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The COVID-19 pandemic has had a substantial adverse impact on the physical and mental health of pregnant and postpartum women, thereby increasing the risk of postpartum depression (PPD). This study aimed to evaluate the effectiveness of a continuous contactless exercise intervention in reducing the risk of depression during the prenatal and postnatal periods. The study utilized an interactive contactless exercise program consisting of Pilates movement over a 16-week period, with 8 weeks during pregnancy and 8 weeks after childbirth. Metabolic and psychological factors related to postpartum depression, including pain, stress, and stress-response markers, were analyzed. The results showed that the exercise intervention significantly alleviated postpartum depression by improving pain (Oswestry Disability Index: Non-exercise, 11.4 ± 14.8 versus Exercise, - 63.1 ± 18.4, p < .001) and stress factors (Edinburgh Postnatal Depression Scale: Non-exercise, 8.8 ± 8.72 versus Exercise, - 37.6 ± 9.13, p < .001; Perceived Stress Scale: Non-exercise, 9.21 ± 9.35 versus Exercise, - 20.7 ± 14.4, p < .001) caused by physical/structural imbalances in postpartum women. Additionally, the intervention improved the metabolic imbalances commonly observed after childbirth, including reductions in triglyceride (Interaction effect, p = .017), insulin (Interaction effect, p = .032), and cortisol levels (Interaction effect, p < .001), which are recognized risk factors for postpartum depression. Taken together, these findings suggest that contactless online exercise interventions can mitigate postpartum depression by addressing metabolic dysregulation that frequently occurs after delivery, especially in situations of social isolation caused by the pandemic.
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COVID-19 , Depressão Pós-Parto , Terapia por Exercício , Humanos , Feminino , Depressão Pós-Parto/prevenção & controle , Gravidez , COVID-19/prevenção & controle , Adulto , Terapia por Exercício/métodos , Período Pós-Parto/psicologia , SARS-CoV-2 , Cuidado Pré-Natal/métodos , Exercício FísicoRESUMO
This study aimed to assess the impact of different resistance training (RT) loads and repetition on muscle damage, intramuscular anabolic signaling, and maximal muscle strength (MMS) in weightlifters. Eighteen male weightlifters were randomly assigned to 8 weeks of supervised RT regimes: high-load, low-repetition (HL), low-load, high-repetition (LH), and combination of HL and LH (COMBI). All groups exhibited a significant increase in skeletal muscle mass (SMM) and growth hormone levels, which ultimately contributed to improvement in MMS as indicated by 1-repetition maximum in the back squat and back muscle strength. Notably, while there were no significant changes in the mTOR protein, the phosphorylation of phosphorylation of p70 ribosomal protein S6 kinase 1 (p70S6K1), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic elongation factor 2 (eEF2), which are involved in muscle cell growth, was significantly affected by the different training regimens. More importantly, LH-RT led to a significant reduction in muscle damage markers, creatine kinase (CK) and lactate dehydrogenase (LDH), suggesting reduced recovery time and fatigue. Our results demonstrated that the LH-RT paradigm could be a viable alternative for weightlifters to enhance MMS and muscle hypertrophy similar to HL-RT, while reducing RT-induced muscle damage, ultimately contributing to the enhancement of exercise performance.
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Músculo Esquelético , Treinamento Resistido , Masculino , Humanos , Músculo Esquelético/metabolismo , Treinamento Resistido/métodos , Força Muscular/fisiologia , Exercício Físico/fisiologia , Creatina Quinase/metabolismoRESUMO
BACKGROUND: The gut-brain axis (GBA) in Parkinson's disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. RESULTS: The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSE-hαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. CONCLUSIONS: The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.
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The COVID-19 pandemic has increased the prevalence of depressive disorders worldwide, requiring alternative treatments beyond medication and psychotherapy. Exercise has positive effects on the brain; therefore, it has emerged as a promising therapeutic option for individuals with depression. Considerable research involving humans and animals offers compelling evidence to support the mental health benefits of physical activity or exercise mediated by the regulation of complex theoretical paradigms. However, challenges such as conducting long-term follow-up assessments and considering individual characteristics remain in human studies despite extensive efforts. While animal studies provide valuable insights into the potential benefits of exercise and its impact on outcomes related to depression and anxiety in rodents exposed to different stress paradigms, translating the findings to humans requires careful evaluation. More research is needed to establish precise exercise prescription guidelines and to better understand the complex relationship between exercise and depressive disorders. Therefore, this concise review explores the evidence supporting exercise intervention as an antidepressant treatment and its underlying mechanisms.
