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1.
J Obstet Gynaecol Can ; 46(3): 102279, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37944818

RESUMO

OBJECTIVES: We record the experiences of staff in a labour, delivery, and obstetric services (LD-OBS) unit in Alberta's largest quaternary medical centre-the Foothills Medical Centre (FMC)-as they navigated hospital policies during the COVID-19 pandemic. We examine how unit leadership applied these policies to better align with care delivery realities while staying true to the interprofessional nature of the unit. METHODS: A total of 12 semi-structured qualitative interviews were conducted with LD-OBS unit staff. Snowball and purposive sampling strategies were used to capture experiences from key informants. Interview transcripts underwent inductive coding. The themes identified through this process were discussed with members of the authorial team until a consensus was reached. RESULTS: FMC LD-OBS team members used 'interprofessional' as a value through which to interpret, adapt, and implement centrally developed COVID-19 policies. These were applied at 3 key moments: reconfiguring the unit, triaging, and rerouting patients, and contesting central personal protective equipment policies. LD-OBS leaders championed the importance of interprofessional collaboration and teamwork in the unit and worked to uphold it as a practice and value. CONCLUSION: The COVID-19 pandemic experience of the FMC LD-OBS unit illustrates the importance of considering interprofessionalism as a core value as policy was developed and implemented. Health authorities, hospitals, and other LD-OBS units may wish to consider how interprofessional work affects policy interpretation among health care teams, and how this may be leveraged to successfully adapt policies to local units, under both pandemic and 'normal' conditions.


Assuntos
COVID-19 , Pandemias , Gravidez , Feminino , Humanos , Pandemias/prevenção & controle , Liderança , Pesquisa Qualitativa , Atenção à Saúde , Equipe de Assistência ao Paciente , Relações Interprofissionais
2.
Bipolar Disord ; 24(4): 392-399, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34599641

RESUMO

OBJECTIVES: While clinical guidelines exist for the management of bipolar disorder (BD), there are significant challenges to their widespread dissemination and implementation in clinical practice. The Canadian Network of Mood and Anxiety Treatment Improving Patient Care and Outcomes in the Treatment of Bipolar Disorder (C-IMPACT BD) web-based application was developed for use at the point-of-care to improve adherence to guidelines for evidence-based pharmacological management of BD. METHODS: C-IMPACT BD uses a point-of-care practice assessment which, via adaptive questioning of patient-specific information, text/video descriptions of the guidelines, and pop-up prompts delivers personalized, evidence-based treatment recommendations for patients with BD. In order to inform quality improvement of the newly developed tool, a sample of Canadian physicians were invited to use the application and record its influence on their prescribing behavior. RESULTS: Of 375 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder for whom a point-of-care practice assessment was completed, a change in therapy was considered for 225 (60.0%). Prior to completing the assessment, 59.6% of these patients were receiving first-line therapy recommended for their phase of illness. Following the assessment, the overall number of patients for whom a first-line recommended therapy was being considered increased significantly to 76.9% (p = 0.0001). CONCLUSIONS: Outcomes suggest that the C-IMPACT BD web-based application has the potential to improve physician adherence to clinical treatment guidelines. Formal research investigations are warranted to explore the impact of this tool on physician prescribing behavior and patient outcomes.


Assuntos
Transtorno Bipolar , Transtorno Bipolar/tratamento farmacológico , Canadá , Humanos , Internet , Sistemas Automatizados de Assistência Junto ao Leito
3.
Bipolar Disord ; 23(8): 767-788, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34599629

RESUMO

OBJECTIVES: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address. METHOD: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. RESULTS: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options. CONCLUSION: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.


