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Objective Current evidence suggests that carpal tunnel syndrome (CTS) involves widespread pressure pain sensitivity as a manifestion of central sensitization. This study aimed to quantify mechanisms driving widespread pressure pain hyperalgesia in CTS by using network analysis. Design Cross-sectional. Setting Urban hospital. Subjects Women with CTS (n=120) who participated in a previous randomized clinical trial. Methods Pain intensity, related function, symptom severity, depressive levels, and pressure pain threshold (PPTs) over the median, radial, and ulnar nerves, as well as the cervical spine, the carpal tunnel, and the tibialis anterior, were collected. Network analysis was used to quantify the adjusted correlations between the modeled variables and to determine the centrality indices of each variable (i.e., the degree of connection with other symptoms in the network). Results The estimated network showed several local associations between clinical variables and the psychophysical outcomes separately. The edges with the strongest weights were those between the PPT over the median nerve and the PPT over the radial nerve (P=0.34), between function and depressive levels (P=0.30), and between the PPT over the carpal tunnel and the PPT over the tibialis anterior (P=0.29 ). The most central variables were PPT over the tibialis anterior (the highest Strength centrality) and PPT over the carpal tunnel (the highest Closeness and Betweenness centrality). Conclusions This is the first study to apply network analysis to understand the multivariate mechanisms of individuals with CTS. Our findings support a model in which clinical symptoms, depression, and widespread pressure pain sensitivity are connected, albeit within separate clusters. The clinical implications of the present findings, such as the development of treatments targeting these mechanisms, are also discussed.

Although changes in muscle morphology and quality in deep neck flexors seem to be clear in patients with whiplash-associated disorders (WAD), evidence for deep neck extensors is heterogeneous. In addition, most studies have used magnetic resonance imaging or computer tomography, which is not available for regular practice. To assess differences in deep neck extensors morphology and quality between patients with WAD and controls with ultrasound imaging (US) and to assess the association of imaging findings with clinical features. One hundred and sixty brightness-mode images at C4/C5 level were acquired in 41 patients with WAD and 39 pain-free controls. Muscle morphology and quality characteristics of the cervical multifidus (CM) and short rotators (SR), clinical pain features and pressure pain thresholds (PPT) were assessed in a blinded design. Between-groups differences in both CM and SR were observed for fatty infiltration percentage (mean: 4.9%; P

Patients with ulnar neuropathy usually experience sensory disturbances, weakness, and decreased function; however, optimal treatment approaches for this condition are not conclusive.A 48-year-old male with cubital tunnel syndrome was previously managed with a multimodal approach including splinting, neural mobilizations, and exercises with no change in symptoms. Approximately 1 year after the initial onset, he received three sessions of ultrasound-guided percutaneous electrical stimulation (PENS) and self-neural glides as a home program.After PENS intervention, the patient experienced a dramatic improvement in function and symptoms as measured by the Disabilities of the Arm, Shoulder and Hand Outcome Measure (DASH) and self-reported version of the Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) pain scale as outcomes. These improvements were maintained after 1, 3, 6, and 12 months. The patient also experienced self-perceived improvement in his condition as measured by the Global Rating of Change (GROC) at each follow-up.A patient with ulnar nerve entrapment at the elbow did not respond to a multimodal conservative care for the previous year. Once the patient was treated with ultrasound-guided PENS targeting the ulnar nerve, full functional recovery and resolution of symptoms were documented. Future clinical studies should examine the effects of PENS in managing neural entrapment syndromes on a statistically powered sample of patients.

Objective: The aim of this study was to compare the effects of dry needling (DN) versus pressure release over scalene muscle trigger points (TrPs) on pain, related disability, and inspiratory vital capacity in individuals with neck pain. Methods: In this randomized, single-blind trial, 30 patients with mechanical neck pain and active TrPs in the scalene musculature were randomly allocated to trigger point dry needling (TrP-DN; n = 15) or pressure release (n = 15) groups. The DN group received a single session of DN of active TrPs in the anterior scalene muscles, and the pressure release group received a single session of TrP pressure release over the same muscle lasting 30 s. The primary outcome was pain intensity as assessed by a numerical pain rate scale (NPRS, 0–10). Secondary outcomes included disability (neck disability index, NDI) and inspiratory vital capacity. Outcomes were assessed at baseline and 1 day (immediately post), 1 week, and 1 month after the treatment session. Data were expressed as mean score difference (Δ) and standardized mean difference (SMD). Results: Patients receiving DN exhibited a greater decrease in pain intensity than those receiving TrP pressure release at 1 month (Δ 1.2 (95% CI–1.8, –0.6), p = 0.01), but not immediately (1 day) or 1 week after. Patients in the DN group exhibited a greater increase in inspiratory vital capacity at all follow-up time points (Δ 281 mm (95% CI 130, 432) immediately after, Δ 358 mm (95% CI 227, 489) 1 week after, and Δ 310 mm (95% CI 180, 440) 1 month after treatment) than those in the pressure release group (p = 0.006). Between-group effect sizes were large at all follow-up time points (1.1 > SMD > 1.3) in favor of DN. Conclusion: This trial suggests that a single session of DN over active TrPs in the scalene muscles could be effective at reducing pain and increasing inspiratory vital capacity in individuals with mechanical neck pain. Future studies are needed to further confirm these results.

The purpose of this study was to assess the effectiveness of the application of kinesio taping in reducing induced pain after dry needling of active trigger points (TrPs) to the upper trapezius muscle.Consecutive patients had mechanical neck pain (n = 34, 44% female) with active TrPs in the upper trapezius muscle. All participants received dry needling into upper trapezius active TrPs. Then, they were randomly divided into a kinesio taping group, which received an adhesive tape (Kinesio Tex), and a control group, which did not receive the taping. The numeric pain rating scale was assessed (0-10) at post-needling; immediately after; and 24 hours, 48 hours, and 72 hours after needling. Neck- and shoulder-related disability was assessed before and 72 hours after needling with the Neck Disability Index (NDI) and the Shoulder Pain and Disability Index, respectively. The pressure pain threshold (PPT) over the TrP was also assessed post-needling, immediately post-intervention, and 72 hours after needling.The analysis of covariance did not find a significant group × time interaction (P = .26) for post-needling soreness: both groups exhibited similar changes in post-needling induced pain (P.001). No significant group × time interactions were observed for changes in NDI (P = .62), SPADI (P = .41), or PPTs (P = .52): similar improvements were found after the needling procedure for the NDI (P.001), Shoulder Pain and Disability Index (P.001), and PPT (P.001). The number of local twitch responses and sex (all, P.30) did not influence the effect for any outcome.The application of kinesio taping after dry needling of active TrPs in the upper trapezius muscle was not effective for reducing post-needling induced pain in people with mechanical neck pain. Further, the application of kinesio taping as a post-needling intervention did not influence short-term changes in disability.

Objective To assess the influence of clinical, psychological, and psychophysical variables on long-term clinical outcomes after the application of either physical therapy or surgery in women presenting with carpal tunnel syndrome (CTS). Methods A secondary analysis of a randomized trial investigating the efficacy of manual therapy including desensitization maneuvers of the central nervous system against surgery in 120 women with CTS was performed. Clinical outcomes including pain intensity, function, or symptom severity were assessed at 6 and 12 months post-intervention. Participants completed at baseline several clinical (pain intensity, function, and symptom severity), psychological (depression), and psychophysical (pressure pain thresholds and pain extent) variables, which were included as predictors. Multiple regression analyses were conducted to assess the relationship between baseline variables and clinical outcomes at 6 and 12 months post-intervention. Results The regression models indicated that higher scores of each clinical outcome (ie, intensity of pain or symptom severity) at baseline predicted better outcomes at 6 and 12 months post-intervention (from 15% to 65% of variance) in both groups. Lower pressure pain thresholds over the carpal tunnel at baseline predicted poorer clinical outcomes at 6 and 12 months post-intervention (from 5% to 20% of variance) in the physical therapy group, whereas higher depressive symptoms at baseline contributed to poorer outcomes at 6 and 12 months post-intervention (from 5% to 15% of the variance) within the surgery group. Conclusion This study found that baseline localized pressure pain sensitivity and depression were predictive of long-term clinical outcomes in women with CTS following physical therapy or surgery, respectively.

