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BACKGROUND: Rural populations consistently experience a disproportionate burden of cancer, including higher incidence and mortality rates, compared to the urban populations. Factors that are thought to contribute to these disparities include limited or lack of access to care and challenges with care coordination (CC). In Hawaii, many patients residing in rural areas experience unique challenges with CC as they require inter-island travel for their cancer treatment. In this focus group study, we explored the specific challenges and positive experiences that impact the CC in rural Hawaii cancer patients. METHODS: We conducted two semi-structured focus group interviews with cancer patients receiving active treatment for any type of cancer (n = 8). The participants were recruited from the rural areas of Hawaii, specifically the Hawaii county and Kauai. Rural was defined using the Rural-Urban Commuting Area Codes (RUCA; rural ≥ 4). The focus group discussions were facilitated using open-ended questions to explore patients' experiences with CC. RESULTS: Content analysis revealed that 47% of the discussions were related to CC-related challenges, including access to care (27.3%), insurance (9.1%), inter-island travel (6.1%), and medical literacy (4.5%). Other major themes from the discussions focused on facilitators of CC (30.3%), including the use of electronic patient portal (12.1%), team-based approach (9.1%), family caregiver support (4.5%), and local clinic staff (4.5%). CONCLUSION: Our findings indicate that there are notable challenges in rural patients' experiences regarding their cancer care coordination. Specific factors such as the lack of oncologist and oncology services, fragmented system, and the lack of local general medical providers contribute to problems with access to care. However, there are also positive factors found through the help of facilitators of CC, notability the use of electronic patient portal, team-based approach, family caregiver support, and local clinic staff. These findings highlight potential targets of interventions to improve cancer care delivery for rural patients. TRIAL REGISTRATION: Not required.
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Grupos Focais , Acessibilidade aos Serviços de Saúde , Neoplasias , População Rural , Humanos , Havaí , Neoplasias/terapia , Feminino , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Idoso , Adulto , Pesquisa Qualitativa , Continuidade da Assistência ao Paciente/organização & administraçãoRESUMO
[Purpose] Virtual reality has been increasingly used to improve the balance performance of older adults; however, the effect remains inconclusive. This study aimed to examine the effects of virtual reality on the balance performance of older adults through a systematic review and meta-analysis. [Methods] The PubMed, MEDLINE, CINAHL, Cochrane Library, and PEDro electronic databases were searched. Only randomized clinical trials published in English from January 1st, 1980, to September 30, 2022, were included and reviewed. Outcome measures included the Berg Balance Scale, Timed Up and Go Test and Activity-specific Balance Confidence scale. [Results] The results showed that virtual reality training for older adults led to significant improvements in Berg Balance Scale scores and Timed Up and Go Test times compared with non-virtual reality training. However, such an outcome was not observed with regard to the Activity-specific Balance Confidence scale. [Conclusion] Virtual reality training is effective in improving both static and dynamic balance among older adults. However, its effect on their self-confidence regarding balance is not significant.
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BACKGROUND: Benign prostate obstruction (BOO) is becoming increasingly important in this aging society. Some urge/stress urinary incontinence (UUI/SUI) still occurs after endoscopic enucleation of the prostate (EEP). It remains unclear how post-EEP incontinence can be avoided. Currently, early apical release to ameliorate the traction of the external sphincter is the best technique for incontinence prevention. OBJECTIVE: To describe our surgical technique of anterior fibromuscular stroma (AFS)-preserved EEP for BOO. DESIGN, SETTING, AND PARTICIPANTS: The medical records of 60 consecutive patients who underwent AFS-preserved EEP for BOO in our center from September 2019 to December 2019 were retrospectively reviewed. SURGICAL PROCEDURE: AFS-preserved EEP starts at the 12 o'clock position of the urethra, and the junction between the AFS and transitional zone (T-zone) was identified. The AFS and T-zone were separated first to protect the AFS in the initial operative procedure. Then, following the usual enucleation procedure, AFS-preserved EEP could be achieved. MEASUREMENTS: Postoperative prostate-specific antigen (PSA), testosterone, urethral stricture, and voiding status, such as incontinence, uroflow, and postvoiding residual urine were assessed. RESULTS AND LIMITATIONS: The data show that AFS-preserved EEP could achieve similar surgical outcomes as other early apical release approaches. CONCLUSIONS: The preserved AFS provides a nice landmark at the 12 o'clock position during EEP.
