Accelerated sarcopenia precedes learning and memory impairments in the P301S mouse model of tauopathies and Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) impairs cognitive functions and peripheral systems, including skeletal muscles. The PS19 mouse, expressing the human tau P301S mutation, shows cognitive and muscular pathologies, reflecting the central and peripheral atrophy seen in AD. METHODS: We analysed skeletal muscle morphology and neuromuscular junction (NMJ) through immunohistochemistry and advanced image quantification. A factorial Analysis of Variance assessed muscle weight, NCAM expression, NMJ, myofibre type distribution, cross-sectional areas, expression of single or multiple myosin heavy-chain isoforms, and myofibre grouping in PS19 and wild type (WT) mice over their lifespan (1-12 months). RESULTS: Significant weight differences in extensor digitorum longus (EDL) and soleus muscles between WT and PS19 mice were noted by 7-8 months. For EDL muscle in females, WT weighed 0.0113 ± 0.0005 compared with PS19's 0.0071 ± 0.0008 (P < 0.05), and in males, WT was 0.0137 ± 0.0001 versus PS19's 0.0069 ± 0.0006 (P < 0.005). Similarly, soleus muscle showed significant differences; females (WT: 0.0084 ± 0.0004; PS19: 0.0057 ± 0.0005, P < 0.005) and males (WT: 0.0088 ± 0.0003; PS19: 0.0047 ± 0.0004, P < 0.0001). Analysis of the NMJ in PS19 mice revealed a marked reduction in myofibre innervation at 5 months, with further decline by 10 months. NMJ pre-terminals in PS19 mice became shorter and simpler by 5 months, showing a steep decline by 10 months. Genotype and age strongly influenced muscle NCAM immunoreactivity, denoting denervation as early as 5-6 months in EDL muscle Type II fibres, with earlier effects in soleus muscle Type I and II fibres at 3-4 months. Muscle denervation and subsequent myofibre atrophy were linked to a reduction in Type IIB fibres in the EDL muscle and Type IIA fibres in the soleus muscle, accompanied by an increase in hybrid fibres. The EDL muscle showed Type IIB fibre atrophy with WT females at 1505 ± 110 µm2 versus PS19's 1208 ± 94 µm2, and WT males at 1731 ± 185 µm2 versus PS19's 1227 ± 116 µm2. Similarly, the soleus muscle demonstrated Type IIA fibre atrophy from 5 to 6 months, with WT females at 1194 ± 52 µm2 versus PS19's 858 ± 62 µm2, and WT males at 1257 ± 43 µm2 versus PS19's 1030 ± 55 µm2. Atrophy also affected Type IIX, I + IIA, and IIA + IIX fibres in both muscles. The timeline for both myofibre and overall muscle atrophy in PS19 mice was consistent, indicating a simultaneous decline. CONCLUSIONS: Progressive and accelerated neurogenic sarcopenia may precede and potentially predict cognitive deficits observed in AD.

Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform.

Peritoneal mesothelioma (PM) is a rare malignancy with poor prognosis, representing about 10-15% of all mesothelioma cases. Herein we apply PM patient-derived tumor organoids (PTOs) in elucidating personalized HIPEC responses to bypass rarity of disease in generating preclinical data. Specimens were obtained from PM patients undergoing cytoreductive surgery with HIPEC. PTOs were fabricated with tumor cells suspended in ECM-hydrogel and treated with HIPEC regimen parameters. Viability and characterization analyses were performed post-treatment. Treatment efficacy was defined as ≥ 50% viability reduction and p < 0.05 compared to controls. From October 2020 to November 2022, 17 tumors from 7 patients were biofabricated into organoids, with 16/17 (94.1%) sites undergoing comparative 37° and 42° treatments with cisplatin and mitomycin C (MMC). Hyperthermic cisplatin and MMC enhanced cytotoxicity which reduced treatment viability by 25% and 22%, respectively, compared to normothermia. Heated cisplatin displayed the greatest cytotoxicity, with efficacy in 12/16 (75%) tumors and an average viability of 38% (5-68%). Heated MMC demonstrated efficacy in 7/16 (43.8%) tumors with an average treatment viability of 51% (17-92.3%). PTOs fabricated from distinct anatomic sites exhibited site-specific variability in treatment responses. PM PTOs exhibit patient and anatomic location treatment responses suggestive of underlying disease clonality. In PM organoids cisplatin is superior to MMC in HIPEC.

