Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 21
Filter
1.
J Forensic Nurs ; 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38488399

ABSTRACT

BACKGROUND: While persons who are incarcerated have high rates of previous trauma, further traumatization can result from the experience of incarceration. The inability to effectively process trauma can lead to maladaptive behavior, a serious concern for correctional administrators. Acquiring the skills to regulate emotions and mitigate feelings of impulsivity help persons who are incarcerated take responsibility for their actions to make better decisions, simultaneously encouraging prosocial behavior, decreasing institutional misconduct, and reducing behaviors that place one at risk for repeated involvement in the criminal justice system. PURPOSE: Trauma-sensitive yoga (TSY) is one correctional intervention that can effectively address misconduct issues. Yet, the specific impact of TSY on populations who are incarcerated has not been empirically investigated. METHODS: A mixed-methods study, utilizing pretest and posttest interviewing, was conducted with male residents in a New York jail who completed a 4-week TSY program. RESULTS: Data indicated that those who participated in TSY experienced statistically significant improvements in self-esteem, self-control, resilience, institutional conduct, self-efficacy, and emotion regulation. Qualitative data also indicated high levels of connectivity with other TSY class participants. IMPLICATIONS: This research implies that cost-effective interventions like TSY have the ability to produce beneficial outcomes within a short time, which is integral to furthering rehabilitative efforts within the transient nature of the jail setting.

2.
Issues Ment Health Nurs ; 45(2): 152-163, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38266232

ABSTRACT

Stress, anxiety and depression, often linked to internalizing/externalizing behaviors, are remarkedly high in a jail-based setting when one's future is uncertain. While research demonstrates that carceral yoga programs can provide physiological/psychological benefits, persons who are incarcerated, who have high rates of trauma-related experiences and mental illness, might benefit more from a trauma sensitive approach. Empirical studies examining the specific impact of trauma sensitive yoga (TSY) on populations who are incarcerated appear unavailable, necessitating this exploratory investigation with male residents in a TSY intervention at a New York jail. Through pre and post-test interviewing and a mixed methods data analysis, data indicated that those who participated in TSY experienced statistically significant increases in overall health, in addition to statistically significant reductions in stress, anxiety, depression and institutional misconduct. Qualitative analyses suggested that male participants experienced transcendence of the jail environment, easing the monotony of the correctional setting. TSY also provided them with new opportunities, the ability to regulate emotions/behaviors and initiate personal growth/changes within. Hence, this research implies that TSY, a benign intervention, easily implemented in a correctional setting, has the ability to beget benefits for persons who are incarcerated within a short period of time. This is vital to providing rehabilitative options within the transient nature of the jail setting.


Subject(s)
Yoga , Humans , Male , Yoga/psychology , Jails , Depression/therapy , Anxiety/therapy , Coping Skills
3.
J Neurointerv Surg ; 14(3): 268-273, 2022 Mar.
Article in English | MEDLINE | ID: mdl-33758066

ABSTRACT

BACKGROUND: It is not clear whether the COVID-19 pandemic and subsequent Society of Neurointerventional Surgery (SNIS) recommendations affected hospital stroke metrics. METHODS: This retrospective cohort study compared stroke patients admitted to a comprehensive stroke center during the COVID-19 pandemic April 1 2020 to June 30 2020 (COVID-19) to patients admitted April 1 2019 to June 30 2019. We examined stroke admission volume and acute stroke treatment use. RESULTS: There were 637 stroke admissions, 52% in 2019 and 48% during COVID-19, with similar median admissions per day (4 vs 3, P=0.21). The proportion of admissions by stroke type was comparable (ischemic, P=0.69; hemorrhagic, P=0.39; transient ischemic stroke, P=0.10). Acute stroke treatment was similar in 2019 to COVID-19: tPA prior to arrival (18% vs, 18%, P=0.89), tPA treatment on arrival (6% vs 7%, P=0.85), and endovascular therapy (endovascular therapy (ET), 22% vs 25%, P=0.54). The door to needle time was also similar, P=0.12, however, the median time from arrival to groin puncture was significantly longer during COVID-19 (38 vs 43 min, P=0.002). A significantly higher proportion of patients receiving ET were intubated during COVID-19 due to SNIS guideline implementation (45% vs 96%, P<0.0001). There were no differences by study period in discharge mRS, P=0.84 or TICI score, P=0.26. CONCLUSIONS: The COVID-19 pandemic did not significantly affect stroke admission volume or acute stroke treatment utilization. Outcomes were not affected by implementing SNIS guidelines. Although there was a statistical increase in time to groin puncture for ET, it was not clinically meaningful. These results suggest hospitals managing patients efficiently can implement practices in response to COVID-19 without impacting outcomes.