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Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Incontinência Urinária , Masculino , Humanos , Próstata/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Terapia a Laser/métodos , Endoscopia/métodos , Hiperplasia Prostática/cirurgia , Prostatectomia/métodos , Ressecção Transuretral da Próstata/métodos , Incontinência Urinária/cirurgiaRESUMO
BACKGROUND: Depressive moods are commonly seen in patients who receive haemodialysis. This can cause a lack of compliance in their treatment procedures and increase the rate of hospitalization. This study aimed to investigate the relationship between social support and degree of depression in middle-aged and elderly patients undergoing haemodialysis and the predictors of depressive symptoms. METHODS: A cross-sectional correlational study was designed with a structured questionnaire survey. Patients over 40 years of age were included from five haemodialysis centres. Measures embraced a demographic and clinical characteristics questionnaire, the Centre for Epidemiologic Studies Depression Scale, and the Personal Resource Questionnaire 2000. Statistical analysis was performed using hierarchical multiple regression analysis. RESULTS: A total of 179 patients over 40 years of age were included from five haemodialysis centres in the analysis. The mean CES-D score was 19.0(12.3); the majority of participants (60.3%) had a CES-D score ≥ 15, indicating likely depressive status. The mean PRQ2000 score was 75.7(15.9). The proportional mean of the PRQ2000 was 72.11%, indicating moderate social support for participants in this study. Data disclosed that marital status, number of comorbidities, exercise behaviour, and social support could significantly predict depressive symptoms; total explanatory variance was 31.3%. CONCLUSION: Health care professionals should identify those at high risk of depressive symptoms when they provide care to the middle-aged and elderly patients undergoing haemodialysis. These findings may lead to greater insights into the nursing and rehabilitative care of patients treated by chronic maintenance haemodialysis.
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Depressão , Diálise Renal , Pessoa de Meia-Idade , Idoso , Humanos , Adulto , Depressão/etiologia , Estudos Transversais , Comorbidade , Inquéritos e QuestionáriosRESUMO
The association between intravascular photobiomodulation (iPBM) and crossed cerebellar diaschisis (CCD) and cognitive dysfunction in patients with traumatic brain injury (TBI) remains unknown. We postulate that iPBM might enable greater neurologic improvements. The objective of this study was to evaluate the clinical impact of iPBM on the prognosis of patients with TBI. In this longitudinal study, patients who were diagnosed with TBI were recruited. CCD was identified from brain perfusion images when the uptake difference of both cerebella was > 20%. Thus, two groups were identified: CCD( +) and CCD( -). All patients received general traditional physical therapy and three courses of iPBM (helium-neon laser illuminator, 632.8 nm). Treatment assemblies were conducted on weekdays for 2 consecutive weeks as a solitary treatment course. Three courses of iPBM were performed over 2-3 months, with 1-3 weeks of rest between each course. The outcomes were measured using the Rancho Los Amigos Levels of Cognitive Functioning (LCF) tool. The chi-square test was used to compare categorical variables. Generalized estimating equations were used to verify the associations of various effects between the two groups. p < 0.05 indicated a statistically significant difference. Thirty patients were included and classified into the CCD( +) and CCD( -) groups (n = 15, each group). Statistics showed that before iPBM, CCD in the CCD( +) group was 2.74 (exp 1.0081) times higher than that of CCD( -) group (p = 0.1632). After iPBM, the CCD was 0.64 (exp-0.4436) times lower in the CCD( +) group than in the CCD( -) group (p < 0.0001). Cognitive assessment revealed that, before iPBM, the CCD( +) group had a non-significantly 0.1030 lower LCF score than that of CCD( -) group (p = 0.1632). Similarly, the CCD( +) group had a non-significantly 0.0013 higher score than that of CCD( -) after iPBM treatment (p = 0.7041), indicating no significant differences between the CCD( +) or CCD( -) following iPBM and general physical therapy. CCD was less likely to appear in iPBM-treated patients. Additionally, iPBM was not associated with LCF score. Administration of iPBM could be applied in TBI patients to reduce the occurrence of CCD. The study failed to show differences in cognitive function after iPBM, which still serves as an alternative non-pharmacological intervention.