Quantitative matching of forensic evidence fragments utilizing 3D microscopy analysis of fracture surface replicas.

Silicone casts are widely used by practitioners in the comparative analysis of forensic items. Fractured surfaces carry unique details that can provide accurate quantitative comparisons of forensic fragments. In this study, a statistical analysis comparison protocol was applied to a set of 3D topological images of fractured surface pairs and their replicas to provide confidence in the quantitative statistical comparison between fractured items and their silicone cast replicas. A set of 10 fractured stainless steel samples were fractured from the same metal rod under controlled conditions and were replicated using a standard forensic casting technique. Six 3D topological maps with 50% overlap were acquired for each fractured pair. Spectral analyses were utilized to identify the correlation between topological surface features at different length scales of the surface topology. We selected two frequency bands over the critical wavelength (greater than two-grain diameters) for statistical comparison. Our statistical model utilized a matrix-variate t-distribution that accounts for overlap between images to model match and non-match population densities. A decision rule identified the probability of matched and unmatched pairs of surfaces. The proposed methodology correctly classified the fractured steel surfaces and their replicas with a posterior probability of match exceeding 99.96%. Moreover, the replication technique shows potential in accurately replicating fracture surface topological details with a wavelength greater than 20 µm, which far exceeds the feature comparison range on most metallic alloy surfaces. Our framework establishes the basis and limits for forensic comparison of fractured articles and their replicas while providing a reliable fracture mechanics-based quantitative statistical forensic comparison.

Patient-Reported Physician Treatment Recommendations and Compliance Among U.S. Adults with Low Back Pain.

Objectives: Numerous recently published clinical care guidelines, including the 2017 American College of Physicians (ACP) Guideline for Low Back Pain (LBP), call for nonpharmacological approaches to pain management. However, little data exist regarding the extent to which these guidelines have been adopted by patients and medical doctors. The study objective was to determine patient-reported treatment recommendations by medical doctors for LBP and patient compliance with those recommendations. Design: This study used a cross-sectional web and mail survey. Settings/Location: The study was conducted among Gallup Panel members across the United States. Subjects: Survey participants included 5377 U.S. adults randomly selected among Gallup Panel members. Of those, 545 reported a visit to a medical doctor within the past year for low back pain and were asked a series of follow-up questions regarding treatment recommendations. Interventions: Participants were asked about medical doctor recommendations for both drug (acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, benzodiazepines, Gabapentin, Neurontin, and cortisone injections) and nondrug (self-care treatments, massage, acupuncture, spinal manipulation, and physical therapy) treatments. Outcome Measures: Participants were asked to indicate if their medical doctor recommended each drug and nondrug therapy for their LBP and if they had followed each of those treatment recommendations. Results: Ninety-six percent of patients who visited a medical doctor for LBP received a recommendation for one or more pain treatments, with 81% reporting that their medical doctor recommended both drug and nondrug therapies. Seventy-six percent of respondents were recommended acetaminophen or NSAIDs, 79% were recommended self-care treatments, 37% were recommended massage, acupuncture, or spinal manipulation, and 60% were recommended physical therapy. Nearly two-thirds of our sample reported that their doctor had recommended prescription medications, including opioids, benzodiazepines, Gabapentin, Neurontin, or cortisone injections. Reported adherence to treatment recommendations ranged from 68% for acupuncture to 94% for NSAIDs. Conclusions: One year after publication of the ACP's Guideline on LBP, patients report that medical doctors recommended both pharmacological and nonpharmacological treatment approaches to patients with LBP. In the majority of cases, a combination of prescription medications and self-care were recommended, illustrating the need for additional research on the effectiveness of multi-modal treatment strategies. Patients reported that they were largely compliant with medical doctor recommendations, underscoring the influence that medical doctors have in directing patient care for LBP. These findings indicate that further work is also needed to explore the impact of personal experience, training, clinical evidence, sociocultural factors, and health plans on medical doctors therapeutic recommendations in the context of back pain.

