Comorbidity clusters in generalized osteoarthritis among female patients: A cross-sectional study.

OBJECTIVES: To investigate the prevalence of comorbidities among female patients with generalized osteoarthritis (GOA) in comparison to an age- and sex matched control group. To identify clusters of comorbidities in both groups. METHODS: An observational, cross-sectional study was conducted. Consecutive female patients with hand and knee osteoarthritis according to the American College of Rheumatology (ACR) classification criteria were invited to participate in the study. A control group of participants without musculoskeletal symptoms, history or evidence of osteoarthritis or inflammatory rheumatic disease were also included. Cardiovascular, obstructive pulmonary, gastrointestinal, endocrine, neurological, malignant diseases and depression were recorded in both groups. In both study groups comorbidity cluster and factor analysis was performed. RESULTS: The study population included 200 GOA and 200 control participants. The following comorbidities were observed adjusted to Bonferroni correction with a significantly higher prevalence among individuals with GOA: hypertension, uterine leiomyoma, gastroesophageal reflux disease, diverticulosis, upper gastrointestinal tract ulcers, depression, diseases with vertigo (benign paroxysmal positional vertigo and vertebrobasilar insufficiency) and surgery due to otoclerosis. In the GOA group 5 clusters were identified with different comorbidity patterns. CONCLUSION: We report a high comorbidity rate in GOA. Cluster analysis allowed us to identify different comorbidity subsets for vascular, gastrointestinal and malignant gynaecological disorders. Further research is required to understand the links between GOA and non-musculoskeletal comorbidities.

Cyclin C: The Story of a Non-Cycling Cyclin.

The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5'-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression.

A new psychometric questionnaire for reporting of somatosensory percepts.

OBJECTIVE: There have been remarkable advances over the past decade in neural prostheses to restore lost motor function. However, restoration of somatosensory feedback, which is essential for fine motor control and user acceptance, has lagged behind. With an increasing interest in using electrical stimulation to restore somatosensory sensations within the peripheral (PNS) and central nervous systems (CNS), it is critical to characterize the percepts evoked by electrical stimulation in a standardized manner with a validated psychometric questionnaire. This will allow comparison of results from applications at various nervous system levels in multiple settings. APPROACH: We compiled a summary of published reports of somatosensory percepts that were elicited by electrical stimulation in humans and used these to develop a new psychometric questionnaire. RESULTS: This new questionnaire was able to characterize subjective evoked sensations with good test-retest reliability (Spearman's correlation coefficients ranging 0.716 ⩽ ρ ⩽ 1.000, p ⩽ 0.005) in 13 subjects receiving stimulation through neural implants in both the CNS and PNS. Furthermore, the new questionnaire captured more descriptors (M = 2.65, SD = 0.91) that would have been missed by being categorized as 'other sensations', using a previous questionnaire (M = 1.40, SD = 0.77, t(12) = -10.24, p < 0.001). Lastly, the new questionnaire was able to capture different descriptors within subjects using different patterns of electrical stimulation (Wilk's Lambda = 0.42, F(3, 10) = 4.58, p = 0.029). SIGNIFICANCE: This new somatosensory psychometric questionnaire will aid in establishing consistency and standardization of reporting in future studies of somatosensory neural prostheses.

Treatment of waste thermal waters by ozonation and nanofiltration.

After their use for heating, e.g. in greenhouses, waste thermal waters may cause environmental problems due to their high contents of ions, and in some cases organic matter (associated with an oxygen demand) or toxic compounds. The aims of this work were to decrease the high organic content of waste thermal water by a combination of ozone treatment and membrane separation, and to investigate the accompanying membrane fouling. The results demonstrated that the chemical oxygen demand and the total organic content can be effectively decreased by a combination of ozone pretreatment and membrane filtration. Ozone treatment is more effective for phenol elimination than nanofiltration alone: with a combination of the two processes, 100% elimination efficiency can be achieved. The fouling index b proved to correlate well with the fouling and polarization layer resistances.

Serum 25(OH)-cholecalciferol concentration is associated with hemoglobin level and erythropoietin resistance in patients on maintenance hemodialysis.

