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Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, a mtSNP associated with reduced PD risk, within the small open reading frame encoding SHLP2. This mtSNP results in an alternative form of SHLP2 (lysine 4 replaced with arginine; K4R). Using targeted mass spectrometry, we detect specific tryptic fragments of SHLP2 in neuronal cells and demonstrate its binding to mitochondrial complex 1. Notably, we observe that the K4R variant, associated with reduced PD risk, exhibits increased stability compared to WT SHLP2. Additionally, both WT and K4R SHLP2 show enhanced protection against mitochondrial dysfunction in in vitro experiments and confer protection against a PD-inducing toxin, a mitochondrial complex 1 inhibitor, in a mouse model. This study sheds light on the functional consequences of the m.2158 T > C mtSNP on SHLP2 and provides insights into the potential mechanisms by which this mtSNP may reduce the risk of PD.
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Mitocôndrias , Doença de Parkinson , Polimorfismo de Nucleotídeo Único , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Animais , Camundongos , Humanos , Polimorfismo de Nucleotídeo Único/genética , Mitocôndrias/metabolismo , DNA Mitocondrial/genética , Fatores de Proteção , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Modelos Animais de Doenças , Masculino , Complexo I de Transporte de Elétrons/metabolismo , Complexo I de Transporte de Elétrons/genética , Peptídeos/genética , Peptídeos/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
Mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), a mitochondrial microprotein, has been described as a novel regulator of glucose and lipid metabolism. In addition to its role as a metabolic regulator, MOTS-c prevents skeletal muscle atrophy in high fat-fed mice. Here, we examined the preventive effect of MOTS-c on skeletal muscle mass, using an immobilization-induced muscle atrophy model, and explored its underlying mechanisms. Male C57BL/6J mice (10 wk old) were randomly assigned to one of the three experimental groups: nonimmobilization control group (sterilized water injection), immobilization control group (sterilized water injection), and immobilization and MOTS-c-treated group (15 mg/kg/day MOTS-c injection). We used casting tape for the immobilization experiment. After 8 days of the experimental period, skeletal muscle samples were collected and used for Western blotting, RNA sequencing, and lipid and collagen assays. Immobilization reduced â¼15% of muscle mass, whereas MOTS-c treatment attenuated muscle loss, with only a 5% reduction. MOTS-c treatment also normalized phospho-AKT, phospho-FOXO1, and phospho-FOXO3a expression levels and reduced circulating inflammatory cytokines, such as interleukin-1b (IL-1ß), interleukin-6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1), in immobilized mice. Unbiased RNA sequencing and its downstream analyses demonstrated that MOTS-c modified adipogenesis-modulating gene expression within the peroxisome proliferator-activated receptor (PPAR) pathway. Supporting this observation, muscle fatty acid levels were lower in the MOTS-c-treated group than in the casted control mice. These results suggest that MOTS-c treatment inhibits skeletal muscle lipid infiltration by regulating adipogenesis-related genes and prevents immobilization-induced muscle atrophy.NEW & NOTEWORTHY MOTS-c, a mitochondrial microprotein, attenuates immobilization-induced skeletal muscle atrophy. MOTS-c treatment improves systemic inflammation and skeletal muscle AKT/FOXOs signaling pathways. Furthermore, unbiased RNA sequencing and subsequent assays revealed that MOTS-c prevents lipid infiltration in skeletal muscle. Since lipid accumulation is one of the common pathologies among other skeletal muscle atrophies induced by aging, obesity, cancer cachexia, and denervation, MOTS-c treatment could be effective in other muscle atrophy models as well.