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BACKGROUND: Blunt cardiac injury (BCI) has a variety of symptoms that may be a potentially life-threatening injury that can lead to death. Depending on the diagnosis of BCI, treatment direction and length of stay may vary. In addition, the utility of other diagnostic tests for cardiac disease as diagnostic tools for BCI remain unclear. The purpose of this study was to investigate the competence of N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac index (C.I) as adjunctive diagnostic tools for BCI. METHODS: From January 2018 to March 2020, severe trauma patients with sternum fracture who were admitted to the traumatic intensive care unit (TICU) were included this study. Patients with sternum fracture, 18 years of age or older, and with an injury severity score > 16 who required intensive care were included. Invasive measurement for the analysis of the pulse contour for C.I monitoring and intravenous blood sampling for NT pro-BNP measurement were performed. Sampling and 12-lead electrocardiogram were performed at different time points as follows: immediately after TICU admission and at 24 h and 48 h after trauma. RESULTS: Among 103; 33 patients with factors that could affect NT pro-BNP were excluded; therefore, 63 patients were included in this study. According to the American Association for the Surgery of Trauma Cardiac Injury Scale, 33 patients were diagnosed with non-BCI, and 30 patients constituted with BCI. The median ages of the patients were 58 (52-69), and 60 (45-69) years in the non-BCI and BCI groups, respectively (p = 0.77). The median NT pro-BNP values were higher in the BCI group on admission, hospital day (HD) 2, and HD 3, however, no statistical difference was observed (125 (49-245) vs. 130 (47-428) pg/mL, p = 0.08, 124 (68-224) vs. 187 (55-519) pg/mL, p = 0.09, and 121(59-225) vs. 133 (56-600) pg/mL, p = 0.17, respectively). On the contrary, significantly lower values were observed in the median C.I measurement on admission and HD 3 in the BCI group (3.2 (2.8-3.5) vs. 2.6 (2.3-3.5) L/min/m2, p < 0.01 and 3.2 (3.1-3.9) vs. 2.9 (2.4-3.2) L/min/m2, p < 0.01, respectively); however, no significant difference was observed on HD 2 (3.4 (3.0-3.7) vs. 2.6 (2.4-3.4) L/min/m2, p = 0.17), Furthermore, The median lactate levels in the BCI group upon admission, HD 2, and HD 3 were significantly higher than those in the non-BCI group (1.8 (1.1-2.6) vs. 3.1 (2.1-4.4) mmol/L, p < 0.01; 1.3 (0.8-2.3) vs. 3.0 (2.2-4.7) mmol/L, p < 0.01; and 1.5 (0.9-1.5) vs. 2.2 (1.3-3.7) mmol/L, p < 0.01, respectively). CONCLUSION: Consecutive values of NT pro-BNP and C.I show no correlation with ECG-based BCI diagnosis. However, lactate level measurement may help in the early recognition of BCI as an adjunctive tool. It should be noted that this is a hypothesis-generating study for BCI diagnosis. Further studies should be conducted in larger populations with a prospective approach.