Patients with lateral elbow pain are often diagnosed with lateral epicondylalgia. Lateral elbow pain is often associated with dysfunction of the wrist extensor muscles; however, in some cases, it can also mimic signs and symptoms of radial nerve dysfunction.In this case report, a 43-year-old man, who was originally referred with a diagnosis of lateral epicondylalgia as a result of playing table tennis and who previously responded favorably to manual therapy and exercise, presented to the clinic for treatment. An exacerbation while participating in a table tennis match resulted in a return of his lateral epicondylalgia symptoms, which did not respond favorably to the same interventions used in his prior course of therapy. Further examination revealed sensitization of the radial nerve, which was treated with 2 sessions of ultrasound-guided percutaneous electrical nerve stimulation and 4 weeks of a low-load, concentric/eccentric exercise program for the wrist extensors.Following this intervention, the patient experienced clinically meaningful improvement in pain intensity (numeric pain-rating scale), function (Patient-Rated Tennis Elbow Evaluation), and related disability (Disabilities of the Arm, Shoulder and Hand questionnaire). The patient progressively exhibited complete resolution of pain and function, which was maintained at 2 years.This case report demonstrates the outcomes of a patient with lateral elbow pain who did not respond to manual therapy and exercise. Once radial nerve trunk sensitivity was identified and the intervention, consisting of ultrasound-guided percutaneous electrical nerve stimulation targeting the radial nerve combined with a low-load exercise program, was applied, a full resolution of pain and function occurred rapidly. Future clinical trials should examine the effect of percutaneous electrical nerve stimulation in the management of nerve-related symptoms associated with musculoskeletal pain conditions.Therapy, level 5.

Carpal tunnel syndrome (CTS) results in substantial societal costs and can be treated either by nonsurgical or surgical approaches.To evaluate differences in cost-effectiveness of manual physical therapy versus surgery in women with CTS.In this randomized clinical trial, 120 women with a clinical and an electromyographic diagnosis of CTS were randomized through concealed allocation to either manual physical therapy or surgery. Interventions consisted of 3 sessions of manual physical therapy, including desensitization maneuvers of the central nervous system, or decompression/release of the carpal tunnel. Societal costs and health-related quality of life (estimated by the European Quality of Life-5 Dimensions [EQ-5D] scale) over 1 year were used to generate incremental cost per quality-adjusted life year ratios for each treatment.The analysis was possible for 118 patients (98%). Incremental quality-adjusted life years showed greater cost-effectiveness in favor of manual physical therapy (difference, 0.135; 95% confidence interval: 0.134, 0.136). Manual therapy was significantly less costly than surgery (mean difference in cost per patient, €2576; P.001). Patients in the surgical group received a greater number of other treatments and made more visits to medical doctors than those receiving manual physical therapy (P = .02). Absenteeism from paid work was significantly higher in the surgery group (P.001). The major contributors to societal costs were the treatment protocol (surgery versus manual therapy mean difference, €106 980) and absenteeism from paid work (surgery versus manual physical therapy mean difference, €42 224).Manual physical therapy, including desensitization maneuvers of the central nervous system, has been found to be equally effective but less costly (ie, more cost-effective) than surgery for women with CTS. From a cost-benefit perspective, the proposed CTS manual physical therapy intervention can be considered.Economic and decision analyses, level 1b. J Orthop Sports Phys Ther 2019;49(2):55-63. Epub 30 Nov 2018. doi:10.2519/jospt.2019.8483.

Rehabilitative ultrasound imaging (RUSI) is used by physical therapists as a feedback tool for measuring changes in muscle morphology during therapeutic interventions such as motor control exercises (MCE). However, a structured overview of its efficacy is lacking. We aimed to systematically review the efficacy of RUSI for improving MCE programs compared with no feedback and other feedback methods. MEDLINE, PubMed, SCOPUS and Web of Science databases were searched for studies evaluating efficacy data of RUSI to improve muscular morphology, quality, and/or function of skeletal muscles and MCE success. Eleven studies analyzing RUSI feedback during MCE were included. Most studies showed acceptable methodological quality. Seven studies assessed abdominal wall muscles, one assessed pelvic floor muscles, one serratus anterior muscle, and two lumbar multifidi. Eight studies involved healthy subjects and three studies clinical populations. Eight studies assessed muscle thickness and pressure differences during MCE, two assessed the number of trials needed to successfully perform MCE, three assessed the retain success, seven assessed the muscle activity with electromyography and one assessed clinical severity outcomes. Visual RUSI feedback seems to be more effective than tactile and/or verbal biofeedback for improving MCE performance and retention success, but no differences with pressure unit biofeedback were found.

Objective Some studies have reported the presence of histological alterations, such as myofiber disorganization and abnormalities in the number and shape of mitochondria, in patients with fibromyalgia syndrome (FMS). Although Ultrasound imaging (US) is used to quantitatively characterize muscle tissues, US studies in patients with FMS are lacking. Therefore, we aimed to describe morphological and qualitative cervical multifidus (CM) muscle US features in women with FMS and to assess their correlation with clinical indicators. Design Observational study. Setting AFINSYFACRO Fibromyalgia Association (Madrid, Spain). Subjects Forty-five women with FMS participated. Methods Sociodemographic variables (e.g., age, height, weight, body mass index) and clinical outcomes (e.g., pain as assessed on a numerical pain rating scale, evolution time, pain-related disability as assessed by the Fibromyalgia Impact Questionnaire) were collected. Images were acquired bilaterally at the cervical spine (C4–C5 level) and measured by an experienced examiner for assessment of muscle morphology (e.g., cross-sectional area, perimeter, and shape) and quality (mean echo intensity and intramuscular fatty infiltration). Side-to-side comparisons and a correlational analysis were conducted. Results No significant side-to-side differences were found for morphology or quality features (P > 0.05). None of the clinical indicators were associated with US characteristics (all, P > 0.05). Conclusion Our results showed no side-to-side differences for CM morphology and quality as assessed with US. No associations between CM muscle morphology or quality and Fibromyalgia Impact Questionnaire, pressure pain threshold, numerical pain rating scale score, or evolution time were observed. Our preliminary data suggest that muscle morphology is not directly related to pain and pain-related disability in women with FMS.

Objective Dry needling is commonly used for the management of patients with musculoskeletal pain. However, the effects of patient expectations are uncertain. Our aim was to determine the effect of patient expectations on short-term clinical outcomes after the application of a single session of dry needling in individuals with neck pain. Methods We conducted a randomized, placebo-controlled clinical trial including 50 patients with mechanical neck pain. Participants received a single session of dry needling or sham needling in a blinded design. Predicted patient expectation was categorized as positive, neutral, or negative. Outcomes including neck pain intensity (visual analog scale, 0–100), pressure pain thresholds, and self-perceived improvement (Global Rating of Change, −7 to +7) were assessed at baseline, 1 day after the intervention (immediately after), and 7 days after the intervention (1 week after) by a blinded assessor. Repeated-measures analyses of covariance were conducted to assess the effects of real/sham needling adjusted by patient expectations. Results Individuals receiving dry needling exhibited better outcomes immediately and 1 week after the intervention than did those receiving sham needling (all P Conclusion This study did not find a significant effect of predicted patient expectations on the short-term effects of dry needling on pain intensity and pressure pain thresholds in people with mechanical neck pain.