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Micropeptídeos , Proteínas Proto-Oncogênicas c-akt , Masculino , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos C57BL , Atrofia Muscular/etiologia , Atrofia Muscular/prevenção & controle , Músculo Esquelético/metabolismo , Fatores de Transcrição/metabolismo , Água , LipídeosRESUMO
Capsid assembly mediated by hepatitis B virus (HBV) core protein (HBc) is an essential part of the HBV replication cycle, which is the target for different classes of capsid assembly modulators (CAMs). While both CAM-A ("aberrant") and CAM-E ("empty") disrupt nucleocapsid assembly and reduce extracellular HBV DNA, CAM-As can also reduce extracellular HBV surface antigen (HBsAg) by triggering apoptosis of HBV-infected cells in preclinical mouse models. However, there have not been substantial HBsAg declines in chronic hepatitis B (CHB) patients treated with CAM-As to date. To investigate this disconnect, we characterized the antiviral activity of tool CAM compounds in HBV-infected primary human hepatocytes (PHHs), as well as in HBV-infected human liver chimeric mice and mice transduced with adeno-associated virus-HBV. Mechanistic studies in HBV-infected PHH revealed that CAM-A, but not CAM-E, induced a dose-dependent aggregation of HBc in the nucleus which is negatively regulated by the ubiquitin-binding protein p62. We confirmed that CAM-A, but not CAM-E, induced HBc-positive cell death in both mouse models via induction of apoptotic and inflammatory pathways and demonstrated that the degree of HBV-positive cell loss was positively correlated with intrahepatic HBc levels. Importantly, we determined that there is a significantly lower level of HBc per hepatocyte in CHB patient liver biopsies than in either of the HBV mouse models. Taken together, these data confirm that CAM-As have a unique secondary mechanism with the potential to kill HBc-positive hepatocytes. However, this secondary mechanism appears to require higher intrahepatic HBc levels than is typically observed in CHB patients, thereby limiting the therapeutic potential.
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Vírus da Hepatite B , Hepatite B Crônica , Hepatócitos , Humanos , Hepatócitos/virologia , Hepatócitos/efeitos dos fármacos , Animais , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Camundongos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Proteínas do Core Viral/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Capsídeo/metabolismo , Capsídeo/efeitos dos fármacos , Fígado/virologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Montagem de Vírus/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
Bumble bees are integral pollinators of native and cultivated plant communities, but species are undergoing significant changes in range and abundance on a global scale. Climate change and land cover alteration are key drivers in pollinator declines; however, limited research has evaluated the cumulative effects of these factors on bumble bee assemblages. This study tests bumble bee assemblage (calculated as richness and abundance) responses to climate and land use by modeling species-specific habitat requirements, and assemblage-level responses across geographic regions. We integrated species richness, abundance, and distribution data for 18 bumble bee species with site-specific bioclimatic, landscape composition, and landscape configuration data to evaluate the effects of multiple environmental stressors on bumble bee assemblages throughout 433 agricultural fields in Florida, Indiana, Kansas, Kentucky, Maryland, South Carolina, Utah, Virginia, and West Virginia from 2018 to 2020. Distinct east versus west groupings emerged when evaluating species-specific habitat associations, prompting a detailed evaluation of bumble bee assemblages by geographic region. Maximum temperature of warmest month and precipitation of driest month had a positive impact on bumble bee assemblages in the Corn Belt/Appalachian/northeast, southeast, and northern plains regions, but a negative impact on the mountain region. Further, forest land cover surrounding agricultural fields was highlighted as supporting more rich and abundant bumble bee assemblages. Overall, climate and land use combine to drive bumble bee assemblages, but how those processes operate is idiosyncratic and spatially contingent across regions. From these findings, we suggested regionally specific management practices to best support rich and abundant bumble bee assemblages in agroecosystems. Results from this study contribute to a better understanding of climate and landscape factors affecting bumble bees and their habitats throughout the United States.
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Mudança Climática , Ecossistema , Animais , Abelhas/fisiologia , Estados Unidos , Biodiversidade , Agricultura , PolinizaçãoRESUMO
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive and rare neuroendocrine tumor, accounting for less than 1% of skin cancers. Metastasis primarily manifests in the cervical lymph nodes but rarely affect the thyroid. METHODS: We report a case of primary head and neck cutaneous MCC with metastasis to the thyroid gland. A review of the literature of MCC with thyroid metastasis was conducted. RESULTS: We identified five cases of MCC with thyroid metastasis. Primary sites included the distal upper and lower extremities, axilla, buttock, and groin. Treatment courses varied including thyroidectomy, immunotherapy, and expectant palliative measures. Time from initial diagnosis to thyroid metastasis ranged from four months to four years. Tissue diagnosis was achieved in 5 of 6 cases. CONCLUSIONS: MCC with thyroid metastasis is rare and likely represents aggressive disease. Despite advances in treatment and surveillance, outcomes for MCC remain poor. Ongoing research may establish predictors for treatment response.
