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Transcranial direct current stimulation (tDCS) over left dorsolateral prefrontal cortex (DLPFC) has shown some potential as an adjunctive intervention for ameliorating negative symptoms of schizophrenia, but its efficacy requires optimization. Recently, 'functional targeting' of stimulation holds promise for advancing tDCS efficacy by coupling tDCS with a cognitive task where the target brain regions are activated by that task and further specifically polarized by tDCS.The study used 48-channel functional near infra-red spectroscopy (fNIRS) aiming to determine a cognitive task that can effectively induce a cortical activation of the left DLPFC in schizophrenia patients with predominant negative symptoms before running a tDCS trial. Sixty schizophrenia patients with predominant negative symptoms completed measures of clinical and psychosocial functioning characteristics and assessments across cognitive domains. Hemodynamic changes during n-back working memory tasks with different cognitive loads (1-back and 2-back) and verbal fluency test (VFT) were measured using fNIRS. For n-back tasks, greater signal changes were found when the task required elevated cognitive load. One sample t-test revealed that only 2-back task elicited significant activation in left DLPFC (t = 4.23, FDR-corrected p = 0.0007). During VFT, patients failed to show significant task-related activity in left DLPFC (one sample t-test, t = -0.25, FDR-corrected p > 0.05). Our study implies that 2-back task can effectively activate left DLPFC in schizophrenia patients with predominant negative symptoms. This neurophysiologically-validated task is considered highly potential to be executed in conjunction with high-definition tDCS for "functional targeting" of the left DLPFC to treat negative symptoms in a double-blind randomized sham-control trial, registered on ClinicalTrials.gov Registry (ID: NCT05582980).
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Esquizofrenia , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Pré-Frontal Dorsolateral , Esquizofrenia/terapia , Córtex Pré-Frontal/fisiologia , Análise Espectral , Método Duplo-CegoRESUMO
AIMS: Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design. METHODS: Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity. RESULTS: All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network. CONCLUSIONS: High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting.
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Background and Objectives: Hearing loss after septicemia has been found in mice; the long-term risk increased 50-fold in young adults in a previous study. Hearing loss after septicemia has not received much attention. The aim of this study was to assess the relationship between septicemia and subsequent hearing loss. Materials and Methods: Inpatient data were obtained from the Taiwan Insurance Database. We defined patients with sensorineural hearing loss and excluded patients under 18 years of age. Patients without hearing loss were selected as controls at a frequency of 1:5. The date of admission was defined as the date of diagnosis. Comorbidities in the 3 years preceding the date of diagnosis were retrieved retrospectively. Associations with hearing loss were established by multiple logistic regression and forward stepwise selection. Results: The odds ratio (OR) for the association between sepsis and hearing loss was 3.052 (95% CI: 1.583-5.884). Autoimmune disease (OR: 5.828 (95% CI: 1.906-17.816)), brain injury (OR: 2.264 (95% CI: 1.212-4.229)) and ischemic stroke (OR: 1.47 (95% CI: 1.087-1.988)) were associated with hearing loss. Conclusions: Our study shows that hearing loss occurred after septicemia. Apoptosis caused by sepsis and ischemia can lead to hair cell damage, leading to hearing loss. Clinicians should be aware of possible subsequent complications of septicemia and provide appropriate treatment and prevention strategies for complications.
