Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset.

VEGF Profile in Early Undifferentiated Arthritis Cohort.

Background and Objectives: Early undifferentiated arthritis (UA) is a group of inflammatory joint diseases that are not classified under any specific rheumatic or connective tissue disorder and might evolve into chronic inflammatory arthritis or may be a self-limiting condition. Early recognition and treatment are crucial for the future course of the disease. Vascular endothelial growth factor (VEGF) is an angiogenic regulator that induces the growth of new capillary blood vessels, which are important in joint invasion and destruction during the progression of chronic inflammatory arthritis. The aim of this study was to assess VEGF levels associated with sociodemographic, clinical, laboratory, and ultrasound findings in the early UA patient cohort as well as to evaluate VEGF as a potential prognostic marker for arthritis outcomes. Materials and Methods: Seventy-six patients with inflammatory arthritis in at least one joint, with a duration of arthritis <12 months at the study entry that did not meet any rheumatic disease classification criteria, were enrolled after informed consent was obtained. Patient's sociodemographic, laboratory data, and clinical disease characteristics were recorded, VEGF levels were measured, and ultrasound (US) of tender and swollen joints was performed. Results: VEGF levels had positive correlation with conventional rheumatic disease activity and diagnostic markers: erythrocyte sedimentation rate (ESR), C−reactive protein (CRP), and rheumatoid factor (RF) (p < 0.05). RF-positive patients had higher VEGF values (p = 0.024). A statistically higher number of patients whose VEGF levels were below the median value presented with active infection (p = 0.046). In patients with a higher number of swollen joints, and a higher score of synovitis and power doppler (PD) seen on US, VEGF levels were statistically significantly higher. Patients who after 12-month follow-up developed rheumatoid arthritis (RA) had statistically higher VEGF levels at baseline compared with those who developed spondyloarthropathies (p = 0.028). Conclusions: This study demonstrated that VEGF levels significantly represented inflammatory processes that were present in the joints (number of swollen joints, synovitis, and PD changes) of the early UA cohort.

Lyme Disease among Patients at an Ambulatory Unit in a Highly Endemic Country: Lithuania.

Background and objectives: Lyme disease is the most common tick-borne infectious disease in Europe, caused by the spirocheta bacteria of Borrelia burgdorferi. Several genospecies of B. burgdorferi are pathogenic to humans. B. burgdorferi sensu stricto, which is prevalent in North America, causes reactive arthritis, whereas B. garinii and B. afzelii, common in Europe, can affect the skin, heart, or nervous system; it has been shown that the clinical symptoms of the disease may be very different. The objective of this study was to identify the baseline characteristics of Lyme disease and to elucidate the frequency of different Lyme disease syndromes in Lithuania. Materials and Methods: Patients who were diagnosed with Lyme disease during an ambulatory visit to the Center of Infectious Diseases, Vilnius University Santaros clinics, from 2014 to 2016, were enrolled in this study. A retrospective material analysis was conducted. Results: In total, 1005 patients were enrolled with the following prevalence of clinical syndromes: erythema migrans (EM), 945 (94.02%); Lyme arthritis, 32 (3.18%); neuroborreliosis, 23 (2.28%); Lyme carditis, 4 (0.39%); and acrodermatitis, 1 (0.09%). Erythema migrans was dominant among middle-aged women, with a rash appearing mainly on the lower extremities. Lyme arthritis mainly manifested among middle-aged women as an oligoarthritis, mostly affecting the knee joint. Neuroborreliosis was seen more often in middle-aged women than men and the main symptom was nervus facialis neuropathy. Lyme carditis, manifested as an atrioventricular block, with a male/female ratio of 3:1, and the median age was 51. Acrodermatitis was diagnosed in a 61-year-old woman, as a painful, red rash on the hand. Conclusions: According to the prevalence of B. garinii and B. afzelii in Europe, previously it was thought that Lyme disease presented as erythema migrans, and less frequently as neuroborreliosis; however, this study revealed that other syndromes may also be seen. In addition, we revealed that the longer it takes for erythema migrans to appear, the greater the likelihood of Lyme arthritis developing.

Epidemiology of Lyme Disease in a Highly Endemic European Zone.

Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infectious disease caused by the spirochete bacteria Borrelia. The risk of infection depends on the geographical area, ecological factors, and human behavior. Clinical manifestations of Lyme borreliosis have a wide range, but the most frequent clinical symptom, which is also a diagnostic symptom, is a skin rash called erythema migrans (EM). The disease is very common worldwide. In Lithuania, the disease frequency is 99.9 cases per 100,000 population (Centre for Communicable Diseases and AIDS, Lithuania, 2017). The main aim of this study was to obtain the baseline characteristics of the disease regarding the infected Lithuanian population. Materials and Methods: We analyzed data from the Centre for Communicable Diseases and AIDS about all Lyme disease (A69.2) diagnosed patients over a three-year period (from 2014 to 2016) in Lithuania. Results: In 2014-2016, 7424 (crude incidence rate 85.4) cases with LB were diagnosed in Lithuania. Most of them (4633 (62.4%)) were identified in women. Older people were more likely to suffer from LB. Urban residents were 2.6 times more often affected that those living in villages. Tick bites were primarily observed in high season months, from May to September (90%), with the highest peak in July. There was a higher number of observed tick bites (p = 0.003) in the urban residents. Erythema migrans occurred in 75.6% LB cases, while other symptoms did not exceed a quarter of all LB cases. There were 7353 (99.6%) cases where LB was confirmed via clinical symptoms and/or laboratory tests. Also, 1720 (23.2%) patients were tested for LB immunoglobulins. Conclusions: This study found a high incidence of Lyme disease in Lithuania. We elucidated the baseline characteristics regarding the infected Lithuanian population which may ease medical clinicians' work on new Lyme diagnoses.

Inadequate evaluation and management of suspected -infections after TKA surgery in Lithuania: a retrospective study of 2,769 patients with 2-year follow-up.

Background and purpose - The evidence-based algorithms for treatment of periprosthetic joint infection (PJI) recommend surgical intervention in combination with the use of systemic antibiotics. However, still it is not unusual to treat total knee arthroplasty (TKA) patients with suspected infection using only antibiotics. We investigated treatment pathways for TKA patients with suspected infection in Lithuania. Patients and methods - Of the 4,069 TKA patients (4,269 knees) registered in the Lithuanian Arthroplasty Register (2013-2015) 2,769 patients (2,825 knees) were interviewed 2 years after the surgery. The patients were asked if they had been subject to antibiotic treatment after the TKA surgery and/or if any additional surgical interventions on the operated knee had been performed. The number of patients treated with antibiotics due to problems in the operated knee was identified and cumulative revision rates (CRR) were calculated. Results - 180 (7%) patients of the total 2,769 reported that they had been prescribed antibiotics after the primary TKA; 132 of these patients (70%) said they had received antibiotics due to problems with the operated knee. The 2-year CRR after TKA in patients not treated with antibiotics was 0.7% (95% CI 0.4-1), as compared with 24% (95% CI 17-32) in those who had used antibiotics due to the problems in the operated knee for more than 1 week. Interpretation - In Lithuania there seems to be a lack of adherence to evidence-based treatment guidelines when infection is suspected after primary TKA.

Validation of Lithuanian Arthroplasty Register Telephone Survey of 2769 Patients Operated for Total Knee Replacement.

Background and objectives: The aim of our study is to validate the registration of knee arthroplasty revisions in the Lithuanian Arthroplasty Register (LAR) and thus give an indication of the accuracy of the published revision rates. Materials and methods: A total of 4269 primary total knee arthroplasties (TKAs) registered in the LAR between 2013 and 2015 were included. Two years after surgery the patients were contacted by phone in order to inquire if they had been subject to revision. The information from the patients was then cross checked against what had been registered in the LAR, and in case of a revision not having been registered hospital charts were investigated. Thus, the patients were followed up with regarding revision and/or death until 2017. A true revision was defined as an addition, exchange, or removal of one or all components. Results: Out of 4269 primary TKAs, we managed to contact and interview 2769 patients. Nine small hospitals were not able to provide contact details (telephone numbers) for 533 patients (549 knees). Sixty-seven patients (67 knees) were deceased (data from the Lithuanian National Census Register) and a further 438 patients (565 knees) appeared to have a wrong or non-valid telephone number, leaving 3031 (3091 knees) patients being contacted. Of those, 262 patients (266 knees) refused to participate in the study which left 2769 responders (2825 knees). Sixty-one patients said that reoperation had been performed on the index knee within two years of their primary surgery. After checking with the clinics, 10 were surgical procedures on the knee but not true revisions by our criteria. Out of the 51 true revisions we found that 46 were registered to the LAR as revised, while five (9.8%) revisions were missing. Conclusions: We conclude that the Lithuanian Arthroplasty Register has a good completeness of registered revision TKAs as only 9.8% of revisions were missing.

Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis.

BACKGROUND AIMS: Stem cells derived from the dental pulp of human exfoliated deciduous teeth (SHEDs) have unique neurogenic properties that could be potentially exploited for therapeutic use. The importance of paracrine SHED signaling for neuro-regeneration has been recognized, but the exact mechanisms behind these effects are presently unknown. In the present study, we investigated the neuro-protective potential of exosomes and micro-vesicles derived from SHEDs on human dopaminergic neurons during oxidative stress-induced by 6-hydroxy-dopamine (6-OHDA). METHODS: ReNcell VM human neural stem cells were differentiated into dopaminergic neurons and treated with 100 µmol/L of 6-OHDA alone or in combination with exosomes or micro-vesicles purified by ultracentrifugation from SHEDs cultivated in serum-free medium under two conditions: in standard two-dimensional culture flasks or on laminin-coated micro-carriers in a bioreactor. Real-time monitoring of apoptosis was performed with the use of time-lapse confocal microscopy and the CellEvent Caspase-3/7 green detection reagent. RESULTS: Exosomes but not micro-vesicles derived from SHEDs grown on the laminin-coated three-dimensional alginate micro-carriers suppressed 6-OHDA-induced apoptosis in dopaminergic neurons by approximately 80% throughout the culture period. Strikingly, no such effects were observed for the exosomes derived from SHEDs grown under standard culture conditions. CONCLUSIONS: Our results suggest that exosomes derived from SHEDs are considered as new potential therapeutic tool in the treatment of Parkinson's disease.

Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy.

BACKGROUND: Inflammatory dilated cardiomyopathy (iDCM) is a common debilitating disease with poor prognosis that often leads to heart failure and may require heart transplantation. The aim of this study was to evaluate sera and biopsy samples from chronic iDCM patients, and to investigate molecular mechanism associated with left ventricular remodeling and disease progression in order to improve therapeutic intervention. METHODS: Patients were divided into inflammatory and non-inflammatory DCM groups according to the immunohistochemical expression of inflammatory infiltrates markers: T-lymphocytes (CD3), active-memory T lymphocyte (CD45Ro) and macrophages (CD68). The inflammation, apoptosis, necrosis and fibrosis were investigated by ELISA, chemiluminescent, immunohistochemical and histological assays. RESULTS: The pro-inflammatory cytokine IL-6 was significantly elevated in iDCM sera (3.3 vs. 10.98 µg/ml; P < 0.05). Sera levels of caspase-9, -8 and -3 had increased 6.24-, 3.1- and 3.62-fold, (P < 0.05) and only slightly (1.3-, 1.22- and 1.03-fold) in biopsies. Significant release of Hsp60 in sera (0.0419 vs. 0.36 ng/mg protein; P < 0.05) suggested a mechanistic involvement of mitochondria in cardiomyocyte apoptosis. The significant MMP9/TIMP1 upregulation in biopsies (0.1931 - 0.476, P < 0.05) and correlation with apoptosis markers show its involvement in initiation of cell death and ECM degradation. A slight activation of the extrinsic apoptotic pathway and the release of hsTnT might support the progression of chronic iDCM. CONCLUSIONS: Data of this study show that significant increase of IL-6, MMP9/TIMP1 and caspases-9, -8, -3 in sera corresponds to molecular mechanisms dominating in chronic iDCM myocardium. The initial apoptotic pathway was more activated by the intramyocardial inflammation and might be associated with extrinsic apoptotic pathway through the pro-apoptotic Bax. The activated intrinsic form of myocardial apoptosis, absence of necrosis and decreased fibrosis are most typical characteristics of chronic iDCM. Clinical use of anti-inflammatory drugs together with specific anti-apoptotic treatment might improve the efficiency of therapies against chronic iDCM before heart failure occurs.

