Relationship of SNCG, S100A4, S100A9 and LCN2 gene expression and DNA methylation in bladder cancer

Microarray analysis of paired cultures of normal and cancerous urothelial cells revealed differences in cytokeratin and adhesion gene expression. Normal cells expressed autocrine growth factor genes more strongly whereas carcinoma cells were distinguished by concomitant expression of urothelial and epidermal differentiation markers. Expression of SNCG, S100A9 and LCN2 was also enhanced. In other cancers, overexpression of SNCG, LCN2 and S100A4 has been ascribed to DNA hypomethylation. We therefore investigated expression and methylation of SNCG, S100A4, S100A9 and LCN2 in urothelial cancer cell lines and tissues. SNCG and S100A4 were overexpressed in some cancer tissues and cell lines, but downregulated in others, whereas LCN2 and S100A9 were upregulated in few cancer cell lines, but regularly in tissues. Normal and cancerous urothelial cells expressing SNCG lacked promoter methylation. SNCG downregulation was associated with hypermethylation and could be reversed by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. S100A4 methylation at regulatory intronic sites and in the promoter region was lowest in leukocytes and fibroblasts, and denser in urothelial cells. Gene expression responded to 5-aza-2'-deoxycytidine. LCN2 promoter methylation was variable and even less consistently related to expression. The S100A9 promoter was partially methylated in nonexpressing cells, but 5-aza-2'-deoxycytidine had no effect. Our data indicate that SNCG methylation is cell type-specific and the gene is hypermethylated in some urothelial cancers. S100A4, S100A9 and LCN2 are genes with moderate CpG-density that show a less stringent relationship between DNA methylation and gene expression. Therefore, changes in methylation of these genes in cancer should be interpreted cautiously.     

Influence of Silica Modulus and Curing Temperature on the Strength of Alkali-Activated Volcanic Ash and Limestone Powder Mortar

This present study evaluates the effect of silica modulus (M_s) and curing temperature on strengths and the microstructures of binary blended alkali-activated volcanic ash and limestone powder mortar. Mortar samples were prepared using mass ratio of combined Na₂SiO_3(aq)/10 M NaOH_(aq) of 0.5 to 1.5 at an interval of 0.25, corresponding to M_s of 0.52, 0.72, 0.89, 1.05 and 1.18, respectively, and sole 10 M NaOH_(aq). Samples were then subjected to ambient room temperature, and the oven-cured temperature was maintained from 45 to 90 °C at an interval of 15 °C for 24 h. The maximum achievable 28-day strength was 27 MPa at M_s value of 0.89 cured at 75 °C. Samples synthesised with the sole 10 M NaOH_(aq) activator resulted in a binder with a low 28-day compressive strength (15 MPa) compared to combined usage of Na₂SiO_3(aq)/10 M NaOH_(aq) activators. Results further revealed that curing at low temperatures (25 °C to 45 °C) does not favour strength development, whereas higher curing temperature positively enhanced strength development. More than 70% of the 28-day compressive strength could be achieved within 12 h of curing with the usage of combined Na₂SiO_3(aq)/10 M NaOH_(aq). XRD, FTIR and SEM + EDX characterisations revealed that activation with combined Na₂SiO_3(aq)/10 M NaOH_(aq) leads to the formation of anorthite (CaAl₂Si₂O₈), gehlenite (CaO.Al₂O₃.SiO₂) and albite (NaAlSi₃O₈) that improve the amorphosity, homogeneity and microstructural density of the binder compared to that of samples synthesised with sole 10 M NaOH_(aq).     

Mobile phone use for a social strategy to improve antiretroviral refill experience at a low-resource HIV clinic: patient responses from Nigeria

In sub-Saharan African areas where antiretroviral (ARV) drugs are not available through community pharmacies, clinic-based pharmacies are often the primary source of ARV drug refills. Social pressure is mounting on treatment providers to adjust ARV refill services towards user-friendly approaches which prioritize patients’ convenience and engage their resourcefulness. By this demand, patients may be signalling dissatisfaction with the current provider-led model of monthly visits to facility-based pharmacies for ARV refill. Mobile phones are increasingly popular in sub-Saharan Africa, and have been used to support ARV treatment goals in this setting. A patient-centred response to on-going social pressure requires treatment providers to view ARV refill activities through the eyes of patients who are negotiating the challenges of day-to-day life while contemplating their next refill appointment. Using focus groups of five categories of adult patients receiving combination ARV therapy, we conducted this cross-sectional qualitative study to provide insight into modifiable gaps between patients’ expectations and experiences of the use of mobile phones in facility-based ARV refill service at a public HIV clinic in Nigeria. A notable finding was patients’ preference for harnessing informal social support (through intermediaries with mobile phones) to maintain adherence to ARV refill appointments when they could not present in person. This evolving social support strategy also has the potential to enhance defaulter tracking. Our study findings may inform the development of ARV refill strategies and the design of future qualitative studies on client–provider communication by mobile phones in under-resourced HIV treatment programmes.     

