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1.
J Gen Intern Med ; 39(8): 1310-1316, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38625482

RESUMO

BACKGROUND: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). OBJECTIVE: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. DESIGN: Survey-based non-randomized cohort study with matched comparators. PARTICIPANTS: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. MAIN MEASURES: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. KEY RESULTS: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. CONCLUSION: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment.


Assuntos
COVID-19 , Depressão , Veteranos , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Depressão/epidemiologia , Depressão/psicologia , Estados Unidos/epidemiologia , Adulto , Idoso , Estudos de Coortes , SARS-CoV-2
2.
J Gen Intern Med ; 39(4): 626-635, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37884839

RESUMO

BACKGROUND: Negative mental health-related effects of SARS-COV-2 infection are increasingly evident. However, the impact on suicide-related outcomes is poorly understood, especially among populations at elevated risk. OBJECTIVE: To determine risk of suicide attempts and other self-directed violence (SDV) after SARS-COV-2 infection in a high-risk population. DESIGN: We employed an observational design supported by comprehensive electronic health records from the Veterans Health Administration (VHA) to examine the association of SARS-COV-2 infection with suicide attempts and other SDV within one year of infection. Veterans with SARS-COV-2 infections were matched 1:5 with non-infected comparators each month. Three periods after index were evaluated: days 1-30, days 31-365, and days 1-365. PARTICIPANTS: VHA patients infected with SARS-COV-2 between March 1, 2020 and March 31, 2021 and matched non-infected Veteran comparators. MAIN MEASURES: Suicide attempt and other SDV events for the COVID-19 and non-infected comparator groups were analyzed using incidence rates per 100,000 person years and hazard ratios from Cox regressions modeling time from matched index date to first event. Subgroups were also examined. KEY RESULTS: 198,938 veterans with SARS-COV-2 (COVID-19 group) and 992,036 comparators were included. Unadjusted one-year incidence per 100,000 for suicide attempt and other SDV was higher among the COVID-19 group: 355 vs 250 and 327 vs 235, respectively. The COVID-19 group had higher risk than comparators for suicide attempts: days 1-30 hazard ratio (HR) = 2.54 (CI:2.05, 3.15), days 31-365 HR = 1.30 (CI:1.19, 1.43) and days 1-365 HR = 1.41 (CI:1.30, 1.54), and for other SDV: days 1-30 HR = 1.94 (CI:1.51, 2.49), days 31-365 HR = 1.32 (CI:1.20, 1.45) and days 1-365 HR = 1.38 (CI:1.26, 1.51). CONCLUSIONS: COVID-19 patients had higher risks of both suicide attempts and other forms of SDV compared to uninfected comparators, which persisted for at least one year after infection. Results support suicide risk screening of those infected with SARS-COV-2 to identify opportunities to prevent self-harm.


Assuntos
COVID-19 , Veteranos , Humanos , SARS-CoV-2 , Tentativa de Suicídio , Registros Eletrônicos de Saúde
3.
Pain Med ; 23(2): 295-304, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34643735

RESUMO

OBJECTIVE: Depression and chronic pain are major problems in American veterans, yet there is limited long-term research examining how they relate to one another in this population. This study examined the relationship between depressive symptoms and pain in U.S. veterans 50 years of age or older. METHODS: This study used data on veterans from the 2002-2016 waves of the Health and Retirement Study (n = 4,302), a large-scale observational study of Americans 50 years of age or older. Measures included a short form of the Center for Epidemiologic Studies Depression scale and two items assessing the presence and degree of pain. Analyses included random-intercept cross-lagged panel models (RI-CLPM). RESULTS: In the RI-CLPM, there were roughly equivalent cross-lagged effects between depressive symptoms and pain. There was also evidence that depressive symptoms and pain have a trait-like component and that these trait-like characteristics are associated. CONCLUSIONS: These findings indicate that depressive symptoms and pain in veterans are stable characteristics in American veterans 50 years of age or older. There appear to be reciprocal effects between the two, whereby deviations in one's typical depressive symptoms predict subsequent deviations in one's pain level and vice versa; however, the size of these effects is very small. These findings suggest that clinicians should treat both depressive symptoms and pain, rather than assume that treatment benefits in one domain will lead to major benefits in another.


