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Pyrazinamide, an antituberculosis but documented toxic drug, is subjected to computational investigation along with the metal complexes via a DFT approach to predict the structure-activity and structure-toxicity relationship. 6-31G(d,p) basis set was used for Zn, Ni, Mn, Fe, and Co, while the SDD basis set was applied to Cu, Cr, Cd, and Hg. Several reactivity parameters and charge distribution were calculated and the reactivity profile was estimated. The complexes were found to be soft and polarizable which could be responsible for their binding with bacterial targets to inhibit their growth. In contrast, pyrazinamide which is found to be hard among all is susceptible to being toxic. Moreover, the electronegative nature of the complexes can endow them with a better antibacterial effect. Since metal complexes have been found to be less toxic and more biologically interactive by computational methods, they can be employed as potent drugs for the cure of tuberculosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of acute kidney injury (AKI) in neonates with acute respiratory distress syndrome (RDS). Study Design: Cross-sectional study. Setting: Neonatal Intensive Care Unit (NICU) of National Institute of Child Health, Karachi, Pakistan. Period: January 2023 to June 2023. Material & Methods: A total of 118 neonates of both genders, born below 37 weeks of gestation and having RDS were analyzed. Demographic, clinical and laboratory parameters were noted. Frequency of AKI was determined while final outcome was noted in terms of discharged or mortality. Results: Of 118 neonates, 55.1% were girls. The mean gestational age: 33.11±1.76 weeks, mean admission age 8.30±9.0 hours, and mean birth weight 1.53±0.27 kg. AKI occurred in 50.8% of neonates with RDS. Mortality was reported in 46.6% cases. Factors associated with AKI included grunting at admission (63.3% vs. 43.1%, p=0.028), need for mechanical ventilation (35.0% vs. 12.1%, p=0.003), and platelet count on admission (p=0.042). Factors associated with mortality included lower Apgar score at minute 5 (p<0.001), resuscitation at delivery (p<0.001), grunting at admission (p=0.005), platelet count at admission (p=0.001), leukocyte count at admission (p=0.003), and the need for mechanical ventilation (p<0.001). Conclusion: Very high frequency of AKI (50.8%) in neonates with acute RDS was noted. Mortality was associated with lower Apgar scores, resuscitation at delivery, grunting at admission, low platelet and leukocyte counts, and the need for mechanical ventilation. [ABSTRACT FROM AUTHOR]

Background: Type-1 diabetes mellitus (T1DM) and autoimmune thyroid disease can occur concomitantly and patients with TIDM have a high risk of other autoimmune conditions like thyroid disease and celiac disease. This study aimed to analyze the association of anti-GAD positive T1DM with anti-thyroid antibodies and celiac disease. Methods: This cross-sectional study was conducted at the Department of Paediatric Endocrinology & Diabetes, National Institute of Child Health, Karachi Pakistan from July 2022 to December 2022. A total of 115 children of both genders aged between 1-18 years having known T1DM were analyzed. Children with chronic kidney disease or chronic liver disease were excluded. Those children were also not included whose parents/caregivers did not wish their children to be part of this research. The blood sample of each child was taken in a sterilized container and sent to an institutional laboratory for biochemical investigations. Results: In a total of 115 patients, 67 (58.3%) were female and 48 (41.7%) males. The mean age was 8.87±3.43 (ranging between 1.5-17 years). The mean HbA1c was 11.86±7.31%. It was found that anti-GAD IgG was having signification association with celiac disease (p<0.001). Significant correlation of anti-GAD positive antibodies with Ttg-IgG antibodies (correlation coefficient=0.303, p=0.001), thyroid peroxidase antibodies (correlation coefficient=0.228, p=0.001). Conclusion: High proportions of children with anti-GAD positive T1DM patients were found to have thyroid disorders and celiac disease. A significant correlation was found between anti-GAD positive antibodies, celiac disease and anti-thyroglobulin antibodies. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in CFTR genes that affect chloride ion channel. The CF is a good nominee for gene therapy as the asymptomatic carriers are phenotypically normal, and the desired cells are accessible for vector delivery. Gene therapy shows promising effects involving the correction of gene or replacement of the mutant gene with the functional one. Accordingly, various viral and non-viral carriers have been investigated. Although viral vectors are efficient, they have some problems, including mutagenesis, host immune response, higher toxicity, and costliness. On the other hand, non-viral vectors have less toxicity and immunogenic response and are easier to prepare. For a successful gene therapy, the cargo must be delivered to the target site. However, various barriers are faced by non-viral vectors, which make the gene delivery to the target site difficult. Extracellular barrier, which is the