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1.
Medicine (Baltimore) ; 99(33): e21669, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872032

RESUMO

BACKGROUND: Whether regional anesthesia (RA) offers better long-term neurodevelopment outcomes compared to general anesthesia (GA) to infants undergoing inguinal herniorrhaphy is still under heated debate. The aim of this meta-analysis is to compare the long-term neurodevelopment impact of RA with GA on infants undergoing inguinal herniorrhaphy. METHODS: A systematic search of MEDLINE, EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, clinicaltrials.gov and controlledtrials.com will be performed. Published eligible randomized controlled trials (RCTs) or quasi-RCTs (including abstracts) through May 20, 2020 with language limit of English will be enrolled in the meta-analysis. Two reviewers will independently conduct the procedures of study selection, data extraction, methodological quality assessment, and risk of bias assessment. The primary outcome is long-term neurodevelopmental state (at 2- and 5-year follow-up) as reflected in the Bayley and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) scales of infants development following surgeries. The secondary outcomes consist of satisfactory intraoperative infants immobility, duration of surgery, any anesthetic failure, the supplement of postoperative analgesia, postoperative apnea, and postoperative bradycardia. The pooled weighted mean differences (WMDs) or odds ratios (ORs) of each outcome measurement and relative 95% confident intervals (CIs) will be calculated. EndNote X8 (Clarivate Analytics) software will be applied to manage all citations. The Cochrane Review Manager version 5.3 software (RevMan 5.3) will be employed for statistical analysis. DISCUSSION: This study will summarize scientific and practical evidence and provide evidence-based individualized decision-making guidance on anesthesia regimen for inguinal herniorrhaphy in infants. REGISTRATION: This protocol was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) on 17 June 2020 (registration number INPLASY202060064).


Assuntos
Anestesia por Condução/efeitos adversos , Anestesia Geral/efeitos adversos , Cognição/efeitos dos fármacos , Herniorrafia/métodos , Desenvolvimento Infantil , Pré-Escolar , Hérnia Inguinal/cirurgia , Humanos , Lactente , Recém-Nascido , Metanálise como Assunto , Revisões Sistemáticas como Assunto
2.
Medicine (Baltimore) ; 99(38): e22370, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957414

RESUMO

BACKGROUND: Dementia among the Japanese aged 65 years or over population is estimated to approach about 700 million cases by 2025, and a corresponding rapid increase in Alzheimer disease (AD) can also be expected. The ballooning number of dementia patients, including AD, is creating major medical and social challenges. At present, only 3 drugs are recognized for the treatment of mild AD, and these are only used to alleviate symptoms. Although new therapies are needed to treat mild AD, insufficient development of disease-modifying drugs is being done. METHODS/DESIGN: The aim of this exploratory, open standard, treatment-controlled, randomized allocation, multicenter trial is to determine the efficacy of the traditional Japanese Kampo medicine hachimijiogan (HJG) on the cognitive dysfunction of mild AD.Eighty-six patients with AD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and as mild AD according to the Mini Mental State Examination (MMSE ≥21) will be included. All will already have been taking the same dose of Donepezil, Galantamine, or Rivastigmine for more than 3 months. The patients will be randomly assigned to receive additional treatment with HJG or to continue mild AD treatment without additional HJG. The primary endpoint is the change from baseline of the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version (ADAS-Jcog). ADAS-Jcog is a useful index for detecting change over time that investigates memory and visuospatial cognition injury from the early stage. The secondary endpoints are the changes from baseline of the Instrumental Activity of Daily Life, Apathy scale, and Nueropsychiatric Inventory scores. In this protocol, we will examine the Geriatric depression scale and do Metabolome analysis as exploratory endpoints. The recruitment period will be from August 2019 to July 2021. DISCUSSION: This is the first trial of Kampo medicine designed to examine the efficacy of HJG for the cognitive dysfunction of patients with mild AD. TRIAL REGISTRATION: This trial was registered on the Japan Registry of Clinical trials on 2 August 2, 2019 (jRCTs 071190018).


