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Introduction: the Achilles tendon is the most resistant tendon structure in the human body. Although it raises an injury prevalence of 24% within the population of runners, which increases exponentially at the international level. Objectives: We analyze the influence of the running technique on the architecture of the Achilles tendon, and we look for other factors that also influence its morphology. Methods: An observational, cross-sectional and descriptive study was carried out; thirty-three healthy habitual running subjects voluntarily participated. We carried out an orthogonal study of the tendon structure, obtaining values of diameter, perimeter, and microcirculation; the results were related to the runners' technique. Results: no significant differences were found regarding the influence of the running technique on the architecture of the Achilles tendon, observing that it was more significantly influenced by gender, height, and training. Conclusions: Although the running technique does not influence the thickness of the Achilles tendon, the influence of the technique on other characteristics of the tendon should continue to be studied.

The level of exercise among older adults is low, particularly among those living in health-care institutions. To gain insight into the perceptions of institutionalized older adults towards the exercise programs developed in long-term care institutions and to identify their wishes and needs regarding these programs, we conducted a qualitative study using focus group discussions. Thirty-six institutionalized participants (≥ 65 years) were recruited. Six common themes emerged: participants' attitudes and motivations towards the exercise programs, self-perceived health, knowledge of the concept of physical exercise, perceived effects of the exercise programs, and wishes or expectations for the exercise programs. The main wishes were to increase frequency of exercise sessions, to exercise outdoor and to increase walking times. The results suggest the need for changes in the development of exercise programs, including changes in the frequency, performance environment and types of exercises performed.

A stroke is a neurological condition with a high impact in terms of physical disability in the adult population, requiring specific and effective rehabilitative approaches. Virtual reality (VR), a technological approach in constant evolution, has great applicability in many fields of rehabilitation, including strokes. The aim of this study was to analyze the effects of a traditional neurological physiotherapy-based approach combined with the implementation of a specific VR-based program in the treatment of patients following rehabilitation after a stroke. Participants (n = 24) diagnosed with a stroke in the last six months were randomly allocated into a control group (n = 12) and an experimental group (n = 12). Both groups received one-hour sessions of neurological physiotherapy over 6 weeks, whilst the experimental group was, in addition, supplemented with VR. Patients were assessed through the Daniels and Worthingham Scale, Modified Ashworth Scale, Motor Index, Trunk Control Test, Tinetti Balance Scale, Berg Balance Scale and the Functional Ambulation Classification of the Hospital of Sagunto. Statistically significant improvements were obtained in the experimental group with respect to the control group on the Motricity Index (p = 0.005), Trunk Control Test (p = 0.008), Tinetti Balance Scale (p = 0.004), Berg Balance Scale (p = 0.007) and the Functional Ambulation Classification of the Hospital of Sagunto (p = 0.038). The use of VR in addition to the traditional physiotherapy approach is a useful strategy in the treatment of strokes.

BACKGROUND: Knee osteoarthritis often leads to chronic pain that frequently becomes disabling.Osteoarthritis has been linked to maladaptive plasticity in the brain, which can contribute to chronic pain. Therapies including neuromodulation and peripheral electrical stimulation are used to counteract the maladaptive plasticity of the brain. OBJECTIVE: To determine the efficacy of the addition of tDCS and TENS to an education and exercise program in reducing pain. METHODS: Over a 2-week study period, 60 participants will complete an exercise and educational intervention. Eligible participants accepting to participate will be subsequently randomized into one of the three treatment groups: 1) Active Transcranial Direct Current Stimulation (tDCS) and active Transcutaneous Electrical Nerve Stimulation (TENS); 2) Active tDCS and sham TENS; 3) Sham tDCS and sham TENS. RESULTS: The primary outcome will be subjective pain intensity. Secondary outcomes: quality of life, physical function, central sensitization, and pain adjuvants (uncertainty, catastrophizing kinesiophobia, adverse events). CONCLUSION: This clinical trial will provide data on the effect that the addition of tDCS and/or TENS to an education and exercise program may have to counteract maladaptive plastic changes and improve the benefits of exercises, and whether the combination of both neuromodulator techniques may have a higher magnitude of effect.

The Burnout Syndrome (BOS) is a psycho-emotional disorder generating sustained stress over time, and inability to cope with the demands in an adaptive manner. The aims of the study were (1) to describe the prevalence of BOS during the third COVID-19 pandemic wave (May-June 2021); (2) to explore the relation of BOS with physical symptoms, and (3) to determine the profile favoring the development of BOS. This cross-sectional descriptive study was conducted amongst a sample of 759 healthcare professionals (HCPs). Data on sociodemographic variables, physical symptoms, the Maslach Burnout Inventory, Cervical Disability Index, and Numeric Pain Rating Scale were collected. The prevalence of BOS was 58.9% (447 subjects); 382 subjects (50.3%) showed high levels of Emotional Exhaustion (EE), whereas 219 participants (28.9%) had high Depersonalization (DP) levels, whilst 135 individuals (17.8%) showed low levels of Personal Fulfillment (PF). Women showed higher levels of EE (Z=-3.46; p = 0.001), whilst men showed higher levels of DP (Z=-2.69; p = 0.007). A total of 579 participants (76.3%) experienced muscle pain. A young nurse working in a hospital, or an emergency department emerges as a specific vulnerable profile. The current study confirms the need to overcome BOS in HCPs, implementing multidimensional tailored intervention to decrease the symptoms.

