A New Instrument for Assessing Work-Related Body Mechanics and Strain in the General Population.

Clinical pain is often linked to poor body mechanics, with individuals sometimes presenting multiple painful disorders. Such disorders may be influenced by behaviors that affect the general resiliency and health of the musculoskeletal system. We aimed to develop a self-reported scale using the Malmö Diet and Cancer Study questions on work-related body mechanical exposures. An expert panel identified 41 variables having content validity for musculoskeletal problems. Exploratory factor analysis was conducted on a random selection of 50% of the cohort (n = 6,789 adults); the remaining was reserved for confirmatory factor analyses (CFA), item response theory (IRT) item calibration, and differential item functioning investigations. Supported by standard measure development methods and fit criteria, the final unidimensional item bank contains 13 items. Overall CFA statistics (root mean square error of approximation = .09; comparative fit index = .96; Tucker-Lewis index = .96; standardized root mean residuals = .05) indicated excellent single-factor model fit and appropriateness of IRT modeling and calibration. Expert review and item information values (score-precision) guided selection of an 8-item short form with acceptable score-level reliabilities (≥.70) for T-scores = 39-80+. This measure provides reliable assessment of body mechanics strain in adults and can be useful when evaluating different contributions to musculoskeletal problems affecting pain-treatment success in future clinical research. PERSPECTIVE: This article presents the development and psychometric properties of a new measure, "Work-related Body Mechanics and Strain Scale (WR-BMSS)." The scale has 13-items or alternatively an 8-item short form. This measure could potentially help clinicians who seek to assess how musculoskeletal problems may contribute to patient pain and disability.

Effects of experimental tooth clenching on pain and intramuscular release of 5-HT and glutamate in patients with myofascial TMD.

OBJECTIVES: It has been suggested that tooth clenching may be associated with local metabolic changes, and is a risk factor for myofascial temporomandibular disorders (M-TMD). This study investigated the effects of experimental tooth clenching on the levels of 5-HT, glutamate, pyruvate, and lactate, as well as on blood flow and pain intensity, in the masseter muscles of M-TMD patients. METHODS: Fifteen patients with M-TMD and 15 pain-free controls participated. Intramuscular microdialysis was performed to collect 5-HT, glutamate, pyruvate, and lactate and to assess blood flow. Two hours after the insertion of a microdialysis catheter, participants performed a 20-minute repetitive tooth clenching task (50% of maximal voluntary contraction). Pain intensity was measured throughout. RESULTS: A significant effect of group (P<0.01), but not of time, was observed on 5-HT levels and blood flow. No significant effects of time or group occurred on glutamate, pyruvate, or lactate levels. Time and group had significant main effects on pain intensity (P<0.05 and <0.001). No significant correlations were identified between: (1) 5-HT, glutamate, and pain intensity; or between (2) pyruvate, lactate, and blood flow. DISCUSSION: This experimental tooth clenching model increased jaw muscle pain levels in M-TMD patients and evoked low levels of jaw muscle pain in controls. M-TMD patients had significantly higher levels of 5-HT than controls and significantly lower blood flow. These 2 factors may facilitate the release of other algesic substances that may cause pain.

Validity and reliability of OIDP and OHIP-14: a survey of Chinese high school students.