Assuntos
Doença de Alzheimer/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Idoso , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Medicina Kampo/métodos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Medicine (Baltimore) ; 99(33): e21242, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871984

RESUMO

Currently there is no effective treatment for vascular dementia (VaD). Pharmacological treatment often lead to severe complications and require drug dosage adjustment. This study investigated the effect of scalp electroacupuncture combined with Memantine in VaD. The safety and antioxidative effect of scalp electroacupuncture were also explored.A retrospective study was conducted and data of inpatients of Linyi Central Hospital with VaD between June 2017 and May 2018 were collected and sorted. The patients were divided into scalp electroacupuncture-medication (A), scalp electroacupuncture (B) and medication (control) (C) groups, in which Memantine was prescribed as medication. Cognitive function, activities of daily living and quality of life assessed by Montreal Cognitive Assessment (MoCA), Barthel index and dementia quality of life questionnaire; the contents of superoxide dismutase, lipid peroxide and nitric oxide in blood samples; and adverse reaction were compared.Data from a total of 150 patients were collected (Group A, n = 55; Group B, n = 50; Group C, n = 45). The post-treatment/follow-up Montreal Cognitive Assessment, Barthel index and dementia quality of life questionnaire scores were significantly improved in all groups compared to pre-treatment (groups A and B, P<.01; group C, P<.05). The improvements were significant for groups A vs C, B vs C (P<0.01, both), and group A vs B (P<.05). The post-treatment/follow-up levels of lipid peroxide and nitric oxide decreased significantly while superoxide dismutase increased significantly in groups A and B compared to pre-treatment (P<.01, both). The differences were significant for groups A vs C, and B vs C (P < .01, both), but not significant between groups A and B (P > .05). There were no significant adverse events occurred during the study and follow-up.In combined treatment, scalp electroacupuncture works in parallel with Memantine and significantly increase the therapeutic effect in VaD with no significant adverse events. Scalp electroacupuncture may have the potential to serve as an option or alternative treatment for VaD. Scalp electroacupuncture may alleviate VaD symptoms through its antioxidative mechanism.


Assuntos
Demência Vascular/terapia , Eletroacupuntura , Memantina/uso terapêutico , Nootrópicos/uso terapêutico , Atividades Cotidianas , Idoso , Biomarcadores/sangue , Cognição/efeitos dos fármacos , Terapia Combinada , Demência Vascular/sangue , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Feminino , Seguimentos , Humanos , Peróxidos Lipídicos/sangue , Masculino , Memantina/efeitos adversos , Óxido Nítrico/sangue , Nootrópicos/efeitos adversos , Qualidade de Vida , Estudos Retrospectivos , Couro Cabeludo , Superóxido Dismutase/sangue , Resultado do Tratamento
4.
Geriatr Gerontol Int ; 20(7): 655-663, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32691925

RESUMO

Many patients in rehabilitation facilities are affected by polypharmacy. Polypharmacy is associated with rehabilitation outcomes and functional recovery. Consequently, a combination of rehabilitation and pharmacotherapy may improve the outcomes of older people undergoing rehabilitation. A recent report described the concept of rehabilitation pharmacotherapy. The concept envisages helping frail older people and people with disabilities to achieve the highest possible body function, activity level and quality of life. There are two key tenets of rehabilitation pharmacotherapy: "pharmacotherapy in consideration of rehabilitation" and "rehabilitation in consideration of pharmacotherapy." "Pharmacotherapy in consideration of rehabilitation" includes use of drugs to treat impairment, activity limitation and participation restriction based on the International Classification of Functioning, Disability, and Health. "Rehabilitation in consideration of pharmacotherapy" refers to tailoring of rehabilitation considering the content of pharmacotherapy. With respect to drugs and motor dysfunction, anticholinergic drugs are associated with dysphagia and fractures. Increased use of potentially inappropriate medications may adversely affect the nutritional status. With respect to activities of daily living, polypharmacy and use of potentially inappropriate medications negatively affect the improvement in motor function during rehabilitation. Potent anticholinergic drugs are more likely to impede the improvement in cognitive function. In this review, we address the concept of rehabilitation pharmacotherapy and discuss its importance from the perspective of polypharmacy, the effect of drugs on disability and disease, nutritional status and activities of daily living. Geriatr Gerontol Int 2020; 20: -.