(1) Background: Patient safety is a discipline of health care management aiming to prevent and reduce errors and harm to patients. The assessment of knowledge and attitudes on patient safety among students in physical therapy is still scarce; no studies have yet explored the changes that internship periods may produce. Objectives: 1. to determine the attitudes and knowledge of students in physical therapy with respect to patient safety in a Spanish University; and 2. to explore changes following a practical internship period. (2) Methods: Longitudinal study. Data from the Attitudes to Patient Safety Questionnaire III (APSQ-III) before and after the internship period were obtained from an initial sample of 125 students and average positive response rates were compared. (3) Results: “Team functioning”, “Importance of patient safety in the curriculum”, and “Error inevitability” displayed the highest scores, in accordance with the current literature. After the internship period, the dimensions “Patient safety training received” (p = 0.001), “Error reporting confidence” (p = 0.044), and “Professional incompetence as an error cause” (p = 0.027) showed significant changes. (4) Conclusions: The current study, highlighting areas of strengths and weaknesses in the knowledge and attitudes of students in physical therapy towards patient safety, may be a foundation to adopt tailored programs to enhance students’ competencies in patient safety.

Many professionals use the handheld dynamometers (HHDs) to assess isometric strength. This study aimed to evaluate the validity, reliability, and sensitivity to change of a DiCI (a new HHD) for the...

Background Despite wide use of the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) 2011, little is known about between-stage transitions and what factors predict worsening transitions in patients with chronic obstructive pulmonary disease (COPD). Objective To investigate the transition frequency between GOLD 2011 stages among patients with stable COPD over a 2-year follow-up, to identify potential non-pulmonary predictor factors for worsening transitions, and to compare transition frequencies between GOLD 2011 stages and the new GOLD 2017 stages. Patients and methods We prospectively included 137 patients with stable COPD (mean age, 66.9 ± 8.3 years). GOLD 2011 and GOLD 2017 stages were measured at baseline, 1-year follow-up, and 2-year follow-up. To evaluate non-pulmonary variables as potential predictors of worsening transitions, we used regression models adjusted for sociodemographic, clinical, and pulmonary variables using generalized estimating equations. Results The study period included 246 opportunities for transition, and 39 worsening transitions occurred within GOLD 2011 stages. Predictors of worsening transitions included BODE index (OR, 1.20; 95% CI, 1.00-1.44), quadriceps strength (OR, 0.87; 95% CI, 0.76-0.99), and limited mobility activities (OR, 1.02; 95% CI, 1.00-1.05). The frequency of worsening transitions for stages B and C differed between GOLD 2011 and GOLD 2017. Stages A and D were the most stable in both classifications. Conclusion Non-pulmonary factors predicted worsening transitions among the GOLD 2011 stages of COPD severity. The choice of GOLD 2011 versus GOLD 2017 may influence transition identification, especially for stages B and C.

Background: To study the impact of crawling before walking (CBW) on network interactions among body composition, the cardiovascular system, lung function, motor competence and physical fitness, at age 7, and to assess the longitudinal association between CBW and body composition, the cardiovascular system, lung function, motor competence, physical fitness and physical activity parameters, at age 7. Method: CBW, body composition, cardiovascular system, lung function, motor competence, physical fitness and physical activity were assessed in seventy-seven healthy Caucasian children. Results: Network analyses revealed that the crawling group had a greater number of links among all the studied variables compared with the non-crawling group. In the longitudinal study, using multiple regression analyses, crawling was independently associated with fat mass (%), fat-to-muscle ratio and systolic blood pressure, with models explaining up to 56.3%, 56.7% and 29.9% of their variance, respectively. Conclusions: CBW during child’s development is a possible modulator in the network interactions between body systems and it could influence future metabolic and cardiovascular health.

Inspiratory muscle training (IMT) is effective in improving postural stability and balance in different clinical populations. However, there is no evidence of these effects in soccer players. A single-blind, two-arm (1:1), randomized, placebo-controlled pilot study on 14 soccer players was performed with the main aim of assessing the effect of IMT on static balance, and secondarily, of examining changes in the respiratory muscle function. The experimental group (EG) received an IMT program with progressive intensity, from 20% to 80%, of the maximal inspiratory pressure (MIP). The sham group (SG) performed the same program with a fixed load of 20% of the MIP. Static balance and respiratory muscle function variables were assessed. A two-factor analysis of variance for repeated measures was used to assess differences after training. Statistical significance was set at p < 0.05. Significant increases were observed in the EG on length of sway under eyes open (from 2904.8 ± 640.0 to 3522.4 ± 509.0 mm, p = 0.012) and eyes closed (from 3166.2 ± 641.3 to 4173.3 ± 390.8 mm, p = 0.004). A significant increase in the maximal voluntary ventilation was observed for both groups (EG p = 0.005; SG p = 0.000). No significant differences existed between the groups. IMT did not improve the static balance in a sample of soccer players. Conducting a high-scale study is feasible and could refine the results and conclusions stemming from the current pilot study.

