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1.
Epilepsy Behav ; 125: 108376, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34775247

RESUMO

BACKGROUND: Social factors are believed to affect mental health in patients with epilepsy (PWE). However, there is still a lack of sufficient manifest proof, given the difficulty of exposing PWE to relatively consistent natural social environments with a low or high level of social interaction to study their significant role. METHODS: This single-center, longitudinal study was conducted via online questionnaires during the coronavirus disease 2019. PWE were recruited from downtown Wuhan and surrounding areas. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 were used to assess psychological status. RESULTS: We analyzed 588 questionnaires completed by 294 PWE who participated in the dual survey. Under lockdown and reopening, the prevalence of anxiety was 13.6%/22.5%, and the prevalence of depression was 19.4%/34.0%. Raising children and seizure-related characteristics, including uncontrolled seizures, seizure exacerbation, seizure frequency ≥ 2/m, and changes in drug regimen, were risk factors in the first and second surveys. A high education level (OR = 1.946, 95% CI = 1.191-3.182), low life satisfaction (OR = 1.940, 95% CI = 1.007-3.737), worry about unanticipated seizures (OR = 2.147, 95% CI = 1.049-4.309), and worry about purchasing medication outside (OR = 2.063, 95% CI = 1.060-4.016) were risk factors for higher scores after reopening. Worry about unanticipated seizures (OR = 3.012, 95% CI = 1.302-6.965) and in-person medical consultation (OR = 2.319, 95% CI = 1.262-4.261) were related to newly diagnosed patients with psychological disorder after reopening. CONCLUSIONS: We identified an association between social variables and epileptic psychiatric comorbidities.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34484399

RESUMO

Our previous studies demonstrated that effects of moxibustion heavily relied on heat-sensitization response, a specific sensation induced by moxibustion in the ill body. On the sensation, long-term potentiation (LTP) of prelimbic cortex was attributed to heat-sensitization responses. The N-methyl-D-aspartic acid (NMDA) receptor plays a key role in LTP induction; however, little is known about the role of NMDA receptor in heat-sensitization response. The present study investigated the role of NMDA receptor in heat-sensitization response, specifically, NMDA receptor was inhibited by competitive glutamatergic antagonist, (±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), observing the frequency of heat-sensitization response in moxibustion treatment and evaluating the conducive outcomes to cerebral infarct rats for rehabilitation. Heat-sensitization response in cerebral infarct rats was regularly measured for all the samples when exposed to moxibustion. Intraperitoneal injection of CPP was conducted, and soon afterwards, a significant drop of heat-sensitization response in all the samples was measured. Moreover, moxibustion efficiency on rehabilitation was unfavourably affected in cerebral infarct rats when compared to vehicle injection control. This indicated that NMDA receptor antagonist made a negative impact on induction of heat-sensitization response and consequently affected cerebral infarct rats to rehabilitate under moxibustion treatment. It also suggested that activating NMDA receptor played a positive part in ischemic stroke rehabilitation, and regulating its activity could be a feasible way to increase heat-sensitization response, improving the effect of moxibustion.

3.
Phys Chem Chem Phys ; 23(33): 18058-18067, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34387292

RESUMO

The kinetic behavior of vapor adsorption on a solid surface in an isobaric-isothermal system is investigated by means of molecular dynamics simulations combined with theoretical studies through a statistical rate theory approach. The molecular insights into the formation and evolution of clusters in the adsorbate are presented. Results show that the argon vapor is adsorbed on the silicon surface as different types of clusters. In the initial stage of adsorption, the empty adsorption sites on the surface decrease, and the adsorbed single-molecule-cluster grows rapidly and dominates the interface. The increasing rate of the adsorbed cluster and the declining rate of the empty adsorption site are dependent on the pressure ratio. For a large pressure ratio, the single-molecule-clusters are aggregated to incubate large clusters, and the fraction of a single-molecule-cluster is decreased with time. When the adsorption isotherm is determined, the chemical potential of the adsorbed cluster is expressed from the zeta isotherm model. Then the adsorption kinetics are analyzed through the statistical rate theory. The molecular exchange rate and the instantaneous driving force are calculated. The higher pressure ratio induces the larger chemical potential difference and accelerates the net adsorption rate. The adsorption kinetics derived from MD simulations are in close agreement with the theoretical analysis of the statistical rate theory.

