Thalassotherapy for fibromyalgia: a randomized controlled trial comparing aquatic exercises in sea water and water pool

The aim of this study was to evaluate the effectiveness of aerobic exercise in water pool compared with aerobic exercise performed in sea by women with fibromyalgia (FM). A total of 46 patients were randomly allocated into two groups: pool group (23 patients) and sea group (23 patients) that performed the same aerobic exercise program. Patients were evaluated baseline and after 12 weeks using: VAS, number of tender points, FIQ, SF-36, PSQI, and BDI. Both groups improved significantly in post-treatment for all the evaluated variables. There were no significant differences between two groups, except for BDI (F = 2.418, P < 0.0001). Aerobic exercise program performed in water (pool or sea) was effective for patients with FM. However, sea water exercises have been shown to bring more advantages related to emotional aspects. Then, exercise performed sea water (thalassotherapy) is an option for effective treatment with low cost for patients with FM.     

Combinatorial detection of autoreactive CD8<Superscript>+</Superscript> T cells with HLA-A2 multimers: a multi-centre study by the Immunology of Diabetes Society T Cell Workshop

Aims/hypothesis

Validated biomarkers are needed to monitor the effects of immune intervention in individuals with type 1 diabetes. Despite their importance, few options exist for monitoring antigen-specific T cells. Previous reports described a combinatorial approach that enables the simultaneous detection and quantification of multiple islet-specific CD8⁺ T cell populations. Here, we set out to evaluate the performance of a combinatorial HLA-A2 multimer assay in a multi-centre setting.

Methods

The combinatorial HLA-A2 multimer assay was applied in five participating centres using centralised reagents and blinded replicate samples. In preliminary experiments, samples from healthy donors were analysed using recall antigen multimers. In subsequent experiments, samples from healthy donors and individuals with type 1 diabetes were analysed using beta cell antigen and recall antigen multimers.

Results

The combinatorial assay was successfully implemented in each participating centre, with CVs between replicate samples that indicated good reproducibility for viral epitopes (mean %CV = 33.8). For beta cell epitopes, the assay was very effective in a single-centre setting (mean %CV = 18.4), but showed sixfold greater variability across multi-centre replicates (mean %CV = 119). In general, beta cell antigen-specific CD8⁺ T cells were detected more commonly in individuals with type 1 diabetes than in healthy donors. Furthermore, CD8⁺ T cells recognising HLA-A2-restricted insulin and glutamate decarboxylase epitopes were found to occur at higher frequencies in individuals with type 1 diabetes than in healthy donors.

Conclusions/interpretation

Our results suggest that, although combinatorial multimer assays are challenging, they can be implemented in multiple laboratories, providing relevant T cell frequency measurements. Assay reproducibility was notably higher in the single-centre setting, suggesting that biomarker analysis of clinical trial samples would be most successful when assays are performed in a single laboratory. Technical improvements, including further standardisation of cytometry platforms, will likely be necessary to reduce assay variability in the multi-centre setting.

     

Host- and microbe-related risk factors for and pathophysiology of fatal Rickettsia conorii infection in Portuguese patients

BACKGROUND: The pathophysiologic mechanisms that determine the severity of Mediterranean spotted fever (MSF) and the host-related and microbe-related risk factors for a fatal outcome are incompletely understood. METHODS: This prospective study used univariate and multivariate analyses to determine the risk factors for a fatal outcome for 140 patients with Rickettsia conorii infection admitted to 13 Portuguese hospitals during 1994-2006 with documented identification of the rickettsial strain causing their infection. RESULTS: A total of 71 patients (51%) were infected with the Malish strain of Rickettsia conorii, and 69 (49%) were infected with the Israeli spotted fever (ISF) strain. Patients were admitted to the intensive care unit (40 [29%]), hospitalized as routine inpatients (95[67%]), or managed as outpatients (5[4%]). Death occurred in 29 adults (21%). A fatal outcome was significantly more likely for patients infected with the ISF strain, and alcoholism was a risk factor. The pathophysiology of a fatal outcome involved significantly greater incidence of petechial rash, gastrointestinal symptoms, obtundation and/or confusion, dehydration, tachypnea, hepatomegaly, leukocytosis, coagulopathy, azotemia, hyperbilirubinemia, and elevated levels of hepatic enzymes and creatine kinase. Some, but not all, of these findings were observed more often in ISF strain-infected patients. CONCLUSIONS: Although fatalities and similar clinical manifestations occurred among both groups of patients, the ISF strain was more virulent than the Malish strain. Multivariate analysis revealed that acute renal failure and hyperbilirubinemia were most strongly associated with a fatal outcome.     

Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE^−/− mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EV-mediated mineral nucleation and evaluate potential therapies for cardiovascular calcification.

Atherosclerotic plaque rupture is the leading cause of myocardial infarction and stroke (1, 2). Studies assessing the correlation between calcium scores and cardiovascular events have demonstrated a predictive power that is superior to and independent from that of lipid scores (3, 4). Additionally, clinical imaging studies have revealed that the risk of plaque rupture is further heightened by the presence of small, “spotty” calcifications, or microcalcifications (5, 6), and cardiovascular risk is inversely correlated with the size of calcific deposits, quantified as a calcium density score (7). Indeed, computational modeling has demonstrated that, while large calcifications can reinforce the fibrous cap (8), microcalcifications (typically 5 to 15 μm in diameter) uniquely mediate an increase in mechanical stress of the relatively soft, collagen-rich fibrous cap (9–12).Histologic studies have revealed the presence of cell-derived vesicles within calcifying atherosclerotic lesions (13–16). The inflammatory environment of the atherosclerotic lesion can induce vascular smooth muscle cells (vSMCs) to take on an osteochondrogenic phenotype and release calcifying extracellular vesicles (EVs) (17–19). Macrophages have also been shown to release procalcifying vesicles (20, 21). Thus, just as bone formation is hypothesized to be an active, cell-driven process (22, 23), mediated by calcifying matrix vesicles, atheroma-associated calcification may similarly be initiated by the production and aggregation of calcifying EVs (11, 20, 24–28).One proposed strategy for halting pathologic calcification has been the use of bisphosphonates (BiPs). BiPs are analogs of pyrophosphate (29), a naturally occurring compound derived in vivo from adenosine triphosphate (ATP) (30). Pyrophosphate binds to calcium phosphate and inhibits calcification via physicochemical mechanisms, namely, by blocking calcium and phosphate ions from forming crystals, preventing crystal aggregation, and preventing mineral transformation from amorphous calcium phosphate to hydroxyapatite (29). BiPs were identified as pyrophosphate analogs that, unlike pyrophosphate itself, resist enzymatic hydrolysis. A second, distinct property of BiPs is the ability to inhibit bone resorption via biological activity directed against osteoclasts following osteoclast endocytosis of the BiP molecule adsorbed to the surface of bone (29, 31). First-generation, or nonnitrogen-containing BiPs, are incorporated into nonhydrolyzable ATP analogs, and induce osteoclast apoptosis by limiting ATP-dependent enzymes. In contrast, nitrogen-containing BiPs inhibit farnesyl pyrophosphate synthetase and thereby induce osteoclast apoptosis (31).In vivo animal investigations have been performed to explore the potential for BiPs to inhibit cardiovascular calcification. Studies of first-generation BiPs revealed that the doses required to inhibit cardiovascular calcification also critically compromised normal bone mineralization (29, 32). However, newer, nitrogen-containing BiPs effectively arrested cardiovascular calcification in animal models at doses that did not compromise bone formation (32). Further, while it has been proposed that BiP treatment modifies cardiovascular calcification via its impact on bone-regulated circulating calcium and phosphate levels, a study in uremic rats demonstrated that BiP treatment inhibited medial aortic calcification with no significant change in plasma calcium and phosphate levels (33). The same study demonstrated that BiP treatment inhibited calcification of explanted rat aortas, indicating that BiPs can act directly on vascular tissue, independent of bone metabolism (33).Retrospective clinical data examining the effect of BiP therapy on cardiovascular calcification has demonstrated conflicting findings and intriguing paradoxes. In women with chronic kidney disease, BiP therapy decreased the mortality rate for patients without a prior history of cardiovascular disease (34), but for those patients with a history of prior cardiovascular events, BiP therapy was associated with an increased mortality rate (35). In another study, BiP therapy correlated with a lower rate of cardiovascular calcification in older patients (>65 y), but a greater rate in younger patients (<65 y) (36). These clinical findings motivated our study, in which we sought to further understand how BiP therapy impacts cardiovascular outcomes. Given that cardiovascular calcification, and especially the presence of microcalcification, is a strong and independent risk factor for adverse cardiac events, and BiPs are prescribed to modulate pathologies of mineralization, we hypothesize that BiPs modulate cardiovascular outcomes by altering the dynamics of cardiovascular calcification.EVs are smaller than the resolution limits of traditional microscopy techniques, hindering studies into the mechanisms of calcification nucleation and growth. We previously developed an in vitro collagen hydrogel platform that allowed the visualization of calcific mineral development mediated by EVs isolated from vSMCs (24). Using superresolution microscopy, confocal, and electron microscopy techniques, we showed that calcification requires the accumulation of EVs that aggregate and merge to build mineral. Collagen serves as a scaffold that promotes associations between EVs that spread into interfibrillar spaces. The resultant mineral that forms within the collagen hydrogel appears spectroscopically similar to microcalcifications in human tissues and allows the study of these structures on the time scale of 1 wk. In this study, we utilized this three-dimensional (3D) acellular platform to examine the direct effect of ibandronate, a nitrogen-containing BiP, on the EV-directed nucleation and growth of microcalcifications, a process that cannot be isolated from cellular and tissue-level mechanisms in a more complex, in vivo system. In parallel, we utilized a mouse model of atherosclerosis to assess the effect of ibandronate therapy on plaque-associated calcification, comparing mineral morphologies between the in vitro and in vivo samples. We hypothesize that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Understanding the EV-specific action of BiPs is imperative both to develop anticalcific therapeutics targeting EV mineralization and to understand one potential mechanism driving the cardiovascular impact of BiPs used in clinical settings.     