Resumen Objetivo El objetivo del estudio fue adaptar un cuestionario de discapacidad en actividades de movilidad (DIAMO-EPOC) incorporando escalas basadas en el marco conceptual de la Clasificacion Internacional del Funcionamiento, Discapacidad y Salud, y examinar su estructura, fiabilidad y validez en una cohorte de pacientes con EPOC. Metodos Un total de 137 pacientes con EPOC estable fueron reclutados. Se disenaron dos escalas de cuatro items cada una y se verifico su estructura mediante analisis factorial y de multirrasgo. Adicionalmente, se calcularon los indices de fiabilidad (consistencia interna y test-retest). La validez de constructo se analizo mediante grupos conocidos y la convergencia-divergencia. Resultados El cuestionario resulto tener 2 escalas, con 4 items cada una, correspondientes a los dominios de la Clasificacion Internacional del Funcionamiento, Discapacidad y Salud «cambiar y mantener la posicion del cuerpo» y «andar y moverse». La fiabilidad y consistencia interna de las escalas resultaron aceptables y el test-retest excelente con CC I de 0,86 y 0,94, respectivamente. Las escalas mostraron una asociacion moderada con la disnea, el estado de salud y la fuerza muscular de los pacientes y una diferente puntuacion entre sujetos con distinto desempeno fisico en la Short Physical Performance Battery. Conclusiones Las dos escalas del cuestionario DIAMO-EPOC son unidimensionales y tienen una solida consistencia interna, estabilidad test-retest y validez, permitiendo identificar areas especificas de movilidad limitada en pacientes con EPOC.

Quorum sensing (QS) has been described in prokaryotes as a mechanism that generates coordinated responses dependent on cell population density. Autoinducers, also named quorum-sensing molecules (QSMs), are accumulated into the medium in parallel to the increase of cell population density. Later work has also established its presence in a number of pathogenic and nonpathogenic filamentous fungi as well as in yeast cells. QSMs have a crucial impact in major aspects of fungal development, including morphogenesis, sexual differentiation, consortia behavior, and apoptosis. Significantly, QS is closely linked to fungal pathogenesis by modulating yeast to hyphae transition and biofilm assembly. In this chapter, we describe current advances in QS mechanisms in fungal species and also discuss the potential use of QSMs in biotechnological applications and as antifungal agents.

The identification of variables that can modulate the efficacy of cue exposure using virtual reality (VR) is crucial. This study aimed to explore determinant variables of cue-elicited alcohol craving and perceived realism (PR) of environments and alcoholic beverages during a VR cue-exposure session among alcohol use disorder (AUD) outpatients. A prospective cohort study was conducted amongst 72 outpatients with AUD from a clinical setting. Alcohol craving experienced during VR exposure and PR of virtual environments and alcoholic drinks were evaluated after a VR session of exposure to alcohol-related contexts and cues. Sociodemographic, psychological and consumption characteristics were examined as possible predicting variables. Multiple linear regression analyses showed that the AUD severity and PR of beverages were predictors of cue-elicited alcohol craving. Educational level, PR of beverages and age were predictors of the PR of VR environments. In relation to the PR of VR beverages, cue-elicited alcohol craving and the PR of environments were predictors. A simple mediational model was also performed to analyze the influence of the PR of beverages on the relationship between the AUD severity and alcohol craving experienced during VR exposure: an indirect or mediational effect was found. PR of alcoholic beverages was (1) a key predictor of the PR of VR environments (and vice versa) and the alcohol craving (and vice versa) experienced during VR cue-exposure sessions using ALCO-VR software among AUD patients and (2) a mediator between AUD severity and cue-elicited alcohol craving.

Background: Although the six-minute-walk test (6MWT) has been used to predict chronic obstructive pulmonary disease (COPD) exacerbations, additional research is necessary to identify more rapid, simpler tests that are directly associated with exacerbations, such as the five-repetition sit-to-stand (5STS) test and 4-m gait speed (4MGS) test. Aims: To determine the ability of the 5STS and 4MGS tests in predicting severe exacerbations in stable COPD over the following year, and to assess the ability of the best prognostic test to identify patients at high risk of hospital admission correctly. Methods: This prospective study included 137 patients with stable COPD. Multiple logistic regression models were constructed to assess whether the 6MWT, 5STS, and 4MGS tests were associated with severe exacerbations in the year following the test. Receiver-operating characteristic curves and the area under the curve (AUC) were evaluated to determine the accuracy of each test for identifying patients with severe exacerbations. Results: Scores of Conclusions: The 5STS test predicted the risk of severe exacerbation within the following year among patients with COPD. The 5STS test could replace the 6MWT for identifying patients at high risk of hospital admission.

In spite of the growing use of the electrical impedance myography (EIM) measures for clinical assessment and follow-up of diseased muscle tissue, reliability studies are scarce. We evaluate the reliability of the (EIM) technique using four adhesive electrodes over the muscle of interest. Intra- and inter-rater reliability was studied within the same session and between sessions. Thirty-one healthy and volunteer subjects aged between 20 and 26 years were recruited. Phase angle, reactance and resistance were assessed for each EIM measurement. Intraclass correlation coefficient (ICC) was used to determine the relative reliability. Absolute reliability was expressed as the standard error of measurement and the minimum detectable change. Relative reliability within the same session and between sessions for the EIM technique was excellent (ICCs > 0.9) concerning both intra- and inter-rater reliability, except for the component reactance. The absolute reliability was very high for the three EIM components. EIM measures using four adhesive electrodes over the area of interest is a reliable technique to assess muscle tissue status. This study confirms that these measurement results barely vary depending on the examiner and the moment. The present study also confirms phase angle as the least affected EIM component by examiner and evaluation moment.

