The Effect of Ankle Muscles Dry Needling on Brain Activity Map Based on fMRI: a Study Protocol for Randomized Controlled Trial.

Importance: Neuromodulation may be one of the underlying mechanisms of dry needling (DN); however, the mechanism has not yet been fully clarified. Objective: This randomized controlled trial is designed to evaluate DN stimulation of the tibialis anterior and peroneus longus muscles in chronic ankle instability (CAI) and healthy subjects, employing functional magnetic resonance imaging (fMRI). Design: Clinical study protocol, SPIRIT compliant. Setting: Brain Mapping Laboratory. Population: A total of thirty participants aged between 18 and 40 years old will be included in this study. Twenty healthy participants will be randomized into 2 groups (real DN and sham DN). Ten patients with CAI will also be recruited to the third group and receive only real DN for comparison. Exposures: Real and sham DN. Main Outcomes and Measures: The voxel count, coordinates of peak activation, and peak intensity will be obtained as primary outcomes to report brain map activation. Measurements will be taken before, during, and after DN treatment. The strength of the ankle dorsiflexors, active dorsiflexion range of motion, and McGill pain questionnaire short-form will be used as secondary outcome measures. Results: The results from this study will be published in peer-reviewed journals and disseminated as presentations at national and international congresses. Conclusion: This trial will explore brain responses to real and sham DN in healthy participants and to real DN in CAI patients. Overall, our results will provide preliminary evidence of the neural mechanism of DN.

Diaphragm and core stabilization exercises in low back pain: A narrative review.

INTRODUCTION: Core stabilization is a vital concept in clinical rehabilitation (including low back pain rehabilitation) and competitive athletic training. The core comprises of a complex network of hip, trunk and neck muscles including the diaphragm. AIMS: The paper aims to discuss the role of the diaphragm in core stability, summarize current evidence and put forth ideal core training strategies involving the diaphragm. METHOD: Narrative review RESULTS: The diaphragm has a dual role of respiration and postural control. Evidence suggests that current core stability exercises for low back pain are superior than minimal or no treatment, however, no more beneficial than general exercises and/or manual therapy. There appears to be a higher focus on the transversus abdominis and multifidi muscles and minimal attention to the diaphragm. We propose that any form of core stabilization exercises for low back pain rehabilitation should consider the diaphragm. Core stabilization program could commence with facilitation of normal breathing patterns and progressive systematic restoration of the postural control role of the diaphragm muscle. CONCLUSION: The role of the diaphragm is often overlooked in both research and practice. Attention to the diaphragm may improve the effectiveness of core stability exercise in low back pain rehabilitation.

Effects of dry needling session frequency on wrist flexor spasticity and motor recovery after stroke: a single-blind randomized clinical trial.

BACKGROUND: Determining the optimal number of dry needling (DN) sessions to satisfactorily treat a stroke patient with spasticity is important from both clinical and economic perspective. OBJECTIVE: To explore the effects of one versus three sessions of DN on spasticity of the wrist flexors and motor recovery after stroke. METHODS: In this single-blind randomized clinical trial, 24 patients were randomly and equally divided into two groups: one group received one session of DN, while the other group received three sessions of DN in one week. Both groups received one minute of DN of the flexor carpi radialis and flexor carpi ulnaris. The outcome measures were the Modified Modified Ashworth Scale (MMAS), passive resistance torque (PRT), wrist active and passive extension range of motion (ROM), and the Brunnstrom Stages of Stroke Recovery (BSSR) measured before, immediately after, and one week after the last DN session. RESULTS: Both groups demonstrated a significant improvement in all outcomes (p < .05). The MMAS scores in both groups meaningfully improved (p < .001). No significant differences were found between the two groups; however, a significant time-by-group interaction was observed for the PRT (p = .02; Cohen's d = 0.23-0.73), wrist active extension ROM (p = .001; Cohen's d = 0.37-0.67), and wrist passive extension ROM (p = .02; Cohen's d = 0.32-1.30). The BSSR significantly improved from 3 to 4 in both groups (p < .001). CONCLUSION: Administering three sessions of DN can effectively improve spasticity and motor function after stroke.

Intramuscular Electrical Stimulation for the Treatment of Trigger Points in Patients with Chronic Migraine: A Protocol for a Pilot Study Using a Single-Case Experimental Design.

