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Nitric oxide (NO), as a vital cellular signalling molecule in physiological processes, has been found to play an important role in various biological functions. In this study, we rationally designed three NO donors by tethering nitrobenzene derivatives to three fluorescent chromophores. NX-NO was found to release NO and exhibit a high fluorescence turn-on signal ratio upon exposure to LED yellow light. Additionally, it had excellent photo-stability and good inhibitory activity against cancer cell proliferation, and was successfully applied to cell imaging. Moreover, we detected the release of NO and fluorescence response in the blood of a mouse, suggesting its potential therapeutic application in living organisms.
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Corantes Fluorescentes , Doadores de Óxido Nítrico , Camundongos , Animais , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico , Fluorescência , Proliferação de CélulasRESUMO
BACKGROUND: Conventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients' recovery. METHODS: In total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2-0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2-0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome. RESULTS: Blood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin. TRIAL REGISTRATION: ChiCTR2200056891,first registered on 22/02/2022.
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Perda Sanguínea Cirúrgica , Pressão Venosa Central , Hepatectomia , Laparoscopia , Milrinona , Nitroglicerina , Vasodilatadores , Humanos , Milrinona/administração & dosagem , Nitroglicerina/administração & dosagem , Hepatectomia/métodos , Masculino , Feminino , Método Duplo-Cego , Laparoscopia/métodos , Pessoa de Meia-Idade , Pressão Venosa Central/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Idoso , Adulto , Complicações Pós-Operatórias/prevenção & controleRESUMO
Identifying violent activities is important for ensuring the safety of society. Although the Transformer model contributes significantly to the field of behavior recognition, it often requires a substantial volume of data to perform well. Since existing datasets on violent behavior are currently lacking, it will be a challenge for Transformers to identify violent behavior with insufficient datasets. Additionally, Transformers are known to be computationally heavy and can sometimes overlook temporal features. To overcome these issues, an architecture named MLP-Mixer can be used to achieve comparable results with a smaller dataset. In this research, a special type of dataset to be fed into the MLP-Mixer called a sequential image collage (SIC) is proposed. This dataset is created by aggregating frames of video clips into image collages sequentially for the model to better understand the temporal features of violent behavior in videos. Three different public datasets, namely, the dataset of National Hockey League hockey fights, the dataset of smart-city CCTV violence detection, and the dataset of real-life violence situations were used to train the model. The results of the experiments proved that the model trained using the proposed SIC is capable of achieving high performance in violent behavior recognition with fewer parameters and FLOPs needed compared to other state-of-the-art models.
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Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.
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Doença de Alzheimer , Ácidos Graxos Ômega-3 , Humanos , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Metanálise em Rede , Ácidos Graxos Ômega-3/uso terapêutico , Cognição , Anti-Inflamatórios/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Therapeutic efficacies of repetitive transcranial magnetic stimulation (rTMS) for improving cognitive functions in patients with deficit/hyperactivity disorder (ADHD) remained unclear. The aim of this meta-analysis was to investigate the therapeutic efficacy of rTMS focusing on different cognitive performances. METHODS: Major databases were searched electronically from inception to February 2023 by using keywords mainly "rTMS" and "ADHD" to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of rTMS for improving cognitive functions assessed by standardized tasks in patients with ADHD. The overall effect size (ES) was calculated as standardized mean difference (SMD) based on a random effects model. RESULTS: Meta-analysis of five RCTs with 189 participants (mean age of 32.78 and 8.53 years in adult and child/adolescent populations, respectively) demonstrated that rTMS was more effective for improving sustained attention in patients with ADHD compared with the control groups (SMD = 0.54, p = 0.001).Our secondary analysis also showed that rTMS was more effective for improving processing speed than the control groups (SMD = 0.59, p = 0.002) but not for enhancing memory or executive function. CONCLUSIONS: Our results supported the therapeutic efficacy of rTMS for improving sustained attention and processing speed. However, the limitation of available data warrants further studies to verify these findings.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulação Magnética Transcraniana , Adulto , Adolescente , Criança , Humanos , Estimulação Magnética Transcraniana/métodos , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Cognição , Função Executiva , Velocidade de ProcessamentoRESUMO