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Lesões Encefálicas Traumáticas , Disfunção Cognitiva , Diásquise , Procedimentos Endovasculares , Terapia com Luz de Baixa Intensidade , Humanos , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/radioterapia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/terapia , Diásquise/fisiopatologia , Diásquise/radioterapia , Estudos Longitudinais , Terapia com Luz de Baixa Intensidade/métodos , Resultado do Tratamento , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
PURPOSE: Investigate components of care for rotator cuff related shoulder pain in workers' compensation in relation to claim outcomes (claim duration, total medical spend, total claim cost, return to work outcome). METHODS: Engagement with (had care, time to care) four components of care (prescribed exercise, imaging, injections, surgery) were obtained from auditing 189 closed workers' compensation files. Associations were analysed between components of care and claim outcomes. RESULTS: 80% received prescribed exercise, 81% imaging, 42% injection and 35% surgery. Median time to imaging (11 days) was shorter than the prescribed exercise (27 days), with injection at 38 days and surgery 118.5 days. With univariable regression analysis higher age, the involvement of legal representation and the presence of rotator cuff pathology from diagnostic imaging (partial thickness tear or full thickness tear) were all associated with increased claim duration, total medical spend, total claim cost and less successful return to work outcomes. After adjusting for these three associations, having an injection or surgery were both positively associated with longer claim duration and greater medical spend, and surgery with greater total claim costs. In general, longer time to receiving components of care was associated with increased claim duration and reduced odds of returning to full duties at work. CONCLUSION: Early management was not consistent with clinical guidelines for managing workers' compensation rotator cuff related shoulder pain. This may negatively affect claims outcomes.
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Manguito Rotador , Indenização aos Trabalhadores , Humanos , Manguito Rotador/cirurgia , Dor de Ombro , Procedimentos Clínicos , AustráliaRESUMO
BACKGROUND: Although cognitive-behavioral therapy is the first-line treatment for insomnia, pharmacotherapy is often prescribed to treat insomnia and related symptoms. In addition, muscle relaxants are commonly prescribed to alleviate muscle soreness when the pain is unbearable. However, pharmacotherapy can lead to numerous side effects. The non-drug strategy intravascular laser irradiation of blood (iPBM) has been advocated to improve pain, wound healing, blood circulation, and blood cell function to relieve insomnia and muscle soreness symptoms. Therefore, we assessed whether iPBM improves blood parameters and compared drug use before and after iPBM therapy. METHODS: Consecutive patients who received iPBM therapy between January 2013 and August 2021 were reviewed. The associations between laboratory data, pharmacotherapies, and iPBM therapy were retrospectively analyzed. We compared patient characteristics, blood parameters, and drug use within the three months before the first treatment and the three months after the last treatment. We also compared the changes before and after treatment in patients who received ≥10 or 1-9 iPBM treatments. RESULT: We assessed 183 eligible patients who received iPBM treatment. Of them, 18 patients reported insomnia disturbance, and 128 patients reported pain in any part of their body. After the treatment, HGB and HCT significantly increased after treatment in both the ≥10 and 1-9 iPBM treatment groups (HGB p < 0.001 and p = 0.046; HCT p < 0.001 and p = 0.029, respectively). Pharmacotherapy analysis revealed no significant differences in drug use before and after treatment, though drug use tended to decrease after iPBM. CONCLUSIONS: iPBM therapy is an efficient, beneficial, and feasible treatment that increases HGB and HCT. While the results of this study do not support the suggestion that iPBM reduces drug use, further larger studies using symptom scales are needed to confirm the changes in insomnia and muscle soreness after iPBM treatment.