Predictors of mortality in patients with rheumatoid arthritis in Lithuania: Data from a cohort study over 10 years.

BACKGROUND AND OBJECTIVE: Increased mortality and shorter survival among rheumatoid arthritis (RA) patients are recognized but not fully explained. This cohort study aimed to identify predictors of mortality among RA patients at a tertiary clinical setting. MATERIALS AND METHODS: Patients with RA were recruited during 1998-2003 and followed up until April 1, 2012, or death whichever happened first. Baseline variables included sociodemographic and disease characteristics, and comorbidities. Cox regression and hazard risk (HR) were computed to estimate risks for mortality. RESULTS: One hundred ninety-one patients were included into the study, 186 patients were eligible for the analysis and of these 131 patients (70.4%) completed the entire period of followed-up while 55 patients (29.6%) died. The average follow up period was equivalent to 9.24 year per person. A Cox regression model identified four major factors having an impact on survival. History of a stroke at baseline was identified as a major factor (HR=5.33; 95% CI, 2.13-13.32). Statistically significant risk factors were also age over 50 years (HR=4.59; 95% CI, 2.04-10.30); education less than 11 years (HR=3.3; 95% CI, 1.72-6.33) and angina pectoris (HR=1.98; 95% CI, 1.03-3.80). CONCLUSIONS: Higher age, lower education and cardiovascular comorbidities were identified as predictors of mortality in this prospective cohort study while disease-related variables were not independent predictors of mortality.

Protective induction of Hsp70 in heat-stressed primary myoblasts: Involvement of MAPKs.

The involvement of extracellular signal-regulated kinases 1 and 2 (ERK1,2), stress kinase p38 and c-Jun NH2 -terminal kinases 1 and 2 (JNK1,2) on Hsp70-upregulation following mild heat shock, and resulting cell protection, was studied on rabbit primary myoblasts. Cells subjected to heat stress (42°C; 60 min) showed a significantly enhanced amount of heat-shock-induced protein 70 (Hsp70), correlating with sustained phosphorylation of MAP kinases ERK1,2, inhibition of p38 and JNK1,2 activation. Induced Hsp70 did not autocrinally suppress activation of transcription factor c-Jun, suggesting involvement of the latter in the protection of myoblasts following heat shock. The inhibition of stress kinases p38, JNK1,2, and MEK1,2 by SP600125, SB203580, and UO126, respectively, established the involvement of JNK1,2 and p38 as upstream, and ERK1,2 as downstream targets of Hsp70 induction. Moreover, the effect of the MEK1,2 inhibitor UO126 revealed a new pathway of c-Jun activation by ERK1,2 in myogenic heat-stressed stem cells. The presented data show that transient activation of JNK1, JNK2, and p38 is necessary for Hsp70 induction and ensuing cell protection. In conclusion, affecting myogenic stem cell protective mechanisms might be a useful strategy in improving stem cell survival and their expanded application in therapy.

Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the RESPOND study.

OBJECTIVE: To compare the efficacy and safety of treatment with infliximab plus methotrexate with methotrexate alone in methotrexate-naive patients with active psoriatic arthritis (PsA). METHODS: In this open-label study, patients 18 years and older with active PsA who were naive to methotrexate and not receiving disease-modifying therapy (N=115) were randomly assigned (1:1) to receive either infliximab (5 mg/kg) at weeks 0, 2, 6 and 14 plus methotrexate (15 mg/week); or methotrexate (15 mg/week) alone. The primary assessment was American College of Rheumatology (ACR) 20 response at week 16. Secondary outcome measures included psoriasis area and severity index (PASI), disease activity score in 28 joints (DAS28) and dactylitis and enthesitis assessments. RESULTS: At week 16, 86.3% of patients receiving infliximab plus methotrexate and 66.7% of those receiving methotrexate alone achieved an ACR20 response (p<0.02). Of patients whose baseline PASI was 2.5 or greater, 97.1% receiving infliximab plus methotrexate compared with 54.3% receiving methotrexate alone experienced a 75% or greater improvement in PASI (p<0.0001). Improvements in C-reactive protein levels, DAS28 response and remission rates, dactylitis, fatigue and morning stiffness duration were also significantly greater in the group receiving infliximab. In the infliximab plus methotrexate group, 46% (26/57) had treatment-related adverse events (AE) and two patients had serious AE, compared with 24% with AE (13/54) and no serious AE in the methotrexate-alone group. CONCLUSIONS: Treatment with infliximab plus methotrexate in methotrexate-naive patients with active PsA demonstrated significantly greater ACR20 response rates and PASI75 improvement compared with methotrexate alone and was generally well tolerated. This trial is registered in the US National Institutes of Health clinicaltrials.gov database, identifier NCT00367237.

