Empatía, agresividad y perdón en contextos de vulnerabilidad, hostilidad y seguridad en niños y adolescentes

Introducción: El objetivo de este artículo fue identificar las variables que mejor predicen las medidas de agresión, empatía y perdón, como también las principales diferencias en contextos vulnerables, hostiles y seguros, en una muestra de niños, niñas y adolescentes pertenecientes a una población vulnerable. Método: se realizó un estudio cuantitativo transversal con una muestra no probabilística incidental de 85 participantes, se emplearon medidas psicométricas para la empatía, agresión y perdón. Los participantes fueron convocados en una fundación de atención a víctimas para realizar una entrevista y aplicar el test. Resultados: Se encontraron efectos estadísticamente significativos entre las variables del modelo verificado, donde la empatía predice la agresión en el contexto hostil, pero no en el vulnerable y seguro. A su vez, la empatía predice el perdón en los contextos vulnerables y seguros, y la agresión predice el perdón en el modelo hostil, pero no es significativo su efecto en el contexto vulnerable y seguro. Además, la empatía tiene un papel clave en la comprensión del perdón, dado que se asocia a conductas agresivas en los contextos de hostilidad, mientras que un modelo de perdón debería ser diferencial en estos contextos. Conclusiones: Los hallazgos de este estudio brindan evidencia empírica que sustenta la importancia de la implementación de estrategias para mejorar las habilidades relacionadas con la empatía en niños y adolescentes, desde la perspectiva de la educación para la paz y el perdón. Además, se demostró que los aspectos como el clima familiar, las vulnerabilidades de los contextos de riesgo y la misma cultura, pueden determinar el desarrollo de habilidades socioemocionales que favorecen el perdón, empatía y otras capacidades interpersonales.

Introduction: The aim of this study was to identify the variables that best predict measures of aggression, empathy, and forgiveness, as well as the main differences in vulnerable, hostile and safe contexts, in a sample of children and adolescents belonging to a vulnerable population. Method: A cross-sectional quantitative study was conducted with a non-probabilistic incidental sample of 85 participants. Psychometric measures of empathy, aggression, and forgiveness were used. The participants were invited to a victim assistance foundation for an interview and test application. Results: Statistically significant effects were found among the variables in the verified model, where empathy predicts aggression in the hostile context, but not in the vulnerable and safe context. In turn, empathy predicts forgiveness in the vulnerable and safe contexts, and aggression predicts forgiveness in the hostile model, but its effect in the vulnerable and safe context is not significant. Furthermore, empathy plays a key role in understanding forgiveness, given that it is associated with aggressive behaviors in the hostile contexts, whereas a forgiveness model should be differential in these contexts. Conclusions: The findings of this study provide empirical evidence that supports the importance of implementing strategies to improve empathy-related skills in children and adolescents, from the perspective of peace education and forgiveness. In addition, it was shown that aspects such as family climate, vulnerabilities of risk contexts and culture itself, can determine the development of socioemotional skills that favor forgiveness, empathy, and other interpersonal skills.

Impact of Gastrointestinal Digestion In Vitro Procedure on the Characterization and Cytotoxicity of Reduced Graphene Oxide.

The growing interest in graphene derivatives is a result of their variety of applications in many fields. Due to their use, the oral route could be a potential way of entrance for the general population. This work assesses the biotransformation of reduced graphene oxide (rGO) after an in vitro digestion procedure (mouth, gastric, intestinal, and colon digestion), and its toxic effects in different cell models (HepG2, Caco-2, and 3D intestinal model). The characterization of rGO digestas evidenced the agglomeration of samples during the in vitro gastrointestinal (g.i.) digestion. Internalization of rGO was only evident in Caco-2 cells exposed to the colonic phase and no cellular defects were observed. Digestas of rGO did not produce remarkable cytotoxicity in any of the experimental models employed at the tested concentrations (up to 200 µg/mL), neither an inflammatory response. Undigested rGO has shown cytotoxic effects in Caco-2 cells, therefore these results suggest that the digestion process could prevent the systemic toxic effects of rGO. However, additional studies are necessary to clarify the interaction of rGO with the g.i. tract and its biocompatibility profile.

