Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Effectiveness of Therapeutic Physical Exercise in the Treatment of Patellofemoral Pain Syndrome: a Systematic Review

[eng] [Purpose] The aim of this study was to analyze the effectiveness of conservative treatment of patellofemoral pain syndrome with physical exercise. [Subjects and Methods] A computer-based review conducted of four databases (PubMed, the Cochrane Library, PEDro, and the University Library) was completed based on the inclusion criteria of patellofemoral pain syndrome patients treated with physical exercise methods and examination with self-reported pain and/or functional questionnaires. [Results] The findings of ten clinical trials of moderate to high quality were evaluated to determine the effectiveness of physical exercise as conservative management for patellofemoral pain syndrome. [Conclusion] The intervention programs that were most effective in relieving pain and improving function in patellofemoral pain syndrome included proprioceptive neuromuscular facilitation stretching and strengthening exercises for the hip external rotator and abductor muscles and knee extensor muscles

Diastasis of Symphysis Pubis and Labor: a Systematic Review

[eng] Symphysis pubis diastasis (SPD) is an infrequent complication of labor that can impair womens' general health through failure of the passive stability of the pelvic girdle. Although conservative approaches are often used to decrease symptoms and interpubic separation, notably few studies have analyzed the effect of these methods on managing the symptoms of women with SPD. The purpose of this study was to review the available literature on the conservative treatment of SPD during pregnancy and labor. A computer-based search using PubMed, PEDro, and CINAHL was performed up to November 2014. We selected all studies that considered women with SPD during pregnancy or labor and treated them with conservative methods and excluded those that included surgical intervention. Eighteen studies were selected, most of which were case reports. Although the overall results of conservative treatment were unclear because of the type and design of the obtained studies, most of the studies reported bed rest in the lateral decubitus position and a pelvic girdle as basic treatments. Additionally, the few clinical trials reported recommended additional physiotherapy, including strengthening and stabilizing exercises, to reduce SPD symptoms

Low power laser stimulation of the bone consolidation in tibial fractures of rats: a radiologic and histopathological analysis

[eng] The objective of this study is to analyze the effectiveness of low power laser irradiation in the bone consolidation of tibial fractures in rats. An experimental, comparative, prospective study with control group was designed. Twenty Wistar rats were grouped into control (n = 10) and experimental groups (n = 10). A tibial fracture, with a mechanical drill, was inflicted in all rats. The experimental group received ten days of low power arsenide-gallium laser irradiation of 850 nm (KLD, Sao Paulo, Brasil)-100 mW, 8 J/cm(2), 64 s. Before and after the laser treatment, a radiologic analysis was carried out in both groups, in which the rats were graded from 0 to IV according the Montoya scale of bone consolidation. Also, we histopathologically analyzed the bone to estimate the proliferation of fibroblasts, bone matrix, and angiogénesis with a microscopy, which were graded as I (thin layer of fibroblasts and osteoid matrix), II (thick layer of fibroblasts and osteoid matrix), or III (thick layer of fibroblasts and osteoid matrix and new blood vessels). Radiologic data showed that the experimental group had a higher bone consolidation of Montoya scale after ten days of laser irradiation compared to control group (P < 0.004). Histopathologic data showed more fibroblasts and angiogenesis presence in the group receiving laser irradiation, compared to control group (P < .002). The low power laser radiation therapy may expedite the bone repair after tibial fractures in rats, according to radiologic and histopathologic analysis

Effectiveness of Dry Needling on the Lower Trapezius in Patients with Mechanical Neck Pain: a Randomized Clinical Trial

[eng] OBJECTIVE: To evaluate the effect of dry needling into a myofascial trigger point (MTrP) in the lower trapezius muscle of patients with mechanical idiopathic neck pain. DESIGN: A single-center, randomized, double-blinded controlled study. SETTING: Patients were recruited from the student population of a local hospital by advertisement in the university clinic from January 2010 to December 2011. PARTICIPANTS: Patients (N=72) with unilateral neck pain, neck pain for ≥3 months, and active trigger points in the lower trapezius muscle were randomly assigned to 1 of 2 treatment groups. All the patients completed the study. INTERVENTIONS: Dry needling in an MTrP in the lower trapezius muscle, or dry needling in the lower trapezius muscle but not at an MTrP. MAIN OUTCOME MEASURES: The visual analog scale (VAS), Neck Pain Questionnaire (NPQ), and pressure-pain threshold (PPT) were assessed before the intervention and 1 week and 1 month postintervention. RESULTS: Treatment with dry needling of the lower trapezius muscle close to the MTrP showed decreases in pain and PPT as well as an improvement in the degree of disability (P<.001) compared with the baseline and control group measurements (P<.001). The dry-needling technique performed in the MTrP showed more significant therapeutic effects (P<.001). CONCLUSIONS: The application of dry needling into an active MTrP of the lower trapezius muscle induces significant changes in the VAS, NPQ, and PPT levels compared with the application of dry needling in other locations of the same muscle in patients with mechanical neck pain

