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1.
Behav Sleep Med ; 21(2): 142-149, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35362345

RESUMEN

INTRODUCTION: Poor sleep is common in our society, particularly for African Americans, and is associated with adverse mental and physical health outcomes. Unwanted, intrusive thoughts contribute to sleep disturbances and can be engendered by living in stressful urban environments, which are disproportionately inhabited by African Americans. Studies of other populations have shown that cognitive coping strategies to manage intrusive thoughts vary in their adaptiveness. OBJECTIVE: To examine the relationship between thought control strategies and insomnia severity in urban residing young-adult African Americans. METHOD: Sixty-four young adult African Americans completed a demographic questionnaire, the Thought Control Questionnaire for Insomnia-revised, and the Insomnia Severity Index. RESULTS: There were moderate to strong positive correlations of aggressive suppression, worry, behavioral distraction, and social avoidance with ISI scores. Poor sleepers endorsed greater use of worry and aggressive suppression than good sleepers. Results from a multiple linear regression analysis revealed that aggressive suppression, social avoidance, and behavioral distraction significantly predicted insomnia severity, and aggressive suppression was the strongest predictor in the model. CONCLUSIONS: These results extend findings of aggressive suppression as a correlate of insomnia severity to an urban-residing young adult African American sample. Future research should identify adaptive approaches and the utility of modifying maladaptive strategies.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Adulto Joven , Negro o Afroamericano , Cognición , Ansiedad/psicología , Sueño
2.
PLoS One ; 17(8): e0272311, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35921368

RESUMEN

Western corn rootworm (WCR), Diabrotica virgifera virgifera, LeConte, is an insect pest that poses a significant threat to the productivity of modern agriculture, causing significant economic and crop losses. The development of genetically modified (GM) crops expressing one or more proteins that confer tolerance to specific insect pests, such as WCR, was a historic breakthrough in agricultural biotechnology and continues to serve as an invaluable tool in pest management. Despite this, evolving resistance to existing insect control proteins expressed in current generation GM crops requires continued identification of new proteins with distinct modes of action while retaining targeted insecticidal efficacy. GM crops expressing insecticidal proteins must undergo extensive safety assessments prior to commercialization to ensure that they pose no increased risk to the health of humans or other animals relative to their non-GM conventional counterparts. As part of these safety evaluations, a weight of evidence approach is utilized to assess the safety of the expressed insecticidal proteins to evaluate any potential risk in the context of dietary exposure. This study describes the food and feed safety assessment of Vpb4Da2, a new Bacillus thuringiensis insecticidal protein that confers in planta tolerance to WCR. Vpb4Da2 exhibits structural and functional similarities to other insect control proteins expressed in commercialized GM crops. In addition, the lack of homology to known toxins or allergens, a lack of acute toxicity in mice, inactivation by conditions commonly experienced in the human gut or during cooking/food processing, and the extremely low expected dietary exposure to Vpb4Da2 provide a substantial weight of evidence to demonstrate that the Vpb4Da2 protein poses no indication of a risk to the health of humans or other animals.


Asunto(s)
Bacillus thuringiensis , Escarabajos , Insecticidas , Animales , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Toxinas de Bacillus thuringiensis , Productos Agrícolas/metabolismo , Endotoxinas/metabolismo , Humanos , Resistencia a los Insecticidas , Insecticidas/farmacología , Larva , Ratones , Control Biológico de Vectores , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Zea mays/genética , Zea mays/metabolismo
3.
Addict Behav ; 134: 107399, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35738158

RESUMEN

INTRODUCTION: The present study sought to determine the relationship between self-reported cannabis use dosage in grams per day with (1) objective sleep outcomes: sleep efficiency (SE), sleep onset latency SOL and number of night-time awakenings (NWAK) (2) if objective and subjective sleep measures, using the PSQI, differed between cannabis users and non-cannabis users. METHODS: Our sample included 178 participants, aged 18-35 years. We collected demographic information, cannabis use in dosage per day and frequency of use, depressive symptoms through the CESD, and subjective sleep reports using the PSQI. After the survey assessment, we monitored sleep using the Phillips Actiwatch Spectrum watch for a minimum of 5 nights. RESULTS: The amount of cannabis consumed per day was inversely related to SOL and SE, and positively related to NWAK. After controlling for covariates, regression models were statistically significant for predicting SOL (ß = -0.369, p <.001), SE (ß = -0.232, p <.05) and NWAK, (ß = -0.318, p <.001), indicating cannabis dosage per day is the strongest predictor for the sleep parameters. Subjective sleep measures did not differ from cannabis users versus non-cannabis users. CONCLUSION: Recreational cannabis use is beneficial for SOL but may be detrimental to SE as those who reported increased cannabis use also had more NWAK. Cannabis may be useful for sleep onset, results suggest that increased use does not aid in sleep maintenance.

