RESUMO
Beginning in 1999, Department of Defense policy directed the military services to develop Combat and Operational Stress Control (COSC) programs to address prevention, early identification, and management of the negative effects of combat and operational stress. The aim of this study is to provide a narrative review of COSC programs and organize them into a prevention framework to clarify gaps and future directions. A systematic search was conducted to identify studies between 2001 and 2020 in peer-reviewed articles or government-sponsored reports describing an evaluation of COSC programs. The target population of these programs was US service members who had participated in an intervention designed to address combat or operational stress in a deployed, operational, or field setting. These programs then were rated for level of evidence and categorized using a tiered prevention model. This search identified 36 published evaluations of 19 COSC programs and interventions from. Most programs were described as effective in addressing target outcomes, with behavioral health outcomes reported for 13 of the 19 identified programs; the remaining six focused on knowledge base and behavior changes. Delivery of these prevention programs also ranged from peer-based implementation to formal treatment, including programs at all prevention levels. COSC interventions show promise for helping service members manage stress, with more than half of the programs showing evidence from studies using randomized designs. Future iterations of COSC program evaluations should explore the development of a joint curriculum using existing content in a tiered prevention framework.
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Militares , Humanos , Estados Unidos , Estresse Psicológico/prevenção & controle , Estresse Ocupacional/prevenção & controle , Distúrbios de Guerra/prevenção & controleRESUMO
The Department of Defense has mandated combat and operational stress control (COSC) efforts for the Services since 1999. Although several COSC-related programs have been implemented, few have undergone evaluation, and no standardized metrics have been established to assess their effectiveness and utility. The purpose of this review was to characterize the content and psychometrics of measures that have been utilized as outcome metrics in evaluations of COSC-related programs and interventions. Systematic literature searches were conducted for publications that: a) evaluated at least one measure from U.S. service members who participated in a program or intervention to prevent or reduce the adverse effects of combat and operational stress; and b) reported U.S. data on the internal consistency, test-retest reliability, convergent validity, and sensitivity/specificity of the identified measures. This process identified 15 measures for which psychometric properties were reviewed for acceptability based on recommended criteria. Identified measures varied from well-validated measures to newer instruments for which more data is needed on one or more of the target psychometric properties. Aside from internal consistency, psychometric data from U.S. military samples were sparse. Results further suggested that some measures might have reduced sensitivity in service members under certain conditions, such as large-scale screening. Additional studies are needed to validate COSC-relevant measures in service members. Future evaluations of programs and interventions for combat and operational stress should select measures that will increase the consistency of the literature, allow comparisons across studies, and ensure alignment with the objectives of identified programs.
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Militares , Psicometria , Psicometria/métodos , Humanos , Militares/psicologia , Estados Unidos , Reprodutibilidade dos Testes , Estresse Psicológico/terapia , Avaliação de Programas e Projetos de Saúde , Avaliação de Resultados em Cuidados de Saúde , Distúrbios de Guerra/terapia , Distúrbios de Guerra/psicologia , Estresse Ocupacional/prevenção & controle , Estresse Ocupacional/terapiaRESUMO
BACKGROUND: The function of exosomes, small extracellular vesicles (sEV) secreted from human adipose-derived stem cells (ADSC), is becoming increasingly recognized as a means of transferring the regenerative power of stem cells to injured cells in wound healing. Exosomes are rich in ceramides and long noncoding RNA (lncRNA) like metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). We identified putative ceramide responsive cis-elements (CRCE) in MALAT1. We hypothesized that CRCE respond to cellular ceramide levels to regulate sEV MALAT1 packaging. MALAT1 levels by many cells exceed those of protein coding genes and it's expression is equally high in exosomes. Ceramide also regulates exosome synthesis, however, the contents of exosome cargo via sphingomyelinase and ceramide synthase pathways has not been demonstrated. METHODS: ADSC were treated with an inhibitor of sphingomyelinase, GW4869, and stimulators of ceramide synthesis, C2- and C6-short chain ceramides, prior