Measurement Properties and Minimal Important Change of the World Health Organization Disability Assessment Schedule 2.0 in Persons With Low Back Pain: A Systematic Review.

OBJECTIVE: To determine the measurement properties and minimal important change (MIC) of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) short (12 questions) and full (36 questions) versions in persons with nonspecific low back pain (LBP). DATA SOURCES: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, APA PsycInfo, and Cochrane Central Register of Controlled Trials (inception to May 2021). STUDY SELECTION: Eligible studies assessed measurement properties or MIC of WHODAS 2.0 in persons with LBP. DATA EXTRACTION: Paired reviewers screened articles, extracted data, and assessed risk of bias using Consensus-Based Standards for Selection of Health Measurement Instruments (COSMIN) and COSMIN-Outcome Measures in Rheumatology checklists. DATA SYNTHESIS: We descriptively synthesized results stratified by measurement property and LBP duration (subacute: 6 weeks to 3 months; chronic: ≥3 months). RESULTS: We screened 297 citations and included 14 studies (reported in 15 articles). Methodological quality of studies was very good for internal consistency and varied between very good and doubtful for construct validity, doubtful for responsiveness, and adequate for all other properties assessed. Evidence suggests that WHODAS 2.0 full version has adequate content validity (2 studies); WHODAS 2.0 short and full versions have adequate structural validity (3 studies), but construct validity is indeterminate (9 studies). WHODAS 2.0 short and full versions have adequate internal consistency (10 studies), and the full version has adequate test-retest and interrater reliability (3 studies) in persons with LBP. Minimal detectable change (MDC) was 10.45-13.99 of 100 for the full version and 8.6 of 48 for the short version in persons with LBP (4 studies). WHODAS 2.0 full version has no floor or ceiling effects, but the short version has potential floor effects in persons with chronic LBP (3 studies). One study estimated MIC for the full version as 4.87 of 100 or 9.74 of 100 (corresponding to 1- and 2-point change on 0- to 10-cm visual analog scale for pain, respectively), and 1 study estimated 3.09-4.68 of 48 for the short version. CONCLUSIONS: In persons with LBP, WHODAS 2.0 full version has adequate content validity, structural validity, internal consistency, and reliability. WHODAS 2.0 short version has adequate structural validity and internal consistency. Construct validity of the short and full versions is indeterminate. Since MDC is estimated to be larger than MIC, users may consider both MIC and MDC thresholds to measure change in functioning for LBP.

Gonadal Hormones and Bone.

In both sexes, estrogen is one of the most essential hormones for maintaining bone integrity. Also, especially in men, androgen has beneficial effects on bone independent of estrogen. However, estrogen replacement therapy for postmenopausal women increases the risk of developing breast cancer and endometrial cancer, and androgen replacement therapy for partial androgen deficiency of the aging male increases the risk of developing prostate cancer. Various mechanisms have been proposed on the effects of gonadal hormones on bone, such as effects through cytokines including IL-6 and effects on the OPG/RANKL ratio. In addition, large amounts of new information deriving from high-throughput gene expression analysis raise the possibility of multiple other effects on bone cells. Both estrogen and androgen exert their effects via the estrogen receptor (ER) or the androgen receptor (AR), which belongs to the nuclear receptor superfamily. Compounds such as selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs) also bind ER and AR, respectively. However, SERMs and SARMs alter the ER or AR structure differently from estrogen or androgen, resulting in other downstream gene responses. As a result they can exert favorable effects on bone while suppressing the undesirable actions of estrogen and androgen. Elucidation of ER and AR ligand-specific and tissue-specific gene regulation mechanisms will also provide information on the signal transduction mechanisms of other nuclear receptors and will be valuable for the development of new therapeutic agents.

The association between psychological and social factors and spinal pain in adolescents.