Reduction in the resident intestinal myelomonocytic cell population occurs during ApcMin/+ mouse intestinal tumorigenesis

With its significant contribution to cancer mortality globally, advanced colorectal cancer (CRC) requires new treatment strategies. However, despite recent good results for mismatch repair (MMR)-deficient CRC and other malignancies, such as melanoma, the vast majority of MMR-proficient CRCs are resistant to checkpoint inhibitor (CKI) therapy. MMR-proficient CRCs commonly develop from precursor adenomas with enhanced Wnt-signalling due to adenomatous polyposis coli (APC) mutations. In melanomas with enhanced Wnt signalling due to stabilized β-catenin, immune anergy and resistance to CKI therapy has been observed, which is dependent on micro-environmental myelomonocytic (MM) cell depletion in melanoma models. However, MM populations of colorectal adenomas or CRC have not been studied. To characterize resident intestinal MM cell populations during the early stages of tumorigenesis, the present study utilized the Apc^Min/+ mouse as a model of MMR-proficient CRC, using enhanced green fluorescent protein (EGFP) expression in the mouse lysozyme (M-lys)^lys-EGFP/+ mouse as a pan-myelomonocytic cell marker and a panel of murine macrophage surface markers. Total intestinal lamina propria mononuclear cell (LPMNC) numbers significantly decreased with age (2.32±1.39×10⁷ [n=4] at 33 days of age vs. 1.06±0.24×10⁷ [n=8] at 109 days of age) during intestinal adenoma development in Apc^Min/+ mice (P=0.05; unpaired Student''s t-test), but not in wild-type littermates (P=0.35). Decreased total LPMNC numbers were associated with atrophy of intestinal lymphoid follicles and the absence of MM/lymphoid cell aggregates in Apc^Min/+ mouse intestine, but not spleen, compared with wild-type mice. Furthermore, during the early stage of intestinal adenoma development, there was a two-fold reduction of M-lys expressing cells (P=0.05) and four-fold reduction of ER-HR3 (macrophage sub-set) expressing cells (P=0.05; two tailed Mann-Whitney U test) in mice with reduced total intestinal LPMNCs (n=3). Further studies are necessary to determine the relevance of these findings to immune-surveillance of colorectal adenomas or MMR-proficient CRC CKI therapy resistance.     

Quality Characteristics of Noodles Produced from Wheat Flour and Modified Starch of African Breadfruit (Artocarpus altilis) Blends

Wheat flour and modified-starch from African breadfruit (MS) were used in ratios of 100:0; 90:10; 80:20; 70:30; 60:40 and 50:50 to produce noodles. Chemical composition, culinary and sensory attributes of the noodles were investigated. The protein, fat, ash, crude fiber, moisture and calorific values of the flour noodles ranged from 4.76 to 0.33%, 0.35 to 0.57%, 0.83 to 0.57%, 0.53 to 0.57%, 8.03 to 0.15% and 349.51 to 355.81 kcal/100 g respectively. Moisture content increased with increasing addition of MS and later reduced. Addition of MS flour up to 30% had no significant effect on the overall acceptance of noodles. The results showed that MS flour can be incorporated up to 30% for noodles to improve the nutrient value without affecting the acceptability. There were no significant difference (p < 0.05) in the sensory attributes of the noodles up till 30% level of inclusion with MS.     

Utilization of health care services in rural and urban areas: a determinant factor in planning and managing health care delivery systems

Background

Disparities in use of healthcare services between rural and urban areas have been empirically attributed to several factors. This study explores the existence of this disparity and its implication for planning and managing healthcare delivery systems.

Objectives

The objectives determine the relative importance of the various predisposing, enabling, need and health services factors on utilization of health services; similarity between rural and urban areas; and major explanatory variables for utilization

Method

A four-stage model of service utilization was constructed with 31 variables under appropriate model components. Data is collected using cross-sectional sample survey of 1086 potential health services consumers in selected health facilities and resident milieu via questionnaire. Data is analyzed using factor analysis and cross tabulation.

Results

The 4-stage model is validated for the aggregate data and data for the rural areas with 3-stage model for urban areas. The order of importance of the factors is need, enabling, predisposing and health services. 11 variables are found to be powerful predictors of utilization.

Conclusion

Planning of different categories of health care facilities in different locations should be based on utilization rates while proper management of established facilities should aim to improve health seeking behavior of people.Keywords/Phrases: Utilization, healthcare Delivery System, Planning, Model, Factor Analysis, Rural and Urban Areas