to collection of conditioned media (CM). sEV were isolated from CM, and then used to treat human dermal fibroblast (HDF) cultures in cell migration scratch assays, and mitochondrial stress tests to evaluate oxygen consumption rates (OCR). RESULTS: Inhibition of sphingomyelinase by treatment of ADSC with GW4869 lowered levels of MALAT1 in small EVs. Stimulation of ceramide synthesis using C2- and C6- ceramides increased cellular, EVs levels of MALAT1. The functional role of sEV MALAT1 was evaluated in HDF by applying EVs to HDF. Control sEV increased migration of HDF, and significantly increased ATP production, basal and maximal respiration OCR. sEV from GW4869-treated ADSC inhibited cell migration and maximal respiration. However, sEV from C2- and C6-treated cells, respectively, increased both functions but not significantly above control EV except for maximal respiration. sEV were exosomes except when ADSC were treated with GW4869 and C6-ceramide, then they were larger and considered microvesicles. CONCLUSIONS: Ceramide synthesis regulates MALAT1 EV content. Sphingomyelinase inhibition blocked MALAT1 from being secreted from ADSC EVs. Our report is consistent with those of MALAT1 increasing cell migration and mitochondrial MALAT1 altering maximal respiration in cells. Since MALAT1 is important for exosome function, it stands that increased exosomal MALAT1 should be beneficial for wound healing as shown with these assays. Video Abstract.
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Fibroblastos , Mitocôndrias , RNA Longo não Codificante , Humanos , Movimento Celular , RNA Longo não Codificante/genética , Esfingomielina Fosfodiesterase , Células-TroncoRESUMO
Excessive dietary intake of fat results in its storage in white adipose tissue (WAT). Energy expenditure through lipid oxidation occurs in brown adipose tissue (BAT). Certain WAT depots can undergo a change termed beiging where markers that BAT express are induced. Little is known about signalling pathways inducing beiging. Here, inhibition of a signalling pathway regulating alternative pre-mRNA splicing is involved in adipocyte beiging. Clk1/2/4 kinases regulate splicing by phosphorylating factors that process pre-mRNA. Clk1 inhibition by TG003 results in beige-like adipocytes highly expressing PGC1α and UCP1. SiRNA for Clk1, 2 and 4, demonstrated that Clk1 depletion increased UCP1 and PGC1α expression, whereas Clk2/4 siRNA did not. TG003-treated adipocytes contained fewer lipid droplets, are smaller, and contain more mitochondria, resulting in proton leak increases. Additionally, inhibition of PKCßII activity, a splice variant regulated by Clk1, increased beiging. PGC1α is a substrate for both Clk1 and PKCßII kinases, and we surmised that inhibition of PGC1α phosphorylation resulted in beiging of adipocytes. We show that TG003 binds Clk1 more than Clk2/4 through direct binding, and PGC1α binds to Clk1 at a site close to TG003. Furthermore, we show that TG003 is highly specific for Clk1 across hundreds of kinases in our activity screen. Hence, Clk1 inhibition becomes a target for induction of beige adipocytes.
Assuntos
Adipócitos , Precursores de RNA , Células 3T3-L1 , Adipócitos/metabolismo , Animais , Biomarcadores/metabolismo , Camundongos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteína Quinase C beta/metabolismo , Precursores de RNA/metabolismo , RNA Interferente Pequeno/metabolismoRESUMO
INTRODUCTION: Affecting more than 3.9 million Americans, the hepatitis C virus (HCV) attacks the liver by causing inflammation. Left untreated, HCV can lead to serious consequences. Targeting high-risk individuals in the inpatient psychiatric setting can lead to increased testing and referral. AIMS: This quality improvement project determined whether an intervention-consisting of a pretest, educational session, posttest, and screening implementation-increased staff knowledge about HCV screening recommendations, identified at-risk individuals, and increased the number of patients screened and referred for treatment. METHOD: An online HCV educational session was provided to 30 staff at a Midwest regional psychiatric unit. An online pre/posttest was conducted to determine staff knowledge and understanding prior to and after the educational session. An HCV screening tool checklist was incorporated into the electronic health record (EHR) system. A 3-month pre/post-intervention chart review was completed to determine the number of patients identified and screened for HCV. RESULTS: A comparison of the 30 staff members' mean pre/posttest scores were calculated using an unpaired t test, showing a prescore mean of 55.15 ± 19.09 and a postscore mean of 85.75 ± 13.44, p < .001. A chi-square analysis indicated that there was a statistically significant post-intervention increase in the percentage of high-risk patients identified (5.6%-36.4%, p < .001) and screened (5.6%-31.4%, p < .001) for HCV compared with pre-intervention. CONCLUSION: The study intervention increased staff knowledge of HCV guidelines and the number of at-risk patients identified and screened for the disease.