Spinal pain, back pain, and/or neck pain begins early in life and is strongly associated with spinal pain in adulthood. Understanding the relationship between psychological and social factors and adolescent spinal pain may be important in both the prevention and treatment of spinal pain in this age group. We aimed to determine if psychological and social factors were associated with spinal pain in a cross-sectional study of a school-based cohort of 1279 Danish adolescents aged 11-13, who were categorized into "any" and "substantial" spinal pain. "Substantial spinal pain" was defined as a lifetime frequency of "sometimes" or "often" and a pain intensity of at least two on the revised Faces Pain Scale. Logistic regression analyses, stratified by sex, were conducted for single and all variables together. Eighty-six percent of participants reported "any spinal pain" and 28% reported "substantial spinal pain". Frequency of psychological and social factors was significantly higher in those with spinal pain compared to those without. As the frequency of psychological and social factors increased, the odds of both "any spinal pain" and "substantial spinal pain" also increased.Conclusion: Psychological and social factors may be important determinants in adolescent spinal pain. What is Known: • Spinal pain begins early in life to reach adult levels by age 18. Spinal pain in adolescence is strongly associated with spinal pain in adulthood. • In adults, psychological and social factors and spinal pain are strongly related; however, this relationship in adolescence is poorly understood. What is New: • Adolescents with spinal pain reported a significantly higher frequency of psychological factors and loneliness and lower levels of pupil acceptance. • Adolescents reporting higher levels of loneliness, lower levels of pupil acceptance, and increased frequency of psychological factors had increased odds of reporting "substantial spinal pain".

Healthy and productive workers: using intervention mapping to design a workplace health promotion and wellness program to improve presenteeism.

BACKGROUND: Presenteeism is a growing problem in developed countries mostly due to an aging workforce. The economic costs related to presenteeism exceed those of absenteeism and employer health costs. Employers are implementing workplace health promotion and wellness programs to improve health among workers and reduce presenteeism. How best to design, integrate and deliver these programs are unknown. The main purpose of this study was to use an intervention mapping approach to develop a workplace health promotion and wellness program aimed at reducing presenteeism. METHODS: We partnered with a large international financial services company and used a qualitative synthesis based on an intervention mapping methodology. Evidence from systematic reviews and key articles on reducing presenteeism and implementing health promotion programs was combined with theoretical models for changing behavior and stakeholder experience. This was then systematically operationalized into a program using discussion groups and consensus among experts and stakeholders. RESULTS: The top health problem impacting our workplace partner was mental health. Depression and stress were the first and second highest cause of productivity loss respectively. A multi-pronged program with detailed action steps was developed and directed at key stakeholders and health conditions. For mental health, regular sharing focus groups, social networking, monthly personal stories from leadership using webinars and multi-media communications, expert-led workshops, lunch and learn sessions and manager and employee training were part of a comprehensive program. Comprehensive, specific and multi-pronged strategies were developed and aimed at encouraging healthy behaviours that impact presenteeism such as regular exercise, proper nutrition, adequate sleep, smoking cessation, socialization and work-life balance. Limitations of the intervention mapping process included high resource and time requirements, the lack of external input and viewpoints skewed towards middle and upper management, and using secondary workplace data of unknown validity and reliability. CONCLUSIONS: In general, intervention mapping was a useful method to develop a workplace health promotion and wellness program aimed at reducing presenteeism. The methodology provided a step-by-step process to unravel a complex problem. The process compelled participants to think critically, collaboratively and in nontraditional ways.

The Effectiveness of Multimodal Care for Soft Tissue Injuries of the Lower Extremity: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: The purpose of this systematic review was to evaluate the effectiveness of multimodal care for the management of soft tissue injuries of the lower extremity. METHODS: We systematically searched MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Random pairs of independent reviewers screened studies for relevance and critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. We included studies with a low risk of bias in our best evidence synthesis. RESULTS: We screened 6794 articles. Six studies had a low risk of bias and addressed the following: plantar heel pain (n = 2), adductor-related groin pain (n = 1), and patellofemoral pain (n = 3). The evidence suggests that multimodal care for the management of persistent plantar heel pain may include mobilization and stretching exercise. An intensive, clinic-based, group exercise program (strengthening, stretching, balance, agility) is more effective than multimodal care for the management of adductor-related groin pain in male athletes. There is inconclusive evidence to support the use of multimodal care for the management of persistent patellofemoral pain. Our search did not identify any low risk of bias studies examining multimodal care for the management of other soft tissue injuries of the lower extremity. CONCLUSION: A multimodal program of care for the management of persistent plantar heel pain may include mobilization and stretching exercise. Multimodal care for adductor-related groin pain is not recommended based on the current evidence. There is inconclusive evidence to support the use of multimodal care for the management of persistent patellofemoral pain.

