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1.
Bipolar Disord ; 24(2): 171-184, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34218509

RESUMO

OBJECTIVE: To investigate the preliminary efficacy of a high n-3 plus low n-6 (H3-L6) dietary intervention in improving mood stability in Bipolar Disorder (BD) when compared to dietary intervention with usual U.S. levels of n-6 and n-3 polyunsaturated fatty acid (PUFA) intakes (control diet, CD). METHODS: This 2-arm, parallel-group, randomized, modified double-blind, controlled 48-week study of 12-week intensive diet intervention in subjects with BD was conducted at a single suburban-rural site in the mid-Atlantic region. Participants with DSM-IV TR BD I or II with hypomanic or depressive symptoms were randomized, stratified on gender (N = 82). The intervention included the provision of group-specific study foods and dietary counseling. Variability of mood symptoms was measured by a twice-daily, 12-week ecological momentary analysis (EMA) paradigm, and group differences were analyzed using multilevel models. Circulating n-3 and n-6 fatty acids were measured at baseline and after 4, 8, and 12 weeks of diet exposure. RESULTS: All 82 randomized participants were included in biochemical analyses. Seventy participants completed at least 2 EMA surveys and were included in primary EMA analyses. Variability in mood, energy, irritability, and pain as measured using EMA was reduced in the H3-L6 group compared to the CD group. No significant differences in mean ratings of mood symptoms, or any other symptom measures, were detected. The dietary intervention effect on target PUFAs significantly differed by the group over time. CONCLUSIONS: A dietary intervention adjunctive to usual care showed preliminary efficacy in improving variability in mood symptoms in participants with BD. TRIAL REGISTRATION: ClinicalTrials.Gov NCT02272010.


Assuntos
Transtorno Bipolar , Ácidos Graxos Ômega-3 , Transtorno Bipolar/psicologia , Transtorno Bipolar/terapia , Dieta , Método Duplo-Cego , Ácidos Graxos Ômega-6 , Humanos
2.
Neuropsychobiology ; 81(1): 51-59, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34320487

RESUMO

INTRODUCTION: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may contribute to the symptom burden in bipolar disorder (BD). Further characterization of cortisol secretion is needed to improve understanding of the connection between mood, sleep, and the HPA axis. Here, we observe diurnal cortisol patterns in individuals with BD and healthy controls (HCs) to determine time points where differences may occur. METHODS: Salivary cortisol was measured at 6 time points (wake, 15, 30, and 45 min after wake, between 2:00 and 4:00 p.m. and 10:00 p.m.) for 3 consecutive days in individuals with symptomatic BD (N = 27) and HC participants (N = 31). A general linear model with correlated errors was utilized to determine if salivary cortisol changed differently throughout the day between the 2 study groups. RESULTS: A significant interaction (F = 2.74, df = 5, and p = 0.02) was observed between the time of day and the study group (BD vs. HC) when modeling salivary cortisol over time, indicating that salivary cortisol levels throughout the day significantly differed between the study groups. Specifically, salivary cortisol in BD was elevated compared to HCs at the 10:00 p.m. time point (p = 0.01). CONCLUSION: Significantly higher levels of cortisol in participants with BD in the night-time suggest that the attenuation of cortisol observed in healthy individuals may be impaired in those with BD. Reregulation of cortisol levels may be a target of further study and treatment intervention for individuals with BD.


Assuntos
Transtorno Bipolar , Hidrocortisona , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Saliva , Sono
3.
Stroke ; 49(2): 384-390, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29301970