Upregulation of iHsp70 by mild heat shock protects rabbit myogenic stem cells: involvement of JNK signalling and c-Jun.

iHsp70 [inducible Hsp70 (heat-shock protein 70)] family members (iHsp70, Hsp72 and Hsp70) are highly conserved proteins that act as molecular chaperones and promote cell survival during various forms of stress. Our data indicate that cultured adult rabbit myoblasts do not express iHsp70 under normal growth conditions, although increased expression was detectable 0.5-72 h following a 42°C heat shock for 15-60 min. The intracellular iHsp70 level reached a maximum 8 h after onset of the heat shock, which correlated with its increased accumulation in nuclei. Inhibition of iHsp70 expression by quercetin showed that sustained activation of JNK (c-Jun N-terminal kinase) 2 and suppression of c-Jun phosphorylation were responsible for myoblast death after heat shock. The data also demonstrate that activation of transcription factor c-Jun depends mostly on JNK1, whereas JNK2 had higher affinity and was translocated to nuclei together with c-Jun. We have also shown that the JNK signalling pathway is an upstream effect of iHsp70 expression. These findings provide further in-depth understanding of the implication of the pro-survival signalling kinases JNK1 and JNK2 and their target, c-Jun, in expression of iHsp70 and regulation of myogenic stem cell survival and death mechanisms after heat shock. Mild heat shock before transplantation might be a way of improving myogenic stem cell survival.

[Recommendations for the prevention and management of tuberculosis in patients treated with tumor necrosis factor alpha inhibitors: a consensus of lithuanian pulmonologists and rheumatologists]. / Tuberkuliozes prevencijos ir gydymo rekomendacijos skiriantnaviko nekrozes faktoriaus alfa blokatorius (Lietuvos pulmonologu ir reumatologu sutarimas)

Patients receiving tumor necrosis factor alpha inhibitors for the treatment of rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) are at high risk of developing tuberculosis during treatment. This article gives the recommendations for the prevention and management of tuberculosis in patients with rheumatic diseases before initiating therapy with tumor necrosis factor alpha inhibitors. They are adapted considering the high prevalence of tuberculosis, high drug resistance of Mycobacterium tuberculosis, and extensive bacille Calmette-Guérin vaccination against tuberculosis in Lithuania. In order to reduce the risk of tuberculosis, the screening should be done before starting antitumor necrosis factor alpha therapy. This includes complete medical history and posterior-anterior, lateral chest radiography. Tuberculin skin test using the Mantoux method with 5 tuberculin units and interferon-gamma release assay should be performed in patients without posttuberculous radiological lesions. If Ghon's complex or untreated posttuberculous lesions are present, or if the results the Mantoux test or interferon-gamma release assay are positive, the patient should be treated for latent tuberculosis. For the treatment of latent tuberculosis, isoniazid and rifampicin are given for 3 months, and the introduction of antitumor necrosis factor alpha therapy is delayed at least for one month. In cases of suspected active Mycobacterium tuberculosis infection, tuberculosis should be confirmed microbiologically or morphologically, and adequate antituberculosis treatment should be initiated.

The Expression of Inflammasomes NLRP1 and NLRP3, Toll-Like Receptors, and Vitamin D Receptor in Synovial Fibroblasts From Patients With Different Types of Knee Arthritis.