Assuntos
Antipsicóticos , Transtorno Bipolar , Antipsicóticos/uso terapêutico , Ansiedade , Aripiprazol/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Canadá , Humanos , Olanzapina/uso terapêutico , Ácido Valproico/uso terapêutico
4.
Rech Soins Infirm ; (146): 95-104, 2021 10 15.
Artigo em Francês | MEDLINE | ID: mdl-35485058

RESUMO

CONTEXT: In ICUs, many patients are intubated. UE is an indicator of the quality of care.Isolation associated with "air" precautions may increase the number of UEs in mechanically ventilated (MV) COVID patients.The main aim of the study was to compare the rate of UE between a COVID-19 period and a control period. The secondary aims were to identify UE risk factors and to study the experience of caregivers during the COVID-19 period. METHOD: The method of choice was a retrospective single center case-control study. MV patients aged ≥ 18 years were eligible in two periods: the control period from 01/02/2020 to 29/02/2020, and the COVID-19 period from 01/03/2020 to 31/03/2020. An anonymous survey was given to ICU caregivers in Vannes Hospital. RESULTS: The UE rate was 17% (n=7) vs. 20% (n=9) control period vs. COVID-19 period (p=0.58), with nocturnal preponderance (75%). A quarter (n=4) of patients fulfill MV weaning criteria at the time of UE. A 71% (n=49) survey response rate was obtained. The COVID-19 period had a higher estimated UE risk for 76% (n=37) of caregivers, who felt that they had a greater workload, difficulties with monitoring, and decreased regular visits to patients' rooms. CONCLUSION: Contrary to the caregiver experience, we reported a similar UE rate over both the COVID-19 period and the control period.


Assuntos
Extubação , COVID-19 , Extubação/efeitos adversos , COVID-19/epidemiologia , Estudos de Casos e Controles , Humanos , Unidades de Terapia Intensiva , Pandemias , Respiração Artificial , Estudos Retrospectivos
5.
Rech Soins Infirm ; 146(3): 95-104, 2021.
Artigo em Francês | MEDLINE | ID: mdl-35724027

RESUMO

CONTEXT: In ICUs, many patients are intubated. UE is an indicator of the quality of care.Isolation associated with "air" precautions may increase the number of UEs in mechanically ventilated (MV) COVID patients.The main aim of the study was to compare the rate of UE between a COVID-19 period and a control period. The secondary aims were to identify UE risk factors and to study the experience of caregivers during the COVID-19 period. METHOD: The method of choice was a retrospective single center case-control study. MV patients aged ≥ 18 years were eligible in two periods: the control period from 01/02/2020 to 29/02/2020, and the COVID-19 period from 01/03/2020 to 31/03/2020. An anonymous survey was given to ICU caregivers in Vannes Hospital. RESULTS: The UE rate was 17% (n=7) vs. 20% (n=9) control period vs. COVID-19 period (p=0.58), with nocturnal preponderance (75%). A quarter (n=4) of patients fulfill MV weaning criteria at the time of UE. A 71% (n=49) survey response rate was obtained. The COVID-19 period had a higher estimated UE risk for 76% (n=37) of caregivers, who felt that they had a greater workload, difficulties with monitoring, and decreased regular visits to patients' rooms. CONCLUSION: Contrary to the caregiver experience, we reported a similar UE rate over both the COVID-19 period and the control period.


Assuntos
Extubação , COVID-19 , Extubação/efeitos adversos , COVID-19/epidemiologia , Estudos de Casos e Controles , Cuidados Críticos/métodos , Humanos , Pandemias , Respiração Artificial , Estudos Retrospectivos
6.
Dig Surg ; 37(4): 292-301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31661689

RESUMO

INTRODUCTION: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC. METHODS: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected. A propensity score matching (PSM; 1:2) was performed and compared patients with clinical tumor (cT) 4 colon cancer who were treated with neoadjuvant CT to patients with cT4 colon cancer treated with adjuvant CT (Fig. 1). RESULTS: A total of 192 patients treated with neoadjuvant CT were compared to 1,954 patients that received adjuvant CT. After PSM, 149 patients in the neoadjuvant group were compared to 298 patients in the control group. No significant differences were found in baseline characteristics after PSM. After neoadjuvant CT, a significant response was observed in 13 (9%) patients with 5 (4%) patients showing a complete response. Complete resection margins (R0) were achieved in 77% in the neoadjuvant group versus 86% in the adjuvant treated group (p = 0.037). Significantly less tumor positive lymph nodes were found in the neoadjuvant group (median 0 vs. 2, p < 0.001). Major complication rates and 5-year overall survival did not differ between both groups (67-65%, p = 0.87). CONCLUSION: Neoadjuvant CT seems safe and feasible with similar long-term survival compared to patients who are treated with adjuvant CT.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Terapia Neoadjuvante , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/efeitos adversos , Colectomia/efeitos adversos , Neoplasias do Colo/cirurgia , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Neoplasia Residual , Países Baixos , Pontuação de Propensão , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida
7.
Issues Ment Health Nurs ; 41(8): 684-690, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32357073