Background: Elastography is a promising imaging technique for evaluating various musculoskeletal tissues which uses acoustic radiation force pulse sequences to generate shear waves, which propagate perpendicular to the ultrasound beam causing transient displacements to calculate the tissues stiffness. Objective: The aims were to assess the validity, inter-examiner reliability and stability of semi-quantitative elastography for calculating strain ratios (SR) in a homogeneous gel phantom in different locations within the image. Methods: A diagnostic accuracy study was performed in a homogeneous stiffness phantom. Two examiners (one novice and one experienced) performed 50 imaging captures in 5 series of 10 captures with 1-minute difference between captures and 30 minutes difference be-tween series. Each examiner assessed the SR in two locations. Difference between-examiners, stability of measurements, SR error and absolute error, mean error of the measurements and coefficient of variation were calculated. Results: The agreement between examiners, validity and stability of measurements were higher in the central area than the lateral limits of the images. Thus, the experience of the examiner showed to be relevant for the concordance of the measurements in the lateral limits of the images (SR difference of 0.13 ± 0.02; p0.05). Conclusion: Semi-quantitative elastography seems to be an accurate tool for assessing stiffness differences within the same image. Further validity and reliability studies in different materials and in-vivo tissues are needed to ensure the utility of this method.

Objective. To evaluate the effects of combining dry needling with other physical therapy interventions versus the application of the other interventions or dry needling alone applied over trigger points (TrPs) associated to neck pain. Databases and Data Treatment. Electronic databases were searched for randomized controlled trials where at least one group received dry needling combined with other interventions for TrPs associated with neck pain. Outcomes included pain intensity, pain-related disability, pressure pain thresholds, and cervical range of motion. The risk of bias (RoB) was assessed using the Cochrane risk of bias tool, methodological quality was assessed with PEDro score, and the quality of evidence was assessed by using the GRADE approach. Between-groups mean differences (MD) and standardized mean difference (SMD) were calculated. Results. Eight trials were included. Dry needling combined with other interventions reduced pain intensity at short-term (SMD −1.46, 95% CI −2.25 to −0.67) and midterm (SMD −0.38, 95% CI −0.74 to −0.03) but not immediately after or at long-term compared with the other interventions alone. A small effect on pain-related disability was observed at short-term (SMD −0.45, 95% CI −0.87 to −0.03) but not at midterm or long-term. The inclusion of dry needling was also effective for improving pressure pain thresholds only at short-term (MD 112.02 kPa, 95% CI 27.99 to 196.06). No significant effects on cervical range of motion or pain catastrophism were observed. Conclusion. Low-to-moderate evidence suggests a positive effect to the combination of dry needling with other interventions for improving pain intensity, pain-related disability, pressure pain thresholds, and cervical range of motion in people with neck pain associated with TrPs at short-term. No midterm or long-term effects were observed.

Vaginal route for drug administration can be exploited for the management of many genital conditions such as microbial infections, cancer, and vaginitis. This route offers various advantages, that is, avoidance of hepatic first-pass effect, ease of application, and the possibility of both local and systemic drug delivery. However, the challenge comes from the continuous changes in the vaginal environment related to its mucus, pH, enzyme activity, microflora, and menstrual cycle. Nanoscale drug delivery systems can reduce the influence of physiological factors on drug efficacy, prolong drug release and reduce dose frequency, minimize adverse effects associated with conventional dosage forms, and enhance patient compliance. Nanoparticle engineering necessitates an in-depth comprehension of their mucus penetration and retention behavior in vaginal mucosa as a function of their size and surface characteristics, and formulation. The most common nanosystems investigated for vaginal administration are reviewed, giving special attention to the recent advances in their development.

Objective The purpose of this study was to evaluate the effects of trigger point (TrP) dry needling alone or as an adjunct to other interventions on pain intensity and related disability in nontraumatic shoulder pain. Methods Ten databases were searched from inception to January 2020 for randomized clinical trials in which at least 1 group received TrP dry needling for shoulder pain of musculoskeletal origin with outcomes collected on pain intensity and related disability. Data extraction including participant and therapist details, interventions, blinding strategy, blinding assessment outcomes, and results were extracted by 2 reviewers. The risk of bias (Cochrane Risk of Bias, Cochrane Guidelines), methodological quality (Physiotherapy Evidence Database score), and evidence level (Grading of Recommendations Assessment, Development, and Evaluation approach) were assessed. The search identified 551 publications with 6 trials eligible for inclusion. Results There was moderate-quality evidence that TrP dry needling reduces shoulder pain intensity with a small effect (mean difference = −0.49 points, 95% CI = −0.84 to −0.13; standardized mean difference = −0.25, 95% CI = −0.42 to −0.09) and low-quality evidence that TrP dry needling improves related disability with a large effect (mean difference = −9.99 points, 95% CI −15.97 to −4.01; standardized mean difference = −1.14, 95% CI −1.81 to −0.47) compared with a comparison group. The effects on pain were only found at short term. The Cochrane Risk of Bias was generally low, but the heterogenicity of the results downgraded the evidence level. Conclusion Moderate- to low-quality evidence suggests positive effects of TrP dry needling for pain intensity (small effect) and pain-related disability (large effect) in nontraumatic shoulder pain of musculoskeletal origin, mostly at short term. Future clinical trials investigating long-term effects are needed. Impact Dry needling is commonly used for the management of musculoskeletal pain. This is the first meta-analysis to examine the effects of dry needling on nontraumatic shoulder pain.

Background and objective To evaluate the effects of percutaneous electrical stimulation (PENS) alone or as an adjunct with other interventions on pain and related disability in musculoskeletal pain conditions. Databases and data treatment Search of MEDLINE, EMBASE, AMED, CINAHL, EBSCO, PubMed, PEDro, Cochrane Library, SCOPUS and Web of Science databases. Randomized controlled trials where at least one group received any form of PENS for musculoskeletal condition. Studies had to include humans and collect outcomes on pain and related disability in musculoskeletal pain. Risk of bias was assessed by the Cochrane Guidelines, the quality of evidence by using the GRADE approach. Standardized mean differences (SMD) were calculated. Results Sixteen studies were included and included heterogeneous musculoskeletal conditions with short- or midterm follow-ups. PENS alone had a large effect (SMD -1.22, 95% CI -1.66 to -0.79) on pain and a small effect (SMD -0.33, 95% CI -0.61 to -0.06) on related disability at short-term as compared with sham. A moderate effect of PENS alone (SMD -0.71, 95% CI -1.23 to -0.19) on pain when compared with other interventions was observed. The inclusion of PENS with other interventions had a moderate effect for decreasing pain at short- (SMD -0.70, 95% CI -1.02 to -0.37) and midterm (SMD -0.68, 95% CI -1.10 to -0.27). No effect at midterm (SMD -0.21, 95% CI -0.52 to 0.10) on related disability was seen. The risk of bias was generally low; but the heterogenicity of the results downgraded the level of evidence. Conclusion There is low level of evidence suggesting the effects of PENS alone or in combination for pain, but not related disability, in musculoskeletal pain. Level of evidence Therapy, level 1a. Registration number: CRD42019131331. Significance This meta-analysis investigating the effectiveness of PENS for the management of pain and related disability in musculoskeletal pain conditions found that PENS could decrease level of pain intensity but not relateddisability in musculoskeletal pain disorders.

ObjectiveTo evaluate the effects of ultrasound-guided percutaneous electrolysis alone or as an adjunct to other interventions on pain and pain-related disability for musculoskeletal pain conditions.Databases and Data TreatmentSearch of MEDLINE database, Allied and Complementary Medicine Database, EMBASE database, Cumulative Index to Nursing & Allied Health Literature database, EBSCO database, PubMed database, Physiotherapy Evidence Database, Cochrane Library database, Scopus database, and Web of Science database. Randomized controlled trials in which at least one group received ultrasound-guided percutaneous electrolysis for treatment of musculoskeletal pain. To be eligible, studies had to include humans and collect outcomes on pain intensity and pain-related disability for musculoskeletal pain syndromes. Data were extracted by two reviewers. The risk of bias was assessed by the Cochrane Guidelines and the quality of evidence was reported using the Grading of Recommendations Assessment, Development and Evaluation approach. Standardized mean differences (SMDs) and random effects were calculated.ResultsTen studies were included. The meta-analysis found that ultrasound-guided percutaneous electrolysis reduced the mean pain intensity by –2.06 (95% confidence interval [CI], –2.69 to –1.42) and the pain intensity as assessed with a visual analog scale or a numeric pain rating scale with a large size effect (SMD = –1.15; 95% CI, –1.48 to –0.81) and also improved pain-related disability with a large size effect (SMD = 0.95; 95% CI, 0.73–1.18) as compared with comparison groups. No differences in effect sizes were found among the short-term, midterm, and long-term follow-ups. The risk of bias was generally low, but the heterogeneity of the overall result downgraded the evidence level. Trials included heterogeneous musculoskeletal pain conditions and short-term, midterm, and long-term follow-ups.ConclusionModerate evidence suggests positive effects of ultrasound-guided percutaneous electrolysis for pain and pain-related disability in musculoskeletal pain conditions relative to a comparison group in the short term, midterm, and long term.

