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To determine the differences in respiratory muscle strength and pulmonary function between patients with chronic neck pain (CNP) and asymptomatic individuals.Databases were MEDLINE, CINAHL, Scopus, Web of Science and EMBASE up to the end of September 2021. Studies with cross-sectional and longitudinal design were selected, with adult patients with CNP and asymptomatic individuals with reports respiratory function.11 studies met the inclusion criteria and 10 were included in the meta-analysis showing a statistically significant reduction in inspiratory/expiratory muscle strength (MIP/MEP) in the patients with CNP compared with the asymptomatic individuals (mean difference (MD) for MIP, -11.67 [-14.57 to -8.77]; MD for MEP, -11.80 [-14.99 to -8.60]) and pulmonary function: vital capacity (standardized mean difference (SMD), -0.31 [-0.56 to -0.06]); maximum voluntary ventilation (SMD, -0.36 [-0.59 to -0.14]); forced vital capacity (SMD, -0.53 [-0.99 to -0.06]); peak expiratory flow (SMD, -0.58 [-1.03 to -0.12]); and forced expiratory volume in the first second (SMD, -0.28 [-0.51 to -0.05]).Patients with CNP have reduced respiratory muscle strength and pulmonary function compared with asymptomatic individuals, and this difference could be clinically meaningful. However, more studies of high methodological quality and longitudinal studies are needed to strengthen the results of this meta-analysis. IMPLICATIONS FOR REHABILITATIONRespiratory dysfunction has been observed in patients with chronic neck pain.Patients with chronic neck pain present a decrease in respiratory muscle strength and pulmonary function compared with asymptomatic individuals.Respiratory pattern disorders should be considered in the clinical context of chronic neck pain.Interventions focused on respiratory muscle training could be helpful for this population.

To assess the current evidence on motor imagery (MI) and action observation (AO) and their influence on functional variables. We conducted 3 meta-meta-analyses (MMA) to determine the effectiveness of MI and AO on arm functionality, performance on activities of daily living and gait mobility in stroke patients. For arm functionality, MMA revealed a statistically significant large effect size (standardised mean difference [SMD] = 1.05; 95 % CI 0.50-1.60; p

ObjectiveTo summarize the cervical physical examination characteristics in subjects with chronic primary headache and compare those with a healthy population and a population with episodic primary headache.DesignSystematic review and meta-analysis.SubjectsHumans ≥18 years old. At least one of the study groups should be constituted by subjects diagnosed with one of the chronic primary headache subtypes according to the International Classification of Headache Disorders, 3rd Edition.ComparisonNeck physical examination outcomes of subjects with chronic primary headache compared with a healthy population or subjects with episodic primary headache.OutcomesForward head posture (FHP), cervical range of movement, motor control, neck muscle activity, and reproduction and resolution of symptoms.MethodsTwo reviewers assessed independently the MEDLINE, EMBASE, WOS, MEDES, PEDro, and CINAHL databases to select observational studies. First, both implemented an agreement for a search strategy. Then, they screened independently for duplicates, titles, abstracts, and full-text information. A meta-analysis was conducted to compare measures between groups.ResultsTwelve studies (N = 1,083) with moderate quality (mean ± SD = 7.75 ± 1.48 on the Newcastle Ottawa Scale) were selected for the qualitative analysis. The meta-analysis showed that patients with chronic primary headache presented greater forward head posture than asymptomatic participants (N = 275, Hg = 0.68, 95% CI = 0.25–1.1, Z = 3.14, P ConclusionsThere is moderate to strong evidence that patients with chronic primary headache present greater FHP than asymptomatic individuals and moderate evidence that patients with chronic primary headache present greater forward head posture than those with episodic primary headache.

INTRODUCTION: The objective was to assess the impact of movement representation techniques (MRT) through motor imagery (MI), action observation (AO) and visual mirror feedback (VMF) and cross-education training (CE) on strength, range of motion (ROM), speed, functional state and balance during experimental immobilization processes in healthy individuals, in patients with injuries that did not require surgery and in those with surgical processes that did or did not require immobilization. EVIDENCE ACQUISITION: MEDLINE, EMBASE, CINAHL and Google Scholar were searched. Thirteen meta-analyses were conducted. EVIDENCE SYNTHESIS: Regarding the immobilized participants, in the healthy individuals, MI showed significant results regarding maintenance of strength and ROM, with low-quality evidence. Regarding the process with no immobilization, VMF and MI techniques showed significant changes in maintaining ROM in patients with injury without surgery, with very low-quality evidence. Results had shown that MI demonstrated significantly higher maintenance of strength and speed in patients undergoing surgery, with low-quality evidence. No significant results were found in ROM. Low-quality evidence showed better results in AO plus usual care compared with usual treatment in isolation with respect to maintenance of functional state and balance. CE training demonstrated maintenance of strength in patients undergoing surgery, with moderate evidence; however, not in healthy experimentally immobilized individuals. VMF did not show significant results in maintaining ROM after surgery without immobilization, nor did MI in maintaining strength after surgery and immobilization. CONCLUSIONS: MRT and CE training have been shown to have a significant impact on the improvement of various motor variables and on physical maintenance in general.

Background and objective Movement representation techniques such as motor imagery (MI) and action observation (AO) could play an important role in the field of rehabilitation of patients with musculoskeletal pain; however, the effects of these tools on clinical pain remain unclear. Our objective is therefore to develop a systematic review and meta-analysis of the effects of MI and AO regarding the pain intensity on patients with musculoskeletal pain. Databases and data treatment MEDLINE, EMBASE, CINAHL and Google Scholar were searched. Last search was run on July 2019. Meta-analysis was conducted to determine the effectiveness on pain intensity in patients with post-surgical pain or chronic pain, and GRADE was used to rate the quality, certainty and applicability of the evidence. Results A total of 10 studies were included. AO or MI were compared versus usual rehabilitation care. The meta-analysis showed statistically significant differences in MI and AO interventions in patients with pain after surgery in six studies, with a large clinical effect (n = 124; SMD = -0.84; 95% CI: -1.47 to -0.21). In patients with chronic pain, results showed statistically significant differences in MI and AO interventions in three studies, with a large clinical effect (n = 83; SMD = -2.14; 95% CI: -3.81 to -0.47). Risk of bias, imprecision and inconsistency decreased the GRADE level of evidence. Conclusions There was very low-quality evidence regarding the effects of movement representation techniques intervention (AO and MI) on pain intensity in patients with post-surgical pain. In addition, there was very low-quality evidence regarding the effects of MI and AO interventions on chronic pain. Significance Movement representation techniques in combination with usual care are capable of producing a decrease in pain intensity compared with conventional treatment, in both post-surgical and chronic pain. However, the very low-quality evidence found regarding these techniques showed that more research is needed for their application in a clinical context.