Osteomuscular symptoms on motorcycles in the city of Rio Branco,Acre, Brazil,West Amazon

Musculoskeletal disorders gradually affect workers in different parts of the world, compromising their occupational health and quality of life. Professionals exposed to these symptoms include the motorcycle taxi driver, whose pain is due to the overuse of the musculoskeletal system and little time to recover it.To identify the prevalence of musculoskeletal symptoms in motorcycle taxi drivers in the city of Rio Branco, Acre, Brazil, West Amazon.Cross-sectional study, involving 296 motorcycle taxi drivers in the city of Rio Branco-Acre, Brazil, male, from December 2016 to February 2017. The Nordic Musculoskeletal Questionnaire was used to collect information related to symptoms (pain, discomfort, or numbness) in the last 7 days of work. For the exclusion criteria were, being female; not reside outside the city of Rio Branco, Acre; having less than 3 months of work activity; not be carrying out their work activities at the time of application of the protocol; be limited by clinical or physical issues at the time of application of the protocol. The data obtained in the questionnaire were entered into the Epidata program (Epidata Association, Odense, Denmark) and then transferred to the STATA 10 statistical program (Stata Corp., College Station), for categorization and statistical analysis.The study population is over 36 years old; most reported having a partner and a higher education level. The average daily working hours of the participants were 12 hours, with the majority working over 12 hours daily. Most of the epidemiological variables factors were associated with musculoskeletal pain when the prevalence and prevalence ratio analyzes were performed. Higher prevalence of musculoskeletal symptoms in the lumbar region is with 17.9%. In the lower limbs, the most affected joint was the ankle (5.7%), followed by the hip (5.07%) and knee (5.07%), respectively. Insomnia was present in 55.35% and self-reported headache in 49.4% of participants.The musculoskeletal disorders generated by the daily service of motorcycle taxi drivers are directly affecting the quality of life of these professionals.     