In vitro safety assessment of reduced graphene oxide in human monocytes and T cells.

Considering the increase in the use of graphene derivatives in different fields, the environmental and human exposure to these materials is likely, and the potential consequences are not fully elucidated. This study is focused on the human immune system, as this plays a key role in the organism's homeostasis. In this sense, the cytotoxicity response of reduced graphene oxide (rGO) was investigated in monocytes (THP-1) and human T cells (Jurkat). A mean effective concentration (EC50-24 h) of 121.45 ± 11.39 µg/mL and 207.51 ± 21.67 µg/mL for cytotoxicity was obtained in THP-1 and Jurkat cells, respectively. rGO decreased THP-1 monocytes differentiation at the highest concentration after 48 h of exposure. Regarding the inflammatory response at genetic level, rGO upregulated IL-6 in THP-1 and all cytokines tested in Jurkat cells after 4 h of exposure. At 24 h, IL-6 upregulation was maintained, and a significant decrease of TNF-α gene expression was observed in THP-1 cells. Moreover, TNF-α, and INF-γ upregulation were maintained in Jurkat cells. With respect to the apoptosis/necrosis, gene expression was not altered in THP-1 cells, but a down regulation of BAX and BCL-2 was observed in Jurkat cells after 4 h of exposure. These genes showed values closer to negative control after 24 h. Finally, rGO did not trigger a significant release of any cytokine at any exposure time assayed. In conclusion, our data contributes to the risk assessment of this material and suggest that rGO has an impact on the immune system whose final consequences should be further investigated.

Immunomodulatory Effects of Cylindrospermopsin in Human T Cells and Monocytes.

Cylindrospermopsin (CYN) is a cyanotoxin with an increasing occurrence, and therefore it is important to elucidate its toxicity profile. CYN has been classified as a cytotoxin, although the scientific literature has already revealed that it affects a wide range of organs and systems. However, research on its potential immunotoxicity is still limited. Thus, this study aimed to evaluate the impact of CYN on two human cell lines representative of the immune system: THP-1 (monocytes) and Jurkat (lymphocytes). CYN reduced cell viability, leading to mean effective concentrations (EC50 24 h) of 6.00 ± 1.04 µM and 5.20 ± 1.20 µM for THP-1 and Jurkat cells, respectively, and induced cell death mainly by apoptosis in both experimental models. Moreover, CYN decreased the differentiation of monocytes to macrophages after 48 h of exposure. In addition, an up-regulation of the mRNA expression of different cytokines, such as interleukin (IL) 2, IL-8, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), was also observed mainly after 24 h exposure in both cell lines. However, only an increase in TNF-α in THP-1 supernatants was observed by ELISA. Overall, these results suggest the immunomodulatory activity of CYN in vitro. Therefore, further research is required to evaluate the impact of CYN on the human immune system.

Differential optineurin expression controls TGFß signaling and is a key determinant for metastasis of triple negative breast cancer.

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype to treat due to its aggressive characteristics and low response to the existing clinical therapies. Distant metastasis is the main cause of death of TNBC patients. Better understanding of the mechanisms underlying TNBC metastasis may lead to new strategies of early diagnosis and more efficient treatment. In our study, we uncovered that the autophagy receptor optineurin (OPTN) plays an unexpected role in TNBC metastasis. Data mining of publicly available data bases revealed that the mRNA level of OPTN in TNBC patients positively correlates with relapse free and distance metastasis free survival. Importantly, in vitro and in vivo models demonstrated that OPTN suppresses TNBC metastasis. Mechanistically, OPTN inhibited the pro-oncogenic transforming growth factor-ß (TGFß) signaling in TNBC cells by interacting with TGFß type I receptor (TßRI) and promoting its ubiquitination for degradation. Consistent with our experimental findings, the clinical TNBC samples displayed a negative correlation between OPTN mRNA expression and TGFß gene response signature and expression of proto-typic TGFß target genes. Altogether, our study demonstrates that OPTN is a negative regulator for TGFß receptor/SMAD signaling and suppresses metastasis in TNBC.