IntroductionChronic musculoskeletal pain is a major health, social, and economic problem. Most of the subjects who suffer from chronic musculoskeletal pain present processes of central sensitization. Temporal summation and conditioned pain modulation are the two most commonly used clinical measures of this. The objective of this review is to evaluate the effects of physical therapy on temporal summation (TS) and conditioned pain modulation (CPM) in patients with chronic musculoskeletal pain.MethodsThis is a systematic review and meta-analysis. We searched the MEDLINE, EMBASE, CINAHL, EBSCO, PubMed, PEDro, Cochrane Collaboration Trials Register, Cochrane Database of Systematic Reviews, and SCOPUS databases. Different mesh terms and key words were combined for the search strategy, with the aim of encompassing all studies that have used any type of physical therapy treatment in patients with chronic musculoskeletal pain and have measured both TS and CPM.ResultsEighteen studies remained for qualitative analysis and 16 for quantitative analysis. Statistically significant differences with a 95% confidence interval (CI) were obtained for TS (–0.21, 95% CI = –0.39 to –0.03, Z = 2.50, P = 0.02, N = 721) and CPM (0.34, 95% CI = 0.12 to 0.56, Z = 2.99, P = 0.003, N = 680) in favor of physical therapy as compared with control. Manual therapy produces a slight improvement in TS, and physical therapy modalities in general improve CPM. No significant differences between the subgroups of the meta-analysis were found. The methodological quality of the studies was high.ConclusionsPhysical therapy produces a slight improvement in central sensitization (CS)–related variables, with TS decreased and CPM increased when compared with a control group in patients with CMP. Only significant differences in TS were identified in the manual therapy subgroup.

PURPOSE To assess the effects of aerobic exercise (AE) on patients with migraine in terms of pain intensity, frequency and duration of migraine, and quality of life. METHODS A systematic review and meta-analysis of randomized controlled trials were conducted. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for relevant outcomes and were pooled in a meta-analysis using the random-effects model. RESULTS A total of 10 articles from 1950 to 2019 were included, involving 508 patients. The meta-analysis showed statistically significant differences in the decrease in pain intensity (five studies, n = 166; SMD = 1.25; 95% CI 0.47-2.04), frequency (six studies, n = 214; SMD = 0.76; 95% CI 0.32-1.2) and duration of migraine (four studies, n = 106; SMD = 0.41; 95% CI 0.03-0.8), in the short-term. In addition, the meta-analysis showed statistically significant differences in the increase in quality of life (four studies, n = 150; SMD = 2.7; 95% CI 1.17-4.24), even though the Egger's test suggested significant evidence of publication bias for the analysis of quality of life (intercept = 5.81; t = 6.97; P = .02). CONCLUSIONS There is low- and moderate-quality evidence that in patients with migraine AE can decrease the pain intensity, frequency and duration of migraine and can also increase quality of life.

OBJECTIVE To develop a mapping and umbrella review with a meta-meta-analysis (MMA) to critically evaluate the current evidence of motor imagery (MI), action observation and mirror therapy (MT) on pain intensity. METHODS The study involved a systematic search of PubMed, PEDro, Scielo, EBSCO and Google Scholar. RESULTS Ten systematic reviews were included in the qualitative synthesis, 70% of which showed high methodological quality. Three reviews found a significant reduction in chronic musculoskeletal pain as the result of applying movement representation methods (MRM) plus usual-care (UC), with a large clinical effect (standardized mean difference [SMD] of -1.47; 95% CI -2.05 to -0.88; heterogeneity Q = 1.66; p = 0.44; I2 = 0%). However, two reviews showed no statistically significant reduction in acute and postsurgical pain as a result of applying MI plus UC. Four reviews showed no significant reduction in phantom limb pain (PLP) as a result of applying MT plus UC interventions. In four reviews, the MMA showed a significant reduction in complex regional pain syndrome (CRPS) as a result of applying MT plus UC, with a large clinical effect (SMD -1.27; 95% CI -1.87 to -0.67; heterogeneity Q = 3.95; p = 0.27; I2 = 24%). In two reviews, the MMA showed no significant differences in poststroke pain as a result of applying MT plus UC. CONCLUSION Results show that MRM could be effective for chronic musculoskeletal pain, with low to moderate-quality evidence. The results also show a reduction in pain intensity through MT interventions in patients with CRPS, although these results were not found in patients with PLP or poststroke pain. SIGNIFICANCE This umbrella review analysed systematic reviews evaluating movement representation techniques, with the aim of synthesizing the available evidence regarding motor imagery, action observation and mirror therapy on pain. The results provide relevant information about the potential clinical use of movement representation techniques in different types of patients with painful conditions.

Objective Telerehabilitation is an option that should be adapted as soon as possible to face the crisis caused by coronavirus disease 2019. An umbrella and mapping review with meta–meta-analysis (MMA) of the available scientific evidence was performed to determine whether telerehabilitation could be an effective alternative to conventional rehabilitation in physical therapist practice. Methods A systematic review of reviews and a synthesis of the findings of all systematic evidence published to date with a visual map and a meta–meta-analysis (MMA) were performed. A systematic search was realized in Cochrane Database of Systematic Reviews, MEDLINE (PubMed), and Google Scholar. Two independent reviewers performed a data analysis and assessed the quality of the included reviews, assessing the risk of bias using ROBIS. Results Twenty-nine articles that met the inclusion criteria were selected and divided according to the type of patient targeted for rehabilitation (patients with cardiorespiratory, musculoskeletal, and neurological conditions). The MMA regarding physical function between telerehabilitation and usual care rehabilitation did not reveal a statistically significant difference for patients with cardiorespiratory and musculoskeletal conditions. For patients with neurological conditions, the MMA revealed a statistically significant but negligible effect size in 6 reviews in favor of telerehabilitation (standardized mean difference = 0.18; 95% CI = 0.03–0.34). Conclusion The results of the present review showed that telerehabilitation offers positive clinical results, even comparable to conventional face-to-face rehabilitation approaches. Impact The advantages of lower cost and less interference by the rehabilitation processes in patients’ daily life could justify implementing telerehabilitation in clinical settings in the coronavirus disease 2019 era.

Background We aimed to determine the presence of alexithymia in patients with craniofacial pain (CFP) compared with asymptomatic individuals. Our secondary aims were to assess the relationship of alexithymia with anxiety and depression levels, as well as to assess the presence of facial emotion recognition deficit. Methods Medline, Scielo and Google Scholar were searched, with the last search performed in 8 September 2021. Standardized mean differences (SMDs) and 95% CIs were calculated for relevant outcomes and were pooled in a meta-analysis using the random effects model. In addition, meta-analyses of correlations and a meta-regression of alexithymia with depression and anxiety were performed. Results Regarding alexithymia, assessed through the Toronto Alexithymia Scale (TAS), the results showed significant differences, with higher values in patients compared with asymptomatic individuals, with a large clinical effect (SMD 0.46; 95% CI [0.22–0.71]; heterogeneity-Q 66.86; p < 0.001; inconsistency (I2) = 81%). We found statistically significant correlations with a small clinical effect of alexithymia with anxiety and depression. The meta-regression showed no significant association between the TAS and anxiety or depression. With respect to facial emotion recognition, the results showed statistically significant differences, with greater recognition difficulty in patients compared with asymptomatic individuals, with a large clinical effect (SMD −1.17; 95% CI [−2.01 to −0.33]; heterogeneity-Q 2.97; p = 0.080; I2 = 66%). Conclusions Patients with CFP showed alexithymia with moderate evidence. There was also moderate evidence indicating that these patients had significant deficits in facial emotion recognition compared with asymptomatic individuals. Furthermore, alexithymia showed statistically significant correlations with anxiety and depression levels.