4.
Emerg Microbes Infect ; 10(1): 1849-1861, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34461813

RESUMO

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a food-borne bacterium that causes acute gastroenteritis in humans and typhoid fever in mice. Salmonella pathogenicity island II (SPI-2) is an important virulence gene cluster responsible for Salmonella survival and replication within host cells, leading to systemic infection. Previous studies have suggested that SPI-2 function to modulate host vesicle trafficking and immune response to promote systemic infection. However, the molecular mechanism and the host responses triggered by SPI-2 remain largely unknown. To assess the roles of SPI-2, we used a differential proteomic approach to analyse host proteins levels during systemic infections in mice. Our results showed that infection by WT S. Typhimurium triggered the reprogramming of host cell metabolism and inflammatory response. Salmonella systemic infection induces an up-regulation of glycolytic process and a repression of the tricarboxylic acid (TCA) cycle. WT-infected tissues prefer to produce adenosine 5'-triphosphate (ATP) through aerobic glycolysis rather than relying on oxidative phosphorylation to generate energy. Moreover, our data also revealed that infected macrophages may undergo both M1 and M2 polarization. In addition, our results further suggest that SPI-2 is involved in altering actin cytoskeleton to facilitate the Salmonella-containing vacuole (SCV) biogenesis and perhaps even the release of bacteria later in the infection process. Results from our study provide valuable insights into the roles of SPI-2 during systemic Salmonella infection and will guide future studies to dissect the molecular mechanisms of how SPI-2 functions in vivo.

5.
Asian J Surg ; 44(10): 1343-1344, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34462196

RESUMO

OBJECTIVE: Scott Triggers is designed to identify potential surgical patients at risk for development of pressure injuries. But it has not been validated for sensitivity and positive predictive value to date. This study aimed to evaluate the reliability and validity of the Scott Triggers for the gastrointestinal surgery patients in China. METHODS: 447 gastrointestinal surgery patients were enrolled by convenience sampling and investigated by Scott Triggers from March to November 2019. RESULTS: 8 patients (1.780%) develop pressure injuries. The Cronbach's alpha was 0.701 and the interrater reliability was 0.915. The content validity of each item of Scott Triggers ranged from 0.667 to 1.0 and the content validity of the whole scale was 0.832, which showed a significant positive relationship and good internal consistent validity. The accumulative variance contribution ratio of common factor was 53.194%. Pearson correlation between Scott Triggers and 3S intraoperative risk assessment scale was -0.708 (P < 0.001). The Youden index was 0.374, the optimal predictive threshold of Scott Triggers was 5.5, the area under receiver operating characteristic (ROC) curve was 0.762, the sensitivity was 0.875, the specificity was 0.499, the positive predictive value was 0.027, and the negative predictive value was 0.996. CONCLUSION: Scott Triggers shows good reliability, validity, and predictive validity in this study, which can be used to assess the risk of stress injury in surgical patients. However, the body mass index needs to be taken into account in further study.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , China/epidemiologia , Humanos , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Inquéritos e Questionários
6.
Toxicol Res (Camb) ; 10(2): 277-283, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33884178