Factors Associated with Health Care Providers' Preference for Forgoing an Oral Lead-In Phase When Initiating Long-Acting Injectable Cabotegravir and Rilpivirine in the SOLAR Clinical Trial.

Cabotegravir and rilpivirine long-acting (LA) antiretroviral therapy (ART) demonstrated similar safety and efficacy in maintaining viral suppression among participants switching from daily oral to LA ART in the Extension Phase of the FLAIR trial. The Phase IIIb SOLAR study comparing efficacy and safety of daily oral versus LA ART every 2 months allowed participants and health care providers (HCPs) to choose an oral lead-in (OLI) before LA initiation or proceed by immediately starting with injections (SWI). We conducted an online survey among SOLAR HCPs (n = 110) in 13 countries to assess reasons for choosing OLI versus SWI. Logistic regression was used to identify factors influencing this decision. Thirty-two percent of HCPs reported a future preference to use OLI, whereas 54% reported a future preference for SWI. HCPs had greater odds of reporting future intentions for SWI if they were from Continental Europe versus North America [adjusted odds ratio (aOR): 3.83, p < 0.05], from sites with a greater number of participants who initiated LA ART without OLI (aOR: 1.56, p < 0.01), and those who reported comfort with the medication safety profile (aOR: 6.39, p < 0.01). HCPs who participated in LA ART trials before SOLAR had decreased odds of reporting a preference for SWI compared to those with no prior LA ART trial experience (aOR: 0.11; p < 0.01). Results indicated higher intentions to SWI over OLI among HCPs initiating participants on LA ART. A major factor associated with SWI was provider comfort with safety data, reinforcing the role of continued training regarding an SWI approach.

Genotoxicity evaluation of graphene derivatives by a battery of in vitro assays.

The interest of graphene materials has increased markedly in the recent years for their promising applications in many fields as food packing. These new applications have caused some concern regarding their safety for consumers since the intake of these materials may increase. In this sense, a battery of in vitro test is required before its use as a food contact material. Then, the aim of this study was to assess the potential mutagenicity and genotoxicity of graphene oxide (GO) and reduced-graphene oxide (rGO) following the recommendations of the European Food Safety Authority (EFSA). Thus, the mouse lymphoma assay (MLA) and the micronucleus test (MN) were performed in L5178YTk ± cells, and the Caco-2 cells were used for the standard and modified comet assays. The results indicated that GO (0-250 µg/mL) was not mutagenic in the MLA. However, rGO revealed mutagenic activity from 250 µg/mL and 125 µg/mL after 4h and 24h of exposure, respectively. In the MN test, negative results were obtained for both compounds at the concentrations assayed (0-250 µg/mL) for GO/rGO. Moreover, no DNA strand breaks, or oxidative DNA damage were detected in Caco-2 cells exposed to GO (0-250 µg/mL) and rGO (0-176.3 µg/mL for 24h and 0-166.5 µg/mL for 48h). Considering the mutagenic potential of rGO observed further investigation is needed to describe its toxic profile.

Coping with the COVID-19 Pandemic: Comparative Case Study of Coping and Resilience in Children From Different Educational Contexts in Colombia.

