Effect of excess dietary copper on proliferation and differentiation of the proerythroblasts and erythrocytes in rats

This research was carried out to test the cytotoxic effects of excess copper in rats. Animals were divided into three groups, each containing five animals. Low dose (2 mg/kg) and high dose (4 mg/kg) of copper sulphate were force-fed into the animal by a stomach tube daily for 3 weeks and the third group was used as the control. At the end of each week, three animals (one of each group) were randomly selected and sacrificed. Blood samples were collected and blood smears were made. The bone marrow was collected from the heads of long-bones and bone marrow smears were also prepared. It was found that the application of copper sulphate doses modulates the proliferation and differentiation of stem cell progenitors and erythrocytes. Several alterations were observed and these were time- and dosedependent. Of these alterations, the predominant existence of giant pro-erythroblasts and promyeloblasts marked the increase of adipose cells and degeneration of pro-erythroblasts among the bone marrow cells. Also observed were hypochromia, anisocytosis, fragmentation and burr-shaped erythrocytes.Key words: Environmental pollution, copper toxicity, stem cells, blood, rats

Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

Improving obstetric care in low-resource settings: implementation of facility-based maternal death reviews in five pilot hospitals in Senegal

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan Africa, maternal and perinatal mortality and morbidity are major problems. Service availability and quality of care in health facilities are heterogeneous and most often inadequate. In resource-poor settings, the facility-based maternal death review or audit is one of the most promising strategies to improve health service performance. We aim to explore and describe health workers' perceptions of facility-based maternal death reviews and to identify barriers to and facilitators of the implementation of this approach in pilot health facilities of Senegal.</p> <p>Methods</p> <p>This study was conducted in five reference hospitals in Senegal with different characteristics. Data were collected from focus group discussions, participant observations of audit meetings, audit documents and interviews with the staff of the maternity unit. Data were analysed by means of both quantitative and qualitative approaches.</p> <p>Results</p> <p>Health professionals and service administrators were receptive and adhered relatively well to the process and the results of the audits, although some considered the situation destabilizing or even threatening. The main barriers to the implementation of maternal deaths reviews were: (1) bad quality of information in medical files; (2) non-participation of the head of department in the audit meetings; (3) lack of feedback to the staff who did not attend the audit meetings. The main facilitators were: (1) high level of professional qualifications or experience of the data collector; (2) involvement of the head of the maternity unit, acting as a moderator during the audit meetings; (3) participation of managers in the audit session to plan appropriate and realistic actions to prevent other maternal deaths.</p> <p>Conclusion</p> <p>The identification of the barriers to and the facilitators of the implementation of maternal death reviews is an essential step for the future adaptation of this method in countries with few resources. We recommend for future implementation of this method a prior enhancement of the perinatal information system and initial training of the members of the audit committee – particularly the data collector and the head of the maternity unit. Local leadership is essential to promote, initiate and monitor the audit process in the health facilities.</p

Environmental Assesment Of Al-Hillah River Pollution at Babil Governorate (IRAQ)

In this study, the environmental characteristics of Al-Hillah River were studied using geoinformatics applications, which is one of the geospatial techniques (GST). Applying this methodology, a geographic information system was developed, and it was supplied with laboratory data for the physical and chemical properties of 16 parameters for 2021. These data were linked to their spatial locations, using radar imagery of the Digital Elevation Model (Shuttle Radar Topography Mission), and Landsat ETM+7 satellite image. The results indicated that Al-Hillah River was affected by the liquid discharges of factories, cities, and farms spread on its sides, especially in the cities of Sadat Al-Hindiya, Al-Hillah, and Al-Hashimiyah. The seasonal changes in the climate affected some characteristics, including water temperature, pH, turbidity, total dissolved solids, and total hardness. The study showed that the concentration of sulfate (SO4) has risen above the permissible limits for the waters of Iraqi rivers. There are relatively high hardness and alkalinity values, but they were within the permissible limits. The study also showed that most of the results of environmental parameters that were used in the laboratory, were within the permissible limits of Iraqi water, except for sulfates. The justification for conducting this study is to help government agencies and decision-makers to adopt a correct vision for development projects that serve Babil Governorate. Also, it is the first time that the environmental characteristics of Al-Hillah River are studied using geoinformatics applications