Subject(s)
COVID-19 , Stroke , Benchmarking , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Stroke/drug therapy , Stroke/therapy , Thrombectomy , Thrombolytic Therapy/methods , Time-to-Treatment , Treatment Outcome
5.
Neurosurgery ; 86(2): E156-E163, 2020 02 01.
Article in English | MEDLINE | ID: mdl-31758197

ABSTRACT

BACKGROUND: Because of the overwhelming benefit of thrombectomy for highly selected trial patients with large vessel occlusion (LVO), some trial-ineligible patients are being treated in practice. OBJECTIVE: To determine the safety and efficacy of thrombectomy in DAWN/DEFUSE-3-ineligible patients. METHODS: Using a multicenter prospective observational study of consecutive patients with anterior circulation LVO who underwent late thrombectomy, we compared symptomatic intracerebral hemorrhage (sICH) and good outcome (90-d mRS 0-2) among DAWN/DEFUSE-3-ineligible patients to trial-eligible patients and to untreated DAWN/DEFUSE-3 controls. RESULTS: Ninety-eight patients had perfusion imaging and underwent thrombectomy >6 h; 46 (47%) were trial ineligible (41% M2 occlusions, 39% mild deficits, 28% ASPECTS <6). In multivariable regression, the odds of a good outcome (aOR 0.76, 95% CI 0.49-1.19) and sICH (aOR 3.33, 95% CI 0.42-26.12) were not different among trial-ineligible vs eligible patients. Patients with mild deficits were more likely to achieve a good outcome (aOR 3.62, 95% CI 1.48-8.86) and less sICH (0% vs 10%, P = .16), whereas patients with ASPECTS <6 had poorer outcomes (aOR 0.14, 95% CI 0.05-0.44) and more sICH (aOR 24, 95% CI 5.7-103). Compared to untreated DAWN/DEFUSE-3 controls, trial-ineligible patients had more sICH (13%BEST vs 3%DAWN [P = .02] vs 4%DEFUSE [P = .05]), but were more likely to achieve a good outcome at 90 d (36%BEST vs 13%DAWN [P < .01] vs 17%DEFUSE [P = .01]). CONCLUSION: Thrombectomy is used in practice for some patients ineligible for the DAWN/DEFUSE-3 trials with potentially favorable outcomes. Additional trials are needed to confirm the safety and efficacy of thrombectomy in broader populations, such as large core infarction and M2 occlusions.


Subject(s)
Brain Ischemia/diagnostic imaging , Brain Ischemia/surgery , Stroke/diagnostic imaging , Stroke/surgery , Thrombectomy/methods , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Thrombectomy/trends , Treatment Outcome
6.
J Neuroimaging ; 30(2): 219-226, 2020 03.
Article in English | MEDLINE | ID: mdl-31762108

