Dyslipidemia in Special Populations, the Elderly, Women, HIV, Chronic Kidney Disease and ESRD, and Minority Groups

This chapter discusses the management of dyslipidemia in special patient populations: the elderly, woman and pregnancy, renal disease, human immunodeficiency virus (HIV), and different racial/ethnic groups. In the elderly, dyslipidemia is often underdiagnosed and undertreated. Consideration for potential atherosclerotic risk-reduction benefits, risk of adverse effects, drug-drug interactions, and patient preferences should precede the initiation of statin therapy. Data on pregnant women are lacking and need future research. Dyslipidemia and its effects on the cardiovascular system in chronic kidney disease (CKD), end-stage renal disease (ESRD), and HIV are dynamic and multimodal. These conditions are states of chronic inflammation, where it is difficult to associate quantities of cholesterol types with outcomes. Among all racial groups, Asian Indians, Filipinos, and Hispanics are at a higher risk for dyslipidemia. Genetic differences in statin metabolism may explain this racial/ethnic difference

Transcription and translation of human F11R gene are required for an initial step of atherogenesis induced by inflammatory cytokines

<p>Abstract</p> <p>Background -</p> <p>The F11 Receptor (F11R; aka JAM-A, JAM-1) is a cell adhesion protein present constitutively on the membrane surface of circulating platelets and within tight junctions of endothelial cells (ECs). Previous reports demonstrated that exposure of ECs to pro-inflammatory cytokines causes insertion of F11R molecules into the luminal surface of ECs, ensuing with homologous interactions between F11R molecules of platelets and ECs, and a resultant adhesion of platelets to the inflamed ECs. The main new finding of the present report is that the first step in this chain of events is the <it>de-novo </it>transcription and translation of F11R molecules, induced in ECs by exposure to inflammatory cytokines.</p> <p>Methods -</p> <p>The experimental approach utilized isolated, washed human platelet suspensions and cultured human venous endothelial cells (HUVEC) and human arterial endothelial cells (HAEC) exposed to the proinflammatory cytokines TNF-alpha and/or IFN-gamma, for examination of the ability of human platelets to adhere to the inflamed ECs thru the F11R. Our strategy was based on testing the effects of the following inhibitors on this activity: general mRNA synthesis inhibitors, inhibitors of the NF-kappaB and JAK/STAT pathways, and small interfering F11R-mRNA (siRNAs) to specifically silence the F11R gene.</p> <p>Results -</p> <p>Treatment of inflamed ECs with the inhibitors actinomycin, parthenolide or with AG-480 resulted in complete blockade of F11R- mRNA expression, indicating the involvement of NF-kappaB and JAK/STAT pathways in this induction. Transfection of ECs with F11R siRNAs caused complete inhibition of the cytokine-induced upregulation of F11R mRNA and inhibition of detection of the newly- translated F11R molecules in cytokine-inflamed ECs. The functional consequence of the inhibition of F11R transcription and translation was the significant blockade of the adhesion of human platelets to inflamed ECs.</p> <p>Conclusion -</p> <p>These results prove that <it>de novo </it>synthesis of F11R in ECs is required for the adhesion of platelets to inflamed ECs. Because platelet adhesion to an inflamed endothelium is crucial for plaque formation in non-denuded blood vessels, we conclude that the <it>de-novo </it>translation of F11R is a crucial early step in the initiation of atherogenesis, leading to atherosclerosis, heart attacks and stroke.</p

From model-driven software development processes to problem diagnoses at runtime

Following the “convention over configuration” paradigm, model-driven software development (MDSD) generates code to implement the “default” behaviour that has been specified by a template separate from the input model. On the one hand, developers can produce end-products without a full understanding of the templates; on the other hand, the tacit knowledge in the templates is subtle to diagnose when a runtime software failure occurs. Therefore, there is a gap between templates and runtime adapted models. Generalising from the concrete problematic examples in MDSD processes to a model-based problem diagnosis, the chapter presents a procedure to separate the automated fixes from those runtime gaps that require human judgments