espanolIntroduccion: la deteccion temprana de la obesidad durante la infancia es de vital importancia para la prevencion de patologias durante la edad adulta. En la actualidad, la evaluacion de la obesidad infantil se realiza principalmente utilizando el indice de masa corporal por edad percentilado, aunque este no aporta informacion sobre la distribucion del tejido adiposo. Un marcador emergente de distribucion de la grasa abdominal es la circunferencia de la cintura (CC). Objetivo: el objetivo de este trabajo fue evaluar las diferencias entre diferentes criterios diagnosticos para definir el sobrepeso y la obesidad con el fin de establecer el punto de corte optimo de la CC en los ninos espanoles.Metodo: se llevo a cabo un estudio observacional transversal de 8241 ninos/as (3-12 anos) en Villanueva de la Canada (Madrid, Espana). Se determinaron el peso, la talla y el perimetro de la cintura atendiendo a los criterios de la Sociedad Internacional para el Avance de la Cineantro-pometria (ISAK). Los valores obtenidos para los criterios diagnosticos (Fundacion Orbegozo (OF), el Grupo Internacional de Obesidad (IOTF) y la Organizacion Mundial de la Salud (OMS)) se compararon utilizando la prueba de McNemar para proporciones emparejadas. El coeficiente kappa (κ) se utilizo para evaluar el grado de acuerdo de las tres clasificaciones. Analizamos la validez del indice de masa corporal (IMC) y el perimetro de la cintura (CC) utilizando el analisis de la curva caracteristica operativa del receptor (ROC). El indice de Youden se utilizo para determinar los valores de corte de la CC que identifican la obesidad infantil.Resultados: se calcularon las prevalencias del sobrepeso y la obesidad de acuerdo con criterios internacionales (IOTF, OMS) y nacionales (FO). Se observo un acuerdo “substancial” para el sobrepeso y la obesidad entre el criterio diagnostico espanol y el IOTF (κ= 0,636), mientras que el acuerdo fue “ligero” entre el criterio espanol y el de la OMS (κ = 0,198). Los puntos de corte de la CC estimados variaron de 54,5 a 88,0 cm, modificandose en funcion de la edad y el sexo. Conclusiones: los puntos de corte de la CC propuestos, establecidos por primera vez para ninos espanoles, son una alternativa simple y valida como criterio diagnostico de obesidad abdominal. EnglishIntroduction: early detection of childhood obesity plays a crucial role in the prevention of diseases during adulthood. At present, the most commonly used screening tool for detecting overweight/obesity in children is the percentile for age of body mass index, although this rate is unable to provide information about fat distribution. An emerging marker of abdominal fat distribution is waist circumference (WC). Objective: the aim of this study was to evaluate the differences between the different diagnostic criteria available to define overweight and obesity in order to establish the optimal WC cut-off values for the Spanish children population. Methods: a cross-sectional study was carried out in 8,241 schoolchildren aged 3 to 12 years from Villanueva de la Canada (Madrid, Spain). WC (cm), weight (kg) and height (cm) were measured according to the recommendations of the Society for the Advancement of Kineanthropometry (ISAK). The values obtained for the diagnostic criteria (Spanish Orbegozo Foundation (OF), the International Obesity Task Force (IOTF), and the World Health Organization (WHO) were compared using McNemar’s test for paired proportions. The kappa coefficient (κ) was used to assess the degree of agreement of the three classifications. We analyzed the validity of body mass index (BMI) and WC using the receiver operating characteristic (ROC) curve analysis. The Youden index was used to determine cut-off values for WC that identify childhood obesity Results: overweight and obesity prevalences were calculated according to the OF, IOTF, and WHO criteria. There was a “substantial” agreement for the overweight and obesity categories between the Spanish criteria and IOTF (κ = 0.636), while agreement was “slight” between the Spanish criteria and those of WHO (κ = 0.198). The estimated cut-off WC criteria ranged from 54.5 to 88.0, varying according to sex and age. Conclusion: the proposed WC cut-off values, stated for the first time in a young Spanish population, are a simple and valid alternative as diagnostic criteria of abdominal obesity.

The present study analyzes at the national level, the presence of circulating Legionella in the artificial aquatic systems of different facilities of all of them state-owned centers throughout Spain for 12 months. 1754 water samples from various state-owned centers were collected from January to December 2014. Samples were collected from the cooling towers and evaporative condensers (CTC), and water distribution networks such as domestic hot water (DHW), cold water for human consumption (CW), sprinkler irrigation systems (SIS), fire sprinkler systems (FSS), and water from decorative fountains (DF). All these facilities are considered, according to current regulations, as potential amplifying systems for bacteria and possible sources of infection by the generation of droplets and aerosols. The isolation and counting of Legionella in water samples was carried out using microbiological culture following the international normative UNE-EN-ISO 11,731:2007 (ISO 11,731:1998) and UNE-EN ISO 8199:2008 (ISO 8199:2005).The quantification of Legionella colonization, the annual distribution, and the geographical distribution of the Legionella isolates recovered in the water were analyzed. Besides, molecular techniques were used for the characterization of the Legionella non-pneumophila isolates. Legionella was recovered from 15.79% of the analyzed water samples. High colonization was more frequently detected in water samples from CTC, DHW, CW, and DF. Regarding the geographic distribution, positive samples of Legionella were obtained in 14 of the 18 Spanish locations analyzed. Legionella non-pneumophila was the most prevalent and was isolated from water samples from 13 different geographical locations (72%). Legionella anisa and Legionella jordanis were the most frequently non-pneumophila species isolated. Legionella donaldsonii was isolated for the first time in the water distribution networks in Spain. Legionella pneumophila sg 2-14 was detected in 13 locations and Legionella pneumophila sg 1 in 11 locations. Therefore, our study concludes that the presence of Legionella pneumophila and Legionella non-pneumophila species in these systems can be a potential threat to public health and should be examined thoroughly with complementary techniques, such as molecular techniques as a screen for routine diagnosis.