Poor performance in the 6-min walk test (6MWT &lt, 350 m) is an important prognostic indicator of mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Little is known about the stability of this state over time and what factors might predict a poor 6MWT performance. To determine the stability of 6MWT performance over a 2-year period in COPD patients participating in annual medical follow-up visits, and to assess the ability of several clinical, pulmonary, and non-pulmonary factors to predict poor 6MWT performance, we prospectively included 137 patients with stable COPD (mean age, 66.9 &plusmn, 8.3 years). The 6MWT was scored at baseline and 2-year follow-up. To evaluate clinical, pulmonary, and non-pulmonary variables as potential predictors of poor 6MWT performance, we used multiple logistic regression models adjusted for age, sex, weight, height, and 6MWT performance at baseline. Poor 6MWT performance was stable over 2 years for 67.4% of patients. Predictors of poor 6MWT performance included a five-repetition sit-to-stand test score &le, 2 (OR, 3.01, 95% CI, 1.22&ndash, 7.42), the percentage of mobility activities with limitations (OR, 1.03, 95% CI, 1.00&ndash, 1.07), and poor 6MWT performance at baseline (OR, 4.64, 95% CI, 1.88&ndash, 11.43). Poor 6MWT performance status was stable for the majority of COPD patients. Lower scores on the five-repetition sit-to-stand test and a higher number of mobility activities with limitations were relevant predictors of poor 6MWT performance over 2 years. Prognostic models based on these non-pulmonary factors can provide non-inferior discriminative ability in comparison with prognostic models based on only pulmonary factors.

Background Although frailty is a frequent occurrence in chronic obstructive pulmonary disease (COPD) patients, evidence on the frequency of frailty transition is scarce. Aims The present study aimed to describe the frailty status transition rates over a 2-year period and their associated clinical outcomes in stable COPD patients, and to determine predictors of improvement in frailty status. Methods We prospectively included 119 patients with stable COPD (mean age ± SD, 66.9 ± 7.9 years) over a follow-up period of 2 years. Frailty was assessed using the Fried criteria (unintentional weight loss, weakness, exhaustion, low activity level, and slow walking speed). Several demographic, clinical, and health-related variables were measured. We calculated the rates for each of the frailty transitions (no change, improvement, or worsening) between baseline and 2 years. Outcomes were compared using one-way analysis of variance and predictors of improvement were identified in multivariate logistic regression. Results After 2 years of follow-up, 21 (17.6%) patients had an improved frailty status, 14 (11.7%) had worsened, and 84 (70.5%) had maintained the same frailty status. The worsening group (vs no change group) had greater dyspnea (p = 0.013) and disability (p = 0.036) and lower handgrip strength (p = 0.001). In contrast, the improved group (vs no change group) had greater handgrip (p

Objective To determine if pre-frail Chronic obstructive pulmonary disease (COPD) patients with poor and non-poor performance in the five-repetition sit-to-stand test (5-STS) had a worse prognosis for hospitalization and mortality at 2 years and for mortality at 5 years than non-frail patients. Methods We prospectively included patients with stable COPD, between 40 and 80 years, from a hospital in Spain. Patients were classified according their performance on the 5-STS test and level of frailty. Timing, number of hospitalizations, length of stay, and timing and rate of mortality were outcome measures. Patients were followed for 2 years for exacerbations and for 5 years for mortality. Kaplan-Meier curves and univariate and multivariate Cox proportional-hazard analyses, ANOVA tests and univariate and multivariate linear and logistic regression models were used. Results Of the 125 patients included, 25.6% were pre-frail with poor performance, 57% pre-frail with non-poor performance, and 17.4% non-frail with non-poor performance. Pre-frail patients with poor performance had a higher number of hospitalizations (adjusted beta: 0.49; 95% CI: 0.01–0.96), mortality rates (odds ratio: 11.33; 95% CI: 1.15–110.81), and risk at 5 years (adjusted hazard ratio: 8.77; 95% CI: 1.02–75.51) than non-frail patients. Pre-frail patients with poor performance also had worse prognoses than non-frail patients with respect to length of hospital stays (increased by 4.16 days) and timing to first hospitalization (HR: 6.01) in unadjusted models, but not when adjusted. Conclusion The COPD prognosis of pre-frail patients with respect to the number of exacerbations with hospitalization and the timing and rate of mortality is dependent of functional performance.

Prospective longitudinal study.To examine the sensitivity of the Mobility Activities Measure for lower extremities and to compare it to the sensitivity of the Physical Functioning Scale (PF-10) and the Patient-Specific Functional Scale (PSFS) at week 4 and week 8 post-hospitalization in outpatient rehabilitation settings.Mobility Activities Measure is a set of short mobility measures to track outpatient rehabilitation progress: its scales have shown good properties but its sensitivity to change has not been reported.Patients with musculoskeletal conditions were recruited at admission in three outpatient rehabilitation settings in Spain. Data were collected at admission, week 4 and week 8 from an initial sample of 236 patients (mean age ± SD = 36.7 ± 11.1).Mobility Activities Measure scales for lower extremity; PF-10; and PSFS.All the Mobility Activities Measure scales were sensitive to both positive and negative changes (the Standardized Response Means (SRMs) ranged between 1.05 and 1.53 at week 4, and between 0.63 and 1.47 at week 8). The summary measure encompassing the three Mobility Activities Measure scales detected a higher proportion of participants who had improved beyond the minimal detectable change (MDC) than detected by the PSFS and the PF-10 both at week 4 (86.64% vs. 69.81% and 42.23%, respectively) and week 8 (71.14% vs. 55.65% and 60.81%, respectively).The three Mobility Activities Measure scales assessing the lower extremity can be used across outpatient rehabilitation settings to provide consistent and sensitive measures of changes in patients' mobility. Implications for rehabilitation All the scales of the Mobility Activities Measure for the lower extremity were sensitive to both positive and negative change across the follow-up periods. Overall, the summary measure encompassing the three Mobility Activities Measure scales for the lower extremity appeared more sensitive to positive changes than the Physical Functioning Scale, especially during the first four weeks of treatment. The summary measure also detected a higher percentage of participants with positive change that exceeded the minimal detectable change than the Patient-Specific Functional Scale and the Physical Functioning Scale at the first follow-up period. By demonstrating their consistency and sensitivity to change, the three Mobility Activities Measures scales can now be considered in order to track patients' functional progress. Mobility Activities Measure can be therefore used in patients with musculoskeletal conditions across outpatient rehabilitation settings to provide estimates of change in mobility activities focusing on the lower extremity.