RESUMO

BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) initiates an ischemic cascade without resulting in frank infarction and, as such, represents a novel model to study the effects of this ischemic cascade and secondary neurodegeneration in humans. METHODS: Patients with suspected TIA underwent acute brain perfusion imaging, and those with acute ischemia were enrolled into a prospective observational study. We collected baseline and 90-day magnetic resonance imaging, including MP-RAGE (high-resolution T1 sequence) and cognitive assessment with the Montreal Cognitive Assessment. Brain morphometry and within patient statistical analysis were performed to identify changes between baseline and 90-day imaging and clinical assessments. RESULTS: Fifty patients with TIA with acute perfusion lesions were studied. All patients experienced a decrease in global cortical gray matter (P=0.005). Patients with anterior circulation TIA (n=31) also had a significant reduction in the volume of the pons (P<0.001), ipsilesional parietal lobe (P<0.001), occipital lobe (P=0.002), frontal lobe (P<0.001), temporal lobe (P=0.003), and thalamus (P=0.016). Patients with an anterior perfusion lesion on acute imaging also had a significant decrease in Montreal Cognitive Assessment between baseline and day 90 (P=0.027), which may be related to the volume of thalamic atrophy (R2=0.28; P=0.009). CONCLUSIONS: In a prospective observational study, patients with TIA confirmed by acute perfusion imaging experienced a significant reduction in global gray matter and focal structural atrophy related to the area of acute ischemia. The atrophy also resulted in a proportional decreased cognitive performance on the Montreal Cognitive Assessment. Further studies are required to identify the mechanisms of this atrophy.


Assuntos
Disfunção Cognitiva/etiologia , Ataque Isquêmico Transitório/complicações , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia/etiologia , Cognição/fisiologia , Feminino , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos
4.
Bipolar Disord ; 20(1): 27-34, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28833866

RESUMO

OBJECTIVE: Chronic, low-level inflammation is associated with symptomatic bipolar disorder (BD) and with chronic insomnia. Disrupted sleep is a feature of episodes of both mania and depression. We examined the effect of neopterin, a marker of cellular immune activation, and kynurenine (KYN), an inflammatory byproduct of the serotonin pathway, on the association between total sleep time and depression severity in BD. METHOD: Twenty-one symptomatic BD participants and 28 healthy controls (HC) were recruited and followed during usual clinical care. At baseline and after symptomatic recovery, total sleep time was objectively measured with actigraphy for 1 week and blood plasma was collected to measure the serotonin precursor tryptophan (TRP), KYN, the KYN/TRP ratio, and neopterin levels. Statistical analyses were conducted using chi-square, independent t tests and hierarchical linear multiple regression models. RESULTS: Total sleep time was correlated positively with depressive severity and negatively with manic severity. TRP was significantly reduced in BD participants compared to HC. KYN, TRP, and the KYN/TRP ratio were associated with depressive severity when total sleep time and body mass index (BMI) were included in the model. The KYN/TRP ratio trended towards a negative association with mania symptoms, controlling for BMI and total sleep time, in acutely symptomatic BD participants. Neopterin was not associated with sleep or mood severity. After usual clinical care, BD participants showed significantly decreased clinical symptoms but no significant differences in sleep phenotype or biomarkers. CONCLUSION: Inflammation, sleep, and mood are closely intertwined. Future research into the effect of inflammation on sleep in BD may lead to clinical markers of outcome.


Assuntos
Transtorno Bipolar , Depressão , Cinurenina/sangue , Neopterina/sangue , Distúrbios do Início e da Manutenção do Sono , Adulto , Afeto/fisiologia , Biomarcadores/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/complicações , Transtorno Bipolar/psicologia , Depressão/sangue , Depressão/diagnóstico , Feminino , Humanos , Inflamação/sangue , Inflamação/psicologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Serotonina/metabolismo , Sono , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Triptofano/sangue
5.
Stroke ; 48(5): 1293-1298, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28404841