Classification with the matrix-variate-t distribution.

Matrix-variate distributions can intuitively model the dependence structure of matrix-valued observations that arise in applications with multivariate time series, spatio-temporal or repeated measures. This paper develops an Expectation-Maximization algorithm for discriminant analysis and classification with matrix-variate t-distributions. The methodology shows promise on simulated datasets or when applied to the forensic matching of fractured surfaces or the classification of functional Magnetic Resonance, satellite or hand gestures images.

Association Among Opioid Use, Treatment Preferences, and Perceptions of Physician Treatment Recommendations in Patients With Neck and Back Pain.

OBJECTIVE: The purpose of this study was to explore the relationship between self-reported use of opioids by patients with neck and back pain and their demographics, pain characteristics, treatment preferences, and recollections of their physicians' opinions regarding treatment options. METHODS: We analyzed 2017 Gallup Poll survey data from 1680 US adults who had substantial spine pain in the past year and used logistic regression to explore the aforementioned relationships. RESULTS: Our multiple regression analysis indicated that adults with neck or back pain severe enough to have sought health care within the last year were more likely to have used opioids in the last year if they (in descending order of marginal impact) had pain that had lasted 1 year or less (adjusted odds ratio [OR] = 34.35, 90% confidence interval [CI] 17.56-74.32); concurrently used benzodiazepines (OR = 6.02, 90% CI 2.95-12.33); had Medicaid as an insurance source (OR = 3.29, 90% CI 1.40-7.48); indicated that they preferred to use pain medications prescribed by a doctor to treat physical pain (OR = 3.24, 90% CI 1.88-5.60); or were not college educated (OR = 1.83, 90% CI 1.05-3.25). Compared with patients aged 65 years and older, those aged 18 to 34 years were less likely to have used opioids in the past year (OR = 0.09, 90% CI 0.01-0.40, 0.50 for 95% CI). Respondents' perceptions of medical doctors' positive or negative opinions regarding a variety of neck and back pain treatment options were not significantly associated with opioid use. CONCLUSIONS: Patients with neck and back pain who use opioids differ from those who do not use opioids in that they are more likely to have pain that is of shorter duration, to use benzodiazepines, to have Medicaid as an insurance source, and to prefer to use pain medications. Those characteristics should be considered when developing opioid use prevention strategies.

Characteristics of US Adults Who Have Positive and Negative Perceptions of Doctors of Chiropractic and Chiropractic Care.

OBJECTIVE: The purpose of this study was to compare characteristics, likelihood to use, and actual use of chiropractic care for US survey respondents with positive and negative perceptions of doctors of chiropractic (DCs) and chiropractic care. METHODS: From a 2015 nationally representative survey of 5422 adults (response rate, 29%), we used respondents' answers to identify those with positive and negative perceptions of DCs or chiropractic care. We used the χ(2) test to compare other survey responses for these groups. RESULTS: Positive perceptions of DCs were more common than those for chiropractic care, whereas negative perceptions of chiropractic care were more common than those for DCs. Respondents with negative perceptions of DCs or chiropractic care were less likely to know whether chiropractic care was covered by their insurance, more likely to want to see a medical doctor first if they were experiencing neck or back pain, less likely to indicate that they would see a DC for neck or back pain, and less likely to have ever seen a DC as a patient, particularly in the recent past. Positive perceptions of chiropractic care and negative perceptions of DCs appear to have greater influence on DC utilization rates than their converses. CONCLUSION: We found that US adults generally perceive DCs in a positive manner but that a relatively high proportion has negative perceptions of chiropractic care, particularly the costs and number of visits required by such care. Characteristics of respondents with positive and negative perceptions were similar, but those with positive perceptions were more likely to plan to use-and to have already received-chiropractic care.

Effects of spinal manipulation on sensorimotor function in low back pain patients--A randomised controlled trial.