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Surdez , Perda Auditiva Neurossensorial , Sepse , Adulto Jovem , Humanos , Animais , Camundongos , Adolescente , Estudos Retrospectivos , Fatores de Risco , Comorbidade , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/epidemiologia , Sepse/complicações , Sepse/epidemiologiaRESUMO
Background and Objectives: Attentional dysfunction has long been viewed as one of the fundamental underlying cognitive deficits in schizophrenia. There is an urgent need to understand its neural underpinning and develop effective treatments. In the process of attention, neural oscillation has a central role in filtering information and allocating resources to either stimulus-driven or goal-relevant objects. Here, we asked if resting-state EEG connectivity correlated with attentional performance in schizophrenia patients. Materials and Methods: Resting-state EEG recordings were obtained from 72 stabilized patients with schizophrenia. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity between 84 intra-cortical current sources determined by eLORETA (exact low-resolution brain electromagnetic tomography) for five frequencies. The Conners' Continuous Performance Test-II (CPT-II) was administered for evaluating attentional performance. Linear regression with a non-parametric permutation randomization procedure was used to examine the correlations between the whole-brain functional connectivity and the CPT-II measures. Results: Greater beta-band right hemispheric fusiform gyrus (FG)-lingual gyrus (LG) functional connectivity predicted higher CPT-II variability scores (r = 0.44, p < 0.05, corrected), accounting for 19.5% of variance in the CPT-II VAR score. Greater gamma-band right hemispheric functional connectivity between the cuneus (Cu) and transverse temporal gyrus (TTG) and between Cu and the superior temporal gyrus (STG) predicted higher CPT-II hit reaction time (HRT) scores (both r = 0.50, p < 0.05, corrected), accounting for 24.6% and 25.1% of variance in the CPT-II HRT score, respectively. Greater gamma-band right hemispheric Cu-TTG functional connectivity predicted higher CPT-II HRT standard error (HRTSE) scores (r = 0.54, p < 0.05, corrected), accounting for 28.7% of variance in the CPT-II HRTSE score. Conclusions: Our study indicated that increased right hemispheric resting-state EEG functional connectivity at high frequencies was correlated with poorer focused attention in schizophrenia patients. If replicated, novel approaches to modulate these networks may yield selective, potent interventions for improving attention deficits in schizophrenia.
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Transtornos Cognitivos , Esquizofrenia , Humanos , Esquizofrenia/complicações , Eletroencefalografia/métodos , Encéfalo , Lobo Temporal , Imageamento por Ressonância MagnéticaRESUMO
Endothelin (ET)-1 regulates adipogenesis and the endocrine activity of fat cells. However, relatively little is known about the ET-1 signaling pathway in preadipocyte growth. We used 3T3-L1 preadipocytes to investigate the signaling pathways involved in ET-1 modulation of preadipocyte proliferation. As indicated by an increased number of cells and greater incorporation of bromodeoxyuridine (BrdU), the stimulation of preadipocyte growth by ET-1 depends on concentration and timing. The concentration of ET-1 that increased preadipocyte number by 51-67% was ~100 nM for ~24-48 h of treatment. ET-1 signaling time dependently stimulated phosphorylation of ERK, c-JUN, STAT3, AMPK, and PKCα/ßII proteins but not AKT, JNK, or p38 MAPK. Treatment with an ETAR antagonist, such as BQ610, but not ETBR antagonist BQ788, blocked the ET-1-induced increase in cell proliferation and phosphorylated levels of ERK, c-JUN, STAT3, AMPK, and PKCα/ßII proteins. In addition, pretreatment with specific inhibitors of ERK1/2 (U0126), JNK (SP600125), JAK2/STAT3 (AG490), AMPK (compound C), or PKC (Ro318220) prevented the ET-1-induced increase in cell proliferation and reduced the ET-1-stimulated phosphorylation of ERK1/2, c-JUN, STAT3, AMPK, and PKCα/ß. Moreover, the SphK antagonist suppressed ET-1-induced cell proliferation and ERK, c-JUN, STAT3, AMPK, and PKC phosphorylation, and the SMase2 antagonist suppressed ET-1-induced cell proliferation. However, neither the p38 MAPK antagonist nor the CerS inhibitor altered the effect of ET-1. The results indicate that ETAR, JAK2/STAT3, ERK1/2, JNK/c-JUN, AMPK, PKC, SphK, and SMase2, but not ETBR, p38 MAPK, or CerS, are necessary for the ET-1 stimulation of preadipocyte proliferation.
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Adipócitos/efeitos dos fármacos , Endotelina-1/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteína Quinase C/genética , Fator de Transcrição STAT3/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Butadienos/farmacologia , Diferenciação Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Antagonistas dos Receptores de Endotelina/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , Nitrilas/farmacologia , Oligopeptídeos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Piperidinas/farmacologia , Proteína Quinase C/metabolismo , Piridinas/farmacologia , Receptores de Endotelina/genética , Receptores de Endotelina/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE-1 prostate epithelial cells, androgen-independent PC-3 PCa cells, and androgen-dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose- and time-dependent manners. Arecoline caused RWPE-1 and PC-3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC-3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N-acetylcysteine blocked the arecoline-induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.
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Areca/química , Arecolina/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Arecolina/química , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias da PróstataAssuntos
Traumatismos em Atletas , Virilha , Virilha/diagnóstico por imagem , Virilha/lesões , Humanos , Masculino , DorRESUMO
Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.