BACKGROUND: Resistance to erythropoiesis-stimulating agents (ESAs) has been observed in patients with chronic kidney disease (CKD) and it is associated with clinical outcomes. The presence of ESA resistance cannot always be explained by the known risk factors of the condition, suggesting that additional factors may be involved. We wanted to test the hypothesis that vitamin D insufficiency is associated with lower hemoglobin (Hb) and ESA resistance in patients on maintenance hemodialysis (HD). METHODS: Data from patients receiving maintenance HD in a single dialysis center were extracted from the medical records in a retrospective chart review. Basic patient characteristics and laboratory data including Hb, serum albumin, intact parathyroid hormone and serum 25(OH)-cholecalciferol (25(OH)D(3)) levels were collected. ESA dose and Kt/V were extracted from the dialysis charts. Correlation analysis and multivariate linear regression analysis were used to reveal potential independent associations between clinical and laboratory parameters and ESA resistance. RESULTS: Data from 142 patients were analyzed. Serum 25(OH)D(3) concentration was significantly correlated with Hb (ρ = 0.186, p < 0.05) and also with ESA dose/Hb index (ρ = 0.230, p < 0.01). In multivariable regression analyses, serum 25(OH)D(3) concentration remained significantly associated with both Hb and ESA dose/Hb index after controlling for potentially important confounders. CONCLUSION: Serum 25(OH)D(3) concentration is independently associated with erythropoietin responsiveness in CKD patients on maintenance HD. If this association will be confirmed, treatment trials looking at the effect of vitamin D supplementation on anemia treatment in CKD patients may be warranted.

Behavioral effects of subthalamic deep brain stimulation in Parkinson's disease.

To date, few studies have utilized standardized measures to assess the neurobehavioral changes that can accompany deep brain stimulation (DBS) of the subthalamic nuclei (STN) for the treatment of Parkinson's disease (PD), yet behavioral changes are the most debated among practitioners. We evaluated behavior with the Frontal Systems Behavior Scale (FrSBe), which includes a large-scale normative sample for self- and collateral ratings and is particularly relevant to PD with subscales assessing Apathy, Disinhibition, and Executive Dysfunction. Data were collected from 16 (11 males) PD patients. All FrSBe subscale scores increased significantly when retrospective preoperative scores and current (postoperative) scores were compared. Self- and collateral FrSBe ratings were not significantly correlated with each other, though for both scores at least half of the group met criteria for a clinically significant level of symptoms postoperatively. No significant correlations were seen for collateral current FrSBE ratings with cognitive or motor variables. Higher self-ratings of behavior characteristic of apathy were related to higher self-ratings of depressive symptoms, and to a smaller decrease in antiparkinsonian medications following surgery. We propose that the standardized assessment of behavioral aspects of executive dysfunction adds information that is largely dissociable from the motor and cognitive assessment of function in PD patients undergoing STN DBS. In future, prospective standardized measurement of behavior may allow for better prediction of which patients will experience significant behavioral issues postoperatively.

Erythropoiesis-stimulating agent withdrawal and oxidative stress in hemodialysis.

AIMS: Variation of the action of erythropoiesis-stimulating agent (ESA) may modify oxidative stress in hemodialyzed (HD) patients. Our aim was to follow changes of oxidative stress during withdrawal and subsequent resumption of ESA therapy. PATIENTS AND METHODS: After a 14-day suspension of epoietin-beta treatment, 11 HD patients received epoietin-beta and 10 patients darbepoietin-alpha. The whole blood oxidized and reduced glutathione (GSSG, GSH) and erythrocyte malondialdehyde (E-MDA) concentrations and the erythrocyte superoxide dismutase (E-SOD) and catalase (E-CAT) activities were determined before the ESA-free interval (baseline) and at Weeks 2, 6, 10 and 14. RESULTS: In both groups, the ratios GSSG/ GSH were increased at Weeks 2 and 6 (p < 0.001). The E-MDA levels were elevated (p < 0.01) and the E-SOD activities were decreased (p < 0.001) at Week 6. By Week 14, these markers had returned to the baseline, whereas the GSH (p < 0.001) and E-CAT activity levels (p < 0.001) had increased. CONCLUSIONS: An increase in oxidative stress was revealed by the ratio GSSG/GSH directly after the short-term withdrawal of epoietin-b therapy in HD. This new finding may have implications in conditions involving transiently depressed ESA action. For both ESAs, the early phase of readministration was associated with similarly increased oxidative stress, with a subsequent return to the baseline level.

Deep brain stimulation of the posterior hypothalamic nucleus reverses akinesia in bilaterally 6-hydroxydopamine-lesioned rats.