In 2020, humanity experienced one of the most complex situations in history: The COVID-19 pandemic, which caused significant social, economic, and educational consequences. Nevertheless, countries and people generally survived. Why? Resilience and the ability to cope are fundamental elements in human, community, and national survival. This study compared the situations experienced by six children from different social and educational backgrounds in Colombia during the COVID 19 pandemic using a collective analysis of cases. Interviews with children's families, as well as observations of the participants and a narrative instrument from the BASIC Ph resiliency model (Lahad, 2016) are used to describe the context, the promoting factors of resilience, and the so-called coping "channels" of each case. Results showed that (a) the difficulties perceived by families during the pandemic were different from those perceived by the children, and (b) the predominant coping channels had an important relationship with factors that promote resilience. Finally, although it is not clear from the present study whether the children developed resilience, they exhibited factors that determine their future development.

In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells.

Cyanotoxins are secondary metabolites produced by different types of cyanobacteria. Among them, Cylindrospermopsin (CYN) and Microcystins (MCs) stand out due to their wide geographical distribution and toxicity in various organs, including the kidney, which is involved in their distribution and elimination. However, the renal toxicity caused by CYN and MCs has hardly been studied. The aim of this work was to assess the cytotoxicity effects caused by CYN and MC-LR in the renal cell line HEK293, and for the first time, the influence of CYN on the gene expression of selected genes in these cells by quantitative real-time PCR (qRT-PCR). CYN caused an upregulation in the gene expression after exposure to the highest concentration (5 µg/mL) and the longest time of exposure (24 h). Moreover, shotgun proteomic analysis was used to assess the molecular responses of HEK293 cells after exposure to the individuals and combinations of CYN + MC-LR. The simultaneous exposure to both cyanotoxins caused a greater number of alterations in protein expression compared to single toxins, causing changes in the cellular, lipid and protein metabolism and in protein synthesis and transport. Further studies are needed to complete the toxicity molecular mechanisms of both CYN and MC-LR at the renal level.

The protein kinase LKB1 promotes self-renewal and blocks invasiveness in glioblastoma.

The role of liver kinase B1 (LKB1) in glioblastoma (GBM) development remains poorly understood. LKB1 may regulate GBM cell metabolism and has been suggested to promote glioma invasiveness. After analyzing LKB1 expression in GBM patient mRNA databases and in tumor tissue via multiparametric immunohistochemistry, we observed that LKB1 was localized and enriched in GBM tumor cells that co-expressed SOX2 and NESTIN stemness markers. Thus, LKB1-specific immunohistochemistry can potentially reveal subpopulations of stem-like cells, advancing GBM patient molecular pathology. We further analyzed the functions of LKB1 in patient-derived GBM cultures under defined serum-free conditions. Silencing of endogenous LKB1 impaired 3D-gliomasphere frequency and promoted GBM cell invasion in vitro and in the zebrafish collagenous tail after extravasation of circulating GBM cells. Moreover, loss of LKB1 function revealed mitochondrial dysfunction resulting in decreased ATP levels. Treatment with the clinically used drug metformin impaired 3D-gliomasphere formation and enhanced cytotoxicity induced by temozolomide, the primary chemotherapeutic drug against GBM. The IC50 of temozolomide in the GBM cultures was significantly decreased in the presence of metformin. This combinatorial effect was further enhanced after LKB1 silencing, which at least partially, was due to increased apoptosis. The expression of genes involved in the maintenance of tumor stemness, such as growth factors and their receptors, including members of the platelet-derived growth factor (PDGF) family, was suppressed after LKB1 silencing. The defect in gliomasphere growth caused by LKB1 silencing was bypassed after supplementing the cells with exogenous PFDGF-BB. Our data support the parallel roles of LKB1 in maintaining mitochondrial homeostasis, 3D-gliomasphere survival, and hindering migration in GBM. Thus, the natural loss of, or pharmacological interference with LKB1 function, may be associated with benefits in patient survival but could result in tumor spread.

Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review.

Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms' homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity.

The polarity protein Par3 coordinates positively self-renewal and negatively invasiveness in glioblastoma.

