Effects of dietary conjugated linoleic acid on DNA adduct formation of PhIP and IQ after bolus administration to female F344 rats

Meats cooked at high temperatures contain mutagenic heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In female Fischer 344 rats, IQ is a multiorgan carcinogen, whereas PhIP induces mammary adenocarcinomas. For IQ and PhIP, N-hydroxylation, catalyzed by microsomal cytochrome P-450 1A1 and/or 1A2, and then esterification, especially O-acetylation, are the principal steps leading to DNA adduct formation. Conjugated linoleic acid (CLA) is a mixture of conjugated linoleic acid isomers found in various meat and dairy products. We have examined the effect of dietary CLA on DNA adduct formation by PhIP and IQ in female Fischer 344 rats. Four-week-old animals were maintained on AIN-76A diet without or with CLA (4% wt/wt) and treated with IQ or PhIP (50 mg/kg by gavage) after two weeks. Animals were killed (4/group) one, four, and eight days later. DNA isolated from mammary epithelial cells, liver, colon, and white blood cells was analyzed for carcinogen-DNA adducts by 32P-postlabeling assays. On Day 1, dietary CLA significantly inhibited adduct formation (82.0%) in mammary epithelial cells in IQ--but not in PhIP-treated rats. In the colon, dietary CLA significantly inhibited PhIP-DNA adduct formation (18.7%) on Day 8 but increased IQ-DNA adduct formation (30.5%) on Day 8. Dietary CLA had no effect on adduct levels in liver or white blood cells. Calf thymus DNA was incubated with N-hydroxy-PhIP or -IQ in the presence of acetyl-CoA. Enzymatic activation was catalyzed by liver or mammary cytosol. A two-week pretreatment with 2% (wt/wt) dietary CLA had no effect on O-acetyltransferase-catalyzed IQ- or PhIP-DNA adduct formation. It is concluded, under certain conditions, that dietary CLA can lower IQ- and PhIP-DNA adduct formation. Overall, however, the major mode of action of CLA is probably by a mechanism other than the inhibition of the N-hydroxylation and subsequent O-acetylation of PhIP or IQ.     

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.     

Pupil Dilation May Affect Retinal Vessel Caliber Measures

Purpose: To assess the effect of pupil dilation on measures of retinal vessel caliber.

Design: Observational study with self-comparisons

Methods: Retinal photographs were taken for both eyes of 25 subjects before and after pupil dilation. Three photographic graders, masked to pupil dilation status, measured the same set of images using a computer-assisted, semi-automatic method. We compared means (standard deviations) of retinal arteriolar caliber equivalent (CRAE) and retinal venular caliber equivalent (CRVE) of the same eyes between pre- and post-dilation images. We assessed concordance correlation coefficients (CC), Bland Altman limits-of-agreements, and used linear mixed models to assess CRAE and CRVE measures associated with pupil dilation (influencing image quality), graders (observers) and right-left eye variation.

Results: We found high CCs for CRAE (0.82-0.94) and CRVE (0.87-0.94) between pre- and post-dilation images of the same eyes across the graders. Bland Altman plots showed that mean differences ranged from 0.55-3.42μm for CRAE and 1.56-2.29μm for CRVE. After adjusting for right-left eye random variation, a significant fixed effect of dilation was evident in mean CRAE in two of the three graders. There was no significant fixed effect of dilation in mean CRVE across all graders. In models including data of both eyes’ measures from pre- and post-dilation images by three graders, the fixed effect for dilation status contributed significantly to CRAE and CRVE variances whereas random effects for graders and dilation status contributed minimally.

Conclusions: Contrary to our hypothesis, we found a systematic effect of pupil dilation on retinal vessel caliber measures.     

Treatment of myofascial trigger points in patients with chronic shoulder pain: a randomized,controlled trial

Background  

Shoulder pain is a common musculoskeletal problem that is often chronic or recurrent. Myofascial trigger points (MTrPs) cause shoulder pain and are prevalent in patients with shoulder pain. However, few studies have focused on MTrP therapy. The aim of this study was to assess the effectiveness of multimodal treatment of MTrPs in patients with chronic shoulder pain.     

Nonanemic Patients Do Not Benefit from Autologous Blood Donation Before Total Hip Replacement

To avoid the potential risks of allogeneic transfusion during total hip arthroplasty (THA), the use of preoperative autologous blood donation (PABD) has been utilized. We performed a retrospective chart review of 283 patients undergoing THA that either donated 1 U of autologous blood (188 patients) or did not donate autologous blood before surgery (95 patients) in order to investigate the difference in postoperative transfusion rate (autologous and allogeneic), the incidence of allogeneic transfusion, and the difference in cost of each protocol. In addition, the study compared transfusion rates in patients with and without preoperative anemia (hemoglobin (Hb) ≤ 12.5 g/dL). At 0.75 transfusions per patient versus 0.22 transfusions per patient, the PABD patients had a significantly higher overall transfusion rate. PABD significantly reduced the need for allogeneic blood in anemic patients (Hb ≤ 12.5 g/dL) from 52.6% to 11.8%. PABD did not have the same affect in nonanemic patients (allogeneic transfusion rate 5.7% versus 4.0%). The study demonstrated that nonanemic patients undergoing THA do not benefit from PABD, but it is effective for anemic patients.