BACKGROUND: To determine the impact of oral diseases on everyday life, measures of oral quality of life are needed. In complementing traditional disease-based measures, they assess the need for oral care to evaluate oral health care programs and management of treatment. To assess the reliability and validity of the Oral Impact of Daily Performance (OIDP) and the short-form Oral Health Impact Profile (OHIP-14) among high school students in Xi'an, the capital of Shanxi province, China. METHODS: Cross-sectional one-stage stratified random cluster sample using high schools as the primary sampling unit. Students completed self-administered questionnaires at school. The survey included the OHIP-14 and OIDP inventories, translated and culturally adapted for China, and global oral health and socio-behavioral measures. RESULTS: A total of 5,608 students participated in the study, with a 93% response rate (mean age 17.2, SD 0.8, 52% females, 45.3% urban residents).The proportion experiencing at least one impact (at any frequency) during the previous six months was 62.9% for the OHIP-14 and 45.8% for the OIDP. Cronbach's alpha measured internal consistency at 0.85 for OHIP-14 and 0.75 for OIDP while Cohen's kappa varied between 0.27 and 0.58 for OHIP-14 items and between 0.23 and 0.65 for OIDP items. Kappa scores for the OHIP-14 and OIDP additive scores were 0.52 and 0.66, respectively. Both measures varied systematically and in the expected direction, with global oral health measures showing criterion validity. The correlation between OIDP and OHIP-14 was rs +0.65. That both measures varied systematically with socio-behavioral factors indicates construct validity. CONCLUSION: Both the OIDP and OHIP-14 inventories had reasonable reliability and construct validity in relation to subjective global oral health indicators among adolescents attending high schools in China and thus appear to be useful oral health -related quality of life measures in this context. Overall, the OHIP-14 and OIDP performed equally well, although OHIP-14 had superior content validity due to its sensitivity towards less severe impacts.

A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity.

The combination of immunostimulatory agents with cytotoxic drugs is emerging as a promising approach for potentially curative tumor therapy, but advances in this field are hindered by the requirement of testing individual combination partners as single agents in dedicated clinical studies, often with suboptimal efficacy. Here, we describe for the first time a novel multipayload class of targeted drugs, the immunocytokine-drug conjugates (IDC), which combine a tumor-homing antibody, a cytotoxic drug, and a proinflammatory cytokine in the same molecular entity. In particular, the IL2 cytokine and the disulfide-linked maytansinoid DM1 microtubular inhibitor could be coupled to the F8 antibody, directed against the alternatively spliced EDA domain of fibronectin, in a site-specific manner, yielding a chemically defined product with selective tumor-homing performance and potent anticancer activity in vivo, as tested in two different immunocompetent mouse models.

Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Group†.

AIMS: The original Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I diagnostic algorithms have been demonstrated to be reliable. However, the Validation Project determined that the RDC/TMD Axis I validity was below the target sensitivity of ≥ 0.70 and specificity of ≥ 0.95. Consequently, these empirical results supported the development of revised RDC/TMD Axis I diagnostic algorithms that were subsequently demonstrated to be valid for the most common pain-related TMD and for one temporomandibular joint (TMJ) intra-articular disorder. The original RDC/TMD Axis II instruments were shown to be both reliable and valid. Working from these findings and revisions, two international consensus workshops were convened, from which recommendations were obtained for the finalization of new Axis I diagnostic algorithms and new Axis II instruments. METHODS: Through a series of workshops and symposia, a panel of clinical and basic science pain experts modified the revised RDC/TMD Axis I algorithms by using comprehensive searches of published TMD diagnostic literature followed by review and consensus via a formal structured process. The panel's recommendations for further revision of the Axis I diagnostic algorithms were assessed for validity by using the Validation Project's data set, and for reliability by using newly collected data from the ongoing TMJ Impact Project-the follow-up study to the Validation Project. New Axis II instruments were identified through a comprehensive search of the literature providing valid instruments that, relative to the RDC/TMD, are shorter in length, are available in the public domain, and currently are being used in medical settings. RESULTS: The newly recommended Diagnostic Criteria for TMD (DC/TMD) Axis I protocol includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain-related TMD (sensitivity ≥ 0.86, specificity ≥ 0.98) and for one intra-articular disorder (sensitivity of 0.80 and specificity of 0.97). Diagnostic criteria for other common intra-articular disorders lack adequate validity for clinical diagnoses but can be used for screening purposes. Inter-examiner reliability for the clinical assessment associated with the validated DC/TMD criteria for pain-related TMD is excellent (kappa ≥ 0.85). Finally, a comprehensive classification system that includes both the common and less common TMD is also presented. The Axis II protocol retains selected original RDC/TMD screening instruments augmented with new instruments to assess jaw function as well as behavioral and additional psychosocial factors. The Axis II protocol is divided into screening and comprehensive self report instrument sets. The screening instruments' 41 questions assess pain intensity, pain-related disability, psychological distress, jaw functional limitations, and parafunctional behaviors, and a pain drawing is used to assess locations of pain. The comprehensive instruments, composed of 81 questions, assess in further detail jaw functional limitations and psychological distress as well as additional constructs of anxiety and presence of comorbid pain conditions. CONCLUSION: The recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings. More comprehensive instruments augment short and simple screening instruments for Axis I and Axis II. These validated instruments allow for identification of patients with a range of simple to complex TMD presentations.