Glioblastoma (GBM) is a brain malignancy characterized by invasiveness to the surrounding brain tissue and by stem-like cells, which propagate the tumor and may also regulate invasiveness. During brain development, polarity proteins, such as Par3, regulate asymmetric cell division of neuro-glial progenitors and neurite motility. We, therefore, studied the role of the Par3 protein (encoded by PARD3) in GBM. GBM patient transcriptomic data and patient-derived culture analysis indicated diverse levels of expression of PARD3 across and independent from subtypes. Multiplex immunolocalization in GBM tumors identified Par3 protein enrichment in SOX2-, CD133-, and NESTIN-positive (stem-like) cells. Analysis of GBM cultures of the three subtypes (proneural, classical, mesenchymal), revealed decreased gliomasphere forming capacity and enhanced invasiveness upon silencing Par3. GBM cultures with suppressed Par3 showed low expression of stemness (SOX2 and NESTIN) but higher expression of differentiation (GFAP) genes. Moreover, Par3 silencing reduced the expression of a set of genes encoding mitochondrial enzymes that generate ATP. Accordingly, silencing Par3 reduced ATP production and concomitantly increased reactive oxygen species. The latter was required for the enhanced migration observed upon silencing of Par3 as anti-oxidants blocked the enhanced migration. These findings support the notion that Par3 exerts homeostatic redox control, which could limit the tumor cell-derived pool of oxygen radicals, and thereby the tumorigenicity of GBM.

Anakinra versus Baricitinib: Different Strategies for Patients Hospitalized with COVID-19.

BACKGROUND: Immunomodulatory drugs have been used in patients with severe COVID-19. The objective of this study was to evaluate the effects of two different strategies, based either on an interleukin-1 inhibitor, anakinra, or on a JAK inhibitor, such as baricitinib, on the survival of patients hospitalized with COVID-19 pneumonia. METHODS: Individuals admitted to two hospitals because of COVID-19 were included if they fulfilled the clinical, radiological, and laboratory criteria for moderate-to-severe disease. Patients were classified according to the first immunomodulatory drug prescribed: anakinra or baricitinib. All subjects were concomitantly treated with corticosteroids, in addition to standard care. The main outcomes were the need for invasive mechanical ventilation (IMV) and in-hospital death. Statistical analysis included propensity score matching and Cox regression model. RESULTS: The study subjects included 125 and 217 individuals in the anakinra and baricitinib groups, respectively. IMV was required in 13 (10.4%) and 10 (4.6%) patients, respectively (p = 0.039). During this period, 22 (17.6%) and 36 (16.6%) individuals died in both groups (p = 0.811). Older age, low functional status, high comorbidity, need for IMV, elevated lactate dehydrogenase, and use of a high flow of oxygen at initially were found to be associated with worse clinical outcomes. No differences according to the immunomodulatory therapy used were observed. For most of the deceased individuals, early interruption of anakinra or baricitinib had occurred at the time of their admission to the intensive care unit. CONCLUSIONS: Similar mortality is observed in patients treated with anakinra or baricitinib plus corticosteroids.

Genotoxicity Evaluation of Propyl-Propane-Thiosulfinate (PTS) from Allium genus Essential Oils by a Combination of Micronucleus and Comet Assays in Rats.

Propyl-propanethiosulfinate (PTS) is a component of Allium essential oils. This organosulfur molecule can be used as a feed additive to decrease the appearance of bacterial resistances caused by the residues of antibiotics. In previous in vitro genotoxicity studies, contradictory results were reported for PTS. In this work, the in vivo genotoxicity of PTS in male and female rats was assessed for the first time, following OECD (Organisation for Economic Co-operation and Development) guidelines. After oral administration (doses: 5.5, 17.4, and 55.0 mg/kg PTS body weight), a combination of the micronucleus (MN) assay (OECD 474) in bone marrow and the standard and enzyme-modified comet assay (OECD 489) was performed. After necropsy, histopathological studies were also carried out. The results did not show the in vivo genotoxicity of PTS at any doses assayed, revealed by the absence of increased MN, and DNA strand breaks or oxidative DNA damage in the standard and enzyme-modified comet assays. The histopathological study revealed that only the highest dose tested (55.0 mg/kg) in the liver and all dose groups in the stomach presented minimal pathological lesions in the organs studied. Consequently, the present work confirms that PTS is not genotoxic at the doses assayed, and it is a promising natural alternative to synthetic preservatives and antibiotics in animal feed.