Bacterial etiology of sexually transmitted infections at a STI clinic in Ghana; use of multiplex real time PCR

Background: Most sexually transmitted infection (STI) management efforts focus on the syndromic approach to diagnose and treat patients. However, most women with STIs have been shown to be entirely asymptomatic, or if symptoms exist, are often missed when either clinical or conventional bacteriologic diagnostic tools are employed.Methods: We assessed the performance of a multiplex real time PCR assay to describe other potential pathogens that could be missed by conventional bacteriological techniques in 200 women attending a routine STI clinic in Kumasi, Ghana.Results: Although a total 78.00% of the women were asymptomatic, 77.1% of them tested positive for at least one bacterial STI pathogen. Mycoplasma genitalium was the most commonly detectable pathogen present in 67.5% of all women. Of those testing positive, 25.0% had single infections, while 38.0% and 19.5% had double and triple infections respectively. Altogether, 86.54% and 90.91% of the symptomatic and asymptomatic women respectively tested positive for at least one pathogen (p&lt;0.05). There were no significant associations (p&lt;0.05) between the clinical manifestations of the symptomatic women and the pathogens detected in their samples.Conclusions: Our study confirmed the importance of complementing the syndromic approach to STI management with pathogen detection and most importantly recognise that STIs in women are asymptomatic and regular empirical testing even for both symptomatic and asymptomatic patients is critical for complete clinical treatment.Funding: EOD (Ellis Owusu-Dabo Research working group, KCCR)Keywords: Etiology, Syndromic, Sexually Transmitted Infections, Multiplex real time PC

LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer

Bulk chemotherapy and drug release strategies for cancer treatment have been associated with lack of specificity and high drug concentrations that often result in toxic side effects. This work presents the results of an experimental study of cancer drugs (prodigiosin or paclitaxel) conjugated to Luteinizing Hormone-Releasing Hormone (LHRH) for the specific targeting and treatment of triple negative breast cancer (TNBC). Injections of LHRH-conjugated drugs (LHRH-prodigiosin or LHRH-paclitaxel) into groups of 4-week-old athymic female nude mice (induced with subcutaneous triple negative xenograft breast tumors) were found to specifically target, eliminate or shrink tumors at early, mid and late stages without any apparent cytotoxicity, as revealed by in vivo toxicity and ex vivo histopathological tests. Our results show that overexpressed LHRH receptors serve as binding sites on the breast cancer cells/tumor and the LHRH-conjugated drugs inhibited the growth of breast cells/tumor in in vitro and in vivo experiments. The inhibitions are attributed to the respective adhesive interactions between LHRH molecular recognition units on the prodigiosin (PGS) and paclitaxel (PTX) drugs and overexpressed LHRH receptors on the breast cancer cells and tumors. The implications of the results are discussed for the development of ligand-conjugated drugs for the specific targeting and treatment of TNBC

Perspectives of Chronic Kidney Disease Patients on Readiness for Advance Care Planning at Komfo Anokye Teaching Hospital, Ghana

This study examined the impact of advance care planning (ACP) on the quality of life for patients with chronic kidney disease (CKD) at Komfo Anokye Teaching Hospital in Ghana. It specifically investigated patients’ perspectives on their readiness for ACP. Utilizing a qualitative descriptive design, one-on-one interviews were conducted with CKD patients at the renal clinic, employing a semi-structured interview guide for thematic analysis of audio data. The findings revealed a gap in understanding among CKD patients, with participants acknowledging their vulnerability to renal failure, often linked to a medical history of diabetes and hypertension. Despite recognizing potential outcomes such as dialysis dependency or death, some patients retained hope for a cure, relying on faith. The initial kidney failure diagnosis induced shock and distress, leading many patients to prefer the comfort and familiarity of home-based care, including dialysis. Meanwhile, a minority favored hospital care to protect their children from psychological trauma. Most patients deemed legal preparations unnecessary, citing limited assets or a lack of concern for posthumous estate execution. These insights emphasize the necessity for targeted education and support in ACP to enhance patient outcomes in chronic kidney disease care and end-of-life planning