RESUMO

BACKGROUND AND PURPOSE: This study aimed to assess the efficacy of modafinil, a wakefulness-promoting agent in alleviating post-stroke fatigue ≥3 months after stroke. We hypothesized that 200 mg of modafinil daily for 6 weeks would result in reduced symptoms of fatigue compared with placebo. METHODS: This single-center phase 2 trial used a randomized, double-blind, placebo-controlled, crossover design. The key inclusion criterion was a multidimensional fatigue inventory score of ≥60. Patients were randomized to either modafinil or placebo for 6 weeks of therapy, then after a 1 week washout period swapped treatment arms for a second 6 weeks of therapy. The primary outcome was the multidimensional fatigue inventory; secondary outcomes included the Montreal cognitive assessment, the Depression, Anxiety, and Stress Scale (DASS), and the Stroke-Specific Quality of Life (SSQoL) scale. The multidimensional fatigue inventory is a self-administered questionnaire with a range of 0 to 100. Treatment efficacy was assessed using linear regression by estimating within-person, baseline-adjusted differences in mean outcomes after therapy. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000350527). RESULTS: A total of 232 stroke survivors were screened and 36 were randomized. Participants receiving modafinil reported a significant decrease in fatigue (multidimensional fatigue inventory, -7.38; 95% CI, -21.76 to -2.99; P<0.001) and improved quality of life (SSQoL, 11.81; 95% CI, 2.31 to 21.31; P=0.0148) compared with placebo. Montreal cognitive assessment and DASS were not significantly improved with modafinil therapy during the study period (P>0.05). CONCLUSIONS: Stroke survivors with nonresolving fatigue reported reduced fatigue and improved quality of life after taking 200 mg daily treatment with modafinil. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368268. Unique identifier: ACTRN12615000350527.


Assuntos
Compostos Benzidrílicos/farmacologia , Fadiga/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Promotores da Vigília/farmacologia , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Qualidade de Vida , Promotores da Vigília/administração & dosagem
6.
Ann Neurol ; 80(2): 286-93, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27352245

RESUMO

OBJECTIVE: Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regardless of thrombolysis administration. METHODS: We used a prospectively collected cohort of acute ischemic stroke patients being assessed for treatment with IV-alteplase, who had CTP before a treatment decision. Volumetric CTP was retrospectively analyded to identify patients with a small perfusion lesion (<15ml in volume). The primary analysis was excellent 3-month outcome in patients with a small perfusion lesion who were treated with alteplase compared to those who were not treated. RESULTS: Of 1526 patients, 366 had a perfusion lesion <15ml and were clinically eligible for alteplase (212 being treated and 154 not treated). Median acute National Institutes of Health Stroke Scale score was 8 in each group. Of the 366 patients with a small perfusion lesion, 227 (62%) were modified Rankin Scale (mRS) 0 to 1 at day 90. Alteplase-treated patients were less likely to achieve 90-day mRS 0 to 1 (57%) than untreated patients (69%; relative risk [RR] = 0.83; 95% confidence interval [CI], 0.71-0.97; p = 0.022) and did not have different rates of mRS 0 to 2 (72% treated patients vs 77% untreated; RR, 0.93; 95% CI, 0.82-1.95; p = 0.23). INTERPRETATION: This large observational cohort suggests that a portion of ischemic stroke patients clinically eligible for alteplase therapy with a small perfusion lesion have a good natural history and may not benefit from treatment. Ann Neurol 2016;80:286-293.


Assuntos
Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Terapia Trombolítica , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
Radiology ; 279(3): 876-87, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26785041

RESUMO

Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was underestimated when brain coverage was 40 mm or less (P < .0001). Conclusion Correct threshold setting and whole-brain coverage CT perfusion allowed differentiation of the penumbra from the ischemic core in patients with acute ischemic stroke. (©) RSNA, 2016 Online supplemental material is available for this article.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Angiografia por Tomografia Computadorizada , Humanos , Angiografia por Ressonância Magnética , Imagem Multimodal
8.
Genetica ; 144(3): 279-87, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27010806