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Contusões Miocárdicas , Peptídeo Natriurético Encefálico , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Biomarcadores/sangue , Biomarcadores/metabolismo , Cuidados Críticos , Unidades de Terapia Intensiva , Lactatos , Contusões Miocárdicas/sangue , Contusões Miocárdicas/metabolismo , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de PeptídeosRESUMO
BACKGROUND: Alzheimer's disease (AD) pathology is associated with complex interactions among multiple factors, involving an intertwined network of various signaling pathways. The polypharmacological approach is an emerging therapeutic strategy that has been proposed to overcome the multifactorial nature of AD by targeting multiple pathophysiological factors including amyloid-ß (Aß) and phosphorylated tau. We evaluated a blood-brain barrier penetrating phosphodiesterase 5 (PDE5) inhibitor, mirodenafil (5-ethyl-2-7-n-propyl-3,5-dihydrro-4H-pyrrolo[3,2-d]pyrimidin-4-one), for its therapeutic effects on AD with polypharmacological properties. METHODS: To evaluate the potential of mirodenafil as a disease-modifying AD agent, mirodenafil was administered to test its effects on the cognitive behaviors of the APP-C105 AD mouse model using the Morris water maze and passive avoidance tests. To investigate the mechanisms of action that underlie the beneficial disease-modifying effects of mirodenafil, human neuroblastoma SH-SY5Y cells and mouse hippocampal HT-22 cells were used to show mirodenafil-induced alterations associated with the cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG)/cAMP-responsive element-binding protein (CREB) pathway, apoptotic cell death, tau phosphorylation, amyloidogenesis, the autophagy-lysosome pathway, glucocorticoid receptor (GR) transcriptional activity, and the Wnt/ß-catenin signaling. RESULTS: Here, mirodenafil is demonstrated to improve cognitive behavior in the APP-C105 mouse model. Mirodenafil not only reduced the Aß and phosphorylated tau burdens in vivo, but also ameliorated AD pathology induced by Aß through the modulation of the cGMP/PKG/CREB signaling pathway, glycogen synthase kinase 3ß (GSK-3ß) activity, GR transcriptional activity, and the Wnt/ß-catenin signaling in neuronal cells. Interestingly, homodimerization and nuclear localization of GR were inhibited by mirodenafil, but not by other PDE5 inhibitors. In addition, only mirodenafil reduced the expression levels of the Wnt antagonist Dickkopf-1 (Dkk-1), thus activating the Wnt/ß-catenin signaling. CONCLUSIONS: These findings strongly suggest that the PDE5 inhibitor mirodenafil shows promise as a potential polypharmacological drug candidate for AD treatment, acting on multiple key signaling pathways involved in amyloid deposition, phosphorylated tau burden, the cGMP/PKG/CREB pathway, GSK-3ß kinase activity, GR signaling, and the Wnt/ß-catenin signaling. Mirodenafil administration to the APP-C105 AD mouse model also improved cognitive behavior, demonstrating the potential of mirodenafil as a polypharmacological AD therapeutic agent.
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Doença de Alzheimer , Neuroblastoma , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , GMP Cíclico , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Camundongos , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Fosforilação , Pirimidinonas , Sulfonamidas , beta Catenina/metabolismo , beta Catenina/uso terapêutico , Proteínas tau/metabolismoRESUMO
Pilates is effective for training the core muscles and stabilizing the hip joints, which provides relief from pelvic pain and low back pain during pregnancy. However, there are no specific guidelines on appropriate physical exercises for pregnant women due to the current pandemic. We aimed to apply the exercise standard proposed by the American College of Obstetricians and Gynecologists to home-based tele-Pilates exercise (HTPE), to determine its effect on the physical and mental health of pregnant women. We randomly divided the subjects into the following two groups who completed 8 weeks of HTPE (50 min/day, 2 days/week): (a) Pilates exercise (PE, n = 7) and (B) non-Pilates exercise (CON, n = 7). HTPE was performed by adjusting the program every 3 weeks, based on pain and physical fitness levels. We measured body composition, muscles of the hip joint, pelvic tilt, Oswestry Disability Index (ODI), and Pittsburgh Sleep Quality Index (PSQI), before and after HTPE. Following HTPE, while the percentage of body fat and body mass index had significantly decreased, the body fat mass did not change in the PE group (p < 0.05). The PE group showed an increase in strength of the left and right hip flexion and hip abduction, compared to the CON group (p < 0.01). The ODI and PSQI were significantly decreased in the PE group (p < 0.05). Therefore, the 8-week HTPE program is an effective exercise for pregnant woman that reduces body fat metabolism and strengthens muscles of the hip joint, thus alleviating pregnancy-induced low back pain and insomnia.
