Comparative Effectiveness of 4 Exercise Interventions Followed by 2 Years of Exercise Maintenance in Multiple Sclerosis: A Randomized Controlled Trial.

OBJECTIVE: To determine the effects of exergaming (EXE) on quality of life (QOL), motor, and clinical symptoms in multiple sclerosis (MS). We compared the effects of EXE, balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group on clinical and motor symptoms and quality of life (QOL) in people with MS (PwMS) and determined the effects of subsequent maintenance programs for 2 years in a hospital setting. DESIGN: A randomized controlled trial, using before-after test design. SETTING: University hospital setting. PARTICIPANTS: Of 82 outpatients with MS, 70 were randomized (N=70), and 68 completed the study. INTERVENTIONS: The initial high-intensity and high-frequency interventions consisted of 25 one-hour sessions over 5 weeks. After the 5-week-long initial intervention, the 2-year-long maintenance programs followed, consisting of 3 sessions per week, each for 1 hour. MAIN OUTCOME MEASURES: The primary outcome: Multiple Sclerosis Impact Scale (MSIS-29). SECONDARY OUTCOMES: Measures 5 aspects of health-related QOL (EuroQol 5-Dimension questionnaire), Beck Depression Inventory, 6-minute walk test (6MWT), Berg Balance Scale (BBS), Tinetti Assessment Tool (TAT), and static BAL (center of pressure). RESULTS: MSIS-29 improved most in EXE (11 points), BAL (6), and CYC (6) (all P<.05). QOL improved most in EXE (3 points), CYC, and BAL (2) (all P<.05). TAT and BBS improved significantly (P<.05) but similarly (P>.05) in EXE, BAL, and CYC. 6MWT improved most in EXE (57m), BAL (32m), and CYC (19m) (all P<.001). Standing sway did not change. Maintenance programs further increased the initial exercise-induced gains, robustly in EXE. CONCLUSIONS: A total of 25 sessions of EXE, BAL, CYC, and PNF, in this order, improved clinical and motor symptoms and QOL, and subsequent 2-year-long thrice weekly maintenance programs further slowed symptom worsening and improved QOL. EXE was the most and PNF was the least effective to improve clinical symptoms, motor function, and QOL in PwMS.

Accumulation of HT-2 toxin from contaminated mushroom compost by edible Agaricus bisporus.

Wheat straw is commonly used as a cellulose source in mushroom compost and could be a secondary source of mycotoxin contamination in the food chain. We cultivated edible Agaricus bisporus and Pleurotus ostreatus on T-2/HT-2 artificially-contaminated mushroom compost and developed and in-house validated an UHPLC-MS/MS method for determination of T-2, HT-2, T2-triol and T2-tetraol in mushroom compost and mushroom basidiocarp. A rapid phase I metabolization of T-2 and HT-2 in mushroom compost was observed. In Agaricus bisporus, basidiocarps 8-15 µg kg-1 accumulation of HT-2 calculated on wet weight was measured. No detectable mycotoxins were found in Pleurotus ostreatus basidiocarp.

Detraining Slows and Maintenance Training Over 6 Years Halts Parkinsonian Symptoms-Progression.

Introduction: There are scant data to demonstrate that the long-term non-pharmaceutical interventions can slow the progression of motor and non-motor symptoms and lower drug dose in Parkinson's disease (PD). Methods: After randomization, the Exercise-only (E, n = 19) group completed an initial 3-week-long, 15-session supervised, high-intensity sensorimotor agility exercise program designed to improve the postural stability. The Exercise + Maintenance (E + M, n = 22) group completed the 3-week program and continued the same program three times per week for 6 years. The no exercise and no maintenance control (C, n = 26) group continued habitual living. In each patient, 11 outcomes were measured before and after the 3-week initial exercise program and then, at 3, 6, 12, 18, 24, 36, 48, 60, and 72 months. Results: The longitudinal linear mixed effects modeling of each variable was fitted with maximum likelihood estimation and adjusted for baseline and covariates. The exercise program strongly improved the primary outcome, Motor Experiences of Daily Living, by ~7 points and all secondary outcomes [body mass index (BMI), disease and no disease-specific quality of life, depression, mobility, and standing balance]. In E group, the detraining effects lasted up to 12 months. E+M group further improved the initial exercise-induced gains up to 3 months and the gains were sustained until year 6. In C group, the symptoms worsened steadily. By year 6, levodopa (L-dopa) equivalents increased in all the groups but least in E + M group. Conclusion: A short-term, high-intensity sensorimotor agility exercise program improved the PD symptoms up to a year during detraining but the subsequent 6-year maintenance program was needed to further increase or sustain the initial improvements in the symptoms, quality of life, and drug dose.

Genetic Investigation of Inverse Psoriasis.