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Lyme disease results from infection of humans with the spirochete Borrelia burgdorferi. The first and most common clinical manifestation is the circular, inflamed skin lesion referred to as erythema migrans; later manifestations result from infections of other body sites. Laboratory diagnosis of Lyme disease can be challenging in patients with erythema migrans because of the time delay in the development of specific diagnostic antibodies against Borrelia. Reliable blood biomarkers for the early diagnosis of Lyme disease in patients with erythema migrans are needed. Here, we performed selected reaction monitoring, a targeted mass spectrometry-based approach, to measure selected proteins that (1) are known to be predominantly expressed in one organ (i.e., organ-specific blood proteins) and whose blood concentrations may change as a result of Lyme disease, or (2) are involved in acute immune responses. In a longitudinal cohort of 40 Lyme disease patients and 20 healthy controls, we identified 10 proteins with significantly altered serum levels in patients at the time of diagnosis, and we also developed a 10-protein panel identified through multivariate analysis. In an independent cohort of patients with erythema migrans, six of these proteins, APOA4, C9, CRP, CST6, PGLYRP2, and S100A9, were confirmed to show significantly altered serum levels in patients at time of presentation. Nine of the 10 proteins from the multivariate panel were also verified in the second cohort. These proteins, primarily innate immune response proteins or proteins specific to liver, skin, or white blood cells, may serve as candidate blood biomarkers requiring further validation to aid in the laboratory diagnosis of early Lyme disease.
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Proteínas de Fase Aguda/análise , Doença de Lyme/sangue , Adulto , Idoso , Biomarcadores/sangue , Western Blotting , Estudos de Casos e Controles , Eritema Migrans Crônico/sangue , Eritema Migrans Crônico/etiologia , Feminino , Humanos , Imunidade Inata , Doença de Lyme/tratamento farmacológico , Doença de Lyme/etiologia , Doença de Lyme/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Especificidade de ÓrgãosRESUMO
In certain regions of New York state, USA, Ixodes scapularis ticks can potentially transmit 4 pathogens in addition to Borrelia burgdorferi: Anaplasma phagocytophilum, Babesia microti, Borrelia miyamotoi, and the deer tick virus subtype of Powassan virus. In a prospective study, we systematically evaluated 52 adult patients with erythema migrans, the most common clinical manifestation of B. burgdorferi infection (Lyme disease), who had not received treatment for Lyme disease. We used serologic testing to evaluate these patients for evidence of co-infection with any of the 4 other tickborne pathogens. Evidence of co-infection was found for B. microti only; 4-6 patients were co-infected with Babesia microti. Nearly 90% of the patients evaluated had no evidence of co-infection. Our finding of B. microti co-infection documents the increasing clinical relevance of this emerging infection.
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Babesia microti , Doença de Lyme , Doenças Transmitidas por Carrapatos , Babesia microti/isolamento & purificação , Babesiose/epidemiologia , Coinfecção , Humanos , New York/epidemiologia , Estudos Prospectivos , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/parasitologiaRESUMO
BACKGROUND: Nursing home providers face challenges in urinary tract infection assessment and treatment, often prescribing unnecessary antibiotics for asymptomatic bacteriuria, a practice that can result in adverse drug reactions, drug resistance, and an increase in antibiotic-associated diarrhea. PURPOSE: The purpose of this project was to replicate the Cooper Urinary Tract Infection Program in another facility and measure its effectiveness. METHODS: Using a pre-post design, this project was implemented at a 120-bed, long-term care and rehabilitation facility located in the Midwest United States. INTERVENTIONS: This project used the multifaceted Cooper Urinary Tract Infection Program that includes the Cooper tool algorithm, didactic education for providers, and change champions. RESULTS: The results were significant improvements in nurse knowledge and reduced rates of urinary tract infections, inappropriate antibiotic treatments, and urinalyses. CONCLUSIONS: These results add to the evidence for implementing the Cooper Urinary Tract Infection Program in long-term care facilities for effective reduction of inappropriate antibiotic usage for urinary tract infection.