4.
J Clin Transl Sci ; 6(1): e145, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36756075

RESUMEN

Introduction: The goal of clinical and translational science (CTS) is to fill gaps in medical knowledge toward improving human health. However, one of our most pressing challenges does not reside within the biological map we navigate to find sustainable cures but rather the moral compass to recognize and overcome racial and ethnic injustices that continue to influence our society and hinder diverse research rigor. The Georgetown-Howard Universities Center for Clinical and Translational Science includes an inter-institutional TL1-funded training program for predoctoral/postdoctoral trainees in Translational Biomedical Science (TBS). Methods: In the fall of 2020, the TBS program responded to the national social justice crisis by incorporating a curriculum focused on structural racism in biomedical research. Educational platforms, including movie reviews, Journal Clubs, and other workshops, were threaded throughout the curriculum by ensuring safe spaces to discuss racial and ethnic injustices and providing trainees with practical steps to recognize, approach, and respond to these harmful biases in the CTS. Workshops also focused on why individuals underrepresented in science are vital for addressing and closing gaps in CTS. Results: Paring analysis using REDCap software de-identified participants after invitations were sent and collected in the system to maintain anonymity for pre- and post-analysis. The Likert scale evaluated respondents' understanding of diverse scientific circumstances. The pre/Fall and post/Spring surveys suggested this curriculum was successful at raising institutional awareness of racial and ethnic biases. Evaluating the effectiveness of our program with other training Clinical and Translational Science Awards (CTSA) consortiums will strengthen both the academic and professional TBS programs.

5.
WMJ ; 120(4): 309-312, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35025180

RESUMEN

BACKGROUND: Interprofessional training for patient safety is essential in developing leaders and advocates who are versed in patient safety science and interprofessional collaboration. We describe an interprofessional patient safety fellowship program and its outcomes over 8 years. METHODS: Programmatic data were reviewed and a survey was sent to all program graduates with a known email address (N = 18). RESULTS: Fellows obtained interprofessional skills, knowledge, and methods of patient safety science, as well as preparation as patient safety experts through didactic and experiential training. Program outcomes included sustained quality improvements, publications (n = 8), presentations (n = 29), and recruitment of graduates into quality and safety leadership positions (67%). DISCUSSION: Facilitators and barriers that influenced the success of the fellowship program were noted at institutional and individual levels. The development and sustainability of interprofessional safety training programs depends on concerted efforts by leadership, academic-practice partnerships, and committed faculty and learners.


Asunto(s)
Becas , Seguridad del Paciente , Curriculum , Humanos , Liderazgo , Mejoramiento de la Calidad
6.
Womens Health Rep (New Rochelle) ; 1(1): 451-458, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33786510

RESUMEN

Background: Prior studies have noted patient reluctance to use contraceptive devices that require insertion into their bodies. We sought to better understand this "foreign body" concern, as well as to clarify how women perceive long-acting reversible contraception (LARC) devices compared with other implanted medical devices. Materials and Methods: We performed semistructured qualitative individual interviews with female obstetric/gynecologic patients and probed their opinions regarding LARC devices. Trained coders analyzed interview content using an inductive iterative approach and identified key themes. Results: We found three major themes in our analysis. First, women frequently expressed uncertainty about where in the body intrauterine devices reside and the impact of a foreign body in that space. Second, women expressed discomfort with the invisibility of the device itself and the "set and forget" feature of LARCs. Finally, when asked to consider contraceptive devices in the context of other implantable medical devices, patients highlighted that contraceptive devices are elective and have alternative options. Conclusions: When women express concerns about contraceptive devices "up in them," they are expressing concerns about how these devices interact with their anatomy and the possibilities of harm and failure. These perceived risks of LARCs may not compare favorably with other contraceptive methods that are not foreign bodies. Understanding this perspective improves our ability to participate in shared decision-making.