ABSTRACT

BACKGROUND AND PURPOSE: The 2018 AHA guidelines recommend perfusion imaging to select patients with acute large vessel occlusion (LVO) for thrombectomy in the extended window. However, the relationship between noncontrast CT and CT perfusion imaging has not been sufficiently characterized >6 hours after last known normal (LKN). METHODS: From a multicenter prospective cohort of consecutive adults who underwent thrombectomy for anterior LVO 0-24 hours after LKN, we correlated baseline core volume (rCBF < 30%) and the Alberta Stroke Program Early CT Scale (ASPECTS) score. We compared perfusion findings between patients with an unfavorable ASPECTS (<6) against those with a favorable ASPECTS (≥6), and assessed findings over time. RESULTS: Of 485 enrolled patients, 177 met inclusion criteria (median age: 69 years, interquartile range [IQR: 57-81], 49% female, median ASPECTS 8 [IQR: 6-9], median core 10 cc [IQR: 0-30]). ASPECTS and core volume moderately correlated (r = -.37). A 0 cc core was observed in 54 (31%) patients, 70% of whom had ASPECTS <10. Of the 28 patients with ASPECTS <6, 3 (11%) had a 0 cc core. After adjustment for age and stroke severity, there was a lower ASPECTS for every 1 hour delay from LKN (cOR: 0.95, 95% confidence of interval [CI]: 0.91-1.00, P = .04). There was no difference in core (P = .51) or penumbra volumes (P = .87) across patients over time. CONCLUSIONS: In this multicenter prospective cohort of patients who underwent thrombectomy, one-third of patients had normal CTP core volumes despite nearly three quarters of patients showing ischemic changes on CT. This finding emphasizes the need to carefully assess both noncontrast and perfusion imaging when considering thrombectomy eligibility.


Subject(s)
Brain Ischemia/diagnostic imaging , Perfusion Imaging/methods , Stroke/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Aged, 80 and over , Alberta , Blood Pressure/physiology , Brain Ischemia/therapy , Endovascular Procedures , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Stroke/physiopathology , Stroke/therapy , Thrombectomy/methods
7.
Stroke ; 50(12): 3449-3455, 2019 12.
Article in English | MEDLINE | ID: mdl-31587660

ABSTRACT

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.


Subject(s)
Blood Pressure/physiology , Endovascular Procedures/methods , Stroke/physiopathology , Stroke/surgery , Aged , Aged, 80 and over , Brain Ischemia/complications , Brain Ischemia/physiopathology , Brain Ischemia/surgery , Cohort Studies , Female , Humans , Male , Middle Aged , Stroke/etiology , Treatment Outcome
8.
J Vasc Interv Neurol ; 10(3): 30-33, 2019 May.
Article in English | MEDLINE | ID: mdl-31308868

ABSTRACT

INTRODUCTION: The limited research on the management of aneurysmal subarachnoid hemorrhages (aSAHs) has not assessed the efficacy of neurology-led care. Our objective was to describe aSAH patients' outcomes after transitioning from a neurosurgery-led intensive care unit (ICU) to a neurology-led multidisciplinary care neurocritical care unit (NCCU). The study hypothesis was that the neurology-led multidisciplinary care would improve patient outcomes. METHODS: This was a retrospective cohort study. We included patients (≥ 18) with aSAHs from 1/16 to 8/16 (pregroup) and from 3/17 to 11/17 (postgroup). The pregroup care was led by a neurosurgeon. The postgroup care included a neurologist, a pulmonary intensivist, a neurocritical care clinical nurse specialist, a neurosurgeon, and euvolemia protocol. The primary outcome was trips to interventional radiology (IR) for vasospasm treatment. Univariate analyses and multivariable ordinal logistic regression were used. RESULTS: There were 99 patients included: 50 in the pregroup and 49 in the postgroup. On average, postgroup patients were 7 years older than the pregroup (p = 0.05); no other demographic or clinical characteristics significantly differed. The 62% higher number of trips to IR for vasospasm treatment, when compared to the pregroup, p < 0.001. CONCLUSIONS: In aSAH patients, the neurology-led multidisciplinary care in the NCCU decreased the odds of repeated procedures for vasospasm treatment. Neurology-led multidisciplinary care could be more cost-effective than the neurosurgical-led care.