RESUMO

Apis mellifera syriaca is the native honeybee subspecies of Jordan and much of the Levant region. It expresses behavioral adaptations to a regional climate with very high temperatures, nectar dearth in summer, attacks of the Oriental wasp and is resistant to Varroa mites. The A. m. syriaca control reference sample (CRS) in this study was originally collected and stored since 2001 from "Wadi Ben Hammad", a remote valley in the southern region of Jordan. Morphometric and mitochondrial DNA markers of these honeybees had shown highest similarity to reference A. m. syriaca samples collected in 1952 by Brother Adam of samples collected from the Middle East. Samples 1-5 were collected from the National Center for Agricultural Research and Extension breeding apiary which was established for the conservation of A. m. syriaca. Our objective was to determine the success of an A. m. syriaca honey bee conservation program using genomic information from an array-based comparative genomic hybridization platform to evaluate genetic similarities to a historic reference collection (CRS). Our results had shown insignificant genomic differences between the current population in the conservation program and the CRS indicated that program is successfully conserving A. m. syriaca. Functional genomic variations were identified which are useful for conservation monitoring and may be useful for breeding programs designed to improve locally adapted strains of A. m. syriaca.


Assuntos
Abelhas/genética , Evolução Biológica , Animais , Cromossomos de Insetos , Hibridização Genômica Comparativa , Amplificação de Genes , Deleção de Genes , Genes de Insetos , Genoma de Inseto
9.
Brain ; 138(Pt 7): 1919-31, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25808369

RESUMO

The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.


Assuntos
Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos
10.
Neuroradiology ; 58(4): 409-15, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26738878

RESUMO

INTRODUCTION: We aimed to assess metabolite profiles in peri-infarct tissue with magnetic resonance spectroscopy (MRS) and correlate these with early and late clinical recovery. METHODS: One hundred ten anterior circulation ischemic stroke patients presenting to hospital within 4.5 h of symptom onset and treated with intravenous thrombolysis were studied. Patients underwent computer tomography perfusion (CTP) scanning and subsequently 3-T magnetic resonance imaging (MRI) 24 h after stroke onset, including single-voxel, short-echo-time (30 ms) MRS, and diffusion- and perfusion-weighted imaging (DWI and PWI). MRS voxels were placed in the peri-infarct region in reperfused penumbral tissue. A control voxel was placed in the contralateral homologous area. RESULTS: The concentrations of total creatine (5.39 vs 5.85 mM, p = 0.044) and N-acetylaspartic acid (NAA, 6.34 vs 7.13 mM ± 1.57, p < 0.001) were reduced in peri-infarct tissue compared to the matching contralateral region. Baseline National Institutes of Health Stroke Score was correlated with glutamate concentration in the reperfused penumbra at 24 h (r (2) = 0.167, p = 0.017). Higher total creatine was associated with better neurological outcome at 24 h (r (2) = 0.242, p = 0.004). Lower peri-infarct glutamate was a stronger predictor of worse 3-month clinical outcome (area under the curve (AUC) 0.89, p < 0.001) than DWI volume (AUC = 0.79, p < 0.001). CONCLUSION: Decreased glutamate, creatine, and NAA concentrations are associated with poor neurological outcome at 24 h and greater disability at 3 months. The significant metabolic variation in salvaged tissue may potentially explain some of the variability seen in stroke recovery despite apparently successful reperfusion.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/metabolismo , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Estudos de Casos e Controles , Creatina/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia
11.
Cytogenet Genome Res ; 145(1): 14-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25896599

RESUMO

This study describes a molecular analysis of partial trisomy 14q and partial trisomy 12p in a 5-year-old male child presenting with dysmorphic features, congenital heart disease and global developmental delay. Chromosomal analysis of the patient with GTG bands revealed a 47,XY,+der(14)t(12;14)(p13;q22)mat karyotype; the mother's karyotype was 46,XX,t(12;14)(p13;q22). Further, oligonucleotide array- CGH studies revealed an amplification of 32.3 Mb in the 14q11.1q22.1 region, substantiating partial trisomy 14q and additionally displaying an amplification of ∼1 Mb in the 12p13.3pter region for partial trisomy 12p. This is the first study to demonstrate a novel association of partial trisomies of 14q and 12p due to a 3:1 segregation of a maternal balanced translocation involving chromosomes 12 and 14. Gene ontology studies indicated 5 potential candidate genes in the amplified regions for the observed congenital anomalies.