Toxicological Evaluation of Piceatannol, Pterostilbene, and ε-Viniferin for Their Potential Use in the Food Industry: A Review.

The application of stilbenes in the food industry is being considered because of their biological activities. Piceatannol, pterostilbene and ε-viniferin have awakened the industry's interest. However, before they can be commercialized, we must first guarantee their safety for consumers. The present work reviews the toxicological studies performed with these stilbenes. A wide variety of studies has demonstrated their cytotoxic effects in both cancer and non-cancerous cell lines. In contrast, although DNA damage was detected by some authors, in vitro genotoxic studies on the effects of piceatannol, pterostilbene, and ε-viniferin remain scarce. None of the three reviewed substances have been evaluated using the in vitro tests required by the European Food Safety Authority (EFSA) as the first step in genotoxicity testing. We did not find any study on the toxic effects of these stilbenes in vivo. Thus, more studies are needed to confirm their safe use before they can be authorized as additive in the food industry.

Healthcare experience among patients with type 2 diabetes: A cross-sectional survey using the IEXPAC tool.

Aim: To assess the experience with health care among patients with type 2 diabetes (T2DM) and to evaluate patients' demographic variables and healthcare-related characteristics which may affect their experience. Methods: A cross-sectional survey was delivered to T2DM adults. Patient experiences were assessed with the 'Instrument for Evaluation of the Experience of Chronic Patients' (IEXPAC) questionnaire, a validated 12-item survey, which describes patient experience within the last 6 months (items 1-11) and hospitalization in the last 3 years (item 12), with possible scores ranging from 0 (worst) to 10 (best experience). Results: A total of 451 T2DM patients responded to the survey (response rate 72.3%; mean age 69.5 ± 10.1 years, 67.8% men). The mean overall IEXPAC score was 5.92 ± 1.80. Mean scores were higher for productive interactions (7.92 ± 2.15) and self-management (7.08 ± 2.27) than for new relational model (1.72 ± 2.01). Only 32.8% of patients who had been hospitalized in the past 3 years reported having received a follow-up call or visit after discharge. Multivariate analyses identified that regular follow-up by the same physician and follow-up by a nurse were associated with a better patient experience. Continuity of healthcare score was higher only in those patients requiring help from others. Conclusions: The areas of T2DM care which may need to be addressed to ensure better patient experience are use of the Internet, new technologies and social resources for patient information and interaction with healthcare professionals, closer follow-up after hospitalization, and a comprehensive multidisciplinary approach with regular follow-up by the same physician and a nurse.

In Vivo Genotoxicity Evaluation of a Stilbene Extract Prior to Its Use as a Natural Additive: A Combination of the Micronucleus Test and the Comet Assay.

Genotoxic data of substances that could be used as food additives are required by the European Food Safety Authority. In this sense, the use of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99), due to its antioxidant and antibacterial activities, has been proposed as an alternative to sulfur dioxide in wine. The aim of this work was to study, for the first time, the in vivo genotoxic effects produced in rats orally exposed to 90, 180, or 360 mg ST-99/kg body weight at 0, 24, and 45 h. The combination of micronucleus assay in bone marrow (OECD 474) and standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach, liver, and blood of exposed animals. The ST-99 revealed no in vivo genotoxicity. These results were corroborated by analytical studies that confirm the presence of stilbenes and their metabolites in plasma and tissues. Moreover, to complete these findings, a histopathological study was performed under light microscopy in liver and stomach showing only slight modifications in both organs at the highest concentration used. The present work confirms that this extract is not genotoxic presenting a good profile for its potential application as a preservative in the wine industry.