Inverse psoriasis is considered to be a rare variant of plaque-type psoriasis and is associated with significantly impaired quality of life. Clinical manifestations and treatment options are somewhat different for each subtype. Identifying genetic variants that contribute to the susceptibility of different types of psoriasis might improve understanding of the etiology of the disease. Since we have no current knowledge about the genetic background of inverse psoriasis, whole exome sequencing was used to comprehensively assess genetic variations in five patients with exclusively inverse lesions. We detected six potentially pathogenic rare (MAF < 0.01) sequence variants that occurred in all investigated patients. The corresponding mutated genes were FN1, FBLN1, MYH7B, MST1R, RHOD, and SCN10A. Several mutations identified in this study are known to cause disease, but roles in psoriasis or other papulosquamous diseases have not previously been reported. Interestingly, potentially causative variants of established psoriasis-susceptibility genes were not identified. These outcomes are in agreement with our hypothesis that the inverse subtype is a different entity from plaque-type psoriasis.

Multi-mycotoxin LC-MS/MS method validation and its application to fifty-four wheat flours in Hungary.

In this study, fifty-four wheat flour and wheat-based products available on the Hungarian market were assessed for twelve mycotoxins. Prior to analysis, a multi-mycotoxin method using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was developed and validated for wheat and wheat-based products. A simple extraction with acetonitrile/water/formic acid (79/20/1 v/v%) was used for sample preparation. The limits of quantitation (LOQ) were between 0.02 and 161 µg kg-1. Good linearity (r2 > 0.995) was achieved for all mycotoxins investigated. Recoveries varied between 88 and 120% at three concentration levels. Based on the low relative matrix effect (RSD < 0.15%) of the different wheat flour samples, matrix-matched calibration was used, which also proved its suitability in proficiency testing (z-scores: -0.6 for DON; +1.5 for OTA; -0.5 for ZEA). DON was the predominant mycotoxin, which contaminated 84% of the investigated samples. Metabolised forms of DON were found in spelt, durum flour and some wheat-based products (D3G in 4 samples, 15Ac-DON in 7 samples). T-2 and HT-2 were the second most frequently detected mycotoxins. All investigated samples complied with current European/Hungarian legislation.

Comparison of QuEChERS and "dilute and shoot" extraction methods for multi-mycotoxin analysis of samples from button mushroom (Agaricus bisporus) cultivation.

Several components of mushroom compost (wheat straw, chicken manure) can be contaminated with mycotoxins posing food health risks to mushroom consumers. To assess the relevance of such contaminations high-throughput analytical methods are needed. In this study, two sample preparation approaches, dilute & shoot (D&S) and modified citrate buffered Quick, Easy, Cheap, Effective, Rugged, Safe (QuEChERS) were compared in terms of extraction efficiency and matrix effect in case of 13 mycotoxins in complex matrices-wheat straw, the growing media and button mushrooms (Agaricus bisporus)-of mushroom cultivation using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). D&S method resulted in recoveries of LB medium, button mushroom and compost for ≥60% in case of all investigated mycotoxins except for DON-3G. However, using modified citrate buffered QuEChERS with 2% acidification of the extraction solvent showed the complete loss of strongly polar DON-3G and fumonisin B1 (FB1). The investigated matrices had suppressive effect on ionization in all target mycotoxins except for FB1. Regarding the use of isotopologues to compensate matrix effect, even U-[13C15]-DON and U-[13C24]-T-2 can also be used to quantify their related metabolites in the studied matrices, using internal standard method.

Evaluation of the Multimycotoxin-Degrading Efficiency of Rhodococcus erythropolis NI1 Strain with the Three-Step Zebrafish Microinjection Method.

The multimycotoxin-degrading efficiency of the Rhodococcus erythropolis NI1 strain was investigated with a previously developed three-step method. NI1 bacterial metabolites, single and combined mycotoxins and their NI1 degradation products, were injected into one cell stage zebrafish embryos in the same doses. Toxic and interaction effects were supplemented with UHPLC-MS/MS measurement of toxin concentrations. Results showed that the NI1 strain was able to degrade mycotoxins and their mixtures in different proportions, where a higher ratio of mycotoxins were reduced in combination than single ones. The NI1 strain reduced the toxic effects of mycotoxins and mixtures, except for the AFB1+T-2 mixture. Degradation products of the AFB1+T-2 mixture by the NI1 strain were more toxic than the initial AFB1+T-2 mixture, while the analytical results showed very high degradation, which means that the NI1 strain degraded this mixture to toxic degradation products. The NI1 strain was able to detoxify the AFB1, ZEN, T-2 toxins and mixtures (except for AFB1+T-2 mixture) during the degradation experiments, which means that the NI1 strain degraded these to non-toxic degradation products. The results demonstrate that single exposures of mycotoxins were very toxic. The combined exposure of mycotoxins had synergistic effects, except for ZEN+T-2 and AFB1+ZEN +T-2, whose mixtures had very strong antagonistic effects.

Qualifying the T-2 Toxin-Degrading Properties of Seven Microbes with Zebrafish Embryo Microinjection Method.