The Effectiveness of Exercise on Recovery and Clinical Outcomes in Patients With Soft Tissue Injuries of the Hip, Thigh, or Knee: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: The purpose of this systematic review was to determine the effectiveness of exercise for the management of soft tissue injuries of the hip, thigh, and knee. METHODS: We conducted a systematic review and searched MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL Plus with Full Text from January 1, 1990, to April 8, 2015, for randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effect of exercise on pain intensity, self-rated recovery, functional recovery, health-related quality of life, psychological outcomes, and adverse events. Random pairs of independent reviewers screened titles and abstracts and assessed risk of bias using the Scottish Intercollegiate Guidelines Network criteria. Best evidence synthesis methodology was used. RESULTS: We screened 9494 citations. Eight RCTs were critically appraised, and 3 had low risk of bias and were included in our synthesis. One RCT found statistically significant improvements in pain and function favoring clinic-based progressive combined exercises over a "wait and see" approach for patellofemoral pain syndrome. A second RCT suggests that supervised closed kinetic chain exercises may lead to greater symptom improvement than open chain exercises for patellofemoral pain syndrome. One RCT suggests that clinic-based group exercises may be more effective than multimodal physiotherapy in male athletes with persistent groin pain. CONCLUSION: We found limited high-quality evidence to support the use of exercise for the management of soft tissue injuries of the lower extremity. The evidence suggests that clinic-based exercise programs may benefit patients with patellofemoral pain syndrome and persistent groin pain. Further high-quality research is needed.

The Association Between Cervical Spine Manipulation and Carotid Artery Dissection: A Systematic Review of the Literature.

OBJECTIVE: Controversy surrounds the safety of cervical spine manipulation. Ischemic stroke secondary to cervical spine manipulation is a hypothesized adverse event. In Canada, the seriousness of these events and their perceived association to cervical spine manipulation has led some members of the public to call for a ban of the procedure. The primary objective of this study was to determine the incidence of internal carotid artery (ICA) dissection after cervical spine manipulation in patients who experience neck pain and its associated disorders. The secondary objective was to determine whether cervical spine manipulation is associated with an increased risk of ICA dissection in patients with neck pain, upper back pain, or headaches. METHODS: We systematically searched MEDLINE, CINAHL, Alternative Health, AMED, Index to Chiropractic Literature, and EMBASE from 1970 to November 2012. Two independent reviewers used standardized criteria to screen the eligibility of articles. We considered cohort studies, case-control studies, and randomized clinical trials that addressed our objectives. We planned to critically appraise eligible articles using the Scottish Intercollegiate Guideline Network methodology. RESULTS: We did not find any epidemiologic studies that measured the incidence of cervical spine manipulation and ICA dissection. Similarly, we did not find any studies that determined whether cervical spine manipulation is associated with ICA dissection. CONCLUSIONS: The incidence of ICA dissection after cervical spine manipulation is unknown. The relative risk of ICA dissection after cervical spine manipulation compared with other health care interventions for neck pain, back pain, or headache is also unknown. Although several case reports and case series raise the hypothesis of an association, we found no epidemiologic studies that validate this hypothesis.

Dentin phosphoprotein binds annexin 2 and is involved in calcium transport in rat kidney ureteric bud cells.