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Terapia com Luz de Baixa Intensidade , Mialgia , Distúrbios do Início e da Manutenção do Sono , Estudos Retrospectivos , Distúrbios do Início e da Manutenção do Sono/radioterapia , Mialgia/radioterapia , Humanos , Taiwan , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Testes Hematológicos , Fármacos Neuromusculares , Hipnóticos e Sedativos , AnalgésicosRESUMO
BACKGROUND AND AIMS: Insulin resistance is a key factor in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We evaluated the importance of subcutaneous abdominal adipose tissue (SAAT) inflammation and both plasma and SAAT-derived exosomes in regulating insulin sensitivity in people with obesity and NAFLD. METHODS: Adipose tissue inflammation (macrophage and T-cell content and expression of proinflammatory cytokines), liver and whole-body insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp and glucose tracer infusion), and 24-hour serial plasma cytokine concentrations were evaluated in 3 groups stratified by adiposity and intrahepatic triglyceride (IHTG) content: (1) lean with normal IHTG content (LEAN; N = 14); (2) obese with normal IHTG content (OB-NL; N = 28); and (3) obese with NAFLD (OB-NAFLD; N = 28). The effect of plasma and SAAT-derived exosomes on insulin-stimulated Akt phosphorylation in human skeletal muscle myotubes and mouse primary hepatocytes was assessed in a subset of participants. RESULTS: Proinflammatory macrophages, proinflammatory CD4 and CD8 T-cell populations, and gene expression of several cytokines in SAAT were greater in the OB-NAFLD than the OB-NL and LEAN groups. However, with the exception of PAI-1, which was greater in the OB-NAFLD than the LEAN and OB-NL groups, 24-hour plasma cytokine concentration areas-under-the-curve were not different between groups. The percentage of proinflammatory macrophages and plasma PAI-1 concentration areas-under-the-curve were inversely correlated with both hepatic and whole-body insulin sensitivity. Compared with exosomes from OB-NL participants, plasma and SAAT-derived exosomes from the OB-NAFLD group decreased insulin signaling in myotubes and hepatocytes. CONCLUSIONS: Systemic insulin resistance in people with obesity and NAFLD is associated with increased plasma PAI-1 concentrations and both plasma and SAAT-derived exosomes. ClinicalTrials.gov number: NCT02706262 (https://clinicaltrials.gov/ct2/show/NCT02706262).
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Citocinas/sangue , Exossomos/metabolismo , Resistência à Insulina , Macrófagos/metabolismo , Células T de Memória/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Gordura Subcutânea Abdominal/metabolismo , Adulto , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Células Cultivadas , Exossomos/imunologia , Feminino , Hepatócitos/metabolismo , Humanos , Insulina/sangue , Fígado/metabolismo , Macrófagos/imunologia , Masculino , Células T de Memória/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/metabolismo , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/diagnóstico , Obesidade/imunologia , Obesidade/fisiopatologia , Gordura Subcutânea Abdominal/imunologia , Técnicas de Cultura de TecidosRESUMO
INTRODUCTION: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improvement in survival outcomes. This study evaluated the pCR in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer after NAC. METHODS: We evaluated 417 patients who were diagnosed with invasive breast cancer and treated with NAC followed by curative surgery between January 2007 and December 2020 and analyzed the pCR for HR-positive and HER2-negative breast cancer. RESULTS: The median age at the time of surgery was 45.4 years, and 9.1% of patients (38 of 417) with HR-positive/HER2-negative status had pCR. Among patients with HR-positive/HER2-negative breast cancer, patients with single HR-positivity had a 20.2% pCR rate, and patients with double HR-positivity had a 4.4% pCR rate. Patients with a high Ki-67 index exhibited a higher pCR rate than those with a lower Ki-67 index (14.5% vs. 3.2%). Patients with single HR-positive and high Ki-67 values exhibited a significantly higher pCR rate than those with double HR-positive and low Ki-67 values (27.8% vs. 2.1%; p < 0.001). CONCLUSION: NAC could improve prognosis in patients with HR-positive/HER2-negative breast cancer with a single HR-positive and high Ki-67 values.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Hormônios/uso terapêutico , Humanos , Antígeno Ki-67/metabolismo , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
BACKGROUND: Stroke is a burdensome cerebral eventthat affects many aspects of daily activities such as motion, speech, memory, vision, and cognition. Intravascular laser irradiation of blood (ILIB) is a novel therapy, going beyond conventional rehabilitation modalities, that is effective in stroke recovery. Homocysteine ââis an important risk factor associated with stroke. However, there are few studies that examine the relationship between ILIB treatment and the level of homocysteine. In recent years, researchers use the single-photon emission computed tomography (SPECT) scan of the brain to evaluate stroke patients and patients with a neurologicdeficit. The present report investigates the clinical effect of ILIB treatment on the level of serum homocysteine, the perfusion change of impaired brain region via SPECT, and the patient's neurologic appearance. CASEPRESENTATION: We focus on a case of a 62-year-old man with subacute stroke accompanied with left hemiparesis and hyperhomocysteinemia, who showed dramatic improvement in muscle power, a decreasing level of homocysteine, and increased blood flow of the right cerebral after three-courseILIB treatment. CONCLUSION: We found that ILIB is effective in lowering serum levels of homocysteine and facilitating cerebral circulation for the patient with subacute stroke.
