Large bone defects requiring invasive surgical procedures have long been a problem for orthopedic surgeons. Despite the use of autologous bone grafting, satisfactory results are often not achieved due to associated limitations. Biomaterials are viable alternatives and have lately been used in association with Stromal Vascular Fraction (SVF), stem cells, and signaling factors for bone tissue engineering (BTE). The objective of the current study was to assess the biocompatibility of Silicon Hydroxyapatite (Si-HA) and to improve osteogenic potential by using autologous adipose-derived SVF with Si-HA in a rabbit bone defect model. Si-HA granules synthesized using a wet precipitation method were used. They were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). A hemolysis assay was used to assess the hemolytic effects of Si-HA, while cell viability was assessed through Alamar Blue assay using MC3T3 mouse osteoblasts. The osteogenic potential of Si-HA both alone and with enzymatically/non-enzymatically-derived SVF (modified) was performed by implantation in a rabbit tibia model followed by histomorphometric analysis and SEM of dissected bone after six weeks. The results showed that Si-HA granules were microporous and phase pure and that the addition of Silicon did not influence Si-HA phase composition. Si-HA granules were found to be non-hemolytic on the hemolysis assay and non-toxic to MC3T3 mouse osteoblasts on the Alamar Blue assay. Six weeks following implantation Si-HA showed high biocompatibility, with increased bone formation in all groups compared to control. Histologically more mature bone was formed in the Si-HA implanted along with non-enzymatically-derived modified SVF. Bone formation was observed on and around Si-HA, reflecting osseointegration. In conclusion, Si-HA is osteoconductive and promotes osteogenesis, and its use with SVF enhances osteogenesis.

Vitamin D deficiency is highly prevalent in Pakistan, but there is limited data on its genetic aspects. This case–control pilot study aimed to determine the association of rs782153744, rs200183599, rs118204011, and rs28934604 with vitamin D deficiency along rs7041 which has been studied in our population. The DNA of a total of 600 subjects (300 cases and 300 controls) was extracted and genotyped by tetra ARMS PCR, followed by Sanger DNA sequencing of exon 4 of the CYP2R1 and CYP27B1 genes and exon 8 of the GC gene. SNP Stat was employed to analyze the data, while logistic regression was used to calculate the p-values and odds ratios (ORs). The R package version R studio (2025.05.1) Build 513 was used to statistically analyze rs782153744. In silico modeling of wild and mutant CYP2R1 and GC proteins was performed in Swiss-Model, Swiss-Dock, Discovery Studio, and PyMol using 3c6g and IJ78 as templates to perform binding pocket analysis of vitamin D3. The rs782153744 showed a protective association in the additive (OR: 0.15, 95% CI: 0.08–0.27, p-value < 0.001), recessive (OR: 0.19, 95% CI: 0.10–0.33, p-value < 0.001), and dominant (OR: 0.19, CI = 0.10–0.33, p-value < 0.001) models, while GC rs7041 (T > A, T > G) displayed a p-value < 0.0001 across all genetic models. Sanger sequencing yielded insignificant results, and the SNPs rs200183599, rs118204011, and rs28934604 had no significant association with vitamin D deficiency. The molecular pocket analysis of wild and mutant CYP2R1 proteins carrying rs782153744 polymorphisms revealed no changes. GC proteins carrying the rs7041 polymorphism revealed a shift in their 3D and 2D configuration, as well as a change in the amino acid residue of the binding pocket of VD3. The risk-associated rs7041 and protective rs782153744 variants back genetic screening for vitamin D deficiency risk stratification, allowing targeted supplementation in predisposed subjects and assisting in formulating a genotype-specific therapeutic approach.

INTRODUCTION:  Erythromycin, a commonly used macrolide antibiotic, has been found to possess potent prokinetic properties and therefore enhances gastrointestinal motor activity. Its motilin agonist action has been clinically exploited for the treatment of patients with chronic functional pseudo-obstruction, gastro-oesophageal reflux, postoperative intestinal dysmotility, gastroparesis secondary to diabetes, and scleroderma, and after surgical vagotomy. OBJECTIVE: The objective of my study is to compare mean time of achieving full enteral feed with oral erythromycin as compared to placebo for treatment of gastrointestinal dysmotility in low birth weight preterm neonates. MATERIALS AND METHODS: Study design: Randomized controlled trial. Setting: Department of paediatrics, Lahore general hospital, Lahore. Duration of study: This study was conducted for 6 months [December 19, 2017 till June 19, 2018]   DATA COLLECTION PROCEDURE: After approval from hospital ethical committee 100 preterm neonates who presented in the paediatrics neonatal unit and emergency department of LGH fulfilling the inclusion criteria were selected. After an informed consent from the parents, the preterm neonates were randomly allocated to two groups using lottery method into Group A and group-B. Preterm neonates assigned to group A received erythromycin (12.5mg/kg/dose every 6 hour through oral route or nasogastric tube). Those allocated to group B received placebo solution (equivalent volume of normal saline orally 6 hourly). Preterm was given oral feed according to protocol (via nasogastric tube, orogastric tube or oral route). Both groups received erythromycin and placebo for 14 days. If patient developed necrotizing enterocolitis or deteriorated after start of study, erythromycin and placebo solution was discontinued. The duration of achieving full enteral feeding, type of milk used was noted in questionnaire along with demographic details of neonate.   RESULTS: The mean age of all cases was 6.74 ± 2.29 days while mean age in Erythromycin group was 6.66 ± 2.48 days and in placebo group was 6.82 ± 2.10 days. In erythromycin group there were 35(70%) male and 15(30%) female cases while in placebo group there 21(42%) male and 29(58%) female cases. In erythromycin group 19(38%) cases were on mother feeding and 31(62%) cases were formula feeding and in placebo group 23(46%) cases were on mother feeding while 27(54%) cases were on formula feeding. The mean time to achieve enteral feeding in erythromycin group was 23.04 ± 4.42 days and in placebo was 26.46 ± 4.95 days. The mean time to achieve enteral feeding was statistically less in erythromycin group was statistically less as compared to placebo group, p-value < 0.001. CONCLUSION: The study concludes that the mean time of achieving full enteral feed with oral erythromycin was significantly less as compared to placebo for treatment of gastrointestinal dysmotility in low birth weight preterm neonates. So, therapeutic effects of erythromycin can be utilized to achieve early feeding. This can also help to minimize the related morbidity and hospital stay. Keywords: Gastrointestinal dysmotility, preterm birth, prematurity, low birth weight, enteral feeding, oral erythromycin