as well as a proposed complementary treatment to traditional pharmacological treatment, also considering the increased risk for these patients of developing metabolic syndrome and "rheumatoid cachexia", an accumulation of adipose tissue accompanied by a decrease in muscle tissue due to catabolic changes due to chronic inflammation and physical inactivity as a consequence of motor difficulties in RA. With the emergence of recent evidence proposing dietary interventions and eating patterns as adjunctive treatment to drug therapy in the management of RA, the following narrative qualitative review proposes reviewing recent evidence on the effectiveness of various proposed dietary interventions in the treatment of rheumatoid arthritis in terms of pain and disease activity, finding between a high heterogeneity of proposed interventions, those dietary patterns with modulating effect on the gut microbiome as Mediterranean diet and its variations in the context of promoting a healthy lifestyle would be positive as a complementary therapy for this disease.

Glomerulonefritis aguda posinfecciosa asociada al virus de la gripe B y enterovirus / Postinfectious acute glomerulonephritis associated to influenza B virus and enterovirus

La glomerulonefritis aguda posinfecciosa (GNAPI) es una lesión inflamatoria con afectación principal del glomérulo generada por una infección extrarrenal. Su patogenia es inmune, desencadenada por gran variedad de gérmenes: bacterias, virus y hongos. La causa más frecuente es la glomerulonefritis posestreptocócica (GNAPE). El caso que presentamos fue causado por gripe B y enterovirus, agentes etiológicos de presentación poco frecuente, con manifestación clínica similar a una glomerulonefritis posestreptocócica. Concluimos que, ante una clínica de síndrome nefrítico, se deben tener en cuenta los antecedentes víricos, para hacer un diagnóstico precoz (AU)

Acute post-infectious glomerulonephritis (APIGN) is an inflammatory lesion with main involvement of the glomerulus triggered by an extrarenal infection. Its pathogenesis is immune, triggered by a wide variety of germs: bacteria, viruses and fungi. The most common cause is poststreptococcal glomerulonephritis (PSAGN). The case that we present was associated to influenza B and enterovirus, etiological agents of infrequent presentation, with clinical manifestations similar to post-streptococcal glomerulonephritis. We conclude that, when faced with a nephritic syndrome clinic, the viral history should be taken into account to make an early diagnosis. (AU)

Results of VOICE: a global survey of disease-specific knowledge and perspectives of real-world patients with CLL.

The Virtual Opinions poll Independent Centered on CLL patients' Experience (VOICE) evaluated patients' knowledge about chronic lymphocytic leukemia (CLL), their perspectives on diagnosis and treatment, and their unmet needs. Clinicians and patient advocacy group representatives developed and distributed the survey from March through December 2022 in 12 countries, and 377 patients with ≥1 line of previous CLL treatment responded from Europe, Latin America, the United States, Australia, Egypt, and Turkey. A majority of them (90%; 336/374) relied on their physicians for information regarding CLL and treatment. If at high risk, respondents prefer oral medications to intravenous (78%; 232/296), fixed duration treatment over treatment until progression (69%; 185/270), outpatient over inpatient treatments (91%; 257/283). Over three-fourths of respondents (78%; 286/368) wanted to be involved in treatment decisions, but a minority actually participated (44%; 138/313). COVID-19 vaccinations were widely available (97%; 273/281), but one-fifth (19%; 63/331) were unaware that CLL increases vulnerability to infections. Most patients' physicians explained their treatment options (84%; 297/355), and 90% (271/301) understood their treatment. Notably, >10% would continue treatment normally if they experienced cardiac problems or arrhythmias, whereas 23% would consider stopping treatment if they developed skin cancer. Treatment-associated side effects affected 27% to 43% of patients. These results in a global patient population highlight gaps in patients' knowledge of risk groups, their susceptibility to infections including COVID, and the side effects of common treatments. Such knowledge can guide the appropriate targeting of patient education initiatives by clinicians, advocates, and policymakers.

