Outcome measures for physical fatigue in individuals with multiple sclerosis: a systematic review.

INTRODUCTION: Physical fatigue can be a common reason for early retirement or sick leave since it appears in the earliest stages of multiple sclerosis (MS). Therefore, a prompt and accurate diagnosis is essential. This systematic review aims to identify and describe the instruments used to assess physical fatigue in MS patients with consideration for the languages used to validate the instruments and their methodological qualities. AREA COVERED: This study has been carried out through 'Medline,' 'Scopus,' 'Cinhal,' and 'Web of Science' databases for all the papers published before 24 January 2020. Three independent authors have chosen the eligible studies based upon pre-set criteria of inclusion. Data collection, data items, and assessment of the risk of bias: the data extraction approach was chosen based on the Cochrane Methods. For data collection, the authors followed the recommendations from the COSMIN initiative. Study quality and risk of bias were assessed using the COSMIN Check List. EXPERT OPINION: 119 publications have been reviewed. The 45 assessment scales can be divided into specific scales for physical fatigue and specific scales for MS. The most popular tools are the Fatigue Severity Scale and the Modified Fatigue Impact Scale.

Bio-Inspired Systems in Nonsurgical Periodontal Therapy to Reduce Contaminated Aerosol during COVID-19: A Comprehensive and Bibliometric Review.

BACKGROUND: On 30 January 2020, a public health emergency of international concern was declared as a result of the new COVID-19 disease, caused by the SARS-CoV-2 virus. This virus is transmitted by air and, therefore, clinical practices with the production of contaminant aerosols are highly at risk. The purpose of this review was to assess the effectiveness of bio-inspired systems, as adjuvants to nonsurgical periodontal therapy, in order to formulate bio-inspired protocols aimed at restoring optimal condition, reducing bacteremia and aerosols generation. METHODS: A comprehensive and bibliometric review of articles published in English. Research of clinical trials (RCTs) were included with participants with chronic or aggressive periodontal disease, that have compared benefits for nonsurgical periodontal therapy (NSPT). RESULTS: Seventy-four articles have been included. For probing depth (PPD) there was a statically significant improvement in laser, probiotic, chlorhexidine groups, such as gain in clinical attachment level (CAL). Bleeding on probing (BOP) reduction was statistically significant only for probiotic and chlorhexidine groups. There were changes in microbiological and immunological parameters. CONCLUSIONS: The use of bio-inspired systems in nonsurgical periodontal treatment may be useful in reducing risk of bacteremia and aerosol generation, improving clinical, microbiological and immunological parameters, of fundamental importance in a context of global pandemic, where the reduction of bacterial load in aerosols becomes a pivotal point of clinical practice, but other clinical trials are necessary to achieve statistical validity.

Comparing different sperm separation techniques for ART, through quantitative evaluation of p53 protein.

CONTEXT: In the last 10 years, assisted reproductive technologies (ARTs) have offered infertile couples an opportunity to complete their reproductive project. However, the high failure rate could be explained with the complex human reproduction system. In ART, the decrease of the success is due to the conditions far from the natural ones. AIMS: The aim of this study is to evaluate deoxyribonucleic acid (DNA) damage of spermatozoa before and after selection procedures, using a new technique able to quantize sperm DNA damage. SETTINGS AND DESIGN: They were involved 43 males domiciled permanently in two areas with different Environmental Impact, HEI (high environmental impact) and LEI (Low environmental impact), they are aged between 24 and 31 years with various degrees of dyspermia. SUBJECTS AND METHODS: The 43 males were divided into two groups: 21 in Group A (EIL) and 22 in Group B (EIH). The samples must be aliquoted into parts of 0.5 mL: Group (a) Control, no processing; Group (b) Swim-up (SUP) from semen; Group (c) classic SUP; Group (d) density gradient centrifugation (DGC). All samples were subjected to a quantitative dosage of p53 protein, before and after processing. STATISTICAL ANALYSIS USED: For the development of the probability and significance of the data, the Student's t-test was used. RESULTS: From our data, it emerges that Groups D and B provide a superior quality about motility, vitality, and apoptosis indexes compared to other conventional techniques. In Group B, apoptosis is comparable to Group D, but they have slightly lower about motility and vitality. Group C is the one that has lower parameters than the other techniques. Regarding the evaluation of p53 protein, the results are conflicting with the evaluation of apoptosis; in fact, in Group D, the values are significantly higher than the other techniques. CONCLUSIONS: Sperm separation is an important moment in ART techniques. From our data, it emerges a greater fragility of DNA in the male spermatozoa who reside permanently in areas with high environmental impact.

p53 Protein Evaluation on Spermatozoa DNA in Fertile and Infertile Males.

