Unsymmetrical DMH – An isomer of 1,2 DMH – Is it potent to induce gastrointestinal carcinoma in rats?

Very few animal studies have used 1,1-dimethyl hydrazine (unsymmetrical dimethyl hydrazine – UDMH) as a carcinogen. This study was designed to investigate the carcinogenicity of UDMH in the gastrointestinal tract in a rat model. We wanted to observe if there were any changes in tissue zinc levels and tissue copper zinc superoxide dismutase (CuZnSOD) enzyme activity during the carcinogenic process, and to compare these values with those of control rats in the medium- and long-term. Six-week-old Wistar rats were given a subcutaneous injection of UDMH (30 mg/kg body wt) twice a week for 20 weeks, and sacrificed after 5 and 9 months of treatment. Tissue zinc levels showed a significant decrease (p<0.05) in the large intestine at 9 months, whereas in the stomach and small intestine there were no significant changes at 5 and 9 months. Tissue CuZnSOD enzyme activity in the stomach, small intestine and large intestine showed no significant decrease at 5 and 9 months as compared to controls. Histologically, the large intestine was normal at 9 months.

This study suggests that UDMH administered at the above dosage was not carcinogenic in this model.     

Prediction of an unfavourable course of low back pain in general practice: comparison of four instruments

BACKGROUND: Several instruments can be used to identify patients with an unfavourable course of low back pain in general practice. However, it is unclear which instrument is the predictor of outcome. AIM: To compare the predictive performance (that is, calibration and discrimination) of risk estimation by GPs with assessments using the Orebro Musculoskeletal Pain Screening Questionnaire, the Low Back Pain Perception Scale (LBPPS), and a prediction rule developed for this purpose. Design of study: A prospective cohort study with 1-year follow-up. SETTING: General practice in The Netherlands. METHOD: The outcome 'unfavourable course of low back pain' was defined as having no clinically important improvement at minimally 50% of the measurements at 6, 13, 26, and 52 weeks. Logistic regression analyses were used to study associations between potential predictors and outcome. RESULTS: In total, 60 GPs recruited 314 patients to the study (16 patients were excluded from analysis due to missing data on the course of low back pain). Over a third of patients (112/298) showed an unfavourable course of low back pain on follow-up. Risk estimation by GPs, the Orebro questionnaire, the LBPPS, and the prediction rule had discriminative ability (area under the curve) of 0.59 (95% CI [confidence intervals] = 0.52 to 0.66); 0.61 (95% CI = 0.54 to 0.67); 0.59 (95% CI = 0.52 to 0.66); and 0.75 (95% CI = 0.69 to 0.81) respectively. The prediction rule included history of low back pain, self-perceived risk to develop chronic low back pain, no solicitous responses of the patient's partner (as reported by the patient), frequent walking at work, and 'pain catastrophising'. CONCLUSION: Although the prediction rule performed best with regard to calibration and discrimination, it needs to be externally validated. Risk estimation by GPs performs as well as other instruments and, at present, seems to be the best available option.     

Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice

Chemerin is an adipokine that regulates adipogenesis and metabolic functions of mature adipocytes mainly through the activation of chemokine‐like receptor 1 (CMKLR1). Elevated levels of chemerin have been found in individuals with obesity, type 2 diabetes, and osteoporosis. This adipokine was identified as an inflammatory and metabolic syndrome marker. Considering that the association between metabolic syndrome and bone health remains unclear, the present study aimed to clarify the role of chemerin in the pathophysiology of bone loss induced by dyslipidemia, particularly modulating osteoclastogenesis. In vitro analyses showed a downregulation of CMKLR1 at the early stage of differentiation and a gradual increase at late stages. Strikingly, chemerin did not modify osteoclast differentiation markers or osteoclast formation; however, it increased the actin‐ring formation and bone resorption activity in mature osteoclasts. The increased bone resorption activity induced by chemerin was effectively inhibited by CMKLR1 antagonist (CCX832). Chemerin boosting mature osteoclast activity involves ERK5 phosphorylation. Moreover, two models of dyslipidemia (high‐fat diet [HFD]‐treated C57/BL6 and db/db mice) exhibited significantly increased level of chemerin in the serum and gingival tissue. Morphometric analysis showed that HFD‐treated and db/db mice exhibited increased alveolar bone loss compared to respective control mice, which was associated with an up‐regulation of chemerin, CMKLR1 and cathepsin K mRNA expression in the gingival tissue. The treatment of db/db mice with CCX832 effectively inhibited bone loss. Antagonism of chemerin receptor also inhibited the expression of cathepsin K in the gingival tissue. Our results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis. © 2016 American Society for Bone and Mineral Research.     