Background Pulmonary rehabilitation is one of the main interventions to reduce the use of health resources, and it promotes a reduction in chronic obstructive pulmonary disease (COPD) costs. mHealth systems in COPD aim to improve adherence to maintenance programs after pulmonary rehabilitation by promoting the change in attitude and behavior necessary for patient involvement in the management of the disease. Objective This study aimed to assess the effects of an integrated care plan based on an mHealth web-based platform (HappyAir) on adherence to a 1-year maintenance program applied after pulmonary rehabilitation in COPD patients. Methods COPD patients from three hospitals were randomized to a control group or an intervention group (HappyAir group). Patients from both groups received an 8-week program of pulmonary rehabilitation and educational sessions about their illness. After completion of the process, only the HappyAir group completed an integrated care plan for 10 months, supervised by an mHealth system and therapeutic educator. The control group only underwent the scheduled check-ups. Adherence to the program was rated using a respiratory physiotherapy adherence self-report (CAP FISIO) questionnaire. Other variables analyzed were adherence to physical activity (Morisky-Green Test), quality of life (Chronic Obstructive Pulmonary Disease Assessment Test, St. George’s Respiratory Questionnaire, and EuroQOL-5D), exercise capacity (6-Minute Walk Test), and lung function. Results In total, 44 patients were recruited and randomized in the control group (n=24) and HappyAir group (n=20). Eight patients dropped out for various reasons. The CAP FISIO questionnaire results showed an improvement in adherence during follow-up period for the HappyAir group, which was statistically different compared with the control group at 12 months (56.1 [SD 4.0] vs 44.0 [SD 13.6]; P=.004) after pulmonary rehabilitation. Conclusions mHealth systems designed for COPD patients improve adherence to maintenance programs as long as they are accompanied by disease awareness and patient involvement in management. Trial Registration ClinicalTrials.gov NCT04479930; https://clinicaltrials.gov/ct2/show/NCT04479930

Objective To assess the effectiveness of cervical manual therapy (MT) on patients with temporomandibular disorders (TMDs) and to compare cervico-craniomandibular MT vs cervical MT. Design Systematic review and meta-analysis (MA). Methods A search in PubMed, EMBASE, PEDro, and Google Scholar was conducted with an end date of February 2019. Two independent reviewers performed the data analysis, assessing the relevance of the randomized clinical trials regarding the studies’ objectives. The qualitative analysis was based on classifying the results into levels of evidence according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results Regarding cervical MT, MA included three studies and showed statistically significant differences in pain intensity reduction and an increase in masseter pressure pain thresholds (PPTs), with a large clinical effect. In addition, the results showed an increase in temporalis PPT, with a moderate clinical effect. MA included two studies on cervical MT vs cervico-craniomandibular MT interventions and showed statistically significant differences in pain intensity reduction and pain-free maximal mouth opening, with a large clinical effect. Conclusions Cervical MT treatment is more effective in decreasing pain intensity than placebo MT or minimal intervention, with moderate evidence. Cervico-craniomandibular interventions achieved greater short-term reductions in pain intensity and increased pain-free MMO over cervical intervention alone in TMD and headache, with low evidence.

Background The aim of the present study was to analyse the incidence, risk ratio (RR) and prognoses of two types of medication-related osteonecrosis of the jaws (MRONJ): denosumab-related osteonecrosis of the jaws (DRONJ) and Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) in cancer patients under treatment with denosumab or zoledronic acid (ZA). Material and Methods An electronic and manual search was conducted for randomized controlled trials (RCTs) until May 2019. Assessment of the identified studies, risk of bias and data extraction were performed independently by two reviewers. The incidence of DRONJ and BRONJ and the RR to develop MRONJ were calculated at 1 year, 2 years and 3 years of exposure. It was also calculated the odds ratio (OR) of their respective prognoses. They were calculated normalizing the values of the individual studies to 1 year, 2 years or 3 years when necessary through robust regression models using a statistical program. Results From 1.277 references identified, 8 RCTs were included, which comprised a total of 13.857 patients with a variety of neoplasms. The incidence of DRONJ in cancer patients under treatment with denosumab ranged from 0.5 to 2.1% after 1 year, 1.1 to 3.0% after 2 years, and 1.3 to 3.2% after 3 years of exposure. The incidence of BRONJ in cancer patients under treatment with ZA ranged from 0.4 to 1.6% after 1 year of exposure, 0.8 to 2.1% after 2 years, and 1.0 to 2.3% after 3 years of exposure. Statistically significant differences were found between denosumab and ZA in the risk of developing MRONJ after 1, 2 and 3 years of exposure. Nevertheless, there were no significant differences in terms of patient prognosis. Conclusions Denosumab is associated with a significantly higher risk of developing MRONJ compared to ZA. Nevertheless, no differences were found in its prognoses. Key words:Denosumab, zoledronic acid, bisphosphonate-associated osteonecrosis of the Jaws, medication-related osteonecrosis of the jaws, neoplasms.

Background Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. Methods Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. Results We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism. Conclusion We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.

Metabolomics, understood as the science that manages the study of compounds from the metabolism, is an essential tool for deciphering metabolic changes in disease. The experiments rely on the use of high-throughput analytical techniques such as liquid chromatography coupled to mass spectrometry (LC-ToF MS). This hyphenation has brought positive aspects such as higher sensitivity, specificity and the extension of the metabolome coverage in a single run. The analysis of a high number of samples in a single batch is currently not always feasible due to technical and practical issues (i.e., a drop of the MS signal) which result in the MS stopping during the experiment obtaining more than a single sample batch. In this situation, careful data treatment is required to enable an accurate joint analysis of multi-batch data sets. This paper summarizes the analytical strategies in large-scale metabolomic experiments, special attention has been given to QC preparation troubleshooting and data treatment. Moreover, labeled internal standards analysis and their aim in data treatment, and data normalization procedures (intra- and inter-batch) are described. These concepts are exemplified using a cohort of 165 patients from a study in asthma.

Background Impairment in mitochondrial biogenesis and function plays a key role in depression and anxiety, both of which being associated with changes in fatty acid and phospholipid metabolism. The antidepressant effects of (R,S)-ketamine have been linked to its conversion into (2S,6S;2R,6R)-hydroxynorketamine (HNK); however, the connection between structure and stereochemistry of ketamine and HNK in the mitochondrial homeostatic response has not yet been fully elucidated at a metabolic level. Methods We used a multi-platform, non-targeted metabolomics approach to study the change in mitochondrial metabolome of PC-12 cells treated with ketamine and HNK enantiomers. The identified metabolites were grouped into pathways in order to assess global responses. Results Treatment with (2R,6R)-HNK elicited the significant change in 49 metabolites and associated pathways implicated in fundamental mitochondrial functions such as TCA cycle, branched-chain amino acid biosynthetic pathway, glycoxylate metabolic pathway, and fatty acid β-oxidation. The affected metabolites included glycerate, citrate, leucine, N,N-dimethylglycine, 3-hexenedioic acid, and carnitine and attenuated signals associated with 9 fatty acids and elaidic acid. Important metabolites involved in the purine and pyrimidine pathways were also affected by (2R-6R)-HNK. This global metabolic profile was not as strongly impacted by treatment with (2S,6S)-HNK, (R)- and (S)-ketamine and in some instances opposite effects were observed. Conclusions The present data provide an overall view of the metabolic changes in mitochondrial function produced by (2R,6R)-HNK and related ketamine compounds and offer an insight into the source of the observed variance in antidepressant response elicited by the compounds.

