Functional Role of MicroRNAs in Embryogenesis

This book chapter will provide an overview of the functional role of microRNAs (miRNAs) in embryogenesis. A brief introduction to embryogenesis and emphasis on the importance of miRNAs in gene regulation will be provided. The biogenesis and mechanism of action of miRNAs will be discussed in detail with a focus on the importance of miRNA-mRNA interaction in gene regulation. The chapter will then delve into the role of miRNAs in early embryonic development, including their importance in the establishment of the three germ layers, cell proliferation, differentiation, and apoptosis during embryogenesis. The role of miRNAs in organogenesis and tissue differentiation, specifically the formation of specific organs such as the heart, lung, liver, and brain, will also be discussed. The chapter will conclude by examining the dysregulation of miRNAs in embryonic development and disease, including teratogenicity, developmental disorders, and developmental cancer. The chapter will summarize the functional roles of miRNAs in embryogenesis and will offer future perspectives and potential therapeutic applications of miRNAs in embryonic development and disease

GENITOFEMORAL NERVE BLOCK AND INTRAOPERATIVE ANALGESIA IN CHILDREN DURING INGUINAL HERNIA REPAIR

ABSTRACT Ilioinguinal and iliohypogastric nerve blocks has been widely used in children undergoing inguinal herniorraphy. This technique may provide insufficient intraoperative analgesia as the inguinal region may receive innervation from genitofemoral nerve. We proposed that the addition of genitofemoral nerve block might improve the quality of analgesia. The objective was to find the efficacy of genitofemoral nerve block in addition to ilioinguinal and iliohypogastric nerve block for better intraoperative pain management in children under going inguinal hernia repair under general anaesthesia. After informed consent, 100 children of 1-10 yrs of age and ASA I or II status undergoing inguinal hernia repair were selected and divided in group I and II of 50 patients each. After induction of general anaesthesia, Group I patients received ilioinguinal and iliohypogastric block using bupivacaine 0.375% at a dose of 0.75 mg/kg, where as patients in group II were given genitofemoral in addition to ilioinguinal and iliohypogastric nerve blocks using bupivacaine 0.375% at a dose of 0.375 mg/kg at each site. Changes in heart rate, systolic, diastolic and mean arterial pressures were recorded before the start of surgery, at skin incision, at sac traction and at the end of surgery as a measure of efficacy of the block. Haemodynamic data was analysed using repeated measures ANOVA. The two groups showed increase in (Heart Rate) but the increase was lesser in group II at sac traction (p<0.05). In group I all patients had an increase in systolic, diastolic and mean arterial pressure at sac traction while the patients in group II showed no change during the study period (p<0.05). We conclude that the addition of a genitofemoral nerve block to ilioinguinal and iliohypogastric nerve blocks may contribute to haemodynamic stability during sac traction indicating better pain relief

From risk to care:the hepatitis C screening and diagnostic cascade in a primary health care clinic in Karachi, Pakistan—a cohort study

Background\ud In the high-prevalence setting of Pakistan, screening, diagnosis and treatment services for chronic hepatitis C (CHC) patients are commonly offered in specialized facilities. We aimed to describe the cascade of care in a Médecins Sans Frontières primary health care clinic offering CHC care in an informal settlement in Karachi, Pakistan.\ud \ud Methods\ud This was a retrospective cohort analysis using routinely collected data. Three different screening algorithms were assessed among patients with one or more CHC risk factors.\ud \ud Results\ud Among the 87 348 patients attending the outpatient clinic, 5003 (6%) presented with one or more risk factors. Rapid diagnostic test (RDT) positivity was 38% overall. Approximately 60% of the CHC patients across all risk categories were in the early stage of the disease, with an aspartate aminotransferase:platelet ratio index score <1. The sequential delays in the cascade differed between the three groups, with the interval between screening and treatment initiation being the shortest in the cohort tested with GeneXpert onsite.\ud \ud Conclusions\ud Delays between screening and treatment can be reduced by putting in place more patient-centric testing algorithms. New strategies, to better identify and treat the hidden at-risk populations, should be developed and implemented

Status of introduction of pneumococcal conjugate vaccine in Pakistan

Streptococcus pneumoniae infection causes a wide spectrum of diseases ranging from acute otitis media to Invasive Pneumococcal Disease (IPD) presenting as pneumonia, meningitis, joint effusions, bacteraemia and septicaemia. Pakistan was the first country in the South Asian region to introduce PCV-10 within the routine immunisation program. Government of Pakistan, with support from Gavi, the Vaccine Alliance and other partners, introduced PCV-10 in phased manner, starting October 2012. Vaccination schedules matched other age-appropriate vaccines offered within existing Routine Immunisation (RI) schedules and were offered at 6, 10 and 14 weeks after birth. Catch up immunization was not done. Few studies conducted before vaccine introduction showed that the burden of IPD and the serotype distribution was similar to other countries in the region. The selection of PCV-10 instead of PCV-13 in Pakistan\u27s Expanded Programme for Immunization (EPI) was based largely on earlier availability of PCV-10, and the impression that there would be marginal gain in serotype coverage from a higher valence vaccine. A few studies are currently underway to assess the impact of PCV introduction in Pakistan\u27s EPI

Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: A modelling analysis

Background: The WHO elimination strategy for hepatitis C virus advocates scaling up screening and treatment to reduce global hepatitis C incidence by 80% by 2030, but little is known about how this reduction could be achieved and the costs of doing so. We aimed to evaluate the effects and cost of different strategies to scale up screening and treatment of hepatitis C in Pakistan and determine what is required to meet WHO elimination targets for incidence.Methods: We adapted a previous model of hepatitis C virus transmission, treatment, and disease progression for Pakistan, calibrating using available data to incorporate a detailed cascade of care for hepatitis C with cost data on diagnostics and hepatitis C treatment. We modelled the effect on various outcomes and costs of alternative scenarios for scaling up screening and hepatitis C treatment in 2018-30. We calibrated the model to country-level demographic data for 1960-2015 (including population growth) and to hepatitis C seroprevalence data from a national survey in 2007-08, surveys among people who inject drugs (PWID), and hepatitis C seroprevalence trends among blood donors. The cascade of care in our model begins with diagnosis of hepatitis C infection through antibody screening and RNA confirmation. Diagnosed individuals are then referred to care and started on treatment, which can result in a sustained virological response (effective cure). We report the median and 95% uncertainty interval (UI) from 1151 modelled runs.Findings: One-time screening of 90% of the 2018 population by 2030, with 80% referral to treatment, was projected to lead to 13·8 million (95% UI 13·4-14·1) individuals being screened and 350 000 (315 000-385 000) treatments started annually, decreasing hepatitis C incidence by 26·5% (22·5-30·7) over 2018-30. Prioritised screening of high prevalence groups (PWID and adults aged ≥30 years) and rescreening (annually for PWID, otherwise every 10 years) are likely to increase the number screened and treated by 46·8% and decrease incidence by 50·8% (95% UI 46·1-55·0). Decreasing hepatitis C incidence by 80% is estimated to require a doubling of the primary screening rate, increasing referral to 90%, rescreening the general population every 5 years, and re-engaging those lost to follow-up every 5 years. This approach could cost US$8·1 billion, reducing to$3·9 billion with lowest costs for diagnostic tests and drugs, including health-care savings, and implementing a simplified treatment algorithm.Interpretation: Pakistan will need to invest about 9·0% of its yearly health expenditure to enable sufficient scale up in screening and treatment to achieve the WHO hepatitis C elimination target of an 80% reduction in incidence by 2030.Funding: UNITAID