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The intermediate filament protein vimentin performs an essential role in cytoskeletal interplay and dynamics, mechanosensing and cellular stress responses. In pathology, vimentin is a key player in tumorigenesis, fibrosis and infection. Vimentin filaments undergo distinct and versatile reorganizations, and behave as redox sensors. The vimentin monomer possesses a central α-helical rod domain flanked by N- and C-terminal low complexity domains. Interactions between this type of domains play an important function in the formation of phase-separated biomolecular condensates, which in turn are critical for the organization of cellular components. Here we show that several oxidants, including hydrogen peroxide and diamide, elicit the remodeling of vimentin filaments into small particles. Oxidative stress elicited by diamide induces a fast dissociation of filaments into circular, motile dots, which requires the presence of the single vimentin cysteine residue, C328. This effect is reversible, and filament reassembly can occur within minutes of oxidant removal. Diamide-elicited vimentin droplets recover fluorescence after photobleaching. Moreover, fusion of cells expressing differentially tagged vimentin allows the detection of dots positive for both tags, indicating that vimentin dots merge upon cell fusion. The aliphatic alcohol 1,6-hexanediol, known to alter interactions between low complexity domains, readily dissolves diamide-elicited vimentin dots at low concentrations, in a C328 dependent manner, and hampers reassembly. Taken together, these results indicate that vimentin oxidation promotes a fast and reversible filament remodeling into biomolecular condensate-like structures, and provide primary evidence of its regulated phase separation. Moreover, we hypothesize that filament to droplet transition could play a protective role against irreversible damage of the vimentin network by oxidative stress.
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PURPOSE: To investigate the abortion views and reproductive concerns of current in vitro fertilization patients after the US Supreme Court Dobbs v. Jackson decision, which overturned the Roe v. Wade decision guaranteeing abortion access. METHODS: This is a cross-sectional survey of English-speaking patients undergoing in vitro fertilization from January to November 2022 at a large academic institution in a state with restricted abortion care. Participants completed a 43-question electronic survey which measured feelings about abortion, future fertility treatments, and embryo disposition both quantitatively and qualitatively. RESULTS: Of 543 eligible patients, 267 (49%) consented to participate when called and were sent the survey. Of those, 180 (67%) completed it, resulting in a total completion rate of 33%. The majority believe abortion should be legal in the case of birth defects (90.8%) or rape or incest (90.3%). A significant proportion (91.4%) expressed concerns about abortion being illegal in the state that they receive infertility care. They reported some concern about making embryos (89.6%), controlling what happens to them (95.4%), and discarding them (94.4%). Patients wrote about their concerns with pursuing fertility treatments, fear of not having access to needed medical care, and the desire to remain close to states with less restrictive abortion laws. CONCLUSIONS: The evolving political landscape surrounding access to reproductive care has created significant concerns regarding legal regulation of these treatments and the disposition of embryos. By understanding patients' concerns, health care providers can more effectively advocate for the protection of fertility treatments and patients' autonomy in embryo disposition.
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Aborto Inducido , Fertilización In Vitro , Humanos , Femenino , Adulto , Fertilización In Vitro/psicología , Fertilización In Vitro/legislación & jurisprudencia , Embarazo , Aborto Inducido/legislación & jurisprudencia , Aborto Inducido/psicología , Estados Unidos , Estudios Transversales , Destinación del Embrión/psicología , Técnicas Reproductivas Asistidas/psicología , Técnicas Reproductivas Asistidas/legislación & jurisprudencia , Encuestas y Cuestionarios , Infertilidad/terapia , Infertilidad/psicología , MasculinoRESUMEN
Recently, the European Commission announced Industry 5.0 as a strategic initiative toward a value-driven industrial transformation. This new paradigm coexists with previous Industry 4.0 revolution that has guided the efforts towards technology driven industrial digitalisation in the past ten years. As part of this Industry 4.0 strategies, numerous KPI-driven evaluation methods were proposed to cover the multiple pillars of smart industry assessment. However, they do not incorporate human workers and actors in a systematic way as drivers for digitalisation processes, as the new Industry 5.0 paradigm argues. This paper addresses this gap by proposing an evaluation methodology that incorporates multiple human actors in the digitalisation process. The final objective of this methodology is to evaluate the direct and indirect benefits of the technology-driven transformation process to achieve the goals of human workers and other human stakeholders. To this end, our methodology provides the basis for proposing assessment tools and instruments for technological and infrastructure integration, process optimisation, new functionalities and human factors benefits, and four core indicators that have been applied to a real case comparing the digitalisation processes of three different companies.