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BACKGROUND A traumatic coronary artery dissection is a rare but severe complication of chest trauma that can result in blockage of the coronary artery. The clinical symptoms can vary considerably, from asymptomatic arrhythmia to acute myocardial infarction and sudden death. This report describes a young man with coronary artery dissection following blunt chest trauma from a motorcycle accident presenting with ventricular fibrillation due to acute myocardial infarction, which was treated with percutaneous transluminal coronary angioplasty and extracorporeal membrane oxygenation. CASE REPORT We present a 21-year-old man with chest contusion from a motorcycle accident who experienced sudden collapse due to ventricular fibrillation and acute myocardial infarction. The patient was resuscitated with extracorporeal membrane oxygenation, and 12-lead electrocardiogram showed sinus tachycardia with a hyperacute T-wave and ST elevation in leads V2-V6. Percutaneous coronary intervention revealed dissection from the ostial to proximal portion of the left anterior descending artery, and traumatic coronary artery dissection was confirmed. He was successfully treated with percutaneous transluminal coronary angioplasty, in which a drug-eluting stent was inserted to enhance blood flow in the left anterior descending artery, resulting in TIMI 2 flow restoration. After 16 days of intensive care, he was discharged and was well at a 3-month follow-up. CONCLUSIONS This report describes a case with the rare association between blunt chest trauma and coronary artery dissection and highlights that coronary artery dissection can result in ST-elevation myocardial infarction. Extracorporeal membrane oxygenation can protect the patient's circulation for coronary angioplasty. Therefore, early detection and intensive resuscitation can prevent disastrous outcomes.
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Acidentes de Trânsito , Motocicletas , Infarto do Miocárdio , Ferimentos não Penetrantes , Humanos , Masculino , Infarto do Miocárdio/terapia , Adulto Jovem , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/terapia , Oxigenação por Membrana Extracorpórea , Vasos Coronários/lesões , Intervenção Coronária Percutânea , Eletrocardiografia , Traumatismos Torácicos/complicações , Dissecção Aórtica/complicações , Dissecção Aórtica/terapia , Stents Farmacológicos , Aneurisma Coronário/terapia , Aneurisma Coronário/etiologia , Angioplastia Coronária com BalãoRESUMO
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is primarily utilized in traumatic noncompressible torso hemorrhage as a temporary approach to buying time until a definite intervention could be obtained. REBOA is mostly reported in inhospital or prehospital settings. Its interhospital transfer use remains controversial. In this report, we present a case with pelvic fracture and hemorrhagic shock who underwent REBOA placement and was transferred from a local hospital to a trauma center successfully for further surgical intervention.
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BACKGROUND: Compared to functional magnetic resonance imaging (fMRI), source localization of a scalp-recorded electroencephalogram (EEG) provides higher temporal resolution and frequency synchronization to better understand the potential neurophysiological origins of disrupted functional connectivity (FC) in major depressive disorder (MDD). The present study aimed to investigate EEG-sourced measures to examine the FC in drug-free patients with MDD. METHOD: Resting-state 32-channel EEG were recorded in 84 drug-free patients with MDD and 143 healthy controls, and the cortical source signals were estimated. Exact low-resolution brain electromagnetic tomography (eLORETA) was used to compute the intracortical activity from regions within the default mode network (DMN) and frontoparietal network (PFN). Lagged phase synchronization was used as a measure of functional connectivity. RESULTS: Compared with control subjects, the MDD group showed greater within-DMN alpha 1 and 2 bands and within-FPN alpha 1, 2, and beta 3 bands. Furthermore, the MDD group showed hyperconnectivity between the DMN and the FPN in the alpha 1 and 2 bands. Finally, higher levels of anhedonia were associated with higher between-network DMN and FPN connectivity in the alpha-1 band. LIMITATIONS: Due to the inherent limitations of eLORETA with predefined seeds, we could not exclude connectivity between regions of interest (ROIs), which may be related to the activity from regions adjacent to the ROIs. CONCLUSIONS: The present findings support the importance of phase-lagged functional dysconnectivity in the neurophysiological mechanisms underlying MDD. Exploring the potential of these patterns as surrogates for treatment responses may advance targeted interventions for depression.