BACKGROUND: Laparoscopic hepatectomy under low central venous pressure (LCVP) is associated with intraoperative organ hypoperfusion, including cerebral hypoperfusion. We hypothesized that a ventilation strategy designed to achieve targeted mild hypercapnia (TMH) (end-tidal carbon dioxide partial pressure [PetCO2] of 45 ± 5 mmHg) rather than targeted normocapnia (TN) (PetCO2 of 30 ± 5 mmHg) would increase regional cerebral oxygen saturation (rSO2) during laparoscopic hepatectomy under LCVP. METHODS: Eighty patients undergoing laparoscopic hepatectomy under LCVP were randomly divided into the TMH group (n = 40) and the TN group (n = 40). Mechanical ventilation was adjusted to maintain the PetCO2 within the relevant range. Cerebral oxygenation was monitored continuously using the FORE-SIGHT system before anesthetic induction until the patient left the operating room. Patient and surgical characteristics, rSO2, intraoperative hemodynamic parameters (CVP, mean artery blood pressure [MAP], and heart rate), PetCO2, intraoperative blood gas analysis results, and postoperative complications were recorded. RESULTS: No significant differences were observed in CVP, MAP, and heart rate between the two groups during surgery. The rSO2 was significantly lower in the TN group on both the left and right sides during the intraoperative period (P < 0.05), while the TMH group had a stable rSO2. In the TN group, the mean rSO2 decreased most during liver parenchymal transection when compared with the baseline value (P < 0.05). The mean (standard deviation) percentage change in rSO2 from baseline to parenchymal transection was - 7.5% (4.8%) on the left and - 7.1% (4.6%) on the right. The two groups had a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings demonstrate that rSO2 is better maintained during laparoscopic hepatectomy under LCVP when patients are ventilated to a PetCO2 of 45 ± 5 mmHg (TMH) than a PetCO2 of 30 ± 5 mmHg (TN). TRIAL REGISTRATION: ChiCTR2100051130(14/9/2021).
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Hipercapnia , Laparoscopia , Humanos , Pressão Venosa Central , Hepatectomia , Estudos Prospectivos , Saturação de Oxigênio , Oxigênio , Complicações Pós-OperatóriasRESUMO
AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.
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COVID-19 , Humanos , Interleucina-6 , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients. METHODS: We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo. RESULTS: This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p < 0.001). The subgroup without concurrent medication had the same result (p < 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p < 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo. CONCLUSION: This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life. TRIAL REGISTRATION: PROSPERO CRD42021269451.
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Síndrome do Intestino Irritável , Melatonina , Humanos , Síndrome do Intestino Irritável/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos Nutricionais , Medição da Dor , Resultado do TratamentoRESUMO
BACKGROUND: Although providing spiritual care is an important part of holistic nursing care for psychiatric patients, factors associated with spiritual care competency in mental health nurses remain unclear. The aim of our study was to explore a possible association of personal and external factors with spiritual care competency in mental health nurses. METHODS: This prospective questionnaire-based cross-sectional study was conducted by inviting mental health nurses from mental health hospitals and tertiary referral centers. Personality traits and spiritual care competency were assessed by using [1] "big-five Mini-Markers" questionnaire, and [2] spiritual care competency scale, respectively. From the 250 mental health nurses being invited, 239 valid questionnaires were valid for final analysis. Statistical analyses including descriptive statistics, ANOVAs, t-tests, and hierarchical multiple regression models were used to investigate the associations between personal/external factors and their spiritual care competency in mental health nurses. RESULTS: The mean age of the 239 participants was 35.96 ± 8.11 and the mean years of working experience was 9.41 ± 7.06. Over 90% of them had no experience of providing spiritual care. There were significant positive correlations of spiritual care competency with the experience of delivering spiritual care (p < 0.001), previous participation in spiritual care education programs (p = 0.045), a longer working experience (p = 0.014), and a higher education level (postgraduate vs. college, p = 0.006), as well as the personality components of "Conscientiousness" (p < 0.001), "Agreeableness" (p < 0.001), "Extraversion" (p = 0.03), and "Openness/Intellect" (p < 0.001). CONCLUSIONS: Both personal and external factors may be related to the self-perception of spiritual care competency among mental health nurses. These findings may help mental health nurses understand the possible positive and negative associations of their personality components with their spiritual care abilities. Moreover, our identification of the positive impacts of educational programs and previous experience of spiritual care on spiritual care competency may underscore the importance of tailoring appropriate training programs to cater for the individual needs of mental health nurses.