Background Tendon dry needling is a potential treatment for tendinopathies. Several hypotheses have been proposed to explain its underlying mechanisms. No studies (to the best of our knowledge) have investigated changes in gene expression. Objective To investigate histological and gene expression changes after the application of dry needling to the healthy Achilles tendons of rats. Methods Six Sprague-Dawley male rats were randomly divided into two groups: no intervention or dry needling. Dry needling consisted of three sessions (once per week) to the Achilles tendon. Molecular expression of several genes involved in tendon repair and remodeling (e.g., Cox2, Mmp2, Mmp9, Col1a1, Col3a1, Vefg, and Scx) was assessed 7 days after the last needling session (day 28) or 28 days after for the no-intervention group. Histological tissue changes were determined with hematoxylin-eosin analyses. Results The hematoxylin-eosin–stained images revealed no substantial differences in collagen structure or the presence of inflammatory cells between the dry needling and no-intervention groups. A significant increase in the molecular expression of Cox2, Mmp2, Col3a1, and Scx genes was observed in Achilles tendons treated with dry needling when compared with the no-intervention group. Conclusion This animal pilot study found that the application of dry needling to the healthy Achilles tendons of rats is able to increase the expression of genes associated with collagen regeneration and tissue remodeling of the extracellular matrix with no further histological damage to the tendon.

To compare the effects of spinal thrust manipulation and electrical dry needling (TMEDN group) to those of nonthrust peripheral joint/soft tissue mobilization, exercise, and interferential current (NTMEX group) on pain and disability in patients with subacromial pain syndrome (SAPS).Randomized, single-blinded, multicenter parallel-group trial.Patients with SAPS were randomized into the TMEDN group (n = 73) or the NTMEX group (n = 72). Primary outcomes included the Shoulder Pain and Disability Index and the numeric pain-rating scale. Secondary outcomes included the global rating of change scale (GROC) and medication intake. The treatment period was 6 weeks, with follow-ups at 2 weeks, 4 weeks, and 3 months.At 3 months, the TMEDN group experienced greater reductions in shoulder pain and disability (Cervicothoracic and upper-rib thrust manipulation combined with electrical dry needling resulted in greater reductions in pain, disability, and medication intake than nonthrust peripheral joint/soft tissue mobilization, exercise, and interferential current in patients with SAPS. The effects were maintained at 3 months.

Panoramic ultrasound (US) is a novel method used to assess linear dimensions, cross-sectional area, fatty infiltrate and echo-intensity features of muscles that cannot be measured with B-mode US. However, a structured overview of its validity and reliability is lacking. MEDLINE, PubMed, SCOPUS and Web of Science databases were systematically searched for studies evaluating reliability or validity data on panoramic US imaging to determine the muscular morphology and/or quality of skeletal muscles. Most studies had acceptable methodological quality. Seventeen studies analyzing reliability (n = 16) or validity (n = 5) were included. Twelve studies assessed cross-sectional area, seven studies assessed echo-intensity, five assessed linear dimensions (fascicle/tendon length, muscle/subcutaneous adipose thickness or between-structure distance) and one assessed intramuscular fat. Panoramic US seems to be a reliable and valid tool for the assessment of muscle morphology and quality in healthy populations at specific locations, particularly the lower extremities. Studies including scanning procedures are needed to confirm these findings in locations not included in this revision and in both clinical and healthy populations.

Percutaneous electrolysis is an emerging intervention proposed for the management of tendinopathies. Tendon pathology is characterized by a significant cell response to injury and gene expression. No study investigating changes in expression of those genes associated with collagen regeneration and remodeling of extracellular matrix has been conducted. The aim of this pilot study was to investigate gene expression changes after the application of percutaneous electrolysis on experimentally induced Achilles tendinopathy with collagenase injection in an animal model. Fifteen Sprague Dawley male rats were randomly divided into three different groups (no treatment vs. percutaneous electrolysis vs. needling). Achilles tendinopathy was experimentally induced with a single bolus of collagenase injection. Interventions consisted of 3 sessions (one per week) of percutaneous electrolysis or just needling. The rats were euthanized, and molecular expression of genes involved in tendon repair and remodeling, e.g., Cox2, Mmp2, Mmp9, Col1a1, Col3a1, Vegf and Scx, was examined at 28 days after injury. Histological tissue changes were determined with hematoxylin&ndash, eosin and safranin O analyses. The images of hematoxylin&ndash, eosin and Safranin O tissue images revealed that collagenase injection induced histological changes compatible with a tendinopathy. No further histological changes were observed after the application of percutaneous electrolysis or needling. A significant increase in molecular expression of Cox2, Mmp9 and Vegf genes was observed in Achilles tendons treated with percutaneous electrolysis to a greater extent than after just needling. The expression of Mmp2, Col1a1, Col3a1, or Scx genes also increased, but did not reach statistical significance. This animal study demonstrated that percutaneous electrolysis applied on an experimentally induced Achilles tendinopathy model could increase the expression of some genes associated with collagen regeneration and remodeling of extracellular matrix. The observed gene overexpression was higher with percutaneous electrolysis than with just needling.

Neuromuscular disorders (NMD) lead to the progressive loss of motor and respiratory functions and a decline in daily activities and participation. We aimed to evaluate respiratory changes and functional outcomes in children attending an aquatic therapy program. Eleven patients diagnosed with NMD (4&ndash, 18 years, Vignos scale 1&ndash, 9) were involved in a 10-week aquatic exercise program. The ventilation variables were: peak cough flow, volumes (forced expiratory volume in one second-FEV1 and inspiratory volume) and respiratory pressures to evaluate strength and oxygen saturation (O2 sat). Functional skills were measured in the aquatic environment (Water Orientation Test Alyn 1) and on dry land, (Pediatric Evaluation of Disability Inventory), together with quality of life (Pediatric Quality of Life Inventory). Our evaluation included several 2 &times, 6 mixed-model repeated measures analysis of covariance (ANCOVA) with time (baseline, post 1 session, pre-post at five weeks and pre-post at 10 weeks). Important improvements in functional skills were observed in and out of the water and children under the age of 11 displayed a significant difference for inspirational volume (p = 0.002) and O2 sat (p = 0.029). Clinical, statistically insignificant changes were found for peak cough flow and expiratory pressures values after aquatic exercise. These results may support a relationship between aquatic exercise in NMD, respiratory outcomes and functional activities in water and on land.

Objectives: To determine the presence of post-needling induced pain in subjects who had suffered a stroke and received trigger point (TrP) dry needling (DN), and to investigate the effects of including TrP-DN into a rehabilitation program for shoulder pain in this population. Methods: A randomized clinical trial was conducted. Sixteen patients who had suffered a stroke and presented with shoulder pain were randomly assigned to receive rehabilitation alone or rehabilitation combined with DN. Both groups received a neurorehabilitation session including modulatory interventions targeting the central nervous system. Patients in the DN group also received a single session of DN over active TrPs in the shoulder musculature. A numerical pain rating scale (NPRS, 0–10) was used to asses post-needling induced pain at 1 min, 24 h, and 72 h after needling. Shoulder pain (NPRS, 0–10) was assessed at baseline, and 3 and 7 days after DN in both groups. Results: Five (62%) patients receiving TrP-DN reported post-needling induced pain. Post hoc analysis found that post-needling induced pain decreased significantly at 24 and 72 h (both p Conclusion: This trial found that 50% of stroke patients receiving DN experienced post-needling induced pain, a side effect that almost disappeared 72 h after the intervention without any additional therapeutic action. In addition, the inclusion of TrP-DN into a rehabilitation session was effective at decreasing shoulder pain in these patients.