Fibra dietaria y microbiota,revisión narrativa de un grupo de expertos de la Asociación Mexicana de Gastroenterología

Dietary fiber intake is one of the most influential and efficacious strategies for modulating the gut microbiota. Said fiber can be digested by the microbiota itself, producing numerous metabolites, which include the short-chain fatty acids (SCFAs). SCFAs have local and systemic functions that impact the composition and function of the gut microbiota, and consequently, human health. The aim of the present narrative review was to provide a document that serves as a frame of reference for a clear understanding of dietary fiber and its direct and indirect effects on health.The direct benefits of dietary fiber intake can be dependent on or independent of the gut microbiota. The use of dietary fiber by the gut microbiota involves several factors, including the fiber's physiochemical characteristics. Dietary fiber type influences the gut microbiota because not all bacterial species have the same capacity to produce the enzymes needed for its degradation. A low-fiber diet can affect the balance of the SCFAs produced. Dietary fiber indirectly benefits cardiometabolic health, digestive health, certain functional gastrointestinal disorders, and different diseases.     

Fungi predatory activity on embryonated <Emphasis Type="Italic">Toxocara canis</Emphasis> eggs inoculated in domestic chickens (<Emphasis Type="Italic">Gallus gallus domesticus</Emphasis>) and destruction of second stage larvae

The objective of this study was to evaluate the infectivity of Toxocara canis eggs after interacting with isolated nematophagous fungi of the species Duddingtonia flagrans (AC001) and Pochonia chlamydosporia (VC4), and test the predatory activity of the isolated AC001 on T. canis second stage larvae after 7 days of interaction. In assay A, 5000 embryonated T. canis eggs previously in contact with the AC001 and VC4 isolated for 10 days were inoculated into domestic chickens (Gallus gallus domesticus), and then these animals were necropsied to collect material (digested liver, intestine, muscles and lungs) at 3-, 7-, 14-, and 21-day intervals after inoculation. In assay A, the results demonstrated that the prior interaction of the eggs with isolated AC001 and VC4 decreases the amount of larvae found in the collected organs. Difference (p?<?0.01) was observed in the medium larvae counts recovered from liver, lung, intestine, and muscle of animals in the treated groups when compared to the animals in the control group. At the end of assay A, a percentage reduction of 87.1 % (AC001) and 84.5 % (VC4) respectively was recorded. In the result of assay B, the isolated AC001 showed differences (p?<?0.01) compared to the control group, with a reduction of 53.4 % in the recovery of L₂. Through these results, it is justified to mention that prior interaction of embryonated T. canis eggs with the tested fungal isolates were efficient in reducing the development and migration of this parasite, in addition to the first report of proven predatory activity on L₂.     

Clinical applicability of nursing outcomes in the evolution of orthopedic patients with Impaired Physical Mobility

AIM:

to evaluate the clinical applicability of outcomes, according to the Nursing Outcomes Classification (NOC) in the evolution of orthopedic patients with Impaired Physical Mobility

METHOD:

longitudinal study conducted in 2012 in a university hospital, with 21 patients undergoing Total Hip Arthroplasty, evaluated daily by pairs of trained data collectors. Data were collected using an instrument containing five Nursing Outcomes, 16 clinical indicators and a five point Likert scale, and statistically analyzed.

RESULTS:

The outcomes Body Positioning: self-initiated, Mobility, Knowledge: prescribed activity, and Fall Prevention Behavior presented significant increases in mean scores when comparing the first and final evaluations (p<0.001) and (p=0.035).

CONCLUSION:

the use of the NOC outcomes makes it possible to demonstrate the clinical progression of orthopedic patients with Impaired Physical Mobility, as well as its applicability in this context.