7.
Dev Dyn ; 249(4): 556-572, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31837063

RESUMEN

BACKGROUND: While many developmentally relevant enhancers act in a modular fashion, there is growing evidence for nonadditive interactions between distinct cis-regulatory enhancers. We investigated if nonautonomous enhancer interactions underlie transcription regulation of the Drosophila segment polarity gene, wingless. RESULTS: We identified two wg enhancers active at the blastoderm stage: wg 3613u, located from -3.6 to -1.3 kb upstream of the wg transcription start site (TSS) and 3046d, located in intron two of the wg gene, from 3.0 to 4.6 kb downstream of the TSS. Genetic experiments confirm that Even Skipped (Eve), Fushi-tarazu (Ftz), Runt, Odd-paired (Opa), Odd-skipped (Odd), and Paired (Prd) contribute to spatially regulated wg expression. Interestingly, there are enhancer specific differences in response to the gain or loss of function of pair-rule gene activity. Although each element recapitulates aspects of wg expression, a composite reporter containing both enhancers more faithfully recapitulates wg regulation than would be predicted from the sum of their individual responses. CONCLUSION: These results suggest that the regulation of wg by pair-rule genes involves nonadditive interactions between distinct cis-regulatory enhancers.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila/embriología , Drosophila/metabolismo , Animales , Blastodermo/embriología , Blastodermo/metabolismo , Tipificación del Cuerpo/genética , Tipificación del Cuerpo/fisiología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Drosophila/genética , Proteínas de Drosophila/genética , Factores de Transcripción Fushi Tarazu/genética , Factores de Transcripción Fushi Tarazu/metabolismo , Regulación del Desarrollo de la Expresión Génica/genética , Regulación del Desarrollo de la Expresión Génica/fisiología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteína Wnt1/genética , Proteína Wnt1/metabolismo
8.
Front Microbiol ; 10: 1533, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31428059

RESUMEN

Erwinia amylovora is a plant pathogen from the Erwiniaceae family and a causative agent of the devastating agricultural disease fire blight. Here we characterize eight lytic bacteriophages of E. amylovora that we isolated from the Wasatch front (Utah, United States) that are highly similar to vB_EamM_Ea35-70 which was isolated in Ontario, Canada. With the genome size ranging from 271 to 275 kb, this is a novel jumbo family of bacteriophages. These jumbo bacteriophages were further characterized through genomic and proteomic comparison, mass spectrometry, host range and burst size. Their proteomes are highly unstudied, with over 200 putative proteins with no known homologs. The production of 27 of these putative proteins was confirmed by mass spectrometry analysis. These bacteriophages appear to be most similar to bacteriophages that infect Pseudomonas and Ralstonia rather than Enterobacteriales bacteria by protein similarity, however, we were only able to detect infection of Erwinia and the closely related strains of Pantoea.

9.
J Psychosom Res ; 121: 88-92, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30955911

RESUMEN

BACKGROUND: Heightened autonomic nervous system (ANS) arousal is a well-established contributor to the effect of stress on adverse cardiovascular health outcomes which disproportionately affect African Americans. ANS arousal is normally attenuated during sleep and compromise of this shift is associated with multiple adverse cardiovascular outcomes. Parasympathetic nervous system (PNS) dominance during sleep can be altered by stress. Racism has been recognized to have many negative health consequences in African Americans. Perceived racism has been linked to ANS activity, however, we are not aware of prior research on racism and nocturnal ANS balance. OBJECTIVE: To examine relationships between perceived racism and nocturnal ANS activity indexed by heart rate variability (HRV) in healthy African American men and women age 18-35. METHODS: Fifty-four participants completed the Perceived Racism Scale and had 24-hour ambulatory electrocardiogram recordings in their homes. Power spectral analysis was used to derive normalized high frequency (nHF) to index PNS activity which was computed by 5-minute epochs during wake and sleep. RESULTS: Endorsement of racism and negative emotional reactions during the past year were inversely related to nHF during time in bed. Multiple regression analysis indicated that negative emotional reactions were a significant predictor of nHF during the sleep period F(2,54) = 4.213, p = .020, R2 = 0.135 (adjusted R2 = 0.103). Relationships during wake were not statistically significant. CONCLUSION: Findings suggest that perseverative thoughts triggered by negative emotional reactions to racism influencing nocturnal ANS activity may be a pathway by which perceived racism affects health. Support: 3UL1TR001409-02S1 and R01HL087995 to Dr. Mellman.