Background and Objectives: Trigger points (TrPs) are prevalent in patients with migraine headaches. Needling interventions targeting TrPs in migraine patients may reduce the intensity and frequency of headaches, yet systematic reviews reveal a lack of robust evidence. Intramuscular electrical stimulation (IMES) is a modality that delivers electrical current into muscles and TrPs, with recent studies suggesting it may amplify the therapeutic effects of dry needling peripherally and centrally. This could be advantageous for patients with migraine and symptomatic TrPs. Materials and Methods: This study will implement a multiple baseline single-case experimental design (SCED). In a clinical setting, a SCED study lends itself to conducting research with only a few patients that each serve as their own controls. In this SCED study, four participants with chronic migraine will be enrolled in a non-concurrent manner and randomized to one of four baseline measurement periods (4, 5, 6 or 7 weeks), leading to four potentially different start dates for each participant in the intervention phase. During the intervention phase, patients will receive five sessions of dry needling with IMES, one session per week for five weeks. The primary outcome measure will be headache frequency, i.e., the reduction in the number of headache days over a one-month period using electronic headache diary data from the Migraine Buddy smartphone application. Secondary outcome measures will be changes in mean migraine pain intensity using a numeric pain rating scale (NPRS), migraine disability using the Migraine Disability Assessment Test (MIDAS), the Headache Impact Test (HIT-6), and changes in selected cervical musculoskeletal impairments including pressure pain thresholds (PPTs) over TrPs, the craniocervical flexion test (CCFT), and cervical active range of motion (AROM). Primary and secondary outcome measures will be analyzed separately using both visual and statistical analyses. Results: Actively recruiting participants. This project was approved by the Mass General Brigham Institutional Review Board (protocol #2023P000931) and is registered with ClinicalTrials.gov (NCT05893914). Conclusions: This study will seek to determine the effects of a five-week intervention period of IMES to TrPs in the posterior cervical muscles of subjects with chronic migraine.

Readily Accessible Strained Difunctionalized trans-Cyclooctenes with Fast Click and Release Capabilities.

The click reaction between a functionalized trans-cyclooctene (TCO) and a tetrazine (Tz) is a compelling method for bioorthogonal conjugation in combination with payload releasing capabilities. However, the synthesis of difunctionalized TCOs remains challenging. As a result, these compounds are poorly accessible, which impedes the development of novel applications. In this work, the scalable and accessible synthesis of a new bioorthogonal difunctionalized TCO is reported in only four single selective high yielding steps starting from commercially available compounds. The TCO-Tz click reaction was assessed and revealed excellent kinetic rates and subsequently payload release was shown with various functionalized derivatives. Tetrazine triggered release of carbonate and carbamate payloads was demonstrated up to 100 % release efficiency and local drug release was shown in a cellular toxicity study which revealed a >20-fold increase in cytotoxicity.

Contracture Knots vs. Trigger Points. Comment on Ball et al. Ultrasound Confirmation of the Multiple Loci Hypothesis of the Myofascial Trigger Point and the Diagnostic Importance of Specificity in the Elicitation of the Local Twitch Response. Diagnostics 2022, 12, 321.

A recent study published in Diagnostics attempted to visualize trigger points and contracture knots with high-definition ultrasound. Based on their findings, the authors reversed the commonly understood meaning of the two terms. However, they did so without providing any convincing evidence. The authors maintained that their sonography images represented trigger points within contracture knots, supporting the multiple loci hypothesis. On review of the paper, both conclusions seem premature and rather speculative.

Intramuscular Electrical Stimulation to Trigger Points: Insights into Mechanisms and Clinical Applications-A Scoping Review.

Intramuscular electrical stimulation (IMES) is a modality used by clinicians to treat myofascial pain. Recent studies have shown positive results for the use of IMES on pain outcomes, yet studies investigating the potential mechanisms of IMES directly to trigger points (TrPs) are lacking. We performed a scoping review of the literature to summarize the current evidence from human and animal studies on the mechanisms of IMES to the TrP location, and to identify gaps in the existing literature. Electronic literature searches were conducted across five databases from inception to 15 August 2022, including PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Scopus and Cochrane Register of Controlled Trials. Four studies met our full criteria for inclusion in this review. Three studies assessed the effects of IMES to TrPs on human subjects with MPS, and only one study used an animal model with experimentally generated TrPs. Based on the results of the included studies, IMES within a TrP region was reported to normalize muscle blood flow, decrease endplate noise of the TrP and elicit antinociceptive effects, at least partially, through engaging supraspinal descending pain inhibitory systems. At present, no clinical implications can be determined on the use of IMES to TrPs due to the limited amount and quality of the available evidence. Further studies investigating the clinical effectiveness and also underlying mechanisms of IMES to TrPs are clearly needed.