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BACKGROUND: No established pharmacological treatment is available for the core symptoms of autism spectrum disorder (ASD). This study aimed at investigating the efficacy of antidepressants for the core and associated symptoms of ASD. METHODS: We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science and ClinicalTrials.gov using the keywords "ASD" and "antidepressants." We searched from database inception to June 2021 for randomized controlled trials of antidepressant use in patients with ASD. We calculated pooled effect sizes based on a random-effects model. RESULTS: Analysis of 16 studies with 899 participants showed improvements in restricted and repetitive behaviours (effect size = 0.27) and global symptoms (effect size = 1.0) in patients with ASD taking antidepressants versus those taking placebos (p ≤ 0.01). We found no differences between the 2 groups (p ≥ 0.36) in terms of dropout rate (odds ratio [OR] = 1.17) or rate of study discontinuation because of adverse events (OR = 1.05). We also noted improvements in irritability and hyperactivity in the antidepressant group (Hedges g = 0.33 and 0.22, respectively, both p < 0.03). Subgroup analyses showed significant effects of medication type (i.e., clomipramine was better than SSRIs) and age (antidepressants were more effective in adults than in children or adolescents) on both restricted and repetitive behaviours and global improvement (p < 0.05). Meta-regression demonstrated that better therapeutic effects were associated with lower symptom severity and older age. LIMITATIONS: The small effect sizes and variations in treatment response that we found warrant further study. CONCLUSION: Our results supported the effectiveness of antidepressants for global symptoms and symptom subdomains of ASD, with tolerable adverse effects. Low symptom severity and adulthood were associated with better outcomes.
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Transtorno do Espectro Autista , Adolescente , Adulto , Antidepressivos/efeitos adversos , Transtorno do Espectro Autista/tratamento farmacológico , Criança , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
BACKGROUND: Several difficulty scoring systems (DSSs) have been proposed for evaluating difficulty of laparoscopic liver resection (LLR) and no study has validated their performance in a hepatocellular carcinoma (HCC)-only cohort at the same time. METHODS: All cases with HCC that underwent LLR from January 2015 to December 2020 in our center were retrospectively collected. Performance of the IWATE-DSS, Halls-DSS, Hasegawa-DSS, and Kawaguchi-DSS in predicting perioperative outcomes was evaluated. Subgroup analyses were conducted to compare perioperative outcomes between surgeons on the learning curve and surgeons that have gone through the learning curve. RESULTS: For all four DSSs, there were significant distributions of applying bleeding control, surgical time, estimated blood loss, postoperative major complications, and postoperative hospital stay among different groups of each DSS (P all < 0.05). Conversion to laparotomy or not was significantly distributed in different groups of the IWATE-DSS (P = 0.006) and Halls-DSS (P = 0.022), while it was not in the Hasegawa-DSS (P = 0.056) and Kawaguchi-DSS (P = 0.183). Trend tests showed that the conversion rates increased with higher DSS points in the IWATE-DSS (P < 0.001) and the Kawaguchi-DSS (P = 0.021), while not in the Halls-DSS (P = 0.064) and the Hasegawa-DSS (P = 0.068). In the medium and advanced/expert difficulty-level subgroups defined by the IWATE-DSS, there were larger estimated blood loss (P in medium-difficulty group = 0.009; P in the advanced/expert difficulty group = 0.004) and longer postoperative hospital stay (P in the medium-difficulty group = 0.012; P in the advanced/expert group = 0.035) in the learner-performed cases. CONCLUSIONS: All DSSs performed well in predicting applying bleeding control, surgical time, estimated blood loss, postoperative major complications, and postoperative hospital stay, while only the IWATE-DSS was able to predict whether conversion to laparotomy or not for HCC patients underwent LLR. The IWATE-DSS was also able to help surgeons on the LLR learning curve choose cases and guide clinical practices.
