Neonatal hyperbilirubinemia in infants with G6PD c563C \u3e T variant

Background: There is a strong correlation between glucose-6-phosphate dehydrogenase (G6PD) deficiency and neonatal hyperbilirubinemia with a rare but potential threat of devastating acute bilirubin encephalopathy. G6PD deficiency was observed in 4–14% of hospitalized icteric neonates in Pakistan. G6PD c.563C \u3e T is the most frequently reported variant in this population. The present study was aimed at evaluating the time to onset of hyperbilirubinemia and the postnatal bilirubin trajectory in infants having G6PD c.563C \u3e T. Methods: This was a case–control study conducted at The Aga Khan University, Pakistan during the year 2008. We studied 216 icteric male neonates who were re-admitted for phototherapy during the study period. No selection was exercised. Medical records showed that 32 were G6PD deficient while 184 were G6PD normal. Each infant was studied for birth weight, gestational age, age at the time of presentation, presence of cephalhematoma, sepsis and neurological signs, peak bilirubin level, age at peak bilirubin level, days of hospitalization, whether phototherapy or exchange blood transfusion was initiated, and the outcome. During hospital stay, each baby was tested for complete blood count, reticulocyte count, ABO and Rh blood type, direct antiglobulin test and quantitative G6PD estimation [by kinetic determination of G6PDH]. G6PDgenotype was analyzed in 32 deficient infants through PCR-RFLP analysis and gene sequencing. Results: G6PD variants c.563C \u3e T and c.131 C \u3e G were observed in 21 (65%) and three (9%) of the 32 G6PD deficient infants, respectively. DNA of eight (25%) newborns remained uncharacterized. In contrast to G6PD normal neonates, infants with c.563C \u3e T variant had significantly lower enzyme activity (mean ± 1SD; 0.3±0.2 U/gHb vs. 14.0±4.5 U/gHb, p\u3c0.001) experienced higher peak levels of total serum bilirubin (mean ± 1SD; 16.8±5.4 mg/dl vs. 13.8±4.6 mg/dl, p=0.008) which peaked earlier after birth (mean ± 1SD 2.9±1.6 vs. 4.3±2.3 days, p=0.007). No statistically significant difference was observed in mean weight, age at presentation, hemoglobin, reticulocyte count, TSH level, hospital stay or in the frequency of initiation of phototherapy or blood exchange between the two groups. Conclusions: We concluded that infants with G6PD c.563C \u3e T variant developed jaundice earlier than infants with normal G6PD enzyme levels. Compared to G6PD normal infants, G6PD c.563C \u3e T carrying infants had significantly low G6PD activity

Gestational diabetes mellitus and the predisposing factors

Objective: To evaluate the occurrence of gestational diabetes mellitus and its association with demographic and anthropometric variables in pregnant women.Methods: This cross-sectional study was conducted at the Aga Khan University Hospital, Abbasi Shaheed Hospital and Memon Hospital in Karachi, from February 2014 to December 2015, and comprised pregnant women who were screened by 75-g 2-hour oral glucose tolerance test, (24-28 weeks of gestation) and classified as per the criteria of the International Association of Diabetes and Pregnancy Study Group. Weight, body mass index and serum glycated haemoglobin levels were measured. Women with pre-gestational diabetes were excluded. SPSS 21 was used for data analysis.Results: Of the 1,210 participants, 208(17.2%) had gestational diabetes, while 1,002(82.8%) did not have the condition. Gestational diabetes was associated with advancing age, deranged glycated haemoglobin, elevated body mass index at booking (p0.05).Conclusions: Pre-existing adiposity and presence of strong family history rendered a considerable number of pregnant women to suffer from gestational diabetes

Managing acute pain in HIV+/AIDS patients: Knowledge and practice trends among emergency physicians of major tertiary care centers of a developing country

Objective: To assess knowledge and practice trends in managing acute pain in patients infected with human immunodeficiency virus (HIV+) or having acquired immunodeficiency syndrome (AIDS) among emergency physicians of four tertiary care hospitals. Acute pain management in such patients is complex because of multiple concomitant painful conditions related to their disease. After obtaining ethical approval and written informed consent, emergency physicians were requested to fill out a questionnaire.Results: Out of 84 physicians who participated, 49 had managed HIV+/AIDS patients during the preceding year. Out of the 49, 30 (61.2%) physicians stated that they used a combination of analgesics for acute pain in these patients. Forty-two (50%) out of the 84 participants believed that routine doses of opioids were adequate for pain relief, while 42 (50%) agreed that pain management was more complex in these patients mainly due to presence of multiple coexisting problems and psychological issues. Only 26 (31%) respondents considered that pain was under-reported and under-treated in these patients, mainly because physicians were more focused on patients\u27 other disease related complications and issues. Formulation of guidelines are recommended for effective acute pain management in these patients encompassing associated issues, including concomitant painful conditions, opioid dependence, psychiatric problems, etc