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Antibacterianos/uso terapêutico , Prescrição Inadequada/efeitos adversos , Assistência de Longa Duração , Inovação Organizacional , Infecções Urinárias/prevenção & controle , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Pessoal de Saúde/educação , Humanos , Masculino , Meio-Oeste dos Estados Unidos , Casas de SaúdeRESUMO
BACKGROUND: Neuroinflammation is a common therapeutic target for traumatic brain injury (TBI) due to its contribution to delayed secondary cell death and has the potential to occur for years after the initial insult. Exosomes from adipose-derived stem cells (hASCs) containing the long noncoding RNA MALAT1 are a novel, cell-free regenerative approach to long-term recovery after traumatic brain injury (TBI) that have the potential to modulate inflammation at the genomic level. The long noncoding RNA MALAT1 has been shown to be an important component of the secretome of hASCs. METHODS: We isolated exosomes from hASC containing or depleted of MALAT1. The hASC-derived exosomes were then administered intravenously to rats following a mild controlled cortical impact (CCI). We followed the rats with behavior, in vivo imaging, histology, and RNA sequencing (RNA Seq). RESULTS: Using in vivo imaging, we show that exosomes migrate into the spleen within 1 h following administration and enter the brain several hours later following TBI. Significant recovery of function on motor behavior as well as a reduction in cortical brain injury was observed after TBI in rats treated with exosomes. Treatment with either exosomes depleted of MALAT1 or conditioned media depleted of exosomes showed limited regenerative effects, demonstrating the importance of MALAT1 in exosome-mediated recovery. Analysis of the brain and spleen transcriptome using RNA Seq showed MALAT1-dependent modulation of inflammation-related pathways, cell cycle, cell death, and regenerative molecular pathways. Importantly, our data demonstrates that MALAT1 regulates expression of other noncoding RNAs including snoRNAs. CONCLUSION: We demonstrate that MALAT1 in hASC-derived exosomes modulates multiple therapeutic targets, including inflammation, and has tremendous therapeutic potential for treatment of TBI.
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Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Encefalite/tratamento farmacológico , Encefalite/etiologia , Exossomos/metabolismo , RNA Longo não Codificante/metabolismo , Regeneração/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Análise por Conglomerados , Modelos Animais de Doenças , Membro Anterior/fisiopatologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Masculino , Transtornos Motores/etiologia , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Equilíbrio Postural/efeitos dos fármacos , RNA Longo não Codificante/genética , Ratos , Ratos Endogâmicos F344 , Regeneração/fisiologia , Fatores de TempoRESUMO
Medically underserved populations suffer disproportionately from disease and poor health, and nursing schools are challenged to prepare nurse practitioner students to effectively care for underserved patients. This article describes one university's endeavor to create and evaluate academic partnerships with HIV/hepatitis C virus primary care clinics in underserved settings. Designated preceptorships and specific preparation of students tailored for this population via online modules were strategies created to increase students' readiness to practice as primary care providers and increase clinical placements for nurse practitioner students. Outcomes include student readiness to practice and student satisfaction with clinics and preceptors.
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Área Carente de Assistência Médica , Profissionais de Enfermagem , Humanos , Preceptoria , Escolas de Enfermagem , Populações VulneráveisRESUMO
We examined the association of mental health staffing and the utilization of primary care/mental health integration (PCMHI) with facility-level variations in adequacy of psychotherapy and antidepressants received by Veterans with new, recurrent, and chronic depression. Greater likelihood of adequate psychotherapy was associated with increased (1) PCMHI utilization by recurrent depression patients (AOR 1.02; 95% CI 1.00, 1.03); and (2) staffing for recurrent (AOR 1.03; 95% CI 1.01, 1.06) and chronic (AOR 1.02; 95% CI 1.00, 1.03) depression patients (p < 0.05). No effects were found for antidepressants. Mental health staffing and PCMHI utilization explained only a small amount of the variance in the adequacy of depression care.