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Carcinoma de Célula de Merkel , Neoplasias Cutâneas , Neoplasias da Glândula Tireoide , Feminino , Humanos , Carcinoma de Célula de Merkel/secundário , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/secundário , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Venous thromboembolism (VTE) poses a major clinical concern due to its life-threatening nature, and obese and morbidly obese patients are thought to be at an increased risk for VTE. The aims of this study were twofold; first, to explore VTE rates in patients who have a body mass index (BMI) > 40 undergoing primary and revision total joint arthroplasty, and second, to investigate aspirin (ASA) efficacy and safety. METHODS: We identified all patients (n = 4,672) who had a BMI > 40 who underwent primary and revision total joint arthroplasty from 2016 to 2022 at a single academic tertiary care center. Patients were stratified by BMI groups: 40 to 44.9 (n = 3,462), 45 to 49.9 (n = 935), and 50+ (n = 275). The primary outcome was any VTE event within 90 days postoperatively. The secondary outcome consisted of wound complications within 90 days postoperatively. RESULTS: The total VTE rate was 0.4% (n = 21) and did not differ statistically between the BMI groups (0.4 versus 0.4 versus 0.7%, P = .669). The VTEs consisted of 6 deep venous thromboses (DVTs), 14 pulmonary embolisms, and one concomitant deep venous thrombosis and pulmonary embolism. The VTE rates were not statistically different between patients who received aspirin 325 mg 0.5% (n = 9), aspirin 81 mg 0.2% (n = 1), aspirin + anticoagulant (AC) 0.5% (n = 6), and AC alone 0.4% (n = 5) (P = .954). In addition, wound complications did not differ significantly between patients who received ASA 325 mg, ASA 81mg, ASA + AC, or AC alone (1.6 versus 1.0 versus 1.8 versus 1.1%, P = .351). CONCLUSIONS: The use of aspirin 325 and 81 mg was found to have similar VTE rates as aspirin + ACs and ACs alone, with no significant increase in wound complications. In patients who have a BMI > 40, the use of aspirin is a safe option for VTE prophylaxis and should be prescribed in the context of the patient who has other risk factors for VTE.
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BACKGROUND: Cefazolin is the standard of care for perioperative antibiotic prophylaxis in total joint arthroplasty (TJA) in the United States. The potential allergic cross-reactivity between cefazolin and penicillin causes uncertainty regarding optimal antibiotic choice in patients who have a reported penicillin allergy (rPCNA). The purpose of this study was to determine the safety of perioperative cefazolin in PCNA patients undergoing primary TJA. METHODS: We identified all patients (n = 49,842) undergoing primary total hip arthroplasty (n = 25,659) or total knee arthroplasty (n = 24,183) from 2016 to 2022 who received perioperative intravenous antibiotic prophylaxis. Patients who had an rPCNA (n = 5,508) who received cefazolin (n = 4,938, 89.7%) were compared to rPCNA patients who did not (n = 570, 10.3%), and to patients who did not have an rPCNA (n = 43,359). The primary outcome was the rate of allergic reactions within 72 hours postoperatively. Secondary outcomes included the rates of superficial infections, deep infections, and Clostridioides difficile infections within 90 days. RESULTS: The rate of allergic reactions was 0.1% (n = 5) in rPCNA patients who received cefazolin, compared to 0.2% (n = 1) in rPCNA patients who did not (P = .48) and 0.02% (n = 11) in patients who have no rPCNA (P = .02). Allergic reactions were mild in all 5 rPCNA patients who received cefazolin and were characterized by cutaneous symptoms (n = 4) or dyspnea in the absence of respiratory distress (n = 1) that resolved promptly with antibiotic discontinuation and administration of antihistamines and/or corticosteroids. We observed no differences in the rates of superficial infections (0.1 versus 0.2%, P = .58), deep infections (0.3 versus 0.4%, P = .68), or C difficile infections (0.04% versus 0%, P = .99) within 90 days in rPCNA patients who received cefazolin versus alternative perioperative antibiotics. CONCLUSIONS: In this series of more than 5,500 patients who had an rPCNA undergoing primary TJA, perioperative prophylaxis with cefazolin resulted in a 0.1% incidence of allergic reactions that were clinically indolent. Cefazolin can be safely administered to most patients, independent of rPCNA severity. LEVEL OF EVIDENCE: III.