9.
J Stroke Cerebrovasc Dis ; 28(9): 2407-2413, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31303438

ABSTRACT

BACKGROUND: To determine the clinical outcomes of perimesencephalic subarachnoid hemorrhages based on the computed tomography (CT) bleeding patterns. METHODS: This retrospective cohort study included: (1) patients (≥18 years) admitted to a comprehensive stroke center (January 2015-May 2018), (2) with angiography-negative, nontraumatic subarachnoid hemorrhage in a perimesencephalic or diffuse bleeding pattern, and (3) had CT imaging performed in ≤ 72 hours of symptom onset. Patients were stratified by location of bleeding on CT: Peri-1: focal prepontine hemorrhage; Peri-2: prepontine with suprasellar cistern +/- intraventricular extension; and diffuse. RESULTS: Of the 39 patients included, 13 were Peri-1, 11 were Peri-2, and 15 were diffuse. The majority were male (n = 26), with a mean (standard deviation) age of 55.3 (11.3) years, who often presented with headache (n = 37) and nausea (n = 28). Overall, patients in Peri-1 were significantly less likely to have hydrocephalus compared to Peri-2 and dSAH (P= .003), and 4 patients required an external ventricular drain. Five patients developed symptomatic vasospasm. Patients in Peri-1, compared to Peri-2 and diffuse, had a significantly shorter median neuro critical care unit length of stay (LOS) and hospital LOS. Most patients (n = 35) had a discharge modified Rankin Score between 0 and 2 with no significant differences found between groups. CONCLUSION: These data suggest that patients with the best clinical course were those in Peri-1, followed by Peri-2, and then diffuse. Because these patients often present with similar clinical signs, stratifying by hemorrhage pattern may help clinicians predict which patients with perimesencephalic subarachnoid hemorrhage develop complications.


Subject(s)
Subarachnoid Hemorrhage/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Disability Evaluation , Female , Health Status , Humans , Length of Stay , Male , Middle Aged , Predictive Value of Tests , Prognosis , Recovery of Function , Retrospective Studies , Risk Factors , Subarachnoid Hemorrhage/classification , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/therapy , Time Factors
10.
J Neurointerv Surg ; 10(9): 823-827, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29352059

ABSTRACT

BACKGROUND AND PURPOSE: Blood pressure variability has been found to contribute to worse outcomes after intravenous tissue plasminogen activator, but the association has not been established after intra-arterial therapies. METHODS: We retrospectively reviewed patients with an ischemic stroke treated with intra-arterial therapies from 2005 to 2015. Blood pressure variability was measured as standard deviation (SD), coefficient of variation (CV), and successive variation (SV). Ordinal logistic regression models were fitted to the outcome of the modified Rankin Scale (mRS) with univariable predictors of systolic blood pressure variability. Multivariable ordinal logistic regression models were fitted to the outcome of mRS with covariates that showed independent predictive ability (P<0.1). RESULTS: There were 182 patients of mean age 63.2 years and 51.7% were female. The median admission National Institutes of Health Stroke Scalescore was 16 and 47.3% were treated with intravenous tissue plasminogen activator. In a univariable ordinal logistic regression analysis, systolic SD, CV, and SV were all significantly associated with a 1-point increase in the follow-up mRS (OR 2.30-4.38, all P<0.002). After adjusting for potential confounders, systolic SV was the best predictor of a 1-point increase in mRS at follow-up (OR 2.63-3.23, all P<0.007). CONCLUSIONS: Increased blood pressure variability as measured by the SD, CV, and SV consistently predict worse neurologic outcomes as measured by follow-up mRS in patients with ischemic stroke treated with intra-arterial therapies. The SV is the strongest and most consistent predictor of worse outcomes at all time intervals.