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Antidepressivos/uso terapêutico , Transtorno Depressivo/terapia , Serviços de Saúde Mental/organização & administração , Admissão e Escalonamento de Pessoal/estatística & dados numéricos , Atenção Primária à Saúde/organização & administração , Psicoterapia/estatística & dados numéricos , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Qualidade da Assistência à Saúde , Estados Unidos , United States Department of Veterans AffairsRESUMO
Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 10(6) hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1' dioactadecyl-3-3-3',3'-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen.
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Tecido Adiposo/transplante , Lesões Encefálicas/cirurgia , Transtornos Cognitivos/cirurgia , Transtornos das Habilidades Motoras/cirurgia , Degeneração Neural/cirurgia , Transplante de Células-Tronco/métodos , Tecido Adiposo/citologia , Fatores Etários , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/cirurgia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Células Cultivadas , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Humanos , Infusões Intravenosas , Masculino , Transtornos das Habilidades Motoras/metabolismo , Transtornos das Habilidades Motoras/patologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Ratos , Ratos Endogâmicos F344 , Distribuição Tecidual/fisiologiaRESUMO
Obesity is characterized by adipocyte hyperplasia and hypertrophy. We previously showed that PKCδ expression is dysregulated in obesity (Carter, G., Apostolatos, A., Patel, R., Mathur, A., Cooper, D., Murr, M., and Patel, N. A. (2013) ISRN Obes. 2013, 161345). Using 3T3L1 preadipocytes, we studied adipogenesis in vitro and showed that expression of PKCδ splice variants, PKCδI and PKCδII, have different expression patterns during adipogenesis (Patel, R., Apostolatos, A., Carter, G., Ajmo, J., Gali, M., Cooper, D. R., You, M., Bisht, K. S., and Patel, N. A. (2013) J. Biol. Chem. 288, 26834-26846). Here, we evaluated the role of PKCδI splice variant during adipogenesis. Our results indicate that PKCδI expression level is high in preadipocytes and decreasing PKCδI accelerated terminal differentiation. Our results indicate that PKCδI is required for mitotic clonal expansion of preadipocytes. We next evaluated the splice factor regulating the expression of PKCδI during 3T3L1 adipogenesis. Our results show TRA2B increased PKCδI expression. To investigate the molecular mechanism, we cloned a heterologous splicing PKCδ minigene and showed that inclusion of PKCδ exon 9 is increased by TRA2B. Using mutagenesis and a RNA-immunoprecipitation assay, we evaluated the binding of Tra2ß on PKCδI exon 9 and show that its association is required for PKCδI splicing. These results provide a better understanding of the role of PKCδI in adipogenesis. Determination of this molecular mechanism of alternative splicing presents a novel therapeutic target in the management of obesity and its co-morbidities.
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Ciclo Celular , Regulação da Expressão Gênica , Proteínas Nucleares/metabolismo , Proteína Quinase C-delta/metabolismo , Proteínas de Ligação a RNA/metabolismo , Células 3T3-L1 , Adipócitos/citologia , Adipogenia , Processamento Alternativo , Animais , Apoptose , Diferenciação Celular , Proliferação de Células , Camundongos , Mutação , Fatores de Processamento de Serina-ArgininaRESUMO
BACKGROUND: Lyme disease patients with erythema migrans are said to have post-treatment Lyme disease symptoms (PTLDS) if there is persistence of subjective symptoms for at least 6 months following antibiotic treatment and resolution of the skin lesion. The purpose of this study was to characterize PTLDS in patients with culture-confirmed early Lyme disease followed for >10 years. METHODS: Adult patients with erythema migrans with a positive skin or blood culture for Borrelia burgdorferi were enrolled in a prospective study beginning in 1991 and followed up at 6 months and annually thereafter to determine the long-term outcome of this infection. The genotype of the infecting strain of B. burgdorferi was evaluated in subjects with PTLDS. RESULTS: One hundred twenty-eight subjects with culture-confirmed early Lyme disease, of whom 55% were male, were followed for a mean ± SD of 14.98 ± 2.71 years (median = 15 years; range = 11-20 years). Fourteen (10.9%) were regarded as having possible PTLDS, but only 6 (4.7%) had PTLDS documented at their last study visit. Nine (64.3%) had only a single symptom. None of the 6 with PTLDS at their last visit was considered to be functionally impaired by the symptom(s). PTLDS was not associated with a particular genotype of B. burgdorferi. CONCLUSIONS: PTLDS may persist for >10 years in some patients with culture-confirmed early Lyme disease. Such long-standing symptoms were not associated with functional impairment or a particular strain of B. burgdorferi.