Asunto(s)
Negro o Afroamericano/psicología , Emociones/fisiología , Frecuencia Cardíaca , Percepción/fisiología , Racismo/psicología , Adolescente , Adulto , Nivel de Alerta/fisiología , Sistema Nervioso Autónomo/fisiopatología , Femenino , Humanos , Masculino , Sueño/fisiología , Adulto Joven
10.
Womens Health Issues ; 28(4): 301-305, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29853173

RESUMEN

OBJECTIVE: To compare long-acting reversible contraceptive (LARC) uptake before and after the Affordable Care Act (ACA) contraceptive mandate among women undergoing a first trimester surgical abortion. STUDY DESIGN: We conducted a retrospective chart review of 867 women undergoing a first trimester surgical abortion at an academic gynecology practice between December 2010 and December 2014 (excluding August to December 2012) to evaluate intrauterine device and contraceptive implant uptake before and after the ACA contraceptive mandate. RESULTS: Before the ACA contraceptive mandate, 79% of privately insured women (213 of 271) had full LARC coverage (no out-of-pocket costs) compared with 92% (298 of 324) after the mandate (p < .001). We found no difference in postabortal LARC uptake before and after the ACA in women with private insurance, Medicaid, or overall. Among all women, 46% chose a postabortal LARC method before the mandate as compared with 48% after the mandate (p = .63). Among privately insured women, 45% used a postabortal LARC method before the mandate as compared with 50% after the mandate (p = .25). One-half of privately insured women (268 of 534) with full or partial LARC coverage used a postabortal LARC method compared with 32% of privately insured women (18 of 56) with no LARC coverage after implementation of the ACA contraceptive mandate (p = .01). CONCLUSIONS: Despite the significant increase in full coverage of LARC among privately insured women, there was no change in postabortal LARC use after the ACA. However, privately insured women with full or partial LARC coverage were more likely to use a postabortal LARC method compared with privately insured women with no LARC coverage after the implementation of the ACA contraceptive mandate.


Asunto(s)
Anticoncepción/economía , Anticonceptivos Femeninos/economía , Gastos en Salud , Cobertura del Seguro/economía , Adolescente , Adulto , Anticoncepción/métodos , Femenino , Humanos , Patient Protection and Affordable Care Act , Embarazo , Primer Trimestre del Embarazo , Estudios Retrospectivos , Estados Unidos , Adulto Joven
11.
Sleep ; 41(6)2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29635440

RESUMEN

Study Objectives: Stressful neighborhood environments are known to adversely affect health and contribute to health disparities but underlying mechanisms are not well understood. Healthy sleep can provide a respite from sustained sympathetic nervous system (SNS) activity. Our objective was to evaluate relationships between neighborhood stress and nocturnal and daytime SNS and parasympathetic nervous system (PNS) activity. Methods: Eighty-five urban-residing African Americans (56.5% female; mean age of 23.0) participated. Evaluation included surveys of neighborhood stress and sleep-related vigilance, and continuous electrocardiogram (ECG) and actigraphic recording in participants' homes from which heart rate variability (HRV) analysis for low frequency/high frequency (LF/HF) ratio and normalized high frequency (nHF), as indicators of SNS and PNS activity, respectively, and total sleep time (TST), and wake after sleep onset were derived. Results: All significant relationships with HRV measures were from the sleep period. Neighborhood disorder correlated negatively with nHF (r = -.24, p = .035). There were also significant correlations of HRV indices with sleep duration and sleep fears. Among females, LF/HF correlated with exposure to violence, r = .39, p = .008, and nHF with census tract rates for violent crime (r = -.35, p = .035). In a stepwise regression, TST accounted for the variance contributed by violent crime to nHF in the female participants. Conclusions: Further investigation of relationships between neighborhood environments and SNS/PNS balance during sleep and their consequences, and strategies for mitigating such effects would have implications for health disparities.


