96 research outputs found
The discovery of PCSK9 inhibitors: A tale of creativity and multifaceted translational research.
Heart failure with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies
Radiation in medicine: Origins, risks and aspirations.
The use of radiation in medicine is now pervasive and routine. From their crude beginnings 100 years ago, diagnostic radiology, nuclear medicine and radiation therapy have all evolved into advanced techniques, and are regarded as essential tools across all branches and specialties of medicine. The inherent properties of ionizing radiation provide many benefits, but can also cause potential harm. Its use within medical practice thus involves an informed judgment regarding the risk/benefit ratio. This judgment requires not only medical knowledge, but also an understanding of radiation itself. This work provides a global perspective on radiation risks, exposure and mitigation strategies
An evaluation of secondary prophylaxis for rheumatic heart disease in rural Egypt.
Although essentially disappeared from the industrialized world, rheumatic heart disease (RHD) is still prevalent in developing countries, with 300,000 new cases identified each year. In Aswan, Egypt, RHD affects about 2.3% of children with over 90% of the cases being subclinical. Secondary prophylaxis has proved to be an effective method of preventing the progression of RHD. However, its efficacy is limited by low patient adherence. A systematic, generalizable tool is necessary to outline, and ultimately address these barriers.A 43-item semi-structured questionnaire was developed based on the three domains outlined by Fishbein (capability, intention, and health care barriers). A preliminary evaluation of the barriers to RHD prophylaxis use in Aswan, Egypt was carried out as a pilot study using this tool. Participants were local school children diagnosed with RHD or flagged as high-risk (as per a set of echocardiographic criteria developed by the Aswan Heart Centre) through a previous screening program of randomly selected 3,062 school children in Aswan.29 patients were interviewed (65.5% adherent to RHD prophylaxis). Compared to non-adherent patients, adherent patients had better understanding of the disease (68.4% versus 20% in the non-adherent group, p = 0.021), and were more aware of the consequences of missing prophylaxis doses (79% versus 40% of non-adherent patients, p = 0.005). Furthermore, 90% of non-adherent patients consciously choose to miss injection appointments (as compared to 31.6% of adherent patients, p = 0.005). Clinic wait time was the most frequently reported deterrent for both groups.A standardized tool that systematically outlines barriers to prophylaxis is a necessary first step to improving adherence to penicillin. Although individually developed tools exist for specific populations, a generalizable tool that takes into account the demographic and cultural differences in the populations of interest will allow for more reliable data collection methodology. Application of this tool will be used to further explore barriers to prophylaxis adherence and inform the basis for the design of future KT interventions
Hepatoprotective effect of basil (Ocimum basilicum L.) on CCl4-induced liver fibrosis in rats
The hepatoprotective effect of basil (Ocimum basilicum) extract against liver fibrosis-induced by carbon tetrachloride (CCl4) was studied in rats. Rats were allocated into five groups: Group I (control group); Group II [CCl4 group; rats were injected subcutaneously with CCl4 (1 ml/kg b.w.) twice weekly for 4 weeks (phenobarbital, 350 mg/L, was added to the drinking water throughout the experiment)]; Group III received daily oral doses of basil extract of 200 mg/kg b.w. along with CCl4 and phenobarbital for 6 weeks; Groups IV and V rats were treated with phenobarbital and CCl4 for 6 weeks then treated daily with oral dose of 200 mg/kg b.w basil extract, or by 300 mg/kg b.w dimethyl diphenyl bicarboxylate (DDB), respectively for 6 weeks. Basil-treatment significantly reduced the liver content of hydroxyproline and significantly increased the activity of hyaluronidase (HAase). The hepatic activity of superoxide dismutase (SOD) was stimulated while the lipid peroxidation was significantly reduced by the effect of basil extract. Treatment with CCl4 significantly increased the activities of transaminases [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], and alkaline phosphatase (ALP). These activities were significantly decreased by basil extract. The higher levels of serum urea and creatinine in CCl4 group were significantly guarded by the protection of basil.Key words: Carbon tetrachloride, liver fibrosis, antioxidant, Ocimum basilicum, dimethyl diphenyl bicarboxylate
Cup versus bottle feeding for hospitalized late preterm infants in Egypt: A quasi-experimental study
