Labile assembly of a tardigrade protein induces biostasis.

Tardigrades are microscopic animals that survive desiccation by inducing biostasis. To survive drying tardigrades rely on intrinsically disordered CAHS proteins, which also function to prevent perturbations induced by drying in vitro and in heterologous systems. CAHS proteins have been shown to form gels both in vitro and in vivo, which has been speculated to be linked to their protective capacity. However, the sequence features and mechanisms underlying gel formation and the necessity of gelation for protection have not been demonstrated. Here we report a mechanism of fibrillization and gelation for CAHS D similar to that of intermediate filament assembly. We show that in vitro, gelation restricts molecular motion, immobilizing and protecting labile material from the harmful effects of drying. In vivo, we observe that CAHS D forms fibrillar networks during osmotic stress. Fibrillar networking of CAHS D improves survival of osmotically shocked cells. We observe two emergent properties associated with fibrillization; (i) prevention of cell volume change and (ii) reduction of metabolic activity during osmotic shock. We find that there is no significant correlation between maintenance of cell volume and survival, while there is a significant correlation between reduced metabolism and survival. Importantly, CAHS D's fibrillar network formation is reversible and metabolic rates return to control levels after CAHS fibers are resolved. This work provides insights into how tardigrades induce reversible biostasis through the self-assembly of labile CAHS gels.

Sense of coherence and its impact on quality of life of patients with systemic lupus erythematosus.

The sense of coherence (SOC) construct refers to a global orientation, which significantly determines the link between stressors, coping with disease and health. The aim of this work was to assess possible associations between SOC and quality of life (QOL) scores among women with SLE. Sixty consecutive SLE women and 88 healthy women were included in the study. QOL was assessed using the SF-36 and the WHO QOL-Bref scales. The SOC has three main sub-scales: comprehensibility, manageability and meaningfulness. Regression analyses were used to study associations between various parameters of SF-36, WHO QOL-Bref, SOC, SLEDAI, indices of end organ damage (SDI), and demographic variables. Mean SLEDAI and SDI scores were 4.5 (SD = 5.6) and 1.29 (SD=2). SLE patients had significantly lower scores for all individual and summary sub-scales in the two QOL questionnaires compared with controls. SLE patients had significantly lower scores for the general, comprehensibility and meaningfulness sub-scales of SOC. No significant correlation was seen between SOC scores and measures of disease activity or end-organ damage. A strong linear correlation was seen between the scores of SOC, general WHO QOL-Bref, and the mental and physical component summary (MCS & PCS) scores of SF36. Age, SOC and SDI significantly affected the PCS score. SOC was the only variable independently associated with MCS. Education and SOC were significantly associated with the general WHO QOL-Bref. Age, education, SDI and SOC were independently associated with QOL of women with SLE.

Vulvar invasive squamous cell carcinoma occurring in a young woman with systemic lupus erythematosus.

BACKGROUND: Although several studies have demonstrated a possible relationship between systemic lupus erythematosus (SLE) and non-Hodgkin's lymphoma, Hodgkin's lymphoma, leukemia and several solid tumors, it is still debatable whether SLE patients have an increased incidence of cancer overall. CASE: We describe a 25-year-old patient with SLE who developed invasive squamous cell carcinoma of the vulva. The patient underwent radical vulvectomy and bilateral groin sentinel lymph node dissection and until to date, one year after surgery, she is alive without evidence of recurrent disease. CONCLUSIONS: Only three cases of vaginal/vulvar cancer associated with SLE have previously been mentioned in the literature, but not described in detail. This is the first detailed case report in the literature of vulvar invasive squamous cell carcinoma occurring in a SLE patient. It can only be speculated that the SLE itself and/or the treatment with immunosuppressive drugs provoked malignant transformation and the development of vulvar squamous cell carcinoma in such a young patient.

Dobutamine stress echocardiography in women with systemic lupus erythematosus: increased occurrence of left ventricular outflow gradient.

Dobutamine stress echocardiography (DSE) is an accurate noninvasive test used for the diagnosis and evaluation of patients with known or suspected coronary artery disease (CAD). The aim of this study was to determine the rate of positive findings in DSE, to define the echocardiographic and clinical characteristics of women with systemic lupus erythematosus (SLE) and to evaluate the safety of DSE in SLE patients. Thirty consecutive SLE patients were enrolled in the study and underwent DSE study. The mean age of patients was 44 years (range 20-76). Mean duration of SLE was 8.1 years and mean SLEDAI was 5.5. None of the DSE tests performed were positive for myocardial ischaemia. A left ventricular outflow gradient (LVOG) was found in 15/28 (54%) patients who completed the test, a result higher than the reported 20% prevalence of this finding in the literature. There were no significant differences in baseline characteristics between patients who developed a gradient and patients in whom a gradient was not found. There were no significant adverse effects during the study. In the general population, LVOG has been reported to be associated with an increased rate of chest discomfort and with a significantly lower prevalence of CAD. Whether this is true for SLE patients requires further study.