Spinopelvic alignment and low back pain after total hip arthroplasty: a scoping review.

OBJECTIVE: Spinopelvic alignment is increasingly considered as an essential factor for maintaining an energy-efficient posture in individuals with normal or pathological status. Although several previous studies have shown that changes in the sagittal spinopelvic alignment may occur in patients undergoing total hip arthroplasty (THA), no review of this area has been completed so far. Thus, the objective of this scoping review was to summarize the evidence investigating changes in spinopelvic alignment and low back pain (LBP) following THA. DATA SOURCES: We adhered to the established methodology for scoping reviews. Four electronic databases were systematically searched from inception-December 31, 2021. STUDY SELECTION: We selected prospective or retrospective observational or intervention studies that included patients with THA. DATA EXTRACTION: Data extraction and levels of evidence were independently performed using standardized checklists. DATA SYNTHESIS: A total of 45 papers were included in this scoping review, involving 5185 participants with THA. Pelvic tilt was the most common parameter measured in the eligible studies (n = 26). The results were not consistent across all studies; however, it was demonstrated that the distribution of pelvic tilt following THA had a range of 25° posterior to 20° anterior. Moreover, decreased sacral slope and lower pelvic incidence were associated with increased risk of dislocation in patients with THA. Lumbar spine scoliosis did not change significantly after THA in patients with bilateral hip osteoarthritis (5.50°(1.16°) vs. 3.73°(1.16°); P-value = 0.29). Finally, one study indicated that LBP improvement was not correlated with postoperative changes in spinopelvic alignment parameters. Several methodological issues were addressed in this study, including no sample size calculation and no type-I error adjustment for outcome multiplicity. CONCLUSIONS: Changes in spinopelvic alignment may occur after THA and may improve with time. Patients with a THA dislocation usually show abnormal spinopelvic alignment compared to patients without a THA dislocation. LBP usually improves markedly over time following THA.

Dry Needling and Antithrombotic Drugs.

Many clinicians increasingly use dry needling in clinical practice. However, whether patients' intake of antithrombotic drugs should be considered as a contraindication for dry needling has not been investigated to date. As far as we know, there are no publications in analyzing the intake of antiplatelet or anticoagulant agents in the context of dry needling techniques. A thorough analysis of existing medications and how they may impact various needling approaches may contribute to improved evidence-informed clinical practice. The primary purpose of this paper is to review the current knowledge of antithrombotic therapy in the context of dry needling. In addition, reviewing guidelines of other needling approaches, such as electromyography, acupuncture, botulinum toxin infiltration, and neck ultrasound-guided fine-needle aspiration biopsy, may provide specific insights relevant for dry needling. Based on published data, taking antithrombotic medication should not be considered an absolute contraindication for dry needling techniques. As long as specific dry needling and individual risks are properly considered, it does not change the risk and safety profile of dry needling. Under specific circumstances, the use of ultrasound guidance is recommended when available.

Dry needling for the treatment of muscle spasticity in a patient with multiple sclerosis: a case report.

BACKGROUND: Spasticity is a common cause of disability in multiple sclerosis (MS), which can negatively affect the patient's walking and balance. OBJECTIVE: To evaluate the immediate effect of dry needling (DN) on spasticity and mobility in a female with MS. CASE DESCRIPTION: In this case, a 38-year-old female with a 4-year history of MS was treated. The hamstring muscles (biceps femoris and semitendinosus) were needled for 1 minute in a single session. The main outcome measures were the Modified Modified Ashworth Scale (MMAS) to evaluate spasticity, the Timed 25-Foot Walk (T25FW) for the assessment of mobility and leg function performance, and stiffness as a biomechanical index of spasticity measured by a dynamometer. The assessments were done before and immediately after DN. OUTCOMES: The MMAS scores decreased in the hamstrings (1 to 0) and quadriceps (2 to 1). The mobility improved as the time for T25FW decreased from 16.30 to 9.29 seconds. The stiffness of hamstring decreased after treatment (0.451 to 0.312). CONCLUSION: One session of DN for the hamstring muscle decreased spasticity and improved mobility in this patient with MS. Further studies are suggested.