New Benzodihydrofuran Derivatives Alter the Amyloid ß Peptide Aggregation: Strategies To Develop New Anti-Alzheimer Drugs.

Alzheimer's disease is a neurodegenerative disorder that is the leading cause of dementia in elderly patients. Amyloid-ß peptide (1-42 oligomers) has been identified as a neurotoxic factor, triggering many neuropathologic events. In this study, 15 chalcones were synthesized employing the Claisen-Schmidt condensation reaction, starting from a compound derived from fomannoxine, a natural benzodihydrofuran whose neuroprotective activity has been proven and reported, and methyl aromatic ketones with diverse patterns of halogenated substitution. As a result, chalcones were obtained, with good to excellent reaction yields from 50 to 98%. Cytotoxicity of the compounds was assessed, and their cytoprotective effect against the toxicity associated with Aß was evaluated on PC-12 cells. Out of the 15 chalcones obtained, only the 4-bromo substituted was cytotoxic at most tested concentrations. Three synthesized chalcones showed a cytoprotective effect against Aß toxicity (over 37%). The 2,4,5-trifluoro substituted chalcone was the most promising series since it showed a cytoprotective impact with more than 60 ± 5% of recovery of cellular viability; however, 3-fluoro substituted compound also exhibited important values of recovery (50 ± 6%). The fluorine substitution pattern was shown to be more effective for cytoprotective activity. Specifically, substitution with fluorine in the 3,5-positions turned out to be particularly effective for cytoprotection. Furthermore, fluorinated compounds inhibited the aggregation rate of Aß, suggesting a dual effect that can be the starting point of new molecules with therapeutic potential.

Análisis de impacto presupuestario de un banco de tejido óseo en un servicio de salud de Chile

El objetivo de la presente investigación fue el realizar un análisis de impacto presupuestario del injerto óseo en un servicio regional de salud chileno en base a un banco de tejido óseo. Se realizó un estudio epidemiológico preliminar para obtener los datos necesarios para el análisis, específicamente sobre procedimientos de injerto óseo en un servicio de salud local del Servicio Salud Concepción (SSC). Esta búsqueda evidenció un total de 6.252 cc de injertos óseos con un costo total de USD $156.000 por año. Se encontró una capacidad potencial de 302 ± 16 cabezas femorales recuperadas por año de los procedimientos de reemplazo total de cadera y que un banco de tejido óseo puede generar un ahorro de USD $145.000 en los costos hospitalarios por año. Este análisis evidenció que en un servicio de salud representativo de Chile existe una dependencia de sustitutos óseos importados y autoinjertos que pueden ser suplidos de manera sustentable con un banco de tejido óseo basado en donaciones de cabezas femorales bajo la legislación vigente de la autoridad sanitaria chilena.

This research aimed to analyze the costs of bone grafting through a bone tissue bank in a Chilean regional health service. Methods: First, we developed a preliminary epidemiological study to obtain the necessary data for the analysis, specifically on bone graft procedures in a local health service (Servicio Salud Concepción). Next, we performed a budget impact analysis. Results: We analyzed a total of 6,252 cc of bone grafts, with a total cost of USD$156,000 per year. We found a potential recovering capacity of 302 ± 16 femoral heads per year from the total hip replacement procedures. Based on these results, bone tissue banks could save USD$145,000 hospital costs annually. Studying a representative health service from Chile, this analysis revealed a dependency on imported bone substitutes and autografts. These requirements can be supplied sustainably by a bone tissue bank based on donations of femoral heads under the current legislation of the Chilean health authority.