RESUMO

Arsenic (As) is a ubiquitous environmental and industrial toxin with known correlates of oxidative stress and cognitive deficits in the brain. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that represents a central cellular antioxidant defense mechanism and transcribes many antioxidant genes. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a well-known nuclear receptor to regulate lipid metabolism in many tissues, and it has been also associated with the control of oxidative stress, neuronal death, neurogenesis and differentiation. The role of Nrf2 and PPARγ in As-induced neurotoxicity is still debated. The present study was designed to investigate the neurobehavioral toxic effect of sub-chronic and middle-dose sodium arsenite exposure in mice hippocampus, as well as the response of Nrf2/PPARγ expression and influence on protein expression levels of their downstream antioxidant genes. Our results showed that mice treated with intraperitoneal injection of sodium arsenite (50 mg/kg body wt.) twice a week for 7 weeks resulted in increased generation of reactive oxygen species and impairment of spatial cognitive function. The present study also found a positive association between Nrf2/PPARγ expression in hippocampus of mice, and activation of antioxidant defenses by the evidently upregulated expression of their downstream genes, including superoxide dismutase, heme oxygenase-1 and glutathione peroxidase-3. Therefore, our findings were helpful for further understanding the role of Nrf2/PPARγ feedback loop in As-induced neurobehavioral toxicity.

7.
Pain Manag Nurs ; 22(6): 764-768, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33674241

RESUMO

BACKGROUND: Epidural (EPI) catheter analgesia is frequently prescribed as a regional analgesic technique to patients with multiple rib fractures (MRF) following surgical stabilization of rib fractures (SSRF). AIMS: We aimed to study the effect of add-on self-care therapy on recovery and quality of life (QoL) in patients on EPI analgesia after surgical stabilization of rib fractures (SSRF). DESIGN/SETTINGS/PARTICIPANTS/SUBJECTS: A total of 267 eligible patients with MRF who received EPI catheter analgesia after SSRF were recruited, and assigned to one of two groups in a random fashion: intervention group received education on self-care therapy, while the control group did not. METHODS: Pain scores, incentive spirometry (IS) volumes, oxygen saturation (SpO2), respiratory rate, hospital length of stay (LoS) and QoL were evaluated. RESULTS: Compared with control group, the intervention group showed significantly improved pain scores, IS volume, respiratory rate, and SpO2. Hospital LoS was shorter for the intervention group than the control group. Overall QoL scores in the intervention group were also significantly better than control patients. CONCLUSIONS: Education on self-care therapy significantly benefited pain management, recovery, and QoL for patients with MRF who received EPI catheter analgesia after SSRF operation.

8.
ACS Omega ; 6(8): 5933-5944, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33681631

RESUMO

In order to investigate the energy transfer mechanism and the nonequilibrium effect during water evaporation in its own pure vapor at low pressures, a series of precise measurements are conducted to obtain the temperature profile near the liquid-vapor interface and the evaporation rates in an annular pool in a closed chamber. The results show that the interface temperature of the vapor side is higher than that of the liquid side when water evaporates in its own pure vapor at low pressures (ranging from 394 to 1467 Pa), the temperature discontinuity across the interface exists in all experimental conditions. The magnitude of the temperature discontinuity is strongly affected by the vapor pressure. A uniform temperature layer with a thickness of about 2 mm is found below the evaporating interface because of the coupling effect of evaporation cooling and thermocapillary convection. The energy required for evaporation is mainly transferred by thermocapillary convection in the uniform temperature layer. Furthermore, the numerical simulation results confirm that the evaporation flux near the cylinders is much larger than that at the middle region, which implies that most of the latent heat required for evaporation is transferred to the interface near the cylinders.

