AEG-1 KNOCKOUT SENSITIZES HEPATOCELLULAR CARCINOMA (HCC) CELLS TO IONIZING RADIATION

Liver cancer is the fourth leading cause of cancer-associated deaths globally, and among primary liver cancers, hepatocellular carcinoma (HCC) encompasses 75-85% of all cases. HCC is a highly lethal disease due to limited treatment options – only a small subset of patients qualify for surgical resection or transplantation; the remaining patients often display resistance to radiation therapy or chemotherapy. Overexpression of the oncogene astrocyte elevated gene-1 (AEG-1) is associated with poorer survival and increased tumor recurrence in HCC, and numerous studies show its role in initiation of hepatocarcinogenesis. A prior study also demonstrated AEG-1 expression inhibits senescence by diminishing the ATM/Chk1/Chk2/p53/p21 DNA damage response (DDR) pathway. The aim of this study is to understand if AEG-1 expression promotes radioresistance in HCC. A CRISPR/Cas9 plasmid system was used to delete AEG-1 in the QGY-7703, HuH7 and DihXY cell lines, which model HCC. The cell lines were then treated with ionizing radiation (IR). We find that knockout of AEG-1 in these cell lines induces sensitivity to IR at 2.5 Gy. In response to radiation, AEG-1 wildtype cells more profoundly upregulate ATR, Chk1, and Chk2 signaling; and also more rapidly induce γH2AX, ATM, and BRCA1 signaling, which sense dsDNA breaks to initiate homologous recombination repair. We conclude that AEG-1 expression protects HCC cells from IR through two mechanisms: 1) rapidly initiating the DNA damage response; and 2) increasing replication fork stabilization. These findings indicate AEG-1 can be a therapeutic target in combination with radiation treatment to improve outcomes for HCC patients who demonstrate radioresistance

Human Dynamics of Street Administration: A Study on Traffic Wardens in Karachi

The study investigated the myriad of psychological and physical stress factors affecting traffic wardens in Karachi. It was hypothesized that traffic wardens do not feel satisfied or stressed with their jobs and also that job tenure has no relation to their job satisfaction and stress. A mixed method approach with 15 semi-structured interviews and 50 survey form was adopted using convenient sampling. Job stress and satisfaction was measured using a self-made questionnaire (a =.797 & .582). Analysis indicated that traffic wardens were satisfied with their jobs and employment duration was not found to be associated with job satisfaction and stress.  

Mortality Trends In Pre COVID And Pandemic Era In A Tertiary Care Setting

Objective: The coronavirus pandemic has emphasized stay-at-home and social distancing policies. Since the beginning of the outbreak of COVID-19, there has been a declining trend of hospital mortality indicating that the pandemic might keep patients from seeking emergency care in a hospital setting. This study was carried out to determine the mortality trends pre-COVID and pandemic periods in a tertiary care hospital. Methods:  Study design: Retrospective observational study Place and Duration: 1st January 2019 to December 2021 at Federal Government Polyclinic (FGPC) Hospital Islamabad It was a retrospective review done on death data of pre-COVID (January-December 2019) and pandemic(January 2020-December 2021) period. Data on death was retrieved from medical male and female wards, medical ICU and isolation ward. The mortality rate was measured for both pre-COVID and pandemic periods along with co-morbid for the pandemic period. Descriptive statistics were measured with the SPSS software version. 23.  Association with age, gender and mortality was observed using a chi-square test taking p value ≤ 0.05 as significant. Result: In this study of the 366 deaths, the average age of patients in the pre-COVID and pandemic era was57.40±17.910 and 64.31±16.065 respectively. The males and females were 50.9% and 49.1% in the pre-COVID period while 61.5% and 38.5% in the pandemic period. The frequency of deaths was 46.7% in the pre COVID and 53.3% in the pandemic period with a p-value <0.05. Patients with co-morbid died more in the pandemic era. Conclusion: It was observed that hospital mortality trends were in decline during the COVID-19 pandemic in our setting which may be associated with lockdown, decreased access to the hospitals or fear of going to hospital