Immunocytokines: a review of molecules in clinical development for cancer therapy.

The concept of therapeutically enhancing the immune system's responsiveness to tumors is long standing. Several cytokines have been investigated in clinical trials for their therapeutic activity in cancer patients. However, substantial side effects and unfavorable pharmacokinetic properties have been a major drawback hampering the administration of therapeutically relevant doses. The use of recombinant antibody-cytokine fusion proteins promises to significantly enhance the therapeutic index of cytokines by targeting them to the site of disease. This review aims to provide a concise and complete overview of the preclinical data and clinical results currently available for all immunocytokines having reached clinical development.

Biodistribution studies with tumor-targeting bispecific antibodies reveal selective accumulation at the tumor site.

Bispecific antibodies are proteins that bind two different antigens and may retarget immune cells with a binding moiety specific for a leukocyte marker. A binding event in blood could in principle prevent antibody extravasation and accumulation at the site of disease. In this study, we produced and characterized two tetravalent bispecific antibodies that bind with high affinity to the alternatively-spliced EDB domain of fibronectin, a tumor-associated antigen. The bispecific antibodies simultaneously engaged the cognate antigens (murine T cell co-receptor CD3 and hen egg lysozyme) and selectively accumulated on murine tumors in vivo. The results, which were in agreement with predictions based on pharmacokinetic modeling and antibody binding characteristics, confirmed that bispecific antibodies can reach abluminal targets without being blocked by peripheral blood leukocytes.

Ubiquitin-specific protease 4 inhibits mono-ubiquitination of the master growth factor signaling kinase PDK1.

BACKGROUND: Phosphorylation by the phospho-inositide-dependent kinase 1 (PDK1) is essential for many growth factor-activated kinases and thus plays a critical role in various processes such as cell proliferation and metabolism. However, the mechanisms that control PDK1 have not been fully explored and this is of great importance as interfering with PDK1 signaling may be useful to treat diseases, including cancer and diabetes. METHODOLOGY/PRINCIPAL FINDINGS: In human cells, few mono-ubiquitinated proteins have been described but in all cases this post-translational modification has a key regulatory function. Unexpectedly, we find that PDK1 is mono-ubiquitinated in a variety of human cell lines, indicating that PDK1 ubiquitination is a common and regulated process. Ubiquitination occurs in the kinase domain of PDK1 yet is independent of its kinase activity. By screening a library of ubiquitin proteases, we further identify the Ubiquitin-Specific Protease 4 (USP4) as an enzyme that removes ubiquitin from PDK1 in vivo and in vitro and co-localizes with PDK1 at the plasma membrane when the two proteins are overexpressed, indicating direct deubiquitination. CONCLUSIONS: The regulated mono-ubiquitination of PDK1 provides an unanticipated layer of complexity in this central signaling network and offers potential novel avenues for drug discovery.

Influence of cross-sectional temporomandibular joint tomography on diagnosis and management decisions of patients with temporomandibular joint disorders.