Deep brain stimulation (DBS) of the basal ganglia motor circuitry is a highly effective treatment for the debilitating motor symptoms of Parkinson's disease (PD). However, recent findings have indicated promising potential for PD therapy with DBS in brain structures outside the basal ganglia. For example, high frequency stimulation of the posterior hypothalamic nucleus (PH) can reverse haloperidol-induced akinesia in rats [Jackson J, Young CK, Hu B, Bland BH (2008) High frequency stimulation of the posterior hypothalamic nucleus restores movement and reinstates hippocampal-striatal theta coherence following haloperidol-induced catalepsy. Exp Neurol 213:210-219]. In the current study, we used the bilateral 6-hydroxydopamine lesion model of Parkinsonian akinesia in male Long-Evans rats to further explore the efficacy of PH DBS. The application of PH DBS in lesioned animals reversed akinesia in an active avoidance paradigm with increased latency compared to pre-lesion performance. The dramatic reversal of akinesia in two models of rodent Parkinsonism by PH DBS warrants further exploration of its therapeutic potential.

Low-intensity pulsed ultrasound for chronic patellar tendinopathy: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Patellar tendinopathy (PT) is a common and significant clinical condition for which there are few established interventions. One intervention that is currently being used clinically to manage PT symptoms is the introduction of low-intensity pulsed ultrasound (LIPUS). The aim of this study was to investigate the clinical efficacy of LIPUS in the management of PT symptoms. METHODS: A randomized, double-blind, placebo-controlled study was conducted. Volunteers with clinically and radiologically confirmed PT were randomly allocated to either an active-LIPUS (treatment) or inactive-LIPUS (placebo) group. LIPUS was self-administered by participants for 20 min/day, 7 days/week for 12 weeks. All participants also completed a daily, standardized eccentric exercise programme based on best practice. Primary outcomes were change in pain during the participant's most aggravating activity in the preceding week, measured on 10 cm visual analogue scales for both usual (VAS-U) and worst (VAS-W) tendon pain. RESULTS: Out of 156 individuals who volunteered, 37 met the eligibility criteria and were randomized to either active-LIPUS (n = 17) or inactive-LIPUS (n = 20). Using an intention-to-treat analysis, VAS-U and VAS-W for the entire cohort decreased by 1.6 +/- 1.9 cm (P < 0.01) and 2.5 +/- 2.4 cm (P < 0.01), respectively. There were no differences between the active- and inactive-LIPUS groups for change in VAS-U (-0.2 cm; 95% CI, -1.5, 1.1 cm) (P = 0.74) or VAS-W (-0.5 cm; 95% CI, -2.1, 1.1 cm) (P = 0.57). A per-protocol analysis provided similar results. CONCLUSIONS: These findings suggest that LIPUS does not provide any additional benefit over and above placebo in the management of symptoms associated with PT.

Surgery for Parkinson's disease improves disability but not impairment components of the UPDRS-II.

The Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (ADL) items have been described as reflecting both disability (true ADL items) and impairment (rather than ADLs). As a result of combining these scores, UPDRS part II scores may not accurately reflect the impact of surgery on ADLs [Hariz G.M., Lindberg M., Hariz M.I., Bergenheim A.T. Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation. Mov Disord 2003;18:373-81.]. The goal of the present study was to assess the metric properties of the ADL section of the UPDRS in terms of its ability to measure surgical change. We tested the effects of unilateral pallidotomy (N=14) and bilateral subthalamic nucleus (STN) DBS (N=11) on both disability and impairment components of the UPDRS-II at uniform follow-up assessment periods of 6 months and 1 year, with a subset of pallidotomy patients (N=9) re-assessed at 2 years. Across the follow-up periods in both patient groups, items identified as best reflecting disability showed significant improvement from pre-surgical levels, whereas items representing impairment showed no overall change. Consistent with this, change in total ADL scores was tempered by the inclusion of the impairment items. Because the measurement of a patient's functional status is important in determining the effectiveness of an intervention, analysis of appropriate items from the UPDRS ADL section is imperative.

Navicular stress fractures: outcomes of surgical and conservative management.

OBJECTIVE: To compare the long term outcomes of the two treatment options for navicular stress fractures: non-weightbearing cast immobilisation and surgical fixation. DESIGN: Retrospective case study. PARTICIPANTS: Subjects aged 18 years and older who had been treated for a navicular stress fracture more than two years previously. MAIN OUTCOME MEASURES: Questionnaire based analogue pain score and function score; tenderness on palpation; abnormality detected on computed tomography (CT). RESULTS: In all, 32 fractures in 26 subjects were investigated. No significant differences were found between surgical and conservative management for current pain (p = 0.984), current function (p = 0.170), or abnormality on CT (p = 0.173). However, surgically treated patients more often remained tender over the "N spot" (p = 0.005), even after returning to competition for two years or more. CONCLUSIONS: Surgical fixation of navicular stress fractures appears to be as effective as conservative management over the longer term. However, there remains a small but measurable degree of pain and loss of function over this period. The value of using "N spot" tenderness as the sole clinical predictor of treatment success requires further investigation, as some patients remained tender despite successful completion of treatment and return to competition.