BACKGROUND: Low back pain (LBP) is a major health problem in industrialized societies. Spinal manipulation (SM) is often used for treating LBP, though the therapeutic mechanisms remain elusive. Research suggests that sensorimotor changes may be involved in LBP. It is hypothesized that SM may generate its beneficial effects by affecting sensorimotor functions. OBJECTIVES: To compare changes in sensorimotor function, as measured by postural sway and response to sudden load, in LBP patients following the delivery of high-velocity low amplitude (HVLA)-SM or low-velocity variable amplitude (LVVA)-SM versus a sham control intervention. DESIGN: A three-arm (1:1:1 ratio) randomized controlled trial. METHODS: A total of 221 participants who were between 21 and 65 years, having LBP intensity (numerical rating scale) ≥4 at either phone screen or the first baseline visit and ≥2 at phone screen and both baseline visits, and Quebec Task Force diagnostic classifications of 1, 2, 3 or 7 were enrolled to receive four SM treatments over two weeks. Study outcomes were measured at the first and fifth visits with the examiners blinded from participant group assignment. RESULTS: The LVVA-SM group demonstrated a significant increase in medial-to-lateral postural excursion on the soft surface at the first visit when compared to the control group. No other significant between-group differences were found for the two sensorimotor tests, whether during the first visit or over two weeks. CONCLUSIONS: It appears that short-term SM does not affect the sensorimotor functions as measured by postural sway and response to sudden load in this study.

Similar Effects of Thrust and Nonthrust Spinal Manipulation Found in Adults With Subacute and Chronic Low Back Pain: A Controlled Trial With Adaptive Allocation.

STUDY DESIGN: A three-arm controlled trial with adaptive allocation. OBJECTIVES: The aim of this study was to compare short-term effects of a side-lying, thrust spinal manipulation (SM) procedure and a nonthrust, flexion-distraction SM procedure in adults with subacute or chronic low back pain (LBP) over 2 weeks. SUMMARY OF BACKGROUND DATA: SM has been recommended in recently published clinical guidelines for LBP management. Previous studies suggest that thrust and nonthrust SM procedures, though distinctly different in joint loading characteristics, have similar effects on patients with LBP. METHODS: Participants were eligible if they were 21 to 54 years old, had LBP for at least 4 weeks, scored 6 or above on the Roland-Morris disability questionnaire, and met the diagnostic classification of 1, 2, or 3 according to the Quebec Task Force Classification for Spinal Disorders. Participants were allocated in a 3:3:2 ratio to four sessions of thrust or nonthrust SM procedures directed at the lower lumbar and pelvic regions, or to a 2-week wait list control. The primary outcome was LBP-related disability using Roland-Morris Disability Questionnaire and the secondary outcomes were LBP intensity using visual analog scale, Fear-Avoidance Beliefs Questionnaire, and the 36-Item Short Form Health Survey. The study was conducted at the Palmer Center for Chiropractic Research with care provided by experienced doctors of chiropractic. Clinicians and patients were not blinded to treatment group. RESULTS: Of 192 participants enrolled, the mean age was 40 years and 54% were male. Improvement in disability, LBP intensity, Fear-Avoidance Beliefs Questionnaire-work subscale, and 36-Item Short Form Health Survey-physical health summary measure for the two SM groups were significantly greater than the control group. No difference in any outcomes was observed between the two SM groups. CONCLUSION: Thrust and nonthrust SM procedures with distinctly different joint loading characteristics demonstrated similar effects in short-term LBP improvement and both were superior to a wait list control. LEVEL OF EVIDENCE: 2.

Public Perceptions of Doctors of Chiropractic: Results of a National Survey and Examination of Variation According to Respondents' Likelihood to Use Chiropractic, Experience With Chiropractic, and Chiropractic Supply in Local Health Care Markets.