Assuntos
Pessoas com Deficiência/reabilitação , Idoso Fragilizado , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Atividades Cotidianas , Idoso , Antagonistas Colinérgicos/efeitos adversos , Cognição/efeitos dos fármacos , Feminino , Humanos , Masculino , Estado Nutricional , Qualidade de Vida
5.
Life Sci ; 257: 118049, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634430

RESUMO

AIMS: Mild traumatic brain injury (mTBI) is an important risk factor for cognitive impairment. Despite intense efforts to develop efficient treatments, the current therapies are not often effective and far from satisfactory. Silymarin has been suggested as a therapeutic agent in the treatment of traumatic brain injury. This study aimed to determine whether silymarin can exert neuroprotective effects on memory impairment following mTBI in mice. MAIN METHODS: After mTBI induction, mice were treated with silymarin once daily for 20 consecutive days by oral gavage. To investigate cognitive functions, animals were subjected to Y-maze, novel-object recognition, and Morris-water maze. Levels of tumor necrosis factor (TNF)-α, glutamate, and brain derived neurotrophic factor (BDNF) were measured in the hippocampus. KEY FINDINGS: Our findings showed that mTBI resulted in a significant decline in memory in the Y-maze and Morris-water maze in both sexes, whereas only impaired cognitive function in males in the novel-object recognition. We found notable increases in TNF-α and glutamate levels in the hippocampus of both sexes, while there was only a significant decrease in hippocampal BDNF in mTBI-induced females. In addition, silymarin treatment improved cognitive impairments in mTBI-induced males but not in females. Silymarin significantly reduced TNF-α and glutamate levels, and increased BDNF levels in the hippocampus of mTBI-induced male but not in female mice. SIGNIFICANCE: This study demonstrates that silymarin treatment sex-dependently improves cognitive impairment in mTBI-induced mice, and suggests that silymarin may be a therapeutic agent for cognitive decline following mTBI in males. Further studies are needed to establish the validity of these findings in humans.


Assuntos
Concussão Encefálica/tratamento farmacológico , Cognição/efeitos dos fármacos , Silimarina/uso terapêutico , Animais , Animais não Endogâmicos , Concussão Encefálica/metabolismo , Lesões Encefálicas/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/fisiologia , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fatores Sexuais , Silimarina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
Medicine (Baltimore) ; 99(22): e20240, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481389

RESUMO

Studies suggest that the use of alpha-blockers increases the risk of dementia in patients with benign prostate hyperplasia (BPH). Due to study limitations, the relationship between the use of alpha-blockers, such as tamsulosin, and the risk of dementia is still unclear. However, alpha1-adrenoreceptors are also present in the brain, so there is potential for adverse effects on cognitive function. Therefore, we investigated possible associations between the use of alpha-blockers and aggravation of cognitive decline in dementia patients using a clinical data analytic solution called the Smart Clinical Data Warehouse (CDW).We retrospectively investigated clinical data using the Smart CDW of Hallym University Medical Center from 2009 to 2019. We enrolled patients with probable Alzheimer disease (AD) who had completed the Mini-Mental State Examination (MMSE) at least twice during follow-up, and who had BPH. We compared the difference in MMSE scores between patients who took tamsulosin for >1000 days and those who did not take any alpha-blocker. We tested the effect of tamsulosin on cognitive decline in patients with AD, using propensity score-matched logistic regression analysis.Eligible cases were included in the tamsulosin (n = 68) or no-medication (n = 153) groups. After propensity score matching, clinical characteristics such as educational attainment and vascular risk factors were similar in the tamsulosin and no-medication groups. The MMSE scores did not differ significantly between the tamsulosin and no-medication groups (P = .470).The results suggest that tamsulosin for BPH is not associated with worsening of the cognitive decline in patients with AD.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Doença de Alzheimer/psicologia , Cognição/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Tansulosina/efeitos adversos , Agentes Urológicos/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso , Doença de Alzheimer/complicações , Data Warehousing , Humanos , Masculino , Pontuação de Propensão , Hiperplasia Prostática/complicações , Análise de Regressão , Estudos Retrospectivos , Tansulosina/uso terapêutico , Agentes Urológicos/uso terapêutico
7.
J Spec Oper Med ; 20(2): 132-135, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32573750

RESUMO

Dietary supplements promoted for brain health and enhanced cognitive performance are becoming increasingly popular. Special Operations Forces (SOF) is likely a prime target for this market as they strive to continually optimize and then sustain their high level of performance at all times. When a dietary supplement hits the market, it is considered safe until it is proven otherwise; yet the majority have not been analyzed for quality or tested for safety. The authors describe issues related to products marketed for brain health and cognitive enhancement and focus on products brought to our attention by the operational communities. The overwhelming majority of product labels were found to be misbranded and some were found to contain prohibited ingredients and drugs. The problematic ingredients in these products are introduced. The Operation Supplement Safety scorecard algorithm is demonstrated as a tool to quickly screen a product for potential safety; it can be used in real-time when considering the use of any dietary supplement product. These resources are available to help SOF medical assets evaluate whether a product's claims may be deceiving and potentially harmful to the health or career of Operators.