Aquatic Therapy for improving Lower Limbs Function in Post-stroke Survivors: A Systematic Review with Meta-Analysis.

BACKGROUND: Lower limb disability is common in chronic stroke patients, and aquatic therapy is one of the modalities used for the rehabilitation of these patients. OBJECTIVES: To summarize the evidence of the effects of aquatic therapy on lower limb disability compared to land-based exercises in post-stroke patients. METHODS: MEDLINE, PsycInfo, CENTRAL, SPORTDiscus, PEDro, PsycBITE, and OT Seeker were searched from inception to January 2019. The search included only randomized clinical trials. Two reviewers independently examined the full text and conducted study selection, data extraction, and quality assessment. Data synthesis was applied to summarize information from the included studies. The quantitative analysis incorporated fixed-effect models. RESULTS: Of the 150 studies identified in the initial search, 17 trials (629 participants) satisfied the eligibility criteria. Aquatic therapy improved balance based on the Berg Balance Scale (BBS) (standardized mean difference [SMD], 0.72; 95% confidence interval [CI], 0.50-0.94; I2 = 67%) compared with land-based exercises (control). Also, aquatic therapy had a small positive effect on walking speed (SMD, -0.45; 95% CI {-0.71 - (-0.19)}; I2 = 57%), based on the results of the 10-m walking test, compared to controls. Aquatic therapy had a small positive effect on mobility (based on Timed Up and Go), (SMD, -0.43; 95% CI {-0.7-(- 0.17)}; I2 = 71%) compared to land-based exercise (control). CONCLUSIONS: Aquatic therapy had a more positive effect on walking speed, balance, and mobility than land-based exercises. Further research is needed to confirm the clinical utility of aquatic therapy for patients following stroke in the long term.

Efficacy of Dry Needling in Treating Scars following Total Hip Arthroplasty: A Case Report.

Background: In this case report of a 31-year-old female, we describe the effects of dry needling on scar tissue following total hip arthroplasty. Case report: A 31-year-old woman underwent an elective bilateral total hip replacement due to a motor vehicle accident. Based on physical examination, the patient had burning pain at the incision site at the time of menstruation and limited hip range of motion worse on the right side. The treatment program consisted of six sessions of dry needling over a three-week period alongside infrared radiation for 20 minutes during each session. The needles were spaced along the entire length of the scar tissue and rotation was performed back and forth across the scar region to release the adhesion between the scar line and the underlying tissue, focusing more on the painful-to-touch spots and adhesive points. Following the completion of the dry needling treatments hip range of motion and the patient's functional outcome improved. Dry needling may be an effective and rapid treatment for scar tissue adhesion after surgical procedures. High-quality randomized-controlled studies are needed to verify the efficacy of this method.

The efficacy of intramuscular electrical stimulation in the management of patients with myofascial pain syndrome: a systematic review.

INTRODUCTION: Myofascial pain syndrome (MPS) is one of the most common disorders causing chronic muscle pain. Almost one-third of patients with musculoskeletal complaints meet the MPS criteria. The aim of this study is to evaluate the effectiveness of intramuscular electrical stimulation (IMES) in patients with MPS through a systematic review method. METHODS: PubMed, Scopus, Embase, ProQuest, PEDro, Web of Science, and CINAHL were systematically searched to find out the eligible articles without language limitations from 1990 to December 30, 2020. All relevant randomized controlled trials that compared the effectiveness of IMES with sham-IMES, dry needling, or exercise therapy in patients with MPS were included. Full texts of the selected studies were critically appraised using Revised Cochrane risk-of-bias tool for randomized trials (RoB2). RESULTS: Six studies (out of 397) had met our inclusion criteria (involving 158 patients) and were entered to the systematic review. Outcome measures examined in these studies included pain, range of motion, pressure pain threshold, biochemical factors, disability, and amount of analgesic use. In the most studies, it has been shown that IMES is more effective than the control group in improving some outcome measurements such as pain. CONCLUSION: There is preliminary evidence from a few small trials suggesting the efficacy of IMES for the care of myofascial pain syndrome. The data support the conduct of larger trials investigating the efficacy of IMES.