Subject(s)
Blood Pressure/physiology , Hypertension/etiology , Stroke/therapy , Thrombectomy/trends , Tissue Plasminogen Activator/administration & dosage , Administration, Intravenous , Aged , Aged, 80 and over , Blood Pressure/drug effects , Female , Follow-Up Studies , Humans , Hypertension/diagnostic imaging , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Retrospective Studies , Stroke/diagnostic imaging , Thrombectomy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
11.
Stroke Vasc Neurol ; 2(1): 1-6, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28959484

ABSTRACT

INTRODUCTION: Increased blood pressure variability (BPV) is detrimental after acute ischaemic stroke, but the interaction between BPV and neuroimaging factors that directly influence stroke outcome has not been explored. METHODS: We retrospectively reviewed inpatients from 2007 to 2014 with acute anterior circulation ischaemic stroke, CT perfusion and angiography at hospital admission, and a modified Rankin Scale (mRS) 30-365 days after stroke onset. BPV indices included SD, coefficient of variation and successive variation of the systolic blood pressure between 0 and 120 hours after admission. Ordinal logistic regression models were fitted to mRS with predictor variables of BPV indices. Models were further stratified by CT perfusion volumetric measurements, proximal vessel occlusion and collateral score. RESULTS: 110 patients met the inclusion criteria. The likelihood of a 1-point rise in the mRS increased with every 10 mm Hg increase in BPV (OR for the 3 BPV indices ranged from 2.27 to 5.54), which was more pronounced in patients with larger ischaemic core volumes (OR 8.37 to 18.0) and larger hypoperfused volumes (OR 6.02 to 15.4). This association also held true for patients with larger mismatch volume, proximal vessel occlusion and good collateral vessels. CONCLUSIONS: These results indicate that increased BPV is associated with worse neurological outcome after stroke, particularly in patients with a large lesion core volume, concurrent viable ischaemic penumbra, proximal vessel occlusion and good collaterals. This subset of patients, who are often not candidates for or fail acute stroke therapies such as intravenous tissue plasminogen activator or endovascular thrombectomy, may benefit from interventions aimed at reducing BPV.


Subject(s)
Blood Pressure , Cerebrovascular Circulation , Collateral Circulation , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/physiopathology , Neuroimaging , Adult , Aged , Blood Pressure Determination , Cerebral Angiography , Computed Tomography Angiography , Disability Evaluation , Female , Humans , Ischemic Stroke/therapy , Male , Middle Aged , Patient Admission , Perfusion Imaging , Predictive Value of Tests , Prognosis , Recovery of Function , Retrospective Studies , Risk Factors , Time Factors
12.
Stroke Res Treat ; 2016: 7670161, 2016.
Article in English | MEDLINE | ID: mdl-27974991

ABSTRACT

Background. Although research suggests that blood pressure variability (BPV) is detrimental in the weeks to months after acute ischemic stroke, it has not been adequately studied in the acute setting. Methods. We reviewed acute ischemic stroke patients from 2007 to 2014 with anterior circulation stroke. Mean blood pressure and three BPV indices (standard deviation, coefficient of variation, and successive variation) for the intervals 0-24, 0-72, and 0-120 hours after admission were correlated with follow-up modified Rankin Scale (mRS) in ordinal logistic regression models. The correlation between BPV and mRS was further analyzed by terciles of clinically informative stratifications. Results. Two hundred and fifteen patients met inclusion criteria. At all time intervals, increased systolic BPV was associated with higher mRS, but the relationship was not significant for diastolic BPV or mean blood pressure. This association was strongest in patients with proximal stroke parent artery vessel occlusion and lower mean blood pressure. Conclusion. Increased early systolic BPV is associated with worse neurologic outcome after ischemic stroke. This association is strongest in patients with lower mean blood pressure and proximal vessel occlusion, often despite endovascular or thrombolytic therapy. This hypothesis-generating dataset suggests potential benefit for interventions aimed at reducing BPV in this patient population.