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Borrelia burgdorferi/isolamento & purificação , Eritema/etiologia , Eritema/patologia , Doença de Lyme/tratamento farmacológico , Doença de Lyme/patologia , Adulto , Idoso , Sangue/microbiologia , Borrelia burgdorferi/classificação , Borrelia burgdorferi/genética , Feminino , Genótipo , Humanos , Doença de Lyme/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pele/microbiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Erythema migrans is the most common manifestation of Lyme disease. Recurrences are not uncommon, and although they are usually attributed to reinfection rather than relapse of the original infection, this remains somewhat controversial. We used molecular typing of Borrelia burgdorferi isolates obtained from patients with culture-confirmed episodes of erythema migrans to distinguish between relapse and reinfection. METHODS: We determined the genotype of the gene encoding outer-surface protein C (ospC) of B. burgdorferi strains detected in cultures of skin or blood specimens obtained from patients with consecutive episodes of erythema migrans. After polymerase-chain-reaction amplification, ospC genotyping was performed by means of reverse line-blot analysis or DNA sequencing of the nearly full-length gene. Most strains were further analyzed by determining the genotype according to the 16S-23S ribosomal RNA intergenic spacer type, multilocus sequence typing, or both. Patients received standard courses of antibiotics for erythema migrans. RESULTS: B. burgdorferi isolates obtained from 17 patients who received a diagnosis of erythema migrans between 1991 and 2011 and who had 22 paired episodes of this lesion (initial and second episodes) were available for testing. The ospC genotype was found to be different at each initial and second episode. Apparently identical genotypes were identified on more than one occasion in only one patient, at the first and third episodes, 5 years apart, but different genotypes were identified at the second and fourth episodes. CONCLUSIONS: None of the 22 paired consecutive episodes of erythema migrans were associated with the same strain of B. burgdorferi on culture. Our data show that repeat episodes of erythema migrans in appropriately treated patients were due to reinfection and not relapse. (Funded by the National Institutes of Health and the William and Sylvia Silberstein Foundation.).
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Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Borrelia burgdorferi/genética , Doença de Lyme/microbiologia , Adulto , Borrelia burgdorferi/classificação , Borrelia burgdorferi/isolamento & purificação , DNA Bacteriano/análise , Diagnóstico Diferencial , Genótipo , Humanos , Doença de Lyme/diagnóstico , Recidiva , Análise de Sequência de DNARESUMO
Increased food intake and lack of physical activity results in excess energy stored in adipocytes, and this imbalance contributes to obesity. New adipocytes are required for storage of energy in the white adipose tissue. This process of adipogenesis is widely studied in differentiating 3T3L1 preadipocytes in vitro. We have identified a key signaling kinase, protein kinase C delta (PKCδ), whose alternative splice variant expression is modulated during adipogenesis. We demonstrate that PKCδII splice variant promotes survival in differentiating 3T3L1 cells through the Bcl2 pathway. Here we demonstrate that resveratrol, a naturally occurring polyphenol, increases apoptosis and inhibits adipogenesis along with disruption of PKCδ alternative splicing during 3T3L1 differentiation. Importantly, we have identified a PKCδII splice variant inhibitor. This inhibitor may be a valuable tool with therapeutic implications in obesity.