Preparation of a probiotic quinoa beverage by enzymatic hydrolysis of its starches and subsequent lactic acid fermentation / Elaboración de una bebida probiótica de quinua por hidrólisis enzimática de sus almidones y posterior fermentación ácido láctica

Background: The concern about consuming healthy foods has increased in recent years. Not only are they expected to comply with essential feeding functions, but they also provide health benefits. Probiotics are one of the main functional components expected to be present in functional foods and beverages. They provide many health benefits and stand out due to their metabolic capacities and adaptability to different habitats. In addition, Quinoa seeds contain valuable quantities of quality protein and nutritional values of carbohydrates, proteins, fats, fibers, and mineral substances for which they are considered an ideal dietary alternative. Objectives: This research aimed to elaborate on a probiotic quinoa beverage, which combines the effect of enzymatic hydrolysis of the starches obtained from its seeds with lactic acid fermentation using probiotic cultures, seeking to enhance its nutritional properties and converting it into a functional beverage. Methods: For this, fermentations were carried out in three different concentrations of probiotic cultures (inoculum): 10%, 5%, 1%, and three other different fermentation times: 8, 10, and 12 hours. pH, Total titrable acidity expressed as lactic acid (%), reducing sugars, and soluble solids were measured. After that, the beverage was formulated with honey, carob, preservatives, and mango flavoring. Results: Statistical analysis indicated optimal conditions were achieved with 10% probiotic cultures and 10 hours of fermentation. The microbiological analysis confirmed the presence of probiotic microorganisms at a concentration of 108 CFU/mL. Proximal analysis indicated that the composition contained 84.6 Kcal, 19.3 g of carbohydrates, and 1.4 g of protein per 100 g of beverage. Conclusions: The probiotic quinoa beverage was produced and can be considered in the group of plant-based foods, as well as a functional beverage, since the probiotic cultures it contains contribute to maintaining the intestinal microbiota and prevent the onset of chronic diseases.

Antecedentes: La preocupación por el consumo alimentos saludables ha aumentado en los últimos años. No solo se espera que cumplan con las funciones esenciales de alimentación, sino que también brinden beneficios para la salud. Los probióticos son uno de los principales componentes funcionales que se espera que estén presentes en los alimentos y bebidas funcionales. Aportan múltiples beneficios para la salud y destacan por sus capacidades metabólicas y adaptabilidad a diferentes hábitats. Además, las semillas de quinua contienen valiosas cantidades de proteína de notable calidad, valores nutricionales de carbohidratos, proteínas, grasas, fibras y sustancias minerales por lo que se consideran una alternativa dietética ideal. Objetivos: Esta investigación tuvo como objetivo elaborar una bebida probiótica de quinua, que combina el efecto de la hidrólisis enzimática de los almidones obtenidos de sus semillas con la fermentación láctica utilizando cultivos probióticos, buscando potenciar sus propiedades nutricionales y convertirla en una bebida funcional. Métodos: Para ello se realizaron fermentaciones en tres concentraciones diferentes de cultivos probióticos (inóculo): 10%, 5%, 1%, y tres distintos tiempos de fermentación: 8, 10 y 12 horas. Se midió pH, Acidez titulable total expresada como ácido láctico (%), azúcares reductores y sólidos solubles. Posteriormente, se formuló la bebida con miel, algarrobina, conservantes y saborizante de mango. Resultados: El análisis estadístico indicó que se lograron condiciones óptimas con 10% de cultivos probióticos y 10 horas de fermentación. El análisis microbiológico confirmó la presencia de microorganismos probióticos a una concentración de 108 UFC/mL. El análisis proximal indicó que la composición contenía 84,6 Kcal, 19,3 g de carbohidratos y 1,4 g de proteína por 100 g de bebida. Conclusiones: la bebida probiótica de quinua fue elaborada y puede ser considerada en el grupo de alimentos de origen vegetal, así como una bebida funcional, ya que los cultivos probióticos que contiene contribuyen al mantenimiento de la microbiota intestinal y previenen la aparición de enfermedades crónicas.