RESUMO

Psychiatric nurses often experience associative stigma. Associative stigma may impact psychiatric nurses' views of their professional identity which ultimately impacts the health care of individuals experiencing mental health concerns. Very little research has been conducted on associative stigma in the western Prairie Provinces, including Manitoba. The authors conducted a secondary analysis on the results of an explanatory sequential mixed methods research study to determine if psychiatric nurses in Manitoba are influenced by associative stigma. Three themes were identified through this analysis, specifically: (1) the perception that RPNs are not "Real" Nurses; (2) lack of recognition of specialized training; and (3) working with a stigmatized population. Associative stigma was intertwined in all of the participants' narratives indicating a need to dismantle associative stigma. Strategies to enhance the public perception of psychiatric nursing and decrease associative stigma within the profession are described.


Assuntos
Enfermeiros Especialistas/psicologia , Enfermagem Psiquiátrica , Estigma Social , Humanos , Manitoba , Identificação Social , Estereotipagem , Inquéritos e Questionários
8.
Issues Ment Health Nurs ; 41(5): 395-403, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32202963

RESUMO

A study regarding the role and uniqueness of psychiatric nursing was conducted with 94 participants from Manitoba, Canada. The primary theme of comprehensive knowledge of mental health, mental illness, and addictions was foundational for the application of the sub-themes of therapeutic relationship, holistic approach, recovery orientation, stigma reduction, and advocacy for change. Values, beliefs, and attitudes towards people with mental illness and addictions need to be instilled in psychiatric nursing students throughout their educational program to provide high quality, compassionate, and safe care. Implications for incorporation of the theme and sub-themes into psychiatric nursing curriculum are described in the paper.


Assuntos
Bacharelado em Enfermagem , Enfermagem Psiquiátrica/educação , Atitude do Pessoal de Saúde , Currículo , Escolaridade , Humanos , Manitoba , Transtornos Mentais/psicologia , Serviços de Saúde Mental , Estigma Social , Inquéritos e Questionários
10.
Aust N Z J Psychiatry ; 51(1): 65-74, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26792829

RESUMO

OBJECTIVE: Previous studies reported decreased N-acetyl aspartate and increased Glx (the sum of glutamate plus glutamine) in bipolar disorder. Since these studies included patients at different stages of illness, it is unknown whether these changes have a causal role or a consequence of multiple episodes and treatments. The studies in early-stage bipolar disorder patients have the potential to provide answers to these issues. Therefore, we evaluated N-acetyl aspartate and Glx levels in hippocampi of first-episode bipolar disorder patients and health subjects at baseline and at 12 months, and examined the impact of episode recurrence on these measures. METHOD: We used single-voxel proton magnetic resonance spectroscopy to compare the hippocampal neurometabolites ( N-acetyl aspartate and Glx) levels between 41 patients with bipolar disorder following recovery from their first-manic episode and 27 matched healthy subjects at recruitment and 12 months later. We also compared N-acetyl aspartate and Glx levels between patients who had a recurrence of a mood episode and those who did not. RESULTS: There was no main effect of either group (diagnosis) or time for hippocampal N-acetyl aspartate and Glx levels in bipolar disorder patients and healthy subjects. We also did not find any group-by-time interaction for the levels of these metabolites. There were also no differences in N-acetyl aspartate and Glx between patients who experienced a recurrence of a mood episode and those who did not over 12-month follow-up. CONCLUSION: Our data suggest that N-acetyl aspartate and Glx levels are not altered in early stage bipolar disorder. Further, these data suggest that episode recurrence in early stages does not have a significant impact on the levels of these metabolites. These may suggest that there may be an early window for intervention to potentially arrest neuroprogression of the disease.