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Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.
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Capsaicina , Dor , Canais de Cátion TRPV , Animais , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Capsaicina/farmacologia , Masculino , Feminino , Camundongos , Dor/metabolismo , Dor/genética , Hormônios Esteroides Gonadais/metabolismo , Ciclo Estral/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Caracteres Sexuais , RNA Mensageiro/metabolismo , RNA Mensageiro/genéticaRESUMO
Giant magnetoelectric coupling and magnetic-field-induced spin state trapping (MIESST) were recently reported in spin crossover materials with polar phases. We discuss these phenomena considering the distinct contributions of the change of the molecular spin state, driven by the magnetic field, and the coupled structural symmetry-breaking during the stepwise change of electric polarisation or MIESST.
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Mixed lineage kinase domain-like (MLKL) is a key signaling protein of necroptosis. Upon activation by phosphorylation, MLKL translocates to the plasma membrane and induces membrane permeabilization, which contributes to the necroptosis-associated inflammation. Membrane binding of MLKL is initially initiated by electrostatic interactions between the protein and membrane phospholipids. We previously showed that MLKL and its phosphorylated form (pMLKL) are S-acylated during necroptosis. Here, we characterize the acylation sites of MLKL and identify multiple cysteines that can undergo acylation with an interesting promiscuity at play. Our results show that MLKL and pMLKL undergo acylation at a single cysteine, with C184, C269, and C286 as possible acylation sites. Using all-atom molecular dynamic simulations, we identify differences that the acylation of MLKL causes at the protein and membrane levels. Through investigations of the S-palmitoyltransferases that might acylate pMLKL in necroptosis, we showed that zDHHC21 activity has the strongest effect on pMLKL acylation, inactivation of which profoundly reduced the pMLKL levels in cells and improved membrane integrity. These results suggest that blocking the acylation of pMLKL destabilizes the protein at the membrane interface and causes its degradation, ameliorating the necroptotic activity. At a broader level, our findings shed light on the effect of S-acylation on MLKL functioning in necroptosis and MLKL-membrane interactions mediated by its acylation.
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Necroptose , Proteínas Quinases , Proteínas Quinases/metabolismo , Fosforilação , Membrana Celular/metabolismo , ApoptoseRESUMO
Although herbal drugs are often considered safe for consumption, there is increasing evidence that some can generate undesirable health effects. However, polyphenols found in certain plants have been shown to provide a range of benefits for human health. In previous work, a standardized and quantified extract (P2Et) obtained from Caesalpinia spinosa (Dividivi) plant showed promising antioxidant, immunomodulatory, and anti-inflammatory properties in animal models of cancer and COVID-19 patients. The extract has also been subjected to genotoxicity, mutagenicity, and 28-day oral chronic toxicity evaluations, demonstrating a good safety profile. To advance preclinical and clinical development, further acute and chronic toxicity evaluations of the P2Et extract were performed. Acute toxicity tests were performed orally in Wistar rats at a dose of 2000 mg/kg, indicating that the lethal dose 50% (LD50) value exceeded 2000 mg/kg and classifying the P2Et extract as category 5 according to the Globally Harmonized System of Classification (GHS). In this work, chronic toxicity tests were conducted for 180 days on Wistar rats and New Zealand rabbits at a dose of 1000 mg/kg under Good Laboratory Practice (GLP) conditions. No weight loss or alterations in biochemical and hematological parameters associated with treatment were observed in the animals, suggesting the absence of toxicity in the assessed parameters. These results indicate that the P2Et extract is safe for oral administration at doses up to 1000 mg/kg body weight over a six-month period.
