Sex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity

Lupus is less common in men than women, and the reason is incompletely understood. Current evidence indicates that lupus flares when genetically predisposed individuals encounter environmental agents that trigger the disease, and that the environmental contribution is mediated at least in part by T cell DNA demethylation. We hypothesized that lupus disease activity is directly related to total genetic risk and inversely related to T cell DNA methylation levels in each patient. Since women are predisposed to lupus in part because of their second X chromosome, we also hypothesized that men would require a greater genetic risk, a greater degree of autosomal T cell DNA demethylation, or both, to achieve a lupus flare equal in severity to women. Genetic risk was determined by genotyping men and women with lupus across 32 confirmed lupus susceptibility loci. The methylation status of two autosomal genes known to demethylate in T cells in proportion to disease activity, KIR2DL4 (KIR) and PRF1, was measured by bisulfite sequencing. Lupus disease activity was determined by the SLEDAI. Interactions between genetic score, T cell DNA demethylation, and the SLEDAI score were compared between the men and women by regression analysis. Combining the degree of DNA demethylation with the genetic risk score for each patient demonstrated that the (genetic risk)/(DNA methylation) ratio increased directly with disease activity in both men and women with lupus. Importantly, men required a greater (genetic risk)/(DNA methylation) ratio to achieve a SLEDAI score equivalent to women (P = 0.010 for KIR and P = 0.0054 for PRF1). This difference was not explained by a difference in the genetic risk or T cell DNA demethylation alone, suggesting a genetic-epigenetic interaction. These results suggest that genetic risk and T cell DNA demethylation interact in lupus patients to influence the severity of lupus flares, and that men require a higher genetic risk and/or greater degree of T cell DNA demethylation to achieve a lupus flare equal in severity to women.     

Cardiogenic shock in autoimmune rheumatologic diseases: an insight on etiologies,management, and treatment outcomes

Heart Failure Reviews - Autoimmune rheumatological disorders are known to have an increased risk for cardiovascular diseases including coronary artery disease (CAD), myocarditis, pericarditis,...     

Supplemented surgical management of resistant pulmonary mycobacterium tuberculosis, 6?years’ experience

Introduction

In patients with resistant pulmonary tuberculosis, proper anti-mycobacterial drugs, lung resection and manipulation of their living environment should result in sputum negativity. In published literature, 10?C15?% of patients continued to be sputum- smear or culture positive or developed a relapse after proper lung resection.

Objectives

The aim of current study was to review results of our surgically treated patients to definerate and possible causes of persistent or relapsing tuberculosis and also to evaluate the efficacy of a program of medical, surgical, physical and nutritional support that was offered to all patients.

Patients and methods

In spite of regular four-drug anti-tuberculosis regimen including rifampin and isonecotenic acid hydrazide for 90?days or more, the examined bronchial lavage was positive for tuberculosis in 167 patients. Consequently, they had lung resection surgery, continued proper medical treatment and a staff supervised manipulation of life style by physiotherapy, nutritional support and education on hygienic measures. Follow up examination and results of sputum smear were analyzed.

Results

After lung resection, four patients (2?%) had prolonged air leak and two(1?%) developed post-pneumonectomyempyema, One patient had a relapse of pulmonary tuberculosis and six(4?%) hadpersistently positive sputum smears. One of them developed broncho-pleural fistula and subsequently died.

Conclusions

Pulmonary resection combined with continuation of proper anti-tuberculous drugs and manipulation of the patient??s life style with nutritional support, education and physio-therapy improved results of lung resection in this group of patients.     

Epidemiology of visceral leishmaniasis in the Jenin District,West Bank: 1989-1998

Fifty patients from rural areas in the Jenin district of the West Bank, Palestinian Authority, were diagnosed with visceral leishmaniasis (VL) between 1989 and 1998. Forty-nine (98%) were younger than 6 years old, the youngest being 9 months. The yearly incident rate of VL in the Jenin district was highest in 1994 (11.8/100,000) and decreased to 1.5/100,000 in 1998; a mortality rate of 4% was recorded. Seventeen (5.5%) of 308 dogs from the Jenin and Ramallah districts of the West Bank were seropositive by enzyme-linked immunosorbent assay in a survey of canine leishmaniasis. Although all the leishmanial strains cultured from humans and dogs were identified as Leishmania infantum by a species-specific polymerase chain reaction, further genetic analysis by restriction fragment length polymorphism of kinetoplast DNA revealed patterns of polymorphism within isolates. The findings indicate that an active focus of potentially fatal VL exits in the Jenin district of the West Bank and that the parasite, vector, and reservoir host are found in this area. The epidemiology of VL in that vicinity follows the pattern of a predominantly infantile disease traditionally found in Middle Eastern countries, without a considerable involvement of immunocompromised adults infected with HIV virus as reported in other regions.     

Validation and inter-rater reliability testing of the Arabic version of speech intelligibility rating among children with cochlear implant

Objectives:To validate and assess the reliability of the new version of an Arabic speech intelligibility rating among different raters.Methods:This cross-sectional analysis was carried out between December 2018 and January 2019. Thirty cochlear-implant (CI) children (study group) and 30 subjects (control group) were enrolled. Study candidates’ speech skills were evaluated using the translated Arabic SIR by parents and original SIR by professions such as speech-language pathologists (SLPs). Inter-rater agreement, test–retest reliability, pre- and post-intervention score (responsiveness test), patient versus control score comparison (discriminant validity), and cross-validation of Arabic SIR have all been assessed.Results:There was a good sense of agreement between the post-operative SIR parents’ assessments and the professional SLPs’ assessments (r=0.920, p<0.001). The mean of study subjects pre- and post-implantation score of Arabic SIR showed a statistically significant difference (p<0.001).Conclusion:The Arabic SIR demonstrated excellent reliability with strong consistency. It showed its clinical ability in distinguishing healthy subjects from patients along with follow up of speech development skills over time. The Arabic SIR can be used by parents to evaluate post-CI progress of their children.