Magnetoliposomes (MLPs) offer many new possibilities in cancer therapy and diagnosis, including the transport of antitumor drugs, hyperthermia treatment, detection using imaging techniques, and even cell migration. However, high biocompatibility and functionality after cell internalization are essential to their successful application. We synthesized maghemite nanoparticles (γ-Fe2O3) by oxidizing magnetite cores (Fe3O4) and coating them with phosphatidylcholine (PC) liposomes, obtained using the thin film hydration method, to generate MLPs. The MLPs were tested in vitro, using human tumor and non-tumor colon cell lines, for cytotoxicity, cell uptake and cellular distribution, and magnetically-induced cell mobility. In addition, blood cells biocompatibility studies were performed. The mean size of the MLPs, with a core of γ-Fe2O3 completely surrounded by PC liposomes, was 90 ± 20 nm, showing a soft magnetic character and a great biocompatibility in all the cell lines assayed including blood cells. Prussian blue staining showed a high MLP cell uptake with maximum internalization at 24 h. TEM analysis showed the MLPs surrounded by the cell membrane and in the cell periphery, suggesting internalization by endocytosis and/or macropinocytosis. Interestingly, the mitochondria presented MLP accumulations, particularly in tumor cells. Finally, MLPs within colon cancer cells were able to induce cell migration when a magnetic field was applied in vitro, indicating the functionality of our nanoformulation. A promising biomedical application of these MLPs is anticipated based on their physical, chemical and biological properties.

Objective To compare the effectiveness of trigger point dry needling (TrP-DN) versus placebo needling, relative to an untreated control group, on pain and quality of life in primary dysmenorrhoea. Methods In this randomised, single blind, parallel-group trial, 56 females with primary dysmenorrhoea were randomly allocated to TrP-DN (n=19), placebo needling (n=18) or no treatment (n=19). Patients in both groups were asked to undertake a stretching exercise of the rectus abdominis daily. The needling group received a single session of TrP-DN to trigger points (TrPs) in the rectus abdominis, and the placebo group received placebo needling. The primary outcome was pain intensity (visual analogue scale). Secondary outcomes were quality of life, use of non-steroidal anti-inflammatory drugs, the number of days with pain, and self-perceived improvement, measured using a Global Rate of Change. Outcomes were assessed at baseline, and 1 and 2 months after the treatment. Results Females receiving TrP-DN exhibited greater decreases (P0.1). Conclusions This trial suggests that a single session of TrP-DN of the rectus abdominis combined with stretching was more effective than placebo needling and stretching alone at reducing pain and the amount of medication used in primary dysmenorrhoea. Trial registration number ACTRN12616000170426.

Objective The purpose of the current randomized clinical trial was to examine the effects of cervical thrust manipulation or sham manipulation on cervicocephalic kinaesthetic sense, pain, pain-related disability, and pressure pain sensitivity in patients with mechanical neck pain. Methods Fifty-four individuals with neck pain were randomly assigned to receive either a cervical manipulation (right or left) or a sham manipulation. Immediate outcomes included cervical kinesthetic sense as assessed by joint position sense error (JPSE) and pressure pain thresholds (PPTs). At 1 week, neck pain intensity (numerical pain rate scale) and neck pain-related disability (Neck Disability Index [NDI]) outcomes were also collected. Results The mixed-model analysis of covariance revealed a significant group × time interaction in favor of the cervical thrust manipulation group for the JPSE on rotation and extension. There was also a significant interaction for changes in PPTs at C5 to C6 and tibialis anterior. At the 1-week follow-up, a significant interaction existed for neck-related disability but not for neck pain at rest, worst pain, or lowest pain experienced the preceding week. Conclusions Our results suggest that cervical spine thrust manipulation improves JPSE, PPT and NDI in participants with chronic mechanical neck pain. Furthermore, changes in JPSE and NDI were large and surpass published minimal detectable changes for these outcome measures. In addition, the effect sizes of PPTs were medium; however, only C5 to C6 zygapophyseal joint exceeded the minimal detectable change. In contrast, cervical thrust manipulation did not improve neck pain intensity at 1 week after the intervention.

Background The scientific evidence proposed by Ikai & Fukunaga1 may be considered as a key point to use other techniques different from conventional ultrasound, such as the ultrasound imaging in the physical therapy field. Since the first reported use of USI by physical therapists, there has been a significant growth in ways in which physical therapists are using USI technology1.

Objective To evaluate the cost-effectiveness of the inclusion of trigger point-dry needling (TrP-DN) into an exercise program for the management of subacromial pain syndrome. Methods Fifty patients with unilateral subacromial pain syndrome were randomized with concealed allocation to exercise alone or exercise plus TrP-DN. Both groups were asked to perform an exercise program targeting the rotator cuff musculature twice daily for five weeks. Patients allocated to the exercise plus TrP-DN group also received dry needling during the second and fourth sessions. Societal costs and health-related quality of life (estimated by EuroQol-5D-5L) over a one-year follow-up were used to generate incremental cost per quality-adjusted life-year (QALY) ratios for each intervention. Results Intention-to-treat analysis was possible for 48 (96%) of the participants. Those in the exercise group made more visits to medical doctors and received a greater number of other treatments (P

Study Design Clinical measurement study. Background Achilles tendinopathy is a prevalent sport-related injury. The Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire is a widely used patient-reported outcome to assess the severity of symptoms for this injury. Objective To adapt the VISA-A questionnaire into Spanish and to assess its psychometric properties. Methods Cross-cultural adaptation was conducted according to recommended guidelines. The Spanish VISA-A (VISA-A-Sp) questionnaire was administered to 210 subjects: 70 healthy students, 70 active at-risk subjects (participating in running and jumping), and 70 patients diagnosed with Achilles tendinopathy. Participants were assessed at baseline and after 3 to 5 days. The injured subjects were also evaluated with a quality-of-life questionnaire (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]) and at discharge. The final VISA-A-Sp was evaluated for reliability, validity, and responsiveness. Results Cronbach alpha for the VISA-A-Sp was greater than .8. The intraclass correlation coefficient (model 2,1) was 0.993 (95% confidence interval: 0.991, 0.995; P.05). In the confirmatory factor analysis, a 1-factor solution obtained a relatively good fit. Subjects with Achilles tendinopathy scored significantly lower than the other 2 groups (P.001). The VISA-A-Sp score within the Achilles tendinopathy group showed significant correlations with SF-36 physical components (Spearman rho0.5, P.001). The standard error of the measurement was 2.53, and the minimal detectable change at the 95% confidence level was 7 points. The responsiveness indicators included an effect size of 2.16 and a standardized response mean of 1.92. Conclusion The VISA-A-Sp showed satisfactory psychometric properties that were comparable to the original English-language version. Therefore, it can be recommended for use in clinical practice and research for assessing the severity of symptoms in Spanish-speaking athletes who suffer from Achilles tendinopathy. J Orthop Sports Phys Ther 2018;48(2):111-120. Epub 13 Dec 2017. doi:10.2519/jospt.2018.7402.

Objectives Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines. Methods Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested. Key findings Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines. Conclusions This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents.