The final step in post-translational processing of Ras and Rho GTPases involves methylation of the prenylated cysteine residue by an isoprenylcysteine-O-carboxyl methyltransferase (ICMT). ICMT activity is essential for cell growth and development in higher eukaryotes, and inhibition of GTPase methylation has become an attractive target in cancer therapy to inactivate prenylated oncoproteins. However, the specificity and dynamics of the GTPase methylation process remain to be fully clarified. Notably, cells lacking Mam4, the ICMT ortholog in the fission yeast Schizosaccharomyces pombe, are viable. We have exploited this feature to analyze the role of methylation on GTPase localization and function. We show that methylation differentially affects GTPase membrane localization, being particularly relevant for plasma membrane tethering and downstream signaling of palmitoylated and farnesylated GTPases Ras1 and Rho2 lacking C-terminal polybasic motifs. Indeed, Ras1 and Rho2 cysteine methylation is required for proper regulation of differentiation elicited by MAPK Spk1 and for stress-dependent activation of the cell integrity pathway (CIP) and its main effector MAPK Pmk1. Further, Mam4 negatively regulates TORC2 signaling by a cross-inhibitory mechanism relying on Rho GTPase methylation. These results highlight the requirement for a tight control of GTPase methylation in vivo to allow adequate GTPase function., This work was supported by grants from Ministerio de Economía y Competitividad (BFU2014-52828-P and BIO2015-69958-P), and Fundación Séneca (19246/PI/14), Spain. European Regional Development Fund (ERDF) co-funding from the European Union.

Hospitalization for acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) is common, but little is known about the impact of hospitalization on the development of disability. The purpose of this study was to determine the rate and time course of functional changes 3 months after hospital discharge for AE-COPD compared with baseline levels 2 weeks before admission, and to identify predictors of functional decline. Methods This was a prospective study including 103 patients (age mean, 71 years; standard deviation, 9.1 years) who were hospitalized with AE-COPD. Number of dependencies in Activities of Daily Living (ADLs) was measured at the preadmission baseline and at weeks 6 and 12 after discharge. Patterns of improvement, no change, and decline were defined over 3 consecutive intervals (baseline and weeks 6 and 12). Trajectories grouped patients with similar time courses of disability. Recovery was defined as returning to baseline function after functional decline. Univariate and multivariate multiple logistic regression was used to determine predictors of functional decline after week 12. Results Six trajectories of functional changes were found. From baseline to 12 weeks, 50% of patients continued to have the same function whereas 31% experienced functional decline after 6 weeks; 16.7% recovered over subsequent weeks. At week 12, as a consequence of all trajectories, 38% of patients showed functional declines compared with baseline function, 57% had not declined, and 6 improved. Length of stay (odds ratio [OR] = 1.12;95% [confidence interval] CI 1.03–1.22), dyspnea (OR = 1.85; 95% CI 1.05–3.26), and frailty (OR = 3.97; 95% CI 1.13–13.92) were independent predictors of functional decline after 12 weeks. Conclusions Hospitalization for AE-COPD is a risk factor for the progression of disability. More than one third of patients hospitalized for AE-COPD declined during the 12 weeks following discharge, with most of this decline occurring by week 6

Recent recommendations for chronic obstructive pulmonary disease (COPD) suggest that evaluation and management should focus on patient health status. Despite the frequency of poor health status and its negative impact on patients with COPD, little is known about how poor or non-poor health status persists and/or remits over time or what factors might predict recovery from a poor health status. The aim was to determine the likelihood of transitioning between poor and non-poor health status in patients with stable COPD followed for 2 years and to investigate factors that might predict recovery from poor health status. We prospectively included 137 patients with stable COPD (mean age, 66.9 years &plusmn, 8.3). Health status was measured at baseline and after 1 and 2 years with the COPD assessment test (CAT). Higher scores indicated worse health status, and 10 was the cut-off score for discriminating between non-poor and poor health status. The likelihoods of annual transitions to new episodes and recovery were calculated. We evaluated demographic, non-respiratory, and respiratory variables as potential predictors with generalized estimating equations. At baseline, 37 patients (27%) reported non-poor health status. Within the group of patients displaying poor health status at the beginning of the year, 176 annual transitions were identified during the study period: 15.9% were transitions to recovery from poor health status. In contrast, of the 70 transitions from a starting non-poor health status, 32.4% worsened. Predictors of transitions to recovery were: current non-smoker status (odds ratio (OR) = 3.88, 95% confidence interval (CI): 0.64&ndash, 5.54) and handgrip strength (OR = 1.08, 95% CI: 1.00&ndash, 1.16). This study suggests that self-reported health status, measured with the CAT, has a dynamic nature in patients with COPD. Annual transitions towards recovery from poor health status are most likely among current non-smoking patients and those with high handgrip strength.

