327 research outputs found

    The Role of Maternal Depression on Treatment Outcome for Children with Externalizing Behavior Problems

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    Studies have shown that, on average, Parent Management Training combined with cognitive-behavioral therapy decreases childrenā€™s externalizing behavior, but some children do not improve through treatment. The current study aimed to examine the role of maternal depression in understanding this variability in treatment outcome. Children with externalizing behavioral problems and their parents were recruited from combined Parent Management Training and Cognitive-Behavioral programs in ā€œreal-worldā€ clinical settings. At pre- and post treatment, maternal depression and childrenā€™s externalizing behavior were assessed. Results showed that treatment was less effective for children of depressed mothers compared to non-depressed mothers and that improvements in maternal depression were associated with improvements in childrenā€™s externalizing behavior. These findings suggest that treatment programs for children with externalizing problems may be able to improve outcomes if maternal depression is a target of intervention

    Alternative initiation and splicing in dicer gene expression in human breast cells

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    INTRODUCTION: Dicer is a ribonuclease that mediates RNA interference both at the transcriptional and the post-transcriptional levels. Human dicer gene expression is regulated in different tissues. Dicer is responsible for the synthesis of microRNAs and short temporal (st)RNAs that regulate the expression of many genes. Thus, understanding the control of the expression of the dicer gene is essential for the appreciation of double-stranded (ds)RNA-mediated pathways of gene expression. Human dicer mRNA has many upstream open reading frames (uORFs) at the 5'-leader sequences (the nucleotide sequence between the 5'-end and the start codon of the major ORF), and we studied whether these elements at the 5'-leader sequences regulate the expression of the dicer gene. METHOD: We determined the 5'-leader sequences of the dicer mRNAs in human breast cells by 5'-RACE and S1-nuclease protection analysis. We have analyzed the functions of the 5'-leader variants by reporter gene expression in vitro and in vivo. RESULTS: We found that the dicer transcripts in human breast cells vary in the sequence of their 5'-leader sequences, and that alternative promoter selection along with alternative splicing of the 5'-terminal exons apparently generate these variations. The breast cell has at least two predominant forms of dicer mRNAs, one of which has an additional 110 nucleotides at the 5'-end. Sequence comparison revealed that the first 80 nucleotides of these mRNA isoforms are encoded by a new exon located approximately 16 kb upstream of the reported start site. There are 30 extra nucleotides added to the previously reported exon 1. The human breast cells studied predominantly express two 5'-leader variants of dicer mRNAs, one with the exons 2 and 3 (long form) and the other without them (short form). By reporter gene expression analysis we found that the exon 2 and 3 sequences at the 5'-leader sequences are greatly inhibitory for the translation of the mRNA into protein. CONCLUSION: Dicer gene expression in human breast cells is regulated by alternative promoter selection to alter the length and composition of the 5'-leader sequence of its mRNA. Furthermore, alternative splicing of its exon 2 and 3 sequences of their pre-mRNA creates a more translationally competent mRNA in these cells

    Health equity issues at the local level: Socio-geography, access, and health outcomes in the service area of the HĆ“pital Albert Schweitzer-Haiti

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    <p>Abstract</p> <p>Background</p> <p>Although health equity issues at regional, national and international levels are receiving increasing attention, health equity issues at the local level have been virtually overlooked. Here, we describe here a comprehensive equity assessment carried out by the HĆ“pital Albert Schweitzer-Haiti (HAS) in 2003. HAS has been operating health and development programs in the Artibonite Valley of Haiti for 50 years.</p> <p>Methods</p> <p>We reviewed all available information arising from a comprehensive evaluation of the programs of HAS carried out in 1999 and 2000. As part of this evaluation, two demographic and health surveys were carried out. We carried out exit interviews with clients receiving primary health care, observations within health facilities, interviews with households related to quality of care, and focus group discussions with community-based health workers. A special study was carried out in 2003 to assess factors determining the use of prenatal care services. Finally, selected findings were obtained from the HAS information system.</p> <p>Results</p> <p>We found markedly reduced access to health services in the peripheral mountainous areas compared to the central plains. The quality of services was more deficient and the coverage of key services was lower in the mountains. Finally, health status, as measured by under-five mortality rates and levels of childhood malnutrition, was also worse in the mountains.</p> <p>Conclusion</p> <p>These findings indicate that local health programs need to give attention to monitoring the health status as well as the quality and coverage of basic services among marginalized groups within the program service area. Health inequities will not be overcome until such monitoring occurs and leaders of health programs ensure that inequities identified are addressed in the local programming of activities. It is quite likely that, within relatively small geographic areas in resource-poor settings around the world, similar, if not even greater, levels of health inequities exist. These inequities need to be measured and addressed in order for health programs to achieve equity and maximum improvement in health status within the population.</p

    Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production

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    Despite recent therapeutic advancements, multiple myeloma (MM) remains incurable and new therapies are needed, especially for the treatment of elderly and relapsed/refractory patients. We have screened a panel of 100 off-patent licensed oral drugs for anti-myeloma activity and identified niclosamide, an anti-helminthic. Niclosamide, at clinically achievable non-toxic concentrations, killed MM cell lines and primary MM cells as efficiently as or better than standard chemotherapy and existing anti-myeloma drugs individually or in combinations, with little impact on normal donor cells. Cell death was associated with markers of both apoptosis and autophagy. Importantly, niclosamide rapidly reduced free light chain (FLC) production by MM cell lines and primary MM. FLCs are a major cause of renal impairment in MM patients and light chain amyloid and FLC reduction is associated with reversal of tissue damage. Our data indicate that niclosamides anti-MM activity was mediated through the mitochondria with rapid loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation and production of mitochondrial superoxide. Niclosamide also modulated the nuclear factor-ĪŗB and STAT3 pathways in MM cells. In conclusion, our data indicate that MM cells can be selectively targeted using niclosamide while also reducing FLC secretion. Importantly, niclosamide is widely used at these concentrations with minimal toxicity

    Aerobic training protects cardiac function during advancing age: a meta-analysis of four decades of controlled studies

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    In contrast to younger athletes, there is comparatively less literature examining cardiac structure and function in older athletes. However, a progressive accumulation of studies during the past four decades offers a body of literature worthy of systematic scrutiny. We conducted a systematic review, meta-analysis and meta-regression of controlled echocardiography studies comparing left ventricular (LV) structure and function in aerobically trained older athletes (>ā€‰45Ā years) with age-matched untrained controls, in addition to investigating the influence of chronological age. statistic. , 95% CI 0.05-1.86, pā€‰=ā€‰0.04). Meta-regression for chronological age identified that athlete-control differences, in the main, are maintained during advancing age. Athletic older men have larger cardiac dimensions and enjoy more favourable cardiac function than healthy, non-athletic counterparts. Notably, the athlete groups maintain these effects during chronological ageing

    Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

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    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Childā€“Pugh score B or C) and a score of >2. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received

    Perinatal and Socioeconomic Risk Factors for Variable and Persistent Cognitive Delay at 24 and 48Ā Months of Age in a National Sample

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    The objective of this paper is to examine patterns of cognitive delay at 24 and 48 months and quantify the effects of perinatal and sociodemographic risk factors on persistent and variable cognitive delay. Using data from 7,200 children in the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B), multiple logistic regression models identified significant predictors of low cognitive functioning at 24 and 48Ā months. Additional multiple logistic models predicting cognitive delay at 48Ā months were estimated separately for children with and without delay at 24Ā months. Of the nearly 1,000 children delayed at 24Ā months, 24.2% remained delayed by 48Ā months; 7.9% of the children not delayed at 24Ā months exhibited delay at 48Ā months. Low and very low birthweight increased cognitive delay risk at 24, but not 48Ā months. Low maternal education had a strongly increasing effect (ORĀ =Ā 2.3 at 24Ā months, ORĀ =Ā 13.7 at 48Ā months), as did low family income (ORĀ =Ā 1.4 at 24Ā months, ORĀ =Ā 7.0 at 48Ā months). Among children delayed at 24Ā months, low maternal education predicted delay even more strongly at 48Ā months (ORĀ =Ā 30.5). Low cognitive functioning is highly dynamic from 24 to 48Ā months. Although gestational factors including low birthweight increase childrenā€™s risk of cognitive delay at 24Ā months, low maternal education and family income are more prevalent in the pediatric population and are much stronger predictors of both persistent and emerging delay between ages 24 and 48Ā months

    Can working with the private for-profit sector improve utilization of quality health services by the poor? A systematic review of the literature

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    BACKGROUND: There has been a growing interest in the role of the private for-profit sector in health service provision in low- and middle-income countries. The private sector represents an important source of care for all socioeconomic groups, including the poorest and substantial concerns have been raised about the quality of care it provides. Interventions have been developed to address these technical failures and simultaneously take advantage of the potential for involving private providers to achieve public health goals. Limited information is available on the extent to which these interventions have successfully expanded access to quality health services for poor and disadvantaged populations. This paper addresses this knowledge gap by presenting the results of a systematic literature review on the effectiveness of working with private for-profit providers to reach the poor. METHODS: The search topic of the systematic literature review was the effectiveness of interventions working with the private for-profit sector to improve utilization of quality health services by the poor. Interventions included social marketing, use of vouchers, pre-packaging of drugs, franchising, training, regulation, accreditation and contracting-out. The search for published literature used a series of electronic databases including PubMed, Popline, HMIC and CabHealth Global Health. The search for grey and unpublished literature used documents available on the World Wide Web. We focused on studies which evaluated the impact of interventions on utilization and/or quality of services and which provided information on the socioeconomic status of the beneficiary populations. RESULTS: A total of 2483 references were retrieved, of which 52 qualified as impact evaluations. Data were available on the average socioeconomic status of recipient communities for 5 interventions, and on the distribution of benefits across socioeconomic groups for 5 interventions. CONCLUSION: Few studies provided evidence on the impact of private sector interventions on quality and/or utilization of care by the poor. It was, however, evident that many interventions have worked successfully in poor communities and positive equity impacts can be inferred from interventions that work with types of providers predominantly used by poor people. Better evidence of the equity impact of interventions working with the private sector is needed for more robust conclusions to be drawn
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