Multicentric Reticulohistiocytosis (Mrh): A Case Report On A Rare Destructive Arthritis.

Multicentric Reticulohistiocytosis is a rare disorder of unknown aetiology which affects skin and joints predominantly. There are no specific laboratory investigations for diagnosis. Diagnosis can be made clinically and on a histopathological basis. There is no consensus on treatment. We report a case from Pakistan with classical presentation who did well on methotrexate and low dose steroids. Prompt diagnosis and early treatment may save from significant disability.

A common missense variant rs874881 of PADI4 gene and rheumatoid arthritis: Genetic association study and in-silico analysis.

The peptidylarginine-deiminase 4 (PADI4) is involved in the post-translational catalytic conversion of arginine into citrulline. The autoantibodies including anti-citrullinated protein antibodies (ACPAs) produced in response to hypercitrullinated proteins are a hallmark of rheumatoid arthritis (RA) autoimmunity. Therefore, the role of a missense variant rs874881 (Gly112Ala) of PADI4 in RA susceptibility was analyzed, along with in-silico analysis of structural and functional impacts of this substitution. We did a case-control association study and in-silico analysis. For the case-control study, confirmed RA cases and healthy controls were recruited. Genotyping for rs874881 (n = 750) was performed through polymerase chain reaction-restriction fragment length polymorphism. Multivariate logistic regression analysis was employed to determine association. The in-silico analysis was carried out through HOPE, VarMap, MutationAssessor, MutPred2, SIFT, PolyPhen, CADD, REVEL and MetaLR. In the case-control study, the rs874881 exhibited a strong association with increased RA susceptibility (G vs C odds ratio = 3.85, 95 % confidence interval = 2.81-5.27). Interaction analysis revealed significant interaction of genotype with smoking and gender (p < 0.05). Significant results (p < 0.05) were also obtained in stratified analysis by presence/absence of comorbidities and radiographic damage. According to in-silico pathogenicity prediction analysis, this Gly112Ala substitution does not exert a major effect on protein structure and function including its enzymatic activity. We report a significant association of PADI4 rs874881 with overall RA susceptibility. To our knowledge, this is the first study to do the interaction and stratified analyses on the PADI4 rs874881 in RA. Similar detailed studies should also be performed in other populations.

Interactions of Chitosan-coated Green Synthesized Silver Nanoparticles using Mentha spicata and Standard Antibiotics against Bacterial Pathogens.

BACKGROUND: Infectious diseases are caused by various multidrug-resistant pathogenic bacteria and in recent scenarios, nanoparticles have been used as innovative antimicrobial agents. AIMS: This current research aimed to evaluate the bactericidal effect of chitosan-coated green synthesized silver nanoparticles using aqueous extract of Mentha spicata (MSaqu) against bacterial pathogens, i.e., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, and Streptococcus pyogenes. METHODS: Synthesis and characterization of silver nanoparticles (MSAgNPs) were carried out via atomic absorption spectrometer and Fourier-transform infrared spectroscopy. Agar well and agar disc diffusion methods were used to assess the antibacterial and synergistic effect of chitosanmediated biogenic silver nanoparticles and standard antibiotics. Three types of interactions, i.e., antagonistic (↓), synergistic (↑), and additive (¥) were observed. RESULTS: Synergistic effect was recorded against Pseudomonas aeruginosa (8.5±0.25 mm↑), Serratia marcescens (19.0±1.0 mm↑), and Klebsiela pneumonia (8.5±0.25 mm↑), an additive effect was exhibited by Escherichia coli (9.0±0.0 mm¥), Streptococcus pyogenes (10.0±0.0 mm¥), and Staphylococcus aureus (7.5±0.25 mm↓) and they showed antagonistic effects when chitosan-coated silver nanoparticles (CLMSAgNPs) were applied compared to chitosan, MSaqu, and MSAgNPs. Interesting antibacterial results were recorded when chitosan-coated Mentha spicata extract and silver nanoparticles were applied along with antibiotics. The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + K were recorded against E. coli (14.5±0.25 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + AML were recorded against E. coli (5.5±0.0 mm), S. pyogenes (10.0±0.0 mm), K. pneumonia (5.5±0.0 mm), and S. aureus (4.0±0.0 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + NOR were recorded against E. coli (16.0±0.0 mm), P. aeruginosa (19.0±0.0 mm), S. marcescens (19.5±0.25 mm), S. pyogenes (11.5.0±0.25 mm), K. pneumonia (23.0±0.0 mm), and S. aureus (8.5±0.25 mm). CONCLUSION: Current findings concluded that chitosan-coated biogenic silver nanoparticles have potential bactericidal effects against infectious pathogens and could be used as forthcoming antibacterial agents.

Association Of Tumour Necrosis Factor-Alpha -308 G/A Promoter Polymorphism With Susceptibility And Disease Profile Of Rheumatoid Arthritis.

BACKGROUND: Single nucleotide polymorphism underlying the auto-immune process governing the pathologic manifestations of rheumatoid arthritis has been the focus of study for quite a while. TNF-alpha -308 G/A promoter polymorphism have been reported to be responsible for a number of manifestations of rheumatoid arthritis. METHODS: This case-control study was conducted at the department of Rheumatology at Pakistan Institute of Medical Sciences Islamabad from 9th May to 9th August 2019 with a focus to determine the Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. One hundred and fifty cases with diagnosed rheumatoid arthritis and 150 age and gender matched controls were enrolled in the study. Their genotyping was done for tumour necrosis factor-alpha - 308 G/A promoter polymorphism. RESULTS: The genotypic analysis showed that GG genotype was the most common genotype found in 118 cases (78.66%) followed by GA (18.66%) and AA genotype (2.6%) p=0.0096 in both cases and controls. Overall, G allele was more common than A in both cases and controls pointing towards the preponderance of G genotype in our population. (p=0.003). However, the GA genotype and A allelotype was more common among cases with rheumatoid arthritis (p <0.05). No significant association of G/A polymorphism with smoking and gender, however, within gender, males had a significantly more expression of the GA genotype and A allelotype (p <0.05). CONCLUSIONS: There is a significantly more expression of the GA genotype and the A allelotype of the TNF-alpha -308 G/A promoter gene in rheumatoid arthritis patients in our population. Similarly, more males, compared to females have increased expression of the GA genotype as well as the A allelotype.