Assuntos
Ácido Aspártico/análogos & derivados , Transtorno Bipolar/metabolismo , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Hipocampo/metabolismo , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adulto , Ácido Aspártico/metabolismo , Feminino , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
11.
Bipolar Disord ; 18(6): 511-519, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27759214

RESUMO

OBJECTIVES: Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change. METHODS: A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BDrecurr ), and patients in sustained remission (BDwell ). RESULTS: The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BDwell and HS. However, the BDrecurr group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BDwell patients involving bilateral frontal, temporal and left parietal regions. CONCLUSIONS: GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal.


Assuntos
Transtorno Bipolar , Emoções/fisiologia , Substância Cinzenta , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Progressão da Doença , Cuidado Periódico , Feminino , Seguimentos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Estudos Prospectivos , Prevenção Secundária/métodos
12.
BMC Public Health ; 16: 10, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26728042

RESUMO

BACKGROUND: Studies suggest that the built environment with high numbers of fast food restaurants and convenience stores and low numbers of super stores and grocery stores are related to obesity, type II diabetes mellitus, and other chronic diseases. Since few studies assess these relationships at the county level, we aim to examine fast food restaurant density, convenience store density, super store density, and grocery store density and prevalence of type II diabetes among counties in South Carolina. METHODS: Pearson's correlation between four types of food outlet densities- fast food restaurants, convenience stores, super stores, and grocery stores- and prevalence of type II diabetes were computed. The relationship between each of these food outlet densities were mapped with prevalence of type II diabetes, and OLS regression analysis was completed adjusting for county-level rates of obesity, physical inactivity, density of recreation facilities, unemployment, households with no car and limited access to stores, education, and race. RESULTS: We showed a significant, negative relationship between fast food restaurant density and prevalence of type II diabetes, and a significant, positive relationship between convenience store density and prevalence of type II diabetes. In adjusted analysis, the food outlet densities (of any type) was not associated with prevalence of type II diabetes. CONCLUSIONS: This ecological analysis showed no associations between fast food restaurants, convenience stores, super stores, or grocery stores densities and the prevalence of type II diabetes. Consideration of environmental, social, and cultural determinants, as well as individual behaviors is needed in future research.


Assuntos
Comércio , Diabetes Mellitus Tipo 2/etiologia , Meio Ambiente , Fast Foods , Diabetes Mellitus Tipo 2/epidemiologia , Ecologia , Planejamento Ambiental , Feminino , Humanos , Masculino , Obesidade/etiologia , Prevalência , Características de Residência , Restaurantes , South Carolina/epidemiologia
13.
Am J Dermatopathol ; 38(7): 549-52, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26981739

RESUMO

Adenomyoepithelioma (AME) is a biphasic neoplasm of epithelial and myoepithelial cells. It is most commonly found in the breast, although rare cases have been reported from the lung, salivary glands, and skin. There are 5 well-documented cases of cutaneous AME in the literature. We report a new case of cutaneous AME. Our case was commingled with apocrine hidrocystoma. This is the first report of cutaneous AME in a male patient and the first to describe SOX10 immunostaining in cutaneous AME. We review the literature on cutaneous AME and note the greater than chance colocalization with other adnexal tumors. We speculate that AME may represent localized overgrowth of myoepithelial cells within a pre-existent sweat gland tumor. Histopathologists should be aware of the potential of SOX10-positive myoepithelial neoplasms to mimic nodular melanocytic proliferations.


Assuntos
Adenomioepitelioma/patologia , Glândulas Apócrinas/patologia , Hidrocistoma/patologia , Neoplasias Complexas Mistas/patologia , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Adenomioepitelioma/química , Adenomioepitelioma/cirurgia , Adulto , Idoso de 80 Anos ou mais , Glândulas Apócrinas/química , Glândulas Apócrinas/cirurgia , Biomarcadores Tumorais/análise , Biópsia , Feminino , Hidrocistoma/química , Hidrocistoma/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/cirurgia , Fatores de Transcrição SOXE/análise , Neoplasias Cutâneas/química , Neoplasias Cutâneas/cirurgia , Neoplasias das Glândulas Sudoríparas/química , Neoplasias das Glândulas Sudoríparas/cirurgia , Resultado do Tratamento
14.
Protein Expr Purif ; 110: 172-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25818999