Background and Objectives: Within the clinical evaluation of multiple pathologies of the lower limb, the measurement of range of motion (ROM) of its joints is fundamental. To this end, there are various tools, from the goniometer as a reference to more recent devices such as inclinometry-based applications, photo capture applications, or motion capture systems. This study aimed to assess the validity, intra-rater, and inter-rater reliability of the VeloFlex system (VS), which is a new camera-based tool designed for tracking joint trajectories and measuring joint ROM. Materials and Methods: Thirty-five healthy volunteers (16 females, aged 18&ndash, 61 years) participated in this study. All participants were assessed on two separate occasions, one week apart. During the first assessment session, measurements were obtained using a goniometer and the VS, whereas, in the second session, only the VS was used. In each assessment session, nine active movements were examined. For each movement, three trials were tested, and the mean of these three measures was used for analysis. To evaluate the concurrent validity and agreement, the Pearson correlation coefficient (r) and Bland-Altmann plots were used. Intra-rater and inter-rater reliability were evaluated using intra-class correlation (ICC), standard error of measurement (SEM), and minimal detectable change (MDC). Results: Both devices showed excellent correlations for all movements (r ranged from 0.992 to 0.999). The intra-rater reliability of the VS was excellent (ICC ranged from 0.93 to 0.99), SEMs ranged from 0.53% to 2.61% and the MDC ranged from 0.68&deg, to 3.26&deg, The inter-rater reliability of the VS was also excellent (ICC ranged from 0.88 to 0.98), SEMs ranged from 0.81% to 4.76% and the MDC ranged from 2.27&deg, to 4.42&deg, Conclusions: The VS is a valid and reliable tool for the measurement of ROM of lower limb joints in healthy subjects.

Quorum sensing (QS), a mechanism of microbial communication dependent on cell density, governs developmental decisions in many bacteria and in some pathogenic and non-pathogenic fungi including yeasts. In these simple eukaryotes this response is mediated by the release into the growth medium of quorum-sensing molecules (QSMs) whose concentration increases proportionally to the population density. To date the occurrence of QS is restricted to a few yeast species. We show that a QS mediated by the aromatic alcohols phenylethanol and tryptophol represses the dimorphic yeast to hypha differentiation in the fission yeast S. japonicus in response to an increased population density. In addition, the stress activated MAPK pathway (SAPK), which controls cell cycle progression and adaptation to environmental changes in this organism, constitutively represses yeast to hypha differentiation both at transcriptional and post-translational levels. Moreover, deletion of its main effectors Sty1 MAPK and Atf1 transcription factor partially suppressed the QS-dependent block of hyphal development under inducing conditions. RNAseq analysis showed that the expression of nrg1+, which encodes a putative ortholog of the transcription factor Nrg1 that represses yeast to hypha dimorphism in C. albicans, is downregulated both by QS and the SAPK pathway. Remarkably, Nrg1 may act in S. japonicus as an activator of hyphal differentiation instead of being a repressor. S. japonicus emerges as an attractive and amenable model organism to explore the QS mechanisms that regulate cellular differentiation in fungi., Author summary Quorum sensing is a relevant mechanism of communication dependent on population density that controls cell development and pathogenesis in microorganisms including fungi. We describe a quorum sensing mediated by the release of aromatic alcohols in the growth medium that blocks hyphal development in the fission yeast Schizosaccharomyces japonicus. This is the first description of such a mechanism in the fission yeast lineage, and confirms its expansion along Ascomycota fungi. The stress-responsive pathway (SAPK), which regulates fungal growth and differentiation, limits hyphal growth in S. japonicus in a constitutive fashion, and nonfunctional SAPK mutants are partially insensitive to quorum sensing and able to form hyphae in high cell density cultures. Nrg1, an important factor that blocks hyphal development in the pathogen Candida albicans, activates hyphal growth in S. japonicus, and its expression is counteracted by both quorum sensing and the SAPK pathway. Nrg1 function may thus have diverged evolutionary in this organism from being a repressor to an activator of hyphal development. S. japonicus emerges as a suitable model organism to explore the intricate mechanisms regulating fungal differentiation.

Determining the predictive variables associated with cannabis use and cannabis-related problems can ease the identification of young cannabis consumers who can benefit from prevention interventions. This study aimed: (1) to describe, among university students, the cannabis use and cannabis-use problems, intention to use cannabis and family climate based on the gender and the people the student lives with; (2) to explore whether the family climate and intention to use cannabis are predictors of cannabis use and cannabis-related problems. The sample was composed of 339 Spanish undergraduates (51.9% females) in a 17-to-25 age range (19.67 ± 1.53). The variables were assessed through a battery based on the ESPAD survey, cannabis abuse screening test, cannabis use intention questionnaire and family climate scale. More men than women had used cannabis in the precedent year and showed greater intention to use cannabis, whereas more women than men showed greater self-efficacy in not using cannabis. The family climate did not predict cannabis use and cannabis-related problems. However, subjective norms and self-efficacy were key predictors of cannabis use and cannabis-use problems, respectively. Different factors seemed to predict the use cannabis in the past year versus cannabis-related problems, and these differences may help inform the development and delivery of preventative efforts.

Alarcos Cieza and colleagues argue that services for children and young people with disability need greater priority