9.
Eur J Neurol ; 28(6): 1992-1999, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33738891

RESUMO

BACKGROUND AND PURPOSE: Spontaneous intracerebral haemorrhage (ICH) with subarachnoid extension (SAHE) predicts poor outcomes and haematoma expansion in spontaneous ICH and is also a potential predictor of the severity of vascular amyloid deposition. The biological underpinnings of SAHE remain elusive. A study was conducted to identify risk factors associated with SAHE. METHODS: A retrospective analysis was performed of an ongoing prospective cohort of primary spontaneous supratentorial ICH patients admitted to Tongji Hospital. SAHE was rated on baseline noncontrast computed tomography images by investigators blinded to the clinical data. RESULTS: A total of 189 patients were enrolled. Apolipoprotein E (APOE) ε2 copies (p = 0.020), but not APOE ε4 copies (p > 0.2), were more common in patients with SAHE in univariate analysis. After controlling for confounding factors in multiple logistic regression, lobar haematoma (odds ratio [OR] 14.21, 95% confidence interval [CI] 5.89-34.33; p < 0.001), large haematoma volume (OR 1.04, 95% CI 1.02-1.06; p < 0.001) and APOE ε2 copies (OR 3.07, 95% CI 1.05-8.97; p = 0.041) were three independent predictors of SAHE. For subgroup analysis stratified by location, APOE ε2 showed a possible association with SAHE in lobar ICH (p = 0.026) but not in deep ICH (p > 0.2). No significant association was found between APOE ε4 copies and either lobar (p > 0.2) or deep ICH (p > 0.2). CONCLUSIONS: The APOE ε2 allele predicts SAHE in spontaneous supratentorial ICH. The association may predominantly apply to lobar ICH. Given the established relationship between the APOE ε2 allele and pathological cerebrovascular changes, our findings suggest that SAHE involves genetically driven vessel pathology.


Assuntos
Apolipoproteínas E , Hemorragia Cerebral , Apolipoproteína E2/genética , Apolipoproteínas E/genética , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/genética , Genótipo , Humanos , Estudos Prospectivos , Estudos Retrospectivos
10.
BMC Med Inform Decis Mak ; 21(1): 50, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568163

RESUMO

BACKGROUND: This study aims to explore the information chain management model of large instrument and equipment inter-working in the operating room (OR) led by information nurses. METHODS: Through the chain management process of large instruments and equipment in the OR, which was based on information nurses, the management model of inter-working and integrating information chain was established, the key links were controlled, and the whole life cycle management of instruments and equipment from expected procurement to scrapping treatment was realized. Using the cluster sampling method, 1562 surgical patients were selected. Among these patients, 749 patients were assigned to the control group before the running mode, and 813 patients were assigned to the observation group after the running mode. The related indexes for large instrument and equipment management in the department before and after the running mode were compared. RESULTS: In the observation group, the average time of equipment registration was (22.05 ± 2.36), the cost was reduced by 2220 yuan/year, and the satisfaction rate of the nursing staff was 97.62%. These were significantly better, when compared to the control group (P < 0.05). Furthermore, the awareness rate of the whole staff for equipment repair application was 95.12%, and the arrival time of maintenance personnel and the examination and approval time of equipment management were greatly shortened (P < 0.05). CONCLUSION: The integrated management model of large instrument and equipment interworking in the OR based on chain flow realizes the whole life cycle management of instruments and equipment, which is essential to improve management efficiency.


Assuntos
Salas Cirúrgicas , Instrumentos Cirúrgicos , Humanos
11.
J Plant Physiol ; 256: 153311, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33249387

RESUMO

The stress responses of plant compete for resources with growth and development. Resource allocations among these processes may have been optimized in plants adapted to natural habitats. Here, nitrogen (N) allocations were compared in leaves of Arabidopsis and Chorispora bungeana, a cryophyte with strong freezing tolerance. The results showed that the two species differed not only in N partitions among N forms and allocations among leaves, but also in their responses to cold stress. Interestingly, leaf protein contents were enhanced in C. bungeana while reduced in Arabidopsis, though the N allocations to leaves were reduced in both plants upon cold stress. Profoundly, when grown at warm temperature, contents of total free amino acids (FAAs) in leaves of C. bungeana were 6-11 times higher than those in Arabidopsis. In contrast, cold treatment induced FAAs accumulation in leaves of Arabidopsis without having significant effect in any leaf of C. bungeana. Considerable discrepancy was also found between the two species in the expressions of nitrate transporter genes and the activities of nitrate assimilation enzymes. Correlation and network analysis showed that most NPFs were clustered in a single network module and had loose relations with protein synthesis in Arabidopsis, while they were distributed in different modules in a decentralized network in C. bungeana. Therefore, our results reveal that C. bungeana may have optimized its N allocation strategy by producing and storing amino acids as efficient N reserve and adopting a decentralized network for N utilization, which may equip the plant with powerful capabilities for environmental adaptions.