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PURPOSE: Surgical pathology reports play an integral role in postoperative management of head and neck cancer patients. Pathology reports of complex head and neck resections must convey critical information to all involved clinicians. Previously, we demonstrated the utility of 3D specimen and defect scanning for communicating margin status and documenting the location of supplemental margins. We introduce a newly designed permanent pathology report which improves documentation of intraoperative margin mapping and extent of corresponding supplemental margins harvested. METHODS: We test the hypothesis that gaps in understanding exist for head and neck resection pathology reports across providers. A cross-sectional exploratory study using human-centered design was implemented to evaluate the existing permanent pathology report with respect to understanding margin status. Pathologists, surgeons, radiation oncologists, and medical oncologists from United States-based medical institutions were surveyed. The results supported a redesign of our surgical pathology template, incorporating 3D specimen / defect scans and annotated radiographic images indicating the location of inadequate margins requiring supplemental margins, or indicating frankly positive margins discovered on permanent section. RESULTS: Forty-seven physicians completed our survey. Analyzing surgical pathology reports, 28/47 (60%) respondents reported confusion whether re-excised supplemental margins reflected clear margins, 20/47 (43%) reported uncertainty regarding final margin status, and 20/47 (43%) reported the need for clarity regarding the extent of supplemental margins harvested intraoperatively. From this feedback, we designed a new pathology report template; 61 permanent pathology reports were compiled with this new template over a 12-month period. CONCLUSION: Feedback from survey respondents led to a redesigned permanent pathology report that offers detailed visual anatomic information regarding intraoperative margin findings and exact location/size of harvested supplemental margins. This newly designed report reconciles frozen and permanent section results and includes annotated radiographic images such that clinicians can discern precise actions taken by surgeons to address inadequate margins, as well as to understand the location of areas of concern that may influence adjuvant radiation planning.
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Neoplasias de Cabeça e Pescoço , Margens de Excisão , Patologia Cirúrgica , Humanos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Estudos Transversais , Patologia Cirúrgica/métodos , Comunicação Interdisciplinar , Imageamento TridimensionalRESUMO
Ultrafast photoinduced phase transitions at room temperature, driven by a single laser shot and persisting long after stimuli, represent emerging routes for ultrafast control over materials' properties. Time-resolved studies provide fundamental mechanistic insight into far-from-equilibrium electronic and structural dynamics. Here we study the photoinduced phase transformation of the Rb0.94Mn0.94Co0.06[Fe(CN)6]0.98 material, designed to exhibit a 75 K wide thermal hysteresis around room temperature between MnIIIFeII tetragonal and MnIIFeIII cubic phases. We developed a specific powder sample streaming technique to monitor by ultrafast X-ray diffraction the structural and symmetry changes. We show that the photoinduced polarons expand the lattice, while the tetragonal-to-cubic photoinduced phase transition occurs within 100 ps above threshold fluence. These results are rationalized within the framework of the Landau theory of phase transition as an elastically-driven and cooperative process. We foresee broad applications of the streaming powder technique to study non-reversible and ultrafast dynamics.
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The aim of this study was to assess the shear wave velocity by LUS elastography (SWE2D) for the evaluation of superficial lung stiffness after COVID-19 pneumonia, according to "fibrosis-like" signs found by Computed Tomography (CT), considering the respiratory function. Seventy-nine adults participated in the study 42 to 353 days from symptom onset. Paired evaluations (SWE2D and CT) were performed along with the assessment of arterial blood gases and spirometry, three times with 100 days in between. During the follow-up and within each evaluation, the SWE2D velocity changed over time (MANOVA, p < 0.05) according to the extent of "fibrosis-like" CT signs by lung lobe (ANOVA, p < 0.05). The variability of the SWE2D velocity was consistently related to the first-second forced expiratory volume and the forced vital capacity (MANCOVA, p < 0.05), which changed over time with no change in blood gases. Covariance was also observed with age and patients' body mass index, the time from symptom onset until hospital admission, and the history of diabetes in those who required intensive care during the acute phase (MANCOVA, p < 0.05). After COVID-19 pneumonia, SWE2D velocity can be related to the extent and regression of "fibrotic-like" involvement of the lung lobes, and it could be a complementary tool in the follow-up after COVID-19 pneumonia.