Semi-quantitative elastography is a promising imaging technique to evaluate tissue stiffness differences, providing data regarding relative stiffness differences between two targets. The aims of this study were to assess the validity, inter-examiner reliability and variability of semi-quantitative elastography for calculating strain ratios (SR) in a homogeneous gel phantom in different locations within the image. A diagnostic accuracy study was performed in a homogeneous stiffness phantom. Four examiners participated (two novice and two experienced). Each examiner assessed the SR in two locations. Difference between examiners, variability of measurements, SR error and absolute error, mean error of the measurements and coefficient of variation were calculated. The agreement between examiners, validity and variability of measurements were higher in the central area than the lateral areas of the images. Thus, the experience of the examiner was relevant for the concordance of the measurements in the lateral areas of the images (SR difference of 0.14 ± 0.05, p &lt, 0.001), but not for the central area (SR difference of 0.05 ± 0.02, p &gt, 0.05). Our data suggested that semi-quantitative elastography is an accurate tool for assessing small magnitude stiffness differences within the same image in central areas, but the experience of the examiner is a determinant factor.

Background Studies have analyzed muscle morphometry of cervical multifidus by using ultrasound imaging, but its reliability is not clearly determined. Objective To investigate intra- and inter-rater reliability of imaging capturing (probe assessment/patient positioning) and imaging calculation (scan assessment) of cervical multifidus cross sectional area (CSA) by considering the assessor's experience in asymptomatic individuals. Design Reliability study. Methods The CSA of C4/C5 cervical multifidus was assessed in 16 asymptomatic subjects. Two examiners performed the imaging capture and also repeated the procedure (probe placement/patient positioning) twice with a 10-min period between each. Other two raters conducted imaging calculations of CSA. Intra-examiner imaging capturing reliability, each rater (experienced and novice) calculated multifidus CSA of both images obtained by each examiner. Inter-examiner imaging capturing reliability, each rater calculated the CSA obtained by each examiner at the first imaging attempt. For imaging calculation reliability, each rater calculated multifidus CSA of all images captured by both examiners. Intra-class correlation coefficients (ICC) and standard error of measurement (SEM) were calculated. Results Intra- (ICC3,1 0.988–0.996, SEM 0.3%–0.7%) and inter- (ICC3,2 0.958–0.965, SEM 2.6%–3.2%) examiner reliability of imaging capturing was excellent. Intra- and inter-rater reliability of imaging calculation was also excellent for both raters (experienced/novice). No significant differences between experienced or novice examiners or testers were found. Conclusions This study found that intra- and inter-examiner/rater reliability of imaging capturing (probe assessment/patient positioning) and imaging calculation (scan assessment) of the cervical multifidus CSA at C4/C5 level was excellent in asymptomatic subjects.

Background In addition to muscle morphology, ultrasound imaging (US) could be a potential tool to determine muscle quality assessing the echo-intensity and using offline software to quantify the percentage of intramuscular fatty infiltration. Objective To investigate intra- and inter-rater image measurement reliability of morphological (i.e., cross-sectional area, perimeter) and echo intensity features (i.e., mean muscular echo intensity, fat echo intensity cut-offs, fatty infiltrates percentage estimation) of deep neck extensors in asymptomatic subjects. Methods Brightness-mode images of the cervical spine at C4/C5 were acquired in 25 asymptomatic subjects (40%women, age: 24 years) by an experienced examiner. Cross-sectional area, perimeter and echo-intensity measures of cervical multifidus and short rotators were measured on two separate days (one-week apart) in a randomized order by two assessors. Intra-class correlation coefficients (ICC), standard error of measurement, minimal detectable change, and mean, absolute and percent errors were calculated. Results Intra- (ICC3,1 0.800–0.989) and inter- (ICC3,2 0.841–0.948) examiner reliability of echo-intensity measures ranged from good to excellent. Women exhibited higher echo-intensity features than men. Intra-examiner reliability of morphological measures was excellent (ICC3,1 0.917–0.974) for multifidus and good-excellent (ICC3,1 0.868–0.987) for short rotators. Inter-examiner reliability of morphological measures also ranged from good to excellent (ICC3,2 0.765–0.965). Men exhibited higher CSA and perimeter than women. No side-to-side differences were observed in any ultrasound measure. Conclusion This study found that intra- and inter-rater image analysis reliability of muscle morphology, mean echo intensity, and fatty infiltration quantification of cervical multifidus and short rotators at C4/C5 level was good-to-excellent in healthy subjects.

5-Fluorouracil (5-FU) is a broad spectrum cytotoxic agent being used in chemotherapy of malignancies. However, 5-FU shows a number of limitations like short half-life, non-selective biodistribution, and the development of drug resistances by tumour cells. It was investigated the potential use of folic acid-decorated and PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (FOL-PEG-PLGA NPs) for the targeted delivery of 5-FU to colon and breast cancers. PEG-PLGA and FOL-PEG-PLGA conjugates were synthesized and characterized. NPs of PLGA, PEG-PLGA, and FOL-PEG-PLGA were prepared by nanoprecipitation under optimal formulation conditions. They were found to be haemocompatible, and exhibited negligible cytotoxicity in normal (CCD-18 and MCF-10A) and tumour (HT-29 and MCF-7) human cell lines. 5-FU loading capabilities were also defined, and the NPs exhibited an initial burst drug release followed by a sustained 5-FU release. In vitro cytotoxicity studies in folate-overexpressed HT-29 colon cancer cells and MCF-7 breast cancer cells demonstrated that the half maximal inhibitory concentration (IC50) of 5-FU-loaded FOL-PEG-PLGA NPs was approximately 4-fold less than that of the 5-FU-loaded PLGA NPs (p

Studies analyzing morphometry of neck extensor musculature have mostly used Magnetic Resonance Imaging (MRI). Panoramic Ultrasound View could be used for obtaining high-quality 2D cross-sectional images with a wide field of view more cost-effectively imaging acquisition by creating an automatic construction of 2D cross-sectional images.To measure neck extensors cross-sectional area (CSA) using panoramic ultrasound view in healthy subjects.Cross-sectional study.Panoramic B-mode ultrasound images of the neck extensor muscles at C4/C5 level were acquired in 25 healthy subjects (40% women, mean age: 24 ± 5 years) by an experienced assessor. The CSA of the upper trapezius, splenius (layer), semispinalis (layer), multifidi, short rotators, and levator scapulae were calculated. The relative percentage in the total neck extensor muscle volume of each CSA was also determined. Sex and side-to-side comparisons were conducted.Men showed larger CSAs than women in all muscles (all, P 0.01). No side-to-side differences were found in either men or women (all, P 0.05). Significant positive associations between CSA with weight (r: 0.654 to 0.375, P 0.01), height (r: 0.386 to 0.581, P 0.05), and BMI (r: 0.369 to 0.563, P 0.05) were found. Men showed greater percentage of upper trapezius and semispinalis muscle layers than women (P 0.01), whereas women had a greater percentage of levator scapulae muscle than men (P 0.01) from the total volume of the neck extensors. No side-to-side differences were found either.The current study describes CSA, as assessed with panoramic ultrasound view, of the neck extensors in healthy people. Men exhibited greater CSA than women with no side-to-side differences.

Background Evidence suggests that medial pterygoid muscle plays an important role in temporomandibular pain. Therapeutic approaches targeting this muscle are needed. Objective To determine if a solid needle accurately penetrates the medial pterygoid muscle during the application of dry needling. Design A cadaveric and human descriptive study. Methods Needling insertion of the medial pterygoid was conducted in 5 fresh cadaver and 5 subjects with temporomandibular pain. Needling insertion was performed using a 40 mm needle inserted at the inferior angle of the mandibular bone. The needle was advanced from an inferior to superior direction into the medial pterygoid to a maximum depth of 30 mm. In cadavers, medial pterygoid placement was assessed by observation after resecting the superficial overlying tissues. In patients, medial pterygoid placement was assessed by self-reported pain referral during insertion. Results Accurate needle penetration of the medial pterygoid was observed in all fresh cadavers and pain referral was reported by 4/5 patients during needling insertion. Conclusion Results from both cadavers and patients support the assertion that needling of the medial pterygoid can be accurately conducted.