Dentin phosphoprotein (DPP) is the most abundant noncollagenous protein in the dentin, where it plays a major role in the mineralization of dentin. However, we and others have shown that in addition to being present in the dentin, DPP is also present in nonmineralizing tissues like the kidney, lung, and salivary glands, where it conceivably has other functions such as in calcium transport. Because annexins have been implicated as calcium transporters, we examined the relationships between DPP and annexins. In this report, we show that DPP binds to annexin 2 and 6 present in a rat ureteric bud cell line (RUB1). Immunofluorescence studies show that annexin 2 and DPP colocalize in these cells. In addition, DPP and annexin 2 colocalize in the ureteric bud branches of embryonic metanephric kidney. In the RUB1 cells and ureteric bud branches of embryonic kidney, colocalization was restricted to the cell membrane. Studies on calcium influx into RUB cells show that in the presence of anti-DPP, there was a 40% reduction of calcium influx into these cells. We postulate that DPP has different functions in the kidney as compared with the odontoblasts. In the odontoblasts, its primary function is in the extracellular mineralization of dentin, whereas in the kidney it may participate in calcium transport.

Antitumor agent cabozantinib decreases RANKL expression in osteoblastic cells and inhibits osteoclastogenesis and PTHrP-stimulated bone resorption.

Cabozantinib, an inhibitor of vascular endothelial growth factor and hepatocyte growth factor signaling, decreases bone lesions in patients with prostate cancer. To determine direct effects of cabozantinib on bone, resorption in neonatal mouse bone organ culture and on gene expression, proliferation, and phenotypic markers in osteoblast and osteoclast cell lines were examined. Cabozantinib, 0.3 and 3 µM, prevented PTHrP-stimulated calcium release from neonatal mouse calvaria. Since the effect on resorption could reflect effects on osteoblasts to prevent osteoclast activation, or direct inhibition of osteoclasts, responses in osteoblastic and osteoclast precursor cell lines were examined. Twenty-four-hour treatment of osteoblastic MC3T3-E1 cells with 3 µM cabozantinib decreased expression of receptor activator of NFkB ligand (RANKL) and alkaline phosphatase. Forty-eight-hour treatment of MC3T3-E1 cells with 3 µM cabozantinib inhibited cell proliferation and decreased MTT activity. Effects on alkaline phosphatase activity were biphasic, with small stimulatory effects at concentrations below 3 µM. When RAW 264.7 osteoclast precursor cells differentiated with 20 ng/ml RANKL were co-treated for 24 h with 3 µM cabozantinib, expression of RANK, TRAP, cathepsin K, alpha v or beta 3 integrin, or NFATc1 were unaffected. Five-day treatment of RANKL-treated RAW 264.7 cells with 3 µM cabozantinib decreased TRAP and MTT activity. The results suggest that the osteoblast could be the initial target, with subsequent direct and indirect effects on osteoclastogenesis leading to decreased resorption. The multiple effects of cabozantinib on the cell microenvironment of bone are consistent with its effectiveness in reducing lesions from prostate cancer metastases.

Is performance in goal oriented head movements altered in patients with tension type headache?

BACKGROUND: Head repositioning tasks have been used in different experimental and clinical contexts to quantitatively measure motor control performance. Effects of pain on sensorimotor control have often been described in various musculoskeletal conditions and may provide relevant information with regard to potential mechanisms underlying tension-type headaches. The purpose of the current study was to compare the performance of patients with tension-type headache and healthy participants in a cervical aiming task using the Fitts' task paradigm. METHODS: Patients with tension-type headache and healthy controls were compared in a cervical aiming task. Participants were asked to move their head as quickly, and precisely as possible to a target under various experimental conditions. Dependent variables included movement time, variable error, constant error and absolute error. RESULTS: As predicted by Fitts' law, decreasing target size and increasing head rotation amplitudes yielded longer movement times in both groups. Participants with tension-type headache, when compared to healthy participants showed a significant increase in both constant and absolute errors for each of the four conditions. CONCLUSION: Decreased motor performance was observed in participants with tension-type headache, likely due to altered motor control of the neck musculature. Future research is warranted to investigate the clinical aspect related to decrease in motor performance.

The reliability of measuring pain distribution and location using body pain diagrams in patients with acute whiplash-associated disorders.