A critical overview of the current myofascial pain literature - January 2021.

Myofascial pain syndrome (MPS), trigger points (TrPs), and dry needling (DN) continue to be of interest to researchers and clinicians worldwide. In this quarterly overview, we included studies from 19 countries, including Pakistan, Iran, Spain, Israel, the US, Australia, Turkey, the UK, China, Italy, Germany, Brazil, Denmark, Canada, Saudi Arabia, Egypt, India, New Zealand, and Thailand. As encouraging as it may be that myofascial pain is being considered worldwide, it is frustrating how many studies do not include a proper control group making them not very useful. It is not clear why researchers would go through the trouble of setting up a study, which requires many hours of work and dedication, and not produce a meaningful paper for clinicians and researchers alike. Fortunately, several papers are high quality studies. This overview covers 39 basic research studies, systematic reviews and meta-analyses, clinical studies, and a few case reports.

Dry Needling for the Treatment of Tension-Type, Cervicogenic, or Migraine Headaches: A Systematic Review and Meta-Analysis.

OBJECTIVE: Dry needling is a treatment technique used by clinicians to relieve symptoms in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. This systematic review's main objective was to assess the effectiveness of dry needling on headache pain intensity and related disability in patients with TTH, CGH, or migraine. METHODS: Medline/PubMed, Scopus, Embase, PEDro, Web of Science, Ovid, Allied and Complementary Medicine Database/EBSCO, Cochrane Central Register of Controlled Clinical Trials, Google Scholar, and trial registries were searched until April 1, 2020, along with reference lists of eligible studies and related reviews. Randomized clinical trials or observational studies that compared the effectiveness of dry needling with any other interventions were eligible for inclusion. Three reviewers independently selected studies, extracted data, and assessed risk of bias. Random-effects meta-analyses were performed to produce pooled-effect estimates (Morris dppc2) and their respective CIs. RESULTS: Of 2715 identified studies, 11 randomized clinical trials were eligible for qualitative synthesis and 9 for meta-analysis. Only 4 trials were of high quality. Very low-quality evidence suggested that dry needling is not statistically better than other interventions for improving headache pain intensity in the short term in patients with TTH (SMD -1.27, 95% CI = -3.56 to 1.03, n = 230), CGH (SMD -0.41, 95% CI = -4.69 to 3.87, n = 104), or mixed headache (TTH and migraine; SMD 0.03; 95% CI = -0.42 to 0.48, n = 90). Dry needling provided significantly greater improvement in related disability in the short term in patients with TTH (SMD -2.28, 95% CI = -2.66 to -1.91, n = 160) and CGH (SMD -0.72, 95% CI = -1.09 to -0.34, n = 144). The synthesis of results showed that dry needling could significantly improve headache frequency, health-related quality of life, trigger point tenderness, and cervical range of motion in TTH and CGH. CONCLUSIONS: Dry needling produces similar effects to other interventions for short-term headache pain relief, whereas dry needling seems to be better than other therapies for improvement in related disability in the short term. IMPACT: Although further high-methodological quality studies are warranted to provide a more robust conclusion, our systematic review suggested that for every 1 or 2 patients with TTH treated by dry needling, 1 patient will likely show decreased headache intensity (number needed to treat [NNT] = 2; large effect) and improved related disability (NNT = 1; very large effect). In CGH, for every 3 or 4 patients treated by dry needling, 1 patient will likely exhibit decreased headache intensity (NNT = 4; small effect) and improved related disability (NNT = 3; medium effect).

Impact of physical therapists' instructions on function and the perception of post-dry needling soreness in mechanical cervical pain; a randomized clinical trial.