Influenza virus vaccination of patients with SLE: effects on generation of autoantibodies.

The sera of 24 women with SLE who received influenza vaccine were tested by ELISA for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood samples were withdrawn at the time of vaccination and 6 and 12 weeks after vaccination. The mean age at enrolment into the study was 46.1 years. The mean disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6 weeks and 5.1 at week 12. The vaccine was not associated with the generation of anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively. Twelve weeks after vaccination none of the patients had anti-Sm, three had anti-Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination six and three patients developed IgG and IgM anticardiolipin antibodies, respectively. In summary, although the influenza virus vaccine is clinically safe for patients with SLE it may trigger the generation of autoantibodies. This effect is usually short term and has no clinical significance.

The role of trace elements in psoriatic patients undergoing balneotherapy with Dead Sea bath salt.

BACKGROUND: A beneficial effect was observed in patients with psoriasis vulgaris following balneotherapy with Dead Sea bath salt. OBJECTIVES: To evaluate the possible role of trace elements in the effectiveness of balneotherapy. METHODS: Serum levels of 11 trace elements were analyzed in 23 patients with psoriasis vulgaris who participated in a double-blind controlled study of balneotherapy with either Dead Sea bath salt (12 patients) or common salt (11 patients). Thirteen healthy volunteers served as controls. RESULTS: The mean pre-treatment serum levels of boron, cadmium, lithium and rubidium were significantly lower in patients compared to controls, whereas the mean pre-treatment serum level of manganese was significantly higher in patients compared to controls. Balneotherapy with Dead Sea bath salt resulted in a significant decrease (P = 0.0051) in the mean serum level of manganese from 0.10 +/- 0.05 mol/L to 0.05 +/- 0.02 mumol/L. The mean reduction in the serum level of manganese differed significantly (P = 0.002) between responders (% Psoriasis Area and Severity Index score reduction > or = 25) and non-responders (% PASI score reduction < 25). Following balneotherapy with Dead Sea bath salt the mean serum level of lithium decreased in responders by 0.01 +/- 0.02 mumol/L, whereas its level in non-responders increased by 0.03 +/- 0.03 mumol/L. (P = 0.015). CONCLUSIONS: Manganese and lithium may play a role in the effectiveness of balneotherapy with Dead Sea bath salt for psoriasis.

Balneotherapy for fibromyalgia at the Dead Sea.

The aim of this study was to evaluate the effectiveness of balneotherapy on patients with fibromyalgia (FM) at the Dead Sea. Forty-eight patients with FM were randomly assigned to a treatment group receiving sulfur baths and a control group. All participants stayed for 10 days at a Dead Sea spa. Physical functioning, FM-related symptoms, and tenderness measurements (point count and dolorimetry) were assessed at four time points: prior to arrival at the Dead Sea, after 10 days of treatment, and 1 and 3 months after leaving the spa. Physical functioning and tenderness moderately improved in both groups. With the exception of tenderness threshold, the improvement was especially notable in the treatment group and it persisted even after 3 months. Relief in the severity of FM-related symptoms (pain, fatigue, stiffness, and anxiety) and reduced frequency of symptoms (headache, sleep problems, and subjective joint swelling) were reported in both groups but lasted longer in the treatment group. In conclusion, treatment of FM at the Dead Sea is effective and safe and may become an additional therapeutic modality in FM. Future studies should address the outcome and possible mechanisms of this treatment in FM patients.

Balneotherapy at the Dead Sea area for patients with psoriatic arthritis and concomitant fibromyalgia.

BACKGROUND: Balneotherapy has been successfully used to treat various rheumatic diseases, but has only recently been evaluated for the treatment of fibromyalgia. Since no effective treatment exists for this common rheumatic disease, complementary methods of treatment have been attempted. OBJECTIVES: To assess the effectiveness of balneotherapy at the Dead Sea area in the treatment of patients suffering from both fibromyalgia and psoriatic arthritis. METHODS: Twenty-eight patients with psoriatic arthritis and fibromyalgia were treated with various modalities of balneotherapy at the Dead Sea area. Clinical indices assessed were duration of morning stiffness, number of active joints, a point count of 18 fibrositic tender points, and determination of the threshold of tenderness in nine fibrositic and in four control points using a dolorimeter. RESULTS: The number of active joints was reduced from 18.4 +/- 10.9 to 9 +/- 8.2 (P < 0.001). The number of tender points was reduced from 12.6 +/- 2 to 7.1 +/- 5 in men (P < 0.003) and from 13.1 +/- 2 to 7.5 +/- 3.7 in women (P < 0.001). A significant improvement was found in dolorimetric threshold readings after the treatment period in women (P < 0.001). No correlation was observed between the reduction in the number of active joints and the reduction in the number of tender points in the same patients (r = 0.2). CONCLUSIONS: Balneotherapy at the Dead Sea area appears to produce a statistically significant substantial improvement in the number of active joints and tender points in both male and female patients with fibromyalgia and psoriatic arthritis. Further research is needed to elucidate the distinction between the benefits of staying at the Dead Sea area without balneotherapy and the effects of balneotherapy in the study population.

The effect of balneotherapy at the Dead Sea on the quality of life of patients with fibromyalgia syndrome.

Fibromyalgia (FS) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points. As there is no effective treatment, patients with this condition have impaired quality of life (QoL). The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS. Forty-eight subjects participated in the study; half of them received balneotherapy, and half did not. Their QoL (using SF-36), psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area, at the end of the 10-day stay, and 1 and 3 months later. A significant improvement was reported on most subscales of the SF-36 and on most symptoms. The improvement in physical aspects of QoL lasted usually 3 months, but on psychological measures the improvement was shorter. Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group. In conclusion, staying at the Dead Sea spa, in addition to balneotherapy, can transiently improve the QoL of patients with FS. Other studies with longer follow-up are needed to support our findings.

Comparative study of osteoarthritis of the contralateral knee joint of male amputees who do and do not play volleyball.

OBJECTIVE: To assess the prevalence of osteoarthritis (OA) of the contralateral knee of men with traumatic amputation who do and do not participate in regular, vigorous physical activity. METHODS: Three groups of patients were assessed. Group 1 consisted of 8 male amputee volleyball players. Group 2 consisted of 24 male amputees who do not play volleyball, and Group 3 was made up of 24 healthy controls matched by age and weight to Group 2. The prevalence of contralateral knee OA in Groups 1 and 2 was assessed by questionnaire, physical examination, and radiographs, and was compared with findings for Group 3. RESULTS: The rate of OA in all amputees (Groups 1 and 2 together) was 65.6%, which was significantly higher than among the controls (p < 0.05). The most common findings among the amputees were patellar and medial osteophytosis of the tibiofemoral joint, with a tendency to medial narrowing of the tibiofemoral joint space. CONCLUSION: Traumatic amputees have a higher prevalence of OA in the knee of the nonamputated leg than matched healthy controls.

[Prevalence of fibromyalgia in type 2 diabetes mellitus].

This study aimed to assess the prevalence of fibromyalgia and other pain characteristics among patients with type 2 diabetes mellitus. We assessed 137 patients with type 2 diabetes mellitus and a control group of 139 patients matched for age and sex that do not suffer from diabetes mellitus. We examined 9 of 18 typical tender points and 4 control points with a dolorimeter. There was no difference in the prevalence of fibromyalgia among men in both groups. However, diabetic men had more tender points than men in the control group and their threshold for pain at the corresponding tender points was significantly lower compared to that of the men in the control group. The diabetic men also reported more pain than patients in the control group. Diabetic women, on the other hand, had a significantly higher prevalence of fibromyalgia than women in the control group: 23.3% versus 10.6% respectively (p = 0.043). There was no significant difference in the number of tender points and the pain threshold in the two groups of women. Diabetic women reported more pain than the women in the control group. In both diabetic men and women the number of tender points and dolorimeter count directly correlated with the duration of diabetes.

Manifestations of three HHV-8-related diseases in an HIV-negative patient: immunoblastic variant multicentric Castleman's disease, primary effusion lymphoma, and Kaposi's sarcoma.

We describe a 73-year-old HIV negative patient who presented with symptomatic hypoglycemia. Over the course of several months she was diagnosed with three human herpesvirus-8 related diseases: multicentric Castleman's disease, primary effusion lymphoma and Kaposi's sarcoma. No improvement was observed following cytotoxic therapy and she died 16 months after her initial presentation. The etiology of the hypoglycemia remained obscure over the course of this patient's disease. This case is the first report of a patient with three human herpesvirus-8 related diseases, and the first report of severe hypoglycemia as the presenting symptom of any of these diseases.

Systemic sclerosis: another rheumatic disease associated with hepatitis C virus infection.

The first case of a patient with chronic infection with hepatitis C virus who developed systemic sclerosis, manifested by severe Raynaud's phenomenon, progressive skin thickening, painful fingertip ulcers, dysphagia and Sjogren's syndrome, is described. The role of interferon therapy is discussed.

Influenza virus vaccination of patients with systemic lupus erythematosus: effects on disease activity.

OBJECTIVE: To determine whether vaccination of patients with systemic lupus erythematosus (SLE) with influenza virus vaccine is associated with exacerbation of SLE. METHODS: The study population comprised 24 patients with SLE who received influenza vaccine (cases group) and 24 other SLE patients who did not receive the vaccine (controls group). The primary outcome measure was the SLE Disease Activity Index (SLEDAI) scores 6 weeks and 12 weeks after vaccination. Secondary outcome measures included: number of SLE flares, defined as any increase in the SLEDAI > or = 3 points, and activity of renal disease. Repeated measurements MANOVA was used to compare the SLEDAI scores of the cases and controls. RESULTS: All patients were women. The mean age at enrollment into the study was 46.1 and 40.6 years for the cases and controls, respectively. The mean disease duration was 9.1 for the cases and 9.3 years for the controls. SLEDAI scores for the cases and controls were 6.6 and 8.9 at vaccination, 4.9 and 6.8 at Week 6, and 5.1 and 6.7 at Week 12, respectively. The SLEDAI scores of the cases and controls at the 3 different assessments were not statistically different (p = 0.28). However, within each group the decrease in the SLEDAI over time was statistically significant (p = 0.02). Three and 6 flares were observed in the cases and controls, respectively, (p = 0.27) during the 12 weeks of followup. Improvement in the renal disease was observed in the cases and controls. CONCLUSION: Influenza virus vaccine is safe for patients with SLE. Patients with SLE should be encouraged to receive the vaccine according to the recommendation given by the Immunization Practices Advisory Committee.

Kingella endocarditis and meningitis in a patient with SLE and associated antiphospholipid syndrome.

We describe a patient with SLE and antiphospholipid syndrome who presented with severe headache and fever. Lumbar puncture analyses indicated meningitis. Kingella kingae was isolated from her blood cultures. A large mobile vegetation was seen on her mitral valve. The association between SLE, Libman-Sacks endocarditis and bacterial endocarditis is discussed.

The role of spa therapy in various rheumatic diseases.

Spa therapy seems to have a role in the treatment of a broad range of joint diseases. It cannot substitute for conventional therapy but can complement it. The improvement reported in some of the studies is of short duration, lasting for months. It should be considered for patients suffering from various types of inflammatory arthritides or noninflammatory arthritides who are symptomatic, despite accepted medical therapy and conservative physiotherapy, if they can afford the expense. The patients should be told that the effectiveness and success of this therapy cannot be predicted in advance. Because we have no way to date, of curing most rheumatic diseases, clinical trials of alternative therapeutic methods are justified. These methods may alleviate patient suffering and are almost totally devoid of serious adverse effects. No studies have been reported that evaluate their cost-effectiveness.

Nabumetone induces less gastrointestinal mucosal changes than diclofenac retard.

The aim of the study was to compare the efficacy and the effects on the mucosa of the gastrointestinal tract (GIT) of nabumetone and diclofenac retard in patients with osteoarthritis (OA). An open, multicentre, randomised, comparative, endoscopy-blind parallel group study included 201 patients with nabumetone and 193 patients with diclofenac retard suffering from moderate to severe OA of the knee or hip joint. Twelve clinical efficacy variables were assessed and a portion of the population underwent gastroduodenoscopy. All patients exhibited significant improvement in pain severity and pain relief (p < 0.001 and p < 0.0001, respectively) but there were no differences between the groups for all the efficacy variables. Eleven per cent of patients on nabumetone and 19% on diclofenac experienced GIT side-effects. Sixty-nine patients with nabumetone and 61 with diclofenac underwent gastroduodenoscopy. The differences in the mucosal grade for the oesophagus, stomach and duodenum at baseline were not significant. In the oesophagus there were significantly less changes after treatment with nabumetone (p = 0.007) than with diclofenac; there were similar findings in the stomach (p < 0.001) but the difference in the duodenum was not significant. This study indicates that nabumetone and diclofenac retard have similar efficacy in the treatment of OA, but nabumetone has significantly fewer GIT side-effects.

Balneotherapy at the Dead Sea area for knee osteoarthritis.

BACKGROUND: Balneotherapy at the Dead Sea area has been applied in various inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis. The efficacy of balneotherapy at the Dead Sea area for the treatment of degenerative rheumatic diseases has not yet been formally evaluated. OBJECTIVE: To evaluate the efficacy of balneotherapy at the Dead Sea area in patients suffering from osteoarthritis of the knees. METHODS: Forty patients were randomly allocated into four groups of 10 patients. Group I was treated by bathing in a sulphur pool, group 2 by bathing in the Dead Sea, group 3 by a combination of sulphur pool and bathing in the Dead Sea, and group 4 served as the control group receiving no balneotherapy. The duration of balneotherapy was 2 weeks. RESULTS: Significant improvement as measured by the Lequesne index of severity of osteoarthritis was observed in all three treatment groups, but not in the control group. This improvement lasted up to 3 months of follow-up in patients in all three treatment groups. CONCLUSION: Balneotherapy at the Dead Sea area has a beneficial effect on patients with osteoarthritis of the knees, an effect that lastas at least 3 months.