Cholangiocarcinoma (CCA) comprises of extra-hepatic cholangiocarcinoma and intrahepatic cholangiocarcinoma cancers as a result of inflammation of epithelium cell lining of the bile duct. The incidence rate is increasing dramatically worldwide with highest rates in Eastern and South Asian regions. Major risk factors involve chronic damage and inflammation of bile duct epithelium from primary sclerosing cholangitis, chronic hepatitis virus infection, gallstones and liver fluke infection. Various genetic variants have also been identified and as CCA develops on the background of biliary inflammation, diverse range of molecular mechanisms are involved in its progression. Among these, the Notch signalling pathway acts as a major driver of cholangiocarcinogenesis and its components (receptors, ligands and downstream signalling molecules) represent a promising therapeutic targets. Gamma-Secretase Inhibitors have been recognized in inhibiting the Notch pathway efficiently. A comprehensive knowledge of the molecular pathways activated by the Notch signalling cascade as well as its functional crosstalk with other signalling pathways provide better approach in developing innovative therapies against CCA.
: Cardiovascular diseases (CVD), primarily inflammatory cardiomyopathy, are characterized by the infiltration of inflammatory cells into the myocardium. It has a relatively high risk of deteriorating heart function and has heterogeneous etiologies. Inflammatory cardiomyopathy is mainly mediated by viral infections but can also be mediated by protozoa, fungal or bacterial infections. Besides that, there are a wide variety of drugs, toxic substances, and systemic immune-mediated diseases that result in the development of cardiovascular diseases (CVDs). Despite broad research, inflammatory cardiomyopathy has a poor prognosis. The roles of the pathogens, host genomic counterparts and environmental triggers in the progression of disease are still under consideration, including the role of some viruses as active inducers and others as bystanders. In this review article, we review the available evidence on the types, pathogenesis and treatment of myocarditis, inflammatory cardiomyopathy, and atherosclerosis with a particular focus on virus-associated cardiac diseases.
Objectives: The objective of the present study is to investigate the role of cystatin C as an early marker of glomerular dysfunction in thalassemia major. Study Design: Cross sectional comparative study. Setting: Department of Biochemistry Post Graduate Medical institute with the Thalassemia Center in Sir Ganga Ram Hospital Lahore. Period: July 2017 and July 2018. Material & Methods: This study examined 90 male children all between the ages of 5-11, using non probability sampling techniques. The children were grouped as 21 healthy male children as control group I and 69 diagnosed male thalassemia major children further subdivided on the basis of serum ferritin level as group II, serum ferritin level <2500ng/ml, group III, serum ferritin level 2500-5000ng/ml and group IV serum ferritin level >5000ng/ml respectively. Individuals with hereditary renal diseases, on steroid therapy, or other co-morbid renal diseases were excluded from the study. Complete blood analysis, serum ferritin, creatinine and cystatin C were measured by Micro lab 300 and solid phase enzyme linked immune sorbent assay (ELISA) respectively. The results were compared by using SPSS version 20. Results: Group I: n=21 healthy children with ferritin between normal range 105.33 ± 30.03, serum creatinine 0.41 ± 0.05, serum cystatin C 0.57 ± 0.14. eGFR-creatinine 133.38±7.63, eGFR-cystatin C 122.9±17.63. Group II: n=20 (β-TM with ferritin <2500ng/ml). Mean ferritin was 1997.5±300.68 ng/ml (P<0.001), creatinine was 0.43± 0.05, serum cystatin C 0.66 ± 0.05 (P<0.05). eGFR-creatinine 121.45±4.89 P<0.05, eGFR-cystatin C 105.15±6.49 P<0.001. Group III: n= 25 (β-TM with ferritin 2500-5000 ng/ml). Mean ferritin level was 3850.0± 718.18 ng /ml (P<0.001), creatinine was 0.5±.07, cystatin C 0.96±0.13 (P<0.001). eGFR-creatinine 103.29±8.26(P<0.001), eGFR-cystatin C 75.75±10.67 (P<0.001). Group IV: n=24 (β-TM with ferritin >5000 ng/ml). Mean ferritin level was 6311.67±1060.61 ng/ml P value (P<0.001), creatinine was 0.57 ± 0.07, cystatin C 1.11 ± 0.09 (P<0.001). eGFR-creatinine 94.42±8.69 (P<0.001), eGFR cystatin C 64.67±4.23(P<0.001). Conclusion: A highly significant positive relation was found between serum ferritin-cystatin C as compared to creatinine among the study groups II, III and IV and significant inverse relationship between cystatin C and eGFR that concluded cystatin C as an early marker of glomerular dysfunction than creatinine in thalassaemia major children.