Assuntos
Depressão , Veteranos , Depressão/epidemiologia , Humanos , Pessoa de Meia-Idade , Dor/epidemiologia
4.
Toxicol Appl Pharmacol ; 386: 114826, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730783

RESUMO

The widespread use and high abuse liability of tobacco products has received considerable public health attention, in particular for youth, who are vulnerable to nicotine addiction. In this study, adult and adolescent squirrel monkeys were used to evaluate age-related metabolism and pharmacokinetics of nicotine after intravenous administration. A physiologically-based pharmacokinetic (PBPK) model was created to characterize the pharmacokinetic behaviors of nicotine and its metabolites, cotinine, trans-3'-hydroxycotinine (3'-OH cotinine), and trans-3'-hydroxycotinine glucuronide (3'-OH cotinine glucuronide) for both adult and adolescent squirrel monkeys. The PBPK nicotine model was first calibrated for adult squirrel monkeys utilizing in vitro nicotine metabolic data, plasma concentration-time profiles and cumulative urinary excretion data for nicotine and metabolites. Further model refinement was conducted when the calibrated adult model was scaled to the adolescents, because adolescents appeared to clear nicotine and cotinine more rapidly relative to adults. More specifically, the resultant model parameters representing systemic clearance of nicotine and cotinine for adolescent monkeys were approximately two- to three-fold of the adult values on a per body weight basis. The nonhuman primate PBPK model in general captured experimental observations that were used for both model calibration and evaluation, with acceptable performance metrics for precision and bias. The model also identified differences in nicotine pharmacokinetics between adolescent and adult nonhuman primates which might also be present in humans.


Assuntos
Nicotina/farmacocinética , Fatores Etários , Animais , Cotinina/metabolismo , Cotinina/urina , Injeções Intravenosas , Fígado/metabolismo , Masculino , Nicotina/administração & dosagem , Nicotina/sangue , Nicotina/urina , Saimiri
5.
Pain Med ; 21(Suppl 2): S62-S72, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33313728

RESUMO

BACKGROUND: Coordinated efforts between the National Institutes of Health, the Department of Defense, and the Department of Veterans Affairs have built the capacity for large-scale clinical research investigating the effectiveness of nonpharmacologic pain treatments. This is an encouraging development; however, what constitutes best practice for nonpharmacologic management of low back pain (LBP) is largely unknown. DESIGN: The Improving Veteran Access to Integrated Management of Back Pain (AIM-Back) trial is an embedded pragmatic cluster-randomized trial that will examine the effectiveness of two different care pathways for LBP. Sixteen primary care clinics will be randomized 1:1 to receive training in delivery of 1) an integrated sequenced-care pathway or 2) a coordinated pain navigator pathway. Primary outcomes are pain interference and physical function (Patient-Reported Outcomes Measurement Information System Short Form [PROMIS-SF]) collected in the electronic health record at 3 months (n=1,680). A subset of veteran participants (n=848) have consented to complete additional surveys at baseline and at 3, 6, and 12 months for supplementary pain and other measures. SUMMARY: AIM-Back care pathways will be tested for effectiveness, and treatment heterogeneity will be investigated to identify which veterans may respond best to a given pathway. Health care utilization patterns (including opioid use) will also be compared between care pathways. Therefore, the AIM-Back trial will provide important information that can inform the future delivery of nonpharmacologic treatment of LBP.


Assuntos
Dor Lombar , Veteranos , Humanos , Dor Lombar/terapia , Manejo da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e Questionários , Fatores de Tempo
7.
Pain Med ; 18(9): 1658-1667, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28122941

RESUMO

OBJECTIVE: To examine pain symptoms and co-occurring psychiatric and functional indices in male and female Iraq/Afghanistan-era veterans. DESIGN: Self-reported data collection and interviews of Iraq/Afghanistan-era veterans who participated in a multisite study of postdeployment mental health. SETTING: Veterans were enrolled at one of four participating VA sites. SUBJECTS: Two thousand five hundred eighty-seven male and 662 female Iraq/Afghanistan-era veterans. METHODS: Nonparametric Wilcoxon rank tests examined differences in pain scores between male and female veterans. Chi-square tests assessed differences between male and female veterans in the proportion of respondents endorsing moderate to high levels of pain vs no pain. Multilevel regression analyses evaluated the effect of pain on a variety of psychiatric and functional measures. RESULTS: Compared with males, female veterans reported significantly higher mean levels of headache ( P < 0.0001), muscle soreness ( P < 0.008), and total pain ( P < 0.0001), and were more likely to report the highest levels of headache ( P < 0.0001) and muscle soreness ( P < 0.0039). The presence of pain symptoms in Iraq/Afghanistan-era veterans was positively associated with psychiatric comorbidity and negatively associated with psychosocial functioning. There were no observed gender differences in psychiatric and functional indices when levels of pain were equated. CONCLUSIONS: Although female Iraq/Afghanistan-era veterans reported higher levels of pain than male veterans overall, male and female veterans experienced similar levels of psychiatric and functional problems at equivalent levels of reported pain. These findings suggest that pain-associated psychological and functional impacts are comparable and consequential for both male and female veterans.