Neumonía por Pneumocystis Jirovecii en paciente adolescente inmunosuprimido no VIH positivo: Un reporte de caso / Pneumocystis Jirovecii pneumonia in a non-HIV immunosuppressed adolescent patient: A case report

Resumen La neumonía en el paciente inmunocomprometido es un reto diagnóstico al cual el clínico se enfrenta cada vez con más frecuencia , al momento de hablar de infiltrados en vidrio esmerilado es menester tener siempre en cuenta la posibilidad de neumonía por Pneumocystis Jirovecii, que por mucho tiempo se pensó como una enfermedad propia del huésped inmunosuprimido con VIH, a través del tiempo se ha manifestado en pacientes con trasplantes de órgano sólido y de precursores hematopoyéticos, asociado a autoinmunidad, al uso crónico de corticoesteroides y más recientemente al uso de terapia biológicas. La descripción de esta enfermedad y sus métodos diagnósticos en huéspedes inmunosuprimidos no VIH no es del todo claro, sabemos que el tratamiento de elección en estos casos es el trimetropin-sulfametoxazol (TMP-SMX) el cual no cuenta con evidencia de alta calidad al momento de plantear una dosis ni un tiempo de duración establecidos. Presentamos el caso de un paciente con diagnóstico de glomerulonefritis por enfermedad de cambios mínimos corticodependiente y quien desarrolló neumonía por Pneumocystis Jirovecii confirmada por histopatología quien recibió tratamiento y tuvo un desenlace positivo.

Abstract The pneumonia in the immunocompromised patient is a diagnostic challenge that the clinician faces more and more frequently, every time we talk about ground glass infiltrates it is necessary to always take into account the possibility of pneumonia due to Neumocystis Jirovecii, which for a long time was thought as a disease of the immunosuppressed host with HIV, but that across the time it has manifested itself in patients with solid organ transplants and hematopoietic precursors, associated with autoimmunity, the chronic use of corticosteroids and more recently the use of biological therapy. The description of this disease and the diagnostic methods in non-HIV immunosuppressed hosts is not entirely clear, we know that the treatment of choice in these cases is trimethropin-sulfamethoxazole (TMP-SMX), which does not have high-quality evidence at the time of a dose or a time of established duration. We present the case of a patient diagnosed with glomerulonephritis due to corticodependent minimal change disease and who suffers from pneumocystis Jirovecii pneumonia confirmed by histopathology, which received treatment and had a positive outcome

Increased MAO-A Activity Promotes Progression of Pulmonary Arterial Hypertension.

Monoamine oxidases (MAOs), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in endothelial cells and cardiomyocytes contributes to vascular dysfunction and progression of left heart failure. We hypothesized that inhibition of MAO-A can be used to treat pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. MAO-A levels in lung and RV samples from patients with PAH were compared with levels in samples from donors without PAH. Experimental PAH was induced in male Sprague-Dawley rats by using Sugen 5416 and hypoxia (SuHx), and RV failure was induced in male Wistar rats by using pulmonary trunk banding (PTB). Animals were randomized to receive either saline or the MAO-A inhibitor clorgyline at 10 mg/kg. Echocardiography and RV catheterization were performed, and heart and lung tissues were collected for further analysis. We found increased MAO-A expression in the pulmonary vasculature of patients with PAH and in experimental experimental PAH induced by SuHx. Cardiac MAO-A expression and activity was increased in SuHx- and PTB-induced RV failure. Clorgyline treatment reduced RV afterload and pulmonary vascular remodeling in SuHx rats through reduced pulmonary vascular proliferation and oxidative stress. Moreover, clorgyline improved RV stiffness and relaxation and reversed RV hypertrophy in SuHx rats. In PTB rats, clorgyline had no direct clorgyline had no direct effect on the right ventricle effect. Our study reveals the role of MAO-A in the progression of PAH. Collectively, these findings indicated that MAO-A may be involved in pulmonary vascular remodeling and consecutive RV failure.