<p>Abstract</p> <p>Background</p> <p>Although previous studies have demonstrated beneficial breastfeeding outcomes when cup feeding rather than bottle feeding was used for feeding preterm infants, cup feeding has not been implemented in Egypt. The aim of the current study was to examine the effect of using cup feeding as an exclusive method of feeding preterm infants during hospitalization on breastfeeding outcomes after discharge.</p> <p>Methods</p> <p>A quasi-experimental design, with the control group studied first, was used to examine the effect of cup feeding for preterm infants on breastfeeding outcomes after discharge. Sixty preterm infants (mean gestational age was 35.13 weeks and mean birth weight was 2150 grams) were recruited during Neonatal Intensive Care Unit (NICU) stay. Control group infants (n = 30) received only bottle feedings during hospitalization and the experimental group (n = 30) received only cup feedings during hospitalization. Both groups were followed up after discharge for six weeks to evaluate infant's breastfeeding behavior and mother's breastfeeding practices. Data were analyzed using descriptive statistics and repeated measures ANOVA for testing the differences between the cup feeding and bottle feeding groups over six weeks after discharge.</p> <p>Results</p> <p>Cup fed infants demonstrated significantly more mature breastfeeding behaviors when compared to bottle fed infants (p < 0.01) over six weeks, and had a significantly higher proportion of breast feedings one week after discharge (p = 0.03).</p> <p>Conclusion</p> <p>Cup fed infants were more exclusively breast fed one week after discharge, supporting the Baby Friendly Hospital Initiative recommendations for using cup feeding and avoiding bottle feeding when providing supplementation for preterm infants. The current study provides initial evidence for the implementation of cup feeding as a method of supplementation for late preterm infants during hospitalization.</p> <p>Trial Registration</p> <p>Clinical Trial NCT00756587.</p
Ethnicity, consanguinity, and genetic architecture of hypertrophic cardiomyopathy
AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by phenotypic heterogeneity that is partly explained by the diversity of genetic variants contributing to disease. Accurate interpretation of these variants constitutes a major challenge for diagnosis and implementing precision medicine, especially in understudied populations. The aim is to define the genetic architecture of HCM in North African cohorts with high consanguinity using ancestry-matched cases and controls. METHODS AND RESULTS: Prospective Egyptian patients (n = 514) and controls (n = 400) underwent clinical phenotyping and genetic testing. Rare variants in 13 validated HCM genes were classified according to standard clinical guidelines and compared with a prospective HCM cohort of majority European ancestry (n = 684). A higher prevalence of homozygous variants was observed in Egyptian patients (4.1% vs. 0.1%, P = 2 × 10-7), with variants in the minor HCM genes MYL2, MYL3, and CSRP3 more likely to present in homozygosity than the major genes, suggesting these variants are less penetrant in heterozygosity. Biallelic variants in the recessive HCM gene TRIM63 were detected in 2.1% of patients (five-fold greater than European patients), highlighting the importance of recessive inheritance in consanguineous populations. Finally, rare variants in Egyptian HCM patients were less likely to be classified as (likely) pathogenic compared with Europeans (40.8% vs. 61.6%, P = 1.6 × 10-5) due to the underrepresentation of Middle Eastern populations in current reference resources. This proportion increased to 53.3% after incorporating methods that leverage new ancestry-matched controls presented here. CONCLUSION: Studying consanguineous populations reveals novel insights with relevance to genetic testing and our understanding of the genetic architecture of HCM
New variant with a previously unrecognized mechanism of pathogenicity in hypertrophic cardiomyopathy
A comparative study of mutation screening of sarcomeric genes (MYBPC3, MYH7, TNNT2) using single gene approach versus targeted gene panel next generation sequencing in a cohort of HCM patients in Egypt
Background: NGS enables simultaneous sequencing of large numbers of associated genes in genetic heterogeneous disorders, in a more rapid and cost-effective manner than traditional technologies. However there have been limited direct comparisons between NGS and more established technologies to assess the sensitivity and false negative rates of this new approach. The scope of the present manuscript is to compare variants detected in MYBPC3, MYH7 and TNNT2 genes using the stepwise dHPLC/ Sanger versus targeted NGS.Methods: In this study, we have analysed a group of 150 samples of patients from the Bibliotheca Alexandrina-Aswan Heart Centre National HCM program. The genetic testing was simultaneously undertaken by high throughput denaturing high-performance liquid chromatography (dHPLC) followed by Sanger based sequencing and targeted next generation deep sequencing using panel of inherited cardiac genes (ICC). The panel included over 100 genes including the 3 sarcomeric genes. Analysis of the sequencing data of the 3 genes was undertaken in a double blinded strategy.Results: NGS analysis detected all pathogenic and likely pathogenic variants identified by dHPLC (50 in total, some samples had double hits). There was a 0% false negative rate for NGS based analysis. Nineteen variants were missed by dHPLC and detected by NGS, thus increasing the diagnostic yield in this co- analysed cohort from 22.0% (33/150) to 31.3% (47/150). Of interest to note that the mutation spectrum in this Egyptian HCM population revealed a high rate of homozygosity in MYBPC3 and MYH7 genes in comparison to other population studies (6/150, 4%). None of the homozygous samples were detected by dHPLC analysis.Conclusion: NGS provides a useful and rapid tool to allow panoramic screening of several genes simultaneously with a high sensitivity rate amongst genes of known etiologic role allowing high throughput analysis of HCM patients and relevant control series in a less characterised population
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