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Homocisteína , Acidente Vascular Cerebral , Encéfalo/irrigação sanguínea , Circulação Cerebrovascular , Humanos , Isquemia , Lasers , Masculino , Pessoa de Meia-Idade , Paresia/complicações , Perfusão/efeitos adversos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a rare disease associated with different level of anterior pituitary hormone deficiency resulting with a variety of clinical manifestations which could limit exercise capacity. Cardiopulmonary exercise test (CPET) is valuable in differential diagnosis of exercise intolerance and exercise prescription. CASE PRESENTATION: An 18-year-old male adolescent was diagnosed with PSIS at 4 years old, had undergone growth hormone supplement until puberty, and was referred to rehabilitation department due to exercise intolerance. We arranged pulmonary function test (PFT) and CPET to clarify the cause of limited capacity. The test result provided evidence of moderate functional impairment (54% of predicted maximal oxygen uptake) mainly affected by physical unfitness without significant cardiovascular or pulmonary limitations. CONCLUSION: CPET serves as a valuable tool for diagnostic purpose. Aerobic and resistance exercise training for the patient should be conducted promptly for better prognosis but under safe circumstances, with criteria which could be provided by CPET results.
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Teste de Esforço , Doenças da Hipófise , Adolescente , Pré-Escolar , Exercício Físico , Teste de Esforço/métodos , Tolerância ao Exercício , Humanos , Masculino , Doenças da Hipófise/complicações , Doenças da Hipófise/diagnóstico , Hipófise/diagnóstico por imagemRESUMO
LMBD1 was previously demonstrated to regulate the endocytosis of insulin receptor on the cell surface and to mediate the export of cobalamin from the lysosomes to the cytosol, but little is known about its function in mitosis. In this study, interactome analysis data indicate that LMBD1 is involved in cytoskeleton regulation. Both immunoprecipitation and GST pulldown assays demonstrated the association of LMBD1 with tubulin. Immunofluorescence staining also showed the colocalization of LMBD1 with microtubule in both interphase and mitotic cells. LMBD1 specifically accelerates microtubule assembly dynamics in vitro and antagonizes the microtubule-disruptive effect of vinblastine. In addition, LMBRD1-knockdown impairs mitotic spindle formation, inhibits tubulin polymerization, and diminishes the mitosis-associated tubulin acetylation. The reduced acetylation can be reversed by ectopic expression of LMBD1 protein. These results suggest that LMBD1 protein stabilizes microtubule intermediates. Furthermore, embryonic fibroblasts derived from Lmbrd1 heterozygous knockout mice showed abnormality in microtubule formation, mitosis, and cell growth. Taken together, LMBD1 plays a pivotal role in regulating microtubule assembly that is essential for the process of cell mitosis.