Activated rheumatoid arthritis (RA) synovial fibroblasts (SFs) are among the most important cells promoting RA pathogenesis. They are considered active contributors to the initiation, progression, and perpetuation of the disease; therefore, early detection of RASF activation could advance contemporary diagnosis and adequate treatment of undifferentiated early inflammatory arthritis (EA). In this study, we investigated the expression of nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing (NLRP)1, NLRP3 inflammasomes, Toll-like receptor (TLR)1, TLR2, TLR4, vitamin D receptor (VDR), and secretion of matrix metalloproteinases (MMPs) in SFs isolated from patients with RA, osteoarthritis (OA), EA, and control individuals (CN) after knee surgical intervention. C-reactive protein, general blood test, anticyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), and vitamin D (vitD) in patients' sera were performed. Cells were stimulated or not with 100 ng/ml tumor necrosis factor alpha (TNF-α) or/and 1 nM or/and 0.01 nM vitamin D3 for 72 h. The expression levels of NLRP1, NLRP3, TLR1, TLR2, TLR4, and VDR in all examined SFs were analyzed by quantitative real-time PCR (RT-qPCR). Additionally, the secretion of IL-1ß by SFs and MMPs were determined by ELISA and Luminex technology. The expression of NLRP3 was correlated with the levels of CRP, RF, and anti-CCP, suggesting its implication in SF inflammatory activation. In the TNF-α-stimulated SFs, a significantly lower expression of NLRP3 and TLR4 was observed in the RA group, compared with the other tested forms of arthritis. Moreover, upregulation of NLRP3 expression by TNF-α alone or in combination with vitD3 was observed, further indicating involvement of NLRP3 in the inflammatory responses of SFs. Secretion of IL-1ß was not detected in any sample, while TNF-α upregulated the levels of secreted MMP-1, MMP-7, MMP-8, MMP-12, and MMP-13 in all patient groups. Attenuating effects of vitD on the expression of NLRP3, TLR1, and TLR4 suggest potential protective effects of vitD on the inflammatory responses in SFs. However, longer studies may be needed to confirm or fully rule out the potential implication of vitD in SF activation in inflammatory arthritis. Both VDR and NLRP3 in the TNF-α-stimulated SFs negatively correlated with the age of patients, suggesting potential age-related changes in the local inflammatory responses.

Prevalence of psychoactive substances use in a Lithuanian women's prison revisited after 5 years.

BACKGROUND: This paper re-examines the prevalence of psychoactive substances (tobacco, alcohol, narcotic drugs) use among inmates in a Lithuanian women's prison. The main goal of this study was to determinate the changes in the use of the psychoactive substances in a women's prison in Lithuania. MATERIAL/METHODS: We accomplished the retesting of the first ever investigation of this kind, carried out in 2004, using the same questionnaire, in the only women's prison in Lithuania. In June 2009, 71 (27.8%) women of 255 inmates of the prison were given questionnaires with information about the aim of the study, stating that the study was voluntary and anonymous, and obtaining permission for release of information. The results were compared with the previous investigation. A statistical analysis was carried out using SPSS 17.0. RESULTS: Tobacco smokers comprised 85.3% of respondents.; the average age at which respondents started to smoke was 14±7.3 years; 57.7% of respondents had tried narcotic drugs at least once; 22.5% of respondents used drugs (in 2004 we had found no drug use in this women's prison); 18.3% of respondents indicated that they narcotic drugs were tried for the first time away, 4.2% - in a custodial establishment. CONCLUSIONS: Psychoactive substances are often used due to their psychological effect. inmates constitute a high-risk group of drug users and distributors of narcotic drugs. Intravenous narcotics stimulating dangerous behavior prevail in Lithuanian prisons. Women in prison are especially prone to smoking.

[Professional socialization of nurses ensuring practice activity]. / Slaugytoju profesine socializacija uztikrinant praktine veikla.