Assuntos
Dor/epidemiologia , Dor/psicologia , Veteranos/psicologia , Adulto , Campanha Afegã de 2001- , Feminino , Humanos , Guerra do Iraque 2003-2011 , Masculino , Pessoa de Meia-Idade , Autorrelato , Distribuição por Sexo , Inquéritos e Questionários , Veteranos/estatística & dados numéricos
8.
Pain Med ; 17(1): 25-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26176345

RESUMO

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann­Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.


Assuntos
Cefaleia/psicologia , Dor/psicologia , Pregnanolona/uso terapêutico , Autorrelato , Transtornos de Estresse Pós-Traumáticos/psicologia , Adulto , Campanha Afegã de 2001- , Afeganistão , Biomarcadores/análise , Feminino , Humanos , Iraque , Guerra do Iraque 2003-2011 , Masculino , Pessoa de Meia-Idade , Veteranos/psicologia
9.
J Psychiatr Res ; 174: 283-288, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38678685

RESUMO

Exposure to toxins-such as heavy metals and air pollution-can result in poor health and wellbeing. Recent scientific and media attention has highlighted negative health outcomes associated with toxic exposures for U.S. military personnel deployed overseas. Despite established health risks, less empirical work has examined whether deployment-related toxic exposures are associated with declines in mental and physical health after leaving military service, particularly among the most recent cohort of veterans deployed after September 11, 2001. Using data from 659 U.S. veterans in the VISN 6 MIRECC Post-Deployment Mental Health Study, we tested whether self-reported toxic exposures were associated with poorer mental and physical health. At baseline, veterans who reported more toxic exposures also reported more mental health, ß = 0.14, 95% CI [0.04, 0.23], p = 0.004, and physical health symptoms, ß = 0.21, 95% CI [0.11, 0.30], p < 0.001. Over the next ten years, veterans reporting more toxic exposures also had greater increases in mental health symptoms, ß = 0.23, 95% CI [0.15, 0.31], p < 0.001, physical health symptoms, ß = 0.22, 95% CI [0.14, 0.30], p < 0.001, and chronic disease diagnoses, ß = 0.15, 95% CI [0.07, 0.23], p < 0.001. These associations accounted for demographic and military covariates, including combat exposure. Our findings suggest that toxic exposures are associated with worsening mental and physical health after military service, and this recent cohort of veterans will have increased need for mental health and medical care as they age into midlife and older age.


Assuntos
Autorrelato , Veteranos , Humanos , Masculino , Veteranos/estatística & dados numéricos , Feminino , Adulto , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Militares/estatística & dados numéricos , Nível de Saúde , Destacamento Militar/estatística & dados numéricos , Ataques Terroristas de 11 de Setembro , Saúde Mental
10.
Front Psychiatry ; 14: 1221762, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575582

RESUMO

Objective: Posttraumatic stress disorder (PTSD) symptoms and pain interfere with daily functioning and quality of life for many combat Veterans. As individuals age, pain symptoms tend to increase whereas PTSD symptoms tend to decrease. PTSD symptoms exacerbate pain, but the nature of this relationship across the aging process is unclear. The purpose of this study was to determine how PTSD symptoms affect the association between age and pain intensity. Methods: Participants in this cross-sectional study included 450 Veterans (80% male) who served after September 11, 2001. PTSD and pain intensity ratings were assessed by the PTSD Checklist for DSM-5 (PCL-5) and the Brief Pain Inventory (BPI), respectively. Hierarchical multiple linear regression evaluated main and interaction effects between age, PTSD symptoms, and pain intensity. Results: Age (B = 0.04, p < 0.001) and PTSD symptoms (B = 0.05, p < 0.001) were positively associated with pain intensity. Age and PTSD symptoms were inversely correlated (r = -0.16, p < 0.001). PTSD symptoms exacerbated the relationship between age and pain intensity (ΔR2 = 0.01, p = 0.036). Specifically, when greater PTSD symptoms were reported at older ages, pain intensity was significantly higher. Conclusion: Results of these analyses suggests that age is important when considering the effects of PTSD symptoms on pain intensity ratings. Specifically, pain intensity ratings are higher in older Veterans with PTSD symptoms. These findings underscore the importance for clinical providers to evaluate trauma history and PTSD symptoms in older Veterans reporting pain symptoms.