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(1) Background: An asthma exacerbation that is not relieved with medication typically requires an emergency room visit (ERV). The coronavirus disease 2019 (COVID-19) pandemic began in Taiwan in January of 2020. The influence of the COVID-19 pandemic on pediatric ERVs in Taiwan was limited. Our aim was to survey pediatric asthma ERVs in the COVID-19 era; (2) Methods: Data were collected from the health quality database of the Taiwanese National Health Insurance Administration from 2019 to 2021. Air pollution and climatic factors in Taipei were used to evaluate these relationships. Changes in the rates of pediatric asthma ERVs were assessed using logistic regression analysis. Poisson regression was used to evaluate the impact of air pollution and climate change; (3) Results: The rate of pediatric asthma ERVs declined in different areas and at different hospital levels including medical centers, regional and local hospitals. Some air pollutants (particulate matter ≤ 2.5 µm, particulate matter ≤ 10 µm, nitrogen dioxide, and carbon monoxide) reduced during the COVID-19 lockdown. Ozone increased the relative risk (RR) of pediatric asthma ERVs during the COVID-19 period by 1.094 (95% CI: 1.095-1.12) per 1 ppb increase; (4) Conclusions: The rate of pediatric asthma ERVs declined during the COVID-19 pandemic and ozone has harmful effects. Based on these results, the government could reduce the number of pediatric asthma ERVs through healthcare programs, thereby promoting children's health.
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PURPOSE: Patients with colorectal cancer (CRC) who present to the emergency department (ED) reportedly have poorer prognoses than other referral sources. The purpose of this study was to compare the clinical presentations and outcomes of patients referred to the hospital from the ED and those referred from non-ED facilities. METHODS: This retrospective medical record review study was conducted from January 1, 2008, to December 31, 2008, and comprised patients newly diagnosed as having CRC admitted to the hospital from the ED or referred from non-ED sources. Patients were admitted for CRC diagnosis confirmation, staging, and treatment. The staging at diagnosis and 2-year mortality were measured. RESULTS: Forty-five (29.2%) patients comprised the ED group, and another 109 (70.8%) patients comprised the non-ED group. Patients in the ED group had significantly longer hospital stays, greater in-hospital mortality, abdominal pain, intestinal obstruction, complications, lower hemoglobin levels, and more proximal than rectosigmoid tumor locations compared with patients referred from other sources. However, there was no statistically significant difference in stage at diagnosis or 2-year mortality rate between the groups. CONCLUSIONS: The ED played a pivotal role in the clinical and diagnostic evaluations of patients with CRC at our institution. Emergency department physicians provided timely diagnoses of CRC because the stage at diagnosis and 2-year mortality rate of ED patients were not compromised compared with that of patients referred from non-ED sources. Efforts should be made to reduce the numbers of patients with late presentations and acute complications associated with in-hospital mortality.
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Neoplasias Colorretais/diagnóstico , Adulto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos RetrospectivosRESUMO
(1) Background: The acute effects of ozone, cold temperature and particulate matter less than 2.5 µm (PM2.5) in size related to asthma attacks are well known worldwide. The adverse effects of ozone and cold temperature on asthma morbidity in Taiwan are still inconclusive. (2) Methods: This retrospective study included patients who had asthma emergency room visits (ERVs) from 1 January 2016 to 31 December 2019 in a regional hospital in Taiwan. The short-term negative effects were estimated using Distributed Lag Non-Linear Models (DLNMs) for the relative risks (RRs) of asthma ERVs associated with PM2.5, ozone and cold temperature exposures within 5 days. (3) Results: There was a significant association between a 10 ppm increase in PM2.5 exposure and asthma ERVs at a 2-day lag (RR 1.166, 95% confidence interval (C.I.): 1.051-1.294). There was a significant association between ozone and asthma ERVs at a 1-day lag (RR 1.179, 95% C.I.: 1.034-1.345). The ambient temperature in cold weather compared with the temperature of minimum asthma ERV showed an RR of 1.214, 95% C.I.: 1.009-1.252 at a 1-day lag. (4) Conclusions: This study provides evidence that short-term exposure to fine suspended particulates, ozone and inverse temperature is associated with asthma exacerbation.