RESUMO

Extracellular signal-regulated kinase 2 (ERK2) is a serine/threonine protein kinase involved in many cellular programs, such as cell proliferation, differentiation, motility and programed cell-death. It is therefore considered an important target in the treatment of cancer. In an effort to support biochemical screening and small molecule drug discovery, we established a robust system to generate both inactive and active forms of ERK2 using insect expression system. We report here, for the first time, that inactive ERK2 can be expressed and purified with 100% homogeneity in the unphosphorylated form using insect system. This resulted in a significant 20-fold yield improvement compared to that previously reported using bacterial expression system. We also report a newly developed system to generate active ERK2 in insect cells through in vivo co-expression with a constitutively active MEK1 (S218D S222D). Isolated active ERK2 was confirmed to be doubly phosphorylated at the correct sites, T185 and Y187, in the activation loop of ERK2. Both ERK2 forms, inactive and active, were well characterized by biochemical activity assay for their kinase function. Inactive and active ERK2 were the two key reagents that enabled successful high through-put biochemical assay screen and structural drug discovery studies.


Assuntos
Baculoviridae/genética , Clonagem Molecular/métodos , Proteína Quinase 1 Ativada por Mitógeno/genética , Plasmídeos/metabolismo , Proteínas Recombinantes de Fusão/genética , Animais , Baculoviridae/metabolismo , Ativação Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Engenharia Genética , Histidina/genética , Histidina/metabolismo , Humanos , Cinética , MAP Quinase Quinase 1/genética , MAP Quinase Quinase 1/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/biossíntese , Proteína Quinase 1 Ativada por Mitógeno/isolamento & purificação , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Fosforilação , Plasmídeos/química , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/isolamento & purificação , Células Sf9 , Spodoptera
15.
Br J Psychiatry ; 205(1): 36-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24764544

RESUMO

BACKGROUND: Although manic episodes reportedly contribute to cognitive deficits in bipolar I disorder, the contribution of depressive episodes is poorly researched. AIMS: We investigated the impact of depressive episodes on cognitive function early in the course of bipolar I disorder. METHOD: A total of 68 patients and 38 controls from the Systematic Treatment Optimization Programme for Early Mania (STOP-EM) first-episode mania programme were examined. We conducted (a) a cross-sectional analysis of the impact of prior depressive episodes on baseline cognitive function and (b) a prospective analysis assessing the contribution of depression recurrence within 1 year following a first episode of mania on cognitive functioning. RESULTS: The cross-sectional analysis showed no significant differences between patients with past depressive episodes compared with those without, on overall or individual domains of cognitive function (all P>0.09). The prospective analysis failed to reveal a significant group×time interaction for cognitive decline from baseline to 1 year (P = 0.99) in patients with a recurrence of depressive episodes compared with those with no recurrence. However, impaired verbal memory at baseline was associated with a depression recurrence within 1 year. CONCLUSIONS: Although deficits in all domains of cognitive function are seen in patients early in the course of bipolar disorder, depressive episodes do not confer additional burden on cognitive function. However, poorer verbal memory may serve as a marker for increased susceptibility to depression recurrence early in the course of illness.


Assuntos
Transtorno Bipolar/complicações , Transtornos Cognitivos/complicações , Cognição/fisiologia , Depressão/complicações , Adolescente , Adulto , Transtorno Bipolar/psicologia , Transtornos Cognitivos/psicologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Adulto Jovem
16.
Bipolar Disord ; 15(6): 657-68, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23919287