Assuntos
Adaptação Fisiológica , Arabidopsis/fisiologia , Brassicaceae/fisiologia , Resposta ao Choque Frio/genética , Resposta ao Choque Frio/fisiologia , Congelamento , Nitrogênio/metabolismo , Arabidopsis/genética , Brassicaceae/genética , Regulação da Expressão Gênica de Plantas
12.
Sleep Med Rev ; 56: 101403, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33360604

RESUMO

The relationship between insomnia and hypertension remains inconclusive. Thus, we conducted a meta-analysis of prospective cohort studies to evaluate the association between insomnia and the risk of hypertension. Relevant prospective cohort studies were searched from PubMed, Embase, and Web of Science from their inception to October 2019. A random-effects model was used to calculate the pooled relative risk (RR) with 95% confidence interval (CI). A total of fourteen prospective cohort studies involving 395,641 participants were included in this study. The pooled RR of insomnia on hypertension was 1.21 (95%CI: 1.10-1.33). An increased risk of hypertension was observed in participants with difficulty maintaining sleep (RR = 1.27; 95%CI: 1.04-1.55) and early morning awakening (RR = 1.14; 95%CI: 1.08-1.20), but was not statistically significant in participants with difficulty falling asleep (RR = 1.14; 95%CI: 0.95-1.37). In addition, the results were statistically significant in the European population (RR = 1.08, 95%CI: 1.02-1.14), but not significant in Asian and American populations (RR = 1.54, 95%CI: 0.98-2.40; RR = 1.21, 95%CI: 0.89-1.65). The study findings indicate that insomnia is associated with a significantly increased risk of hypertension. This may have substantial implications for the prevention of hypertension in individuals with insomnia symptoms.


Assuntos
Hipertensão , Distúrbios do Início e da Manutenção do Sono , Grupo com Ancestrais do Continente Asiático , Humanos , Hipertensão/epidemiologia , Estudos Prospectivos , Risco , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia
13.
Carbohydr Polym ; 250: 116985, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049870

RESUMO

In this study, citric acid (CA) esterified canna starch was firstly synthesized with the aid of vacuum, microwave and infrared radiation treatment. The changes in structural, physicochemical properties and in vitro digestibility of the modified starch were then investigated. The maximum degree of substitution (DS) reached 0.273 and the maximum thermo-stable resistant starch (RS) content reached 86.5 %. FT-IR confirmed the esterification reaction had successfully occurred, XRD and DSC results revealed that the crystalline and endothermic peaks of the samples disappeared after CA-treated, and TGA showed that the thermal degradation temperatures were above 280 °C. SEM showed the destroyed surface of the starch granules. All modified samples were lighter and generally whiter than native canna starch in color. These results suggest that the aid of vacuum treatment, microwave and infrared radiations for CA esterified of canna starch is an effective method for preparing high content of thermally stable RS4.