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Citoesqueleto/fisiologia , Microtúbulos/fisiologia , Mitose , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Proteínas de Transporte Nucleocitoplasmático/fisiologia , Tubulina (Proteína)/química , Animais , Ciclo Celular , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas de Transporte Nucleocitoplasmático/genética , Domínios e Motivos de Interação entre Proteínas , Fuso Acromático/fisiologiaRESUMO
PURPOSE: To verify the role of lactate dehydrogenase to albumin (LDH/ALB) ratio as an independent prognostic factor for mortality due to the lower respiratory tract infection (LRTI) in the emergency department (ED). METHODS: We reviewed the electronic medical records of patients who were admitted to the ED for the management of LRTI between January 2018 and December 2020. Initial vital signs, laboratory data, and patient severity scores in the ED were collected. The LDH/ALB ratio was compared to other albumin-based ratios (blood urea nitrogen to albumin ratio, C-reactive protein to albumin ratio, and lactate to albumin ratio) and severity scales (pneumonia severity index, modified early warning score, CURB-65 scores), which are being used as prognostic factors for in-hospital mortality. Multivariable logistic regression was performed to identify independent risk factors. RESULTS: The LDH/ALB ratio was higher in the non-survivor group than in the survivor group (median [interquartile range]: 217.6 [160.3;312.0] vs. 126.4 [100.3;165.1], p < 0.001). In the comparison of the area under the receiver operating characteristic curve (AUC) for predicting in-hospital mortality, the AUC of the LDH/ALB ratio (0.808, 95% confidence interval: 0.757-0.842, p < 0.001) was wider than other albumin-based ratios and severity scales, except the blood urea nitrogen to albumin ratio. In the multivariable logistic regression analysis, the LDH/ALB ratio independently affected in-hospital mortality. CONCLUSION: The LDH/ALB ratio may serve as an independent prognostic factor for in-hospital mortality in patients with LRTI.
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L-Lactato Desidrogenase/sangue , Infecções Respiratórias/sangue , Albumina Sérica/análise , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/mortalidade , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Guillain-Barré syndrome (GBS) often develops after a respiratory or gastrointestinal infection. A few cases have been reported on GBS following elective spinal surgery not preceded by an infectious disease. In patients with underlying upper motor neuron disease such as a spinal cord injury, concurrent development of lower motor neuron diseases, such as GBS, could be overlooked. Here, we present an uncommon case of an 87-year-old man with GBS that had developed after an operation for a traumatic cervical spinal cord injury. After surgery, he showed weakness over all four limbs with paresthesia, but he was able to hold a standing position with minimal assistance. Unfortunately, his muscle strength over his four limbs gradually weakened from two to four weeks later, and he became almost completely paralyzed. Cerebrospinal fluid (CSF) studies revealed albuminocytologic dissociation. A nerve conduction study (NCS) indicated an acute axonal polyneuropathy superimposed on chronic sensorimotor polyneuropathy. Thus, the patient was diagnosed with GBS. However, the patient's family declined immune-modulatory therapy due to personal reasons. The patient progressed into respiratory failure and remained ventilator-dependent before his death three years later. This case highlights the importance of taking GBS into account when postoperative weakness occurs in patients with spinal cord injury, and a worse prognosis if GBS is left untreated.
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Medula Cervical , Síndrome de Guillain-Barré , Polineuropatias , Insuficiência Respiratória , Traumatismos da Medula Espinal , Idoso de 80 Anos ou mais , Medula Cervical/cirurgia , Síndrome de Guillain-Barré/etiologia , Humanos , Masculino , Polineuropatias/complicações , Insuficiência Respiratória/etiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgiaRESUMO
Type I and type III interferons (IFNs) are the frontline of antiviral defense mechanisms that trigger hundreds of downstream antiviral genes. In this study, we observed that MERS-CoV nucleocapsid (N) protein suppresses type I and type III IFN gene expression. The N protein suppresses Sendai virus-induced IFN-ß and IFN-λ1 by reducing their promoter activity and mRNA levels, as well as downstream IFN-stimulated genes (ISGs). Retinoic acid-inducible gene I (RIG-I) is known to recognize viral RNA and induce IFN expression through tripartite motif-containing protein 25 (TRIM25)-mediated ubiquitination of RIG-I caspase activation and recruitment domains (CARDs). We discovered that MERS-CoV N protein suppresses RIG-I-CARD-induced, but not MDA5-CARD-induced, IFN-ß and IFN-λ1 promoter activity. By interacting with TRIM25, N protein impedes RIG-I ubiquitination and activation and inhibits the phosphorylation of transcription factors IFN-regulatory factor 3 (IRF3) and NF-κB that are known to be important for IFN gene activation. By employing a recombinant Sindbis virus-EGFP replication system, we showed that viral N protein downregulated the production of not only IFN mRNA but also bioactive IFN proteins. Taken together, MERS-CoV N protein functions as an IFN antagonist. It suppresses RIG-I-induced type I and type III IFN production by interfering with TRIM25-mediated RIG-I ubiquitination. Our study sheds light on the pathogenic mechanism of how MERS-CoV causes disease.IMPORTANCE MERS-CoV causes death of about 35% of patients. Published studies showed that some coronaviruses are capable of suppressing interferon (IFN) expression in the early phase of infection and MERS-CoV proteins can modulate host immune response. In this study, we demonstrated that MERS-CoV nucleocapsid (N) protein suppresses the production of both type I and type III IFNs via sequestering TRIM25, an E3 ubiquitin ligase that is essential for activating the RIG-I signaling pathway. Ectopic expression of TRIM25 rescues the suppressive effect of the N protein. In addition, the C-terminal domain of the viral N protein plays a pivotal role in the suppression of IFN-ß promoter activity. Our findings reveal how MERS-CoV evades innate immunity and provide insights into the interplay between host immune response and viral pathogenicity.