T-2 mycotoxin degradation and detoxification efficiency of seven bacterial strains were investigated with zebrafish microinjection method in three steps ((1) determination of mycotoxin toxicity baseline, (2) examination of bacterial metabolites toxicity, (3) identification of degradation products toxicity). Toxicity of T-2 was used as a baseline of toxic effects, bacterial metabolites of strains as control of bacterial toxicity and degradation products of toxin as control of biodegradation were injected into one-cell stage embryos in the same experiment. The results of in vivo tests were checked and supplemented with UHPLC-MS/MS measurement of T-2 concentration of samples. Results showed that the Rhodococcus erythropolis NI1 strain was the only one of the seven tested (R. gordoniae AK38, R. ruber N361, R. coprophilus N774, R. rhodochrous NI2, R. globerulus N58, Gordonia paraffinivorans NZS14), which was appropriated to criteria all aspects (bacterial and degradation metabolites of strains caused lower toxicity effects than T-2, and strains were able to degrade T-2 mycotoxin). Bacterial and degradation metabolites of the NI1 strain caused slight lethal and sublethal effects on zebrafish embryos at 72- and 120-h postinjection. Results demonstrated that the three-step zebrafish microinjection method is well-suited to the determination and classification of different bacterial strains by their mycotoxin degradation and detoxification efficiency.

Mycotoxin Biodegradation Ability of the Cupriavidus Genus.

The biodegradation and biodetoxification ability of five prominent mycotoxins, namely aflatoxin B1 (AFB1), ochratoxin-A (OTA), zearalenone (ZON), T-2 toxin (T-2) and deoxynivalenol (DON) of Cupriavidus genus were investigated. Biological methods are the most appropriate approach to detoxify mycotoxins. The Cupriavidus genus has resistance to heavy metals and can be found in several niches such as root nodules and aquatic environments. The genus has 17 type strains, 16 of which have been investigated in the present study. According to the results, seven type strains can degrade OTA, four strains can degrade AFB1, four strains can degrade ZON and three strains can degrade T-2. None of the strains can degrade DON. The biodetoxification was measured using different biotests. SOS-chromotest was used for detecting the genotoxicity of AFB1, the BLYES test was used to evaluate the oestrogenicity of ZON, and the zebrafish embryo microinjection test was conducted to observe the teratogenicity of OTA, T-2 and their by-products. Two type strains, namely C. laharis CCUG 53908T and C. oxalaticus JCM 11285T reduced the genotoxicity of AFB1, whilst C. basilensis DSM 11853T decreased the oestrogenic of ZON. There were strains which were able to biodegrade more than two mycotoxins. Two strains degraded two mycotoxins, namely C. metalliduriens CCUG 13724T (AFB1, T-2) and C. oxalaticus (AFB1, ZON) whilst two strains C. pinatubonensis DSM 19553T and C. basilensis degraded three toxins (ZON, OTA, T-2) and C. numazuensis DSM 15562T degraded four mycotoxins (AFB1, ZON, OTA, T-2), which is unique a phenomenon amongst bacteria.

Advances in phototherapy for psoriasis and atopic dermatitis.

Introduction: Phototherapy has long been used for the treatment of inflammatory skin diseases, such as psoriasis and atopic dermatitis. The most frequent treatment approach utilizes ultraviolet (UV) light, however, recently, different lasers and low-level light therapies (LLLT) emitting wavelengths in the spectrum of the visible light have also been tried for the treatment of inflammatory skin diseases with variable success.Areas covered: This review provides an update on the different forms of phototherapy used for the treatment of psoriasis and atopic dermatitis. The proposed mechanism of action of the different phototherapeutical approaches are covered, including the immunosuppressive effect of UV light, the anti-inflammatory effect of vascular lasers and the LLLT induced photobiomodulation. The clinical efficacy of the different treatment options is also discussed.Expert opinion: Based on the efficacy and safety, NB-UVB represents the gold standard for treating psoriasis and atopic dermatitis. The UVB excimer laser and excimer lamp might be the best option for clearing localized therapy-resistant lesions. Home UV phototherapy systems might promote treatment adherence and better compliance of the patients. Vascular lasers, IPLs and LLLT, however, can not currently be recommended for the treatment of inflammatory skin diseases because of the lack of well-controlled studies.

New oxidative decomposition mechanism of estradiol through the structural characterization of a minute impurity and its degradants.

Herein we discuss the structure elucidation of a labile estradiol-related degradant, X1. X1 was detected at Gedeon Richter as an unknown trace impurity in a pharmaceutical formulation containing estradiol (1a) and norethisterone acetate (NA) as active ingredients. The structural identification of X1 proved to be an unusually complex task involving an initial structural hypothesis based on some limited analytical data (UV) obtained from the formulation, synthetic work targeting the proposed structure, chromatographic enrichment from the synthetic reaction mixture, (HPLC)-MS and MS-MS studies of the formulation and of samples from the synthesis using almost all available ionization modes, preparative LC enrichment, and the complementary use of off-line and on-line NMR techniques. Based on these results, X1 was finally characterized as a new oxidative product of estradiol, containing an epoxy function over the C9-C10 bond. During the structure determination of X1 its secondary and tertiary decomposition products were also identified as a new secoepoxy (6) and a known seco derivative (5a) of estradiol, respectively. On this basis a new oxidative decomposition mechanism of estradiol and its analogues could be proposed. A generalization of the mechanism of this pathway can more readily explain the formation of some oxidative secosteroid degradants than the mechanism proposed earlier in the literature.