Gestational Diabetes Mellitus (GDM) causes severe short- and long-term complications for the mother, fetus and neonate, including type 2-diabetes (T2DM) later in life. In this pilot study, GC-Q/MS analysis was applied for plasma metabolomics fingerprinting of 24 healthy and 24 women with GDM at different stages of gestation (second and third trimester) and postpartum (one and three months). Multivariate (unsupervised and supervised) statistical analysis was performed to investigate variance in the data, identify outliers and for unbiased assessment of data quality. Plasma fingerprints allowed for the discrimination of GDM pregnant women from controls both in the 2nd and 3rd trimesters of gestation. However, metabolic profiles tended to be similar after delivery. Follow up of these women revealed that 4 of them developed T2DM within 2 years postpartum. Multivariate PLS-DA models limited to women with GDM showed clear separation 3 months postpartum. In the 2nd trimester of gestation there was also a clear separation between GDM women that were normoglycemic after pregnancy and those with recognized postpartum T2DM. Metabolites that had the strongest discriminative power between these groups in the 2nd trimester of gestation were 2-hydroxybutyrate, 3-hydroxybutyrate, and stearic acid. We have described, that early GDM comprises metabotypes that are associated with the risk of future complications, including postpartum T2DM. In this pilot study, we provide evidence that 2-hydroxybutyrate and 3-hydroxybutyrate may be considered as future prognostic biomarkers to predict the onset of diabetic complications in women with gestational diabetes after delivery.

In the liver, obesity is often manifested by the clinical disorder of the Non-Alcoholic Fatty Liver Disease (NAFLD). A proportion of NAFLD patients develop hepatic inflammation, known as Non-Alcoholic Steatohepatitis (NASH), which can end up in cirrhosis, or Hepatocellular Carcinoma (HCC). In this scenario, partial hepatectomy (PH) is an alternative to promote liver regeneration. However, as liver regeneration is impaired in NASH patients, more knowledge about its metabolic condition is needed to improve the regenerative response of the liver in this pathological condition. Although extensively employed, the panoply of molecular alterations involved in the regenerative response of the liver after partial hepatectomy PH is far from being fully characterized. Metabolic fingerprinting (metabolomics) is a powerful tool to help in the elucidation of complex metabolic networks, by means of a blind, naïve approach to study which metabolic nodes (metabolites) show the biggest variations between conditions. The objective of the present study was to gain deeper knowledge about the metabolic processes involved in the NASH animal model, and particularly in the effect of PH by using metabolomics. For achieving such information, twelve 8-week-old male C57BL/6 J mice, fed commercial chow (control diet) or methionine and choline-Deficient diet (MCD) for three weeks were subjected to PH and sacrificed 2 weeks later. Livers were removed and submitted to metabolic profiling analysis through RP-LC/MS (qTOF), GC/MS (qTOF) and CE/MS(TOF). More than 3000 different features were detected and repeated measurements one-way ANOVA analysis was performed to unveil significant features. MCD diet induced changes (p, This work has been partially funded by the Ministerio de Ciencia, Innovación y Universidades of Spain (MICINN RTI2018-095166-B-I00, MICINN/FEDER RTI2018-094052-B-100) and Comunidad de Madrid of Spain (S2017/BMD-3684 MOIR2-CM). A.M.V. received funding from CIBERdem (ISCIII, Spain)."

A lack of viable hits, increasing resistance, and limited knowledge on mode of action is hindering drug discovery for many diseases. To optimize prioritization and accelerate the discovery process, a strategy to cluster compounds based on more than chemical structure is required. We show the power of metabolomics in comparing effects on metabolism of 28 different candidate treatments for Leishmaniasis (25 from the GSK Leishmania box, two analogues of Leishmania box series, and amphotericin B as a gold standard treatment), tested in the axenic amastigote form of Leishmania donovani. Capillary electrophoresis-mass spectrometry was applied to identify the metabolic profile of Leishmania donovani, and principal components analysis was used to cluster compounds on potential mode of action, offering a medium throughput screening approach in drug selection/prioritization. The comprehensive and sensitive nature of the data has also made detailed effects of each compound obtainable, providing a resource to assist in further mechanistic studies and prioritization of these compounds for the development of new antileishmanial drugs.

Ibai López-de-Uralde-Villanueva,1–4 Hector Beltran-Alacreu,1–3 Alba Paris-Alemany,1–4 Santiago Angulo-Díaz-Parreño,2,3,5 Roy La Touche1–4 1Department of Physiotherapy, Faculty of Health Science, 2Research Group on Movement and Behavioral Science and Study of Pain, The Center for Advanced Studies University La Salle, Universidad Autónoma de Madrid, Aravaca, Madrid, Spain; 3Institute of Neuroscience and Craniofacial Pain (INDCRAN), Madrid, Spain; 4Hospital La Paz Institute for Health Research, IdiPAZ, Madrid, Spain; 5Faculty of Medicine, Universidad San Pablo CEU, Madrid, Spain Objectives: This cross-sectional correlation study explored the relationships between craniocervical posture and pain-related disability in patients with chronic cervico-craniofacial pain (CCFP). Moreover, we investigated the test–retest intrarater reliability of two craniocervical posture measurements: head posture (HP) and the sternomental distance (SMD). Methods: Fifty-three asymptomatic subjects and 60 CCFP patients were recruited. One rater measured HP and the SMD using a cervical range of motion device and a digital caliper, respectively. The Spanish versions of the neck disability index and the craniofacial pain and disability inventory were used to assess pain-related disability (neck disability and craniofacial disability, respectively). Results: We found no statistically significant correlations between craniocervical posture and pain-related disability variables (HP and neck disability [r=0.105; P>0.05]; HP and craniofacial disability [r=0.132; P>0.05]; SMD and neck disability [r=0.126; P>0.05]; SMD and craniofacial disability [r=0.195; P>0.05]). A moderate positive correlation was observed between HP and SMD for both groups (asymptomatic subjects, r=0.447; CCFP patients, r=0.52). Neck disability was strongly positively correlated with craniofacial disability (r=0.79; P>0.001). The test–retest intrarater reliability of the HP measurement was high for asymptomatic subjects and CCFP patients (intraclass correlation coefficients =0.93 and 0.81, respectively) and for SMD (intraclass correlation coefficient range between 0.76 and 0.99); the test–retest intrarater reliability remained high when evaluated 9 days later. The HP standard error of measurement range was 0.54–0.75 cm, and the minimal detectable change was 1.27–1.74 cm. The SMD standard error of measurement was 2.75–6.24 mm, and the minimal detectable change was 6.42–14.55 mm. Independent t-tests showed statistically significant differences between the asymptomatic individuals and CCFP patients for measures of craniocervical posture, but these differences were very small (mean difference =1.44 cm for HP; 6.24 mm for SMD). The effect sizes reached by these values were estimated to be small for SMD (d=0.38) and medium for HP (d=0.76). Conclusion: The results showed no statistically significant correlations between craniocervical posture and variables of pain-related disability, but a strong correlation between the two variables of disability was found. Our findings suggest that small differences between CCFP patients and asymptomatic subjects exist with respect to the two measurements used to assess craniocervical posture (HP and SMD), and these measures demonstrated high test–retest intrarater reliability for both CCFP patients and asymptomatic subjects. Keywords: measurement, neck pain, rehabilitation, reliability, reproducibility of results, temporomandibular disorders&nbsp