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Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Proteína DEAD-box 58/metabolismo , Interferon Tipo I/biossíntese , Interferons/biossíntese , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Proteínas do Nucleocapsídeo/metabolismo , Transdução de Sinais , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Linhagem Celular , Infecções por Coronavirus/genética , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/genética , Interferons/genética , Regiões Promotoras Genéticas , Ligação Proteica , Receptores Imunológicos , Fatores de Transcrição , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Interferon lambdaRESUMO
PURPOSE: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients. METHODS: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. RESULTS: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033-0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432-3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778-19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042-0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups. CONCLUSION: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Genes BRCA1 , Genes BRCA2 , Mutação , Adulto , Fatores Etários , Proteína BRCA1/biossíntese , Neoplasias da Mama/metabolismo , Feminino , Expressão Gênica , Testes Genéticos , Humanos , Imuno-Histoquímica , Estadiamento de Neoplasias , República da Coreia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: Sepsis induces gut barrier dysfunction characterized by increased gut epithelial apoptosis and increased intestinal permeability. The cytokine IL-22 has been demonstrated to regulate gut barrier function. Type-3 innate lymphoid cells (ILC3) are the predominate source of IL-22 in the GI tract. We hypothesized that sepsis may cause changes to the gut ILC3/IL-22 axis. MATERIALS AND METHODS: Sepsis was induced in WT and IL-22 KO mice by Pseudomonas aeruginosa pneumonia. Changes in gut-associated leukocyte populations were determined by flow-cytometry and ILC-associated transcripts were measured by RT-PCR. The effect of sepsis on gut permeability, pulmonary microbial burden, gut epithelial apoptosis, and survival was compared between WT and IL-22-/- mice. RESULTS: Sepsis resulted in a significant decrease in the number of ILC3 in the gut, with a reciprocal increase in type-1 ILC (ILC1). Consistent with prior reports, sepsis was associated with increased gut permeability; however there was no difference in gut permeability, gut epithelial apoptosis, pulmonary microbial burden, or survival between WT and IL-22-/- mice. CONCLUSIONS: Septic pneumonia causes a decrease in gut-associated ILC3 and an associated reciprocal increase in ILC1. This may reflect inflammation-induced conversion of ILC3 to ILC1. Constitutive systemic IL-22 deficiency does not alter sepsis-induced gut barrier dysfunction.
Assuntos
Mucosa Intestinal/imunologia , Linfócitos , Pneumonia Bacteriana/imunologia , Infecções por Pseudomonas/imunologia , Sepse/imunologia , Animais , Masculino , Camundongos Endogâmicos C57BL , Pneumonia Bacteriana/complicações , Infecções por Pseudomonas/complicaçõesRESUMO
BACKGROUND: Global aphasia without hemiparesis (GAWH) is a rare stroke syndrome characterized by the dissociation of motor and language functions. Here, we present a case of GAWH with the patient later regaining speech fluency. CASE PRESENTATION: A 73-year-old man was admitted to our emergency department immediately after an episode of syncope. On arrival, we noted his global aphasia but without any focal neurologic signs. Computed tomography (CT) perfusion scans showed a large hypodense region over his left perisylvian area. Under the impression of acute ischaemic stroke, he received recombinant tissue plasminogen activator (rtPA) injection and was treated as an inpatient. The patient was later discharged with GAWH status and received regular speech rehabilitation. After 14 months of rehabilitation, the patient gradually recovered his language expression ability. The degree of aphasia was evaluated with the Concise Chinese Aphasia Test (CCAT), and we obtained brain single photon emission computed tomography (SPECT) scans to assess cerebral blood flow. CONCLUSION: A patient with severe impairments of Broca's and Wernicke's areas was able to talk fluently despite being unintelligible. SPECT revealed relative high level of radioactivity uptake in the right frontal lobe, suggesting the deficits in speech fluency could have been compensated by the right hemisphere. Although this is a single case demonstration, the results may strengthen the role of the right hemisphere in GAWH patients and suggests additional study that examines the possible benefits of stimulating activity at right homologous regions for recovering language function after global aphasia.
