In vitro Anti-proliferative and Apoptotic Activities of Eurycoma longifolia Jack (Simaroubaceae) on HL-60 Cell Line

Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma longifolia root extracts on HL-60 leukemic cells.Methods: HL-60 cells were treated with different partially purified sub-fractions (F1 – F3) derived from the resin chromatography of the crude methanol root extract of E. longifolia roots, at different doses andtime points. The anti-proliferative activity of E. longifolia was assessed via cell counting and trypan blue exclusion. Apoptosis was evaluated via Annexin-V FITC/IP and Hoechst staining. Flow cytometry and Wright staining were used to assess its differentiation activities.Results: F1 showed unremarkable growth inhibition rate while F2 and F3 showed growth inhibitory effects with median inhibitory concentration (IC50) values of 15.2 and 28.6 ìg/ml, respectively. Treatment with F2 and F3 (100 ìg/ml) for 96 h increased cell death from 3.3 to 95.5 and 76.3 %,respectively. Treatment with F2 (50 ìg/ml) induced apoptosis by 14, 19.5 and 25 % after 24, 48 and 72 h, respectively. No differentiation activity was observed, as indicated by absence of myeloid maturation and a non-significant CD14 positivity (p > 0.05).Conclusion: E. longifolia extract (F2) showed promising anti-leukemic activity and can be a candidate for the development of a drug for the treatment of acute promyelocytic leukemia (APL).Keywords: Acute promyelocytic leukemia (APL), HL-60 cells, Eurycoma longifolia, Apoptosis, Antiproliferation, Differentiatio

Identification of the genomic mutation in Epha4rb-2J/rb-2J mice

The EphA4 receptor tyrosine kinase is involved in numerous cell-signalling activities during embryonic development. EphA4 has the ability to bind to both types of ephrin ligands, the ephrinAs and ephrinBs. The C57BL/6J-Epha4rb-2J/GrsrJ strain, denoted Epha4rb-2J/rb-2J, is a spontaneous mouse mutant that arose at The Jackson Laboratory. These mutants exhibited a synchronous hind limb locomotion defect or “hopping gait” phenotype, which is also characteristic of EphA4 null mice. Genetic complementation experiments suggested that Epha4rb-2J corresponds to an allele of EphA4, but details of the genomic defect in this mouse mutant are currently unavailable. We found a single base-pair deletion in exon 9 resulting in a frame shift mutation that subsequently resulted in a premature stop codon. Analysis of the predicted structure of the truncated protein suggests that both the kinase and sterile α motif (SAM) domains are absent. Definitive determination of genotype is needed for experimental studies of mice carrying the Epha4rb-2J allele, and we have also developed a method to ease detection of the mutation through RFLP. Eph-ephrin family members are reportedly expressed as numerous isoforms. Hence, delineation of the specific mutation in EphA4 in this strain is important for further functional studies, such as protein–protein interactions, immunostaining and gene compensatory studies, investigating the mechanism underlying the effects of altered function of Eph family of receptor tyrosine kinases on phenotype

Preventing type 2 diabetes mellitus in Qatar by reducing obesity, smoking, and physical inactivity: mathematical modeling analyses.

BACKGROUND: The aim of this study was to estimate the impact of reducing the prevalence of obesity, smoking, and physical inactivity, and introducing physical activity as an explicit intervention, on the burden of type 2 diabetes mellitus (T2DM), using Qatar as an example. METHODS: A population-level mathematical model was adapted and expanded. The model was stratified by sex, age group, risk factor status, T2DM status, and intervention status, and parameterized by nationally representative data. Modeled interventions were introduced in 2016, reached targeted level by 2031, and then maintained up to 2050. Diverse intervention scenarios were assessed and compared with a counter-factual no intervention baseline scenario. RESULTS: T2DM prevalence increased from 16.7% in 2016 to 24.0% in 2050 in the baseline scenario. By 2050, through halting the rise or reducing obesity prevalence by 10-50%, T2DM prevalence was reduced by 7.8-33.7%, incidence by 8.4-38.9%, and related deaths by 2.1-13.2%. For smoking, through halting the rise or reducing smoking prevalence by 10-50%, T2DM prevalence was reduced by 0.5-2.8%, incidence by 0.5-3.2%, and related deaths by 0.1-0.7%. For physical inactivity, through halting the rise or reducing physical inactivity prevalence by 10-50%, T2DM prevalence was reduced by 0.5-6.9%, incidence by 0.5-7.9%, and related deaths by 0.2-2.8%. Introduction of physical activity with varying intensity at 25% coverage reduced T2DM prevalence by 3.3-9.2%, incidence by 4.2-11.5%, and related deaths by 1.9-5.2%. CONCLUSIONS: Major reductions in T2DM incidence could be accomplished by reducing obesity, while modest reductions could be accomplished by reducing smoking and physical inactivity, or by introducing physical activity as an intervention

Serum Procalcitonin (PCT) - Is there a Role as an Early Biomarker in Infected Diabetic Foot Ulcer (IDFU) Patients?