RESUMO

OBJECTIVES: Executive function impairments are a core feature of bipolar I disorder (BD-I), not only present during acute episodes but also persisting following remission of mood symptoms. Despite advances in knowledge regarding the neural basis of executive functions in healthy subjects, research into morphological abnormalities underlying the deficits in BD-I is lacking. METHODS: Patients with BD-I within three months of sustained remission from their first manic episode (n = 41) underwent neuropsychological testing and a 3T magnetic resonance imaging scan and were compared to healthy subjects matched for age, sex, and premorbid IQ (n = 30). Group dorsolateral prefrontal cortex (DLPFC; Brodmann areas 9 and 46) and caudate volumes were examined and analyzed for relationships with the average score from three computerized tests of executive function: Spatial Working Memory, Stockings of Cambridge, and Intradimensional/Extradimensional Shift. RESULTS: Right caudate volumes were enlarged in patients (z = 3.57, p < 0.05 corrected). No differences in DLPFC volumes were found. Patients showed large deficits in executive function relative to healthy subjects (d = -0.92, p < 0.001). While in healthy subjects, a larger right (r = +0.39, p < 0.05) and left (r = +0.44, p < 0.05) caudate was associated with better executive function score, in patients, larger right (r = -0.36, p < 0.05) and left (r = -0.34, p < 0.05) volumes correlated with poorer performance. CONCLUSIONS: Although the etiology of gray matter changes is unknown, volume increases in the right caudate may be an important factor underlying executive function impairments during remission in patients with BD-I.


Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/patologia , Transtornos Cognitivos/etiologia , Corpo Estriado/patologia , Função Executiva/fisiologia , Lobo Frontal/patologia , Adolescente , Adulto , Progressão da Doença , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Análise de Regressão , Adulto Jovem
17.
Mol Cell Proteomics ; 10(10): M111.009829, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21685499

RESUMO

Huntingtin (Htt) is a protein with a polyglutamine stretch in the N-terminus and expansion of the polyglutamine stretch causes Huntington's disease (HD). Htt is a multiple domain protein whose function has not been well characterized. Previous reports have shown, however, that post-translational modifications of Htt such as phosphorylation and acetylation modulate mutant Htt toxicity, localization, and vesicular trafficking. Lysine acetylation of Htt is of particular importance in HD as this modification regulates disease progression and toxicity. Treatment of mouse models with histone deacetylase inhibitors ameliorates HD-like symptoms and alterations in acetylation of Htt promotes clearance of the protein. Given the importance of acetylation in HD and other diseases, we focused on the systematic identification of lysine acetylation sites in Htt23Q (1-612) in a cell culture model using mass spectrometry. Myc-tagged Htt23Q (1-612) overexpressed in the HEK 293T cell line was immunoprecipitated, separated by SDS-PAGE, digested and subjected to high performance liquid chromatography tandem MS analysis. Five lysine acetylation sites were identified, including three novel sites Lys-178, Lys-236, Lys-345 and two previously described sites Lys-9 and Lys-444. Antibodies specific to three of the Htt acetylation sites were produced and confirmed the acetylation sites in Htt. A multiple reaction monitoring MS assay was developed to compare quantitatively the Lys-178 acetylation level between wild-type Htt23Q and mutant Htt148Q (1-612). This report represents the first comprehensive mapping of lysine acetylation sites in N-terminal region of Htt.


Assuntos
Doença de Huntington/metabolismo , Lisina/análise , Proteínas do Tecido Nervoso/química , Proteínas Nucleares/química , Processamento de Proteína Pós-Traducional , Acetilação , Animais , Anticorpos , Encéfalo/metabolismo , Progressão da Doença , Células HEK293 , Inibidores de Histona Desacetilases/farmacologia , Humanos , Proteína Huntingtina , Doença de Huntington/genética , Lisina/metabolismo , Espectrometria de Massas , Camundongos , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Estrutura Terciária de Proteína
18.
J Addict Med ; 17(6): e374-e381, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37934531