Reciprocal relationship between expression of hypoxia inducible factor 1α (HIF-1α) and the pro-apoptotic protein Bid in ex vivo colorectal cancer

Hypoxia inducible factor 1 (HIF-1) represses the transcription of pro-apoptotic bid in colorectal cancer cells in vitro. To assess the clinical relevance of this observation, HIF-1α and Bid were assessed in serial sections of 39 human colorectal adenocarcinomas by immunohistochemistry. In high HIF-1α nuclear-positive cell subpopulations, there was a significant reduction in Bid expression (ANOVA, P=0.04). Given the role of Bid in drug-induced apoptosis, these data add impetus to strategies targeting HIF-1 for therapeutic gain

Characterisation of prostate cancer lesions in heterozygous Men1 mutant mice

<p>Abstract</p> <p>Background</p> <p>Mutations of the <it>MEN1 </it>gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome. Our group and others have shown that <it>Men1 </it>disruption in mice recapitulates MEN1 pathology. Intriguingly, rare lesions in hormone-dependent tissues, such as prostate and mammary glands, were also observed in the <it>Men1 </it>mutant mice.</p> <p>Methods</p> <p>To study the occurrence of prostate lesions, we followed a male mouse cohort of 47 <it>Men1</it>^+/-mice and 23 age-matched control littermates, starting at 18 months of age, and analysed the prostate glands from the cohort.</p> <p>Results</p> <p>Six <it>Men1</it>^+/-mice (12.8%) developed prostate cancer, including two adenocarcinomas and four <it>in situ </it>carcinomas, while none of the control mice developed cancerous lesions. The expression of menin encoded by the <it>Men1 </it>gene was found to be drastically reduced in all carcinomas, and partial LOH of the wild-type <it>Men1 </it>allele was detected in three of the five analysed lesions. Using immunostaining for the androgen receptor and p63, a basal epithelial cell marker, we demonstrated that the menin-negative prostate cancer cells did not display p63 expression and that the androgen receptor was expressed but more heterogeneous in these lesions. Furthermore, our data showed that the expression of the cyclin-dependent kinase inhibitor CDKN1B (p27), a <it>Men1 </it>target gene known to be inactivated during prostate cell tumorigenesis, was notably decreased in the prostate cancers that developed in the mutant mice.</p> <p>Conclusion</p> <p>Our work suggests the possible involvement of <it>Men1 </it>inactivation in the tumorigenesis of the prostate gland.</p

Intramyocardial Transplantation of Undifferentiated Rat Induced Pluripotent Stem Cells Causes Tumorigenesis in the Heart

BACKGROUND: Induced pluripotent stem cells (iPSCs) are a novel candidate for use in cardiac stem cell therapy. However, their intrinsic tumorigenicity requires further investigation prior to use in a clinical setting. In this study we investigated whether undifferentiated iPSCs are tumorigenic after intramyocardial transplantation into immunocompetent allogeneic recipients. METHODOLOGY/PRINCIPAL FINDINGS: We transplanted 2 × 10(4), 2 × 10(5), or 2 × 10(6) cells from the established rat iPSC line M13 intramyocardially into intact or infarcted hearts of immunocompetent allogeneic rats. Transplant duration was 2, 4, or 6 weeks. Histological examination with hematoxylin-eosin staining confirmed that undifferentiated rat iPSCs could generate heterogeneous tumors in both intracardiac and extracardiac sites. Furthermore, tumor incidence was independent of cell dose, transplant duration, and the presence or absence of myocardial infarction. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that allogeneic iPSC transplantation in the heart will likely result in in situ tumorigenesis, and that cells leaked from the beating heart are a potential source of tumor spread, underscoring the importance of evaluating the safety of future iPSC therapy for cardiac disease

Please understand when I cry out in pain: women's accounts of maternity services during labour and delivery in Ghana