Referrals for movement disorder surgery: under-representation of females and reasons for refusal.

OBJECTIVE: Referral of movement disorder patients for deep brain stimulation surgery was examined to determine whether referred patients were representative of gender proportions in our population, and reasons why patients do not proceed to surgery. METHODS: Demographic information on referrals to the surgical program was retrospectively reviewed from our database and from a detailed chart review. RESULTS: Although almost equal numbers of movement disorder patients are male and female, of the 91 patients referred for surgery, only 31% were female. Sixty-one percent of referred patients did not undergo surgery. Of these, the majority were denied for medical reasons, including cognitive decline (21%), psychiatric concerns (5%) and neurological reasons (42%). CONCLUSIONS: Almost one-third of patients referred for movement disorder surgery were denied for medical reasons. This underscores the importance of evaluation of all potential patients by a multidisiplinary team to fully assess suitablity for stereotactic surgery. Interestingly, women were under-represented in those referred. In order that all appropriate patients have the opportunity to consider surgery, education of both physicians and patients, and different strategies to approach females regarding surgery may allow more patients to benefit from this treatment.

Is vascularity more evident after exercise? Implications for tendon imaging.

OBJECTIVE: The objective of our study was to investigate the effect of activity on tendon vascularity in 17 abnormal patellar tendons. CONCLUSION: Tendon vascularity is significantly increased by activity (p < 0.001). From this finding, we infer that imaging abnormal tendons with color Doppler sonography to detect neovascularization may be most useful after the patient exercises. Investigations to determine how much activity is necessary to ensure maximal vascularity is detected by Doppler sonography are required.

High reproducibility of patellar tendon vascularity assessed by colour Doppler ultrasonography: a reliable measurement tool for quantifying tendon pathology.

BACKGROUND: This study examined whether patellar tendon vascularity could be quantified accurately in the clinical setting using colour Doppler ultrasonography. METHODS: A sonographer and two radiologists visually estimated tendon vascularity in millimetres in 74 tendons during ultrasound (US) examination and from hard copy films. These estimates were then compared to the length of vessels measured from the digital image in millimetres and the correlation between them was determined. A subset of 16 tendons was used to compare the estimates of vascularity by two examiners at US examination. RESULTS: The estimation of vascular length at US examination correlated highly with the measured vascular length (r = 0.92; 95% confidence interval (CI) 0.87 to 0.94), as did the length estimated from the films (r = 0.94; 95% CI 0.9 to 0.96). The correlation between examiners was 0.84 (95% CI 0.51 to 0.94) for the estimates made during US examination and 0.85 (95% CI 0.59 to 0.95) for the vessel lengths measured from the digital images. CONCLUSIONS: These excellent correlations indicate that tendon vascularity can be reliably estimated using colour Doppler ultrasonography and tendon vascularity could therefore be used by clinicians to rate clinical change. This method of quantifying tendon vascularity could also be used in research to investigate the effects of tendon treatments on vascularity.

Cadmium induced apoptotic changes in chromatin structure and subphases of nuclear growth during the cell cycle in CHO cells.

CHO cells were grown in the presence of 1 mu M CdCl(2) and subjected to ATP-dependent replicative DNA synthesis after permeabilization. By decreasing the density of the cell culture replicative DNA synthesis was diminishing. At higher than 2 x 10(6) cell/ml concentration Cd had virtually no effect on the rate of DNA replication. Growth at higher cell concentrations could be suppressed by increasing Cd concentration. After Cd treatment cells were synchronized by counterflow centrifugal elutriation. Cadmium toxicity on cell growth in early and mid S phase led to the accumulation of enlarged cells in late S phase. Flow cytometry showed increased cellular and nuclear sizes after Cd treatment. As the cells progressed through the S phase, 11 subpopulations of nuclear sizes were distinguished. Apoptotic chromatin changes were visualized by fluorescent microscopy in a cell cycle dependent manner. In the control untreated cells the main transitory forms of chromatin corresponded to those we have published earlier (veil-like, supercoiled chromatin, fibrous, ribboned structures, chromatin strings, elongated prechromosomes, precondensed chromosomes). Cadmium treatment caused: (a) the absence of decondensed veil-like structures and premature chromatin condensation in the form of apoptotic bodies in early S phase (2.2-2.4 average C-value), (b) the absence of fibrous structures, the lack of supercoiled chromatin, the appearance of uncoiled ribboned chromatin and perichromatin semicircles, in early mid S phase (2.5-2.9 C), (c) the presence of perichromatin fibrils and chromatin bodies in mid S phase (2.9-3.2 C), (d) early intra-nuclear inclusions, elongated forms of premature chromosomes, the extrusion and rupture of nuclear membrane later in mid S phase (3.3-3.4 C), (e) the exclusion of chromatin bodies and the formation of clusters of large-sized perichromatin granules in late S phase (3.5-3.8 C) and (f) large extensive disruptions and holes in the nuclear membrane and the clumping of incompletely folded chromosomes (3.8-4. C).