Neuroprotective Properties of Eudesmin on a Cellular Model of Amyloid-ß Peptide Toxicity.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. One of the hallmarks in AD is amyloid-ß peptide (Aß) accumulation, where the soluble oligomers of Aß (AßOs) are the most toxic species, deteriorating the synaptic function, membrane integrity, and neuronal structures, which ultimately lead to apoptosis. Currently, there are no drugs to arrest AD progression, and current scientific efforts are focused on searching for novel leads to control this disease. Lignans are compounds extracted from conifers and have several medicinal properties. Eudesmin (Eu) is an extractable lignan from the wood of Araucaria araucana, a native tree from Chile. This metabolite has shown a range of biological properties, including the ability to control inflammation and antibacterial effects. OBJECTIVE: In this study, the neuroprotective abilities of Eu on synaptic failure induced by AßOs were analyzed. METHODS: Using neuronal models, PC12 cells, and in silico simulations we evaluated the neuroprotective effect of Eu (30 nM) against the toxicity induced by AßOs. RESULTS: In primary cultures from mouse hippocampus, Eu preserved the synaptic structure against AßOs toxicity, maintaining stable levels of the presynaptic protein SV2 at the same concentration. Eu also averted synapsis failure from the AßOs toxicity by sustaining the frequencies of cytosolic Ca2+ transients. Finally, we found that Eu (30 nM) interacts with the Aß aggregation process inducing a decrease in AßOs toxicity, suggesting an alternative mechanism to explain the neuroprotective activity of Eu. CONCLUSION: We believe that Eu represents a novel lead that reduces the Aß toxicity, opening new research venues for lignans as neuroprotective agents.

[Effect of the forward head syndrome in the development of temporomandibular disorders]. / Efecto del síndrome de cabeza adelantada en el desarrollo de trastornos temporomandibulares.

Bad habits, such as poor posture during the use of technological devices, poor abdominal control and oral breathing pattern can lead to a forward head position, which has important implications for the entire future of the individual, especially at the stomatognathic system. There is a strong association between temporomandibular disorders and forward head syndrome. Where the muscular component is the main affected, with the appearance of more trigger points at the level of the sternocleidomastoid muscles, upper trapezius, rectus capitis posterior and upper oblique capitis. Degenerative changes in the temporomandibular joint have been observed, but evidence is still lacking to ensure that Forward Head Syndrome is the etiological factor.

[Budget impact analysis of the implementation of a bone tissue bank in a Chilean health service]. / Análisis de impacto presupuestario de un banco de tejido óseo en un servicio de salud de Chile.

This research aimed to analyze the costs of bone grafting through a bone tissue bank in a Chilean regional health service. Methods: First, we developed a preliminary epidemiological study to obtain the necessary data for the analysis, specifically on bone graft procedures in a local health service (Servicio Salud Concepción). Next, we performed a budget impact analysis. Results: We analyzed a total of 6,252 cc of bone grafts, with a total cost of USD$156,000 per year. We found a potential recovering capacity of 302 ± 16 femoral heads per year from the total hip replacement procedures. Based on these results, bone tissue banks could save USD$145,000 hospital costs annually. Studying a representative health service from Chile, this analysis revealed a dependency on imported bone substitutes and autografts. These requirements can be supplied sustainably by a bone tissue bank based on donations of femoral heads under the current legislation of the Chilean health authority.

Effect of conservative treatment of pelvic floor dysfunctions in women: An umbrella review.