BACKGROUND: To investigate the impact of physical therapists' instructions on the perception of post dry needling (DN) soreness and function in patients with mechanical neck pain. METHODS: Seventy-five patients with neck pain were randomly assigned to three groups: "positive" group (n = 25) received positive verbal input; "negative" group (n = 25) received negative verbal input, and control group (n = 25) did not receive any input about post-needling soreness. All three groups received DN of a trigger point in the upper trapezius muscle. The subjective pain experience, pressure pain threshold (PPT), and neck disability Index (NDI) were assessed before and after DN. RESULTS: Patients in all groups showed improvement in pain, PPT and NDI. There were no significant differences in pain (P = 0.41) and PPT (P = 0.68) in the positive and negative groups compared with the control group. Significant difference in function was seen with the NDI after DN of patients in the positive and negative groups compared with the control group (P = 0.011, standard error: 1.08-1.5). CONCLUSION: Considering that the power of our study may be too low to draw more definitive conclusions, DN appears to be an effective technique to improve pain and mechanical hyperalgesia. The experience of post-needling soreness does not appear to influence the outcome of DN on pain, PPT, and NDI. Post-needling soreness does not seem to be a limiting factor in achieving acceptable outcomes, especially when clinicians offer DN within a therapeutic emphasizing a positive patient response. This study questions whether any treatments need to be offered to patients receiving DN.

A critical overview of the current myofascial pain literature - October 2020.

With this edition, we welcome Dr. Orlando Mayoral from Toledo, Spain as a new contributor to this quarterly myofascial literature review. Dr. Mayoral has been studying myofascial pain since the early 1990-ies. He translated the Travell and Simons Trigger Point Manuals into Spanish (Simons et al., 2004), and contributed to many scientific studies, case reports, book chapters, and books (Mayoral del Moral and Salvat Salvat, 2017). In the current review, we included several trigger point (TrP) prevalence studies as well as the usual high volume of dry needling (DN) studies. But of particular interest are the basic research studies that increasingly support multiple aspects of the integrated TrP hypothesis.

Dry Needling for Hamstring Flexibility: A Single-Blind Randomized Controlled Trial.

CONTEXT: Hamstring muscle tightness is one of the most common problems in athletic and healthy people. Dry needling (DN) was found to be an effective approach for improving muscle flexibility, but there is no study to compare this approach with static stretching (SS) as a common technique for the increase of muscle length. OBJECTIVE: To compare the immediate effects of DN and SS on hamstring flexibility in healthy subjects with hamstring tightness. STUDY DESIGN: A single-blind randomized controlled trial. SETTING: A musculoskeletal physiotherapy clinic at Tehran University of Medical Sciences. SUBJECTS: Forty healthy subjects (female: 32, age range: 18-40 y) with hamstring tightness were randomly assigned into 2 groups of DN and SS. INTERVENTION: The DN group received a single session of DN on 3 points of the hamstring muscles, each for 1 minute. The SS group received a single session of SS of the hamstrings, consisting of 3 sets of 30-second SS with a 10-second rest between sets in the active knee extension test (AKET) position. MAIN OUTCOME MEASURES: The AKET, muscle compliance, passive peak torque, and stretch tolerance were measured at the baseline, immediately, and 15 minutes after the interventions. RESULTS: Improvements in all outcomes was better for the DN group than for the SS group. DN increased muscle compliance significantly 15 minutes after the intervention, but it did not improve in the SS group. CONCLUSION: DN is effective in improving hamstring flexibility compared with SS. One session of DN can be an effective treatment for hamstring tightness and increase hamstring flexibility. The improvements suggest that DN is a novel treatment for hamstring flexibility.

A critical overview of the current myofascial pain literature - July 2020.

We are sad to report that following this issue, Dr. Li-Wei Chou will no longer be able to contribute to this quarterly literature overview. Unfortunately, his work responsibilities have increased to such an extent that they need to take priority. On behalf of the team, we would like to thank Dr. Chou for his thoughtful and balanced reviews during the past few years. Not only were we able to include an occasional Chinese-language study, he also was able to assist us in interpreting more complex medical studies. Li-Wei, we wish you all the best professionally and personally, and of course, we cannot wait until our paths will cross again sometime in the future! You may have noted that this overview article was missing from the January 2020 issue of the journal due to an administrative mix up. With the current issue we aimed to catch up and therefore, you will find a greater number of reviewed articles than usual. It becomes increasingly challenging to cover the wide range of the published myofascial pain and trigger point (TrP) literature just due to its volume. In this edition, we included 10 basic research articles, 4 reviews, 14 articles on dry needling (DN), acupuncture, and injections, 3 on manual therapies, and 4 on other clinical approaches.