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Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor's transcriptional output. However, the feed-forward mechanisms that shape cell-type-specific transcriptional fulcrums for steroid receptors are unidentified. Herein, we found that a common feed-forward mechanism between GREB1 and steroid receptors regulates the differential effect of GREB1 on steroid hormones in a physiological or pathological context. In physiological (receptive) endometrium, GREB1 controls P4-responses in uterine stroma, affecting endometrial receptivity and decidualization, while not affecting E2-mediated epithelial proliferation. Of mechanism, progesterone-induced GREB1 physically interacts with the progesterone receptor, acting as a cofactor in a positive feedback mechanism to regulate P4-responsive genes. Conversely, in endometrial pathology (endometriosis), E2-induced GREB1 modulates E2-dependent gene expression to promote the growth of endometriotic lesions in mice. This differential action of GREB1 exerted by a common feed-forward mechanism with steroid receptors advances our understanding of mechanisms that underlie cell- and tissue-specific steroid hormone actions.
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Endometriosis , Proteínas de Neoplasias , Receptores de Esteroides , Animales , Femenino , Humanos , Ratones , Endometriosis/genética , Endometriosis/metabolismo , Endometrio/metabolismo , Estrógenos/metabolismo , Proteínas de Neoplasias/metabolismo , Progesterona/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Esteroides/metabolismoRESUMEN
A 6-year-old castrated male greyhound dog was referred for hemophagocytic histiocytic sarcoma (HHS) diagnosed following splenectomy. Severe thrombocytopenia, mild hypoalbuminemia, mild hypocholesterolemia, and mild hyperbilirubinemia were present. Abdominal ultrasound findings were concerning for hepatic metastasis. Doxorubicin and zoledronate combination therapy was initiated. The dog improved clinically and its thrombocytopenia, hypoalbuminemia, and hyperbilirubinemia resolved. The dog appeared well for 147 d before tumor progression was noted. The dog was treated with lomustine as a final measure, with no response. The dog survived for 6 mo with chemotherapy. To the authors' knowledge, this is the first report of clinical benefit of chemotherapy for HHS. Key clinical message: Doxorubicin should be considered for treating canine HHS since this variant of the disease is historically refractory to lomustine. Further research regarding efficacy of doxorubicin and zoledronate should be pursued.
Traitement à la doxorubicine et au zolédronate chez un chien atteint de sarcome histiocytaire hémophagocytaire. Un lévrier mâle castré de 6 ans a été vu pour un sarcome histiocytaire hémophagocytaire (HHS) diagnostiqué à la suite d'une splénectomie. Une thrombopénie sévère, une hypoalbuminémie légère, une hypocholestérolémie légère et une hyperbilirubinémie légère étaient présentes. Les résultats de l'échographie abdominale étaient préoccupants quant aux métastases hépatiques. Un traitement associant doxorubicine et zolédronate a été instauré. Le chien s'est amélioré cliniquement et sa thrombocytopénie, son hypoalbuminémie et son hyperbilirubinémie ont disparu. Le chien semblait en bonne santé pendant 147 jours avant de constater une progression tumorale. Le chien a été traité avec de la lomustine comme mesure finale, sans réponse. Le chien a survécu 6 mois grâce à la chimiothérapie. À la connaissance des auteurs, il s'agit du premier rapport faisant état d'un bénéfice clinique de la chimiothérapie pour le HHS.Message clinique clé :La doxorubicine doit être envisagée pour traiter le HHS canin puisque cette variante de la maladie est historiquement réfractaire à la lomustine. Des recherches plus approfondies concernant l'efficacité de la doxorubicine et du zolédronate devraient être poursuivies.(Traduit par Dr Serge Messier).