OBJECTIVES: The purpose of this study was to determine whether general perceptions of doctors of chiropractic (DCs) varied according to likeliness to use chiropractic care, whether particular demographic characteristics were associated with chiropractic care use, and whether perception of DCs varied according to the per-capita supply of DCs in local health care markets. METHODS: We performed a secondary analysis of results from a 26-item nationally representative survey of 5422 members of The Gallup Panel that was conducted in the spring of 2015 (response rate, 29%) that sought to elicit the perceptions and use of DCs by US adults. We compared survey responses across: (1) respondents who had different likelihoods to use DCs for treatment of neck or back pain and (2) respondents who had different experiences using DCs. We linked respondents' zip codes to hospital referral regions for which we had the per-capita supply of DCs. Using the χ(2) test, we examined relationships between likeliness to use a DC, experience using a DC, respondent demographic variables, perceptions of DCs, and the per-capita supply of DCs in the local health care market. RESULTS: Most (61.4%) respondents believed that chiropractic care was effective at treating neck and back pain, 52.6% thought DCs were trustworthy, and 24.2% thought chiropractic care was dangerous; however, as respondents' likelihood to use a DC increased, perceptions of effectiveness and trustworthiness increased, and perceptions of danger decreased. Of all 5422 survey respondents, 744 or 13.7% indicated that they had seen a DC within the last 12 months. As one moved from distant to more recent experience using a DC, respondents were more likely to be female, married, white, and employed; those who had a distant history of using a DC were older and more likely to be retired than the other groups. A higher per-capita supply of DCs was associated with higher utilization rates and showed a more favorable regard for DCs. CONCLUSIONS: US adults often use chiropractic care, generally regard DCs favorably, and largely perceive that chiropractic care is safe. Where there is a higher per-capita supply of DCs in the local health care market, utilization and positive perceptions of chiropractic are higher.

Consensus Recommendations to NCCIH from Research Faculty in a Transdisciplinary Academic Consortium for Complementary and Integrative Health and Medicine.

BACKGROUND: This commentary presents the most impactful, shared priorities for research investment across the licensed complementary and integrative health (CIH) disciplines according to the Academic Consortium for Complementary and Alternative Health Care (ACCAHC). These are (1) research on whole disciplines; (2) costs; and (3) building capacity within the disciplines' universities, colleges, and programs. The issue of research capacity is emphasized. DISCUSSION: ACCAHC urges expansion of investment in the development of researchers who are graduates of CIH programs, particularly those with a continued association with accredited CIH schools. To increase capacity of CIH discipline researchers, we recommend National Center for Complementary and Integrative Health (NCCIH) to (1) continue and expand R25 grants for education in evidence-based healthcare and evidence-informed practice at CIH schools; (2) work to limit researcher attrition from CIH institutions by supporting career development grants for clinicians from licensed CIH fields who are affiliated with and dedicated to continuing to work in accredited CIH schools; (3) fund additional stand-alone grants to CIH institutions that already have a strong research foundation, and collaborate with appropriate National Institutes of Health (NIH) institutes and centers to create infrastructure in these institutions; (4) stimulate higher percentages of grants to conventional centers to require or strongly encourage partnership with CIH institutions or CIH researchers based at CIH institutions, or give priority to those that do; (5) fund research conferences, workshops, and symposia developed through accredited CIH schools, including those that explore best methods for studying the impact of whole disciplines; and (6) following the present NIH policy of giving priority to new researchers, we urge NCCIH to give a marginal benefit to grant applications from CIH clinician-researchers at CIH academic/research institutions, to acknowledge that CIH concepts require specialized expertise to translate to conventional perspectives. SUMMARY: We commend NCCIH for its previous efforts to support high-quality research in the CIH disciplines. As NCCIH develops its 2016-2020 strategic plan, these recommendations to prioritize research based on whole disciplines, encourage collection of outcome data related to costs, and further support capacity-building within CIH institutions remain relevant and are a strategic use of funds that can benefit the nation's health.

Improving Our Nation's Health Care System: Inclusion of Chiropractic in Patient-Centered Medical Homes and Accountable Care Organizations.

OBJECTIVE: This report summarizes the closing plenary session of the Association of Chiropractic Colleges Educational Conference-Research Agenda Conference 2014. The purpose of this session was to examine patient-centered medical homes and accountable care organizations from various speakers' viewpoints and to discuss how chiropractic could possibly work within, and successfully contribute to, the changing health care environment. DISCUSSION: The speakers addressed the complex topic of patient-centered medical homes and accountable care organizations and provided suggestions for what leadership strategies the chiropractic profession may need to enhance chiropractic participation and contribution to improving our nation's health. CONCLUSION: There are many factors involved in the complex topic of chiropractic inclusion in health care models. Major themes resulting from this panel included the importance of building relationships with other professionals, demonstrating data and evidence for what is done in chiropractic practice, improving quality of care, improving health of populations, and reducing costs of health care.