Assuntos
Anormalidades Múltiplas/genética , Transtornos Dismórficos Corporais/genética , Deficiências do Desenvolvimento/genética , Cardiopatias Congênitas/genética , Trissomia/genética , Pré-Escolar , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 14/genética , Hibridização Genômica Comparativa , Humanos , Masculino
12.
Stroke ; 45(1): 127-33, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24302482

RESUMO

BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is a perfusion magnetic resonance imaging (MRI) technique that does not require contrast administration and thus may be more practical in hyperacute stroke than susceptibility-weighted bolus-tracking perfusion-weighted imaging (PWI). However, a threshold for ASL measurement of the ischemic penumbra needs to be determined. METHODS: A total of 58 patients with acute hemispheric ischemic stroke were imaged within 6 hours of symptom onset with MRI including ASL, diffusion-weighted MRI (DWI), and PWI, after perfusion computed tomography (CTP). Patients had repeat MRI at 24 hours. On repeat imaging, 32 patients did not reperfuse and were used to determine the penumbra threshold. A receiver-operating curve and a volumetric analysis were undertaken to identify the ASL-cerebral blood flow (CBF) threshold for the acute penumbra compared with the 24-hour DWI lesion in patients without reperfusion and with the acute PWI and CTP-Tmax thresholds. RESULTS: An ASL-CBF threshold of 40% showed the highest area under the curve (AUC) for detection of the acute penumbra, defined by 24-hour DWI in nonreperfused patients (AUC 0.76, 95% confidence interval, 0.63-0.85), and was also accurate compared with the acute PWI-Tmax+6 seconds penumbral threshold (AUC 0.79, 95% confidence interval, 73-84) and acute CTP-Tmax 5.5 seconds penumbral threshold (AUC 0.77, 95% confidence interval, 72-84). Using a perfusion-to-diffusion mismatch ratio of 1.8:1, an ASL-CBF 40% mismatch compared with PWI-Tmax+ 6 seconds-DWI and CTP mismatch showed good sensitivity (0.81) and specificity (0.71). CONCLUSIONS: ASL-DWI mismatch shows potential to identify salvageable tissue in hyperacute stroke.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Marcadores de Spin , Acidente Vascular Cerebral/diagnóstico , Área Sob a Curva , Intervalos de Confiança , Humanos , Processamento de Imagem Assistida por Computador , Estudos Prospectivos , Curva ROC , Terapia Trombolítica , Tomografia Computadorizada por Raios X
13.
Addict Sci Clin Pract ; 19(1): 56, 2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39061093

RESUMO

BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.


Assuntos
Fissura , Sinais (Psicologia) , Avaliação Momentânea Ecológica , Receptor do Peptídeo Semelhante ao Glucagon 1 , Liraglutida , Transtornos Relacionados ao Uso de Opioides , Humanos , Fissura/efeitos dos fármacos , Método Duplo-Cego , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Liraglutida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Feminino , Masculino , Adulto , Tratamento Domiciliar/métodos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Stroke ; 44(8): 2327-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23696547

RESUMO

BACKGROUND AND PURPOSE: There is a temporal relationship between cannabis use and stroke in case series and population-based studies. METHODS: Consecutive stroke patients, aged 18 to 55 years, who had urine screens for cannabis were compared with a cohort of control patients admitted to hospital without cardiovascular or neurological diagnoses. RESULTS: One hundred sixty of 218 (73%) ischemic stroke/transient ischemic attack patients had urine drug screens (100 men; mean [SD] age, 44.8 [8.7] years). Twenty-five (15.6%) patients had positive cannabis drug screens. These patients were more likely to be men (84% versus 59%; χ2: P=0.016) and tobacco smokers (88% versus 28%; χ2: P<0.001). Control urine samples were obtained from 160 patients matched for age, sex, and ethnicity. Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex, and ethnicity, cannabis use was associated with increased risk of ischemic stroke/transient ischemic attack (odds ratio, 2.30; 95% confidence interval, 1.08-5.08). However after adjusting for tobacco use, an association independent of tobacco could not be confirmed (odds ratio, 1.59; 95% confidence interval, 0.71-3.70). CONCLUSIONS: This study provides evidence of an association between a cannabis lifestyle that includes tobacco and ischemic stroke. Further research is required to clarify whether there is an association between cannabis and stroke independent of tobacco. CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier: ACTRN12610000198022.