Experienced vs inexperienced inter-examiner reliability on location and classification of myofascial trigger point palpation to diagnose lateral epicondylalgia: an observational cross-sectional study

[eng] The purpose was to evaluate the interexaminer reliability of experienced and inexperienced examiners on location and classification of myofascial trigger points (MTrPs) in two epicondylar muscles and the association between the MTrP found and the diagnosis of lateral epicondylalgia (LE). Fifty-two pianists (some suffered LE) voluntarily participated in the study. Three physiotherapists (one inexperienced in myofascial pain) examined, located, and marked MTrPs in the extensor carpi radialis brevis (ECRB) and extensor digitorum communis (EDC) muscles. Forearms were photographed and analyzed to establish the degree of agreement on MTrPs diagnosis. Data showed 81.73% and 77.88% of agreement on MTrP classification and 85.58% and 72.12% on MTrP location between the expert evaluators for ECRB and EDC, respectively. The agreement on MTrP classification between experienced and inexperienced examiners was 54.81% and 51.92% for ECRB and 50.00% and 55.77% for EDC. Also, agreement on MTrP location was 54.81% and 60.58% for ECRB and 48.08% and 48.08% for EDC. A strong association was found between presence of relevant MTrPs, LE diagnosis, and forearm pain when the examiners were experts. The analysis of location and classification of MTrPs in the epicondylar muscles through physical examination by experienced evaluators is reliable, reproducible, and suitable for diagnosing LE

Manual Therapy in joint and nerve structures combined with exercises in the treatment of recurrent ankle sprains: a randomized, controlled trial

[eng] BACKGROUND: Recurrent ankle sprains often involve residual symptoms for which subjects often perform proprioceptive or/and strengthening exercises. However, the effectiveness of mobilization to influence important nerve structures due to its anatomical distribution like tibial and peroneal nerves is unclear. OBJETIVES: To analyze the effects of proprioceptive/strengthening exercises versus the same exercises and manual therapy including mobilizations to influence joint and nerve structures in the management of recurrent ankle sprains. STUDY DESIGN: A randomized single-blind controlled clinical trial. METHOD: Fifty-six patients with recurrent ankle sprains and regular sports practice were randomly assigned to experimental or control group. The control group performed 4 weeks of proprioceptive/strengthening exercises; the experimental group performed 4 weeks of the same exercises combined with manual therapy (mobilizations to influence joint and nerve structures). Pain, self-reported functional ankle instability, pressure pain threshold (PPT), ankle muscle strength, and active range of motion (ROM) were evaluated in the ankle joint before, just after and one month after the interventions. RESULTS: The within-group differences revealed improvements in all of the variables in both groups throughout the time. Between-group differences revealed that the experimental group exhibited lower pain levels and self-reported functional ankle instability and higher PPT, ankle muscle strength and ROM values compared to the control group immediately after the interventions and one month later. CONCLUSIONS: A protocol involving proprioceptive and strengthening exercises and manual therapy (mobilizations to influence joint and nerve structures) resulted in greater improvements in pain, self-reported functional joint stability, strength and ROM compared to exercises alone

Stimuli-SoS: a model-based approach to derive stimuli generators for simulations of systems-of-systems software architectures

Abstract Background Systems-of-systems (SoS) are alliances of independent and interoperable software-intensive systems. SoS often support critical domains, being required to exhibit a reliable operation, specially because people’s safety relies on their services. In this direction, simulations enable the validation of different operational scenarios in a controlled environment, allowing a benchmarking of its response as well as revealing possible breaches that could lead to failures. However, simulations are traditionally manual, demanding a high level of human intervention, being costly and error-prone. A stimuli generator could aid in by continuously providing data to trigger a SoS simulation and maintaining its operation. Methods We established a model-based approach termed Stimuli-SoS to support the creation of stimuli generators to be used in SoS simulations. Stimuli-SoS uses software architecture descriptions for automating the creation of such generators. Specifically, this approach transforms SoSADL, a formal architectural description language for SoS, into dynamic models expressed in DEVS, a simulation formalism. We carried out a case study in which Stimuli-SoS was used to automatically produce stimuli generators for a simulation of a flood monitoring SoS. Results We run simulations of a SoS architectural configuration with 69 constituent systems, i.e., 42 sensors, 9 crowdsourcing systems, and 18 drones. Stimuli generators were automatically generated for each type of constituent. These stimuli generators were capable of receiving the input data from the database and generating the expected stimuli for the constituents, allowing to simulate constituent systems interoperations into the flood monitoring SoS. Using Stimuli-SoS, we simulated 38 days of flood monitoring in little more than 6 h. Stimuli generators correctly forwarded data to the simulation, which was able to reproduce 29 flood alerts triggered by the SoS during a flooding event. In particular, Stimuli-SoS is almost 65 times more productive than a manual approach to producing data for the same type of simulation. Conclusions Our approach succeeded in automatically deriving a functional stimuli generator that can reproduce environmental conditions for simulating a SoS. In particular, we presented new contributions regarding productivity and automation for the use of a model-based approach in SoS engineering