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Enfermedades de los Perros , Sarcoma Histiocítico , Hipoalbuminemia , Trombocitopenia , Perros , Animales , Masculino , Sarcoma Histiocítico/tratamiento farmacológico , Sarcoma Histiocítico/veterinaria , Sarcoma Histiocítico/patología , Ácido Zoledrónico/uso terapéutico , Hipoalbuminemia/tratamiento farmacológico , Hipoalbuminemia/veterinaria , Lomustina , Doxorrubicina/uso terapéutico , Trombocitopenia/veterinaria , Hiperbilirrubinemia/tratamiento farmacológico , Hiperbilirrubinemia/veterinaria , Enfermedades de los Perros/diagnósticoRESUMEN
Infertility can affect all people, regardless of race, ethnicity, or socioeconomic status. Barriers to quality fertility care include access, financial limitations, education, and social stigmas. Although racial disparities in outcomes of assisted reproductive technology can be largely attributed to the influences of systemic racism (not race), we can make changes to improve equity of care. We propose strategies in the areas of advocacy, clinical setting, community, and outcomes to address the racial disparities.
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Fertilidad , Equidad en Salud , Humanos , Etnicidad , Hispánicos o Latinos , Negro o AfroamericanoRESUMEN
Introduction: In the process of growing societies, and especially in the digital era we live in, there is a need for a strong push for innovation that puts citizens at the center of the process from the beginning to build more resilient, cooperative and flexible communities. Different collaborative design approaches have emerged in recent decades, one of the most interesting being Living Labs, which involves user-centered design and co-creative innovation that bring together different actors and roles. However, although these new methodologies are harnessing creativity, some aspects of this new, more ecosystemic and complex vision are not clearly understood: possible barriers, how to facilitate local and operational solutions, overcoming institutional blockage, integrating new roles, etc. Methods: The incorporation of the Quintuple Helix as a driver to ensure greater coordinated participation of local actors has proven its usefulness and impact during the re-adaptation of LifeSpace (previously named Smart House Living Lab), managed by the Polytechnic University of Madrid (Spain), a transformation based on the experiences and lessons learned during the large-scale ACTIVAGE pilot funded by the European Commission, more specifically at the Madrid Deployment Site. It involved more than 350 older adult people and other stakeholders from different areas, including family members, formal and informal caregivers, hospital service managers, third-age associations, and public service providers, forming a sense of community, which was called MAHA. Results: The living lab infrastructure evolved from a single multi-purpose environment to incorporate three harmoniously competing environments: (1) THE LAB: Headquarters for planning, demonstration, initial design phases and entry point for newcomers to the process, (2) THE CLUB: Controlled interaction environment where returning users validate solutions, focusing mainly on AHA services (MAHA CLUB), such as exergames, social interaction applications, brain training activities, etc. (3) THE NEIGHBOURHOOD: Real-life environments for free and open interaction between actors and implementation of previously validated and tested solutions. Conclusion: The Quintuple Helix model applied in LifeSpace's new vision allows a coordinated involvement of a more diverse set of actors, beyond the end-users and especially those who are not traditionally part of research and innovation processes.
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Encéfalo , Ecosistema , Humanos , Anciano , Entrenamiento Cognitivo , Familia , EspañaRESUMEN
As cancer therapies continue to improve, the survival rates of adolescent and young adult patients have increased. Consequently, considering patient quality of life after cancer, including family building, has become an essential aspect of establishing a treatment plan. However, the gonadotoxic nature of many chemotherapeutic agents limits the option of using one's own gamete for family building. In recent years, significant advancements have been made in oncofertility, particularly vitrification of oocytes. Unfortunately, as with many areas of medicine, health disparities limit those that can access and utilize fertility preservation prior to cancer treatment. This review aims to shed light on existing disparities in oncofertility for female patients, to offer recommendations to enhance education, access, and advocacy, as well as identify potential areas for future research.