Aim: To evaluate the acceptability and feasibility of the multiple mini interviews for selecting medical students for admission in a medical institution. Methods: The current cross-sectional descriptive study is a 12-item questionnaire-based survey with a four-point Likert scale to record the anonymous responses of the candidate students’ and the interviewer faculty perceptions. Descriptive statistics were used to analyze the data quantitatively with IBM SPSS Version 25. The study evaluated the acceptability and feasibility of the utility of multiple mini-interviews (MMIs) as an assessment tool for the medical students’ selection in the admission process at Avicenna Medical College, Lahore, Pakistan. Results: A total of 438 candidate students and 42 interviewer/assessor faculty members participated in the study. Most of the candidate students (92.2%) of candidates and 97.6% of interviewer faculty regarded MMIs better than the traditional interviews for the selection of medical students. Further, 99.4% of candidate students and 97.6% of interviewer faculty were satisfied with the MMI process’s general arrangements. Finally, a hundred percent interviewer faculty and 96.8% of candidate students perceived MMIs as a feasible assessment tool for the admission process of the medical institutions. Conclusion: The overall positive responses of the candidate students and the interviewer faculty for the acceptability and feasibility of the MMI process as an assessment tool in the admission process to select medical students provide evidence for future research on the use of MMIs. In addition, other medical institutions can adapt or modify the MMI process per the available finances and resources within their local settings. Keywords: Multiple mini-interviews, Medical college admission process, acceptability, feasibility.
Background: Procalcitonin has been used globally as indicator marker of sepsis to define bacteremia or blood stream infection for early patient management or antibiotic therapy. Blood culture refers to a microbiological culture of a peripheral blood sample. The blood cultures help to determine the presence of systemic infections, such as septicaemia. If the culture is positive, the causative micro-organism can usually be identified, and antibiotic sensitivity testing performed. On the other hand, the sensitivity of procalcitonin in comparison to its specificity to certain bacterial infections is still in question. Methodology: In this study, we selected 309 patients without restriction of age gender with pre-diagnosed sepsis or septic shock syndrome. Blood culture samples were collected in bactAlert media plus culture bottles and were incubated in BactAlert 3D semi-automated blood culture system; blood sample was collected for serum procalcitonin on immunoassay principle. Results: Out of 309, a total 87 blood cultures were positive and PCT was positive in 134 whereas 179 were PCT negative. In positive PCT, 63 were having bacterial growth in their blood culture while 71 were with negative blood culture. Although in total, 179 PCT were negative, only 16 were having bacterial growth in blood culture samples whereas all others revealed no growth that showed maximum number of positive blood cultures were having PCT positive but not all PCT positive demonstrated bacterial growth in blood culture suggesting that the bacteremia or sepsis can only be suspected with positive PCT. In addition, blood culture positive or negative results cannot be predicted by PCT value to make diagnostic confirmation of sepsis. Keywords: Procalcitonin (PCT), Blood culture, Sepsis, 95%CI; confidence interval, IQR; Interquartile range
Background: Diabetes mellitus (DM) is considered main dangerous feature for the expansion of cardiac metabolic and coronary disorders. Chronic Heart failure along conserved ejection fraction (EF %) were distinguished by the dysfunction of left ventricle diastolic phase (LVDD). Aim: Aim of subjects with elevated serum cortisol or hydrocortisone level establish with Cushing’s syndrome has to be related with the progression of the LVDD. Methodology: We select 42 patients Diagnosed with (DM) and 40 subjects with no DM. Which was underwent echocardiography assessment at multiple hospitals of Lahore within two years of duration. The functions of left ventricle were estimate and the percentage of before time diastolic rate from inflow to trans-mitral before time diastolic rate be considered while guide for diastolic purpose. Concentration of serum cortisol in Plasma, glucose levels, serum fasting cholesterol and triglyceride levels, along by means of anti glycemic medications plus additional scientific distinctiveness was estimated, as well as along its relationship among E/A was resolute by means of only one variable and multiple variable analysis. Results: Multiple variable linear regression study illustrate that log of E/A were confidently associated by age factor (P=0.018), blood pressure systolic phase (P=0.003) and hydrocortisone (P=0.037), in subjects of diabetes mellitus. Multiple variable analysis illustrate that hydrocortisone were completely associated by means of age (P=0.016) and glycated hemoglobin (P=0.011). Therefore no relationship found among E/A and serum hydrocortisone levels in control subjects. Conclusion: Raised levels of hydrocortisone concentration might elevate the possibility of rising in subjects of diabetes mellitus. Keywords: Diabetes mellitus, left ventricle diastolic function, serum hydrocortis
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