OBJECTIVE: The objective of this study was to measure the interexaminer reliability of scoring pain distribution using paper and electronic body pain diagrams in patients with acute whiplash-associated disorder and to assess the intermethod reliability of measuring pain distribution and location using paper and electronic diagrams. METHODS: We conducted an interexaminer reliability study on 80 participants recruited from a randomized controlled trial on the conservative management of acute grade I/II whiplash-associated disorder. Participants were assessed for inclusion/exclusion criteria by an experienced clinician. As part of the baseline assessment, participants independently completed paper and electronic pain diagrams. Diagrams were scored independently by 2 examiners using the body region method. Interexaminer and intermethod reliability was computed using intraclass correlation coefficients (ICCs) for pain distribution and κ coefficient for pain location. We used Bland-Altman plots to compute limits of agreement. RESULTS: The interexaminer reliability was ICC = 0.925 for paper and ICC = 0.997 for the electronic body pain diagram. The intermethod reliability for measuring pain distribution ranged from ICC = 0.63 to ICC = 0.93. For pain location, the intermethod reliability varied from κ = 0.23 (posterior neck) to κ = 0.90 (right side of the face). CONCLUSIONS: We found good to excellent interexaminer reliability for scoring 2 versions of the body pain diagram. Pain distribution and pain location were reliably and consistently measured on body pain diagrams using paper and electronic methods; therefore, clinicians and researchers may choose either medium when using body pain diagrams.

The reliability of body pain diagrams in the quantitative measurement of pain distribution and location in patients with musculoskeletal pain: a systematic review.

OBJECTIVE: The purpose of this study was to perform a systematic review of test-retest, intraexaminer, and interexaminer reliability of measuring pain location and distribution using the body pain diagram. METHODS: We conducted a systematic review of the literature using a search conducted in Medline, CINAHL, and Nursing and Allied Health from inception to March 1, 2012. Articles were screened and selected by pairs of reviewers using predetermined inclusion criteria. Internal validity was assessed independently by 2 reviewers using a modified version of the QUADAS instrument. Articles with adequate internal validity were included in the best evidence synthesis. RESULTS: We reviewed 10 studies. Of those, 6 were included in the best evidence synthesis. We found varying levels of evidence that pain location and pain distribution can be measured reliably using the body pain diagram in patients with acute and chronic low back pain with or without radiculopathy. The test-retest reliability for measuring pain distribution ranged from intraclass correlation coefficient of 0.58 to 0.94. Similarly, the test-retest reliability for measuring pain location ranged from kappa (κ) of 0.13 to 0.85. The intraexaminer and interexaminer reliability for measuring pain distribution were intraclass correlation coefficient of 0.99 and 0.99, respectively. The intraexaminer and interexaminer reliability for measuring pain location ranged from κ of 0.77 to 0.88 and 0.61 to 1.00, respectively. CONCLUSIONS: We found important variations in the test-retest reliability of pain location and distribution across different test-retest scenarios and across body regions. The intraexaminer and interexaminer reliability for the measurement of pain distribution and pain location using the body pain diagram in patients with acute and chronic low back pain with or without radiculopathy are adequate.

Risk factors of multiple pulmonary emboli in an elite Ironman triathlete: a case report.

Objective: To present a unique case of pulmonary embolism (PE) in an elite-Ironman triathlete and review athlete-specific risk factors associated with venous thromboembolism (VTE). Case presentation: A 57-year-old male triathlete presented for chiropractic care of midback pain and dyspnea one day before competition. During competition, he was removed and unable to complete the event with dyspnea, chest, and midback pain. Vitals revealed prolonged elevated resting heart rate. He was triaged to the hospital with a high index of suspicion for PE. He was diagnosed with multiple PE in both lungs. Summary: VTE is not normally considered in athletes. A combination of athlete-specific risk factors may predispose athletes to a higher propensity of VTE. Due to life-threatening consequences, it is important to include a differential diagnosis of VTE in patients presenting with midback pain and dyspnea.