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EEG studies indicated that schizophrenia patients had increased resting-state theta-band functional connectivity, which was associated with negative symptoms. We recently published the first study showing that theta (6 Hz) transcranial alternating current stimulation (tACS) over left prefrontal and parietal cortices during a working memory task for accentuating frontoparietal theta-band synchronization (in-phase theta-tACS) reduced negative symptoms in schizophrenia patients. Here, we hypothesized that in-phase theta-tACS can modulate theta-band large-scale networks connectivity in schizophrenia patients. In this randomized, double-blind, sham-controlled trial, patients received twice-daily, 2 mA, 20-min sessions of in-phase theta-tACS for 5 consecutive weekdays (n = 18) or a sham stimulation (n = 18). Resting-state electroencephalography data were collected at baseline, end of stimulation, and at one-week follow-up. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity. Lagged phase synchronization (LPS) was used to measure whole-brain source-based functional connectivity across 84 cortical regions at theta frequency (5-7 Hz). EEG data from 35 patients were analyzed. We found that in-phase theta-tACS significantly reduced the LPS between the posterior cingulate (PC) and the parahippocampal gyrus (PHG) in the right hemisphere only at the end of stimulation relative to sham (p = 0.0009, corrected). The reduction in right hemispheric PC-PHG LPS was significantly correlated with negative symptom improvement at the end of the stimulation (r = 0.503, p = 0.039). Our findings suggest that in-phase theta-tACS can modulate theta-band large-scale functional connectivity pertaining to negative symptoms. Considering the failure of right hemispheric PC-PHG functional connectivity to predict improvement in negative symptoms at one-week follow-up, future studies should investigate whether it can serve as a surrogate of treatment response to theta-tACS.
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Resistin and suppressors of cytokine signaling (SOCSs) have been reported to regulate prostate cancer (PCa) cell proliferation and survival, respectively. Whether any of the SOCS molecules mediate the mitogenic effect of resistin on PCa cells is unknown. Using PC-3 human PCa cells, we found that resistin upregulates the expression of SOCS3 and SOCS5 mRNA, but not SOCS7 mRNA, in a dose- and time-dependent manner. The resistin-induced increases in SOCS3 and SOCS5 expression and cell proliferation were prevented by pretreatment with specific inhibitors of the TLR4, ERK, p38 MAPK, JNK, PI3K, and JAK2 proteins. However, pretreatment with a TLR2 inhibitor had no effect on resistin-mediated SOCS3 and SOCS5 expression. In addition, the effects of resistin on SOCS3, SOCS5, and SOCS7 mRNA levels were cell type-specific. Overexpression of either SOCS3 or SOCS5 enhanced further resistin-stimulated growth of PC-3 cells, whereas silencing SOCS3 or SOCS5 antagonized resistin-increased cell growth. Further PCa tissue analysis demonstrated higher levels of RETN, TLR4, SOCS3, and SOCS5 mRNAs in cancer tissues than benign prostate hyperplasia and indicated positive correlations among RETN, TLR4, and SOCS5. These data suggest that SOCS5, TLR4, and, to a lesser extent, SOCS3 can mediate the mitogenic effect of resistin on PC-3 PCa cells.
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Próstata , Neoplasias da Próstata , Humanos , Masculino , Células PC-3 , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Resistina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
Background: Anaphylaxis is a potentially fatal condition; in severe cases of anaphylaxis, the cardiovascular system is often heavily involved. Adrenaline (epinephrine) is a cornerstone of the initial treatment of anaphylaxis. The use of epinephrine remains below expectations in clinical practice. Whether the underuse of epinephrine affects the prognosis of patients with anaphylaxis is still unclear. Materials and methods: This retrospective study included patients with anaphylaxis between 2011 and 2020 who were admitted to an emergency department (ED) in Taiwan. All patients were divided into two groups based on the use of epinephrine (or not), and we compared the demographic characteristics, allergens, clinical manifestations, management, and patient outcomes. Results: We reviewed the records of 314 subjects (216 males, 98 females; mean age: 52.78 ± 16.02 years) who visited our ED due to anaphylaxis; 107 (34.1%) and 207 (65.9%) patients were categorized into the epinephrine use group and the non-epinephrine use group, respectively. Arrival via ambulance (p = 0.019), hypotension (p = 0.002), airway compromise (p < 0.001) and altered consciousness (p < 0.001) were the deciding factors for epinephrine use among anaphylactic patients in the ED. The epinephrine use group had higher rates of other inotropic agent usage and fluid challenge. More than 90% of patients received bed rest, steroids, antihistamines, and monitoring. The epinephrine use group had a longer ED length of stay (387.64 ± 374.71 vs. 313.06 ± 238.99 min, p = 0.03) and a greater need of hospitalization. Among all severe symptoms, hypotension was the most tolerated decision factor for not using epinephrine. In this retrospective analysis, some patients with serious anaphylaxis did not experience adverse outcomes or death even without the use of epinephrine at ED admission. Emergent care focuses first on the airway, breathing, and circulation (ABC) and may compensate for the underusage of epinephrine. This could be the reason why epinephrine was underused among patients with anaphylaxis in the ED. Conclusion: In summary, early ABC management continues to play an important role in treating patients with severe anaphylaxis, even when epinephrine is not immediately available in clinical scenarios.