INTRODUCTION AND OBJECTIVES: Protein p53 role in the spermatogenesis is demonstrated, it guarantees both the appropriate quality and quantity of mature spermatozoa. In this observational study we evaluate the eventual correlation between "corrected" p53 concentration on human spermatozoa DNA and male fertility potential. MATERIALS AND METHODS: Our work is based on an observational study made of 169 male in a period between March 2012 and February 2017. The entire study group is composed by 208 male partners aged between 26-38 years with ejaculate volume from 0.6 to 5.8 mL and heterogeneous seminal valuation: 86/208 (41,3%) normospermic; 19/208 (9,1%) mild oligospermic; 51/208 (24,5%) moderate oligospermic to; 52/208 (25,1%) with severe oligospermic. The "control" group A includes 39 male partners considered "fertile", because we did the p53 "corrected" test on their spermatozoa after 28 ± 3,5 days from the positives of their partners pregnancy test (betaHCG> 400 m U/m L). The group B, subdivided in B1, B2 and B3, includes 169 male partners for a observational period of 60 months. This partners don't report previous conceptions, they aren't smokers, don't make use neither of alcohol nor drugs and don't present pathologic varicocele studied with ecoColorDoppler. They are all married or stable cohabitants from a period of 27-39 months and report to have frequent sex without protection with their partners. Determination of p53 procedure: To separate the spermatozoa from seminal fluid we utilized the Differex™ kit System and the DNA IQ™ kit (Promega). For the p53 test we used the direct DuoSet IC kit and quantitative (R&D System). The p53 values were corrected in respect to the spermatozoa concentration expressed in ng/millions of spermatozoa. RESULTS: Group A (39 male) presents "correct" p53 values that vary from 0.35 to 3.20 ng/millions of spermatozoa and group B presents values that vary from 0.68 to 14.53. From group B (48 male) in the observational period we have recorded 21 pregnancies with initial "correct" p53 values that vary from a minimum of 0.84 to a maximum of 3.29. In the subgroup B1 we obtained 8 pregnancies from male partners with a "correct" p53 concentration included between 0.84 to 1.34. In the subgroup B2 we obtained 13 pregnancies from male partners with a "correct" p53 concentration included between 1.66 and 3.29. In the subgroup B3 (121 male) there weren't neither pregnancies nor miscarriages and "correct" p53 values were included between 3.58 and 14.53. CONCLUSION: The results show that the member of the group A with values of 'corrected' p53 between 0.35 and 3.20 were considered "Fertile", although in the observational period 3 miscarriages happened for 3 partners. 36 partners on 39 (92,3%) had a p53 concentration inferior to 1.65, this value were considered as the extreme to identify this group. The member of the group B1 had "corrected" p53 concentration that were included in the group. In the group B2 were observe 13 pregnancies, so its member were considered "potentially fertile" In the group B3 (121 male) weren't observe neither pregnancies nor miscarriages, so its member were considered "potentially infertile". If further studies confirm these data, we will consider the p53 test ELISA inspected in "correct" p53 as a new and accurate marker of the potential of male fertility.

Remission and rheumatoid arthritis: data on patients receiving usual care in twenty-four countries.

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis.

OBJECTIVE: To determine whether levels of B cell activating factor (BAFF), a member of the tumor necrosis factor family, relate to autoantibody levels, disease activity, and response to treatment in patients with early rheumatoid arthritis (ERA). METHODS: BAFF was measured by ELISA in 48 early RA patients; 21 were examined serially. These data were compared with 49 controls with longstanding RA (LSRA), 48 disease controls (DC), and 50 healthy controls (HC). RESULTS: BAFF levels were higher in ERA, compared with DC and HC [median 4.3 ng/ml (5th-95th: 0.8-38.8) vs 0.9 ng/ml (5th-95th: 0.7-4.5) and 2.0 ng/ml (5th-95th: 0.7-5.68), respectively; p <10(-4 )both comparisons], but not with LSRA controls [median 8.7 ng/ml (5th-95th: 0.8-46.1); p = nonsignificant]. BAFF correlated with the titers of IgM rheumatoid factor and anti-cyclic citrullinated peptide autoantibody (r = 0.76 and r = 0.49; p < 0.00001, p = 0.0001 for the 2 correlations), and with the number of swollen joints (r = 0.37; p = 0.01). The followup study of 21 methotrexate-treated ERA patients revealed reduced levels of BAFF, with parallel improvement in clinical activity and decrease in autoantibody titers. CONCLUSION: Elevated BAFF in a subset of ERA patients is related to autoantibody levels and synovitis. BAFF level diminished with treatment, along with autoantibody titers, suggesting a rationale to treat ERA patients with BAFF-targeted agents.

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study.

INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy.

OBJECTIVES: To analyze the association of interleukin (IL-1) gene polymorphisms with susceptibility to, and severity of, rheumatoid arthritis (RA) patients, comparing them with the genotype distribution in healthy controls. Also, to assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra plasma levels and response to therapy. PATIENTS AND METHODS: We tested the allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors (HBDs). The patients were categorized into two subgroups in relation to the response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA patients with active disease despite MTX therapy. This group received antitumor necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX-NR). RESULTS: None of the two IL-1B (-511 and +3953) gene polymorphisms were significantly different in frequency between RA patients and healthy controls. We observed an increased frequency of the rare allele IL1RN*3 in RA patients with active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and healthy controls (0.8%). Interestingly, RA patients whose genotypes included the IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1-Ra, but comparable levels of IL-1beta with regard to subjects with the presence of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953 genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in RA patients. Carriers of the IL1RN*2 allele responded better to infliximab therapy. CONCLUSIONS: The results of this study provide evidence of an association between the IL1RN*long allele and RA, the strongest association being observed in RA patients with an aggressive disease resistant to MTX treatment.