15.
J Knee Surg ; 29(3): 224-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26838971

ABSTRACT

The purpose of this study was to use a large hospital database to assess: (1) length of hospital stay (LOS) and (2) discharge status among patients undergoing total knee arthroplasty (TKA) with or without the use of a liposomal bupivacaine suspension injection. We utilized an all-payer hospital administrative database from July 1, 2013 to June 30, 2014. We then selected patients age 18 years or older who had an inpatient stay for TKA in the data window based on International Classification of Diseases, Ninth Revision (ICD-9) procedure codes (ICD-9-CM = 81.54), which resulted in 103,152 TKA patients. Patients who had nerve blocks were excluded, which resulted in 94,828 TKA patients. The TKA cohort who received a liposomal bupivacaine suspension consisted of 14,668 patients (9,211 females; 5,457 males) who had a mean age of 66 years, while the TKAs without injections or block consisted of 80,160 patients (49,699 females; 30,461 males) who had a mean age of 66 years. Analyses of LOS were performed using a linear model, controlling for age, sex, race, region, Charlson index, and operating time. Discharge status to home versus rehabilitation or short-term nursing facility was evaluated using logistic regression analysis controlling for the above covariates. The adjusted mean LOS for the injection cohort was significantly shorter at 2.58 days compared with 2.98 days in the no injection cohort. The unadjusted distribution of patients being discharged to home compared with short-term nursing facility or rehabilitation was higher in the injection cohort compared with the cohort who did not receive injections (73.2 vs. 66.6%). Logistic regression analysis demonstrated that there was a higher likelihood of being discharged to home with liposomal bupivacaine. Patients who underwent TKA with liposomal bupivacaine had a significantly shorter LOS and a higher likelihood of being discharged to home. These results suggest that liposomal bupivacaine may represent a promising addition to current pain management regimens. Furthermore, it may limit pain following surgery, which may allow patients to ambulate earlier and have improved outcomes.


Subject(s)
Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee , Bupivacaine/administration & dosage , Pain, Postoperative/prevention & control , Aged , Female , Humans , Length of Stay , Liposomes , Male , Middle Aged , Patient Discharge , Retrospective Studies
16.
Clin Neurol Neurosurg ; 126: 103-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25240131

ABSTRACT

Refractory status epilepticus is a disease associated with high morbidity and mortality, which does not always respond to standard treatments, and when they fail, alternative modalities become crucial. Therapeutic hypothermia slows nerve conduction in vitro, and has been shown to abort seizures in animal models. Therapeutic hypothermia has been experimentally used in humans since 1963 for a variety of intracranial pathologies. More recently there have been multiple reports demonstrating the effectiveness of therapeutic hypothermia in treating refractory status epilepticus. We report a case of super-refractory status epilepticus successfully treated with therapeutic hypothermia, complimented by a historical and literature review of this modality. While there is limited evidence, and some risks associated with therapeutic hypothermia, it should be considered as a reasonable and potentially effective treatment option for refractory status epilepticus.


Subject(s)
Drug Resistance/physiology , Hypothermia, Induced/methods , Status Epilepticus/therapy , Adult , Female , Humans
17.
Nat Med ; 13(12): 1476-82, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18059283

ABSTRACT

Exercise has many health benefits, including antidepressant actions in depressed human subjects, but the mechanisms underlying these effects have not been elucidated. We used a custom microarray to identify a previously undescribed profile of exercise-regulated genes in the mouse hippocampus, a brain region implicated in mood and antidepressant response. Pathway analysis of the regulated genes shows that exercise upregulates a neurotrophic factor signaling cascade that has been implicated in the actions of antidepressants. One of the most highly regulated target genes of exercise and of the growth factor pathway is the gene encoding the VGF nerve growth factor, a peptide precursor previously shown to influence synaptic plasticity and metabolism. We show that administration of a synthetic VGF-derived peptide produces a robust antidepressant response in mice and, conversely, that mutation of VGF in mice produces the opposite effects. The results suggest a new role for VGF and identify VGF signaling as a potential therapeutic target for antidepressant drug development.