Objectif: Présenter un cas unique d'embolie pulmonaire (EP) chez un triathlète Ironman d'élite et passer en revue les facteurs de risque spécifiques aux athlètes associés à la thrombo-embolie veineuse. Présentation du cas: Un triathlète de 57 ans s'est présenté pour des soins chiropratiques en raison de douleurs au milieu du dos et de dyspnée un jour avant la compétition. Pendant la compétition, il a été évacué et incapable de terminer l'épreuve en raison d'une dyspnée, d'une douleur thoracique et d'une douleur lombaire. Les signes vitaux ont révélé une élévation prolongée de la fréquence cardiaque au repos. Il a été transféré à l'hôpital avec une forte suspicion d'EP. On lui a diagnostiqué une EP multiple dans les deux poumons. Synthèse: La thrombo-embolie veineuse n'est normalement pas envisagée chez les athlètes. Une combinaison de facteurs de risque spécifiques aux athlètes peut les prédisposer à une plus grande propension à la thrombo-embolie veineuse. En raison des conséquences potentiellement mortelles, il est important d'inclure un diagnostic différentiel de la thrombo-embolie veineuse chez les patients souffrant de douleurs lombaires et de dyspnée.

Regulation of breast cancer-induced bone lesions by ß-catenin protein signaling.

Breast cancer patients have an extremely high rate of bone metastases. Morphological analyses of the bones in most of the patients have revealed the mixed bone lesions, comprising both osteolytic and osteoblastic elements. ß-Catenin plays a key role in both embryonic skeletogenesis and postnatal bone regeneration. Although this pathway is also involved in many bone malignancy, such as osteosarcoma and prostate cancer-induced bone metastases, its regulation of breast cancer bone metastases remains unknown. Here, we provide evidence that the ß-catenin signaling pathway has a significant impact on the bone lesion phenotype. In this study, we established a novel mouse model of mixed bone lesions using intratibial injection of TM40D-MB cells, a breast cancer cell line that is highly metastatic to bone. We found that both upstream and downstream molecules of the ß-catenin pathway are up-regulated in TM40D-MB cells compared with non-bone metastatic TM40D cells. TM40D-MB cells also have a higher T cell factor (TCF) reporter activity than TM40D cells. Inactivation of ß-catenin in TM40D-MB cells through expression of a dominant negative TCF4 not only increases osteoclast differentiation in a tumor-bone co-culture system and enhances osteolytic bone destruction in mice, but also inhibits osteoblast differentiation. Surprisingly, although tumor cells overexpressing ß-catenin did induce a slight increase of osteoblast differentiation in vitro, these cells display a minimal effect on osteoblastic bone formation in mice. These data collectively demonstrate that ß-catenin acts as an important determinant in mixed bone lesions, especially in controlling osteoblastic effect within tumor-harboring bone environment.

Pre-rehabilitation scores of functioning measured using the World Health Organization Disability Assessment Schedule in persons with nonspecific low back pain: a scoping review.

Knowledge of the pre-rehabilitation generic status of functioning in individuals with low back pain is necessary to understand the clinical utility of rehabilitation care. We conducted a scoping review to describe the pre-rehabilitation functioning status of persons with nonspecific low back pain using the World Health Organization Disability Assessment Schedule (WHODAS)-36 or WHODAS-12. We searched multiple databases from 2010 to 2021 for studies reporting pre-rehabilitation scores using WHODAS in persons with low back pain. Reviewers independently screened articles and extracted data, and we descriptively summarized results by the duration of low back pain (acute/subacute <3 months; chronic ≥3 months), and the WHODAS version. Of 1770 citations screened, eight citations were relevant. Five studies were conducted in Europe, two in America, and one in the African Region (mostly high-income countries). In persons with acute low back pain, the mean WHODAS-36 pre-rehabilitation summary score (complex scoring) was 22.8/100 (SD = 15.4) (one study). In persons with chronic low back pain, the mean WHODAS-36 summary score (complex scoring) ranged from 22.8/100 (SD = 5.7) to 41.5/100 (SD = 13.8) (two studies). For WHODAS-12 in persons with chronic low back pain, the mean summary score was 11.4/48 (SD = 8.7) or 14.4/48 (SD = 9.4) using simple scoring (two studies), and 25.8/100 (SD = 2.2) using complex scoring (one study). No floor or ceiling effects were observed in WHODAS-36 summary scores for chronic low back pain. Our scoping review comprehensively summarizes available studies reporting pre-rehabilitation levels of functioning using WHODAS in persons with low back pain. Persons with low back pain seeking rehabilitation have moderate limitations in functioning, and limitations level tends to be worse with chronic low back pain.