Assuntos
Cognição/efeitos dos fármacos , Cognição/fisiologia , Suplementos Nutricionais , Militares/psicologia , Suplementos Nutricionais/efeitos adversos , Humanos
8.
Cell Mol Biol (Noisy-le-grand) ; 66(3): 39-47, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32538745

RESUMO

This study was designed to investigate the expressions and roles of MMP-9 and HMGB1 in peripheral blood of patients with epilepsy and their relationship with the cognitive function and to explore factors affecting the prognosis of epilepsy patients. A total of 127 patients with epilepsy were collected in the study group and 120 healthy subjects receiving a physical examination at the same time were collected in the control group. The MMP-9 and HMGB1 expressions and their diagnostic value for epilepsy were compared between the two groups. The relationship between MMP-9 and HMGB1 expression levels and the clinical-pathological features and the Mini-mental State Evaluation Scale (MMSE) of patients from the study group were also analyzed. The serum levels of MMP-9 and HMGB1 in the study group were significantly higher than those in the control group (P< 0.001), and were greatly decreased after the treatment (P<0.001). The ROC curve showed that MMP-9 and HMGB1 combined detection had a good diagnostic efficiency for epilepsy. MMP-9 was much related to the type and disease duration of epilepsy (P< 0.05). HMGB1 was significantly associated with disease duration, seizure, and previous treatment history of epilepsy (P< 0.050). According to the Pearson correlation coefficient analysis, the expressions of MMP-9 and HMGB1 were negatively correlated with MMSE scores of the study group (P< 0.001). Logistic regression analysis showed that the duration of disease, seizures, MMP-9, and HMGB1 were independent risk factors for the prognosis of epilepsy. The expression levels of MMP-9 and HMGB1 in peripheral blood of patients with epilepsy are significantly increased, and negatively correlated with neurological function scores. They have potential involvement in the occurrence and development of epilepsy, which makes them significant for the diagnosis and treatment of epilepsy in the future.


Assuntos
Epilepsia/sangue , Epilepsia/diagnóstico , Proteína HMGB1/sangue , Metaloproteinase 9 da Matriz/sangue , Adulto , Idoso , Cognição/efeitos dos fármacos , Cognição/fisiologia , Epilepsia/tratamento farmacológico , Epilepsia/psicologia , Feminino , Proteína HMGB1/metabolismo , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise de Regressão , Fatores de Risco , Convulsões
10.
Arch Biochem Biophys ; 689: 108470, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32592802

RESUMO

The accumulation of lipid as a result of long-term consumption of a high-fat diet (HFD) may lead to metabolic and brain dysfunction. Atorvastatin, a recommended first-line lipid-lowering agent, has shown beneficial effects on metabolic and brain functions in several models. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was approved as an effective therapeutic drug for dyslipidemia patients. However, few studies have reported on the effect of this PCSK9 inhibitor on brain function. In addition, the comparative efficacy on the improvement of metabolic and brain functions between PCSK9 inhibitor and atorvastatin in obese models have not been elucidated. We hypothesized that PCSK9 inhibitor improves metabolic and brain functions in an obese model to a greater extent than atorvastatin. Thirty-two female rats were fed with either a normal diet (ND) or HFD for 15 weeks. At week 13, ND rats were given normal saline and HFD rats were given either normal saline, atorvastatin (40 mg/kg/day) or PCSK9 inhibitor (4 mg/kg/day) for 3 weeks. Oxidative stress, blood brain barrier breakdown, microglial hyperactivity, synaptic dysplasticity, apoptosis, amyloid proteins production in the hippocampus and cognitive decline were found in HFD-fed rats. Atorvastatin and PCSK9 inhibitor therapies equally attenuated hippocampal apoptosis and amyloid protein production in HFD-fed rats. Interestingly, PCSK9 inhibitor had the greater efficacy than atorvastatin on the amelioration of hippocampal oxidative stress, blood brain barrier breakdown, microglial hyperactivity, synaptic dysplasticity in the hippocampus and cognitive decline. These findings suggest that PCSK9 inhibitor may be another drug of choice for improving brain function in the obese condition with discontinued statin therapy.