Asunto(s)
Sistema Nervioso Autónomo/fisiología , Negro o Afroamericano/psicología , Características de la Residencia , Sueño/fisiología , Estrés Psicológico/fisiopatología , Estrés Psicológico/psicología , Actigrafía/métodos , Adulto , Estudios Transversales , Electrocardiografía/métodos , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estrés Psicológico/diagnóstico , Encuestas y Cuestionarios , Vigilia/fisiología
12.
J Sleep Res ; 26(4): 510-515, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28211138

RESUMEN

Compromised sleep and increased sympathetic nervous system (SNS) activity are implicated in the pathogenesis of, and disparities in, cardiovascular disease. Parasympathetic dominance during sleep may be important for cardiovascular health. Sleep and autonomic balance influence immune activity, which impacts atherogenesis. We evaluated relationships between autonomic balance during sleep and morning levels of the immune activating cytokines, C-reactive protein (CRP) and interleukin (IL)-6. Ninety-four (59 female) young adult African Americans without medical conditions and substance use disorders spent 2 consecutive nights in a clinical research unit for sleep recordings and blood drawing on awakening. Cardiac tracings from the second sleep recording were analysed for heart rate variability (HRV). Body mass index was the only non-HRV measure correlated with cytokine levels. Indicators of SNS activity for the presleep, and first non-rapid eye movement (REM) and REM sleep periods were correlated independently with morning IL-6 levels. Altered autonomic balance during sleep may be a modifiable factor that influences immune activation.


Asunto(s)
Sistema Nervioso Autónomo/fisiología , Negro o Afroamericano , Citocinas/sangre , Oscuridad , Mediadores de Inflamación/sangre , Sueño/inmunología , Sueño/fisiología , Índice de Masa Corporal , Proteína C-Reactiva/análisis , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Interleucina-6/sangre , Masculino , Sueño REM/fisiología , Sistema Nervioso Simpático/fisiología , Factores de Tiempo , Adulto Joven
13.
Physiol Behav ; 164(Pt A): 11-8, 2016 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-27169331

RESUMEN

Posttraumatic stress disorder (PTSD) has been associated with sleep disturbances including alterations in sleep stages and recently, elevated nocturnal autonomic nervous system (ANS) arousal (i.e., dominance of the sympathetic nervous system over the parasympathetic nervous system). Data suggest that sleep contributes to the regulation of ANS activity. In our previous ambulatory heart rate variability (HRV) monitoring study, strong relationships between sleep and nocturnal ANS activity in resilient participants (i.e., individuals who had never had PTSD despite exposure to high-impact trauma) were not seen with PTSD. In this study, we examined the impact of PTSD vs. resilience on ANS activity as a function of sleep stage and time of sleep. Participants (age 18-35) with current PTSD (n=38) and resilience (n=33) completed two overnight polysomnography recordings in a lab setting. The second night electrocardiogram was analyzed for frequency domain HRV parameters and heart rate within rapid-eye-movement (REM) and non-REM (NREM) sleep periods. Results indicated that ANS arousal indexed by HRV was greater during REM compared with NREM sleep and that the REM-NREM difference was greater in the PTSD than in the resilient participants. This effect of PTSD was reduced to non-significance when analyses controlled for REM sleep percentage, which was lower with PTSD. Exploratory analyses revealed that the REM-NREM difference in HRV was correlated with REM sleep percentage in resilient participants, but not with PTSD. In contrast with our data from home settings, the present study did not find increased overall nocturnal ANS arousal with PTSD. Analyses did reveal higher heart rate during initial NREM sleep with more rapid decline over the course of NREM sleep with PTSD compared with resilience. Findings suggest that elevated ANS arousal indexed by heart rate with PTSD is specific to the early part of sleep and possible impairment in regulating ANS activity with PTSD related to REM sleep.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Fases del Sueño/fisiología , Trastornos por Estrés Postraumático/complicaciones , Adolescente , Adulto , Electrocardiografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Polisomnografía , Índices de Gravedad del Trauma , Adulto Joven
14.
Stress ; 19(2): 235-47, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27023221

RESUMEN

Childhood stress and trauma are associated with substance use disorders in adulthood, but the neurological changes that confer increased vulnerability are largely unknown. In this study, maternal separation (MS) stress, restricted to the pre-weaning period, was used as a model to study mechanisms of protracted effects of childhood stress/traumatic experiences on binge drinking and impulsivity. Using an operant self-administration model of binge drinking and a delay discounting assay to measure impulsive-like behavior, we report that early life stress due to MS facilitated acquisition of binge drinking and impulsivity during adulthood in rats. Previous studies have shown heightened levels of corticotropin releasing factor (CRF) after MS, and here, we add that MS increased expression levels of GABA(A) α2 subunit in central stress circuits. To investigate the precise role of these circuits in regulating impulsivity and binge drinking, the CRF1 receptor antagonist antalarmin and the novel GABA(A) α2 subunit ligand 3-PBC were infused into the central amygdala (CeA) and medial prefrontal cortex (mPFC). Antalarmin and 3-PBC at each site markedly reduced impulsivity and produced profound reductions on binge-motivated alcohol drinking, without altering responding for sucrose. Furthermore, whole-cell patch-clamp studies showed that low concentrations of 3-PBC directly reversed the effect of relatively high concentrations of ethanol on α2ß3γ2 GABA(A) receptors, by a benzodiazepine site-independent mechanism. Together, our data provide strong evidence that maternal separation, i.e. early life stress, is a risk factor for binge drinking, and is linked to impulsivity, another key risk factor for excessive alcohol drinking. We further show that pharmacological manipulation of CRF and GABA receptor signaling is effective to reverse binge drinking and impulsive-like behavior in MS rats. These results provide novel insights into the role of the brain stress systems in the development of impulsivity and excessive alcohol consumption.


Asunto(s)
Consumo de Bebidas Alcohólicas/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Conducta Impulsiva/fisiología , Privación Materna , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Receptores de GABA-A/metabolismo , Estrés Psicológico/metabolismo , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/metabolismo , Animales , Condicionamiento Operante/efectos de los fármacos , Etanol/administración & dosificación , Femenino , Masculino , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Pirimidinas/farmacología , Pirroles/farmacología , Ratas , Ratas Sprague-Dawley , Factores de Riesgo , Autoadministración , Vitamina B 12/análogos & derivados
15.
Neuropsychopharmacology ; 40(6): 1549-59, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25567426

RESUMEN

Alcohol dependence is a complex disorder that initiates with episodes of excessive alcohol drinking known as binge drinking. It has a 50-60% risk contribution from inherited susceptibility genes; however, their exact identity and function are still poorly understood. We report that alcohol-preferring P rats have innately elevated levels of Toll-like receptor 4 (TLR4) and monocyte chemotactic protein-1 (MCP-1) that colocalize in neurons from the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA). To examine the potential role of a TLR4/MCP-1 signal, we used Herpes Simplex Virus (HSV) vectors (amplicons) that retain in vivo neurotropism. Infusion of amplicons for TLR4 or MCP-1 siRNA into the CeA or VTA from the P rats inhibited target gene expression and blunted binge drinking. A similarly delivered amplicon for scrambled siRNA did not inhibit TLR4 or MCP-1 expression nor reduce binge drinking, identifying a neuronal TLR4/MCP-1 signal that regulates the initiation of voluntary alcohol self-administration. The signal was sustained during alcohol drinking by increased expression of corticotropin-releasing factor and its feedback regulation of TLR4 expression, likely contributing to the transition to alcohol dependence.


Asunto(s)
Consumo de Bebidas Alcohólicas/metabolismo , Núcleo Amigdalino Central/metabolismo , Quimiocina CCL2/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Neuronas/metabolismo , Receptor Toll-Like 4/metabolismo , Área Tegmental Ventral/metabolismo , Animales , Consumo Excesivo de Bebidas Alcohólicas/metabolismo , Línea Celular , Núcleo Amigdalino Central/efectos de los fármacos , Depresores del Sistema Nervioso Central/administración & dosificación , Quimiocina CCL2/genética , Etanol/administración & dosificación , Predisposición Genética a la Enfermedad , Vectores Genéticos , Ratones , ARN Interferente Pequeño , Ratas , Autoadministración , Simplexvirus/genética , Receptor Toll-Like 4/genética , Área Tegmental Ventral/efectos de los fármacos
16.
Nature ; 512(7515): 445-8, 2014 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-25164755

RESUMEN

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.