OBJECTIVE: Due to their high worldwide prevalence, pelvic floor dysfunctions (PFD's) are a public health problem. There is high heterogeneity in the types and effectiveness of conservative treatment. The objective was to analyze the scientific evidence on conservative treatment of PFDs in women. METHODS: Umbrella review, covering MEDLINE (1950-2019), Scopus (1960-2019), Web of Science (1980-2019), and Cochrane Library (2000-2019). Inclusion criterion: review on conservative treatments about pelvic floor disorders in the adult women, in Spanish or English; exclusion criterion: studies about other urological, gynecological, and coloproctological pathologies, among others. RESULTS: Thirty-two reviews (2000-2019) and 12 meta-analyses were included. 53.1% showed an improvement on urinary incontinence. Pelvic floor muscle training worked on 70.6% of them, followed by electrical stimulation and estrogen (11.7%), and weight loss (5.9%). 6.3% of reviews and meta-analyses fulfilled all items in PRISMA, and 93.7% of them fulfilled more than 60% of the checklist. 60% de los ítems. CONCLUSIONS: PFMT and weight loss are the most effective treatments for UI, but there is no evidence for other PFDs. The methodological quality of conservative treatments must be improved for a more effective treatment of PFDs in women. Pelvic floor muscle training and weight loss are the most effective treatments for urinary incontinence. Only 6.3% of the reviews fulfilled all PRISMA ítems.

Microglial Activation Modulated by P2X4R in Ischemia and Repercussions in Alzheimer's Disease.

There are over 80 million people currently living who have had a stroke. The ischemic injury in the brain starts a cascade of events that lead to neuronal death, inducing neurodegeneration which could lead to Alzheimer's disease (AD). Cerebrovascular diseases have been suggested to contribute to AD neuropathological changes, including brain atrophy and accumulation of abnormal proteins such as amyloid beta (Aß). In patients older than 60 years, the incidence of dementia a year after stroke was significantly increased. Nevertheless, the molecular links between stroke and dementia are not clearly understood but could be related to neuroinflammation. Considering that activated microglia has a central role, there are brain-resident innate immune cells and are about 10-15% of glial cells in the adult brain. Their phagocytic activity is essential for synaptic homeostasis in different areas, such as the hippocampus. These cells polarize into phenotypes or subtypes: the pro-inflammatory M1 phenotype, or the immunosuppressive M2 phenotype. Phenotype M1 is induced by classical activation, where microglia secrete a high level of pro- inflammatory factors which can cause damage to the surrounding neuronal cells. Otherwise, M2 phenotype is the major effector cell with the potential to counteract pro-inflammatory reactions and promote repair genes expression. Moreover, after the classical activation, an anti-inflammatory and a repair phase are initiated to achieve tissue homeostasis. Recently it has been described the concepts of homeostatic and reactive microglia and they had been related to major AD risk, linking to a multifunctional microglial response to Aß plaques and pathophysiology markers related, such as intracellular increased calcium. The upregulation and increased activity of purinergic receptors activated by ADP/ATP, specially P2X4R, which has a high permeability to calcium and is mainly expressed in microglial cells, is observed in diseases related to neuroinflammation, such as neuropathic pain and stroke. Thus, P2X4R is associated with microglial activation. P2X4R activation drives microglia motility via the phosphatidylinositol-3-kinase (PI3K)/Akt pathway. Also, these receptors are involved in inflammatory-mediated prostaglandin E2 (PGE2) production and induce a secretion and increase the expression of BDNF and TNF-α which could be a link between pathologies related to aging and neuroinflammation.

Consenso de leucemia mieloide aguda en México / Mexican consensus in acute myeloid leukemia in Mexico

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Abstract Acute myeloid leukemia (AML) comprises a heterogeneous group of hematopoietic cell neoplasms of myeloid lineage that arise from the clonal expansion of their precursors in the bone marrow, interfering with cell differentiation, leading to a syndrome of bone marrow failure. AML is a consequence of genetic and epigenetic changes (point mutations, gene rearrangements, deletions, amplifications, and arrangements in epigenetic changes that influence gene expression) in hematopoietic precursor cells, which create a clone of abnormal cells that are capable of proliferating but cannot differentiate into mature hematopoietic cells or undergo programmed cell death. The diagnosis requires more than 20% myeloid blasts in the bone marrow and certain cytogenic abnormalities. Treatment will depend on age, comorbidities, and cytogenetic risk among the most frequent.