AIM: To assess whether changes in diagnoses and management of temporomandibular joint disorder (TMJD) patients are influenced by radiographic findings and if there is an association between specific radiologic alterations and management strategy changes. METHODS: A total of 204 patients with TMJ symptoms were examined using the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Diagnoses and management were first decided without the aid of radiographs. Management categories were: pharmacology, physiotherapy, counseling and behavioral treatment, occlusal stabilization, surgery, additional examinations, and referrals, each with subcategories. Sagittal TMJ tomograms were assessed for the presence of flattening, erosion, osteophyte, and sclerosis in the TMJ components. Diagnoses and management were reevaluated after gaining access to the radiographs and radiographic classifications. Logistic regression analyses were performed with changes in management as the dependent variable and age and radiographic findings as the independent variables. RESULTS: Diagnosis was changed for 56 patients, mainly from arthralgia to osteoarthritis. Management was changed for 55 patients. Most changes occurred in pharmacology and physiotherapy followed by counseling and behavioral treatment, occlusal stabilization, referrals, additional examinations, and surgery. Changes were mostly within the categories, and the highest number of changes was seen in pharmacology, physiotherapy, and counseling and behavioral treatment. Radiographic degenerative findings increased the chance of change (any change) (odds ratio [OR] ⋝ 2.03) and the chance of change in pharmacology (OR ⋝ 2.56) and physiotherapy (OR = 2.48) separately. No other significant associations were found. CONCLUSION: Radiographic degenerative findings increased the chance of changes in management strategy. However, 73% of the TMJD patients had no changes in management after radiographic examination. In cases with changes, these were mainly adjustments within management categories.

Prediction of postoperative pain after mandibular third molar surgery.

AIMS: To evaluate the predictive potential of preoperative psychological and psychophysiological variables in estimating severity of postoperative pain following mandibular third molar surgery (MTMS). METHODS: Following ethical committee approval and informed consent, 40 consecutive patients scheduled for MTMS were included. Preoperative psychometric indicators of anxiety, depression, and vulnerability were evaluated by patient questionnaires. Thermal thresholds and heat pain perception (1 second phasic stimuli: 44 degrees C to 48 degrees C) were evaluated with quantitative sensory testing techniques. Standardized surgery was performed during local anesthesia. Postoperative pain management was with rescue paracetamol and ibuprofen. The patients were instructed to record each day their pain at rest and during dynamic conditions, and their requirement of analgesics for 14 days following surgery. RESULTS: Thirty-eight patients completed the study. Eight patients were readmitted because of pain. During the postoperative period, one or more episodes of moderate to severe pain (> 30 on a visual analog scale) was reported by 60% (23/38) at rest, 63% (24/38) during mouth-opening, and 73% (28/38) during eating. In a multiple regression model, the combination of psychological vulnerability and heat pain perception rendered a predictive model that could account for 15 to 30% of the variance in postoperative pain during resting and dynamic conditions (P = .03 to .001). CONCLUSION: Implementation of clinically relevant preoperative screening methods may offer more efficacious postoperative pain therapies to pain-susceptible individuals undergoing mandibular third molar surgery. J Orofac Pain 2010;24:189-196.

Osseous changes and condyle position in TMJ tomograms: impact of RDC/TMD clinical diagnoses on agreement between expected and actual findings.

OBJECTIVE: The objective of this study was to evaluate the impact of clinical TMJ diagnosis, gender, and age on the agreement between expected and actual radiographic findings. STUDY DESIGN: A total of 204 patients with TMJ symptoms were examined using the Research Diagnostic Criteria (RDC/TMD). Expected radiographic findings were recorded. TMJ tomograms in closed and open mouth position were assessed for osseous changes and condyle position. Expected and actual findings were compared. Logistic regression analyses were performed with agreement on radiographic findings as the dependent variable and with clinical RDC/TMD diagnoses, gender and age as the independent variables. RESULTS: The number of radiographic findings was mostly underestimated. A clinical diagnosis of osteoarthritis and age increased the chance of overestimating osseous changes. Disc displacement and age decreased the chance of agreement on certain condyle positions. CONCLUSION: Tomography often revealed unexpected findings. It was not possible to select particular patient groups who would benefit more or less from a radiographic examination.