Carpal tunnel syndrome is the most common nerve compression disorder of the upper extremity, and it is traditionally considered a peripheral neuropathy associated with a localized compression of the median nerve just at the level of the carpal tunnel. Surgery and physiotherapy are treatment approaches commonly used for this condition; however, conflicting clinical outcomes suggest that carpal tunnel syndrome may be more complex. There is evidence supporting the role of peripheral nociception from the median nerve in carpal tunnel syndrome; however, emerging evidence also suggests a potential role of central sensitization. The presence of spreading pain symptoms (e.g. proximal pain), widespread sensory changes, or bilateral motor control impairments in people presenting with strictly unilateral sensory symptoms supports the presence of spinal cord changes. Interestingly, bilateral sensory and motor changes are not directly associated with electrodiagnostic findings. Other studies have also reported that patients presenting with carpal tunnel syndrome exhibit neuroplastic brainstem change supporting central sensitization. Current data would support the presence of a central sensitization process, mediated by the peripheral drive originating in the compression of the median nerve, in people with carpal tunnel syndrome. The presence of altered nociceptive gain processing should be considered in the treatment of carpal tunnel syndrome by integrating therapeutic approaches aiming to modulate long-lasting nociceptive barrage into the central nervous system (peripheral drive) and strategies aiming to activate endogenous pain networks (central drive).

Background Evidence suggests that suboccipital musculature plays an important role in headache. Proper therapeutic approaches targeting this muscle are needed. Objective Our aim was to determine with fresh cadavers and ultrasound imaging if a solid needle is able to properly penetrate the obliquus capitis inferior muscle during the application of dry needling. Design A cadaveric and human descriptive study. Methods Needling insertion and ultrasound imaging of the obliquus capitis inferior muscle was conducted on 10 pain-free healthy subjects and 5 fresh cadavers. Needling insertion was performed using a 40 mm needle inserted midway between the spinous process of C2 and transverse process of C1. The needle was advanced from a posterior to anterior direction into the obliquus capitis inferior muscle with an inferior-lateral angle to reach the lamina of C2. For the cadaveric study, the obliquus capitis inferior placement was verified by resecting the superficial upper trapezius, splenius capitis, and semispinalis capitis muscles. For ultrasographic study, a linear transducer was aligned with the long axis of the obliquus capitis inferior muscle after needle insertion. Results Both the cadaveric and ultrasonic studies showed that the needle penetrated the obliquus capitis inferior muscle during its insertion and that the tip of the needle rested against C2 laminae, thereby reaching the targeted muscle. Conclusion This anatomical and ultrasound imaging study supports the assertion that needling insertion of the obliquus capitis inferior muscle can be properly conducted by an experienced clinician.

Introduction: One of the most important characteristics of bronchiolitis is bronchial hypersecretion. The High-frequency chest wall compression (HFCWC) is aimed at the elimination of these secretions. Our aim was to evaluate the efficacy of respiratory physiotherapy (RP) techniques such as prolonged slow expiratory and provoked cough, compared to HFCWC in outpatient children with mild and moderate bronchiolitis according to the scale of clinical severity proposed by Wang. Methods: Randomized clinical trial with parallel double-blind groups. 91 children were randomized into two groups: RP group, and those who previously received the HFCWC with a Vest (SmartVest®) (Vest group). Results: The mean of age was 7.9±2,6 months, weighted 8.15 ± 1.37 kg, and 0.69 ± 0.07 m height. We did not find statistically significant differences in most of the variables: HR (t = -0.63, P = 0.53) nor in the respiratory frequency (t = 0.50, P = 0.56), nor in the extracted mucus (t = 1.02, P = 0.31), although more was extracted in the RP group (RP 50.3±29.2 vs VEST 45± 20.2), neither in the Wang scale (t = 0.46, P = 0.64) despite the fact that more patients switched to a normal value in the VEST group (RP 50% vs VEST 66%). Nevertheless, significant changes were observed in SaO2 (t =-2.55, P Conclusions: The inclusion of a single session of RP or combined with the vest clinically improve the Wang scale and are equally effective in terms of HR, RR and the amount of mucus collected in the short term in children with bronchiolitis.

Background The WHO states that a maximum of 10% of the daily total caloric intake should correspond to the consumption of free sugars. It has been described in a theoretical way that an excessive intake of free sugars may originate, on the one hand, a pancreatic affectation, and on the other hand, an impairment of the connective tissue. Therefore, in this labour is posed the possibility of the affectation of the thoracolumbar fascia (TLF) due to its metameric relationship with the pancreas due to an excessive consumption of free sugars. Methods An experimental, randomised, prospective and single-blind analytical research is proposed. 4 women were divided into 2 groups, control and experimental ones, by a simple randomization process. Control group subjects had to follow their usual diet while experimental group subjects carried out a low-free sugars diet. Two sonographic measurements were performed using the Toshiba Xario100 ultrasound with a 70 mm linear ultrasound probe, one pre-intervention and another post-intervention, 4 weeks after the beginning of the diets. A blinded external examiner measured the thickness with mode B sonography and the elasticity with an elastography in the L2-L3 interspinous space, and the distances’ difference between L2 and L3 spinous process in anatomical position and in maximum spine flexion position with mode B sonography. Results An intra-examiner statistical analysis was carried out by implementing the t-Student test for related samples in order to study the pre-post differences in dependent variables. No statistically significant changes (p Conclusions The results suggest that a low-free sugars diet produces no improvements in the L2-L3 interspinous opening, neither in the thickness or the elasticity of the TLF in the L2-L3 interspinous space. To confirm the results, prospective randomised clinical trials with equal representation of both genders, larger samples and longer follow-ups are needed. Likewise, we recommend future studies using expert examiners that compare their measurements with a gold standard test.

Objective: The objective of this study was to investigate somatosensory nerve fiber function by applying different quantitative sensory testing including thermal, mechanical, and vibration thresholds over latent trigger points (TrP) and in its associated referred pain area. Methods: A total of 20 patients with unilateral latent TrPs in the extensor carpi radialis brevis were included. Warmth detection threshold (WDT), cold detection threshold (CDT) and heat/cold pain thresholds (HPT, CPT), mechanical detection (MDT) and pain (MPT) thresholds, vibration threshold (VT), and pressure pain thresholds (PPT) were blinded assessed over the TrP, in the referred pain area, and in the respective contralateral mirror areas. A multilevel mixed-model ANOVA with site (TrP, referred pain area) and side (real or contralateral) as within-patient factors and sex as between-patients factor was conducted. Results: No significant differences for thermal detection (WDT, CDT) or thermal pain thresholds (HPT, CPT) were found (all, Ps>0.141). The assessments over the TrP area showed lower PPT and MDT compared with the mirror contralateral TrP area (P

Sunitinib (Su) is currently approved for treatment of several malignances. However, along with the benefits of disease stabilization, cardiovascular toxicities have also been increasingly recognized. The aim of this study was to analyze which mechanisms are involved in the cardiotoxicity caused by Su, as well as to explore the potential cardioprotective effects of l-carnitine (LC). To this end, four groups of Wistar rats were used: (1) control; (2) rats treated with 400mg LC/kg/day; (3) rats treated with 25mg Su/kg/day; and (4) rats treated with LC+Su simultaneously. In addition, cultured rat cardiomyocytes were treated with an inhibitor of nuclear factor kappa B (NF-κB), in order to examine the role of this transcription factor in this process. An elevation in the myocardial expression of pro-inflammatory cytokines, together with an increase in the mRNA expression of NF-κB, was observed in Su-treated rats. These results were accompanied by an increase in the expression of pro-fibrotic factors, nitrotyrosine and NOX 2 subunit of NADPH oxidase; and by a decrease in that of collagen degradation factor. Higher blood pressure and heart rate levels were also found in Su-treated rats. All these alterations were inhibited by co-administration of LC. Furthermore, cardiotoxic effects of Su were blocked by NF-κB inhibition. Our results suggest that: (i) inflammatory and fibrotic processes are involved in the cardiac toxicity observed following treatment with Su; (ii) these processes might be mediated by the transcription factor NF-κB; (iii) LC exerts a protective effect against arterial hypertension, cardiac inflammation and fibrosis, which are all observed after Su treatment.