Sex-specific effects of estrogen and androgen on gene expression in human monocyte-derived osteoclasts.

Estrogen and androgen are both critical for the maintenance of bone, but the target cells, mechanisms, and responses could be sex-specific. To compare sex-specific actions of estrogen and androgen on osteoclasts, human peripheral blood mononuclear precursor cells from adult Caucasian males (n = 3) and females (n = 3) were differentiated into osteoclasts and then treated for 24 h with 17ß-estradiol (10 nM) or testosterone (10 nM). Gene expression was studied with a custom designed qPCR-based array containing 94 target genes related to bone and hormone action. In untreated osteoclasts, 4 genes showed significant gender differences. 17ß-estradiol significantly affected 12 genes in osteoclasts from females and 6 genes in osteoclasts from males. Fifteen of the 18 17ß-estradiol-responsive genes were different in the cells from the two sexes; 2 genes affected by 17ß-estradiol in both sexes were regulated oppositely in the two sexes. Testosterone significantly affected 6 genes in osteoclasts from females and 2 genes in osteoclasts from males; all except one were different in the two sexes. 17ß-estradiol and testosterone largely affected different genes, suggesting that conversion of testosterone to 17ß-estradiol had a limited role in the responses. The findings indicate that although osteoclasts from both sexes respond to 17ß-estradiol and testosterone, the effects of both 17ß-estradiol and testosterone differ in the two sexes, highlighting the importance of considering gender in the design of therapy.

Osteoclastogenic activity and RANKL expression are inhibited in osteoblastic cells expressing constitutively active Gα(12) or constitutively active RhoA.

Gα(12)-RhoA signaling is a parathyroid hormone (PTH)-stimulated pathway that mediates effects in bone and may influence genetic susceptibility to osteoporosis. To further elucidate effects of the pathway in osteoblasts, UMR-106 osteoblastic cells were stably transfected with constitutively active (ca) Gα(12) or caRhoA or dominant negative (dn) RhoA and co-cultured with RAW 264.7 cells to determine effects on hormone-stimulated osteoclastogenesis. Whereas PTH and calcitriol-stimulated osteoclastogenesis in co-cultures with UMR-106 cells expressing pcDNA or dominant negative RhoA, the osteoclastogenic effects of PTH and calcitriol were significantly attenuated when the UMR-106 cells expressed either caRhoA or caGα(12). These inhibitory effects were partially reversed by the Rho kinase inhibitor Y27632. None of the constructs affected osteoclastogenesis in untreated co-cultures, and the constructs did not inhibit the osteoclastogenic responses to receptor activator of NFκB ligand (RANKL). To investigate the mechanism of the inhibitory effects of caGα(12) and caRhoA, expression of RANKL, osteoprotegerin (OPG), osteopontin (OPN), and intercellular adhesion molecule-1 (ICAM) in response to PTH or calcitriol was examined in the UMR-106 cells. In the cells expressing pcDNA or dnRhoA, PTH and calcitriol increased RANKL mRNA and decreased OPG mRNA, whereas these effects were absent in the cells expressing caGα(12) or caRhoA. Basal expression of RANKL and OPG was unaffected by the constructs. The results suggest that Gα(12)-RhoA signaling can inhibit hormone-stimulated osteoclastogenesis by effects on expression of RANKL and OPG. Since PTH can stimulate the Gα(12)-RhoA pathway, the current findings could represent a homeostatic mechanism for regulating osteoclastogenic action.

A case-series of patients with musculoskeletal conditions in an underserved community in Moca, Dominican Republic.

