Lower serum DHEAS levels are associated with a higher degree of physical disability and depressive symptoms in middle-aged to older African American women

BACKGROUND: Changes in androgen levels and associations with chronic disease, physical and neuropsychological function and disability in women over the middle to later years of life are not well understood and have not been extensively studied in African American women. AIMS: The present cross-sectional analysis reports such levels and associations in community dwelling, African American women aged 49-65 years from St. Louis, Missouri. METHODS: A home-based physical examination and a health status questionnaire were administered to randomly sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength, physical and neuropsychological function and disability levels were assessed. Blood was drawn and assayed for total testosterone (T), sex hormone-binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2), adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and cytokine receptors (sIL2r, sIL6r, sTNFr1 and sTNFr2). Multiple linear regression modelling was used to identify the best predictors of testosterone, DHEAS and free androgen index (T/SHBG). RESULTS: Seventy-four percent of women were menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2 declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI remained stable. Total T and DHEAS levels were strongly correlated. In this population sample there were no independent associations of either total T or FAI with indicators of functional limitations, disability or clinically relevant depressive symptoms. Unlike total T and FAI, lower DHEAS levels were independently associated with both higher IADL scores (indicating a higher degree of physical disability) and higher CESD scores (indicating a higher degree of clinically relevant depressive symptoms). CONCLUSION: There is an age-related decline in serum DHEAS in African American women. Lower DHEAS levels appear to be associated with a higher degree of physical disability and depressive symptoms in this population.     

A Bayesian model of the disambiguation of gravitoinertial force by visual cues

The otoliths are stimulated in the same fashion by gravitational and inertial forces, so otolith signals are ambiguous indicators of self-orientation. The ambiguity can be resolved with added visual information indicating orientation and acceleration with respect to the earth. Here we present a Bayesian model of the statistically optimal combination of noisy vestibular and visual signals. Likelihoods associated with sensory measurements are represented in an orientation/acceleration space. The likelihood function associated with the otolith signal illustrates the ambiguity; there is no unique solution for self-orientation or acceleration. Likelihood functions associated with other sensory signals can resolve this ambiguity. In addition, we propose two priors, each acting on a dimension in the orientation/acceleration space: the idiotropic prior and the no-acceleration prior. We conducted experiments using a motion platform and attached visual display to examine the influence of visual signals on the interpretation of the otolith signal. Subjects made pitch and acceleration judgments as the vestibular and visual signals were manipulated independently. Predictions of the model were confirmed: (1) visual signals affected the interpretation of the otolith signal, (2) less variable signals had more influence on perceived orientation and acceleration than more variable ones, and (3) combined estimates were more precise than single-cue estimates. We also show that the model can explain some well-known phenomena including the perception of upright in zero gravity, the Aubert effect, and the somatogravic illusion.     

Ionophore and Biometal Modulation of P-glycoprotein Expression and Function in Human Brain Microvascular Endothelial Cells

Purpose

Biometals such as zinc and copper have been shown to affect tight junction expression and subsequently blood-brain barrier (BBB) integrity. Whether these biometals also influence the expression and function of BBB transporters such as P-glycoprotein (P-gp) however is currently unknown.

Methods

Using the immortalised human cerebral microvascular endothelial (hCMEC/D3) cell line, an in-cell western assay (alongside western blotting) assessed relative P-gp expression after treatment with the metal ionophore clioquinol and biometals zinc and copper. The fluorescent P-gp substrate rhodamine-123 was employed to observe functional modulation, and inductively coupled plasma mass spectrometry (ICP-MS) provided information on biometal trafficking.

Results

A 24-h treatment with clioquinol, zinc and copper (0.5, 0.5 and 0.1 μM) induced a significant upregulation of P-gp (1.7-fold) assessed by in-cell western and this was confirmed with western blotting (1.8-fold increase). This same treatment resulted in a 23% decrease in rhodamine-123 accumulation over a 1 h incubation. ICP-MS demonstrated that while t8his combination treatment had no effect on intracellular zinc concentrations, the treatment significantly enhanced bioavailable copper (4.6-fold).

Conclusions

Enhanced delivery of copper to human brain microvascular endothelial cells is associated with enhanced expression and function of the important efflux pump P-gp, which may provide therapeutic opportunities for P-gp modulation.

     

Bonded versus banded first molar attachments: a randomized controlled clinical trial

OBJECTIVE: To compare the clinical failure rates of bonded first molar tubes with those of cemented bands during fixed appliance therapy. DESIGN: Prospective randomized controlled clinical trial. SETTING: Two UK hospital orthodontic clinics, February 2001-December 2004. PARTICIPANTS: Hospital waiting list patients needing fixed appliances (n = 110). METHOD: Patients were randomly allocated to two groups. Experimental group patients (n = 55) received single first molar tubes (n = 181) bonded with a no-mix chemically cured composite (Rely-A-Bond) after a 30-second etch. Control group patients (n = 55) were treated with bands (n = 186) cemented with Intact glass ionomer cement (GIC). First-time failures were recorded together with the time of failure. All patients were followed to the end or discontinuation of treatment. RESULTS: First-time failures: bands = 18.8%; bonds = 33.7 %. Bonded tubes were more likely to fail [RR 2.4; 95% CI (1.4, 4.1)] compared with bands. Experimental group patients also had more bracket failures (P = 0.009), when analysed at patient level. CONCLUSION: First molar tubes bonded with Rely-A-Bond composite showed a significantly higher first-time failure rate than bands cemented with Intact GIC.     