Residency application statements can predict postresidency training

We sought to evaluate whether residency application statements regarding expected career paths are accurate predictors of early postresidency career paths. We evaluated 162 residents who completed a categorical medicine residency at Georgetown University Hospital between 1990 and 1998 to determine if their stated career plans (generalist practice, subspecialization, or undecided) at application predicted activity immediately after residency. Of 130 residents with defined postresidency plans at application, most 78 (60%) followed those career paths after graduation; 18 (67%) of 27 pursued their initial interest in generalist practice, and 60 (58%) of 103 pursued their stated interest in subspecialty training. We also noted a movement of residents toward generalism (79 [49%] of 162), despite low initial interest (27 [17%] of 162).     

Hip Labral Reconstruction: Techniques and Outcomes

Purpose of ReviewWith increased understanding of the biomechanical function of the acetabular labrum, more attention has been directed towards surgical techniques that preserve or restore normal joint anatomy. While labral repair has been shown to produce superior outcomes to labral debridement, repair is not always possible in the setting of severe labral intrasubstance tearing or deficiency. These patients were previously left without suitable arthroscopic treatment options.Recent FindingsLabral reconstruction is an emerging procedure that has been shown to offer promising outcomes for traditionally difficult-to-treat hip pathology. Short- and mid-term follow-up studies have consistently demonstrated significant improvement in patient-reported outcomes, function, and patient satisfaction postoperatively, often despite less favorable preoperative characteristics.SummaryLabral reconstruction is a viable arthroscopic treatment option that has been shown to reliably produce clinically meaningful results in patients with severe labral pathology that is not amenable to repair/refixation or augmentation.     

Increasing sexually transmitted infection rates in young men having sex with men in the Netherlands, 2006–2012

Background

Men having sex with men (MSM) remain the largest high-risk group involved in on-going transmission of sexually transmitted infections (STI), including HIV, in the Netherlands. As risk behaviour may change with age, it is important to explore potential heterogeneity in risks by age. To improve our understanding of this epidemic, we analysed the prevalence of and risk factors for selected STI in MSM attending STI clinics in the Netherlands by age group.

Methods

Analysis of data from the national STI surveillance system for the period 2006–2012. Selected STI were chlamydia, gonorrhoea, infectious syphilis and/or a new HIV infection. Logistic regression was used to identify factors associated with these selected STI and with overall STI positivity. Analyses were done separately for MSM aged younger than 25 years and MSM aged 25 years and older.

Results

In young MSM a significant increase in positivity rate was seen over time (p?<?0.01), mainly driven by increasing gonorrhoea diagnoses, while in MSM aged 25 and older a significant decrease was observed (p?<?0.01). In multivariate analyses for young MSM, those who were involved in commercial sex were at higher risk (OR: 1.5, 95% CI: 1.2-1.9). For MSM aged 25 years and older this was not the case. Having a previous negative HIV test was protective among older MSM compared to those not tested for HIV before (OR: 0.8, 95% CI: 0.8-0.8), but not among younger MSM.

Conclusions

MSM visiting STI clinics remain a high-risk group for STI infections and transmission, but are not a homogenous group. While in MSM aged older than 25 years, STI positivity rate is decreasing, positivity rate in young MSM increased over time. Therefore specific attention needs to be paid towards targeted counselling and reaching particular MSM sub-groups, taken into account different behavioural profiles.