first barrier, include nucleases, negatively charged serum proteins, blood cells, and activated immune system. Ciliated epithelium, mucus gel, apical surface glycocalyx, and plasma membrane come in the second category of the barriers. Furthermore, the third category, which is related to the intracellular barriers, includes endosome and lysosome, cytoplasmic nucleases, viscous environment of cytoplasm with different proteins, and finally nuclear membrane. Various approaches have been proposed to increase the systematic delivery of vectors and enhance their efficiency. Some of these approaches include surface coating with inert polymers, modification of surface charge with anionic polymers, and enhancement of endocytosis and reduction of toxicity by using polyethylene glycol. This review paper was conduct to highlight the barriers faced by nonviral vectors when carrying a genetic payload to the lungs. This study also involved the investigation of the strategies and different types of modifications targeted toward the improvement of the efficiency of non-viral vectors. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is rapid decrease of renal function. AKI has been resulted in significant morbidity and mortality. The term RIFLE consist of risk, injury, failure, loss, and end-stage renal disease. A modified version of this criteria pRIFLE is used in pediatric population with AKI, for the severity assessment and its outcome. Therefore early intervention can be made. This study helps to make recommendations based on pRIFLE criteria for severity and outcome. Objectives: To determine severity and outcome of AKI in pediatric population using pediatric RIFLE criteria. Study design, settings and duration: It was a descriptive case series carried out in departments of Pediatric ICU and pediatric nephrology unit at National Institute of Child Health (NICH), Karachi from August 2010 to March 2011. Patients and Methods: Total ninety seven children with acute kidney injury (AKI) were included in this study. Schwartz equation was applied for calculation of estimated glomerular filtration rate (eGFR) and severity of AKI was assessed using pRIFLE criteria at presentation and then on daily basis till discharge. Outcome was labeled as death or alive. Data entered and analyzed by using SPSS version 19.0. Results: The pediatric RIFLE identified those at risk, injury, and failure in 16 (16.5%), 25 (25.8%), and 56 (57.7%) patients respectively. Outcome in term of mortality was observed in 11.3% cases. There was 6.3% death in those at risk, 17.9% (10/56) in those with failure and no significant in injury. Conclusion: There are significant number of patients in renal failure due to AKI, this implies lack of early detection of AKI and delayed referral to the pediatric tertiary care hospital so "pRIFLE criteria" can be widely used by all pediatricians for early detection of children with AKI in risk category so that early interventions may halt the progression of AKI to failure. [ABSTRACT FROM AUTHOR]

AbstractInterleukin-2 has emerged as a potent protein-based drug to treat various cancers, AIDS, and autoimmune diseases. Despite its immense requirement, the production procedures are inefficient to meet the demand. Therefore, efficient production procedures must be adopted to improve protein yield and decrease procedural loss. This study analyzed cytoplasmic and periplasmic IL-2 expression for increased protein yield and significant biological activity. The study is focused on cloning IL-2 into a pET-SUMO and pET-28a vector that expresses IL-2 in soluble form and inclusion bodies, respectively. Both constructs were expressed into different E. coli expression strains, but the periplasmic and cytoplasmic expression of IL-2 was highest in overnight culture in Rosetta 2 (DE3). Therefore, E. coli Rosetta 2 (DE3) was selected for large-scale production and purification. Purified IL-2 was characterized by SDS-PAGE and western blotting, while its biological activity was determined using MTT bioassay. The results depict that the periplasmic and cytoplasmic IL-2 achieved adequate purification, yielding 0.86 and 0.51 mg/mL, respectively, with significant cytotoxic activity of periplasmic and cytoplasmic IL-2. Periplasmic IL-2 has shown better yield and significant biological activity in vitro which describes its attainment of native protein structure and function. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that is caused by a mutation in the NF1 gene, which is located on chromosome 17q11.2, which encodes for a protein known as "Neurofibromin", which acts as an inhibitor of oncogene RAS. This gene mutation causes tumours to grow on nerves which results in other systemic abnormalities such as skin changes, bone and eye abnormalities, hormonal imbalances, and diversity in achievement of puberty with neurologic complications. NF1 has a wide variety of associations in context with puberty. It is important to determine the cause of precocious and delayed puberty in order to establish an early treatment plan, to lead a successful prognosis, and decrease complications. The case reports of two patients presenting with dichotomous pubertal variation in association with NF1 are presented.