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Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome that predominantly affects women without cardiovascular risk factors. In transplant patients, spontaneous coronary artery dissection is an extremely rare condition, having been described in only three patients, in whom vascular damage secondary to the use of anticalcineurinics is postulated as a probable mechanism. We report a spontaneous coronary dissection in a female who received a heart transplant at 34 years of age. The diagnosis was made in a follow-up coronary angiography three years after transplantation, supplemented with optical coherence tomography. A percutaneous coronary revascularization of the involved artery was performed, with good immediate results and at one year of follow-up.
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Humanos , Feminino , Doenças Vasculares/etiologia , Doenças Vasculares/diagnóstico por imagem , Transplante de Coração/efeitos adversos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Angiografia Coronária , DissecaçãoRESUMO
Abstract: Introduction: IHD has become an important long-term end point for RA patients independent of traditional CVRF. Therefore, cardiovascular injury and mortality might be due to the presence of a chronic systematic inflammatory response. Nonetheless, there is a gap in its diagnosis since symptoms remain silent until major events occur. Objective: We aimed to evaluate by gated single-photon emission computed tomography (g-SPECT). Myocardial perfusion in asymptomatic Mexican patients with RA and at least one traditional CVRF, and without history of angina. Patients and methods: A prospective study with a total number of 91 patients was conducted. We evaluated CVRF and RA characteristics. We non-invasively assessed them with g-SPECT to reveal ischemia, territories and severity. We calculated relative risks and 95% CI of ischemia given the associated variables. Results: 22 (24.2%) patients presented ischemia, half of them in the LAD territory. Regarding CVRF and disease's characteristics; only smokers and patients under a steroid treatment were at more risk to present ischemia (0.49 [0.24 to 0.98] and 2.04 [1.01 to 4.14], respectively) with a p = 0.046. Conclusion: We have contributed with additional evidence to strategically diagnose IHD in patients with RA even if they have no symptoms and independently of the existence of cardiovascular risk factors to prevent and reduce cardiovascular mortality.
Resumen: Introducción: La IC se ha convertido en un importante punto de partida a largo plazo para los pacientes con AR independientemente de los FRCV tradicionales. Por lo tanto, las lesiones cardiovasculares y la mortalidad podrían deberse a la presencia de una respuesta inflamatoria sistemática crónica. Sin embargo, hay una brecha en su diagnóstico ya que los síntomas permanecen en silencio hasta que ocurren eventos importantes. Objetivo: Evaluar mediante tomografía computarizada de emisión de un solo fotón (g-SPECT). Perfusión miocárdica en pacientes mexicanos asintomáticos con AR y al menos un FRCV tradicional, sin antecedentes de angina. Pacientes y métodos: Se realizó un estudio prospectivo con un número total de 91 pacientes. Se evaluaron las características FRCV y AR. Los evaluamos de forma no invasiva con g-SPECT para revelar isquemia, territorios y severidad. Se calcularon los riesgos relativos la isquemia de 95% dadas las variables asociadas. Resultados: Veintidós (24.2%) pacientes presentaron isquemia, la mitad de ellos en territorio LAD. Respecto a los FRCV y características de la enfermedad; sólo los fumadores y los pacientes sometidos a un tratamiento con esteroides presentaron mayor riesgo de presentar isquemia (0.49 [0.24 a 0.98] y 2.04 [1.01 a 4.14], respectivamente) con p = 0.046. Conclusión: Hemos aportado pruebas adicionales para diagnosticar la isquemia estratégicamente en los pacientes con AR, incluso si no tienen síntomas y con independencia de la existencia de factores de riesgo cardiovascular para prevenir y reducir la mortalidad cardiovascular.