Objective Our aim was to systematically review and meta-analyze the effectiveness of therapeutic patient education for migraine. Methods A literature search of multiple electronic databases (MEDLINE, EMBASE, PEDro, CINAHL, and PsychINFO) was conducted to identify randomized control trials (RCTs) published in the English and Spanish languages up to and including May 2013. Two reviewers independently selected the studies, conducted the quality assessment (Delphi list), and extracted the results. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was used throughout the systematic review and meta-analysis. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated for relevant outcome measures (headache frequency, headache disability, self-efficacy, depressive symptoms, and quality of life) and pooled in a meta-analysis using the random effects model. Results Fourteen RCTs were included in the systematic review. Only nine studies were included in the meta-analysis. The median quality score was 6.14 ± 1.29 (range: 5–9). There was strong-moderate evidence for intermediate-term effectiveness of therapeutic patient education on headache frequency (five studies: N = 940, SMD = −0.24, 95% CI of −0.48 to −0.01, P = 0.03), headache disability (four studies: N = 799, SMD = −1.02, 95% CI of −1.95 to −0.08, P = 0.03), and quality of life (three studies: N = 674, SMD = 0.36, 95% CI of 0.05–0.67, P = 0.02). There was no evidence for either short-term or intermediate-term effectiveness of therapeutic patient education on self-efficacy or depressive symptoms. Conclusion This systematic review revealed strong-moderate evidence for intermediate-term effectiveness of therapeutic patient education for migraine. Further high-quality RCTs are required for conclusive determination of its effectiveness.

[Purpose] The aim of this study was to determine the inter-rater and intra-rater reliability of the mandibular range of motion (ROM) considering the neutral craniocervical position when performing the measurements. [Subjects and Methods] The sample consisted of 50 asymptomatic subjects. Two raters measured four mandibular ROMs (maximal mouth opening (MMO), laterals, and protrusion) using the craniomandibular scale. Subjects alternated between raters, receiving two complete trials per day, two days apart. Intra- and inter-rater reliability was determined using intra-class correlation coefficients (ICCs). Bland-Altman analysis was used to assess reliability, bias, and variability. Finally, the standard error of measurement (SEM) and minimal detectable change (MDC) were analyzed to measure responsiveness. [Results] Reliability was good for MMO (inter-rater, ICC= 0.95−0.96; intra-rater, ICC= 0.95−0.96) and for protrusion (inter-rater, ICC= 0.92−0.94; intra-rater, ICC= 0.93−0.96). Reliability was moderate for lateral excursions. The MMO and protrusion SEM ranged from 0.74 to 0.82 mm and from 0.29 to 0.49 mm, while the MDCs ranged from 1.73 to 1.91 mm and from 0.69 to 0.14 mm respectively. The analysis showed no random or systematic error, suggesting that effect learning did not affect reliability. [Conclusion] A standardized protocol for assessment of mandibular ROM in a neutral craniocervical position obtained good inter- and intra-rater reliability for MMO and protrusion and moderate inter- and intra-rater reliability for lateral excursions.

A year-long longitudinal study was undertaken to evaluate the presence of Cryptosporidium spp. in drinking water treatment plants (DWTPs), wastewater treatment plants (WWTPs) and freshwater bathing beaches (FBBs) from the central area of Spain. Water samples were collected according to USEPA Method 1623, and concentrated by the IDEXX Filta-Max® system. Cryptosporidium species were detected based on PCR-restriction fragment length polymorphism and sequence analyses of the ssuRNA gene. C. hominis and/or C. parvum isolates were subtyped by DNA sequencing of the Gp60 gene. Among 150 samples, 23 (15.3%) were positive by IFAT and 40 (26.7%) by PCR. Cryptosporidium spp. was more frequent in WWTPs (26.2 and 50.8%) and FBBs (12.5 and 17.5%) by IFAT and PCR respectively. Effluent waters from DWTPs were negative for this parasite suggesting that they are suitable for public use. Tertiary treatment in the WWTPs demonstrated a high removal efficiency of Cryptosporidium in the samples evaluated. Cryptosporidium species identified included C. hominis, C. parvum, C. ubiquitum, C. andersoni and C. muris. Subtyping analysis revealed C. hominis IbA10G2 and IeA11G3T3 alleles, which is the first report of the latter in water samples. Cryptosporidium highest frequency was observed in winter and spring. Our data provide information about the occurrence and diversity of Cryptosporidium in water of human use from the central area of Spain.

Objectives Several authors have evaluated different pain measurements, including quantitative sensory testing (QST), temporal summation (TS), and conditioned pain modulation (CPM) in order to determine the presence of central sensitization (CS) and its influence on patients with temporomandibular disorders (TMD). Since there are no convincing studies about this topic, the purpose of this study was to conduct a review of the studies involving CS-related measures in TMD patients. Methods A meta-analysis of case-control and cohort/cross sectional studies was conducted. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for relevant QST outcomes and pooled in a meta-analysis using the random effects model. Twenty-two studies (eleven case-control and eleven cross sectional studies) met the inclusion criteria; eight were included in the meta-analysis (five cross-sectional and three case-control). Patients with TMD had decreased pressure pain thresholds in both trigeminal (five studies; n = 1,985; SMD = −1.55, 95% CI −2.23 to −0.77; P < 0.01) and remote areas (five studies; n = 1,985; SMD = −1.92, 95% CI −2.95 to −0.89; P < 0.01). When analyzing for thermal hyperalgesia (hot and cold pain thresholds), differences were not found in trigeminal areas or remote areas in patients with TMD. The TS qualitative analysis showed strong evidence of spinal hyperexcitability for mechanically evoked pain. Conclusion These meta-analyses support the existence of differences in widespread pressure pain sensitivity in patients with TMD when compared with asymptomatic subjects. Spinal and central hyperexcitability can be found in TMD patients as shown by an increase in mechanical TS.

Legionnaires' disease is a severe form of pneumonia, with worldwide relevance, caused by Legionella spp. Approximately 90% of all cases of legionellosis are caused by Legionella pneumophila, but other species can also be responsible for this infection. These bacteria are transmitted by inhalation of aerosols or aspiration of contaminated water. In Spain, environmental studies have demonstrated the presence of Legionella non-pneumophila species in drinking water treatment plants and water distribution networks. Aware that this evidence indicates a risk factor and the lack of routine assays designed to detect simultaneously diverse Legionella species, we analyzed 210 urine samples from patients presenting clinical manifestations of pneumonia using a semi-nested PCR for partial amplification of the 16S rDNA gene of Legionella and a diagnostic method used in hospitals for Legionella antigen detection. In this study, we detected a total of 15 cases of legionellosis (7.1%) and the first case of Legionnaires' disease caused by L. anisa in Spain. While the conventional method used in hospitals could only detect four cases (1.9%) produced by L. pneumophila serogroup 1, using PCR, the following species were identified: Legionella spp. (10/15), L. pneumophila (4/15) and L. anisa (1/15). These results suggest the need to change hospital diagnostic strategies regarding the identification of Legionella species associated with this disease. Therefore, the detection of Legionella DNA by PCR in urine samples seems to be a suitable alternative method for a sensitive, accurate and rapid diagnosis of Legionella pneumonia, caused by L. pneumophila and also for L. non-pneumophila species.

