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1.
Psychol Med ; 54(6): 1142-1151, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37818656

RESUMO

BACKGROUND: Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory. METHOD: One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics. RESULTS: Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model. CONCLUSIONS: Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.


Assuntos
Transtorno Depressivo Maior , Transtornos Psicóticos , Humanos , Olanzapina/uso terapêutico , Depressão , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Sertralina/uso terapêutico
2.
Mol Psychiatry ; 28(8): 3305-3313, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37258617

RESUMO

The effect of antipsychotic medication on resting state functional connectivity in major depressive disorder (MDD) is currently unknown. To address this gap, we examined patients with MDD with psychotic features (MDDPsy) participating in the Study of the Pharmacotherapy of Psychotic Depression II. All participants were treated with sertraline plus olanzapine and were subsequently randomized to continue sertraline plus olanzapine or be switched to sertraline plus placebo. Participants completed an MRI at randomization and at study endpoint (study completion at Week 36, relapse, or early termination). The primary outcome was change in functional connectivity measured within and between specified networks and the rest of the brain. The secondary outcome was change in network topology measured by graph metrics. Eighty-eight participants completed a baseline scan; 73 completed a follow-up scan, of which 58 were usable for analyses. There was a significant treatment X time interaction for functional connectivity between the secondary visual network and rest of the brain (t = -3.684; p = 0.0004; pFDR = 0.0111). There was no significant treatment X time interaction for graph metrics. Overall, functional connectivity between the secondary visual network and the rest of the brain did not change in participants who stayed on olanzapine but decreased in those switched to placebo. There were no differences in changes in network topology measures when patients stayed on olanzapine or switched to placebo. This suggests that olanzapine may stabilize functional connectivity, particularly between the secondary visual network and the rest of the brain.


Assuntos
Antipsicóticos , Transtorno Depressivo Maior , Humanos , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Olanzapina/uso terapêutico , Sertralina/uso terapêutico , Benzodiazepinas , Quimioterapia Combinada , Imageamento por Ressonância Magnética
3.
Neuropsychobiology ; 82(3): 168-178, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37015192

RESUMO

INTRODUCTION: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy. METHODS: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse. RESULTS: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer's disease had a significantly decreased likelihood of relapse. CONCLUSION: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.


Assuntos
Antipsicóticos , Sertralina , Masculino , Humanos , Feminino , Olanzapina/uso terapêutico , Sertralina/uso terapêutico , Depressão , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Genômica , Método Duplo-Cego
4.
J Sport Rehabil ; 31(3): 286-293, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34768238

RESUMO

CONTEXT: Anterior cruciate ligament (ACL) injuries are a common and devastating injury in women's soccer. Several risk factors for ACL injury have been identified, but have not yet been examined as potentially dynamic risk factors, which may change throughout a collegiate soccer season. DESIGN: Prospective cohort study. METHODS: Nine common clinical screening assessments for ACL injury risk, consisting of range of motion, movement quality, and power, were assessed in 29 Division I collegiate women's soccer players. Preseason and midseason values were compared for significant differences. Change scores for each risk factor were also correlated with cumulative training loads during the first 10 weeks of a competitive soccer season. RESULTS: Hip external rotation range of motion and power had statistically significant and meaningful differences at midseason compared with preseason, indicating they are dynamic risk factors. There were no significant associations between the observed risk factor changes and cumulative training load. CONCLUSIONS: Hip external rotation range of motion and power are dynamic risk factors for ACL injury in women's collegiate soccer athletes. Serial screening of these risk factors may elucidate stronger associations with injury risk and improve prognostic accuracy of screening tools.


Assuntos
Lesões do Ligamento Cruzado Anterior , Futebol/lesões , Lesões do Ligamento Cruzado Anterior/epidemiologia , Lesões do Ligamento Cruzado Anterior/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Movimento/fisiologia , Estudos Prospectivos , Amplitude de Movimento Articular , Fatores de Risco
5.
Psychol Med ; : 1-7, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33766150

RESUMO

BACKGROUND: Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression. METHODS: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse. RESULTS: Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups. CONCLUSIONS: PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.