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Resumen La conciencia de los formadores del área de la salud para promover la conducta ética en la formación de estudiantes de odontología se constata en los planes de estudio de pregrado. El presente estudio busca develar las diferentes formas utilizadas para enseñar estas materias. Para ello, se revisa manualmente la literatura publicada en bases de datos indexadas en SciELO en los años 1999-2014, que se encuentran bajo el título ciencias de la salud, humanidades, ciencias sociales aplicadas, a las que se puede acceder on-line, a texto completo, gratuito, en forma anónima y también en las siguientes revistas especializadas de educación en salud: Journal of Dental Education (ADEA), Journal of Medical Education (AMM), con los mismos títulos, durante el mismo periodo y a través del motor de búsqueda PubMed vía Medline. Los resultados arrojan 43 artículos de pertinencia temática. Se concluye que la enseñanza de bioética en los planes de estudio de pregrado en las escuelas de odontología es creciente y se diferencia según los entornos educativos y culturales en que se desarrolla; las formas de enseñanza mencionadas como más eficientes son el aprendizaje basado en casos y el aprendizaje basado en problemas; la formación de odontólogos íntegros requiere que la enseñanza de estas materias esté a cargo de equipos profesionales interdisciplinarios suficientemente preparados.
Abstract The awareness of educators in the health sciences with respect to promoting ethical conduct when instructing dental students is reflected in the undergraduate curriculum. This study is intended to discover the different ways these subjects are taught. A manual review of the literature published in databases indexed in SciELO during the years from 1999 to 2014 was done to that end, under the heading health sciences, humanities, applied social sciences, specifically literature that can be accessed in full, free of charge and anonymously. Also reviewed was the literature in two specialized journals in the area of health education; namely, the Journal of Dental Education (ADEA) and the Journal of Medical Education (AMM), with the same titles, during the same period, and through the PubMed search engine, via Medline. The results show 43 articles of thematic relevance. The conclusion is that education in bioethics, as part of the undergraduate curriculum at dental schools, is increasing and differs according to the educational and cultural environment where it is imparted. Case-based learning and problem-based learning are mentioned as being the most efficient methods of instruction. Training dentists to be well-rounded professionals requires these subjects to be taught by interdisciplinary teams that are sufficiently prepared to do so.
Resumo A consciência dos formadores da área da saúde para promover a conduta ética na formação de estudantes de odontologia constata-se nos planos de estudo de graduação. O presente estudo procura revelar as diferentes formas utilizadas para ensinar essas matérias. Para isso, revisa-se manualmente a literatura publicada em bancos de dados indexados em SciELO nos anos 1999-2014, que se encontram sob o título ciências da saúde, humanidades, ciências sociais aplicadas, às quais pode se acessar on-line, a texto completo, gratuito, em forma anônima e também nas seguintes revistas especializadas de educação em saúde: Journal of Dental Education (ADEA), Journal of Medical Education (AMM), com os mesmos títulos, durante o mesmo período e por meio do motor de busca PubMed via Medline. Os resultados mostram 43 artigos de pertinência temática. Conclui-se que o ensino de bioética nos planos de estudo de pós-graduação nas Escolas de Odontologia é crescente e se diferencia segundo os meios educativos e culturais em que se desenvolve; as formas de ensino mencionadas como mais eficientes são a aprendizagem baseada em casos e a aprendizagem baseada em problemas; a formação de odontólogos íntegros requer que o ensino dessas matérias esteja a cargo de equipes profissionais interdisciplinares suficientemente preparadas.