Assuntos
Anticolesterolemiantes/uso terapêutico , Atorvastatina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Obesidade/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Cognição/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Feminino , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Pró-Proteína Convertase 9/metabolismo , Ratos
11.
Arq. neuropsiquiatr ; 78(6): 342-348, June 2020. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1102258

RESUMO

BACKGROUND: Hepatitis C can be defined as an infectious disease that develops an inflammatory activity, which may cause an impairment in the central nervous system, may cause cognitive impairments and symptoms of depression. OBJECTIVE: The objective of this study was to verify the cognitive performance of patients with chronic hepatitis C before and after treatment with simeprevir, sofosbuvir, and daclatasvir. METHODS: A prospective study was carried out in three stages: before, right after treatment, and six months after. Fifty-eight patients under clinical follow-up were evaluated at the Emílio Ribas Infectology Institute, in São Paulo, Brazil. The following instruments were used: sociodemographic questionnaire, Lawton's Scale, Beck's Depression Inventory, and a battery of neuropsychological tests that evaluated: intellectual function, memory, attention, executive function, and motor and processing speed). For statistical analysis, the analyses described (mean, frequency, and standard deviation), chi-square, and ANOVA were used. RESULTS: Most of the participants were male (n=30, 51.7%), with a mean of 58.23±8.79 years, mean schooling of 9.75±4.43 years. Comparing the results of neuropsychological evaluations (before, just after completion of drugs, and six months), a significant improvement was observed in relation to the acquisition of new knowledge (p=0.03), late visual memory (p=0.01), and tendency towards alternate attention (p=0.07). CONCLUSION: The treatment of the hepatitis C virus improved cognitive performance, especially in relation to memory


INTRODUÇÃO: A hepatite C pode ser definida como uma doença infecciosa, que se desenvolve por uma atividade inflamatória, que pode gerar um comprometimento no Sistema Nervoso Central, podendo ocasionar prejuízos cognitivos e sintomas de depressão. OBJETIVO: O objetivo deste estudo foi verificar o desempenho cognitivo de pacientes com hepatite C crônica antes e após o tratamento com simeprevir, sofosbuvir e daclatasvir. MÉTODOS: Foi realizado um estudo prospectivo em três etapas: antes, logo após o tratamento e seis meses depois. Foram avaliados 58 pacientes em acompanhamento clínico no Instituto de Infectologia Emílio Ribas, em São Paulo, Brasil. Foram utilizados os seguintes instrumentos: questionário sociodemográfico, Escala de Lawton, Inventário de Depressão de Beck e uma bateria de testes neuropsicológicos que avaliaram: função intelectual, memória, atenção, função executiva e velocidade motora e de processamento). Para análise estatística, foram utilizadas as análises descritas (média, frequência e desvio padrão), qui-quadrado e ANOVA. RESULTADOS: A maioria dos participantes era do sexo masculino (n=30, 51,7%), com média de 58,23±8,79 anos, escolaridade média de 9,75±4,43 anos. Comparando os resultados das avaliações neuropsicológicas (antes, logo após a finalização dos medicamentos e seis meses), observou-se melhora significativa em relação à aquisição de novos conhecimentos (p=0,03), memória visual tardia (p=0,01) e tendência em relação a atenção alternada (p=0,07). CONCLUSÃO: O tratamento do vírus da hepatite C melhorou o desempenho cognitivo, principalmente em relação à memória


Assuntos
Humanos , Masculino , Feminino , Hepatite C/tratamento farmacológico , Cognição/efeitos dos fármacos
12.
Medicine (Baltimore) ; 99(20): e20159, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443331

RESUMO

Postoperative delirium (PD), characterized by acute onset of global impairment in consciousness and cognition, is a common complication following major surgeries and is often associated with adverse outcomes. Because of the multiple comorbidities of the patient along with extensive nature of the surgery, patients undergoing surgery for bone metastases may be prone to developing PD. However, no study exists regarding PD in patients who undergo surgery for bone metastases.Two hundred seventy six patients with mean age of 64 years (range, 16-94) who underwent surgery for bone metastases were reviewed. The diagnosis of PD was made by the psychiatrist, according to fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Possible perioperative clinic-pathologic factors that may be associated with the development of PD were investigated.Among the 276 patients, 9% (n = 25) developed PD. On multivariate logistic regression analysis, history of psychiatric disorders (odds ratio [OR] = 9.63; 95% confidence interval [CI] 1.78-21.74, P = .004), high preoperative serum C-reactive protein (CRP) level (OR = 1.17; 95% CI 1.06-1.29, P = .001), low preoperative serum albumin level (OR = 0.13; 95% CI 0.03-0.48, P = 0.002), and high dose of opioid analgesics received in the immediate postoperative period (OR = 1.05; 95% CI 1.01-1.07, P = .001) were independently associated with the development of PD. Patients with PD had lower survival (log rank, P = .001) than patients without PD.Incidence of PD is considerable in patients undergoing surgery for bone metastases. History of psychiatric disorders, preoperative serum albumin and CRP levels, and the dose of postoperative opioid analgesics are associated with the development of PD.