Urine fingerprints from Schistosoma mansoni infected and control animals were acquired with ultra performance liquid chromatography-MS (UPLC-MS) and compared with the urine fingerprints obtained by CE by applying the same set of multivariate analysis tools. Principal component analysis of the aligned data provided a time trajectory where the infection was observed after 30 days with UPLC-MS and CE. Two main markers describing infected and control, respectively - phenyl acetyl glycine (PAG) and hippurate - were selected to illustrate the use of orthogonal partial least-square discriminant analysis in determining the discriminatory confidence. PAG was found to be significantly related to the disease (high covariance and correlation), whereas hippurate was found to be nonsignificant as an indicator. Orthogonal partial least-square discriminant analysis models were validated for sensitivity and specificity. Multivariate data analysis derived from two different detection systems showed that CE-UV and UPLC-MS found equivalent results. This work gives additional mechanistic insight into the progress of the S. mansoni infection; the biochemical role and specificity of PAG as a biomarker is yet to be determined.

Fingerprinting together with statistical analysis is often employed to compare samples in metabonomic studies of a disease. Correlation algorithms can aid by extracting information based on the variation patterns of key metabolites. This information can be linked to metabolite identification or to specific up/down-regulated biochemical pathways. Matlab-based software employing the Pearson's correlation algorithm was applied to urine electropherograms from 20 mice infected with the schistosoma parasite. The fingerprints were the sum of electropherograms analysed with normal and reverse polarity, in two different modes MEKC and CZE and with two different capillaries (uncoated and polyacrylamide coated) to provide a broad picture of the samples. Hippurate, a metabolite that was depleted in the infected group and is present in both polarities, was chosen as a test variable; it correlated with itself to a p value of

Schistosoma mansoni infection in mice has been fingerprinted using CE to study the capabilities of this technique as a diagnostic tool for this parasitic disease. Two modes of separation were used in generating the electrophoretic data, with each untreated urine sample the following methods were applied: (i) a fused-silica capillary, operating with an applied potential of 18 kV, in micellar EKC (MEKC) and (ii) a polyacrylamide-coated capillary, operating with an applied potential of -20 kV under zonal CZE conditions. By combining normal and reverse polarities in the data treatment we have extracted more information from the samples, which is a better approach for CE metabolomics. The traditional problems associated with variability in electrophoretic peak migration times for analytes were countered by using a dynamic programming algorithm for the electropherograms alignment. Principal component analyses of these aligned electropherograms and partial least square discriminant analysis (PLS-DA) data are shown to provide a valuable means of rapid and sample classification. This approach may become an important tool for the identification of biomarkers, diagnosis and disease surveillance.

Background: Yogurt has traditionally been considered a probiotic-carrier food with health-promoting effects. Despite the universal assumption of this assertion, several researchers have evaluated the real capability of the yogurt bacteria Lactobacillus delbrueckii subsp bulgaricus and Streptococcus thermophilus to survive and proliferate in the human intestine and have found contradictory results. Objective: This double-blind crossover study assessed the qualitative and quantitative effects of fresh and heat-treated yogurt on bacterial intestinal microbiota from healthy subjects. Design: The subjects were divided into experimental (n = 63) and control (n = 16) groups. The experimental group consumed fresh and heat-treated yogurt for 15 d according to a crossover design with a washout period of 2 wk. Three different fecal samples per individual were recovered: at baseline, after fresh yogurt intake, and after heat-treated yogurt intake. Qualitative changes in microbiota were studied by denaturing gel gradient electrophoresis (DGGE) with universal and lactic acid bacteria (LAB) 16S-rRNA primers. Quantitative changes in LAB, Clostridium coccoides, Clostridium perfringens, and Bacteroides groups were analyzed by real-time polymerase chain reaction. Results: A particular DGGE stable band pattern was observed in each sample. No significant qualitative differences were detected in any fecal sample. However, a significantly higher density of LAB and C. perfringens and a significant decrease in the density of Bacteroides was observed after consumption of both types of yogurt. Microbiota density was not significantly different between the fresh and heat-treated yogurt groups, except for LAB, which was significantly greater in the fresh yogurt group. Conclusion: The main change in human microbiota observed after yogurt consumption was an increase in the density of LAB and C. perfringens to the detriment of Bacteroides. Bacterial changes were not different after the consumption of fresh and heat-treated yogurt.

Our aim was to systematically review and meta-analyze the effectiveness of graded activity (GA) or graded exposure (GEXP) for chronic nonspecific low back pain (CNSLBP).A literature search of multiple databases (MEDLINE, EMBASE, PEDro, CINAHL, and PsychINFO) was conducted to identify randomized control trials (RCTs). Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for relevant outcome measures (pain intensity, disability, quality of life, and catastrophizing).Thirteen RCTs met the inclusion criteria. Only nine studies were included in the meta-analysis. GA was significantly more effective than the control group (CG) for improvements in disability in the short term (three studies: n = 254, SMD = -0.3, 95% CI -0.55 to -0.05, P = 0.02) and long term (two studies: n = 238, SMD = -0.53, 95% CI -0.79 to -0.27, P0.0001). GA was significantly less effective than GEXP for the improvement of disability in the short term (two studies: n = 105, SMD = 0.39, 95% CI 0.003-0.78, P = 0.048). GA was also significantly less effective than GEXP at improving catastrophizing in the short term (two studies: n = 105, SMD = 0.48, 95% CI 0.09-0.87, P = 0.02).Limited evidence has been found to show that GA significantly reduces disability in the short and long term when compared with the CG in CNSLBP. There is moderate evidence that GEXP more effectively decreases catastrophizing than GA in the short term. No difference was found between GA and other exercise for any variable.