BACKGROUND: This study was undertaken to investigate women's accounts of interactions with health care providers during labour and delivery and to assess the implications for acceptability and utilisation of maternity services in Ghana. METHODS: Twenty-one individual in-depth interviews and two focus group discussions were conducted with women of reproductive age who had delivered in the past five years in the Greater Accra Region. The study investigated women's perceptions and experiences of care in terms of factors that influenced place of delivery, satisfaction with services, expectations of care and whether they would recommend services. RESULTS: One component of care which appeared to be of great importance to women was staff attitudes. This factor had considerable influence on acceptability and utilisation of services. Otherwise, a successful labour outcome and non-medical factors such as cost, perceived quality of care and proximity of services were important. Our findings indicate that women expect humane, professional and courteous treatment from health professionals and a reasonable standard of physical environment. Women will consciously change their place of delivery and recommendations to others if they experience degrading and unacceptable behaviour. CONCLUSION: The findings suggest that inter-personal aspects of care are key to women's expectations, which in turn govern satisfaction. Service improvements which address this aspect of care are likely to have an impact on health seeking behaviour and utilisation. Our findings suggest that user-views are important and warrant further investigation. The views of providers should also be investigated to identify channels by which service improvements, taking into account women's views, could be operationalised. We also recommend that interventions to improve delivery care should not only be directed to the health professional, but also to general health system improvements

Harnessing Expression Data to Identify Novel Candidate Genes in Polycystic Ovary Syndrome

Novel pathways in polycystic ovary syndrome (PCOS) are being identified in gene expression studies in PCOS tissues; such pathways may contain key genes in disease etiology. Previous expression studies identified both dickkopf homolog 1 (DKK1) and DnaJ (Hsp40) homolog, subfamily B, member 1 (DNAJB1) as differentially expressed in PCOS tissue, implicating them as candidates for PCOS susceptibility. To test this, we genotyped a discovery cohort of 335 PCOS cases and 198 healthy controls for three DKK1 single nucleotide polymorphisms (SNPs) and four DNAJB1 SNPs and a replication cohort of 396 PCOS cases and 306 healthy controls for 1 DKK1 SNP and 1 DNAJB1 SNP. SNPs and haplotypes were determined and tested for association with PCOS and component phenotypes. We found that no single nucleotide polymorphisms were associated with PCOS risk; however, the major allele of rs1569198 from DKK1 was associated with increased total testosterone (discovery cohort P = 0.0035) and dehydroepiandrosterone sulfate (replication cohort P = 0.05). Minor allele carriers at rs3962158 from DNAJB1 had increased fasting insulin (discovery cohort P = 0.003), increased HOMA-IR (discovery cohort P = 0.006; replication cohort P = 0.036), and increased HOMA-%B (discovery cohort P = 0.004). Carriers of haplotype 2 at DNAJB1 also had increased fasting insulin, HOMA-IR, and HOMA-%B. These findings suggest that genetic variation in DKK1 and DNAJB1 may have a role in the hyperandrogenic and metabolic dysfunction of PCOS, respectively. Our results also demonstrate the utility of gene expression data as a source of novel candidate genes in PCOS, a complex and still incompletely defined disease, for which alternative methods of gene identification are needed

A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs

Human induced pluripotent stem cells (hiPSCs) hold enormous potential, however several obstacles impede their translation to industrial and clinical applications. Here we describe a platform to efficiently generate, characterize and maintain single cell and feeder-free (FF) cultured hiPSCs by means of a small molecule cocktail media additive. Using this strategy we have developed an effective multiplex sorting and high-throughput selection platform where individual clonal hiPSC lines are readily obtained from a pool of candidate clones, expanded and thoroughly characterized. By promoting survival and self-renewal, the selected hiPSC clones can be rapidly expanded over multiple FF, single-cell passages while maintaining their pluripotency and genomic stability as demonstrated by trilineage differentiation, karyotype and copy number variation analysis. This study provides a robust platform that increases efficiency, throughput, scale and quality of hiPSC generation and facilitates the industrial and clinical use of iPSC technology