Assuntos
Neoplasias Ósseas/cirurgia , Delírio/etiologia , Metástase Neoplásica/patologia , Idoso , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Neoplasias Ósseas/secundário , Proteína C-Reativa/análise , Cognição/efeitos dos fármacos , Cognição/fisiologia , Comorbidade , Delírio/epidemiologia , Delírio/mortalidade , Delírio/psicologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
13.
Medicine (Baltimore) ; 99(20): e20177, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443335

RESUMO

BACKGROUND: Although many studies have reported the effects of dexmedetomidine on cognitive function (CF) in elderly patients after laparoscopic cholecystectomy (LCT), to this date, its effects are still not well understood. The aim of this study is to produce a qualitative synthesis of assessing the effects of dexmedetomidine on CF in elderly patients after LCT. METHODS: We will conduct a comprehensive search in Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Scopus, VIP Database, WANGFANG Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from the commencement to March 31, 2020 without restrictions of language and publication status. In addition, we will also search grey literature, including conference abstracts, dissertations, reference lists of included studies and relevant reviews. All potential studies will be identified independently by 2 authors to determine their inclusion against previously defined eligibility criteria. The quality of selected papers will be assessed using Cochrane risk of bias tool. All statistical analysis will be performed using RevMan 5.3 software. RESULTS: This study will provide a synthesis of the current available data on assessing the effects of dexmedetomidine on CF in elderly patients after LCT. CONCLUSIONS: Its findings will provide qualitative evidence to better understand the effects of dexmedetomidine on CF in elderly patients after LCT.INPLASY Registration Number: INPLASY202040030.


Assuntos
Analgésicos não Entorpecentes/farmacologia , Colecistectomia Laparoscópica/métodos , Cognição/efeitos dos fármacos , Dexmedetomidina/farmacologia , Idoso , Analgésicos não Entorpecentes/uso terapêutico , China/epidemiologia , Dexmedetomidina/uso terapêutico , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança
14.
Toxicol Appl Pharmacol ; 398: 115028, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360636

RESUMO

NADPH oxidase (NOX) has been identified as a crucial contender of oxidative damage in Alzheimer's disease (AD). However, the capability of diapocynin, a NOX inhibitor, to offer neuroprotection in AD models is still a matter of debate. Hence, the current work is dedicated to investigate the influence of diapocynin on cognitive impairment prompted by ovariectomy combined with D-galactose injection in rats (an AD animal model), and to elucidate the signaling mechanisms regulating diapocynin-induced effects. Female rats were exposed to ovariectomy or sham operation. Ovariectomized rats were injected intraperitoneally with D-galactose (150 mg/kg/day) for 70 days and, on day 43, they were orally treated with diapocynin (10 mg/kg/day) for 28 days. Diapocynin amended cognitive functions as confirmed using novel object recognition and Morris water maze tests along with histopathological improvement. It caused a prominent decrement in ß-secretase, p-tau, and amyloid ß, contrary to α-secretase elevation in hippocampus and hampered neuroinflammation and oxidative stress, manifested by declined levels of NOX1, tumor necrosis factor-α, and nuclear factor-kappa B p65. In addition, diapocynin augmented synaptophysin, brain-derived neurotrophic factor, and phospho-cAMP response element binding protein and enhanced protein expression of phosphorylated forms of phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3ß (GSK-3ß), protein kinase B (Akt), extracellular signal-regulated kinase (ERK) 1/2, ERK kinase kinase (Raf-1), and ERK kinase (MEK) 1/2, while inhibiting those of c-Jun and c-Jun N-terminal kinase (JNK). In conclusion, diapocynin attenuated memory impairment and AD-like anomalies via activating Raf-1/MEK/ERK and PI3K/Akt/GSK-3ß, while inhibiting JNK/c-Jun signaling cascades.