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The remarkable potential of human endometrium to undergo spontaneous remodeling is shaped by controlled spatiotemporal gene expression patterns. Although hormone-driven transcription shown to govern these patterns, the post-transcriptional processing of these mRNA transcripts, including the mRNA splicing in the endometrium is not studied yet. Here, we report that the splicing factor, SF3B1 is central in driving alternative splicing (AS) events that are vital for physiological responses of the endometrium. We show that loss of SF3B1 splicing activity impairs stromal cell decidualization as well as embryo implantation. Transcriptomic analysis revealed that SF3B1 depletion decidualizing stromal cells led to differential mRNA splicing. Specifically, a significant upregulation in mutually exclusive AS events (MXEs) with SF3B1 loss resulted in the generation of aberrant transcripts. Further, we found that some of these candidate genes phenocopy SF3B1 function in decidualization. Importantly, we identify progesterone as a potential upstream regulator of SF3B1-mediated functions in endometrium possibly via maintaining its persistently high levels, in coordination with deubiquitinating enzymes. Collectively, our data suggest that SF3B1-driven alternative splicing plays a critical role in mediating the endometrial-specific transcriptional paradigms. Thus, the identification of novel mRNA variants associated with successful pregnancy establishment may help to develop new strategies to diagnose or prevent early pregnancy loss.
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Cysteine residues can undergo multiple posttranslational modifications with diverse functional consequences, potentially behaving as tunable sensors. The intermediate filament protein vimentin has important implications in pathophysiology, including cancer progression, infection, and fibrosis, and maintains a close interplay with other cytoskeletal structures, such as actin filaments and microtubules. We previously showed that the single vimentin cysteine, C328, is a key target for oxidants and electrophiles. Here, we demonstrate that structurally diverse cysteine-reactive agents, including electrophilic mediators, oxidants and drug-related compounds, disrupt the vimentin network eliciting morphologically distinct reorganizations. As most of these agents display broad reactivity, we pinpointed the importance of C328 by confirming that local perturbations introduced through mutagenesis provoke structure-dependent vimentin rearrangements. Thus, GFP-vimentin wild type (wt) forms squiggles and short filaments in vimentin-deficient cells, the C328F, C328W, and C328H mutants generate diverse filamentous assemblies, and the C328A and C328D constructs fail to elongate yielding dots. Remarkably, vimentin C328H structures resemble the wt, but are strongly resistant to electrophile-elicited disruption. Therefore, the C328H mutant allows elucidating whether cysteine-dependent vimentin reorganization influences other cellular responses to reactive agents. Electrophiles such as 1,4-dinitro-1H-imidazole and 4-hydroxynonenal induce robust actin stress fibers in cells expressing vimentin wt. Strikingly, under these conditions, vimentin C328H expression blunts electrophile-elicited stress fiber formation, apparently acting upstream of RhoA. Analysis of additional vimentin C328 mutants shows that electrophile-sensitive and assembly-defective vimentin variants permit induction of stress fibers by reactive species, whereas electrophile-resistant filamentous vimentin structures prevent it. Together, our results suggest that vimentin acts as a break for actin stress fibers formation, which would be released by C328-aided disruption, thus allowing full actin remodeling in response to oxidants and electrophiles. These observations postulate C328 as a "sensor" transducing structurally diverse modifications into fine-tuned vimentin network rearrangements, and a gatekeeper for certain electrophiles in the interplay with actin.
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Actinas , Filamentos Intermedios , Filamentos Intermedios/química , Actinas/genética , Actinas/química , Vimentina/genética , Vimentina/química , Cisteína/metabolismo , Oxidantes/metabolismoRESUMEN
AIM: Benzodiazepines (BZDs) are one of the most used drugs to control symptoms in patients with acute heart failure (HF). However, the evidence on its safety is inconclusive. The objective was to describe the characteristics of patients admitted for HF and treated with BZDs and to assess the relationship of this treatment and mortality. PATIENTS AND METHODS: We performed a cross-sectional, multicentre (74 Spanish hospitals), cohort study. Patients admitted for HF were divided depending on whether they were treated with BZDs or not. Propensity score analysis matched patients in both groups in a 1:1 manner according to different factors. The primary outcome was mortality at day 7. Secondary outcomes were mortality at days 30 and 180, as well as readmissions and emergency room visits at 180 days. RESULTS: We included 1855 patients: 639 (34.4%) had prescribed BZDs treatment versus 1216 (65.6%) who had not been treated. Patients receiving BZDs had advanced heart disease, severe symptoms, need more HF intensive treatment and higher mortality. After propensity matching 381 balanced paired cases were included in each group. Treatment with BZDs was not associated with greater risk of mortality at day 7 of index hospitalization (7.6% vs 5.2%, adjusted OR 1.49, 95% CI 0.83-2.68, p = 0.186). There were also no differences between groups in terms of mortality at day 30 and 180, readmissions or visits to the emergency room. CONCLUSIONS: Our data support that benzodiazepines could be safely used for improving symptoms. in patients admitted for acute HF in terms of short-medium term mortality.