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Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Hemorragia Pós-Operatória/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: To investigate the feasibility of purse string suture pancreaticojejunostomy in complete laparoscopic pancreaticoduodenectomy for patients with an undilated pancreatic duct. METHODS: We retrospectively reviewed a database of 113 patients with undilated pancreatic ducts who had undergone laparoscopic pancreaticoduodenectomy (LPD) with purse string suture pancreaticojejunostomy to analyze the perioperative outcomes. RESULTS: One hundred thirteen patients underwent successful LPD. The surgery time was 353 ± 41 min, the time required for pancreaticojejunostomy was 27 ± 5 min, and the hospital stay after surgery was 16 ± 8 days. Fifteen patients suffered postoperative complications, including twelve patients with pancreatic fistula, one with bile leakage, one with gastroparesis (complicated with abdominal infection), and one with abdominal bleeding. No perioperative death occurred. CONCLUSIONS: Purse string suture pancreaticojejunostomy is safe and feasible for patients with an undilated pancreatic duct.
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Laparoscopia , Pancreaticojejunostomia , Humanos , Laparoscopia/efeitos adversos , Ductos Pancreáticos/cirurgia , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Suturas/efeitos adversosRESUMO
BACKGROUND/OBJECTIVES: Obesity has recently been recognized as a neurocognitive disorder involving circuits associated with the reward system and the dorsolateral prefrontal cortex (DLPFC). Noninvasive brain stimulation (NIBS) has been proposed as a strategy for the management of obesity. However, the results have been inconclusive. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and acceptability of different NIBS modalities for weight reduction in participants with obesity. METHODS: Randomized controlled trials (RCTs) examining NIBS interventions in patients with obesity were analyzed using the frequentist model of NMA. The coprimary outcome was change in body mass index (BMI) and acceptability, which was calculated using the dropout rate. RESULTS: Overall, the current NMA, consisting of eight RCTs, revealed that the high-frequency repetitive transcranial magnetic stimulation (TMS) over the left DLPFC was ranked to be associated with the second-largest decrease in BMI and the largest decrease in total energy intake and craving severity, whereas the high-frequency deep TMS over bilateral DLPFC and the insula was ranked to be associated with the largest decrease in BMI. CONCLUSION: This pilot study provided a "signal" for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on weight reduction in participants with obesity by different NIBS interventions.
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Obesidade , Estimulação Magnética Transcraniana , Redução de Peso/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Obesidade/fisiopatologia , Obesidade/terapia , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods: We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results: Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations: Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion: The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.
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Lesões Encefálicas Traumáticas/complicações , Depressão/terapia , Transtorno Depressivo Maior/terapia , Metilfenidato/farmacologia , Inibidores da Captação de Neurotransmissores/farmacologia , Psicoterapia , Depressão/etiologia , Transtorno Depressivo Maior/etiologia , Humanos , Metanálise em RedeRESUMO
N-methyl-D-aspartate (NMDA) receptor channels are activated by glutamate (or NMDA) and glycine. The channels also undergo desensitization, which denotes decreased channel availability, after prolonged exposure to the activating ligands. Glycine apparently has a paradoxical negative effect on desensitization, as the increase in ambient glycine in concentrations required for channel activation would increase sustained NMDA receptor currents. We hypothesized that this classical "glycine-dependent desensitization" could be glycine-dependent activation in essence. By performing electrophysiological recordings and biophysical analyses with rat brain NMDA receptors heterogeneously expressed in Xenopus laevis oocytes, we characterized that the channel opened by "only" NMDA (in nominally glycine-free condition probably with the inevitable nanomolar glycine) would undergo a novel form of deactivation rather than desensitization, and is thus fully available for subsequent activation. Moreover, external tetrapentylammonium ions (TPentA), tetrabutylammonium ions, and tetrapropylammonium ions (TPA, in higher concentrations) block the pore and prohibit channel desensitization with a simple "foot-in-the-door" hindrance effect. TpentA and TPA have the same voltage dependence but show different flow dependence in binding affinity, revealing a common binding site at an electrical distance of ~0.7 from the outside yet differential involvement of the flux-coupling region in the external pore mouth. The smaller tetraethylammonium ion and the larger tetrahexylammonium and tetraheptylammonium ions may block the channel but could not affect desensitization. We conclude that NMDA receptor desensitization requires concomitant binding of both glycine and glutamate, and thus movement of both GluN1 and GluN2 subunits. Desensitization gate itself embodies a highly restricted pore reduction with a physical distance of ~4 Å from the charged nitrogen atom of bound tetraalkylammonium ions, and is located very close to the activation gate in the bundle-crossing region in the external pore vestibule.