14.
Integr Cancer Ther ; 19: 1534735420954912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32909468

RESUMO

This research aimed to investigate the effects of resistance exercise on symptoms, physical function, and quality of life (QoL) in gastrointestinal cancer patients undergoing chemotherapy. Patients were quasi-randomly divided into the resistance exercise group and the relaxation control group, and machine-based resistance exercise was performed twice a week for 12 weeks under the guidance of experienced therapists. The QoL of patients was analyzed by EORTC-QLQ-C30. Resistance exercise training significantly reduced the incidences of lack of energy (inter-group P = .011), nausea (inter-group P = .007), acid reflux (inter-group P = .042), and back pain (inter-group P = .0009). Twelve weeks of resistance exercise training significantly elevated the muscular strength of leg press (inter-group P = .021) and leg extension (inter-group P = .041), and the muscular endurance of leg press (inter-group P = .005). The participants' performance in 6-m fast walk (inter-group P = .008), 6-m backwards walk (inter-group P = .016), and chair rise (inter-group P = .031) were dramatically improved. Fatigue (inter-group P = .024) and appetite loss (inter-group P = .012) in the resistance exercise group were significantly lower than the relaxation control group. In conclusion, the beneficial effects of resistance exercise on symptoms, physical function and QoL in gastrointestinal cancer patients undergoing chemotherapy were demonstrated. Resistance exercise training reduced the incidences of nausea and acid reflux, improved physical function, and alleviated fatigue and appetite loss in gastrointestinal cancer patients undergoing chemotherapy.


Assuntos
Neoplasias Gastrointestinais , Treinamento de Força , Exercício Físico , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Força Muscular , Qualidade de Vida
15.
Epilepsia ; 61(9): 1884-1893, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32761900

RESUMO

OBJECTIVE: Stress is a known trigger for seizures in patients with epilepsy (PWE). However, the association between stress and seizures has not been thoroughly investigated. In December 2019, an outbreak of coronavirus disease (COVID-19) occurred in Wuhan, Hubei province, China, causing tremendous collateral stress. This study was designed to evaluate the influence of the COVID-19 outbreak on seizures in PWE in the most severely affected area, Wuhan, and its surrounding cities. METHODS: In this single-center, cross-sectional study, PWE were surveyed via online questionnaires between February 23 and March 5, 2020. Collected data included demographic information, epilepsy-related characteristics (seizure type, frequency, antiepileptic drugs [AEDs], and medication management), direct and perceived threat of COVID-19, and changes in seizures during the outbreak. Psychological comorbidities were evaluated by the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 items, and Insomnia Severity Index (ISI). Multivariate logistic regression was used to identify precipitants for seizure exacerbation. RESULTS: We received 362 completed questionnaires after excluding 12 duplicates (response rate = 63.51%). A total of 31 (8.56%) patients had increased seizures during the outbreak. Exposure history to COVID-19 (P = .001), uncontrolled seizure after AED therapy (P = .020), seizure frequency of two or more times per month before the outbreak (P = .005), change of AED regimen during the outbreak (AED reduction, withdrawal, replacement, skipping altogether; P = .002), and worry about the adverse effect of the outbreak on overall seizure-related issues (severity = moderate to critical; P = .038) were risk factors for increased seizures. SIGNIFICANCE: A minority of PWE experienced seizure exacerbation during the outbreak of COVID-19. Stress, uncontrolled seizures, and inappropriate change in AED regimen were associated with increased seizures. Based on these findings, stress might be an independent precipitant for triggering seizures in some PWE.


Assuntos
COVID-19/psicologia , Epilepsia/psicologia , Convulsões/psicologia , Estresse Psicológico/psicologia , Exacerbação dos Sintomas , Adolescente , Adulto , Idoso , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Inquéritos e Questionários , Adulto Jovem
16.
Clin Exp Pharmacol Physiol ; 47(10): 1731-1739, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32424975

RESUMO

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris water maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Aß1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Post-translational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlights the importance of PTMs in neurodegenerative diseases. In this study, we used western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs.

17.
Arthritis Res Ther ; 22(1): 65, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228698

RESUMO

OBJECTIVES: Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN). METHODS: We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up. RESULTS: The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0-10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod. CONCLUSIONS: Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.