6.
J Clin Psychopharmacol ; 41(2): 196-199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33587400

RESUMO

PURPOSE/BACKGROUND: Electroconvulsive therapy (ECT) is effective in the treatment of acute episodes of psychotic depression. However, no adequately powered studies have directly investigated the efficacy of antipsychotic pharmacotherapy in relapse prevention of psychotic depression after ECT. In the absence of such literature, we reviewed the clinical practice of 4 academic medical centers that have made research contributions in the treatment of psychotic depression over the past 20 years. METHODS/PROCEDURES: We reviewed medical records of patients with a diagnosis of psychotic depression who received 1 or more acute courses of ECT over the span of 3 years. Chi-square tests were used to compare pharmacotherapy prescribed at the time of completion of ECT. FINDINGS/RESULTS: A total of 163 patients received 176 courses of ECT for separate episodes of psychotic depression. The combination of an antidepressant plus an antipsychotic was the most common regimen, ranging from 61.9% to 85.5% of all prescriptions. One center added lithium in 45.5% of cases treated with the combination of an antidepressant plus an antipsychotic. An antipsychotic alone was prescribed in less than 10% of cases. An antidepressant alone or other drug combinations were rare. IMPLICATIONS/CONCLUSIONS: The combination of an antidepressant plus an antipsychotic was the most commonly prescribed regimen at the completion of ECT for relapse prevention in patients with psychotic depression acutely treated with ECT. Although this report offers a view of the clinical practice of 4 academic medical centers, it also points to the need of randomized controlled trials on continuation pharmacotherapy after treatment of psychotic depression with ECT.


Assuntos
Depressão/prevenção & controle , Eletroconvulsoterapia/métodos , Transtornos Psicóticos/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Depressão/terapia , Quimioterapia Combinada , Feminino , Humanos , Compostos de Lítio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/psicologia , Recidiva , Estudos Retrospectivos , Prevenção Secundária/métodos
7.
Am J Geriatr Psychiatry ; 29(7): 645-654, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33268022

RESUMO

OBJECTIVE: To examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine. METHODS: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures. RESULTS: Participants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18-59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures. CONCLUSION: Older patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not.


Assuntos
Antipsicóticos , Sertralina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/efeitos adversos , Benzodiazepinas/efeitos adversos , Depressão , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Sertralina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
8.
Am J Epidemiol ; 189(1): 27-33, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31595954

RESUMO

Advances in cancer screening methods have opened avenues for incidental findings and cancer overdiagnosis. We performed a secondary analysis of the National Lung Screening Trial (enrollment from 2002-2004), a randomized controlled trial comparing low-dose computed tomography (LDCT; n = 26,722) with chest radiography (CXR; n = 26,732) for lung cancer detection, to examine incidental findings related to thyroid cancer (ThCa). Three screening rounds were included, and median follow-up was 6.6 years for LDCT and 6.5 years for CXR. Radiologists reported lung and non-lung-related abnormalities. In the LDCT arm, 5.7%, 4.7%, and 4.5% of participants had abnormalities above the diaphragm (AADs) detected at baseline, year 1, and year 2, respectively, compared with 2.3%, 1.5%, and 1.3% in the CXR arm. In the LDCT arm, 205 AADs (7.0%) were thyroid-related. Overall, 60 ThCas were reported, 35 in the LDCT arm and 25 in the CXR arm (P = 0.2). In the LDCT arm, participants with a prior AAD had a 7.8-fold increased risk (95% confidence interval: 4.0, 15.1) of ThCa compared with those who did not have an AAD. Early and persistent excess of ThCas diagnosed earlier in the LDCT arm suggests overdiagnosis. The use of sensitive screening modalities for early detection of lung cancer might result in the discovery of thyroid incidentalomas.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico , Radiografia Torácica/estatística & dados numéricos , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Idoso , Feminino , Humanos , Achados Incidentais , Neoplasias Pulmonares/etiologia , Masculino , Uso Excessivo dos Serviços de Saúde , Pessoa de Meia-Idade , Estudos Prospectivos , Fumar/efeitos adversos , Neoplasias da Glândula Tireoide/epidemiologia , Estados Unidos/epidemiologia
10.
Water Sci Technol ; 82(12): 2920-2928, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33341781

RESUMO

Phosphorus (P) discharge from wastewater treatment plants into the environment contributes to eutrophication issues. Reactive media filters represent an effective, simple and cost-effective solution to decrease the P content. Previous research used various experimental designs and often synthetic wastewater, making assessment of real-world performance difficult. This study assesses the impact of the hydraulic retention time (HRT) on P removal using real wastewater to refine design criteria for full-scale installations. Four media were compared in column experiments for >200 days. Different HRTs were applied and initially the media achieved low P effluent concentrations of >0.1 mg/L PO4-P, increasing over time. Best P removal was observed for the highest HRT with on average >99%. HRT was seen to be the driving factor for P removal rather than media capacity. Three of the four materials showed pH levels above 12 initially, decreasing over time. Water quality parameters, including organics, solids and metals, were monitored. In-depth analysis confirmed formation of calcium phosphate precipitation on the media's surface. The results suggest the importance of an optimal HRT to achieve high P removal and show that the reactive media application is an appropriate technology for P removal on small sites if the elevated pH is addressed.


Assuntos
Fósforo , Águas Residuárias , Eliminação de Resíduos Líquidos
11.
Angew Chem Int Ed Engl ; 59(1): 424-428, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31609507

RESUMO

Excellent conversion efficiencies of over 20 % and facile cell production have placed hybrid perovskites at the forefront of novel solar cell materials, with CH3 NH3 PbI3 being an archetypal compound. The question why CH3 NH3 PbI3 has such extraordinary characteristics, particularly a very efficient power conversion from absorbed light to electrical power, is hotly debated, with ferroelectricity being a promising candidate. This does, however, require the crystal structure to be non-centrosymmetric and we herein present crystallographic evidence as to how the symmetry breaking occurs on a crystallographic and, therefore, long-range level. Although the molecular cation CH3 NH3 + is intrinsically polar, it is heavily disordered and this cannot be the sole reason for the ferroelectricity. We show that it, nonetheless, plays an important role, as it distorts the neighboring iodide positions from their centrosymmetric positions.

12.
N Engl J Med ; 375(15): 1438-1447, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27732805

RESUMO

BACKGROUND: The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002). RESULTS: After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality. CONCLUSIONS: Although the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Detecção Precoce de Câncer , Mamografia , Uso Excessivo dos Serviços de Saúde , Estadiamento de Neoplasias , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Reações Falso-Positivas , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Invasividade Neoplásica , Programa de SEER
13.
JAMA ; 322(7): 622-631, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429896

RESUMO

Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission. Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent. Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017. Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline. Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c). Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016). Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain. Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.


Assuntos
Transtornos Psicóticos Afetivos/tratamento farmacológico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Olanzapina/uso terapêutico , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Antipsicóticos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/efeitos adversos , Modelos de Riscos Proporcionais , Prevenção Secundária , Sertralina/uso terapêutico , Adulto Jovem
14.
Res Sports Med ; 27(1): 21-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30084269