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Ácido Glutâmico/metabolismo , Glicina/metabolismo , Ativação do Canal Iônico/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Relação Dose-Resposta a Droga , Agonistas de Aminoácidos Excitatórios/metabolismo , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Ácido Glutâmico/farmacologia , Glicina/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Ligantes , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/antagonistas & inibidores , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Ratos , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/genética , Xenopus laevisRESUMO
Intracellular pH plays an important role in various biological processes; abnormal pH changes in the intracellular compartment leads to the production of free radicals, the disruption of membrane contractility, inappropriate apoptosis, and necrosis, resulting in serious illness. Although fluorescent probes have widely been used to detect pH levels owing to their high sensitivity and specificity, there is still a demand for near-infrared (NIR) fluorescent probes with high Stokes shift. Here, a NIR fluorescent probe, PipDC, comprising N-ethyl piperazine (response unit) and naphthyl dicyanoisophorone (fluorophore), was designed for pH sensing. The probe has an extremely large Stokes shift (290 nm), and its fluorescence intensity at 730 nm sharply increases when the environment changes from basic to acidic owing to the protonation of piperazine, which results in the quenching of the photoinduced electron transfer effect. It exhibited a specific response to acidic microenvironments regardless of other interfering substances. In addition, PipDC operates well in the lysosome environment in living cells and displays an off-on fluorescence response with pH alterations. Together, these results suggest that PipDC is a promising fluorescent probe for intracellular pH sensing.
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Corantes Fluorescentes/química , Isocianatos/química , Teoria da Densidade Funcional , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Isocianatos/síntese química , Lisossomos/química , Estrutura Molecular , Imagem ÓpticaRESUMO
OBJECTIVE: To analyze the roles of multidisciplinary team (MDT) in the diagnosis and treatment of suspected cases of coronavirus disease 2019 (COVID-19). METHODS: The clinical data of 48 patients with suspected COVID-19 admitted in Jinhua Municipal Central Hospital from January 21, 2020 to March 20, 2020 were retrospectively analyzed. RESULTS: In the 48 suspected cases, 18 were diagnosed with COVID-19, and 30 were excluded. Each of the confirmed cases were discussed among MDT for 2 to 12 times with an average of (4.7±3.2) times; while for non-COVID-19 patients were discussed for 2 to 4 times with an average of (2.3±0.6) times. With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination. Except one transferred patient, all 17 confirmed COVID-19 patients were cured and discharged. There was no cross-infection occurred in suspected patients during the hospitalization. There were no deaths and no medical staff infections. CONCLUSIONS: The efficiency of diagnosis and treatment for suspected COVID-19 patients can be improved with MDT, particularly for complicated cases.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Comunicação Interdisciplinar , Pandemias , Equipe de Assistência ao Paciente , Pneumonia Viral , Betacoronavirus/isolamento & purificação , COVID-19 , China , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Humanos , Equipe de Assistência ao Paciente/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2 , Resultado do TratamentoRESUMO
A fluorogenic probe based on the novel fluorophore 5-triazole-quinoline was developed for the detection of hydrogen sulfide, an endogenous signaling molecule associated with the development of various diseases. The lysosome-targeted probe Lyso-HS was synthesized via C-H direct azidation from 8-aminoquinoline; it was able to detect H2S in 1 min and exhibited excellent turn-on ability with 95-fold fluorescence enhancement based on a new fluorochrome. The high quenching efficiency was further verified using time-dependent density functional theory (TDDFT). The probe also exhibited high selectivity and a low detection limit (as low as 214.5 nM), which has practical applications for disease detection and monitoring.
Assuntos
Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Quinolinas/química , Triazóis/química , Células A549 , Células Hep G2 , Humanos , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Espectrometria de Fluorescência/métodosRESUMO
BACKGROUND: Music therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis. METHODS: We compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression. RESULTS: The main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course. CONCLUSIONS: Our meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity.