Secukinumab and Dead Sea Climatotherapy Impact Resolved Psoriasis Skin Differently Potentially Affecting Disease Memory.

Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory.

A study of the effect of half-day climatotherapy on changes in salivary cortisol levels.

In our previous study setting, climatotherapy programme consisted of six sessions - four in the mid-mountain area and two in a flat park. For all sessions, the subjects underwent climatotherapy in the morning under slightly cool conditions. During each session, the subjects' blood pressure, pulse rate, skin temperature, blood lactate, salivary cortisol and mood profile were recorded, and meteorological data were collected at the sites. We hypothesised that exercise habits, changes in mood profile and effective temperatures during the session, and physical exertion during the climatic terrain cure would affect salivary cortisol levels. Subjects were 30 (spring) and 29 (autumn). Multiple linear regression analyses were performed to examine the determinants of the change in salivary cortisol levels. In the mountain setting, salivary cortisol was elevated, even though the sessions took place in the descending phase of the circadian salivary cortisol variation; however, the post-session cortisol increase was not significant. Increased post-session salivary cortisol was significantly associated with female gender, older age, higher BMI, lower body fat, less daily physical activity, increased blood lactate, increased 'Tension-Anxiety' and 'Depression-Dejection' moods, and decreased 'Anger-Hostility' mood. The increase in cortisol may have been due to older age, a predominance of females, and the increased blood lactate due to the mountainous terrain. In the flat park, the significant decrease in postsession salivary cortisol was related to the descending circadian phase of circadian cortisol variation and the low physical demands of the sessions.

Benefits of an accelerated climatotherapy programme for busy people: comparisons according to area and season.

An accelerated climatotherapy programme was evaluated for use with busy people in mid-mountain and flat lowland areas. A total of 43 urban residents participated in this climatotherapy programme. Participants' blood pressure, pulse rate, peripheral skin temperature and levels of salivary amylase, salivary cortisol and blood lactate were measured, and they completed the Profile of Mood Status questionnaire. In the mid-mountain area, which had a cooler environment and long uphill paths, participants' percentage of maximum pulse rate (70.01%) to estimated maximum heart rate was higher than that (59.67%) of participants in the flat lowland area, suggesting that the mid-mountain area was suitable for endurance training. At both sites, the decrease in peripheral skin temperature during the climatic terrain cure suggested that our programme was properly implemented with a cool body surface in accordance with our purpose. Negative moods improved quickly, suggesting that the forest environment and the fresh-air rest cure may have relaxed participants. In late spring and early autumn, the mood of approximately 25% of participants improved to an Iceberg profile, which is associated with positive mental states and athletic peak performance, after climatotherapy. On the other hand, the weather in early spring and late autumn was more likely to facilitate maintenance of a cool body surface during the climatic terrain cure. With the support of individualized feedback provided after the climatotherapy sessions, three participants developed regular exercise habits, serving as a good example of the effectiveness of our climatotherapy programme to elicit behavioural change.

Climatotherapy for asthma: Research progress and prospect.

Asthma affects over 300 million people globally and is a cause of substantial burden of disease, including both premature death and reduced quality of life in people of all ages. Although both genetic and environmental factors play an important role in the pathogenesis of asthma, the rising trend of asthma and other allergic diseases over recent decades is thought to be largely caused by alteration in environmental conditions. Thus, a considerable amount of attention has been paid to environmental modification for the treatment and management of asthma, including household allergen reduction and/or irritant removal. More advanced environmental modification strategies (e.g., health resort medical rehabilitation, high-altitude climate therapy and multiple-hit interventions) have also been suggested. Research advances have been made over the past decades, but major challenges and opportunities coexist in this emerging field. Concerted efforts are required to tackle these formidable challenges.

[The role of health resort factors in preconception preparation of patients with reproductive disorders]. / Rol' sanatorno-kurortnykh faktorov v pregravidarnoi podgotovke patsientok s narusheniyami reproduktivnoi funktsii.

Reproductive dysfunction is a multifactorial problem, for the correction of which the most difficult are cases of pathology comorbidity. Individual preconception preparation, taking into account risk factors, is recognized as an effective measure to increase the chances of conception and prevent reproductive losses. OBJECTIVE: Optimization of treatment and rehabilitation measures at the preconception stage in patients with reproductive disorders. MATERIAL AND METHODS: The effectiveness of the use of natural and preformed physical factors in the preconception preparation of 180 women who underwent medical and rehabilitation measures in the health resort of the Altai Territory - the resort town of Belokurikha (Group 1, 79 patients) and outpatient conditions in the city of Barnaul (Group 2, 101 patients). Comprehensive spa treatment included climatotherapy, a combination of various methods: balneotherapy, peloidtherapy, physiotherapy and a prolonged course of herbal medicine. RESULTS: In patients of the 1st group, who underwent a course of rehabilitation treatment in a sanatorium-resort environment, compared with patients of the 2nd group, early reproductive losses were less common during pregnancy (7.1% and 20.7%, respectively; p=0.04) and more frequent term deliveries occurred (92.8% and 77.2%, respectively; p=0.02). The most significant predictors of the ineffectiveness of preconception preparation were the presence in patients of: chronic cystitis and autoimmune thyroiditis with hypothyroidism; oligomenorrhea at the time of pregnancy planning; aggravated by early reproductive losses and long-term wearing of intrauterine contraception history; burdened heredity for violation of carbohydrate metabolism. CONCLUSION: Comprehensive preconception preparation in the sanatorium-resort conditions of Belokurikha helps to increase the fertility of patients with reproductive disorders, the trophostimulating effect in the genital organs and the restoration of endometrial reception, which makes it possible to recommend this method for use in clinical practice.

Climatotherapy at the Dead Sea for psoriasis is a highly effective anti-inflammatory treatment in the short term: An immunohistochemical study.

Climatotherapy is a well-described treatment of psoriasis. Dead Sea climatotherapy (DSC) in Israel consists of intensive sun and Dead Sea bathing and is very effective in improving clinical and patient-reported outcomes. However, the effect of DSC has not been widely studied. We aimed to investigate the effect of DSC on psoriasis skin using quantitative immunohistochemistry techniques and analysis of blood samples. Skin punch biopsies from 18 psoriasis patients from a previous cohort study were used. Biopsies were obtained from non-lesional skin and from a psoriasis target lesion at baseline. A biopsy was acquired from the target lesion after DSC. Among patients who achieved complete visual clearance, a biopsy was also obtained at relapse. Blood samples were obtained at the same time points. We performed haematoxylin and eosin staining and quantitative immunohistochemical analysis of CD3, CD4, CD8, CD11c, CD103, CD163, CD207, forkhead box P3, Ki67 and myeloperoxidase. We performed blood tests of cholesterol, c-reactive protein, glucose, haemoglobin A1c and triglycerides. All skin biomarkers except for CD207 were decreased after DSC. At relapse, none of the biomarkers were significantly different from the baseline lesional measurements. Total CD207 staining correlated with psoriasis area and severity index at baseline while CD163 staining correlated with psoriasis area and severity index at EOT. No changes were observed in selected blood tests during the study. Consistent with clinical results, DSC is highly effective in the short term almost normalising all investigated biomarkers. However, at relapse, biomarkers were upregulated to the baseline level.

[Climate-therapy at seaside resorts in modern medical and wellness practice]. / Klimatolechenie na primorskikh kurortakh v sovremennoi meditsinskoi i ozdorovitel'noi praktike.

A scientific review is devoted to the study of the coastal climate in the resort treatment role of patients with chronic diseases and its impact on the health and life quality of the population of the seacoasts. The sources were the Cochrane Library, PubMed MEDLINE, MedlinePlus, PedRO, Google Scholar, British Medical Journal, Elsevier, The Global Wellness Institute, eLIBRARY.ru. The review includes 40 publications including 22 domestic and 18 foreign ones on clinical and surrogate outcomes of climate-therapy at seaside resorts in the structure of spa treatment in patients with chronic diseases. The health problems among the population of the seacoasts are considered. The features of conducting evidence-based studies in assessing the effects of climate procedures are noted. The analysis of the therapeutic and health-improving effect results of the seaside climate and the associated forms of thalassotherapy - terrenkur, swimming, aqua gymnastics, sea bathing, heliotherapy, landscape therapy, and the use of maricultureis carried out. The article presents statistically reliable data on the favorable outcomes of treatment of chronic forms of musculoskeletal, skin, pulmonary and cardiac pathology under the influence of thalassotherapy methods. It was found that the effectiveness of climate-therapy in oncological practice, the treatment of pollinosis, the use of algae and other maricultures has been insufficiently proven: the possibility of percutaneous permeability to seawater and its components. The risk of developing negative meteorological reactions during climate-therapy was noted.

The effects of viewing a winter forest landscape with the ground and trees covered in snow on the psychological relaxation of young Finnish adults: A pilot study.

Forest bathing is an outdoor activity, and it might be a promising preventive treatment for social problems involving stress. A vast number of studies confirm the positive effects of this activity on people's health. Nevertheless, little is known about the influence of winter forest bathing when conducted in an environment with snow cover on the ground and trees. Thus, a crossover experiment was designed in this study, with the participation of twenty-two healthy university students from Finland. During the experiment, a short exposition by a forest environment or landscape with buildings (as a control) was applied. Participants self-reported their psychological relaxation before and after the exposition, and the results were analyzed and compared. The mood, emotions, restorativeness, and subjective vitality were recorded as indices reflecting the psychological relaxation effect. The negative mood indices decreased significantly after exposition by the snow-covered environment, but the positive 'vigor' indices did not increase or decrease significantly. The level of negative emotions increased after the exposition with the control environment. Likewise, positive emotions decreased after the interaction with the control. Restorativeness was significantly increased after the exposition by the experimental forest but decreased after the viewing of the control buildings. The size of the effect in terms of restorativeness was the highest in this experiment. The subjective vitality was lowered as affected by the control, but it did not increase or decrease after the exposition with the experimental forest. There is probably an effect from the slight interruption in the process from the influence of the forest greens on participants because their vigor and vitality did not increase after the exposition with this environment in the study. However, snow might influence the participants as a calming and emotion-lowering component of the environment, but this idea needs to be further explored with the involvement of participants from other countries who would be viewing forest environments with snow cover and whose psychological relaxation could be measured.

[Therapeutic effects of climototherapy: scientomatrical analysis of evidence-based studies]. / Lechebnye effekty klimatoterapii: naukometricheskii analiz dokazatel'nykh issledovanii.

OBJECTIVE: Scientometrical analysis of studies the use of climatotherapy methods and formulation of guidelines based on the evidence obtained during the analysis. MATERIAL AND METHODS: The article presents the data of scientometrical analysis of 40 publications on the use of climatotherapy in spa practice. RESULTS: Clinical effects and proposed mechanisms of action of the proven efficacy climatotherapy methods - aerotherapy, heliotherapy and thalassotherapy for the patients with various chronic diseases are presented. The clinical directions for the using of climatotherapy methods in climatic resorts are highlighted. CONCLUSIONS: Regular generalization and analysis of existing evidence-based studies is required, as well as the implementation of new high-quality randomized controlled clinical trials to study the effects of climate therapy on a wide range of patients with common socially significant diseases.

Evaluation of the Feasibility of a Two-Week Course of Aquatic Therapy and Thalassotherapy in a Mild Post-Stroke Population.

Strokes are a leading cause of disability in developed countries. Patients with disabilities need rehabilitation to improve their physical functioning, mental status, and quality of life. Currently, no high-quality evidence can be found attesting the benefits of any of the interventions that are nowadays used. Water-based exercise may improve the physical conditions and quality of life of people in the post-stroke phase. The objective of this study is to test whether aquatic therapy in an enriched environment at the seaside (a thalassotherapy center) could play a role in this condition. A quasi-experimental prospective study consisting of a specific program assessed 62 patients with a mild-moderate disability pre- and post-2 weeks of intensive treatment. They followed a thalassotherapy regimen including aquatic therapy in a sea water pool at 32-34 °C for 45 min daily five times a week. The outcomes measured were the Berg Balance scale, the Timed Up and Go test, the 10-meter walking test, the 6-min walking test, the Pain Visual Analogue Scale, the WHO Well-being index, EuroQoL VAS and EuroQoL 5D. We observed a significant improvement in all outcomes measured (p < 0.001, except mobility EuroQoL p < 0.05), except in the other four dimensions of the EuroQoL 5D and 10-metre walking test (NS). Conclusion: A two-week intensive course of aquatic therapy and thalassotherapy may be beneficial in the short term by reducing pain and improving the functional status and overall well-being of post-stroke patients.

Microbiological quality and safety of commercialized thalassotherapy products based on marine mud and algae extracts in Tunisia.

A total of 15 samples of thalassotherapy products, distributed in Tunisia in their intact and final state of production, was analyzed to determine their microbiological safety status. The result shows the absence of pathogenic bacteria (Staphylococcus aureus, Candida albicans, Salmonella, Pseudomonas aeruginosa and coliforms). The incidence of contamination by Gram-positive Bacilli (mesophelic bacteria, aerobic and anaerobic spore forming bacteria, anaerobic sulphite-reducing bacteria) was found to be higher in products composed by mud and extract of alga. The biochemical and molecular identification of the major contaminant show that Bacilli were the most covered from 75% of the thalassotherapy products. Mineral analysis (organic matter, Fe, Mg, Ca, Na d K, Al, Si and Ti) shows strong composition on Aluminum and Silica. Cytotoxicity study of six thalassotherapy products and three essential oil extracts (Menthol, Clove and Eucalyptus) did not show any cytotoxic effect. Furthermore, antibacterial acitivity of 5 essentila oils, against 30 isolates of the genus Bacillus and 10 reference strains, has been characterized showing an interesting bactericidal potential of the extract of menthol and Eucalyptus.

Long-term evaluation of climatotherapy for psoriasis.

Climatotherapy (CT) is a treatment with immediate high clearance rate for chronic psoriasis, but evidence of long-term effects is scarce. Assessment of the impact of a single CT treatment on disease activity and quality of life was carried out at 4- to 6-month follow-ups. A prospective study of patients with psoriasis undergoing 4 weeks of CT in Israel describes long-term outcomes of CT. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were assessed before CT and at an average of 5 months after return. Assessment of the eligibility for CT takes place twice a year. A total of 49 patients (28/21 M/F) participated. Pretreatment PASI was 2.6 to 18.7 (mean 8.1 ± 3.8) vs control PASI 0 to 16.9 (mean 5 ± 2.8), (P < .0001). Mean ΔPASI was 3.2 (39.5% reduction). PASI 75 was achieved by 11/49 patients; 10/49 had increased PASI. The mean DLQI score was 16.1 (range 2-30); 10.6 at follow-up (range 0-28), and 33 patients achieved DLQI minimal clinically important difference (P < .0001). Age, sex, number of previous CT, and duration of observation period did not affect endpoints. CT and unmonitored self-treatment induces PASI 75 in one-fifth patients at follow-up 4 to 6 months later. Six of 10 patients report a clinically important improvement of patients' quality of life as measured by DLQI.

Dead Sea climatotherapy versus topical steroid treatment for atopic dermatitis children: long-term follow-up study.

The aim of this study was to compare long-term results of 4 weeks Dead Sea climatotherapy at the Deutsches Medizinisches Zentrum, Israel to those obtained by classical topical treatment for moderate-to-severe atopic dermatitis. Seventy-two children from the Czech Republic were divided into three groups of 24 and treated during three periods (March 2014, October 2014 and March 2015) with gradually increasing sun exposure during 28 consecutive days. Forty-four children were treated with steroid creams at the Department of Dermatovenereology, Third Faculty of Medicine, Charles University and University Hospital of Kralovske Vinohrady, Prague, Czech Republic. The primary outcome was the change in the SCORing Atopic Dermatitis (SCORAD) index, recorded after 1 month of treatment (immediately after DSC) and 3, 6, 9, 12, and 18 months later in Prague. The mean SCORAD improvement was 87.5 ± 13.4% after 4 weeks at the Dead Sea and 86.1 ± 11.3% after 1 month of treatment with steroid creams in the Czech Republic. All 44 patients treated in Prague participated in this 18-month follow-up study, whereas only 47 patients (65.3%) after DSC treatment. Good clinical results were maintained in both groups and mean SCORAD values were stable and low, around 5.

Skin Microbiome Compositional Changes in Atopic Dermatitis Accompany Dead Sea Climatotherapy.

Dead Sea climatotherapy (DSC) is a well-established therapeutic modality for the treatment of several diseases, including atopic dermatitis. Skin microbiome studies have shown that skin microbiome diversity is anticorrelated with both atopic dermatitis severity and concurrent Staphylococcus aureus overgrowth. This study aimed to determine whether DSC induces skin microbiome changes concurrent with clinical improvements in atopic dermatitis. We sampled 35 atopic dermatitis patients and ten healthy controls on both the antecubital and popliteal fossa. High-resolution microbial community profiling was attained by sequencing multiple regions of the 16S rRNA gene. Dysbiosis was observed in both lesional and nonlesional sites, which was partially attenuated following treatment. Severe AD skin underwent the most significant community shifts, and Staphylococcus epidermidis, Streptococcus mitis and Micrococcus luteus relative abundance were significantly affected by Dead Sea climatotherapy. Our study highlights the temporal shifts of the AD skin microbiome induced by Dead Sea climatotherapy and offers potential explanations for the success of climatotherapy on a variety of skin diseases, including AD.

Multidisciplinary Biopsychosocial Program for Chronic Musculoskeletal Pain at the Dead Sea.

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation for patients presenting with rheumatic diseases has been shown to produce better results in a warm climate. Dead Sea Climatotherapy (DSC) has been successfully used for decades to treat many patients with rheumatic diseases. OBJECTIVES: To evaluate the short-term improvement of Norwegian patients who presented with chronic pain following a multidisciplinary biopsychosocial approach to treatment combined with DSC. Both objective and subjective clinical parameters were evaluated. METHODS: This retrospective study included a statistical analysis of 938 patients presenting with rheumatoid arthritis and ankylosing spondylitis (n=105), osteoarthritis (n=342), fibromyalgia (n=374), and other orthopedic conditions (n=117). Clinical assessments were conducted before and after a 3 week treatment program at the Dead Sea. RESULTS: Six parameters improved significantly in the rheumatoid arthritis and ankylosing spondylitis group as well as in the osteoarthritis group. Five parameters in the fibromyalgia group improved, while two improved in the orthopedic conditions group. Overall, major significant changes occurred in the pain self-assessment, joint motility, and daily activities scores. CONCLUSIONS: A 3-week multidisciplinary biopsychosocial program combined with DSC induced positive changes in the clinical parameters of Norwegian patients presenting with chronic musculoskeletal pain.

The Effect of Pulmonary Rehabilitation in Mountain Environment on Exercise Capacity and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis.

BACKGROUND We aimed to test the effectiveness of the pulmonary rehabilitation in a mountain environment on the pulmonary function, physical performance, dyspnea, affective factors, and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB), as well as to determine predictors of clinical improvement. MATERIAL AND METHODS 128 consecutive patients (90 diagnosed with COPD and 38 diagnosed with CB) underwent comprehensive pulmonary rehabilitation for a duration of 3 weeks in one of 3 mountain health resorts in the High Tatras. The examination included spirometry (FEV1 and FEV1/FVC), 6-minute walk test (6MWT), Borg scale of dyspnea, and assessment of depression (Zung score), anxiety (Beck score), and QoL using the SF-36 scales. RESULTS After the study intervention, all patients in both monitored groups demonstrated significant improvements in objective measurements in which large treatment effect was achieved (for FEV1 η²=0.218, for 6MWT η²=0.771). Similarly, in subjective measurements a large effect was achieved (for the Beck score: η²=0.599, for the Zung score: η²=0.536). QoL improved after the intervention in all the monitored SF-36 scales in both groups (P<0.001 for all). In patients with COPD, the improvement of exercise capacity was positively correlated with baseline 6MWT and FEV1, and negatively with the Beck anxiety score and the Borg dyspnea score, whereas, only improvement in the mental summary component of QoL was negatively correlated with baseline 6MWT and FEV1 (P<0.05 for all). CONCLUSIONS Rehabilitation in a mountain environment has proven to be effective in both the reported diagnoses of COPD and CB. Improvements in both functional and subjective indicators were observed. These findings support the use of this treatment modality.

Predictors of benefit from high-altitude climate therapy in adults with severe asthma.

BACKGROUND: High-altitude climate therapy has been shown to benefit patients with severe asthma but it is not known which patients benefit most from this treatment. In the current study we aimed to identify clinical, functional and inflammatory predictors of favourable outcome of high-altitude climate therapy. METHODS: This is a secondary analysis of a prospective cohort including 136 adult patients with a diagnosis of severe refractory asthma, referred to the Dutch Asthma Centre in Davos (1600 metres above sea level), Switzerland. They had assessments of medication usage, asthma-related quality of life (Asthma-related Quality of Life Questionnaire, AQLQ), asthma control, body mass index (BMI), sino-nasal symptoms, fatigue, lung function (forced expiratory volume in one second, FEV1), exercise tolerance, allergy and inflammation (fraction of exhaled nitric oxide, blood eosinophils) at entry and after 12 weeks of treatment. Five clinically relevant outcomes were considered: AQLQ, oral corticosteroid dose, FEV1, body mass index and blood eosinophils. Independent predictors of beneficial outcome were identified by multiple linear regression analysis. RESULTS: Lower blood eosinophil counts (p < 0.01), younger age (p = 0.02) and poorer asthma control (p < 0.01) were independently associated with greater reduction in the dose of oral corticosteroids. Lower fatigue score at baseline (p = 0.01) was associated with greater weight loss (reduction in BMI). Higher levels of total IgE at baseline (p < 0.01), and higher doses of inhaled corticosteroids (p = 0.03) were associated with greater decreases in blood eosinophils. There were no predictors for improvement in AQLQ or FEV1. CONCLUSIONS: The beneficial effect of high-altitude climate therapy in adults with severe asthma can be predicted by patient characteristics, such as age, blood eosinophils and degree of asthma control before admission.