Confidence interval procedures for system reliability and applications to competing risks models.

System reliability depends on the reliability of the system's components and the structure of the system. For example, in a competing risks model, the system fails when the weakest component fails. The reliability function and the quantile function of a complicated system are two important metrics for characterizing the system's reliability. When there are data available at the component level, the system reliability can be estimated by using the component level information. Confidence intervals (CIs) are needed to quantify the statistical uncertainty in the estimation. Obtaining system reliability CI procedures with good properties is not straightforward, especially when the system structure is complicated. In this paper, we develop a general procedure for constructing a CI for the system failure-time quantile function by using the implicit delta method. We also develop general procedures for constructing a CI for the cumulative distribution function (cdf) of the system. We show that the recommended procedures are asymptotically valid and have good statistical properties. We conduct simulations to study the finite-sample coverage properties of the proposed procedures and compare them with existing procedures. We apply the proposed procedures to three applications; two applications in competing risks models and an application with a k-out-of-s system. The paper concludes with some discussion and an outline of areas for future research.

Adding chiropractic manipulative therapy to standard medical care for patients with acute low back pain: results of a pragmatic randomized comparative effectiveness study.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To assess changes in pain levels and physical functioning in response to standard medical care (SMC) versus SMC plus chiropractic manipulative therapy (CMT) for the treatment of low back pain (LBP) among 18 to 35-year-old active-duty military personnel. SUMMARY OF BACKGROUND DATA: LBP is common, costly, and a significant cause of long-term sick leave and work loss. Many different interventions are available, but there exists no consensus on the best approach. One intervention often used is manipulative therapy. Current evidence from randomized controlled trials demonstrates that manipulative therapy may be as effective as other conservative treatments of LBP, but its appropriate role in the healthcare delivery system has not been established. METHODS: Prospective, 2-arm randomized controlled trial pilot study comparing SMC plus CMT with only SMC. The primary outcome measures were changes in back-related pain on the numerical rating scale and physical functioning at 4 weeks on the Roland-Morris Disability Questionnaire and back pain functional scale (BPFS). RESULTS: Mean Roland-Morris Disability Questionnaire scores decreased in both groups during the course of the study, but adjusted mean scores were significantly better in the SMC plus CMT group than in the SMC group at both week 2 (P < 0.001) and week 4 (P = 0.004). Mean numerical rating scale pain scores were also significantly better in the group that received CMT. Adjusted mean back pain functional scale scores were significantly higher (improved) in the SMC plus CMT group than in the SMC group at both week 2 (P < 0.001) and week 4 (P = 0.004). CONCLUSION: The results of this trial suggest that CMT in conjunction with SMC offers a significant advantage for decreasing pain and improving physical functioning when compared with only standard care, for men and women between 18 and 35 years of age with acute LBP.

Effect of spinal manipulation on sensorimotor functions in back pain patients: study protocol for a randomised controlled trial.