Long-term clinical evaluation of bracket failure with a self-etching primer: a randomized controlled trial

OBJECTIVE: A long-term comparison of the failure rates of orthodontic brackets bonded with either a self-etching primer (SEP) or conventional etch and primer (AE). DESIGN: Prospective randomized controlled clinical trial. SETTING: UK district general hospital with one operator, 2003-6. PARTICIPANTS: Hospital waiting list patients needing fixed appliances (n=60). METHOD: Experimental (SEP) group patients (n=30) received pre-adjusted edgewise brackets (n=438) bonded with Transbond Plus following manufacturer's instructions. Control (AE) group patients (n=30, brackets n=433) were bonded using a 15-second conventional etch and primer (Transbond XT). In both groups brackets were light-cured for 20 seconds. First-time bond failures were recorded with the time of failure. Bracket bonding time was recorded. All patients were followed to the end or discontinuation of treatment. RESULTS: Bracket failure rates: SEP=4.8%, AE=3.5%, P=0.793. Mean placement time per bracket (seconds): SEP=75.5 (+/-6.7; 95% CI=72.9, 78.0), AE=97.7 (+/-9.1; 95% CI=94.3, 101.2) P=0.000. CONCLUSION: There was no difference in the failure rates of brackets bonded with either Transbond Plus SEP or conventional AE using Transbond XT paste. Bonding with SEP was significantly faster than using conventional AE.     

Sagittal curvature of total knee replacements predicts in vivo kinematics

BACKGROUND: It is known that in vivo kinematics after total knee replacement is influenced by the design of the implant. The goal of this study was to show that the sagittal curvature of two different knee prostheses differing in geometric design predicts their in vivo motion behavior. METHODS: Three-dimensional tibio-femoral displacements of two prosthesis designs (single radius vs. dual radius) were measured during knee extension under weight bearing conditions by in vivo video fluoroscopy. Finite helical axes were computed to represent the tibio-femoral motions. Angular deviation alpha and the spatial localization deviation delta were used to characterize the motions. Angular deviation is the angle between each incremental finite helical axis and the medio-lateral axis of the femoral component of the prosthesis. The spatial localization deviation is the distance between each finite helical axis and the center of the femoral component of the prosthesis. Statistical comparisons were performed using the median and the interquartile range of the angular deviation and the spatial localization deviation. FINDINGS: The single-radius design showed finite helical axes concentrated at a single axis near to the medio-lateral axis of the femoral component. The angular and spatial localization deviation of the dual radius design were larger compared to the single radius design, exhibiting finite helical axes varying between two axes. INTERPRETATION: Video fluoroscopy in combination with finite helical axis analysis proved to be suitable methods to evaluate the in vivo kinematical behavior of total knee arthroplasty, which can be useful for implant designers. Knowledge of in vivo kinematics can also provide surgeons with more background information about the total knee arthroplasty models they implant.     

Comparison of patient reported outcomes after Triathlon? and Kinemax Plus prostheses

INTRODUCTION

The Triathlon^® (Stryker, Kalamazoo, MI, US) total knee replacement was designed to improve patient function and survivorship. The aim of this study was to determine whether the Triathlon^® prosthesis produces better patient reported outcomes than a previous design by the same manufacturer, the Kinemax Plus.

METHODS

The outcome of 233 knees of patients with a mean age of 68 years (range: 40–80 years) who received the Kinemax Plus prosthesis were compared with the outcomes of 220 knees of patients with a mean age of 70 years (range: 42–90 years) who received the Triathlon^® prosthesis. Data were collected via postal questionnaire prior to surgery as well as at 8–12 weeks and at 1 year following surgery. Validated questionnaires were used including the WOMAC^® (Western Ontario and McMaster Universities) pain and function scales, the Knee injury and Osteoarthritis Outcome Score quality of life scale and the self-administered patient satisfaction scale.

RESULTS

This study found that patients who had the Triathlon^® prosthesis had significantly better pain relief (p<0.0001), function (p=0.028), knee related quality of life (p<0.0001) and satisfaction (p=0.0003) at three months after surgery than those who received the Kinemax Plus prosthesis. In addition, knee related quality of life (p=0.002) and satisfaction (p=0.021) were significantly higher at one year after surgery in Triathlon^® patients.

CONCLUSIONS

The findings suggest that return to function and reduction in pain may occur more quickly in patients with a Triathlon^® prosthesis than in those with the Kinemax Plus.     

H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK

Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.     

Provider type influences adherence to lifestyle changes in chronic pancreatitis

Background/Objectives: Alcohol and smoking cessation are recommended in chronic pancreatitis. The aim of this study is to measure the rates of alcohol and smoking cessation counselling among providers and adherence to recommendations.MethodsRetrospective cohort study of chronic pancreatitis patients at a tertiary hospital. Provider types were defined as primary care (PCP), gastroenterologist, or pancreas specialist. Pairwise comparisons and multivariable analysis were conducted to assess the relation between provider type and smoking/alcohol cessation.ResultsOf 256 patients with chronic pancreatitis, 142 (55.5%) consumed alcohol and 130 (91.5%) were advised to stop. Alcohol cessation was advised to 88.9, 96.0 and 92.5% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively. Sixty-one patients (46.9%) were compliant with the recommendation: 31.3, 44.0 and 54.1% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, others nonsignificant). In multivariable analysis, patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation compared to those followed by PCP (OR = 4.31, CI 1.52–12.20, p = 0.006). Smoking cessation was advised to all the 127 current smokers (100%). Fifty-six (44.1%) were compliant with the recommendation: 24.1, 58.3 and 47.3% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, PCP vs. Gastroenterologist: p = 0.01, others nonsignificant). Multivariable analysis did not confirm this finding.ConclusionsThe majority of providers counsel for alcohol/smoking cessation. Less than half the patients follow the recommendations. Patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation.