14 resultados para Mental retardation facilities

em Duke University


Relevância:

80.00% 80.00%

Publicador:

Resumo:

Angelman syndrome (AS) is a neurobehavioral disorder associated with mental retardation, absence of language development, characteristic electroencephalography (EEG) abnormalities and epilepsy, happy disposition, movement or balance disorders, and autistic behaviors. The molecular defects underlying AS are heterogeneous, including large maternal deletions of chromosome 15q11-q13 (70%), paternal uniparental disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%). Although patients with UBE3A mutations have a wide spectrum of neurological phenotypes, their features are usually milder than AS patients with deletions of 15q11-q13. Using a chromosomal engineering strategy, we generated mutant mice with a 1.6-Mb chromosomal deletion from Ube3a to Gabrb3, which inactivated the Ube3a and Gabrb3 genes and deleted the Atp10a gene. Homozygous deletion mutant mice died in the perinatal period due to a cleft palate resulting from the null mutation in Gabrb3 gene. Mice with a maternal deletion (m-/p+) were viable and did not have any obvious developmental defects. Expression analysis of the maternal and paternal deletion mice confirmed that the Ube3a gene is maternally expressed in brain, and showed that the Atp10a and Gabrb3 genes are biallelically expressed in all brain sub-regions studied. Maternal (m-/p+), but not paternal (m+/p-), deletion mice had increased spontaneous seizure activity and abnormal EEG. Extensive behavioral analyses revealed significant impairment in motor function, learning and memory tasks, and anxiety-related measures assayed in the light-dark box in maternal deletion but not paternal deletion mice. Ultrasonic vocalization (USV) recording in newborns revealed that maternal deletion pups emitted significantly more USVs than wild-type littermates. The increased USV in maternal deletion mice suggests abnormal signaling behavior between mothers and pups that may reflect abnormal communication behaviors in human AS patients. Thus, mutant mice with a maternal deletion from Ube3a to Gabrb3 provide an AS mouse model that is molecularly more similar to the contiguous gene deletion form of AS in humans than mice with Ube3a mutation alone. These mice will be valuable for future comparative studies to mice with maternal deficiency of Ube3a alone.

Relevância:

80.00% 80.00%

Publicador:

Resumo:

Gliomagenesis is driven by a complex network of genetic alterations and while the glioma genome has been a focus of investigation for many years; critical gaps in our knowledge of this disease remain. The identification of novel molecular biomarkers remains a focus of the greater cancer community as a method to improve the consistency and accuracy of pathological diagnosis. In addition, novel molecular biomarkers are drastically needed for the identification of targets that may ultimately result in novel therapeutics aimed at improving glioma treatment. Through the identification of new biomarkers, laboratories will focus future studies on the molecular mechanisms that underlie glioma development. Here, we report a series of genomic analyses identifying novel molecular biomarkers in multiple histopathological subtypes of glioma and refine the classification of malignant gliomas. We have completed a large scale analysis of the WHO grade II-III astrocytoma exome and report frequent mutations in the chromatin modifier, alpha thalassemia mental retardation x-linked (ATRX), isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), and mutations in tumor protein 53 (TP53) as the most frequent genetic mutations in low grade astrocytomas. Furthermore, by analyzing the status of recurrently mutated genes in 363 brain tumors, we establish that highly recurrent gene mutational signatures are an effective tool in stratifying homogeneous patient populations into distinct groups with varying outcomes, thereby capable of predicting prognosis. Next, we have established mutations in the promoter of telomerase reverse transcriptase (TERT) as a frequent genetic event in gliomas and in tissues with low rates of self renewal. We identify TERT promoter mutations as the most frequently mutated gene in primary glioblastoma. Additionally, we show that TERT promoter mutations in combination with IDH1 and IDH2 mutations are able to delineate distinct clinical tumor cohorts and are capable of predicting median overall survival more effectively than standard histopathological diagnosis alone. Taken together, these data advance our understanding of the genetic alterations that underlie the transformation of glial cells into neoplasms and we provide novel genetic biomarkers and multi – gene mutational signatures that can be utilized to refine the classification of malignant gliomas and provide opportunity for improved diagnosis.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

BACKGROUND: Most information about the lifetime prevalence of mental disorders comes from retrospective surveys, but how much these surveys have undercounted due to recall failure is unknown. We compared results from a prospective study with those from retrospective studies. METHOD: The representative 1972-1973 Dunedin New Zealand birth cohort (n=1037) was followed to age 32 years with 96% retention, and compared to the national New Zealand Mental Health Survey (NZMHS) and two US National Comorbidity Surveys (NCS and NCS-R). Measures were research diagnoses of anxiety, depression, alcohol dependence and cannabis dependence from ages 18 to 32 years. RESULTS: The prevalence of lifetime disorder to age 32 was approximately doubled in prospective as compared to retrospective data for all four disorder types. Moreover, across disorders, prospective measurement yielded a mean past-year-to-lifetime ratio of 38% whereas retrospective measurement yielded higher mean past-year-to-lifetime ratios of 57% (NZMHS, NCS-R) and 65% (NCS). CONCLUSIONS: Prospective longitudinal studies complement retrospective surveys by providing unique information about lifetime prevalence. The experience of at least one episode of DSM-defined disorder during a lifetime may be far more common in the population than previously thought. Research should ask what this means for etiological theory, construct validity of the DSM approach, public perception of stigma, estimates of the burden of disease and public health policy.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

BACKGROUND: The proportion of births attended by skilled health personnel is one of two indicators used to measure progress towards Millennium Development Goal 5, which aims for a 75% reduction in global maternal mortality ratios by 2015. Rwanda has one of the highest maternal mortality ratios in the world, estimated between 249-584 maternal deaths per 100,000 live births. The objectives of this study were to quantify secular trends in health facility delivery and to identify factors that affect the uptake of intrapartum healthcare services among women living in rural villages in Bugesera District, Eastern Province, Rwanda. METHODS: Using census data and probability proportional to size cluster sampling methodology, 30 villages were selected for community-based, cross-sectional surveys of women aged 18-50 who had given birth in the previous three years. Complete obstetric histories and detailed demographic data were elicited from respondents using iPad technology. Geospatial coordinates were used to calculate the path distances between each village and its designated health center and district hospital. Bivariate and multivariate logistic regressions were used to identify factors associated with delivery in health facilities. RESULTS: Analysis of 3106 lifetime deliveries from 859 respondents shows a sharp increase in the percentage of health facility deliveries in recent years. Delivering a penultimate baby at a health facility (OR = 4.681 [3.204 - 6.839]), possessing health insurance (OR = 3.812 [1.795 - 8.097]), managing household finances (OR = 1.897 [1.046 - 3.439]), attending more antenatal care visits (OR = 1.567 [1.163 - 2.112]), delivering more recently (OR = 1.438 [1.120 - 1.847] annually), and living closer to a health center (OR = 0.909 [0.846 - 0.976] per km) were independently associated with facility delivery. CONCLUSIONS: The strongest correlates of facility-based delivery in Bugesera District include previous delivery at a health facility, possession of health insurance, greater financial autonomy, more recent interactions with the health system, and proximity to a health center. Recent structural interventions in Rwanda, including the rapid scale-up of community-financed health insurance, likely contributed to the dramatic improvement in the health facility delivery rate observed in our study.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

UNLABELLED: BACKGROUND: Primary care, an essential determinant of health system equity, efficiency, and effectiveness, is threatened by inadequate supply and distribution of the provider workforce. The Veterans Health Administration (VHA) has been a frontrunner in the use of nurse practitioners (NPs) and physician assistants (PAs). Evaluation of the roles and impact of NPs and PAs in the VHA is critical to ensuring optimal care for veterans and may inform best practices for use of PAs and NPs in other settings around the world. The purpose of this study was to characterize the use of NPs and PAs in VHA primary care and to examine whether their patients and patient care activities were, on average, less medically complex than those of physicians. METHODS: This is a retrospective cross-sectional analysis of administrative data from VHA primary care encounters between 2005 and 2010. Patient and patient encounter characteristics were compared across provider types (PA, NP, and physician). RESULTS: NPs and PAs attend about 30% of all VHA primary care encounters. NPs, PAs, and physicians fill similar roles in VHA primary care, but patients of PAs and NPs are slightly less complex than those of physicians, and PAs attend a higher proportion of visits for the purpose of determining eligibility for benefits. CONCLUSIONS: This study demonstrates that a highly successful nationwide primary care system relies on NPs and PAs to provide over one quarter of primary care visits, and that these visits are similar to those of physicians with regard to patient and encounter characteristics. These findings can inform health workforce solutions to physician shortages in the USA and around the world. Future research should compare the quality and costs associated with various combinations of providers and allocations of patient care work, and should elucidate the approaches that maximize quality and efficiency.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The rivalry between the men's basketball teams of Duke University and the University of North Carolina-Chapel Hill (UNC) is one of the most storied traditions in college sports. A subculture of students at each university form social bonds with fellow fans, develop expertise in college basketball rules, team statistics, and individual players, and self-identify as a member of a fan group. The present study capitalized on the high personal investment of these fans and the strong affective tenor of a Duke-UNC basketball game to examine the neural correlates of emotional memory retrieval for a complex sporting event. Male fans watched a competitive, archived game in a social setting. During a subsequent functional magnetic resonance imaging session, participants viewed video clips depicting individual plays of the game that ended with the ball being released toward the basket. For each play, participants recalled whether or not the shot went into the basket. Hemodynamic signal changes time locked to correct memory decisions were analyzed as a function of emotional intensity and valence, according to the fan's perspective. Results showed intensity-modulated retrieval activity in midline cortical structures, sensorimotor cortex, the striatum, and the medial temporal lobe, including the amygdala. Positively valent memories specifically recruited processing in dorsal frontoparietal regions, and additional activity in the insula and medial temporal lobe for positively valent shots recalled with high confidence. This novel paradigm reveals how brain regions implicated in emotion, memory retrieval, visuomotor imagery, and social cognition contribute to the recollection of specific plays in the mind of a sports fan.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

All of us are taxed with juggling our inner mental lives with immediate external task demands. For many years, the temporary maintenance of internal information was considered to be handled by a dedicated working memory (WM) system. It has recently become increasingly clear, however, that such short-term internal activation interacts with attention focused on external stimuli. It is unclear, however, exactly why these two interact, at what level of processing, and to what degree. Because our internal maintenance and external attention processes co-occur with one another, the manner of their interaction has vast implications for functioning in daily life. The work described here has employed original experimental paradigms combining WM and attention task elements, functional magnetic resonance imaging (fMRI) to illuminate the associated neural processes, and transcranial magnetic stimulation (TMS) to clarify the causal substrates of attentional brain function. These studies have examined a mechanism that might explain why (and when) the content of WM can involuntarily capture visual attention. They have, furthermore, tested whether fundamental attentional selection processes operate within WM, and whether they are reciprocal with attention. Finally, they have illuminated the neural consequences of competing attentional demands. The findings indicate that WM shares representations, operating principles, and cognitive resources with externally-oriented attention.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

People living with HIV (PLWH) experience greater psychological distress than the general population. Evidence from high-incomes countries suggests that psychological interventions for PLWH can improve mental health symptoms, quality of life, and HIV care engagement. However, little is known about the effectiveness of mental health interventions for PLWH in low and middle-income countries (LMICs), where the large majority of PLWH reside. This systematized review aims to synthesize findings from mental health intervention trials with PLWH in LMICs to inform the delivery of mental health services in these settings. A systematic search strategy was undertaken to identify peer-reviewed published papers of intervention trials addressing negative psychological states or disorders (e.g., depression, anxiety) among PLWH in LMIC settings. Search results were assessed against pre-established inclusion and exclusion criteria. Data from papers meeting criteria were extracted for synthesis. Twenty-six papers, published between 2000 and 2014, describing 22 unique interventions were identified. Trials were implemented in sub-Saharan Africa (n=13), Asia (n=7), and the Middle East (n=2), and addressed mental health using a variety of approaches, including cognitive-behavioral (n=18), family-level (n=2), and pharmacological (n=2) treatments. Four randomized controlled trials reported significant intervention effects in mental health outcomes, and eleven preliminary studies demonstrated promising findings. Among the limited mental health intervention trials with PLWH in LMICs, few demonstrated efficacy. Mental health interventions for PLWH in LMICs must be further developed and adapted for resource-limited settings to improve effectiveness.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

BACKGROUND: The HIV/AIDS epidemic is a significant public health concern in North Carolina, and previous research has pointed to elevated mental health distress and substance use among HIV-infected populations, which may impact patients' adherence to medications. The aims of this study were to describe the prevalence of mental health and substance use issues among patients of a North Carolina HIV clinic, to examine differences by demographic characteristics, and to examine factors associated with suboptimal adherence to HIV medications. METHODS: This study was a secondary analysis of clinical data routinely collected through a health behavior questionnaire at a large HIV clinic in North Carolina. We analyzed data collected from February 2011 to August 2012. RESULTS: The sample included 1,398 patients. Overall, 12.2% of patients endorsed current symptomology indicative of moderate or severe levels of depression, and 38.6% reported receiving a psychiatric diagnosis at some point in their life. Additionally, 19.1% had indications of current problematic drinking, and 8.2% reported problematic drug use. Nearly one-quarter (22.1%) reported suboptimal adherence to HIV medications. Factors associated with poor adherence included racial/ethnic minority, age less than 35 years, and indications of moderate or severe depression. LIMITATIONS: The questionnaire was not completed systematically in the clinic, which may limit generalizability, and self-reported measures may have introduced social desirability bias. CONCLUSION: Patients were willing to disclose mental health distress, substance use, and suboptimal medication adherence to providers, which highlights the importance of routinely assessing these behaviors during clinic visits. Our findings suggest that treating depression may be an effective strategy to improve adherence to HIV medications.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

BACKGROUND: Accurate detection of persons in need of mental healthcare is crucial to reduce the treatment gap between psychiatric burden and service use in low- and middle-income (LAMI) countries. AIMS: To evaluate the accuracy of a community-based proactive case-finding strategy (Community Informant Detection Tool, CIDT), involving pictorial vignettes, designed to initiate pathways for mental health treatment in primary care settings. METHOD: Community informants using the CIDT identified screen positive (n = 110) and negative persons (n = 85). Participants were then administered the Composite International Diagnostic Interview (CIDI). RESULTS: The CIDT has a positive predictive value of 0.64 (0.68 for adults only) and a negative predictive value of 0.93 (0.91 for adults only). CONCLUSIONS: The CIDT has promising detection properties for psychiatric caseness. Further research should investigate its potential to increase demand for, and access to, mental health services.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The process of determining the level of care and specific postacute care facility for stroke patients has not been adequately studied. The objective of this study was to better understand the factors that influence postacute care decisions by surveying stroke discharge planners. Requests were sent to discharge planners at 471 hospitals in the Northeast United States to complete an online survey regarding the factors impacting the selection of postacute care. Seventy-seven (16%) discharge planners completed the online survey. Respondents were mainly nurses and social workers and 73% reported ≥20 years healthcare experience. Patients and families were found to be significantly more influential than physicians (P < 0.001) and other clinicians (P = 0.04) in influencing postdischarge care. Other clinicians were significantly more influential than physicians (P < 0.001). Insurance and quality of postacute care were the factors likely to most affect the selection of postacute care facility. Insurance was also identified as the greatest barrier in the selection of level of postacute care (70%; P < 0.001) and specific postacute care facility (46%; P = 0.02). More than half reported that pressure to discharge patients quickly impacts a patients' final destination. Nonclinical factors are perceived by discharge planners to have a major influence on postacute stroke care decision making.