Eccentric decline squat protocol offers superior results at 12 months compared with traditional eccentric protocol for patellar tendinopathy in volleyball players.

BACKGROUND: Conservative treatment of patellar tendinopathy has been minimally investigated. Effective validated treatment protocols are required. OBJECTIVES: To investigate the immediate (12 weeks) and long term (12 months) efficacy of two eccentric exercise programmes for the treatment of patellar tendinopathy. METHODS: This was a prospective randomised controlled trial of 17 elite volleyball players with clinically diagnosed and imaging confirmed patellar tendinopathy. Participants were randomly assigned to one of two treatment groups: a decline group and a step group. The decline group were required to perform single leg squats on a 25 degrees decline board, exercising into tendon pain and progressing their exercises with load. The step group performed single leg squats on a 10 cm step, exercising without tendon pain and progressing their exercises with speed then load. All participants completed a 12 week intervention programme during their preseason. Outcome measures used were the Victorian Institute of Sport Assessment (VISA) score for knee function and 100 mm visual analogue scale (VAS) for tendon pain with activity. Measures were taken throughout the intervention period and at 12 months. RESULTS: Both groups had improved significantly from baseline at 12 weeks and 12 months. Analysis of the likelihood of a 20 point improvement in VISA score at 12 months revealed a greater likelihood of clinical improvements in the decline group than the step group. VAS scores at 12 months did not differ between the groups. CONCLUSIONS: Both exercise protocols improved pain and sporting function in volleyball players over 12 months. This study indicates that the decline squat protocol offers greater clinical gains during a rehabilitation programme for patellar tendinopathy in athletes who continue to train and play with pain.

Are unilateral and bilateral patellar tendinopathy distinguished by differences in anthropometry, body composition, or muscle strength in elite female basketball players?

BACKGROUND: Overuse injury to the patellar tendon (patellar tendinopathy) is a major reason for interrupted training and competition for elite athletes. In both sexes, the prevalence of unilateral and bilateral tendinopathy has been shown to differ. It has been proposed that bilateral pathology may have a different aetiology from unilateral pathology. Investigation of risk factors that may be unique to unilateral and bilateral patellar tendinopathy in female athletes may reveal insights into the aetiology of this condition. OBJECTIVES: To examine whether anthropometry, body composition, or muscle strength distinguished elite female basketball players with unilateral or bilateral patellar tendinopathy. METHODS: Body composition, anthropometry, and muscle strength were compared in elite female basketball players with unilateral (n = 8), bilateral (n = 7), or no (n = 24) patellar tendinopathy. Body composition was analysed using a dual energy x ray absorptiometer. Anthropometric measures were assessed using standard techniques. Knee extensor strength was measured at 180 degrees /s using an isokinetic dynamometer. z scores were calculated for the unilateral and bilateral groups (using the no tendinopathy group as controls). z scores were tested against zero. RESULTS: The tibia length to stature ratio was approximately 1.3 (1.3) SDs above zero in both the affected and non-affected legs in the unilateral group (p<0.05). The waist to hip ratio was 0.66 (0.78) SD above zero in the unilateral group (p<0.05). In the unilateral group, leg lean to total lean ratio was 0.42 (0.55) SD above zero (p<0.07), the trunk lean to total lean ratio was 0.63 (0.68) SD below zero (p<0.05), and leg fat relative to total fat was 0.47 (0.65) SD below zero (p<0.09). In the unilateral group, the leg with pathology was 0.78 (1.03) SD weaker during eccentric contractions (p<0.07). CONCLUSIONS: Unilateral patellar tendinopathy has identifiable risk factors whereas bilateral patellar tendinopathy may not. This suggests that the aetiology of these conditions may be different. However, interpretation must respect the limitation of small subject numbers.