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Adipogenia , Processamento Alternativo , Apoptose , Proteína Quinase C-delta/antagonistas & inibidores , Estilbenos/química , Células 3T3-L1 , Animais , Diferenciação Celular , Regulação Enzimológica da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polifenóis/química , Proteína Quinase C-delta/genética , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Resveratrol , TransfecçãoRESUMO
Although two-tier testing is standard practice in both the United States and Europe for the serologic diagnosis of Lyme borreliosis (LB), the test kits generally differ. The purpose of this study was to determine if the testing used in the United States will detect LB acquired in Europe and vice versa. Testing was performed on a convenience sample of archived sera from 40 LB patients from Austria and 39 from the United States, using first- and second-tier test kits from both the United States and Europe. The sensitivity of four first-tier tests from Europe and two first-tier tests from the United States was similar. Thus, two-tier testing was compared to the C6 ELISA as the first-tier test, since it is licensed in both the United States and Europe. The sensitivity of C6 two-tier testing with US assays was 9/40 (22.5 % [95 % CI 10.8-38.5 %]) for detection of LB acquired in Europe, and just 20.0 % (95 % CI 2.5-55.6 %) in the ten European patients with neurologic involvement. These results differed significantly from the sensitivity of European C6 two-tier testing that was 70.0 % (95 % CI 53.5-83.4 %) overall (p < 0.001) and 90.0 % (95 % CI 55.5-99.7 %) for the European patients with neurologic manifestations specifically (p = 0.016). In contrast, the sensitivity of European and US C6 two-tier testing was similar for detection of LB acquired in the United States. Two-tier serologic testing with the US test kits may be unsatisfactory for detection of LB acquired in Europe. First-tier testing with an assay such as the C6 ELISA should be considered as a stand-alone diagnostic strategy in such cases.
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Doença de Lyme/diagnóstico , Testes Sorológicos , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Borrelia burgdorferi/imunologia , Ensaio de Imunoadsorção Enzimática , Europa (Continente) , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Doença de Lyme/imunologia , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Testes Sorológicos/normas , Estados UnidosRESUMO
Endothelial function typically precedes clinical manifestations of cardiovascular disease and provides a potential mechanism for the associations observed between cardiovascular disease and sleep quality. This study examined how subjective and objective indicators of sleep quality relate to endothelial function, as measured by brachial artery flow-mediated dilation (FMD). In a clinical research centre, 100 non-shift working adults (mean age: 36 years) completed FMD testing and the Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain the following measures: slow wave sleep, percentage rapid eye movement (REM) sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and follow-up multiple regressions examined how FMD related to subjective (i.e., Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography-derived) indicators of sleep quality. After FMD showed bivariate correlations with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency, further examination with separate regression models indicated that these associations remained significant after adjustments for sex, age, race, hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps < 0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality Index increased (indicating decreased subjective sleep quality) and percentage REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer subjective sleep quality and adverse changes in REM sleep were associated with diminished vasodilation, which could link sleep disturbances to cardiovascular disease.
Assuntos
Percepção/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Sono REM/fisiologia , Vasodilatação/fisiologia , Adulto , Índice de Massa Corporal , Artéria Braquial/patologia , Artéria Braquial/fisiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polissonografia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/psicologia , Fumar , Classe Social , Estresse Psicológico , Adulto JovemRESUMO
BACKGROUND: Prayer is often used to cope with racism-related stress. Little is known about its impact on cardiovascular function. PURPOSE: This study examined how prayer coping relates to cardiovascular reactivity (CVR), post-stress recovery, and affective reactivity in response to racism-related stress. METHODS: African American women (n =81; mean age=20 years) reported their use of prayer coping on the Perceived Racism Scale and completed anger recall and racism recall tasks while undergoing monitoring of systolic and diastolic blood pressure (DBP), heart rate, heart rate variability (HRV), and hemodynamic measures. Prayer coping was examined for associations with CVR, recovery, and affective change scores using general linear models with repeated measures. RESULTS: Higher prayer coping was associated with decreased state stress and DBP reactivity during racism recall (p's<0.05) and with decreased DBP and increased HRV during racism recall recovery(p's<0.05). CONCLUSIONS: Coping with racism by utilizing prayer may have cardiovascular benefits for African American women.