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PURPOSE: The molecular mechanisms by which physical exercise produces beneficial effects on pathologic features and behavioral symptoms of Alzheimer's disease (AD) are not well understood. Herein, we examined whether regular moderate exercise could improve cognitive function and produce transcriptomic responses in the brain. METHODS: Four groups of mice were studied: nontransgenic control, mice expressing the human presenilin-2 wild type, mice expressing the human presenilin-2 with the N141I mutation (Tg-PS2m), and Tg-PS2m that were subjected to treadmill exercise (TE) at a speed of 10 m·min-1 for 50 min·d-1, 5 d·wk-1, for 6 wk (Tg-PS2m/Ex). RESULTS: Tg-PS2m/Ex mice exhibited increased preference in exploring a novel object than Tg-PS2m in the novel object recognition test, whereas differences observed in the water maze test and passive avoidance test were not significant. Western blot and histological analyses using amyloid oligomer (A11) and ß-amyloid (6E10) antibody indicated that amyloid oligomer-reactive bands and plaque deposition in the hippocampus were reduced, although not significantly, after TE. Transcriptomic (RNA-sequencing) analysis and subsequent protein analysis revealed that the cell cycle regulatory gene, Cdc28 protein kinase regulatory subunit 2 (Cks2), was decreased, and the cell cycle- and apoptotic cell death-related factors, including cyclin D1, proliferating cell nuclear antigen, and cleaved caspase-3, were increased in the hippocampus of Tg-PS2m, whereas TE reversed their altered expression. CONCLUSIONS: The results support the hypothesis that the pathologic features and behavioral symptoms of AD caused by accumulation of amyloid ß-peptide in hippocampus, causing aberrant cell cycle reentry and apoptosis, can be reversed by regular exercise.
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Doença de Alzheimer , Quinases relacionadas a CDC2 e CDC28 , Presenilina-2/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteínas de Ciclo Celular , Cognição , Modelos Animais de Doenças , Humanos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Presenilina-2/genéticaRESUMO
BACKGROUND: To determine whether the background of BALB/c substrains affects the response to anti-tumor drugs, we measured for alterations in tumor growth, histopathological structure of the tumor, and expressions of tumor-related proteins in three BALB/c substrains derived from different sources (BALB/cKorl, BALB/cA and BALB/cB), after exposure to varying concentrations of cisplatin (0.1, 1 and 5 mg/kg). RESULTS: Cisplatin treatment induced similar responses for body and organ weights, serum analyzing factors, and blood analyzing factors in all BALB/c substrains with CT26 syngeneic tumor. Few differences were detected in the volume and histopathological structure of the CT26 tumor. Growth inhibition of CT26 tumors after exposure to cisplatin was greater in the BALB/cB substrain than BALB/cKorl and BALB/cA substrains, and a similar pattern was observed in the histopathological structure of tumors. However, the expression levels of other tumor-related factors, including Ki67, p27, p53, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3 (Cas-3), matrix metallopeptidase 2 (MMP2) and vascular endothelial growth factor (VEGF) proteins, were constantly maintained in the tumors of all three substrains after cisplatin treatment. A similar decrease pattern was observed for the expressions of inflammatory cytokines, including interleukin (IL)-1ß, IL-6 and IL-10, in the CT26 tumors of the three BALB/c substrains. CONCLUSIONS: Taken together, results of the present study indicate that the genetic background of the three BALB/c substrains has no major effect on the therapeutic responsiveness of cisplatin, except growth and histopathology of the CT26 syngeneic tumor.