11.
Health Equity ; 7(1): 570-580, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731781

RESUMO

Introduction: Women experience numerous barriers to patient-centered health care (e.g., lack of continuity). Such barriers are amplified for women from marginalized communities. Virtual care may improve equitable access. We are conducting a partner-engaged, qualitative evidence synthesis (QES) of patients' and providers' experiences with virtual health care delivery for women. Methods: We use a best-fit framework approach informed by the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability framework and Public Health Critical Race Praxis. We will supplement published literature with qualitative interviews with women from underrepresented communities and their health care providers. We will engage patients and other contributors through multiple participatory methods. Results: Our search identified 5525 articles published from 2010 to 2022. Sixty were eligible, of which 42 focused on women and 24 on provider experiences. Data abstraction and analysis are ongoing. Discussion: This work offers four key innovations to advance health equity: (1) conceptual foundation rooted in an antiracist action-oriented praxis; (2) worked example of centering QES on marginalized communities; (3) supplementing QES with primary qualitative information with populations historically marginalized in the health care system; and (4) participatory approaches that foster longitudinal partnered engagement. Health Equity Implications: Our approach to exploring virtual health care for women demonstrates an antiracist praxis to inform knowledge generation. In doing so, we aim to generate findings that can guide health care systems in the equitable deployment of comprehensive virtual care for women.

12.
J Neurotrauma ; 40(7-8): 649-664, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36324218

RESUMO

Military service members are at increased risk for mental health issues, and comorbidity with mild traumatic brain injury (mTBI) is common. Largely overlapping symptoms between conditions suggest a shared pathophysiology. The present work investigates the associations among white matter microstructure, psychological functioning, and serum neuroactive steroids that are part of the stress-response system. Diffusion-weighted brain imaging was acquired from 163 participants (with and without military affiliation) and free-water-corrected fractional anisotropy (FAT) was extracted. Associations between serum neurosteroid levels of allopregnanolone (ALLO) and pregnenolone (PREGNE), psychological functioning, and whole-brain white matter microstructure were assessed using regression models. Moderation models tested the effect of mTBI and comorbid post-traumatic stress disorder (PTSD) and mTBI on these associations. ALLO is associated with whole-brain white matter FAT (ß = 0.24, t = 3.05, p = 0.006). This association is significantly modulated by PTSD+mTBI comorbidity (ß = 0.00, t = 2.50, p = 0.027), although an mTBI diagnosis alone did not significantly impact this association (p = 0.088). There was no significant association between PREGNE and FAT (p = 0.380). Importantly, lower FAT is associated with poor psychological functioning (ß = -0.19, t = -2.35, p = 0.020). This study provides novel insight into a potential common pathophysiological mechanism of neurosteroid dysregulation underlying the high risk for mental health issues in military service members. Further, comorbidity of PTSD and mTBI may bring the compensatory effects of the brain's stress response to their limit. Future research is needed to investigate whether neurosteroid regulation may be a promising tool for restoring brain health and improving psychological functioning.