Integrating temperature-dependent life table data into Insect Life Cycle Model for predicting the potential distribution of Scapsipedus icipe Hugel & Tanga

Open Access Journal; Published online: 25 Sept 2019Scapsipedus icipe Hugel and Tanga (Orthoptera: Gryllidae) is a newly described edible cricket species. Although, there is substantial interest in mass production of S. icipe for human food and animal feed, no information exists on the impact of temperature on their bionomics. Temperature-dependent development, survival, reproductive and life table parameters of S. icipe was generated and integrated into advanced Insect Life Cycle Modeling software to describe relative S. icipe population increase and spatial spread based on nine constant temperature conditions. We examined model predictions and implications for S. icipe potential distribution in Africa under current and future climate. These regions where entomophagy is widely practiced have distinctly different climates. Our results showed that S. icipe eggs were unable to hatch at 10 and 40˚C, while emerged nymphs failed to complete development at 15˚C. The developmental time of S. icipe was observed to decrease with increased in temperature. The lowest developmental threshold temperatures estimated using linear regressions was 14.3, 12.67 and 19.12˚C and the thermal constants for development were 185.2, 1111.1- and 40.7-degree days (DD) for egg, nymph and pre-adult stages, respectively. The highest total fecundity (3416 individuals/female/generation), intrinsic rate of natural increase (0.075 days), net reproductive rate (1330.8 female/female/generation) and shortest doubling time (9.2 days) was recorded at 30˚C. The regions predicted to be suitable by the model suggest that S. icipe is tolerant to a wider range of climatic conditions. Our findings provide for the first-time important information on the impact of temperature on the biology, establishment and spread of S. icipe across the Africa continent. The prospect of edible S. icipe production to become a new sector in food and feed industry is discussed

Joint effect of water and sanitation practices on childhood diarrhoea in sub-Saharan Africa

Background: Diarrhoea remains the major cause of morbidity and mortality of children under five years in Africa. Several studies have shown that inadequate and unsafe water, lack of sanitation, and poor hygiene practices are complex issues for different pathogens and accountable for the occurrence of diarrhoea diseases. We assessed the combined effect of household’s source of drinking water and type of toilet facility and residential wellbeing on the incidence of childhood diarrhoea in 33 Sub-Saharan Africa countries while accounting for relevant compositional and contextual factors. Methods: The 2010–2019 datasets from the Demographic and Health Surveys were drawn for analyses. The outcome variable used in this study was the incidence of childhood diarrhoea. Three negative log-log generalized linear regression models were then sequentially fitted to the data to examine the joint effect of household water and sanitation practices on child diarrhoea. The results were presented using crude odds ratios (CORs) and adjusted odds ratios (AORs) at 95% confidence intervals (CIs). Using ArcGIS software, maps were design to unveil the spatial distribution of key variables. Findings: Approximately 16% of the 307,741 mothers interviewed reported an incidence of diarrhoea disease among children under-five years in their households. The results showed that a household depending on an unimproved source of drinking water and with an unimproved type of toilet facility was not significantly associated with childhood diarrhoea. However, those with improved drinking water but an unimproved type of toilet facility had higher odds of reporting childhood diarrhoea (AOR = 1.020, 95% CI = 1.003-1-036) compared to those in households with both improved source of drinking water and type of toilet facility. Across the geographical regions, Eastern (aOR = 1.102, 95% CI = 1.084–1.120) and Central Africa (aOR = 1.102, 95% CI = 1.083–1.121) were more likely to experience child diarrhoea. Conclusion: Water and sanitation practices such as the source of drinking water and toilet facility, and geographic region had significant effects on childhood diarrhoea in sub-Saharan Africax. The findings suggest the need for multi-sectoral actions that recognise the geo-spatial and temporal characteristics identified in the study through regional to national policies. Water and sanitation community-based interventions that seek to improve equitable access to safe water and sanitation in the sub-region should be intensified