RESUMO

The purpose of this study was to examine associations between ankle dorsiflexion (ankle-DF) displacement and knee and hip kinematics and kinetics during a jump-landing task in females following anterior cruciate ligament reconstruction (ACLR). Females (n = 23) with a history of unilateral ACLR (≥ 6-months post-ACLR) underwent a three-dimensional lower extremity biomechanical evaluation. Pearson Product Moment (r) correlations assessed associations between ankle-DF displacement and knee and hip kinematic and kinetic variables. On the involved-limb, individuals with lesser ankle-DF displacement demonstrated greater knee abduction displacement during the loading phase (r = -0.645, p = 0.001). On the uninvolved-limb, individuals with greater ankle-DF displacement demonstrated greater hip flexion displacement (r = 0.599, p = 0.003) and knee flexion displacement (r = -0.545, p = 0.007). There were no other significant associations between ankle-DF displacement and ankle, knee, or hip biomechanical variables on either limb (p > 0.05). Our findings demonstrate that reduced ankle-DF motion appears to share a different relationship between the involved- and uninvolved-limbs in females post-ACLR.


Assuntos
Articulação do Tornozelo/fisiologia , Reconstrução do Ligamento Cruzado Anterior , Articulação do Quadril/fisiologia , Articulação do Joelho/fisiologia , Amplitude de Movimento Articular , Adolescente , Adulto , Fenômenos Biomecânicos , Teste de Esforço , Feminino , Humanos , Movimento , Adulto Jovem
15.
Hippocampus ; 28(7): 457-470, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29742814

RESUMO

Technology allowing genetically targeted cells to be modulated by light has revolutionized neuroscience in the past decade, and given rise to the field of optogenetic stimulation. For this, non-native, light activated proteins (e.g., channelrhodopsin) are expressed in a specific cell phenotype (e.g., glutamatergic neurons) in a subset of central nervous system nuclei, and short pulses of light of a narrow wavelength (e.g., blue, 473 nm) are used to modulate cell activity. Cell activity can be increased or decreased depending on which light activated protein is used. We review how the greater precision provided by optogenetics has transformed the study of neural circuits, in terms of cognition and behavior, with a focus on learning and memory. We also explain how optogenetic modulation is facilitating a better understanding of the mechanistic underpinnings of some neurological and psychiatric conditions. Based on this research, we suggest that optogenetics may provide tools to improve memory in neurological conditions, particularly diencephalic amnesia and Alzheimer's disease.


Assuntos
Transtornos da Memória/terapia , Optogenética/métodos , Doença de Alzheimer/complicações , Animais , Demência/complicações , Humanos , Transtornos da Memória/etiologia , Optogenética/tendências
16.
N Engl J Med ; 382(1): 96-98, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31875514

Assuntos
Neoplasias , Humanos
17.
Cancer ; 123(4): 592-599, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-27911486

RESUMO

BACKGROUND: Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial. METHODS: The PLCO trial randomized subjects from 1993 to 2001 to an intervention or control arm. Intervention-arm men received annual PSA tests for 6 years and digital rectal examinations for 4 years. This study used a linkage with the National Death Index to extend mortality follow-up to a maximum of 19 years after randomization. RESULTS: Men were randomized to the intervention arm (n = 38,340) or the control arm (n = 38,343). The median follow-up time was 14.8 years (25th/75th, 12.7/16.5 years) in the intervention arm and 14.7 years (25th/75th, 12.6/16.4 years) in the control arm. There were 255 deaths from prostate cancer in the intervention arm and 244 deaths from prostate cancer in the control arm; this meant a rate ratio (RR) of 1.04 (95% confidence interval [CI], 0.87-1.24). The RR for all-cause mortality was 0.977 (95% CI, 0.950-1.004). It was estimated that 86% of the men in the control arm and 99% of the men in the intervention arm received any PSA testing during the trial, and the estimated yearly screening-phase PSA testing rates were 46% and 84%, respectively. CONCLUSIONS: Extended follow-up of the PLCO trial over a median of 15 years continues to indicate no reduction in prostate cancer mortality for the intervention arm versus the control arm. Because of the high rate of control-arm PSA testing, this finding can be viewed as showing no benefit of organized screening versus opportunistic screening. Cancer 2017;123:592-599. © 2016 American Cancer Society.