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Ventricular fibrillation (VF) is a life-threatening cardiac arrhythmia that can lead to loss of cardiac function and sudden cardiac death. The most common cause of VF is ischemic cardiomyopathy, especially in the context of an acute coronary event. Prompt treatment with resuscitation and defibrillation can be lifesaving. Refractory VF, or pulseless ventricular tachycardia (pVT), refers to cases that do not respond to traditional advanced cardiac life-support (ACLS) measures, and it has a low survival rate. Some new life-saving interventions and novel techniques have been proposed as viable treatment options for patients presenting with refractory VF/pVT out-of-hospital cardiac arrest; these include extracorporeal membrane oxygenation (ECMO), esmolol, stellate ganglion block (SGB), and double sequential defibrillation (DSD). Recently, DSD has been discussed and used more frequently, but its survival rate is still not promising. We report a case of refractory VF caused by acute myocardial infarction that was treated with ACLS, DSD, ECMO, and cardiac catheterization in sequence, with a successful outcome.
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Green tea epigallocatechin gallate (EGCG) and microRNA (miRNA) molecules modulate obesity. Nevertheless, it is still unknown whether EGCG modulates fat cell growth via miRNA-related signaling. In this study, white preadipocytes were used to examine whether the antimitogenic effect of EGCG on fat cells is regulated by the miR-143/MAPK7 pathway. We showed that EGCG upregulated the levels of miR-143, but not miR-155, in 3T3-L1 preadipocytes. Moreover, EGCG downregulated MAPK7 mRNA and protein levels time- and dose-dependently. MAPK7 expression increased during 3T3-L1 cell proliferation. miR-143 overexpression in the absence of EGCG mimicked the effects of EGCG to suppress preadipocyte growth and MAPK7 expression, whereas knockdown of miR-143 antagonized the EGCG-altered levels of miR-143, MAPK7, and pERK1/2 and reversed the EGCG-inhibited cell growth. These findings suggest that EGCG inhibits 3T3-L1 cell growth via miR-143/MAPK7 pathway.
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Catequina , MicroRNAs , Camundongos , Animais , Células 3T3-L1 , Chá , Catequina/farmacologia , MicroRNAs/genética , RNA MensageiroRESUMO
Schizophrenia is associated with increased resting-state large-scale functional network connectivity in the gamma frequency. High-frequency transcranial random noise stimulation (hf-tRNS) modulates gamma-band endogenous neural oscillations in healthy individuals through the application of low-amplitude electrical noises. Yet, it is unclear if hf-tRNS can modulate gamma-band functional connectivity in patients with schizophrenia. We performed a randomized, double-blind, sham-controlled clinical trial to contrast hf-tRNS (N = 17) and sham stimulation (N = 18) for treating negative symptoms in 35 schizophrenia patients. Short continuous currents without neuromodulatory effects were applied in the sham group to mimic real-stimulation sensations. We used electroencephalography to investigate if a five-day, twice-daily hf-tRNS protocol modulates gamma-band (33-45 Hz) functional network connectivity in schizophrenia. Exact low resolution electromagnetic tomography (eLORETA) was used to compute intra-cortical activity from regions within the default mode network (DMN) and fronto-parietal network (FPN), and functional connectivity was computed using lagged phase synchronization. We found that hf-tRNS reduced gamma-band within-DMN and within-FPN connectivity at the end of stimulation relative to sham stimulation. A trend was obtained between the change in within-FPN functional connectivity from baseline to the end of stimulation and the improvement of negative symptoms at the one-month follow-up (r = -0.49, p = 0.055). Together, our findings suggest that hf-tRNS has potential as a network-level approach to modulate large-scale functional network connectivity pertaining to negative symptoms of schizophrenia.