PURPOSE: To describe characteristics and activity limitations of new patients with musculoskeletal conditions presenting to the World Spine Care (WSC) clinic located in the underserved community of Moca, Dominican Republic. METHODS: We conducted a prospective case series of consecutive adults between October 12 and December 5, 2015. A survey of valid and reliable measures including: Body pain diagram, Wong-Baker FACES® pain rating scale, Spine Functional Index (SFI), Lower Limb Functional Index (LLFI), Upper Limb Functional Index (ULFI) and the 12-item Short Form Health Survey (SF-12v2) was administered to collect socio-demographics, expectation of recovery, comorbidities, and self-reported health status data. RESULTS: Forty-two patients (23 females and 19 males) were included. The most common primary complaint was lower back pain (40.5%; 17/42) and 57% (24/42) of individuals reported pain that interfered with their ability to function and engage in daily activities. Half of the patients presented with two complaints. Complaints were similar between genders. Most patients (64%; 27/42) reported chronic pain (> 6 months) and 97% (41/42) reported believing that they would recover. Twenty-one percent (9/42) self-reported being diagnosed with depression and/or anxiety at some point in their life. In addition, most (57%; 24/42) individuals reported below average physical and mental health related quality of life. CONCLUSIONS: This study is the first to describe characteristics of patients seeking care at the WSC clinic in Moca, Dominican Republic. Most patients attending the clinic suffer from persistent spine complaints that interfere with their ability to function and engage in daily activities. Nevertheless, the patients have positive expectations of recovery.

Incidence and risk factors for musculoskeletal disorders of the elbow in baseball pitchers: a systematic review of the literature.

OBJECTIVE: To determine the incidence and risk factors of musculoskeletal disorders of the elbow in baseball pitchers. DESIGN: Systematic review. DATA SOURCES: Medline, CINAHL, Cochrane, PubMed and SportDiscus from onset to July 7, 2018. ELIGIBILITY CRITERIA: Eligible studies included randomized controlled trials, cohort studies and case-control studies. Independent pairs of reviewers screened titles and abstracts for eligibility. Relevant articles were critically appraised for internal validity using the SIGN criteria. We included low risk of bias studies in our best evidence synthesis. RESULTS: We retrieved 4502 articles, 39 were critically appraised and nine had a low risk of bias. These were included in the evidence synthesis. The incidence of musculoskeletal disorders of the elbow ranges from 2.3% in adolescent pitchers to 40.6% in youth pitchers. Evidence suggests that pitch characteristics, inadequate rest, biomechanical and anthropometric factors may be risk factors of UCL tears. SUMMARY/CONCLUSION: Baseball pitchers develop musculoskeletal disorders of the elbow. There is little high-quality evidence to understand the etiology. Preliminary evidence suggests the risk factors are multifactorial.PROSPERO Trial Registration Number: CRD42018092081.

OBJECTIF: Établir l'incidence et facteurs de risque de troubles musculosquelettiques du coude chez le lanceur de baseball. MÉTHODOLOGIE: Revue exhaustive. SOURCES DES DONNÉES: Medline, CINAHL, Cochrane, PubMed et SportDiscus depuis le début jusqu'au 7 juillet 2018. CRITÈRES D'ADMISSIBILITÉ: Les études admissibles étaient des essais comparatifs à répartition aléatoire, des études de cohortes et des études de cas-témoins. Des pairs examinateurs indépendants ont trié des titres et des résumés satisfaisant les critères d'admissibilité. On a évalué la validité interne des articles pertinents en utilisant les critères SIGN. On a tenu compte d'un faible risque d'études faussées dans notre meilleure synthèse de preuves. RÉSULTATS: Sur les 4 502 articles retenus, 39 ont été évalués d'une façon critique; neuf présentaient un risque de parti pris. Ceux-ci ont été inclus dans la synthèse de preuves. L'incidence des troubles musculosquelettiques du coude variait de 2,3 % chez les lanceurs adolescents à 40,6 % chez les jeunes lanceurs. Les données semblent indiquer que les caractéristiques du lancer, un repos insuffisant, des facteurs biomécaniques et anthropométriques pourraient être des facteurs de risque de déchirure du ligament collatéral de l'ulna (LCU). RÉSUMÉ/CONCLUSION: Les lanceurs de baseball développent des troubles musculosquelettiques au coude. Il existe peu de preuves de grande qualité permettant de comprendre l'étiologie de ces troubles. Les données préliminaires semblent indiquer que les causes sont multifactorielles.Numéro d'enregistrement d'essai PROSPERO : CRD42018092081.