Assuntos
Detecção Precoce de Câncer , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Idoso , American Cancer Society , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
19.
Am J Geriatr Psychiatry ; 25(6): 672-679, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28285771

RESUMO

OBJECTIVE: To characterize cognitive function at baseline and investigate the relationship between change in cognition, depression, and psychosis after treatment among older adults with major depressive disorder with psychotic features. METHODS: This was a secondary analysis of a double-blind, randomized, controlled treatment trial at inpatient and outpatient settings at four academic health centers on "Young Old" (aged 60-71 years, N = 71) and "Older" (aged 72-86 years, N = 71) participants diagnosed with psychotic depression. Olanzapine plus sertraline or olanzapine plus placebo were given until week 12 or termination. RESULTS: At baseline, Young Old and Older participants did not differ on measures of depression severity or global cognition, information processing speed, and executive function. Improvement in depressive and psychotic symptoms from baseline to treatment end was similar in both the Young Old and Older groups. However, improvement in depressive symptoms was significantly associated with improvement in global cognitive function in Young Old participants but not in Older participants. CONCLUSION: Cognitive dysfunction was not a detriment to improvement in symptoms of psychotic major depression in our geriatric patients. Young Old and Older patients improved to a similar degree on measures of depression and delusions from baseline to treatment end. However, improvement in cognition over the course of treatment was more prominent in the Young Old group than in the Older group.


Assuntos
Benzodiazepinas/uso terapêutico , Cognição/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Sertralina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Envelhecimento/psicologia , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtorno Depressivo Maior/complicações , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Transtornos de Início Tardio/complicações , Transtornos de Início Tardio/tratamento farmacológico , Pessoa de Meia-Idade , Olanzapina , Transtornos Psicóticos/complicações , Resultado do Tratamento
20.
J Strength Cond Res ; 31(11): 3146-3157, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29068865

RESUMO

Peck, KY, DiStefano, LJ, Marshall, SW, Padua, DA, Beutler, AI, de la Motte, SJ, Frank, BS, Martinez, JC, and Cameron, KL. Effect of a lower extremity preventive training program on physical performance scores in military recruits. J Strength Cond Res 31(11): 3146-3157, 2017-Exercise-based preventive training programs are designed to improve movement patterns associated with lower extremity injury risk; however, the impact of these programs on general physical fitness has not been evaluated. The purpose of this study was to compare fitness scores between participants in a preventive training program and a control group. One thousand sixty-eight freshmen from a U.S. Service Academy were cluster-randomized into either the intervention or control group during 6 weeks of summer training. The intervention group performed a preventive training program, specifically the Dynamic Integrated Movement Enhancement (DIME), which is designed to improve lower extremity movement patterns. The control group performed the Army Preparation Drill (PD), a warm-up designed to prepare soldiers for training. Main outcome measures were the Army Physical Fitness Test (APFT) raw and scaled (for age and sex) scores. Independent t tests were used to assess between-group differences. Multivariable logistic regression models were used to control for the influence of confounding variables. Dynamic Integrated Movement Enhancement group participants completed the APFT 2-mile run 20 seconds faster compared with the PD group (p < 0.001), which corresponded with significantly higher scaled scores (p < 0.001). Army Physical Fitness Test push-up scores were significantly higher in the DIME group (p = 0.041), but there were no significant differences in APFT sit-up scores. The DIME group had significantly higher total APFT scores compared with the PD group (p < 0.001). Similar results were observed in multivariable models after controlling for sex and body mass index (BMI). Committing time to the implementation of a preventive training program does not appear to negatively affect fitness test scores.


Assuntos
Exercício Físico/fisiologia , Extremidade Inferior/fisiologia , Militares , Movimento/fisiologia , Aptidão Física/fisiologia , Adolescente , Índice de Massa Corporal , Teste de Esforço , Feminino , Humanos , Traumatismos da Perna , Masculino , Risco , Estados Unidos , Exercício de Aquecimento , Adulto Jovem
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