Assuntos
Afasia de Wernicke/etiologia , Afasia/etiologia , AVC Isquêmico/complicações , Idoso , Afasia/reabilitação , Afasia de Wernicke/reabilitação , Humanos , Masculino , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
The inflammatory response to infection or injury dramatically increases the hematopoietic demand on the bone marrow to replace effector leukocytes consumed in the inflammatory response. In the setting of infection, pathogen-associated molecular patterns induce emergency hematopoiesis, activating hematopoietic stem and progenitor cells to proliferate and produce progeny for accelerated myelopoiesis. Sterile tissue injury due to trauma also increases leukocyte demand; however, the effect of sterile tissue injury on hematopoiesis is not well described. We find that tissue injury alone induces emergency hematopoiesis in mice subjected to polytrauma. This process is driven by IL-1/MyD88-dependent production of G-CSF. G-CSF induces the expansion of hematopoietic progenitors, including hematopoietic stem cells and multipotent progenitors, and increases the frequency of myeloid-skewed progenitors. To our knowledge, these data provide the first comprehensive description of injury-induced emergency hematopoiesis and identify an IL-1/MyD88/G-CSF-dependent pathway as the key regulator of emergency hematopoiesis after injury.
Assuntos
Fator Estimulador de Colônias de Granulócitos/imunologia , Hematopoese/imunologia , Interleucina-1/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Ferimentos e Lesões/imunologia , Animais , Fator Estimulador de Colônias de Granulócitos/genética , Hematopoese/genética , Interleucina-1/genética , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Ferimentos e Lesões/genética , Ferimentos e Lesões/patologiaRESUMO
All living beings on earth are influenced by the circadian rhythm, the rising and the setting of the sun. The ubiquitous effect of exercise is widely believed to maximize health benefits but has not been formally investigated for cardiac responses in the exercise-induced circadian rhythms. We hypothesized that the exercise-related proteome is differentially influenced by circadian rhythm and analyzed the differences between the effects of morning and evening exercise. Twenty-four Sprague-Dawley rats were randomly divided into four groups (n = 6 per group): morning control, morning exercise, evening control, and evening exercise groups. The exercise groups were subjected to 12-week treadmill exercise (5 days/week) performed either during daytime or nighttime. After 12 weeks, the physiological characteristics (e.g., body weight, heart weight, visceral fat, and blood metabolites), cardiovascular capacity (ejection fraction (%) and fractional shortening (%)), circadian gene expression levels (clock, ball1, per1, per2, cry1, and cry2), and the proteomic data were obtained and subjected to univariate and multivariate analysis. The mRNA levels of per1 and cry2 increased in the evening group compared with those in the morning group. We also found that per2 decreased and cry2 increased in the evening exercise groups. The evening exercise groups showed more decreased triacylglycerides and increased blood insulin levels than the morning exercise group. The principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis indicated that the circadian rhythm differently influenced the protein networks of the exercise groups. In the morning exercise group, the transcription-translation feedback loop (TTFL) (clock, per1, per2, cry1, and cry2) formed a protein-protein interaction network with Nme2, Hint1, Ddt, Ndufb8, Ldha, and Eef1a2. In contrast, the TTFL group appeared close to Maoa, Hist2h4, and Macrod1 in the evening exercise group. Interestingly, the evening exercise group decreased the mRNA level of per2 but not per1. Per1 and Per2 are known to transport Cry1 and Cry2 into the nucleus. Taken together, we summarized the characteristics of enriched proteins in the aspect of their molecular function, cellular component, and biological process. Our results might provide a better understanding of the circadian effect on exercise-related proteins.