Need of physical and chemical restraints: Experiences at inpatient psychiatric ward in a tertiary care hospital in Karachi, Pakistan

In psychiatry, agitated / aggressive patients are often treated with de-escalation techniques. If this does not work, physical or chemical restrains are required; but in the event of resistance, seclusion is applied. We report the findings of baseline study of experiences of physical and chemical restraints in a tertiary care hospital in Karachi, where 104 files were evaluated retrospectively. The mean age of patients was 32.5 ±14.3 years with 54.8% men, while the average length of stay was 11.5 ±9.3 days. Agitation, violent behaviour, and aggression were the most common indications for restraints. In total, 94.5% of patients had both physical and chemical restraints with the latter being used as the first choice in 70 patients; whereas, 67.1% of patients\u27 families were not informed before application of restraints. The seclusion need assessment was conducted in 4.1% of patients

Determinants of Increasing Trend of Self-Medication in a Pakistani Community

Purpose: To determine the major reasons, sources, diseases and drugs responsible for increasing trend of self-medication.Method: A community-based cross-sectional survey was carried out in the district of Faisalabad in Pakistan. Respondents (1488) were classified on the basis of age, sex, education, lifestyle and their economical level. A questionnaire was distributed among the sample population to collect data.Results: Majority of respondents involved in self-medication were aged between 15 and 20 years. Family members (N = 717, 48 %) were considered the major source of information for self-medicated drugs. Lack of time (N = 504, 37 %) while economic issues (N = 485, 33 %) were the major reasons for self-medication. Medical stores were the source of drug purchase by 1087 (73 %) respondents. Headache (N = 772, 52 %) and fever (N = 600, 40 %) were the main indications for self-medication while 694 respondents reported that they engage in single-dose self-medication. Paracetamol (N = 689, 46 %), other analgesics (N = 488, 33 %),  non-steroidal anti-inflammatory (N = 680, 46 %) were reported to be used frequently for self-medication.Conclusion: Self-medication is prevalent in the Pakistani community due to easy access to over the counter (OTC) and prescription-only medicines  (POM). This may lead to untoward effects in consumers of the products. Special interventions by relevant regulatory agencies regarding the sale of the drugs are therefore required.Keywords: Self-medication, OTC drugs, Pharmacist

Assessment of apparent diffusion coefficient values as predictor of aggressiveness in peripheral zone prostate cancer: comparison with Gleason score

Purpose. To determine association between apparent diffusion coefficient value on diffusion-weighted imaging and Gleason score in patients with prostate cancer. Methods. This retrospective case series was conducted at Radiology Department of Aga Khan University between June 2009 and June 2011. 28 patients with biopsy-proven prostate cancer were included who underwent ultrasound guided sextant prostate biopsy and MRI. MRI images were analyzed on diagnostic console and regions of interest were drawn. Data were entered and analyzed on SPSS 20.0. ADC values were compared with Gleason score using one-way ANOVA test. Results. In 28 patients, 168 quadrants were biopsied and 106 quadrants were positive for malignancy. 89 lesions with proven malignancy showed diffusion restriction. The mean ADC value for disease with a Gleason score of 6 was 935mm(2)/s (SD = 248.4mm(2)/s); Gleason score of 7 was 837mm(2)/s (SD = 208.5mm(2)/s); Gleason score of 8 was 614mm(2)/s (SD = 108mm(2)/s); and Gleason score of 9 was 571mm(2)/s (SD = 82mm(2)/s). Inverse relationship was observed between Gleason score and mean ADC values. Conclusion. DWI and specifically quantitative ADC values may help differentiate between low-risk (Gleason score, 6), intermediate-risk (Gleason score, 7), and high-risk (Gleason score 8 and 9) prostate cancers, indirectly determining the aggressiveness of the disease