Objetivo: Identificar los factores que influyen en cambios en la ansiedad de los cuidadores tres meses después del alta hospitalaria por exacerbación aguda de la Enfermedad Pulmonar Obstructiva Crónica (EPOC). Metodología: Estudio longitudinal. Participaron 87 cuidadores de pacientes hospitalizados por exacerbación aguda de EPOC. Se midió la ansiedad en el momento de la hospitalización y tres meses después del alta. Además, se midieron potenciales factores asociados a su cambio en cuatro dominios: Contexto del cuidado, demandas del cuidado, recursos y características del paciente. Utilizamos regresiones logísticas múltiples univariadas y multivariadas para determinar los cambios en la ansiedad tres meses después. Resultados: Presentaron ansiedad en el momento de la hospitalización el 57,5% de los cuidadores. De ellos, el 44% había remitido su ansiedad tres meses después del alta hospitalaria. Sin embargo, el 22% de los cuidadores quienes no habían presentado ansiedad en el momento de la hospitalización se mostraron ansiosos a los 3 meses. La gravedad de la EPOC y no recibir apoyo de otro cuidador disminuyó las probabilidades de remisión de la ansiedad. La sobrecarga moderadamente alta incrementa las probabilidades de presentar nuevos síntomas de ansiedad. Conclusiones: La percepción de los síntomas de la ansiedad es dinámica. Los cuidadores pueden recuperarse si reciben ayuda de otro cuidador o si el paciente al que cuidan no está en un estado severo de EPOC. ABSTRACT: Objective: To identify the factors that influence changes in caregivers anxiety status three months after discharge for acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Methodology: Longitudinal study. Participants included 87 caregivers of patients hospitalized for acute exacerbation of COPD. Anxiety was measured at the time of hospitalization and three months after discharge. We measured factors from four domains: context of care, caregiving demands, caregiver resources, and patient characteristics. We used multiple univariate and multivariate logistic regressions to determine changes in anxiety three months later. Univariate and multivariate multiple logistic regressions were used to determine changes in anxiety three months later. Results: A total of 57.5% of caregivers reported anxiety at the time of hospitalization. Of these, 44% had a remission of their anxiety three months after discharge. However, 22% of caregivers who had not experienced anxiety at the hospitalization became anxious at 3 months. The severity of COPD and not receiving help from another caregiver decreased the likelihood of remission of anxiety. Moderately high overload increases the likelihood of experiencing anxiety symptoms. Conclusions: The perception of anxious symptoms is dynamic. Caregivers are likely to recover from anxiety when they receive help from another caregiver and if the patient they are caring for does not have severe COPD.

The two PKC orthologs Pck1 and Pck2 in the fission yeast Schizosaccharomyces pombe operate in a redundant fashion to control essential functions, including morphogenesis and cell wall biosynthesis, as well as the activity of the cell integrity pathway and its core element, the MAPK Pmk1. We show here that, despite the strong structural similarity and functional redundancy of these two enzymes, the mechanisms regulating their maturation, activation, and stabilization have a remarkably distinct biological impact on both kinases. We found that, in contrast to Pck2, putative in vivo phosphorylation of Pck1 within the conserved activation loop, turn, and hydrophobic motifs is essential for Pck1 stability and biological functions. Constitutive Pck activation promoted dephosphorylation and destabilization of Pck2, whereas it enhanced Pck1 levels to interfere with proper downstream signaling to the cell integrity pathway via Pck2. Importantly, although catalytic activity was essential for Pck1 function, Pck2 remained partially functional independent of its catalytic activity. Our findings suggest that early divergence from a common ancestor in fission yeast involved important changes in the mechanisms regulating catalytic activation and stability of PKC family members to allow for flexible and dynamic control of downstream functions, including MAPK signaling., This work was supported by Ministerio de Economía y Competitividad Grants BFU2014-52828-P and BIO2015-69958-P, Fundación Séneca Grant 19246/PI/14, and European Regional Development Fund co-funding from the European Union.

In the fission yeast Schizosaccharomyces pombe, Wee1-dependent inhibitory phosphorylation of the highly conserved Cdc2/Cdk1 kinase determines the mitotic onset when cells have reached a defined size. The receptor of activated C kinase (RACK1) is a scaffolding protein strongly conserved among eukaryotes which binds to other proteins to regulate multiple processes in mammalian cells, including the modulation of cell cycle progression during G(1)/S transition. We have recently described that Cpc2, the fission yeast ortholog to RACK1, controls from the ribosome the activation of MAPK cascades and the cellular defense against oxidative stress by positively regulating the translation of specific genes whose products participate in the above processes. Intriguingly, mutants lacking Cpc2 display an increased cell size at division, suggesting the existence of a specific cell cycle defect at the G(2)/M transition. In this work we show that protein levels of Wee1 mitotic inhibitor are increased in cells devoid of Cpc2, whereas the levels of Cdr2, a Wee1 inhibitor, are down-regulated in the above mutant. On the contrary, the kinetics of G(1)/S transition was virtually identical both in control and Cpc2-less strains. Thus, our results suggest that in fission yeast Cpc2/RACK1 positively regulates from the ribosome the mitotic onset by modulating both the protein levels and the activity of Wee1. This novel mechanism of translational control of cell cycle progression might be conserved in higher eukaryotes.

The receptor of activated C kinase (RACK1) is a protein highly conserved among eukaryotes. In mammalian cells, RACK1 functions as an adaptor to favor protein kinase C (PKC)-mediated phosphorylation and subsequent activation of c-Jun NH2-terminal kinase mitogen-activated protein kinase. Cpc2, the RACK1 orthologue in the fission yeast Schizosaccharomyces pombe, is involved in the control of G2/M transition and interacts with Pck2, a PKC-type protein member of the cell integrity Pmk1 mitogen-activated protein kinase (MAPK) pathway. Both RACK1 and Cpc2 are structural components of the 40S ribosomal subunit, and recent data suggest that they might be involved in the control of translation. In this work, we present data supporting that Cpc2 negatively regulates the cell integrity transduction pathway by favoring translation of the tyrosine-phosphatases Pyp1 and Pyp2 that deactivate Pmk1. In addition, Cpc2 positively regulates the synthesis of the stress-responsive transcription factor Atf1 and the cytoplasmic catalase, a detoxificant enzyme induced by treatment with hydrogen peroxide. These results provide for the first time strong evidence that the RACK1-type Cpc2 protein controls from the ribosome the extent of the activation of MAPK cascades, the cellular defense against oxidative stress, and the progression of the cell cycle by regulating positively the translation of specific gene products involved in key biological processes.