Assuntos
Concussão Encefálica , Militares , Neuroesteroides , Transtornos de Estresse Pós-Traumáticos , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão , Encéfalo , Concussão Encefálica/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/complicações
13.
Workplace Health Saf ; 70(1): 24-30, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35037511

RESUMO

BACKGROUND: U.S. meat and poultry processing workers experienced a disproportionate burden of COVID-19 illness following the declaration of the COVID-19 pandemic. Managing prevention and surveillance activities for COVID-19 prevention required additional work for occupational health nurses. The purpose of this project was to conduct a cost analysis for two staffing options to address the increased workload for occupational health nurses. METHODS: An economic quality improvement design was used for this study. The project was performed at a meat and poultry processing plant with 1,800 employees and six occupational health nurses. Two staffing options were considered. Option 1 was to continue to pay current occupational health nurses overtime, and Option 2 was to hire a COVID-dedicated nurse to manage the increased workload. A cost analysis was conducted for wages per hour plus benefits at three time points: 3 months, 1 year, and 3 years. FINDINGS: Costs for Option 1 (continuing overtime) at 3 months, 1 year, and 3 years were estimated at US$27,370, US$109,517, and US$328,550, respectively. Costs for Option 2 (hiring a COVID-dedicated nurse) at 3 months, 1 year, and 3 years were estimated at US$44,279, US$94,979, and US$230,179, respectively. CONCLUSIONS/APPLICATION TO PRACTICE: Hiring a dedicated COVID nurse would save the processing plant extensive salary costs by Year 3. Reducing overtime had the potential to decrease the COVID-19-related workload and potential experiences of fatigue and burnout in occupational health nurses.


Assuntos
COVID-19 , Enfermeiras e Enfermeiros , Custos e Análise de Custo , Humanos , Pandemias , SARS-CoV-2 , Carga de Trabalho
14.
J Interpers Violence ; 37(11-12): NP10007-NP10035, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33435809

RESUMO

Moral injury is an array of symptoms theorized to develop in response to morally injurious events, defined as events that challenge one's core moral beliefs and expectations about the self, others, and world. Recent measures of moral injury have distinguished self-directed moral injury (e.g., moral injury symptoms that emerge following the perpetration of morally injurious events) from other-directed moral injury, the symptoms of which are believed to stem from one's response to actions that others have committed (e.g., within-rank violence, failures of leadership, and acts of betrayal committed by trusted others or institutions). Using a convenience sample of 154 primarily former military women, the present study examined if other-directed moral injury symptoms (e.g., anger, betrayal, and mistrust) associated with military experience would mediate the association between military sexual harassment and mental health and substance abuse symptoms. Results demonstrated that 85.8% (n = 127) of the of this sample of women veterans reported experiencing sexual harassment during their military service. Using a single mediation model, we further demonstrated that other-directed moral injury mediated the association between sexual harassment experience and mental health symptoms. Given the percentage of women veterans who reported sexual harassment, these results suggest that additional training for military members, and particularly, military leaders, is necessary to begin to reduce sexual harassment. In addition, mental health providers who work with current and former military members should consider how other-directed moral injury may be associated with mental health symptoms among women veterans who have experienced sexual harassment while in the military.


Assuntos
Militares , Assédio Sexual , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Veteranos , Feminino , Humanos , Saúde Mental , Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Veteranos/psicologia
15.
Biochim Biophys Acta ; 1801(8): 951-9, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20488256

RESUMO

The neurosteroid allopregnanolone has pronounced neuroprotective actions, increases myelination, and enhances neurogenesis. Evidence suggests that allopregnanolone dysregulation may play a role in the pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. Our prior data demonstrate that allopregnanolone is reduced in prefrontal cortex in male patients with AD compared to male cognitively intact control subjects, and inversely correlated with neuropathological disease stage (Braak and Braak). We therefore determined if allopregnanolone levels are also reduced in AD patients compared to control subjects in temporal cortex, utilizing a larger set of samples from both male and female patients. In addition, we investigated if neurosteroids are altered in subjects who are APOE4 allele carriers. Allopregnanolone, dehydroepiandrosterone (DHEA), and pregnenolone levels were determined in temporal cortex postmortem samples by gas chromatography/mass spectrometry, preceded by high performance liquid chromatography (40 subjects with AD/41 cognitively intact control subjects). Allopregnanolone levels are reduced in temporal cortex in patients with AD (median 2.68 ng/g, n=40) compared to control subjects (median 5.64 ng/g, n=41), Mann-Whitney p=0.0002, and inversely correlated with Braak and Braak neuropathological disease stage (Spearman r=-0.38, p=0.0004). DHEA and pregnenolone are increased in patients with AD compared to control subjects. Patients carrying an APOE4 allele demonstrate reduced allopregnanolone levels in temporal cortex (Mann-Whitney p=0.04). In summary, our findings indicate that neurosteroids are altered in temporal cortex in patients with AD and related to neuropathological disease stage. In addition, the APOE4 allele is associated with reduced allopregnanolone levels. Neurosteroids may be relevant to the neurobiology and therapeutics of AD.