The clinical use of 5-fluorouracil, one of the drugs of choice in colon cancer therapy, is limited by a nonuniform oral absorption, a short plasma half-life, and by the development of drug resistances by malignant cells. We hypothesized that the formulation of biodegradable nanocarriers for the efficient delivery of this antitumor drug may improve its therapeutic effect against advanced or recurrent colon cancer. Hence, we have engineered two 5-fluorouracil-loaded nanoparticulate systems based on the biodegradable polymers poly(butylcyanoacrylate) and poly(ε-caprolactone). Drug incorporation to the nanosystems was accomplished by entrapment (encapsulation/dispersion) within the polymeric network during nanoparticle synthesis, i.e., by anionic polymerization of the monomer and interfacial polymer disposition, respectively. Main factors determining 5-fluorouracil incorporation within the polymeric nanomatrices were investigated. These nanocarriers were characterized by high drug entrapment efficiencies and sustained drug-release profiles. In vitro studies using human and murine colon cancer cell lines demonstrated that both types of nanocarriers significantly increased the antiproliferative effect of the encapsulated drug. In addition, both nanoformulations produced in vivo an intense tumor growth inhibition and increased the mice survival rate, being the greater tumor volume reduction obtained when using the poly(ε-caprolactone)-based formulation. These results suggest that these nanocarriers may improve the antitumor activity of 5-fluorouracil and could be used against advanced or recurrent colon cancer.

The purpose of this study was to evaluate the effects of including 1 session of trigger point dry needling (TrP-DN) into a multimodal physiotherapy treatment on pain and function in postoperative shoulder pain.Twenty patients (5 male; 15 female; age, 58 ± 12 years) with postoperative shoulder pain after either open reduction and internal fixation with Proximal Humeral Internal Locking System plate plate or rotator cuff tear repair were randomly divided into 2 groups: physiotherapy group (n = 10) who received best evidence physical therapy interventions and a physical therapy plus TrP-DN group (n = 10) who received the same intervention plus a single session of TrP-DN targeted at active TrPs. The Constant-Murley score was used to determine pain, activities of daily living, range of motion, and strength, which was captured at baseline and 1 week after by an assessor blinded to group assignment.Analysis of variance showed that subjects receiving TrP-DN plus physical therapy exhibited greater improvement in the Constant-Murley total score (P.001) and also activities of daily living (P.001) and strength (P = .019) subscales than those receiving physical therapy alone. Between-group effect sizes were large in favor of the TrP-DN group (0.97SMD1.45). Both groups experienced similar improvements in pain (P.001) and range of motion (P.001).Our results suggest that including a single session of TrP-DN in the first week of a multimodal physical therapy approach may assist with faster increases in function in individuals with postoperative shoulder pain.

The use of doxorubicin (DOX), one of the most effective antitumor molecules in the treatment of metastatic breast cancer, is limited by its low tumor selectivity and its severe side effects. Colloidal carriers based on biodegradable poly(butylcyanoacrylate) nanoparticles (PBCA NPs) may enhance DOX antitumor activity against breast cancer cells, thus allowing a reduction of the effective dose required for antitumor activity and consequently the level of associated toxicity. DOX loading onto PBCA NPs was investigated in this work via both drug entrapment and surface adsorption. Cytotoxicity assays with DOX-loaded NPs were performed in vitro using breast tumor cell lines (MCF-7 human and E0771 mouse cancer cells), and in vivo evaluating antitumor activity in immunocompetent C57BL/6 mice. The entrapment method yielded greater drug loading values and a controlled drug release profile. Neither in vitro nor in vivo cytotoxicity was observed for blank NPs. The 50% inhibitory concentration (IC50) of DOX-loaded PBCA NPs was significantly lower for MCF-7 and E0771 cancer cells (4 and 15 times, respectively) compared with free DOX. Furthermore, DOX-loaded PBCA NPs produced a tumor growth inhibition that was 40% greater than that observed with free DOX, thus reducing DOX toxicity during treatment. These results suggest that DOX-loaded PBCA NPs have great potential for improving the efficacy of DOX therapy against advanced breast cancers., This investigation was funded by FEDER, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III (FIS) through projects Nos PI11/01862 and PI11/02571, and by the Consejería de Salud de la Junta de Andalucía through project No PI-0338. The authors wish to express their gratitude to G Ortiz Ferron (CIC, University of Granada, Spain) for his skillful assistance with cytometry experiments.

Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogenTrypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug forT. b. gambienseacute infection. Anin vitroeffectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore,in vivotherapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases.

Study Design Randomized controlled trial. Background Evidence suggests that multimodal interventions that include exercise therapy may be effective for patellofemoral pain (PFP); however, no study has investigated the effects of trigger point (TrP) dry needling (DN) in people with PFP. Objectives To compare the effects of adding TrP DN to a manual therapy and exercise program on pain, function, and disability in individuals with PFP. Methods Individuals with PFP (n = 60) recruited from a public hospital in Valencia, Spain were randomly allocated to manual therapy and exercises (n = 30) or manual therapy and exercise plus TrP DN (n = 30). Both groups received the same manual therapy and strengthening exercise program for 3 sessions (once a week for 3 weeks), and 1 group also received TrP DN to active TrPs within the vastus medialis and vastus lateralis muscles. The pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS; 0-100 scale) was used as the primary outcome. Secondary outcomes included other subscales of the KOOS, the Knee Society Score, the International Knee Documentation Committee Subjective Knee Evaluation Form (IKDC), and the numeric pain-rating scale. Patients were assessed at baseline and at 15-day (posttreatment) and 3-month follow-ups. Analysis was conducted with mixed analyses of covariance, adjusted for baseline scores. Results At 3 months, 58 subjects (97%) completed the follow-up. No significant between-group differences (all, P>.391) were observed for any outcome: KOOS pain subscale mean difference, -2.1 (95% confidence interval [CI]: -4.6, 0.4); IKDC mean difference, 2.3 (95% CI: -0.1, 4.7); knee pain intensity mean difference, 0.3 (95% CI: -0.2, 0.8). Both groups experienced similar moderate-to-large within-group improvements in all outcomes (standardized mean differences of 0.6 to 1.1); however, only the KOOS function in sport and recreation subscale surpassed the prespecified minimum important change. Conclusion The current clinical trial suggests that the inclusion of 3 sessions of TrP DN in a manual therapy and exercise program did not result in improved outcomes for pain and disability in individuals with PFP at 3-month follow-up. Level of Evidence Therapy, level 1b. Prospectively registered July 27, 2015 at www.clinicaltrials.gov (NCT02514005). J Orthop Sports Phys Ther 2017;47(6):392-401. doi:10.2519/jospt.2017.7389.

Colorectal cancer is the third most common cancer in both men and women and has shown a progressive increase over the past 20 years. Current chemotherapy has major limitations, and a novel therapeutic approach is required. Given that neoplastic transformation of colon epithelial cells is a consequence of genetic and epigenetic alterations, RNA interference (RNAi) has been proposed as a new therapeutic strategy that offers important advantages over conventional treatments, with high specificity and potency and low toxicity. RNAi has been employed as an effective tool to study the function of genes, preventing their expression and leading to the development of new approaches to cancer treatment. In malignancies, including colon cancer, RNAi is being used for "silencing" genes that are deregulated by different processes such as gene amplification, mutation, or overexpression and may be the cause of oncogenesis. This strategy not only provides information on the involvement of certain genes in colon cancer, but also opens up a new perspective for its treatment. However, most studies have used adenovirus or lentivirus vectors to transport RNAi into tumor cells or tumors in animal models, because several technical obstacles must be overcome before RNAi can be used in the clinical setting. The aim of this study was to review current knowledge on the use of RNAi techniques in the treatment of colon cancer.