Assuntos
Isquemia Encefálica/epidemiologia , Cannabis/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Isquemia Encefálica/urina , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Feminino , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/urina , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Acidente Vascular Cerebral/urina , Transtornos Relacionados ao Uso de Substâncias/urina , Nicotiana/efeitos adversos , Adulto Jovem
15.
Front Genet ; 13: 786825, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35646087

RESUMO

The wonder fruit pomegranate (Punica granatum, family Lythraceae) is one of India's economically important fruit crops that can grow in different agro-climatic conditions ranging from tropical to temperate regions. This study reports high-quality de novo draft hybrid genome assembly of diploid Punica cultivar "Bhagwa" and identifies its genomic features. This cultivar is most common among the farmers due to its high sustainability, glossy red color, soft seed, and nutraceutical properties with high market value. The draft genome assembly is about 361.76 Mb (N50 = 40 Mb), ∼9.0 Mb more than the genome size estimated by flow cytometry. The genome is 90.9% complete, and only 26.68% of the genome is occupied by transposable elements and has a relative abundance of 369.93 SSRs/Mb of the genome. A total of 30,803 proteins and their putative functions were predicted. Comparative whole-genome analysis revealed Eucalyptus grandis as the nearest neighbor. KEGG-KASS annotations indicated an abundance of genes involved in the biosynthesis of flavonoids, phenylpropanoids, and secondary metabolites, which are responsible for various medicinal properties of pomegranate, including anticancer, antihyperglycemic, antioxidant, and anti-inflammatory activities. The genome and gene annotations provide new insights into the pharmacological properties of the secondary metabolites synthesized in pomegranate. They will also serve as a valuable resource in mining biosynthetic pathways for key metabolites, novel genes, and variations associated with disease resistance, which can facilitate the breeding of new varieties with high yield and superior quality.

16.
J Clin Sleep Med ; 16(12): 2009-2019, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-32780015

RESUMO

STUDY OBJECTIVES: The insomnia with objective short sleep duration phenotype is associated with increased risk for adverse health outcomes, physiological hyperarousal, and a blunted response to cognitive behavioral therapy for insomnia (CBT-I). Whether insomnia with objective short sleep duration responds better to pharmacological treatment compared to CBT-I has not been examined. METHODS: Participants included 15 patients with chronic insomnia (86.7% female), aged 45.3 ± 8.1 years. Eight patients were randomized to CBT-I and 7 to trazodone. Patients were examined with 2 weeks of actigraphy, salivary cortisol, and the insomnia severity index at 3 time points (pretreatment, 3-month posttreatment, and 6-month follow-up). Mixed between-within-subjects analysis of variance and univariate analysis of covariance were conducted to assess the impact of trazodone and CBT-I on patients' total sleep time, salivary cortisol, and insomnia severity index scores across the 3 time points. RESULTS: Trazodone, but not CBT-I, significantly lengthened total sleep time (when measured with actigraphy) both at posttreatment (51.01 minutes vs -11.73 minutes; P = .051; Cohen's d = 1.383) and at follow-up (50.35 minutes vs -7.56 minutes; P = .012; Cohen's d = 1.725), respectively. In addition, trazodone, but not CBT-I, showed a clinically meaningful decrease in salivary cortisol from pretreatment to posttreatment (-36.07% vs -11.70%; Cohen's d = 0.793) and from pretreatment to follow-up (-21.37% vs -5.79%; Cohen's d = 0.284), respectively. Finally, there were no differences on insomnia severity index scores between the trazodone and the CBT-I groups. CONCLUSIONS: The current preliminary, open-label, randomized trial suggests that trazodone, but not CBT-I, significantly improves objective sleep duration and reduces hypothalamic-pituitary-adrenal axis activation, suggesting a differential treatment response in the insomnia with objective short sleep duration phenotype. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Study of Trazodone & Cognitive Behavioral Therapy to Treat Insomnia; URL: https://clinicaltrials.gov/ct2/show/NCT01348542; Identifier: NCT01348542.