Assuntos
Doença de Alzheimer/patologia , Pregnanolona/análise , Lobo Temporal/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Estudos de Casos e Controles , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Cromatografia Líquida de Alta Pressão , Cognição/fisiologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Mudanças Depois da Morte , Pregnanolona/metabolismo , Lobo Temporal/metabolismo
16.
Cureus ; 13(4): e14665, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-34055516

RESUMO

Cerebral venous sinus thrombosis (CVT) is a rare but potentially life-threatening condition that presents with non-specific symptoms. This condition is more common in women and can be associated with local infection and hypercoagulable conditions, including protein C and S deficiency, factor V Leiden mutation, anti-thrombin III deficiency, thrombophilia, vasculitis, and malignancy. We report the case of a 24-year-old man who presented with a left temporal headache and right upper and lower extremity paresthesia. He also experienced impaired vision (altered spatial sensation), dental pain, bruxism, nausea, and vomiting. Magnetic resonance imaging and magnetic resonance venography of the brain revealed widespread thrombosis of the cerebral sinuses as well as left superior cerebral cortical veins bilaterally. No evidence of venous infarct was found. Subsequent hematologic evaluation showed the presence of heterozygous factor V Leiden mutation. Testing of family members subsequently revealed the presence of this same mutation in his mother and all three siblings, although there was no family history of stroke, hypercoagulability, or atypical headaches. The patient was started on low-molecular-weight heparin and later transitioned to apixaban. Progression of his headache and visual abnormalities led to the discovery of increased intracranial pressure as demonstrated by papilledema and characteristic findings on computed tomography scan. He was treated with acetazolamide with improvement of his symptoms. CVT is uncommon and can be a diagnostic challenge due to its atypical presentation. Clinicians should consider this diagnosis in patients with a subacute onset of atypical headache, especially when accompanied by seizures, focal neurological deficits, or altered consciousness.

17.
Psychol Serv ; 18(2): 275-284, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31750696

RESUMO

Although major depressive disorder (MDD) is a frequent diagnosis among women seeking care in the Veterans Health Administration, little is known about its course. For example, recurrence of MDD and its predictors have been investigated in civilians, but not among female veterans. Because female veterans differ from their civilian counterparts and from male veterans on demographic variables, including race, ethnicity, marital status, and educational level, it is important to identify factors affecting MDD course within this population. We investigated frequency and correlates of recurrent MDD among female veterans and their male counterparts. From a postdeployment research registry of 3,247 participants (660 women and 2,587 men), we selected those with a current episode of MDD (141 women and 462 men). For each sex, we compared those diagnosed with recurrent MDD with those experiencing a single episode on demographics, comorbid diagnoses, family history of mental illness, traumatic experiences, combat exposure, and social support. In contrast to findings in most civilian samples, recurrent MDD was significantly more frequent in female (70.2%) than in male (45.2%) depressed veterans, χ²(1) = 26.96, p < .001. In multivariable analyses, recurrence among women was associated with greater experiences of childhood abuse and more trauma during military service and with lower rates of posttraumatic stress disorder. Among men, recurrence was associated with older age, family history of psychiatric hospitalization, more postmilitary trauma, and lifetime anxiety disorder and with lower likelihood of war zone deployment. Trauma was associated with recurrence in both sexes, but the features of traumatic events differed in women and men. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Transtorno Depressivo Maior , Militares , Transtornos de Estresse Pós-Traumáticos , Veteranos , Idoso , Criança , Depressão , Transtorno Depressivo Maior/epidemiologia , Feminino , Humanos , Masculino , Caracteres Sexuais , Transtornos de Estresse Pós-Traumáticos/epidemiologia
18.
Work ; 68(4): 981-992, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867366

RESUMO

BACKGROUND: As millions of workers have shifted to telework, special accommodations for workers with respect to ergonomics may be required to ensure the workforce remains healthy. METHODS: A survey about home office ergonomics and discomfort was sent to faculty, staff, and administrators by email and was completed by 843 individuals. RESULTS: Over 40%of the participants reported moderate to severe discomfort (severe low/middle back pain, moderate discomfort in eyes/neck/head, and discomfort in the upper back/shoulders). Laptops (always and often) were widely used (85%) with most using the laptop monitor (55%) of all respondents. Further, less than 45%of the seating conditions were reported as having adjustable arm rests. CONCLUSION: As teleworking in makeshift offices becomes more common, the risk of significant discomfort and potentially more serious musculoskeletal disorders may result from poor static postures. Companies may need to accommodate workers by allowing them to take home office chairs, external monitors, keyboards, and mice as laptops are insufficient, ergonomically.