BACKGROUND: Low back pain (LBP) is a recognized public health problem, impacting up to 80% of US adults at some point in their lives. Patients with LBP are utilizing integrative health care such as spinal manipulation (SM). SM is the therapeutic application of a load to specific body tissues or structures and can be divided into two broad categories: SM with a high-velocity low-amplitude load, or an impulse "thrust", (HVLA-SM) and SM with a low-velocity variable-amplitude load (LVVA-SM). There is evidence that sensorimotor function in people with LBP is altered. This study evaluates the sensorimotor function in the lumbopelvic region, as measured by postural sway, response to sudden load and repositioning accuracy, following SM to the lumbar and pelvic region when compared to a sham treatment. METHODS/DESIGN: A total of 219 participants with acute, subacute or chronic low back pain are being recruited from the Quad Cities area located in Iowa and Illinois. They are allocated through a minimization algorithm in a 1:1:1 ratio to receive either 13 HVLA-SM treatments over 6 weeks, 13 LVVA-SM treatments over 6 weeks or 2 weeks of a sham treatment followed by 4 weeks of full spine "doctor's choice" SM. Sensorimotor function tests are performed before and immediately after treatment at baseline, week 2 and week 6. Self-report outcome assessments are also collected. The primary aims of this study are to 1) determine immediate pre to post changes in sensorimotor function as measured by postural sway following delivery of a single HVLA-SM or LVVA-SM treatment when compared to a sham treatment and 2) to determine changes from baseline to 2 weeks (4 treatments) of HVLA-SM or LVVA-SM compared to a sham treatment. Secondary aims include changes in response to sudden loads and lumbar repositioning accuracy at these endpoints, estimating sensorimotor function in the SM groups after 6 weeks of treatment, and exploring if changes in sensorimotor function are associated with changes in self-report outcome assessments. DISCUSSION: This study may provide clues to the sensorimotor mechanisms that explain observed functional deficits associated with LBP, as well as the mechanism of action of SM. TRIAL REGISTRATION: This trial is registered in ClinicalTrials.gov, with the ID number of NCT00830596, registered on January 27, 2009. The first participant was allocated on 30 January 2009 and the final participant was allocated on 17 March 2011.

Glucocorticoids suppress growth in neonatal cardiomyocytes co-expressing AT(2) and AT(1) angiotensin receptors.

BACKGROUND: Perinatal glucocorticoid treatment is associated with hypertrophic cardiomyopathy, but the cellular mechanism is controversial. An underlying interaction between glucocorticoids and the renin-angiotensin system may be important, but whether glucocorticoids modulate angiotensin II (AngII)-dependent cardiomyocyte growth responses in the neonate has not been investigated. OBJECTIVES: The major aim of this investigation was to determine whether glucocorticoids modulate the neonatal cardiomyocyte growth response to AngII. In particular we sought evidence to determine whether angiotensin II type 2 (AT(2)) receptor co-expression with angiotensin II type 1 (AT(1)) receptor is of specific importance in this modulatory function. METHODS: In this study, we used AT(1) and AT(2) receptor-expressing adenoviruses (Ad-AT(1) and Ad-AT(2)) in a well-defined in vitro neonatal cardiomyocyte culture model to assess whether glucocorticoids affect cardiomyocyte growth responses (i.e. total protein content). RESULTS: Following addition of AngII (0.1 micromol/l) to neonatal cardiomyocytes infected with Ad-AT(1) alone, a significant growth response was measured (133.2 +/- 4.8%). Expression of Ad-AT(2) alone induced a approximately 20% increase in total cellular protein content, which was unaffected by addition of AngII. Neither corticosterone (1 micromol/l) nor dexamethasone (1 micromol/l) had any significant effect on the AT(1)- or AT(2)-mediated growth responses. In contrast, the growth response to AngII was augmented following co-expression of AT(2) and AT(1) receptors (149.2 +/- 4.2%), which was reduced by approximately 20% in the presence of either corticosterone or dexamethasone (p < 0.05). CONCLUSIONS: The present study provides novel evidence that glucocorticoids suppress neonatal cardiomyocyte growth responsiveness when AT(2 )and AT(1) receptor subtypes are co-expressed.

Health professions education and integrative healthcare.

Over the past three decades, evidence has accumulated that demonstrates that the US healthcare system as currently structured is untenable given the cost of healthcare, poor outcomes associated with this cost, imminent shortages in many categories of health professionals, and underutilization of other health professionals. The system also faces other challenges, such as the lack of access to care and a growing demand by consumers for healthcare that offers choice, quality, convenience, affordability, and personalized care. Workforce analyses estimating needs and anticipated shortages of health professionals are projected on the current healthcare system, which generally does not include integrative healthcare and does not include complementary and alternative medicine (CAM) practitioners. This paper examines the opportunities and implications of going beyond the current paradigm of workforce planning and health professions education and offers recommendations that detail how the health of the public may be served by incorporating an integrative health perspective into health professions education and workforce planning, deployment, and utilization.