Assuntos
Cromonas/uso terapêutico , Aplicação de Novas Drogas em Teste/métodos , Nefrite Lúpica/tratamento farmacológico , Terapia de Salvação/métodos , Sulfonamidas/uso terapêutico , Adolescente , Adulto , Estudos de Coortes , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução/métodos , Nefrite Lúpica/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
18.
Phys Chem Chem Phys ; 22(18): 10123-10131, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32347228

RESUMO

This work presents a series of molecular dynamics simulations of argon adsorption on a silicon substrate with different lattice orientations. From the simulation results, the density profiles are discussed and the amount of adsorbed particles is obtained at different pressures. It is found that the solid surface orientation has a great influence on the density distributions and atomic arrangements near the surface. With the collected data, the thermal constants derived from the expression of zeta adsorption isotherms are determined. The calculated isotherms agree well with the simulation results. Also, from a microscopic point of view, the molecular insights show that the structures of the adsorbates are present as clusters with different numbers of particles. The size of the clusters changes with pressure. At a relatively small pressure ratio, most of the clusters consist of a single molecule. As the pressure ratio increases, larger sized clusters appear, forming various cluster-types. The molecular cluster distributions are closely consistent with the basic approximation of the zeta adsorption isotherm. Furthermore, the surface adsorption sites determined from molecular dynamics simulation show good agreement with that predicted by the zeta isotherm model, which reaffirms the effectiveness of the theoretical model. When the isotherm is extended to a pressure ratio greater than unity, a finite amount of adsorption is predicted and the wetting conditions are obtained. Affected by the solid surface orientations, the pressure ratio at wetting for the silicon substrate with the (111) surface plane is larger than those of the (100) and (110) surfaces, indicating that a higher subcooling is required for the wetting transition.

19.
J Patient Saf ; 16(4): e284-e291, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-30633065

RESUMO

OBJECTIVES: The aim of this study was to assess patient safety culture (PSC) in maternal and child health (MCH) institutions in China and its individual, organizational, and regional variations. METHODS: Using the PSC survey for MCH institutions (PSCS-MCHI), 2021 valid respondents from 25 participating institutions were investigated in three regions (Beijing, Zhejiang, and Jiangxi) of China. Patient safety culture and its subscale scores (1-5) and factors associated with PSC as revealed by multilevel modeling. RESULTS: The respondents had an average PSC score of 3.55 (SD = 0.35), with subscale scores ranging between 2.46 ("staffing and workload") and 4.02 ("work commitment"). There were limited regional differences in PSC: a three-level regression model was only confirmed for the subscale "staff empowerment" (P = 0.006). However, significant organizational variations in PSC were evident: a two-level regression model was assumed for the PSC scale and nine subscales (P < 0.001). The fixed-effect models showed that male respondents, frontline workers, those who were in their mid-career (11-20 y), overloaded (≥9 hours), and had a masters or higher degree reported worse PSC. Frontline workers were less positive than managers in ratings on "managerial response to risks" (-0.11 [-0.20 to -0.02]), "management support" (-0.18 [-0.28 to -0.07]), and "staff empowerment" (-0.23[-0.35 to -0.11]). CONCLUSIONS: Patient safety culture in MCH institutions is shaped by organizational and individual characteristics. We observed a gap in perceived PSC between frontline worker, who are less positive, and managers. Actions for improving PSC should consider interventions on organizational management (such as appropriate staffing and workload management) and engagement of frontline workers in the development of management and training activities.


Assuntos
Saúde da Criança/normas , Saúde Materna/normas , Análise Multinível/métodos , Segurança do Paciente/normas , Gestão da Segurança/métodos , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Adulto Jovem
20.
Mol Psychiatry ; 25(2): 476-490, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31673123

RESUMO

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.


Assuntos
Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , China , Proteínas de Ligação a DNA/metabolismo , Família , Feminino , Predisposição Genética para Doença/genética , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Mutação/genética , Pais , Transtornos de Tique/genética , Síndrome de Tourette/complicações , Fatores de Transcrição/genética , Sequenciamento Completo do Exoma/métodos
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