Assuntos
Acetofenonas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Compostos de Bifenilo/farmacologia , Cognição/efeitos dos fármacos , Galactose/metabolismo , Nootrópicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Animais , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Memória/efeitos dos fármacos , Ratos , Ratos Wistar
15.
Psychol Aging ; 35(4): 517-528, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32352804

RESUMO

Adequate hydration is essential for health, with even mild forms of dehydration often having negative effects on cognition and well-being. Despite evidence of higher risk for dehydration among older adults, links between dehydration and cognitive or well-being outcomes have not been established in old age. In this study, we used longitudinal data from the Berlin Aging Study II (age range 60-89) to investigate whether trajectories of cognitive functioning (digit symbol, N = 1,111) and well-being (Diener satisfaction with life, N = 1,066; Socio-Economic Panel Study life satisfaction, N = 1,067; and Lawton morale, N = 1,067) are associated with objective dehydration (osmolarity; 33% dehydrated). Our results revealed that higher dehydration was associated with steeper decline in cognitive functioning and well-being over time, and lower well-being among those with higher body mass index. These associations were independent of sociodemographic and physical health characteristics. Our findings highlight the importance of adequate hydration for preserved cognition and well-being across old age. We discuss potential mechanisms and consider practical implications arising from our results. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Envelhecimento/fisiologia , Cognição/efeitos dos fármacos , Desidratação/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino
16.
Nat Commun ; 11(1): 2484, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424276

RESUMO

DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer's disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/patologia , Encéfalo/patologia , Dano ao DNA , DNA Glicosilases/metabolismo , Histona Desacetilase 1/metabolismo , Estresse Oxidativo , Acetilação , Envelhecimento/genética , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Sequência de Bases , Benzofenonas/farmacologia , Cognição/efeitos dos fármacos , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Ontologia Genética , Guanina/análogos & derivados , Guanina/metabolismo , Memória/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Regiões Promotoras Genéticas/genética
17.
Nat Commun ; 11(1): 2555, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444624

RESUMO

Fetal alcohol exposure (FAE) is the leading preventable developmental cause of cognitive dysfunction. Even in the absence of binge drinking, alcohol consumption during pregnancy can leave offspring deficient. However, the mechanisms underlying these deficiencies are unknown. Using a mouse model of gestational ethanol exposure (GEE), we show increased instrumental lever-pressing and disruption of efficient habitual actions in adults, indicative of disrupted cognitive function. In vivo electrophysiology reveals disrupted action encoding in dorsolateral striatum (DLS) associated with altered habit learning. GEE mice exhibit decreased GABAergic transmission onto DLS projection neurons, including inputs from parvalbumin interneurons, and increased endocannabinoid tone. Chemogenetic activation of DLS parvalbumin interneurons reduces the elevated lever pressing of GEE mice. Pharmacologically increasing endocannabinoid tone mimics GEE effects on cognition and synaptic transmission. These findings show GEE induces long-lasting deficits in cognitive function that may contribute to human FAE, and identify potential mechanisms for future therapeutic targeting.


Assuntos
Corpo Estriado/fisiopatologia , Etanol/efeitos adversos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Animais , Cognição/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Etanol/metabolismo , Feminino , Desenvolvimento Fetal , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linhagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
18.
Anesthesiology ; 133(1): 154-164, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32384291

RESUMO

BACKGROUND: Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive-emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks. METHODS: A randomized, double-blind, crossover, placebo-controlled study (NCT02467517) included 20 patients with neuropathic pain. Each ketamine-naïve patient received one infusion every 35 days in a random order: ketamine (0.5 mg/kg)/placebo or ketamine (0.5 mg/kg)/magnesium sulfate (3g) or placebo/placebo.The primary endpoint was the area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints included pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires. RESULTS: Daily pain intensity was not significantly different between the three groups (n = 20) over 35 days (mean area under the curve = 185 ± 100, 196 ± 92, and 187 ± 90 pain score-days for ketamine, ketamine/magnesium, and placebo, respectively, P = 0.296). The effect size of the main endpoint was -0.2 (95% CI [-0.6 to 0.3]; P = 0.425) for ketamine versus placebo, 0.2 (95% CI [-0.3 to 0.6]; P = 0.445) for placebo versus ketamine/magnesium and -0.4 (95% CI [-0.8 to 0.1]; P = 0.119) for ketamine versus ketamine/magnesium. There were no significant differences in emotional, sleep, and quality of life measures. During placebo, ketamine, and ketamine/magnesium infusions, 10%, 20%, and 35% of patients respectively reported at least one adverse event. CONCLUSIONS: The results of this trial in neuropathic pain refuted the hypothesis that ketamine provided pain relief at 5 weeks and cognitive-emotional benefit versus placebo and that a combination with magnesium had any additional analgesic effect.