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BACKGROUND: As a laboratory animal resource, the ICR mouse is commonly used in a variety of research fields. However, information on differences in exercise-related characteristics in ICR mice derived from different lineages and the underlying mechanisms remains to be elucidated. In this study, we investigated the intrinsic exercise capacity and a magnitude of response to acute exercise, and sought to identify mechanisms contributing to difference in Korl:ICR (a novel ICR lineage recently established by the National Institute of Food and Drug Safety Evaluation, Korea) and two commercialized ICR lineages derived from different origins (viz., A:ICR mouse from Orient Bio Com, the United States, and B:ICR mouse from Japan SLC Inc., Japan). RESULTS: Results showed that despite no significant difference in body weight and weight-proportioned tissue mass of heart and skeletal muscles among groups, the relatively low intrinsic exercise capacity and exaggerated response to acute exercise were identified in B:ICR comparted with Korl:ICR and A:ICR, as reflected by total work and lactate threshold (LT). Also, the mitochondrial efficiency expressed as the complex 1 and complex 1 + 2 respiratory control ratio (RCR) values for cardiac mitochondrial O2 consumption in B:ICR was significantly lower than that in Korl:ICR with higher level of state 2 respiration by glutamate/malate and UCP3 expression in cardiac muscle. CONCLUSIONS: Taken together, these results indicate that the intrinsic exercise capacity of ICR mouse varies according to lineages, suggesting the role of cardiac mitochondrial coupling efficiency as a possible mechanism that might contribute to differences in the intrinsic exercise capacity and magnitude of response to exercise.
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BACKGROUND: Totally implantable central venous access ports (TICVAPs) have increasingly been used in pediatric patients because they provide reliable venous access. However, many complications associated with TICVAPs have been reported. Here, we aimed to analyze the risk factors of stuck fragment of TICVAPs during removal in children and recommend the appropriate periods of use or exchange. METHODS: We retrospectively reviewed the medical records of 121 patients, including 147 cases of TICVAP insertion, between January 2010 and July 2020. RESULTS: Among these, 98 cases in 72 patients involved of TICVAP removal, with 8 patients having had incomplete TICVAP removal resulting in a stuck fragment of the catheter in the central venous system (Group S). All Group S patients were male and had acute leukemia, and their TICVAPs were used for chemotherapy. Compared with the complete removal group (Group N), stuck fragment in Group S were significantly found in patients diagnosed with acute leukemia than those with other diagnoses (p < 0.001). Indwelling duration and body weight change during TICVAP indwelling were significantly longer and larger in Group S, respectively (p < 0.001). In multivariate logistic regression analysis, indwell duration (odds ratio [OR], 1.13; 95% confidence interval [Cl] 1.02-1.37, p = 0.10), body weight change during indwell (OR, 1.00; 95% Cl 0.83-1.18, p = 0.97), and platelet count at TICVAP insertion (OR, 0.98; 95% Cl 0.95-0.99; p = 0.48) showed an increased trend of risk for a stuck catheter. CONCLUSIONS: We suggest prophylactic catheter exchange before indwell duration of 46 months (area under the curve [AUC], 0.949; 95% Cl 0.905-0.993) and body weight change up to 9.9 kg (AUC, 0.903; 95% Cl 0.840-0.966) to prevent a catheter from becoming stuck, especially in children with rapidly growing acute leukemia. Management of a stuck fragment remains controversial in asymptomatic patients, and we suggest careful, close observation rather than aggressive and invasive treatment.
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Cateterismo Venoso Central , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Criança , Remoção de Dispositivo , Análise Fatorial , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Retroaortic innominate vein (RIV) is a rare vascular abnormality. Although RIV itself is asymptomatic, its presence in patients with partial anomalous pulmonary venous return (PAPVR) to the superior vena cava (SVC) is surgically challenging because a simple Warden procedure is impossible. CASE PRESENTATION: A 16-year-old girl was diagnosed with tetralogy of Fallot, secundum, and sinus venosus atrial septal defect (ASD) at birth. She underwent total correction of tetralogy of Fallot and ASD closure at the age of 14-months. However, the diagnosis of PAPVR was missed. At the age of 16, she developed dyspnea on exercise. Echocardiography demonstrated severe pulmonary regurgitation, mild tricuspid regurgitation, and D-shaped left ventricle with paradoxical septal motion along with RIV and sinus venous ASD. Computed tomography confirmed RIV and PAPVR. Systemic and pulmonary venous blood pathways were separated by bovine pericardial patch, and pulmonary valve replacement was performed. Postoperative echocardiography demonstrated improvement of D-shaped left ventricle and laminar flow through the SVC and pulmonary veins. Postoperative computed tomography showed a well-reconstructed SVC and pulmonary venous pathway without stenosis. After an uneventful postoperative course, patient was discharged. CONCLUSIONS: PAPVR in patients with RIV may be surgically challenging to repair. We report the first case of successfully repaired PAPVR associated with RIV.