Introduction: Infected diabetic foot ulcers may lead to serious complications if not recognised in the early stage. Diagnosis of infection is particularly challenging at that stage; thus, a sensitive inflammatory biomarker may be helpful. We aimed to evaluate the role of procalcitonin (PCT) as an early biomarker for infected diabetic foot ulcers (IDFU). Materials and method: This cross-sectional study was conducted at Klinik Rawatan Keluarga (KRK), Orthopedic clinic and wards in Hospital Universiti Sains Malaysia (USM) from May 2020 to December 2020. A total of 264 participants were recruited and divided into three groups: 50 diabetic patients with no ulcers (control), 107 patients with non-infected diabetic foot ulcers (NIDFU), and 107 patients with infected diabetic foot ulcers (IDFU). The level of PCT was taken for all patients. Total white count (TWC) and C- reactive protein (CRP) were taken only for IDFU patients. Diagnosis of infection was based on the Infectious Disease Society of America-International Working Group of Diabetic Foot (IDSA-IMWGDF), and the severity of infection was graded according to the Wagner Classification. Results: The level of PCT was higher in IDFU than in NIDFU and diabetic patient, with a median (IQR) of 0.355 (0.63) ng/mL, 0.077 (0.15) ng/mL and 0.028 (0.02) ng/mL, respectively. PCT and CRP showed moderate positive correlations in IDFU patients (p<0.001). The sensitivity and specificity were 63.6% and 83.2%, respectively, at the best cut-off at 0.25 ng/mL. Conclusion: PCT is a valuable biomarker for the diagnosis of infection; however, it adds little value in the early diagnosis of IDFU in view of its low sensitivity

The providers of health services in Lebanon: a survey of physicians

BACKGROUND: Emerging from civil distress carries with it major challenges to reforming a health system. One such challenge is to ensure an adequate supply of competent human resources. The objective of this study was to assess the supply of physicians in Lebanon in 1998, with an assessment of their practice patterns and capacity building. METHODS: Lists of members of physician's associations were examined to determine the number of physicians in Lebanon and their geographical distribution. A self-administered survey targeted 388 physicians (5%) randomly stratified by the five regions of Lebanon. Some 377 providers reported information on their demographic profile, practice patterns and development. Further, information on continuing education activities was acquired. RESULTS: In Lebanon, the overall physician-to-population ratio was 248 per 100, 000, characterized by an evident maldistribution at the intracountry regional level. Physicians worked 38 hours per week examining on average 21 patients per day, with an average time of 30 minutes spent per visit. They also reported spending 11% of their time waiting for patients. Respondents reported a very wide range of income, with 90% earning less than USD 2,000 per month. Moreover, the continuing education profile revealed a total of 43.7 hours per year, similar to that required for board certification in many developed countries. Conference attendance was the dominant continuing education activity (95% of respondents) and consumed most of the time allotted for continuing education, reported at 32 hours per year. DISCUSSION AND CONCLUSION: Various economic indicators point to an oversupply of physicians in Lebanon and a poor allocation of their time for capacity building. Therefore, it is crucial for decision-makers to closely monitor the increasing supply of providers and institute appropriate intervention strategies, taking into consideration appropriate provision of good-quality services and ensuring that continuing education activities are well established, organized and monitored

Typhoid ulcer causing life-threatening bleeding from Dieulafoy's lesion of the ileum in a seven-year-old child: a case report

<p>Abstract</p> <p>Introduction</p> <p>We describe a case of rare complication of typhoid fever in a seven-year-old child and review the literature with regard to other rare causes of bleeding per rectum. Dieulafoy's lesion is an uncommon but important cause of recurrent gastrointestinal bleeding. Dieulafoy's lesion located extragastrically is rare. We report a case of typhoid ulcer with Dieulafoy's lesion of the ileum causing severe life-threatening bleeding and discuss the management of this extremely uncommon entity.</p> <p>Case presentation</p> <p>As a complication of typhoid fever, a seven-year-old Kurdish girl from Northern Iraq developed massive fresh bleeding per rectum. During colonoscopy and laparotomy, she was discovered to have multiple bleeding ulcers within the Dieulafoy's lesion in the terminal ileum and ileocecal region.</p> <p>Conclusion</p> <p>Although there is no practical way of predicting the occurrence of such rare complications, we emphasize in this case report the wide array of pathologies that can result from typhoid fever.</p

Defining and Detecting Crossover-Interference Mutants in Yeast

The analysis of crossover interference in many creatures is complicated by the presence of two kinds of crossovers, interfering and noninterfering. In such creatures, the values of the traditional indicators of interference are subject not only to the strength of interference but also to the relative frequencies of crossing over contributed by the two kinds. We formalize the relationship among these variables and illustrate the possibilities and limitations of classical interference analysis with meiotic tetrad data from wild-type Saccharomyces cerevisiae and from mlh1 and ndj1 mutants

A gene-centric analysis of activated partial thromboplastin time and activated protein C resistance using the HumanCVD focused genotyping array.

Activated partial thromboplastin time (aPTT) is an important routine measure of intrinsic blood coagulation. Addition of activated protein C (APC) to the aPTT test to produce a ratio, provides one measure of APC resistance. The associations of some genetic mutations (eg, factor V Leiden) with these measures are established, but associations of other genetic variations remain to be established. The objective of this work was to test for association between genetic variants and blood coagulation using a high-density genotyping array. Genetic association with aPTT and APC resistance was analysed using a focused genotyping array that tests approximately 50 000 single-nucleotide polymorphisms (SNPs) in nearly 2000 cardiovascular candidate genes, including coagulation pathway genes. Analyses were conducted on 2544 European origin women from the British Women's Heart and Health Study. We confirm associations with aPTT at the coagulation factor XII (F12)/G protein-coupled receptor kinase 6 (GRK6) and kininogen 1 (KNG1)/histidine-rich glycoprotein (HRG) loci, and identify novel SNPs at the ABO locus and novel locus kallikrein B (KLKB1)/F11. In addition, we confirm association between APC resistance and factor V Leiden mutation, and identify novel SNP associations with APC resistance in the HRG and F5/solute carrier family 19 member 2 (SLC19A2) regions. In conclusion, variation at several genetic loci influences intrinsic blood coagulation as measured by both aPTT and APC resistance