The synovial- lining cells have been involved with rheumatoid arthritis (RA) through the secretion of various cytokines and chemokines. Increased levels of these cytokines and chemokines are seen first in the synovial and subsequently in the bloodstream of RA patients. The synovial and circulating levels of CXCL8, CXCL12, and CXCL13 are higher in the RA patients than in the healthy subjects, causing migration of immune cells to the joints, which is associated with increased joint destruction. We aimed to evaluate the effects of autologous mesenchymal stem cells intravenous administration on plasma levels of CXCL8, CXCL12 and CXCL13 at 1, 6, and 12 month follow-up periods in refractory RA patients. 13 patients with refractory RA received autologous mesenchymal stem cells (MSCs). The ELISA technique was used to evaluate the plasma level of these chemokines. CXCL8 levels were significantly decreased at month 6 after MSCs transplantation in comparison with pre-injection level, and the concentration of this chemokine was significantly increased at month 12 in comparison with the month 6 after injection (P less then 0.05). The levels of CXCL12 and CXCL13 were insignificantly decreased at months 1 and 6 after the MSCs transplantation. The interaction of MSCs after migration to the inflamed joints with CXCL8-producing cells could be one but not the only possible mechanism that reduces its production in the joints and subsequently in the plasma of RA patients. CXCL8 reduction as a consequence of MSCs application returned to pre-injection levels after 12 months. Therefore, increasing the dose of MSCs and replication of injections may maintain the potential anti-inflammatory effects of MSCs on the production of CXCL8 as an inflammatory mediator in patients with refractory RA.Homozygous mutations of PROS1, encoding vitamin K-dependent protein S (PS), have been reported so far to be associated with purpura fulminans, a characteristic fatal venous thromboembolic disorder. The current work for the first time reports the clinical phenotype in patients with juvenile retinitis pigmentosa harboring a novel likely pathogenic variant in thePROS1 gene. Whole-exome sequencing was performed on probands of a cohort with inherited retinal disease. Detailed phenotyping was performed, including clinical evaluation, electroretinography, fundus photography and spectral-domain optical coherence tomography. Analysis of whole-exome and Sanger sequencing led to the identification of a homozygous missense substitution (c.G122Cp.R41P) in PROS1 in affected individuals from two unrelated consanguineous families of Persian origin which had classic retinitis pigmentosa with no history of venous thromboembolic disorder. This variant was segregated, fully congruous with the phenotype in all family members. Consistently, none of 1000 unrelated healthy individuals from the same population carried the mentioned variant, according to Iranian national genome database (Iranome) and additional in-house exome control data. This study provides inaugural clinical traces for different role of PS as a ligand for TAM receptor-mediated efferocytosis at the retinal pigmented epithelium; the R41P variant may affect proper folding of PS needed for γ-carboxylation and extra-cellular secretion. That conformational change may also lead to defective apoptotic cell phagocytosis resulting in postnatal degeneration of photoreceptors.Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuropathy of the peripheral nervous system with a wide range of severity and age of onset. CMT patients share similar phenotypes which make it often impossible to identify the disease types based on clinical presentation and electrophysiological studies alone. In recent years, novel genetic diagnostic approaches such as whole exome sequencing (WES) has provided a ground for accurate diagnosis of CMT through identification of the disease-causing mutation(s).  https://www.selleckchem.com/products/caspofungin-acetate.html  In the present study, that approach was effectively employed. Two unrelated large pedigrees with multiple affected cases of various pattern of inheritance (one autosomal dominant and one X-linked) were included. Clinical and electrophysiological data were obtained. DNA sample from each pedigree's proband was subjected to WES. Data analysis was performed using an in-house developed pipeline, adopted from GATK and ANNOVAR. Candidate variant segregation was evaluated by PCR-based Sanger sequencing. A known but extremely rare (unreported in the Middle Easterners) mutation in BSCL2 (c.C269Tp.S90L) as well as a novel hemizygous variant in GJB1 (c.G224Cp.R75P) were identified and segregations were confirmed by Sanger sequencing. This study supports effectiveness of WES for genetic diagnosis of CMT in undiagnosed families.Objectives Robust data on the impact of comorbidities on health in people with osteoarthritis (OA) are lacking, despite its potential importance for patient management. Objectives were to determine coexisting conditions in people with OA in primary care and whether more comorbidities were linked with individual health status. Methods A retrospective analysis of 23,892 patients with knee and hip OA was conducted to determine comorbidities present (number/clusters) and how these linked with pain intensity (0-100), widespread pain (site numbers), medication usage (paracetamol, nonsteroidal anti-inflammatory drugs, opioids), quality of life EuroQol five dimension scale (EQ-5D), and physical function (walking speed) using independent t-tests or χ 2 test. Results Sixty-two percent of people with OA treated in primary care had at least one comorbidity; hypertension (37%), heart disease (8%), and diabetes (7%) being most common. Outcome measures worsened with more comorbidities (0-4+ comorbidities); pain intensity [mean (SD)] 46(22)-57(21); number of painful sites 3.7(3.0)-6.3(5.4); quality of life 0.73(0.10)-0.63(0.15); walking speed 1.57 m/s (0.33)-1.24 m/s (0.31), while the proportion of people using pain medication increased from 0 to 2 comorbidities (58-69%; p less then 0.001), with an increase in opioid use from 4.6% to 19.5% with more comorbidities (0-4+ comorbidities). Conclusion Most people with knee or hip OA in primary care have at least one other long-term condition. A greater number of comorbidities is linked with worsening health, highlighting the importance of screening for comorbidities when treating patients with OA. It is important for clinicians to consider how OA treatments will interact and affect other common comorbidities.