Asunto(s)
Caenorhabditis elegans/genética , Drosophila melanogaster/genética , Perfilación de la Expresión Génica , Transcriptoma/genética , Animales , Caenorhabditis elegans/embriología , Caenorhabditis elegans/crecimiento & desarrollo , Cromatina/genética , Análisis por Conglomerados , Drosophila melanogaster/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica/genética , Histonas/metabolismo , Humanos , Larva/genética , Larva/crecimiento & desarrollo , Modelos Genéticos , Anotación de Secuencia Molecular , Regiones Promotoras Genéticas/genética , Pupa/genética , Pupa/crecimiento & desarrollo , ARN no Traducido/genética , Análisis de Secuencia de ARN
17.
J Shoulder Elbow Surg ; 22(3): 396-402, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22944077

RESUMEN

BACKGROUND: Controversy exists regarding the optimal technique of subscapularis mobilization during shoulder arthroplasty. The purpose of this study was to compare healing rates and subscapularis fatty infiltration in patients undergoing a lesser tuberosity osteotomy (LTO) versus subscapularis peel for exposure during shoulder arthroplasty. MATERIALS AND METHODS: Eighty-seven patients, with a mean age of 67.8 ± 10.9 years, undergoing shoulder arthroplasty, were randomized to receive either an LTO (n = 43) or peel (n = 44). Computed tomography scans were conducted preoperatively and at 12 months postoperatively. Outcome variables included healing rates and subscapularis Goutallier fatty infiltration grade, as well as subscapularis strength and Western Ontario Osteoarthritis of the Shoulder Index and American Shoulder and Elbow Surgeons outcome scores. RESULTS: Computed tomography imaging was available in 91% (n = 79) of the cohort. The healing rates for the peel (100%) and for the LTO (95%) did not differ significantly (P = .493). Preoperatively, the mean fatty infiltration grade for the peel (mean, 0.53) was not significantly different (P = .925) from the LTO (mean, 0.54). Postoperatively, the Goutallier mean fatty infiltration grade for the peel (mean, 0.95) did not differ significantly (P = .803) from the LTO (mean, 0.9). A significant increase in subscapularis fatty infiltration grade occurred postoperatively from the preoperative status (peel, P = .003; LTO, P = .0002). No statistically significant associations were observed between postoperative fatty infiltration grades and subscapularis strength, Western Ontario Osteoarthritis of the Shoulder Index scores, or American Shoulder and Elbow Surgeons scores. DISCUSSION: No statistically significant differences were observed in the healing rates or subscapularis fatty infiltration grades between the peel and the LTO. This trial does not show any clear difference in radiologic and clinical outcomes of one subscapularis management technique over the other.


Asunto(s)
Artroplastia de Reemplazo/métodos , Osteoartritis/cirugía , Articulación del Hombro/diagnóstico por imagen , Tendones/diagnóstico por imagen , Cicatrización de Heridas , Tejido Adiposo/diagnóstico por imagen , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Músculo Esquelético/cirugía , Osteotomía , Recuperación de la Función , Tendones/patología , Tendones/cirugía , Tomografía Computarizada por Rayos X
18.
Nature ; 489(7414): 101-8, 2012 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-22955620

RESUMEN

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.


Asunto(s)
ADN/genética , Enciclopedias como Asunto , Genoma Humano/genética , Anotación de Secuencia Molecular , Secuencias Reguladoras de Ácidos Nucleicos/genética , Transcripción Genética/genética , Transcriptoma/genética , Alelos , Línea Celular , ADN Intergénico/genética , Elementos de Facilitación Genéticos , Exones/genética , Perfilación de la Expresión Génica , Genes/genética , Genómica , Humanos , Poliadenilación/genética , Isoformas de Proteínas/genética , ARN/biosíntesis , ARN/genética , Edición de ARN/genética , Empalme del ARN/genética , Secuencias Repetitivas de Ácidos Nucleicos/genética , Análisis de Secuencia de ARN
19.
J Bone Joint Surg Am ; 94(14): 1249-57, 2012 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-22810395