Subject(s)
Antidepressive Agents/pharmacology , Depressive Disorder/metabolism , Exercise , Gene Expression Profiling , Hippocampus/metabolism , Neuropeptides/metabolism , Physical Conditioning, Animal , Animals , Drug Design , Humans , Mice , Mice, Inbred C57BL , Nerve Growth Factors , Oligonucleotide Array Sequence Analysis , PC12 Cells , Rats
18.
Methods ; 37(3): 238-46, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16308153

ABSTRACT

Microarray chips produced by commercial vendors and academic laboratories are mostly generic in nature to facilitate wide applicability. With the sequencing of the human, mouse, and rat genomes, the thrust is to expand clone and oligonucleotide sets and increase the number of genes represented on a particular array. This is appropriate for discovery based investigations where microarray technology has been successfully utilized. However, array technology can also be employed to perform hypothesis based studies if optimized chips can be produced with relevant content. Existing array technology available at core facilities can be effectively utilized to produce a custom microarrays with genes that are most relevant to the research interests of individual investigators or research groups for use as a standard molecular tool. The power of this technology can be harnessed to further our understanding of specific biological problems without involvement in extensive data mining and analysis. The custom microarray approach is presented with procedural details for design and production in the context of neurobiological investigations.


Subject(s)
Neurosciences/methods , Oligonucleotide Array Sequence Analysis/methods , Animals , Buffers , DNA Primers , DNA, Complementary/chemical synthesis , Electrophoresis, Agar Gel/methods , Gene Expression Profiling/methods , Humans , Oligonucleotide Array Sequence Analysis/instrumentation , Polymerase Chain Reaction/methods , Quality Control , RNA/isolation & purification
19.
Brain Res Mol Brain Res ; 129(1-2): 185-8, 2004 Oct 22.
Article in English | MEDLINE | ID: mdl-15469895

ABSTRACT

Electroconvulsive seizure (ECS) is a well-established non-chemical antidepressant that is effective in the treatment of severe depression and also in subjects resistant to chemical antidepressant treatment. Although the molecular mechanism governing the antidepressant efficacy of ECS is unknown, recent work suggests that an amplification of growth/neurotrophic signaling might play a role in mediating the therapeutic effects. In this context, we examined the regulation of growth factor receptor bound 2 (Grb2), an important adaptor molecule in several growth factor signaling cascades. In situ hybridization analysis revealed a more than 2-fold induction of Grb2 mRNA in the hippocampal dentate gyrus as well as superficial and deep layers of the cortex with both acute and chronic ECS. Grb2 also exhibited a time-dependent induction 4 and 8 h after acute ECS, returning to basal levels at 24 h. These results provide further evidence of increased growth factor signaling in response to ECS.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Electroshock , Seizures , Adaptor Proteins, Signal Transducing/genetics , Animals , Brain/anatomy & histology , Brain/metabolism , GRB2 Adaptor Protein , In Situ Hybridization , Male , Rats , Rats, Sprague-Dawley , Signal Transduction/physiology
20.
J Bacteriol ; 186(13): 4285-94, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15205431

ABSTRACT

A long-term goal is to characterize the full range of genetic diversity within Streptococcus pyogenes as it exists in the world today. Since the emm locus is subject to strong diversifying selection, emm type was used as a guide for identifying a genetically diverse set of strains. This report contains a description of multilocus sequence typing based on seven housekeeping loci for 495 isolates representing 158 emm types, yielding 238 unique combinations of sequence type and emm type. A genotypic marker for tissue site preference (emm pattern) revealed that only 17% of the emm types displayed the marker representing strong preference for infection at the throat and that 39% of emm types had the marker for skin tropism, whereas 41% of emm types harbored the marker for no obvious tissue site preference. As a group, the emm types bearing the emm pattern marker indicative of no obvious tissue site preference were far less likely to have two distinct emm types associated with the same sequence type than either of the two subpopulations having markers for strong tissue tropisms (P < 0.002). In addition, all genetic diversification events clearly ascribed to a recombinational mechanism involved strains of only two of the emm pattern-defined subpopulations, those representing skin specialists and generalists. The findings suggest that the population genetic structure differs for the tissue-defined subpopulations of S. pyogenes. The observed differences may partly reflect differential host immune selection pressures.


Subject(s)
Antigens, Bacterial/classification , Bacterial Outer Membrane Proteins/classification , Carrier Proteins/classification , Streptococcus pyogenes/genetics , Chromosome Mapping , Genetic Variation , Streptococcus pyogenes/classification
SELECTION OF CITATIONS
SEARCH DETAIL
...