Assuntos
COVID-19 , Ergonomia , Doenças Musculoesqueléticas/prevenção & controle , Doenças Profissionais/prevenção & controle , Teletrabalho , Adulto , Periféricos de Computador , Humanos , Pandemias , SARS-CoV-2 , Universidades
19.
Eur J Neurosci ; 32(11): 1836-42, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20955472

RESUMO

The central nucleus of the amygdala (CeA) plays a critical role in regulating the behavioral, autonomic and endocrine response to stress. Dopamine (DA) participates in mediating the stress response and DA release is enhanced in the CeA during stressful events. However, the electrophysiological effects of DA on CeA neurons have not yet been characterized. Therefore, the purpose of this study was to identify and characterize the effect of DA application on electrophysiological responses of CeA neurons in coronal brain sections of male Sprague-Dawley rats. We used whole-cell patch-clamp electrophysiological techniques to record evoked synaptic responses and to determine basic membrane properties of CeA neurons both before and after DA superfusion. DA (20-250 µM) did not significantly alter membrane conductance over the voltage range tested. However, DA significantly reduced the peak amplitude of evoked inhibitory synaptic currents in CeA neurons. Pretreatment with the D(2) receptor antagonist eticlopride failed to significantly block the inhibitory effects of DA. In contrast, pretreatment with the D(1) receptor antagonist SCH-23390 significantly reduced the effects of DA on evoked inhibitory neurotransmission in these neurons. Moreover, bath superfusion of the specific D(1) receptor agonist SKF-39393, but not the D(2) receptor agonist quinpirole, significantly reduced peak amplitude of evoked inhibitory synaptic events. DA reduced the frequency of miniature IPSCs without altering the amplitude, while having no effect on the amplitude of IPSCs elicited by pressure application of GABA. These results suggest that DA may modulate inhibitory synaptic transmission in CeA through D(1) receptor activation primarily by a presynaptic mechanism.


Assuntos
Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/fisiologia , Dopamina/farmacologia , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Animais , Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Masculino , Neurônios/citologia , Técnicas de Patch-Clamp , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo , Salicilamidas/farmacologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/farmacologia
20.
Pain Med ; 11(10): 1469-76, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20735755

RESUMO

OBJECTIVE: Nearly half of Operation Enduring Freedom/Operation Iraqi Freedom veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABA(A) receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans. DESIGN: We determined serum neurosteroid levels by gas chromatography/mass spectrometry (allopregnanolone, pregnenolone) or radioimmunoassay (dehydroepiandrosterone [DHEA], progesterone, DHEA sulfate [DHEAS]) in 90 male veterans who served in the U.S. military after September 11, 2001. Self-reported pain symptoms were assessed in four areas (low back pain, chest pain, muscle soreness, headache). Stepwise linear regression analyses were conducted to investigate the relationship between pain assessments and neurosteroids, with the inclusion of smoking, alcohol use, age, and history of traumatic brain injury as covariates. SETTING: Durham VA Medical Center. RESULTS: Allopregnanolone levels were inversely associated with low back pain (P=0.044) and chest pain (P=0.013), and DHEA levels were inversely associated with muscle soreness (P=0.024). DHEAS levels were positively associated with chest pain (P=0.001). Additionally, there was a positive association between traumatic brain injury and muscle soreness (P=0.002). CONCLUSIONS: Neurosteroids may be relevant to the pathophysiology of self-reported pain symptoms in this veteran cohort, and could represent future pharmacological targets for pain disorders.


Assuntos
Neurotransmissores/metabolismo , Dor/metabolismo , Adulto , Afeganistão , Lesões Encefálicas/complicações , Desidroepiandrosterona/farmacologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Modelos Lineares , Masculino , Militares , Medição da Dor , Pregnanolona/sangue , Fumar/metabolismo , Estados Unidos , Veteranos
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