Assuntos
Humanos , Estudantes de Odontologia , Saúde , Educação em Odontologia , Ética , Fenômenos Fisiológicos DentáriosRESUMO
El angioedema hereditario es una enfermedad genética rara, autosómica dominante, con una aparición de 1:10 000 a 1:50 000 habitantes, que presenta como síntoma principal episodios de edema definido, doloroso, deformante con ausencia de prurito, generalmente localizado en las extremidades. El diagnóstico se realiza basado en anamnesis, examen físico y determinación de C4, C1 - INH, cuyos niveles séricos deben encontrarse bajos. Se presenta el caso de un paciente masculino de 33 años que asiste a consulta con un edema deformante en el rostro y en las extremidades superiores, refiere que en su familia un abuelo presentó un cuadro semejante y sus dos hijos tienen estos síntomas. Los exámenes realizados reflejaron: C3: 87 mg/dL, C4: 10 mg/dL y actividad funcional de C1-INH: 33 por ciento; el resto de los estudios hormonales e inmunológicos mostraron valores dentro de los rangos normales. Se diagnosticó como angioedema hereditario tipo II y se impuso tratamiento profiláctico con Danazol (200 mg); el paciente lleva cuatro meses sin episodios(AU)
Hereditary angioedema is a rare genetic autosomal dominant disease with an appearance from 1:10 000 to 1:50 000, which main symptom is defined episodes of painful deforming edema with absence of pruritus, usually located in extremities. Diagnosis is based on anamnesis, physical examination and determination of C4, C1-INH, where low serum must be found. We present a male patient aged 33, who attends a consultation with disfiguring edema in the face and upper extremities reporting that in his family a grandfather presented a similar symptom as well as his two sons. The tests made reflected: C3: 87 mg / dl, C4: 10 mg / dl and functional activity of C1-INH: 33 percernt; other hormonal and immunological studies showed values within normal ranges. He was diagnosed as hereditary angioedema type II and received prophylactic treatment with Danazol (200 mg); the patient has now been four months without episodes(AU)
Assuntos
Humanos , Masculino , Adulto , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Angioedemas Hereditários/diagnóstico , Danazol/uso terapêuticoRESUMO
Introducción: la rinitis alérgica es un trastorno sintomático, con inflamación de la mucosa nasal mediada por IgE e inducida por la exposición a alérgenos. Sus tres síntomas cardinales son la obstrucción nasal, los estornudos y la rinorrea. La rinitis alérgica es un problema global que va aumentando su prevalencia. Objetivo: evaluar la efectividad del montelukast en los niños con rinitis alérgica persistente perteneciente al Policlínico René Ávila Reyes de Holguín durante el periodo de octubre de 2012 a febrero de 2013. Método: se realizó un estudio analítico prospectivo en 20 pacientes pediátricos con rinitis alérgica persistente con edades entre los 6 y 19 años. Las variables estudiadas fueron sexo, edad, otras enfermedades alérgicas, síntomas nasales diurnos, síntomas nocturnos, síntomas oculares diurnos y valor total de eosinófilos. Se utilizó la prueba de McNemar con un p=0,01. Resultados: predominaron 12 pacientes del sexo masculino, (60,0%), 16 pacientes con asma bronquial (80,0%) y 8 con dermatitis atópica (40,0%). Antes del tratamiento 20 niños presentaban prurito nasal, luego del mismo solo un niño mantuvo esta condición (5,0%); 16 niños presentaban congestión nasal (80,0%) después del tratamiento solo un niño conservó esta condición (5,0%). Antes del tratamiento solo un paciente presentaba valores normales de la eosinófilos y luego del mismo esta cifra aumentó a 17 niños para el 85,0%. Conclusiones: en el grupo de estudio predominaron los pacientes masculinos, adolescentes y con asma bronquial. El montelukast fue efectivo en el manejo y control de los síntomas de los pacientes con rinitis alérgica.
Introduction: Allergic rhinitis is an IgE-mediated inflammation of the nasal mucosa induced after allergen exposure and presents with the 3 cardinal symptoms of sneezing, nasal obstruction, and rhinorrhea. Allergic rhinitis is a global health problem and is increasing in prevalence. Objective: to evaluate the effectiveness of montelukast in children with persistent allergic rhinitis in the Rene Avila Reyes Polyclinic, in Holguín, from October 2012 to February 2013. Methods: a prospective analytical study was performed including 20 patients aged from 6 to 19 years old. The variables analyzed in the study were: sex, age, other allergicdiseases, nasal symptoms in the day, symptoms in the night, and ocular symptoms in the day and total eosinophils. For comparative analysis we used the McNemar test p=0.01. Results: 12 patients (60.0%) of male sex were found, 16 (80.0%) with Bronchial Asthma and 8 (40.0%) with atopic dermatitis. Before the treatment 20 patients had nasal itch, 16 had nasal obstruction and 1 patient had normal levels of eosinophils. After treatment with montelukast 1 patient (5.0%) had nasal itch and nasal obstruction and 3 patients had high levels of eosinophils. Conclusions: in the population had prevalence of male patients, adolescents and with Bronchial Asthma. Montelukast was effective for managing and control of symptoms the patients with Allergic Rhinitis.