The increasing antibiotic resistance of human pathogens and their tolerance mechanisms to antimicrobial agents highlight the need for new therapeutic strategies. The phenomenon of quorum sensing (QS) is mediated by small signaling molecules, and plays major roles in bacterial physiology and ecology. Since its discovery more than 40 years ago, QS has been shown in many microorganisms, including animal and plant pathogens, and extensive studies have revealed that, among other physiological properties, virulence is often controlled by QS mechanisms. These findings prompt a move for novel ways to control microbial populations, changing the focus from traditional bacteriostatic or bacteriolytic agents to new compounds targeting QS systems. Consequently, natural and synthetic QS-interfering compounds (QSIs) that neither destroy nor inhibit the growth of pathogens, but modulate microbial phenotypes by attenuating virulence, are now being characterized. QSI agents can be potentially utilized to reduce the spread of infection or to improve the removal of pathogens. Moreover, the pharmacological targeting of nonessential functions, such as virulence factors or biofilm formation, may alleviate the development of resistance by lessening the need of using conventional agents which, by themselves, select for resistance. The usefulness of these kinds of compounds against infection does not just rely on being a therapy but also in representing a prophylactic approach to avoid invasion of materials where infection can initiate. Some relevant developments on these topics are discussed.

Mitogen-activated protein kinases (MAPKs) define a specific group of eukaryotic protein kinases which regulate a number of cellular functions by transducing extracellular signals to intracellular responses. Unlike other protein kinases, catalytic activation of MAPKs by MAPKKs depends on dual phosphorylation at two tyrosine and threonine residues within the conserved TXY motif, and this has been proposed to occur in an ordered fashion, where the initial phosphorylation on tyrosine is followed by phosphorylation at the threonine residue. However, monophosphorylated MAPKs also exist in vivo, and although threonine phosphorylated isoforms retain some catalytic activity, their functional significance remains to be further elucidated. In the fission yeast Schizosaccharomyces pombe MAPKs Sty1 and Pmk1 control multiple aspects of fission yeast life cycle, including morphogenesis, cell cycle, and cellular response to a variety of stressful situations. In this work we show that a trapping mechanism increases MAPKK binding and tyrosine phosphorylation of both Sty1 and Pmk1 when subsequent phosphorylation at threonine is hampered, indicating that a sequential and likely processive mechanism might be responsible for MAPK activation in this simple organism. Whereas threonine-monophosphorylated Sty1 showed a limited biological activity particularly at the transcriptional level, threonine-monophosphorylated Pmk1 was able to execute most of the biological functions of the dually phosphorylated kinase. Thus, threonine monophosphorylated MAPKs might display distinct functional relevance among eukaryotes.

The activation of neutral trehalase (Ntp1) by metabolic and physical stresses in Schizosaccharomyces pombe is dependent on protein kinases Pka1 or Sck1. Mutant ntp1 alleles altered for potentially phosphorylatable serine residues within the regulatory domain of the enzyme were integrated under the control of the native promoter in an ntp1-deleted background. The trehalase variants were expressed to a level similar to that of wild type trehalase from control cells. Wild type trehalase protein accumulated and became activated upon stress while a single change in the evolutionary conserved perfect consensus site for Pka1-dependent phosphorylation (Ser71), as well as point mutations in two other putative phosphorylation sites (Ser6, Ser51), produced inactive trehalases unresponsive to stress. Trehalose content in the trehalase mutated strains increased upon salt stress to a level comparable to that shown by an ntp1-deleted mutant. When exposed to heat shock, trehalose hyperaccumulated in the ntp1-null strain lacking trehalase protein and this phenotype was shown by some (Ser71), but not all, strains with serine mutated trehalases. The mutant trehalases retained the ability to form complexes with trehalose-6-phosphate synthase. These data support a role of potentially phosphorylated specific sites for the activation of S. pombe neutral trehalase and for the heat shock-induced accumulation of trehalose.

In Schizosaccharomyces pombe, glucose concentrations below a certain threshold trigger the stress-activated protein kinase (SAPK) signal transduction pathway and promote increased transcription of Atf1-dependent genes coding for the general stress response. Removal of glucose specifically induces the nuclear accumulation of green fluorescent protein-labeled Pap1 (GFP-Pap1) and the expression of genes dependent on this transcription factor. In contrast, depletion of the nitrogen source triggers the SAPK pathway but does not activate Pap1-dependent gene transcription, indicating that carbon stress rather than growth arrest leads to an endogenous oxidative condition that favors nuclear accumulation of Pap1. The reductant agents glutathione or N-acetylcysteine suppress the nuclear accumulation of GFP-Pap1 induced by glucose deprivation without inhibiting the activation of the MAPK Sty1. In addition, cells expressing a mutant GFP-Pap1 unable to accumulate into the nucleus upon hydrogen peroxide-mediated oxidative stress failed to show this protein into the nucleus in the absence of glucose. These results support the concept of a concerted action between the SAPK pathway and the Pap1 transcription factor during glucose exhaustion by which glucose limitation induces activation of the SAPK pathway prior to the oxidative stress caused by glucose deprivation. The ensuing induction of Atf1-dependent genes (catalase) decreases the level of hydroperoxides allowing Pap1 nuclear accumulation and function. Congruent with this interpretation, glucose-depleted cells show higher adaptive response to exogenous oxidative stress than those maintained in the presence of glucose.