Assuntos
Terapia Cognitivo-Comportamental , Distúrbios do Início e da Manutenção do Sono , Trazodona , Adulto , Feminino , Humanos , Sistema Hipotálamo-Hipofisário , Masculino , Pessoa de Meia-Idade , Fenótipo , Sistema Hipófise-Suprarrenal , Sono , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Trazodona/uso terapêutico , Resultado do Tratamento
17.
BMC Res Notes ; 12(1): 791, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801608

RESUMO

OBJECTIVE: Our aim was to study within-person variability in mood, cognition, energy, and impulsivity measured in an Ecological Momentary Assessment paradigm in bipolar disorder by using modern statistical techniques. Exploratory analyses tested the relationship between bipolar disorder symptoms and hours of sleep, and levels of pain, social and task-based stress. We report an analysis of data from a two-arm, parallel group study (bipolar disorder group N = 10 and healthy control group N = 10, with 70% completion rate of 14-day surveys). Surveys of bipolar disorder symptoms, social stressors and sleep hours were completed on a smartphone at unexpected times in an Ecological Momentary Assessment paradigm twice a day. Multi-level models adjusted for potential subject heterogeneity were adopted to test the difference between the bipolar disorder and health control groups. RESULTS: Within-person variability of mood, energy, speed of thoughts, impulsivity, pain and perception of skill of tasks was significantly higher in the bipolar disorder group compared to health controls. Elevated bipolar disorder symptom domains in the evening were associated with reduced sleep time that night. Stressors were associated with worsening of bipolar disorder symptoms. Detection of symptoms when an individual is experiencing difficulty allows personalized, focused interventions.


Assuntos
Afeto , Transtorno Bipolar/psicologia , Avaliação Momentânea Ecológica , Sono , Estresse Psicológico , Transtorno Bipolar/diagnóstico , Humanos , Dor/psicologia , Cooperação do Paciente , Autorrelato , Smartphone
19.
J Affect Disord ; 229: 247-253, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29329056

RESUMO

BACKGROUND: Bipolar disorder (BD) is associated with sleep misperception. The objective of this study was to investigate the correlation between subjective and objective measures of sleep in persons with symptomatic bipolar disorder (BDS) compared to healthy controls (HC). METHODS: We studied 24 BDS and 30 HC subjects similar in age, race and sex. Subjective sleep was measured with Pittsburgh Sleep Quality Index (PSQI) and objective sleep with 7-days of actigraphy. Absolute discrepancy variables were calculated by subtracting objective sleep latency (SL) and total sleep time (TST) on actigraphy from their respective subjective estimates from PSQI. Mood symptoms were measured with Young Mania Rating Scale and Hamilton Depression Rating Scale. RESULTS: In the BDS group, subjective TST did not significantly correlate with objective TST, while it correlated in the HC group. The BDS group had significantly higher absolute discrepancy between subjective and objective SL and TST compared to the HC group. Multivariable regression analysis showed that severity of depression was associated with greater absolute discrepancy between subjective and objective TST within the BDS group. LIMITATIONS: Subjects are from a tertiary care center and were on medications for treatment of BD symptoms. CONCLUSION: There is low correlation between subjective and objective TST in BDS subjects and more severe depressive symptoms are associated with greater absolute discrepancy in TST. Objective rather than subjective measures of sleep, such as actigraphy, may be needed to evaluate sleep in BD subjects. Cognitive-behavioral interventions to address sleep misperception and associated depressed mood may be indicated in BD.


Assuntos
Transtorno Bipolar/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Actigrafia , Adulto , Afeto , Estudos de Casos e Controles , Transtorno Depressivo/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/complicações
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