Mutational landscape of head and neck squamous cell carcinomas in a South Asian population

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type globally and contributes significantly to burden of disease in South Asia. In Pakistan, HNSCC is anmong the most commonly diagnosed cancer in males and females. The increasing regional burden of HNSCC along with a unique set of risk factors merited a deeper investigation of the disease at the genomic level. Whole exome sequencing of HNSCC samples and matched normal genomic DNA (n=7) was performed. Significant somatic single nucleotide variants (SNVs) were identified and pathway analysis performed to determine frequently affected signaling pathways. We identified significant, novel recurrent mutations in ASNS (asparagine synthetase) that may affect substrate binding, and variants in driver genes including TP53, PIK3CA, FGFR2, ARID2, MLL3, MYC and ALK. Using the IntOGen platform, we identified MAP kinase, cell cycle, actin cytoskeleton regulation, PI3K-Akt signaling and other pathways in cancer as affected in the samples. This data is the first of its kind from the Pakistani population. The results of this study can guide a better mechanistic understanding of HNSCC in the population, ultimately contributing new, rational therapeutic targets for the treatment of the disease

Ontogeny of mammalian metabolizing enzymes in humans and animals used in toxicological studies

It is well recognized that expression of enzymes varies during development and growth. However, an in-depth review of this acquired knowledge is needed to translate the understanding of enzyme expression and activity into the prediction of change in effects (e.g. kinetics and toxicity) of xenobiotics with age. Age-related changes in metabolic capacity are critical for understanding and predicting the potential differences resulting from exposure. Such information may be especially useful in the evaluation of the risk of exposure to very low (mu g/kg/day or ng/kg/day) levels of environmental chemicals. This review is to better understand the ontogeny of metabolizing enzymes in converting chemicals to either less-toxic metabolite(s) or more toxic products (e.g. reactive intermediate[s]) during stages before birth and during early development (neonate/infant/child). In this review, we evaluated the ontogeny of major phase I and phase II metabolizing enzymes in humans and commonly used experimental animals (e.g. mouse, rat, and others) in order to fill the information gap

THE APPENDIX: A REPORT

Appendix is a small finger-like tube, about 7cm to 10cm long, attached to the cecum just below ileocecal valve. It was considered a vestigial organ for a long time, but recent studies correlate its important role in immune function and maintenance of gut micro biota. Inflammation of appendix is called acute appendicitis. The incidence of appendicitis all over the world is 233 per 100,000 populations per year1. Appendectomy (surgical removal of appendix) is the most common abdominal surgical emergency worldwide. More research needs to be done to establish the exact cause of increased incidence of acute appendicitis during (time mentioned). Only in this way we can avoid such an outbreak in future

Towards a Carbon Neutral and Sustainable Campus: Case Study of NED University of Engineering and Technology

Globally, universities are evaluating and targeting to reduce their carbon emissions and operate on a sustainable basis. The overall aim of this study revolves in addressing the following three questions: (1) How to calculate carbon footprint, including indicators selection, criteria, and measurement, for higher education institutions? (2) How to evaluate impact and effectiveness of various mitigation strategies in context of a higher education institution? (3) What are the possible limitations of approach selected for carbon footprint calculation. This paper presents estimation of the carbon footprint of NED University using a carbon calculator along with the identification of sources with maximum contribution to its carbon footprint. The carbon footprint of the NED University main campus for 2017 was calculated to be approximately 21,500 metric tons of equivalent CO2 and carbon footprint per student was 1.79 metric tons of equivalent CO2. Scope 1 and Scope 2 emissions each contributed nearly 7% of the carbon footprint, while Scope 3 emissions accounted for 85.6% of the carbon footprint. Major interventions such as switching to renewables, usage of energy efficient appliances, electric vehicles, and massive tree plantation inside and outside the campus were identified as the most effective mitigation strategies

Towards a Carbon Neutral and Sustainable Campus: Case Study of NED University of Engineering and Technology

Globally, universities are evaluating and targeting to reduce their carbon emissions and operate on a sustainable basis. The overall aim of this study revolves in addressing the following three questions: (1) How to calculate carbon footprint, including indicators selection, criteria, and measurement, for higher education institutions? (2) How to evaluate impact and effectiveness of various mitigation strategies in context of a higher education institution? (3) What are the possible limitations of approach selected for carbon footprint calculation. This paper presents estimation of the carbon footprint of NED University using a carbon calculator along with the identification of sources with maximum contribution to its carbon footprint. The carbon footprint of the NED University main campus for 2017 was calculated to be approximately 21,500 metric tons of equivalent CO2 and carbon footprint per student was 1.79 metric tons of equivalent CO2. Scope 1 and Scope 2 emissions each contributed nearly 7% of the carbon footprint, while Scope 3 emissions accounted for 85.6% of the carbon footprint. Major interventions such as switching to renewables, usage of energy efficient appliances, electric vehicles, and massive tree plantation inside and outside the campus were identified as the most effective mitigation strategies