UNLABELLED: The aim of this study was to evaluate professional socialization of nurses and its association with assurance of practice activity. MATERIAL AND METHODS: The study was carried out in randomly selected Lithuanian health care institutions from January to June 2007. A total of 1300 nurses, enrolled in the study, were divided into three groups according to the position held by participants: general practice nurses, 77.8%; senior nurses and leaders, 10.7%; and 4th-year students of general nurse education program, 11.5%. A questionnaire-based survey was carried out. The data were processed with SPSS 15.0 statistical software. Descriptive and multidimensional statistical methods were applied in the study. The matrix model, integrating characteristics of nurses' professional socialization and dimensions of practice activity and disclosing parameters and indicators of assurance of these processes, was applied for data analysis. RESULTS: The respondents favorably evaluated the aspects ensuring professional socialization and practice activity such as "professional activity," "motivators of professional activity," "professional characteristic," "system of professional values," and "professional behavior." The respondents unfavorably evaluated the following parameters: "security of professional self-expression and self-education," "professional development," "professional expectations," and "implementation of institution strategies." CONCLUSIONS: For the evaluation of nurses' professional socialization and practice activity, a theoretical model was created, and nine diagnostic criteria, integrating the characteristics of professional socialization and dimensions of practice activity, were formulated. A significant positive correlation was determined among the majority of the diagnostic criteria of the intercorrelation matrix of theoretical model. Having summarized the attitude of nurses toward professional socialization and the provision of practice activity, both favorable and unfavorable aspects of assessment tendencies of these processes were revealed. The study results and nonparametric analysis showed that sociodemographic factors have an impact on nurses' attitudes toward professional socialization and the assurance of practice activity.

The influence of mean blood pressure on arterial stiffening and endothelial dysfunction in women with rheumatoid arthritis and systemic lupus erythematosus.

OBJECTIVE: To investigate the carotid-radial pulse wave velocity, augmentation index, and flow-mediated dilation of the brachial artery and factors possibly influencing them in women with rheumatoid arthritis and systemic lupus erythematosus. MATERIAL AND METHODS: A total of 63 women with rheumatoid arthritis, 31 with systemic lupus erythematosus, and 72 controls, aged 18-55 years, were examined. Parameters of arterial stiffness, augmentation index and carotid-radial pulse wave velocity, were obtained by applanation tonometry (Sphygmocor (v.7.01) AtCor Medical). Flow-mediated dilatation of the brachial artery, reflecting endothelial function was determined by ultrasound system (Logiq 7, General Electric). RESULTS: The groups of women with rheumatoid arthritis and systemic lupus erythematosus lupus differed from controls regarding augmentation index (P<0.001; P=0.008) and did not differ between each other. Women with systemic lupus erythematosus differed from controls regarding pulse wave velocity (P=0.018), while women with rheumatoid arthritis - did not. Flow-mediated dilatation in both the groups of diseases was not different from controls. In rheumatoid arthritis patients, mean blood pressure was the main explanatory factor for augmentation index and pulse wave velocity; vessel diameter and high-density lipoprotein cholesterol - for flow-mediated dilatation. In women with systemic lupus erythematosus, pulse wave velocity was not related to any of the pending parameters; augmentation index was dependent on organ damage index, age, and mean blood pressure, and flow-mediated dilatation on vessel diameter, body mass index, and disease duration. CONCLUSIONS: The mean blood pressure was the major and the only one risk factor of arterial stiffening in rheumatoid arthritis, while the disease damage index played the most important role in the systemic lupus erythematosus group. The mean blood pressure in the systemic lupus erythematosus group was not as important as in the rheumatoid arthritis group, though may have a partial influence.

[Cross-cultural adaptation and validation of Lithuanian questionnaires for the spondyloarthropathies]. / Spondiloartropatiju klausimynu lietuviu kalba pritaikymas ir ju tinkamumo ivertinimas.

UNLABELLED: Original English questionnaires--Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Patient Global Score, and Bath Ankylosing Spondylitis Disease Activity Index--are designed to evaluate health, physical and psychical state of patients with spondyloarthropathies and to assess efficiency of the treatment. OBJECTIVE: The objective of the study was to adapt Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Patient Global Score, Bath Ankylosing Spondylitis Disease Activity Index questionnaires to the Lithuanian context and examine their psychometric aspects: reliability and validity. PATIENTS AND METHODS: Validation and linguistic and cultural adaptation of Lithuanian questionnaires were performed according to the requirements for adaptation of the international questionnaires. Psychometric features of Lithuanian questionnaires were examined in 139 patients with spondyloarthropathies. The validity of questionnaires was tested by comparing these questionnaires with Health Assessment Questionnaire Modified for Spondyloarthropathies, metrology indices (tragus-to-wall distance, lateral flexion, modified Schober's distance, intermalleolar distance), pain intensity, patient's well-being, physician's assessment of the disease activity, and total enthesis count. The reliability of questionnaires was assessed by determining internal consistency of scales and scale stability and by calculating the intraclass correlation coefficient. RESULTS: The linguistic and cultural adaptation of these questionnaires was made during the study. Internal consistency was high for functional and disease activity index (Cronbach alpha>/=0.80) and moderate for the Bath Ankylosing Spondylitis Patient Global Score (Cronbach alpha=0.58). High stability in regard to time was characteristic of all three questionnaires (intraclass correlation coefficient >0.95). A significant association between the separate questions of examined instruments, their joint results and other factors reflecting patient's health was established. CONCLUSIONS: Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Patient Global Score, and Bath Ankylosing Spondylitis Disease Activity Index questionnaires in Lithuanian fully correspond to psychometric requirements. They are appropriate and relevant in assessing the influence of spondyloarthropathies on a patient's health.

The safety and efficacy of light emitting diodes-based ultraviolet A1 phototherapy in bleomycin-induced scleroderma in mice.

PURPOSE: To define the efficacy and safety of narrowband ultraviolet A1 (UVA1) for the treatment of dermal fibrosis in bleomycin-induced mouse model of scleroderma. MATERIALS AND METHODS: 42 DBA/2 strain mice were included in the study: healthy mice and mice with established scleroderma, treated with high or medium dose of UVA1. Non-treated groups served as control. The equipment emitting 365±5nm UVA1 radiation was used in the study. The average cumulative doses were 1200J/cm2 for high and 600J/cm2 for medium dose course. Histological analysis was performed for the evaluation of the dermal thickness and mast cells density. The expressions of p53 and Ki-67 proteins were assessed by immunohistochemical analyses. RESULTS: Skin thickness of mice with scleroderma, treated with high and medium dose of UVA1, were lower (272.9±113.2µm and 394±125.9µm, respectively) in comparison to the dermal thickness of non-treated animals (599±55.7µm). The dermal mast cells count in mice with scleroderma was reduced after high and medium dose treatment to 11±1.7 and 13±2.2, respectively, as compared to that in non-treated mice (23±3.0). No significant upregulation of p53 nor Ki-67 proteins was observed in the skin of healthy mice and mice with scleroderma after high- and medium-dose of UVA1. CONCLUSIONS: The results of this study indicate that 365nm UVA1 with the cumulative doses of 1200J/cm2 and 600J/cm2 is safe and effective for the dermal fibrosis treatment.

Microcarrier culture enhances osteogenic potential of human periodontal ligament stromal cells.

Regeneration of periodontal tissue represents a major challenge to modern tissue engineering, since cell-based therapies require large amounts of periodontal ligament stromal cells (PLSC), which can be obtained only by in vitro expansion. Ideally, the period of the in vitro expansion should be optimized for the generation of large enough numbers of pre-specified progenitor cells ready to contribute to the restoration of periodontal tissues. In the present study, we used a commercially available, three-dimensional culturing platform and alginate microcarrier cell culture system for the propagation of human PLSCs, which were derived using the explant outgrowth method. Induction of osteogenic differentiation resulted in rapid and robust mineralization of the extracellular matrix in PLSCs grown on microcarriers, but not in PLSCs grown under standard culture conditions. Gene expression studies revealed upregulation of osteogenesis-related genes, BMP2, ALP, RUNX2, MSX2, cementum protein 23, bone sialoprotein, osteopontin and periostin, in undifferentiated and differentiating microcarrier cultures of PLSCs. In addition, the microcarrier culture enhanced the expression of ß-catenin, intermediate filament protein vimentin and focal adhesion proteins vinculin and paxillin. Our study shows that microcarrier culture allows rapid generation of large numbers of PLSCs pre-specified towards an osteogenic-like phenotype. This method may be useful for the development of new tissue engineering protocols for the reconstruction of periodontal tissues.