Assuntos
Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Ketamina/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Neuralgia/tratamento farmacológico , Adulto , Idoso , Cognição/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Emoções , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Feminino , Humanos , Infusões Intravenosas , Ketamina/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neuralgia/psicologia , Medição da Dor/efeitos dos fármacos , Resultado do Tratamento
19.
J Stroke Cerebrovasc Dis ; 29(7): 104754, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32370925

RESUMO

BACKGROUND AND AIM: It is unclear whether blood pressure (BP) is associated with cognition after stroke. We examined associations between systolic and diastolic BP (SBP, DBP), pulse pressure (PP), mean arterial pressure (MAP), and cognition, each measured 90 days after stroke. METHODS: Cross-sectional analysis of prospectively obtained data of 432 dementia-free subjects greater than or equal to 45 (median age, 66; 45% female) with stroke (92% ischemic; median NIH stroke score, 3 [IQR, 2-6]) from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) project in 2011-2013. PRIMARY OUTCOME: Modified Mini-Mental Status Examination (3MSE; range, 0-100). SECONDARY OUTCOMES: Animal Fluency Test (AFT; range, 0-10) and Trail Making Tests A and B (number of correct items [range, 0-25]/completion time [Trails A: 0-180 seconds; Trails B: 0-300 second]). Linear or tobit regression adjusted associations for age, education, and race/ethnicity as well as variables significantly associated with BP and cognition. RESULTS: Higher SBP, lower DBP, higher PP, and lower MAP each were associated with worse cognitive performance for all 4 tests (all P < .001). After adjusting for patient factors, no BP measures were associated with any of the 4 tests (all P > .05). Lower cognitive performance was associated with older age, less education, Mexican American ethnicity, diabetes, higher stroke severity, more depressive symptoms, and lower BMI. Among survivors with hypertension, anti-hypertensive medication use 90 days after stroke was significantly associated with higher AFT scores (P = .02) but not other tests (P > .15). CONCLUSIONS: Stroke survivors' BP levels were not associated with cognitive performance at 90 days independent of sociodemographic and clinical factors.


Assuntos
Pressão Sanguínea , Transtornos Cognitivos/etnologia , Cognição , Hipertensão/etnologia , Acidente Vascular Cerebral/etnologia , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Estudos Transversais , Avaliação da Deficiência , Grupo com Ancestrais do Continente Europeu , Função Executiva , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Testes de Estado Mental e Demência , Americanos Mexicanos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prognóstico , Fatores de Risco , Determinantes Sociais da Saúde/economia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Texas/epidemiologia , Fatores de Tempo
20.
Psychopharmacology (Berl) ; 237(7): 1989-2005, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388619

RESUMO

RATIONALE: Abuse of the psychostimulant methamphetamine (METH) can cause long-lasting damage to brain monoaminergic systems and is associated with profound mental health problems for users, including lasting cognitive impairments. Animal models of METH exposure have been useful in dissecting the molecular effects of the drug on cognition, but many studies use acute, non-contingent "binge" administrations of METH which do not adequately approximate human METH use. Long-term METH exposure via long-access (LgA) self-administration paradigms has been proposed to more closely reflect human use and induce cognitive impairments. OBJECTIVE: To better understand the role of contingency and patterns of exposure in METH-induced cognitive impairments, we analyzed behavioral and neurochemical outcomes in adult male rats, comparing non-contingent "binge" METH administration with contingent (LgA) METH self-administration and non-contingent yoked partners. RESULTS: Binge METH (40 mg/kg, i.p., over 1 day) dramatically altered striatal and hippocampal dopamine, DOPAC, 5-HT, 5-HIAA, BDNF, and TrkB 75 days after drug exposure. In contrast, 6-h LgA METH self-administration (cumulative 24.8-48.9 mg METH, i.v., over 16 days) altered hippocampal BDNF in both contingent and yoked animals but reduced striatal 5-HIAA in only contingent animals. Neurochemical alterations following binge METH administration were not accompanied by cognitive deficits in Morris water maze, novel object recognition, or Y-maze tests. However, contingent LgA METH self-administration resulted in impaired spatial memory in the water maze. CONCLUSIONS: Overall, substantial differences in neurochemical markers between METH exposure and self-administration paradigms did not consistently translate to deficits in cognitive tasks, highlighting the complexity of correlating METH-induced neurochemical changes with cognitive outcomes.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Metanfetamina/administração & dosagem , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Cognição/fisiologia , Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Ratos , Ratos Wistar , Autoadministração/psicologia
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