Objective. Our aim was to systematically review and meta-analyze the effectiveness of graded activity (GA) or graded exposure (GEXP) for chronic nonspecific low back pain (CNSLBP). Methods. A literature search of multiple databases (MEDLINE, EMBASE, PEDro, CINAHL, and PsychINFO) was conducted to identify randomized control trials (RCTs). Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated for relevant outcome measures (pain intensity, disability, quality of life, and catastrophizing). Results. Thirteen RCTs met the inclusion criteria. Only nine studies were included in the metaanalysis. GA was significantly more effective than the control group (CG) for improvements in disability in the short term (three studies: n 5 254, SMD 52 0.3, 95% CI 20.55 to 20.05, P 5 0.02) and long term (two studies: n 5 238, SMD 52 0.53, 95% CI 20.79 to 20.27, P < 0.0001). GA was significantly less effective than GEXP for the improvement of disability in the short term (two studies: n 5 105, SMD 5 0.39, 95% CI 0.003–0.78, P 5 0.048). GA was also significantly less effective than GEXP at improving catastrophizing in the short term (two studies: n 5 105, SMD 5 0.48, 95% CI 0.09–0.87, P 5 0.02). Conclusion. Limited evidence has been found to show that GA significantly reduces disability in the short and long term when compared with the CG in CNSLBP. There is moderate evidence that GEXP more effectively decreases catastrophizing than GA in the short term. No difference was found between GA and other exercise for any variable.

The role of non-targeted metabolomics with its discovery power is constantly growing in many different fields of science. However, its biggest advantage of uncovering the unexpected is turning into one of its biggest bottlenecks, particularly in metabolite identification. Among different methods for metabolite identification or ID confirmation, tandem MS analysis plays a very important role. However, this method is limited to only certain types of MS analysers, making for example TOF-MS inaccessible for this type of metabolite identification. To overcome this, in-source fragmentation has been used to fragment molecules and obtain product ions. Since the molecule of interest is not isolated prior to its fragmentation, the acquired spectrum contains many different signals arising from the fragmentation of all compounds present in the sample. Therefore, to assign product ions to their precursors, a novel use of correlation analysis was tested with r ≥0.9 as an assignation of a product ion belonging to the precursor. This method and chosen cut-off was tested on three different sample complexity levels: conducting the analysis on a single standard, mix of co-eluting standards and on a plasma sample. Obtained results clearly proved the effectiveness of the proposed methodology for metabolite ID confirmation. Moreover, the proposed strategy can be successfully applied for semi-quantification of co-eluting molecules with the same monoisotopic mass but that differ in fragmentation pattern. The proposed methodology can greatly improve the robustness and throughput of identification in metabolomics studies by use of TOF-MS, which is crucial to obtain meaningful and trustful results.

Background Grip testing is commonly used as an objective measure of strength in the hand and upper extremity and is frequently used clinically as a proxy measure of function. Increasing knowledge of hand biomechanics, muscle strength, and prehension patterns can provide us with a better understanding of the functional capabilities of the hand. The objectives of this study were to determine the contribution of ulnar digits to overall grip strength in individuals with thumb carpometacarpal (CMC) osteoarthritis (OA). Methods Thirty-seven subjects participated in the study. This group consisted of 19 patients with CMC OA (aged 60–88 years) and 18 healthy subjects (60–88 years). Three hand configurations were used by the subjects during grip testing: use of the entire hand (index, middle, ring, and little fingers) (IMRL); use of the index, middle, and ring fingers (IMR); and use of only the index and middle fingers (IM). Results Grip strength findings for the two groups found that compared to their healthy counterparts, CMC OA patients had, on average, a strength deficiency of 45.6, 35.5, and 28.8% in IMRL, IMR, and IM, respectively. The small finger contribution to grip is 14.3% and the ring and small finger contribute 34% in subjects with CMC OA. Discussion Grip strength decreases as the number of digits contributing decreased in both groups. The ulnar digits contribution to grip strength is greater than one third of total grip strength in subjects with CMC OA. Individuals with CMC OA demonstrate significantly decreased grip strength when compared to their healthy counterparts.

Background Manual therapies are generally requested by patients with tension type headache. Objective To compare the efficacy of multimodal manual therapy vs. pharmacological care for the management of tension type headache pain by conducting a meta-analysis of randomized controlled trials. Methods PubMed, MEDLINE, EMBASE, AMED, CINAHL, EBSCO, Cochrane Database of Systematic Reviews, Cochrane Collaboration Trials Register, PEDro and SCOPUS were searched from their inception until June 2014. All randomized controlled trials comparing any manual therapy vs. medication care for treating tension type headache adults were included. Data were extracted and methodological quality assessed independently by two reviewers. We pooled headache frequency as the main outcome and also intensity and duration. The weighted mean difference between manual therapy and pharmacological care was used to determine effect sizes. Results Five randomized controlled trials met our inclusion criteria and were included in the meta-analysis. Pooled analyses found that manual therapies were more effective than pharmacological care in reducing frequency (weighted mean difference –0.8036, 95% confidence interval –1.66 to –0.44; three trials), intensity (weighted mean difference –0.5974, 95% confidence interval –0.8875 to –0.3073; five trials) and duration (weighted mean difference –0.5558, 95% confidence interval –0.9124 to –0.1992; three trials) of the headache immediately after treatment. No differences were found at longer follow-up for headache intensity (weighted mean difference –0.3498, 95% confidence interval –1.106 to 0.407; three trials). Conclusion Manual therapies were associated with moderate effectiveness at short term, but similar effectiveness at longer follow-up for reducing headache frequency, intensity and duration in tension type headache than pharmacological medical drug care. However, due to the heterogeneity of the interventions, these results should be considered with caution at this stage.

Background Recent research has shown a relationship of craniomandibular disability with neck-pain-related disability has been shown. However, there is still insufficient information demonstrating the influence of neck pain and disability in the sensory-motor activity in patients with headache attributed to temporomandibular disorders (TMD). The purpose of this study was to investigate the influence of neck-pain-related disability on masticatory sensory-motor variables. Methods An experimental case–control study investigated 83 patients with headache attributed to TMD and 39 healthy controls. Patients were grouped according to their scores on the neck disability index (NDI) (mild and moderate neck disability). Initial assessment included the pain catastrophizing scale and the Headache Impact Test-6. The protocol consisted of baseline measurements of pressure pain thresholds (PPT) and pain-free maximum mouth opening (MMO). Individuals were asked to perform the provocation chewing test, and measurements were taken immediately after and 24 hours later. During the test, patients were assessed for subjective feelings of fatigue (VAFS) and pain intensity. Results VAFS was higher at 6 minutes (mean 51.7; 95% CI: 50.15-53.26) and 24 hours after (21.08; 95% CI: 18.6-23.5) for the group showing moderate neck disability compared with the mild neck disability group (6 minutes, 44.16; 95% CI 42.65-45.67/ 24 hours after, 14.3; 95% CI: 11.9-16.7) and the control group. The analysis shows a decrease in the pain-free MMO only in the group of moderate disability 24 hours after the test. PPTs of the trigeminal region decreased immediately in all groups, whereas at 24 hours, a decrease was observed in only the groups of patients. PPTs of the cervical region decreased in only the group with moderate neck disability 24 hours after the test. The strongest negative correlation was found between pain-free MMO immediately after the test and NDI in both the mild (r = −0.49) and moderate (r = −0.54) neck disability groups. VAFS was predicted by catastrophizing, explaining 17% of the variance in the moderate neck disability group and 12% in the mild neck disability group. Conclusion Neck-pain-related disability and pain catastrophizing have an influence on the sensory-motor variables evaluated in patients with headache attributed to TMD.