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Veias Braquiocefálicas/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Diagnóstico Ausente/efeitos adversos , Veias Pulmonares/cirurgia , Síndrome de Cimitarra/cirurgia , Adolescente , Animais , Aorta/anormalidades , Aorta/diagnóstico por imagem , Veias Braquiocefálicas/anormalidades , Veias Braquiocefálicas/diagnóstico por imagem , Bovinos , Dispneia/etiologia , Dispneia/cirurgia , Ecocardiografia , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/cirurgia , Humanos , Veias Pulmonares/anormalidades , Veias Pulmonares/diagnóstico por imagem , Reoperação , Síndrome de Cimitarra/diagnóstico , Tomografia Computadorizada por Raios X , Veia Cava Superior/anormalidades , Veia Cava Superior/cirurgiaRESUMO
Treating cardiac injuries following blunt trauma to the chest requires thorough examination, accurate diagnosis, and therapeutic plan. We present two cases; pulmonary vein rupture and left atrial appendage laceration, both as a result of blunt chest trauma. Through these cases, our team learned the importance of maintaining hemodynamic stability during the examination of injured cardiac structures. And based on the comprehensive cardiac examination, a decision to surgically intervene with median sternotomy via cardiopulmonary bypass was made, saving lives of the patient. This report introduces how such decision was made based on what supporting evidence and the diagnostic process leading to the initiation of surgical intervention. This report may help with decision-making process when confronted by blunt cardiac injury patients who need cardiac exploration.
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Traumatic pulmonary giant hematoma, resulting from blunt trauma, is a relatively rare event. Here, we report the rare case of a patient with a giant traumatic pulmonary hematoma that was associated with blunt trauma. A 50-year-old man was admitted to our medical center after a fall from a height of 5 m. He was diagnosed with pulmonary contusion, and tests showed a huge pulmonary hematoma of approximately 8.2 × 5.3 × 13.2 cm in the left lung field along with other significant injuries. Treatment comprised of aggressive coagulation management, broad-spectrum antibiotics, and pulmonary hygiene. The patient's symptoms gradually improved and magnetic resonance scan revealed that he did not develop an abscess formation. No complications were seen at the 6 months follow-up visit. If the above mentioned measures would have failed to control the bleeding or secondary infection, then emergency surgery would have been warranted. Awareness of this kind of injury and efforts to reduce infection are important to guide the giant traumatic pulmonary hematoma to the benign course.
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Brain iron increases with age and abnormal brain iron metabolism is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD). The iron-regulatory effect of furin, a ubiquitously expressed proconvertase, might play an important role in AD. Therefore, there is an urgent need to study the effect of furin on iron regulation in AD. For that purpose, we aimed to determine the role of physical exercise in AD associated with brain iron dyshomeostasis. Treadmill exercise attenuated the AD-related abnormal brain iron regulation by furin in vivo, as demonstrated via experiments in aged APP-C105 mice. Next, we examined whether treadmill exercise decreases excessive iron, directly affecting amyloid-ß (Aß) production through the regulation of α-secretase-dependent processing of amyloid protein precursor (APP) involved in the modulation of furin activity. We first observed that cognitive decline and Aß-induced neuronal cell death were induced by disruption of APP processing via excess iron-induced disruption of furin activity in aged APP-C105 mice. The induced cognitive decline and cell death were attenuated by treadmill exercise. This result suggests that treadmill exercise alleviated cognitive decline and Aß-induced neuronal cell death by promoting α-secretase-dependent processing of APP through low iron-induced enhancement of furin activity. This is concomitant with decreasing levels of lipid peroxidation products and promoting antioxidant defense enzyme capacities. Therefore, iron-targeted therapeutic strategies involving treadmill exercise might be useful for patients with AD.