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Benzodiazepinas , Insuficiencia Cardíaca , Humanos , Benzodiazepinas/efectos adversos , Estudios de Cohortes , Puntaje de Propensión , Estudios Transversales , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
This retrospective cohort study assessed the accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT-A) and carrier screening in a single academic Reproductive Endocrinology and Infertility (REI) clinic. A total of 420 patients were evaluated with 219 patients counseled by a REI physician only and 201 patients after the addition of a genetic counselor (GC) to the REI clinic team. Cycles initiated before hiring of a GC (pre-GC) were assessed from June 2018 to December 2018 and after integration of a GC (post-GC) from March 2019 to August 2019. Additionally, information regarding carrier screening was collected if available in the medical record. Results showed more patients utilized PGT-A post-GC (9.5% vs. 5.5%), although the difference between groups did not reach statistical significance (p = 0.12). Individuals who were screened post-GC or who started screening pre-GC and continued screening post-GC were screened for a larger number of conditions than if they were only screened pre-GC (median pre-GC = 3, post-GC = 27, pre- and post-GC = 274; p < 0.0001). The change in practice from using physician-only counseling to counseling with accessibility to a GC did not change the utilization of PGT-A in a single clinic.
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Consejeros , Diagnóstico Preimplantación , Embarazo , Femenino , Humanos , Diagnóstico Preimplantación/psicología , Estudios Retrospectivos , Transferencia de Embrión/métodos , Pruebas Genéticas/métodos , Fertilización In Vitro , AneuploidiaRESUMEN
Hospitals need to optimize patient care, as, among other factors, life expectancy has increased due to improvements in sanitation, nutrition, and medicines. Hospitalization-at-home (HaH) could increase admission efficiency, moderate costs, and reduce the demand for beds. This study aimed to provide data on the feasibility, acceptability, and effectiveness of the integration of IoT-based technology to support the remote monitoring and follow-up of patients admitted to HaH units, as well as the acceptability of IoT-based solutions in healthcare processes. The need for a reduction in the number of admission days, the percentage of admissions after discharge, and the actions of the emergency services during admission were the most relevant findings of this study. Furthermore, in terms of patient safety and trust perception, 98% of patients preferred this type of digitally-supported hospitalization model and up to 95% were very satisfied. On the professional side, the results showed a reduction in work overload and an increase in trust when the system was adopted.
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Servicios de Atención de Salud a Domicilio , Participación del Paciente , Humanos , Hospitalización , Alta del Paciente , ConfidencialidadRESUMEN
Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.
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Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Humanos , Metilación de ADN , Epilepsia del Lóbulo Temporal/genética , Lóbulo Temporal , Hipocampo , Amígdala del Cerebelo , Epilepsia Refractaria/genéticaRESUMEN
AIMS: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. METHODS: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. RESULTS: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100ß) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. CONCLUSIONS: We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.
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Epilepsia del Lóbulo Temporal , Epilepsia , Humanos , Astrocitos/patología , Tetraploidía , Encéfalo/patología , Neuronas/patología , Epilepsia/patología , Hipocampo/patología , Epilepsia del Lóbulo Temporal/patología , Proteínas Supresoras de TumorRESUMEN
The coronavirus disease of 2019 (COVID-19) has been a cause of significant morbidity and mortality worldwide. Among the short- and long-term consequences of COVID-19, myocarditis is a disease to be taken into consideration. Myocarditis, in general, is related to a poor prognosis. However, the epidemiology and prognosis of myocarditis related to COVID-19 are currently unknown. While vaccination against COVID-19 is of great benefit at a public health level, the risk of myocarditis should be considered in the context of the global benefits of vaccination. In this narrative review, we will summarize the etiopathogenic bases, the epidemiology, the clinical manifestations, the course, diagnosis, prognosis, and the treatment of myocarditis related to SARS-CoV-2, as well as myocarditis secondary to mRNA vaccines.