RESUMO

OBJECTIVES: The primary objectives of this study were to describe the demographics and clinical characteristics of patients who were treated with buprenorphine extended-release versus buprenorphine-naloxone sublingual tablets versus methadone in a real-world setting and to evaluate the difference in nonfatal overdose events between treatment cohorts. METHODS: This study was a retrospective chart review of patients with opioid use disorder initiating opioid agonist therapy in Canada during the outset of the COVID-19 pandemic (March 11, 2020 to October 31, 2021). Three treatment cohorts were defined by the initial prescribed opioid agonist therapy regimen: buprenorphine extended-release, buprenorphine-naloxone sublingual tablets, and methadone. Baseline characteristics, as well as treatment status, overdose events, and substance use 6 months after treatment initiation were collected using a standardized form. RESULTS: Nine clinics provided data on 379 patient cases. The incidence rate (number of events per 100 person-years) for a self-reported nonfatal overdose was 46.8 (n = 18), 19.3 (n = 10), and 1.7 (n = 1) in the methadone, buprenorphine-naloxone sublingual tablets, and buprenorphine extended-release cohorts, respectively. The risk-adjusted difference for the proportion of patients with nonfatal overdose was 8.59% (95% confidence interval, 3.10-14.08%; P = 0.0022) for methadone versus buprenorphine extended-release and 6.51% (95% confidence interval, 1.46-11.56%; P = 0.0115) for buprenorphine-naloxone sublingual tablets versus buprenorphine extended-release. CONCLUSIONS: Buprenorphine extended-release was associated with lower rates of nonfatal overdose events compared with daily opioid agonist therapy. Given the limitations of this naturalistic, retrospective design, further prospective studies are needed to validate these findings and demonstrate the potential for long-acting opioid agonist therapy in addressing the opioid crisis.


Assuntos
Buprenorfina , COVID-19 , Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides , Combinação Buprenorfina e Naloxona , Pandemias , Estudos Retrospectivos , Metadona
19.
Mol Vis ; 18: 730-43, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22509103

RESUMO

PURPOSE: To identify key genes differentially expressed in the human retinal pigment epithelium (hRPE) following low-level West Nile virus (WNV) infection. METHODS: Primary hRPE and retinal pigment epithelium cell line (ARPE-19) cells were infected with WNV (multiplicity of infection 1). RNA extracted from mock-infected and WNV-infected cells was assessed for differential expression of genes using Affymetrix microarray. Quantitative real-time PCR analysis of 23 genes was used to validate the microarray results. RESULTS: Functional annotation clustering of the microarray data showed that gene clusters involved in immune and antiviral responses ranked highly, involving genes such as chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-C motif) ligand 5 (CCL5), chemokine (C-X-C motif) ligand 10 (CXCL10), and toll like receptor 3 (TLR3). In conjunction with the quantitative real-time PCR analysis, other novel genes regulated by WNV infection included indoleamine 2,3-dioxygenase (IDO1), genes involved in the transforming growth factor-ß pathway (bone morphogenetic protein and activin membrane-bound inhibitor homolog [BAMBI] and activating transcription factor 3 [ATF3]), and genes involved in apoptosis (tumor necrosis factor receptor superfamily, member 10d [TNFRSF10D]). WNV-infected RPE did not produce any interferon-γ, suggesting that IDO1 is induced by other soluble factors, by the virus alone, or both. CONCLUSIONS: Low-level WNV infection of hRPE cells induced expression of genes that are typically associated with the host cell response to virus infection. We also identified other genes, including IDO1 and BAMBI, that may influence the RPE and therefore outer blood-retinal barrier integrity during ocular infection and inflammation, or are associated with degeneration, as seen for example in aging.


Assuntos
Células Epiteliais/imunologia , Expressão Gênica/imunologia , Epitélio Pigmentado da Retina/imunologia , Vírus do Nilo Ocidental/fisiologia , Apoptose/genética , Apoptose/imunologia , Quimiocinas/genética , Quimiocinas/imunologia , Células Epiteliais/citologia , Células Epiteliais/virologia , Perfilação da Expressão Gênica , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Família Multigênica , Análise de Sequência com Séries de Oligonucleotídeos , Cultura Primária de Células , Proteômica , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/virologia , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia , Carga Viral
20.
Dermatol Online J ; 18(4): 13, 2012 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-22559028

RESUMO

Non-melanoma skin cancer (NMSC) is the most common cancer in humans. Basal cell carcinoma accounts for 75 percent to 80 percent of NMSC. We report a primary cutaneous BCC on the upper chest in which vascular invasion was demonstrated by histopathology and the unique application of dual immunohistochemistry.


Assuntos
Vasos Sanguíneos/patologia , Carcinoma Basocelular/patologia , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Pele/irrigação sanguínea , Neoplasias Cutâneas/cirurgia
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