DNA polymerase eta (Pol η) is a Y-family translesion polymerase responsible for synthesizing new DNA across UV-damaged templates. It is recruited to replication forks following mono-ubiquitination of the PCNA DNA clamp. This interaction is mediated by PCNA-interacting protein motifs within Pol η, as well as by its C-terminal ubiquitin-binding zinc finger (UBZ) domain. Previous work has suggested that Pol η itself is mono-ubiquitinated at four C-terminal lysine residues, which is dependent on prior ubiquitin-binding by its UBZ domain. Here, we show that Pol η can be modified at the same lysine residues by the ubiquitin-like protein, NEDD8. Like ubiquitination, this modification is driven by non-covalent interactions between NEDD8 and the UBZ domain. While only a small proportion of Pol η is mono-NEDDylated under normal conditions, these levels rapidly increase following inhibition of the COP9 signalosome, revealing that mono-NEDDylation is maintained under strong negative regulation. Finally, we demonstrate that mono-NEDDylation prevents Pol η foci formation in UV-C irradiated cells, suggesting that this modification prevents Pol η from participating in translesion DNA synthesis. These results thereby reveal a new mechanism by which human Pol η is regulated by ubiquitin-like proteins.
Objective: To identify the predictors of glycaemic control in children and adolescents with type-1 diabetes mellitus. Method: The analytical, cross-sectional study was conducted at the Paediatric Endocrinology Department of the National Institute of Child Health, Karachi, from June to November 2024, and comprised children of both genders aged 2-18 years having definite diagnosis of type-1 diabetes mellitus with a disease duration >1 year. Glycated haemoglobin >7.5% was labelled as poor glycaemic control. Association of glycaemic control with various socio-demographic, clinical and management-related characteristics was explored. Data was analysed using SPSS 26. Results: Of the 163 children, 83(50.9%) were girls. The overall median age at the time of presentation was 12.0 years (interquartile range: 9.0-14.0 years). The median glycated haemoglobin was 8.4% (interquartile range: 7.2-10.6). Good and poor glycaemic control was noted in 58(35.6%) and 105(74.4%) subjects, respectively. Primary caregiver being the father was independently associated with higher odds of poor glycaemic control (p=0.039). Insulin non-adherence (p=0.019) and irregular blood glucose monitoring (p<0.001) were significant independent predictors of poor glycaemic control. Patients with a check-up interval >2 months had higher odds of poor glycaemic control (p=0.010). Conclusion: The prevalence of poor glycaemic control was high among children and adolescents with type-1 diabetes mellitus. Key glycaemic control indicators included adherence to insulin and blood glucose monitoring, caregiver involvement, and regular healthcare visits. Key Words: Adolescent, Caregivers, Child, Glycaemic control, Insulin, Type-1 diabetes mellitus.
To assess dental maturity and overall dental health status in children with β-thalassemia major (β-TM) compared with healthy controls, and to examine their associations with selected clinical, anthropometric, and laboratory parameters. A hospital-based observational case-control study was conducted at Dow International Dental College (DIDC), Dow University of Health Sciences (DUHS), between March 10, 2025, and August 5, 2025. Fifty children with β-TM and fifty healthy controls aged 5–16 years were recruited using purposive sampling. Dental maturity was assessed using Nolla’s method via orthopantomograms. Periodontal and dental health was assessed using simplified periodontal screening score, the Silness–Löe Plaque Index, and tooth mobility, which were subsequently combined to generate an overall dental health grade. Data on transfusion frequency, serum ferritin, hemoglobin, and body mass index (BMI) were recorded. Analysis was performed in R software using bivariate tests, multivariable regression models adjusted for age, sex, and BMI, and age-restricted sensitivity analysis. Delayed dental maturity was observed in 56
Parenteral nutrition (PN) preparations are listed as high-alert medications and have a high probability of medication errors (MEs). Board-certified Nutrition Support Pharmacists (BCNSPs) can play an important role in reducing PN-associated complications by highlighting the gaps in the PN prescribing process. This study aimed to determine the impact of BCNSP-led PN review on the identification and documentation of prescribing MEs (PMEs) to optimize quality and safety in PN prescribing processes. This QI quasi-experimental study included all neonates admitted to a level III neonatal intensive care unit (NICU) and prescribed PN. All identified and recognized PN-PMEs documented by pharmacists were evaluated in pre-and post-implementation-phases. In the pre-phase, the PN-duty pharmacist reviewed all the neonatal PN-orders while located in the pharmacy, and in the post-phase, a clinically involved BCNSP performed this task. All PN-PMEs were categorized into ten types. Predictors of PN-PMEs were analyzed through logistic regression. PN-orders were prescribed to 98 and 112 neonates in pre-and post-phases, respectively. For demographic and clinical variables, neonates were comparable. A median of 12 (range = 9 − 19) vs. 15 (range = 12–22) PN-orders/day were reviewed in pre-and post-phases. Documented PN-PMEs for all PN orders were significantly higher in the post-phase (212/2577, 8.23
Background: Pediatric critical care remains a major challenge in low- and middle-income countries (LMICs) because of the limited PICU capacity. This often forces critically ill children to be managed in emergency departments (EDs) for long periods, exhausting the already scarce resources. This delays care and contributes to poor outcomes. The purpose of this study was to describe the characteristics, triage levels, and outcomes of children admitted from the ED to the PICU at a tertiary hospital in Pakistan. Methods We reviewed charts of all children between 1 month and 18 years who were admitted from the ED to the PICU during 2021. Information on age, sex, presenting symptoms, diagnosis, triage level, ED resource use, length of stay, and outcomes was collected. Results: Among 418 patients, most were under 5 years of age (66.9%) and male (58.6%). The majority (83%) arrived in the ED as P1 (critical) triage. Respiratory diseases were the leading cause of PICU transfer (30.6%), followed by infectious illnesses (21.2%) and central nervous system disorders (15.7%). Pneumonia (18.5%), septic shock (13.2%), and meningoencephalitis (9.4%) were frequent diagnoses. These groups also consumed the greatest share of ED resources. By contrast, trauma, gastrointestinal, and endocrine/metabolic disorders required fewer transfers and shorter stays. Conclusion: In this LMIC setting, most children transferred from ED to PICU were very young and critically ill with respiratory, infectious, or CNS diseases. Earlier transfer and expansion of intermediate-level PICUs may help reduce ED strain and improve outcomes. Clearer admission and transfer guidelines are also needed to avoid unnecessary PICU use and preserve limited resources.