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Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/biossíntese , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Teste de Esforço/métodos , Ferro/metabolismo , Doença de Alzheimer/psicologia , Doença de Alzheimer/terapia , Animais , Morte Celular/fisiologia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/terapia , Teste de Esforço/psicologia , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/psicologiaRESUMO
BACKGROUND: Inflammatory bowel disease (IBD), including both Crohn's disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. RESULTS: Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitis-related clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1ß) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. CONCLUSIONS: These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.
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Sepsis, one of the most fatal diseases in the world, is known to culminate in multiple organ failure due to an uncontrolled inflammatory response. Hence, the use of animal models in sepsis research is very important to study complex immune responses. The current study was undertaken to compare commercial stocks with KFDA stocks of DBA/2 mice as an animal model for sepsis study. To compare responses of DBA/2 mice to lipopolysaccharides (LPS)-induced sepsis, we measured altered characteristics of various factors associated with sepsis, including survival curves, organ failure and inflammatory response, in DBA/2Korl stock and two commercial stocks (DBA/2A and DBA/2B). Survival rates after LPS exposure were similar for DBA/2Korl and DBA/2B; however, for times over 20 h, survival rates were reduced and concentration dependent in DBA/2A. In order to evaluate multiple organ failure caused by sepsis, H&E stains were evaluated for liver and spleen tissues obtained in the early (2 h) and later (20 h) stages after exposure to LPS; no significant differences were observed between the three stocks. mRNA and protein levels of proinflammatory cytokines were assessed for evaluating inflammatory reactions, and were found to increase in a dose-dependent manner in most DBA/2 mice after LPS treatment. However, no changes were observed in the mRNA levels of proinflammatory cytokines at 20 h after LPS exposure in the DBA/2A stock. The induction of inflammation-mediated factors by LPS exposure did not induce alterations in the mRNA levels of COX-2 and iNOS in all three DBA/2 stocks. Our results indicate that response of DBA/2Korl to LPS-induced sepsis is similar to the two commercial DBA/2 stocks, thus representing its potential as a useful biological resource established in Korea.
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Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.
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BACKGROUND: The long-term complication rates of open repair and thoracic endovascular aortic repair (TEVAR) have not yet been determined. Therefore, this study aimed to compare the long-term outcomes and aortic reintervention rates between open repair and TEVAR in patients with descending thoracic aortic pathologies. METHODS: Between January 2002 and December 2017, 230 patients with descending thoracic aortic pathologies underwent surgery. Of these, 136 patients were included in this retrospective study: 45 patients (10, 2, and 33 with dissection, penetrating atherosclerotic ulcer, and pseudoaneurysm, respectively) underwent open repair and 91 patients (27, 1, and 63 with dissection, penetrating atherosclerotic ulcer, and pseudoaneurysm, respectively) underwent TEVAR. The primary end points were in-hospital mortality, and short-term complications. The secondary end points were long-term mortality and reintervention rates. Based on the propensity score matching (PSM), 35 patients who underwent open repair were matched to 35 patients who underwent TEVAR (ratio = 1:1). RESULTS: The mean follow-up period was 70.2 ± 51.9 months. Shorter intensive care unit and hospital stay were seen in the TEVAR group than in the open repair group before and after PSM (p < 0.001 and p < 0.001, respectively). However, in-hospital mortality, and spinal cord ischemia were not significantly different among the two groups (before PSM: p = 0.068 and p = 0.211, respectively; after PSM: p = 0.303 and p = 0.314, respectively). The cumulative all-cause death and aorta-related death showed no significant differences between the two groups (before PSM: p = 0.709 and p = 0.734, respectively; after PSM: p = 0.888 and p = 0.731, respectively). However, aortic reintervention rates were higher in the TEVAR group than in the open repair group before and after PSM (p = 0.006 and p = 0.013, respectively). CONCLUSION: The TEVAR group was superior in short-term recovery outcomes but had higher reintervention rates compared to the open repair group. However, there were no significant differences in long-term survival between the two groups.
Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Adulto , Idoso , Dissecção Aórtica/cirurgia , Falso Aneurisma/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/cirurgia , Aterosclerose/cirurgia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Úlcera/cirurgiaRESUMO
[This corrects the article DOI: 10.1186/s42826-020-00063-z.].