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Alexander disease is a fatal neurological disorder caused by mutations in the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP), which is key for astrocyte homeostasis. These mutations cause GFAP aggregation, astrocyte dysfunction and neurodegeneration. Remarkably, most of the known GFAP mutations imply a change by more nucleophilic amino acids, mainly cysteine or histidine, which are more susceptible to oxidation and lipoxidation. Therefore, we hypothesized that a higher susceptibility of Alexander disease GFAP mutants to oxidative or electrophilic damage, which frequently occurs during neurodegeneration, could contribute to disease pathogenesis. To address this point, we have expressed GFP-GFAP wild type or the harmful Alexander disease GFP-GFAP R239C mutant in astrocytic cells. Interestingly, GFAP R239C appears more oxidized than the wild type under control conditions, as indicated both by its lower cysteine residue accessibility and increased presence of disulfide-bonded oligomers. Moreover, GFP-GFAP R239C undergoes lipoxidation to a higher extent than GFAP wild type upon treatment with the electrophilic mediator 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Importantly, GFAP R239C filament organization is altered in untreated cells and is earlier and more severely disrupted than GFAP wild type upon exposure to oxidants (diamide, H2O2) or electrophiles (4-hydroxynonenal, 15d-PGJ2), which exacerbate GFAP R239C aggregation. Furthermore, H2O2 causes reversible alterations in GFAP wild type, but irreversible damage in GFAP R239C expressing cells. Finally, we show that GFAP R239C expression induces a more oxidized cellular status, with decreased free thiol content and increased mitochondrial superoxide generation. In addition, mitochondria show decreased mass, increased colocalization with GFAP and altered morphology. Notably, a GFP-GFAP R239H mutant recapitulates R239C-elicited alterations whereas an R239G mutant induces a milder phenotype. Together, our results outline a deleterious cycle involving altered GFAP R239C organization, mitochondrial dysfunction, oxidative stress, and further GFAP R239C protein damage and network disruption, which could contribute to astrocyte derangement in Alexander disease.
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La edición 65 del boletín NotiSalud andinas presenta la salud en los países andinos y los retos frente a la covid-19:La Seguridad alimentaria es un derecho. Cuidemos la tierra con una producción sostenible. Actividades de junio: Reunión de autoridades nacionales de Salud de la región Andina. Encuentro regional: Desigualdades múltiples en salud en la región Andina; I reunión proyecto Fortalecimiento de la toma de decisiones en el control de la pandemia COVID-19 mediante la vigilancia genómica en los países de Bolivia, Colombia, Ecuador y Perú. Ciclo de webinars ORAS-CONHU de junio: Un planeta sano para el bienestar de todas las personas. Nuestra responsabilidad, nuestra oportunidad; Enfoques innovadores para enfrentar el cáncer de próstata en la región Andina; Situación mundial de la viruela símica: prevención, diagnóstico y tratamiento; Consumo de alcohol y otras drogas en el contexto de la pandemia por COVID-19; Desnutrición infantil y seguridad alimentaria
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Abastecimiento de Alimentos , COVID-19 , Perú , Venezuela , Bolivia , Colombia , Infecciones por Coronavirus , EcuadorRESUMEN
PURPOSE: To study patient satisfaction with new patient telehealth visits in a reproductive endocrinology and infertility (REI) office. METHODS: A cross-sectional study in a university-based fertility clinic was completed including all new patients seen via telehealth between March 1, 2021, and August 19, 2021. Primary outcomes were perceived patient satisfaction, access, and preferences to telehealth visits. RESULTS: A total of 351 participants were contacted, 61.8% (n = 217) agreed to participate in the study, and 28.8% (n = 101) completed the survey. There were no significant differences in age, BMI, distance from clinic, or length of infertility with response to survey. Ninety-three percent of responders would use telehealth services again and were satisfied with the telehealth system. Telehealth improved access to healthcare for 88% and travel time for 96%. The median distance from clinic was 24 miles, and there was no significance difference in preference for telehealth visits over in person visits (p = 0.696). CONCLUSIONS: In the era of COVID-19, healthcare implementation has dramatically changed with a drastic increase in telehealth services. Based on our survey, majority of patients were satisfied with telehealth visits and believed it saved travel time while improving access to REI care. Despite no differences in patient preference for in person versus telehealth depending on their distance from clinic, this is reassuring because patients are satisfied with telehealth for reasons other than distance from clinic.