RESUMEN

BACKGROUND: Controversy exists regarding the optimal technique for arthroscopic rotator cuff repair. The purpose of this multicenter, randomized, double-blind controlled study was to compare the functional outcomes and healing rates after use of single-row and double-row suture techniques for repair of the rotator cuff. METHODS: Ninety patients undergoing arthroscopic rotator cuff repair were randomized to receive either a single-row or a double-row repair. The primary objective was to compare the Western Ontario rotator cuff index (WORC) score at twenty-four months. Secondary objectives included comparison of the constant and american shoulder and elbow surgeons (ASES) scores and strength between groups. Anatomical outcomes were assessed with magnetic resonance imaging (MRI) or ultrasonography to determine the postoperative healing rates. RESULTS: Baseline demographic data including age (p = 0.29), sex (p = 0.68), affected side (p = 0.39), and rotator cuff tear size (p = 0.28) did not differ between groups. The WORC score did not differ significantly between groups at any time point (p = 0.48 at baseline, p = 0.089 at three months, p = 0.52 at six months, p = 0.83 at twelve months, and p = 0.60 at twenty-four months). The WORC score at each postoperative time point was significantly better than the baseline value. The Constant score, ASES score, and strength did not differ significantly between groups at any time point. Logistic regression analysis demonstrated that a smaller initial tear size and double-row fixation were associated with higher healing rates. CONCLUSIONS: No significant differences in functional or quality-of-life outcomes were identified between single-row and double-row fixation techniques. A smaller initial tear size and a double-row fixation technique were associated with higher healing rates as assessed with ultrasonography or MRI. LEVEL OF EVIDENCE: Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Lesiones del Manguito de los Rotadores , Manguito de los Rotadores/cirugía , Técnicas de Sutura , Adulto , Anciano , Canadá , Método Doble Ciego , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Calidad de Vida , Resistencia a la Tracción
20.
J Bone Joint Surg Am ; 94(24): 2239-46, 2012 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-23318614

RESUMEN

BACKGROUND: Controversy exists regarding the optimal technique of subscapularis tendon mobilization during shoulder arthroplasty. The purpose of the present randomized double-blind study was to compare two of these techniques-lesser tuberosity osteotomy and subscapularis peel-with regard to muscle strength and functional outcomes. METHODS: Patients undergoing shoulder arthroplasty were randomized to undergo either a lesser tuberosity osteotomy or a subscapularis peel. The primary outcome was subscapularis muscle strength as measured with an electronic handheld dynamometer at twenty-four months postoperatively. Secondary outcomes included the Western Ontario Osteoarthritis of the Shoulder Index and American Shoulder and Elbow Surgeons scores. A sample size calculation determined that eighty-six patients provided 90% power with a 0.79 effect size to detect a significant difference between groups. RESULTS: Forty-three patients were allocated to subscapularis osteotomy, and forty-four patients were allocated to subscapularis peel. Eighty-three percent of the study cohort returned for the twenty-four-month follow-up. The primary outcome of subscapularis muscle strength at twenty-four months revealed no significant difference (p = 0.131) between the lesser tuberosity osteotomy group (mean [and standard deviation], 4.4 ± 2.9 kg) and the subscapularis peel group (mean, 5.5 ± 2.6 kg). Comparison of secondary outcomes, including the Western Ontario Osteoarthritis of the Shoulder Index and American Shoulder and Elbow Surgeons scores, demonstrated no significant differences between groups at any time point. Compared with baseline measures, mean subscapularis muscle strength, Western Ontario Osteoarthritis of the Shoulder Index score, and American Shoulder and Elbow Surgeons score all improved significantly in both groups at twenty-four months (p < 0.001). DISCUSSION: No significant differences in the primary or secondary outcomes of function were identified between the lesser tuberosity osteotomy group and the subscapularis peel group. For the parameters investigated, this trial does not demonstrate any clear advantage of one subscapularis treatment technique over the other.


Asunto(s)
Artroplastia de Reemplazo/métodos , Osteoartritis/cirugía , Osteotomía/métodos , Articulación del Hombro/cirugía , Tendones/cirugía , Anciano , Placas Óseas , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Masculino , Fuerza Muscular/fisiología , Técnicas de Sutura , Resultado del Tratamiento
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