The cholesterol-raising diterpenes from coffee beans increase serum lipid transfer protein activity levels in humans

Cafestol and kahweol–diterpenes present in unfiltered coffee— strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61–64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48–54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (±S.D.) activity of cholesterylester transfer protein by 18±12% and of phospholipid transfer protein by 21±14% (both P<0.001). Relative to cafestol alone, kahweol had no significant additional effects. Lecithin:cholesterol acyltransferase activity was reduced by 11±12% by cafestol plus kahweol (P=0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins

Intra-and interobserver reliability of determining the femoral footprint of the torn anterior cruciate ligament on MRI scans

BACKGROUND: Re-injury rates following reconstruction of the anterior cruciate ligament (ACL) are significant; in more than 20% of patients a rupture of the graft occurs. One of the main reasons for graft failure is malposition of the femoral tunnel. The femoral origin of the torn ACL can be hard to visualize during arthroscopy, plus many individual variation in femoral origin anatomy exists, which may lead to this malpositioning. To develop a patient specific guide that may resolve this problem, a preoperative MRI is needed to identify the patient specific femoral origin of the ACL. The issue here is that there may be a difference in the reliability of identification of the femoral footprint of the ACL on MRI between different observers with different backgrounds and level of experience. The purpose of this study was to determine the intra- and interobserver reliability of identifying the femoral footprint of the torn ACL on MRI and to compare this between orthopedic surgeons, residents in orthopedic surgery and MSK radiologists.METHODS: MR images of the knee joint were collected retrospectively from 20 subjects with a confirmed rupture of the ACL. The 2D (coronal, sagittal, transversal) proton-density (PD) images were selected for the segmentation procedure to create 3D models of the femurs. The center of the femoral footprint of the ACL on 20 MRI scans, with visual feedback on 3D models (as reference) was determined twice by eight observers. The intra- and interobserver reliability of determining the center of the femoral footprint on MRI was evaluated. Intraclass correlation coefficients (ICCs) were calculated for the X, Y and Z coordinates separately and for a 3D coordinate.RESULTS: The mean 3D distance between the first and second assessment (intraobserver reliability) was 3.82 mm. The mean 3D distance between observers (interobserver reliability) was 8.67 mm. ICCs were excellent (&gt; 0.95), except for those between the assessments of the two MSK radiologists of the Y and Z coordinates (0.890 and 0.800 respectively). Orthopedic surgeons outscored the residents and radiologists in terms of intra- and interobserver agreement.CONCLUSION: Excellent intraobserver reliability was demonstrated (&lt; 4 mm). However the results of the interobserver reliability manifested remarkably less agreement between observers (&gt; 8 mm). An orthopedic background seems to increase both intra- and interobserver reliability. Preoperative planning of the femoral tunnel position in ACL reconstruction remains a surgical decision. Experienced orthopedic surgeons should be consulted when planning for patient specific instrumentation in ACL reconstruction.</p

Folding, Design and Determination of Interaction Potentials Using Off-Lattice Dynamics of Model Heteropolymers

We present the results of a self-consistent, unified molecular dynamics study of simple model heteropolymers in the continuum with emphasis on folding, sequence design and the determination of the interaction parameters of the effective potential between the amino acids from the knowledge of the native states of the designed sequences.Comment: 8 pages, 3 Postscript figures, uses RevTeX. Submitted to Physical Review Letter

Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of pre beta-high-density lipoproteins

High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated pre beta-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of pre beta-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of pre beta-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of pre beta-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, pre beta-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of pre beta-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport

Facilitators and barriers for the implementation of exercise are medicine in routine clinical care in Dutch university medical centres:a mixed methodology study on clinicians' perceptions

Objectives Despite the many proven advantages of a physically active lifestyle in patient populations, prescription of exercise is currently not widely implemented in routine clinical practice. The aims of this study were twofold: (1) to assess perceptions of clinicians on the current practice of exercise is medicine (E=M) prescription in two Dutch university medical centres and (2) to determine their perceived barriers and facilitators for the implementation of E=M in routine clinical care in Dutch university medical centres. Design A mixed methodologies study, using both online questionnaires and semi-structured interviews. Setting Dutch university medical centres. Participants Clinicians working within the departments of medical oncology, orthopaedics and rehabilitation medicine of two university medical centres. Results Forty-five clinicians (response rate of 51%) completed the questionnaire, and 19 clinicians were interviewed. The results showed that even though clinicians had a positive attitude towards prescribing E=M, only a few reported to regularly prescribe E=M to their patients. The 52 identified facilitators and barriers for implementation of E=M were categorised into four main themes: (1) beliefs toward the implementation of E=M (eg, clinicians knowledge and skills, and social support), (2) factors related to the patient perspective (eg, patient priorities or motivation), (3) factors related to the referral options (eg, knowledge of and trust in local referral options) and (4) practical considerations when implementing E=M (eg, time constraints). Conclusions Our study showed that even though many clinicians have a positive attitude toward an active lifestyle, many are not prescribing E=M on a regular basis. In order for clinicians to effectively implement E=M, strategies should focus on increasing clinicians E=M referral skills, improving clinicians knowledge of E=M referral options and develop a support system to ensure that E=M is high on the priority list of clinicians

Backbone and side chain NMR assignments for the intrinsically disordered cytoplasmic domain of human neuroligin-3

Neuroligins act as heterophilic adhesion molecules at neuronal synapses. Their cytoplasmic domains interact with synaptic scaffolding proteins, and have been shown to be intrinsically disordered. Here we report the backbone and side chain 1H, 13C and 15N resonance assignments for the cytoplasmic domain of human neuroligin 3

The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

Background: Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design: The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion: The TOPSHOCK study is the first randomised controlled trial that directly compares the effectiveness of focused shockwave therapy and radial shockwave therapy, both in combination with eccentric decline squat training, for treating patellar tendinopathy. Trial registration: Trial registration number NTR2774

The recovery after Achilles tendon rupture:a protocol for a multicenter prospective cohort study

BackgroundAchilles tendon rupture (ATR) is a common sports injury, with a rising incidence and significant impairments. Due to the lack of treatment guidelines, there is no consensus about diagnostic methods, primary treatment (non-surgical or surgical) and rehabilitation. It is hypothesized that this lack of consensus and guidelines leads to sub-optimal recovery and higher societal costs.The primary aim of this study is to give a broad insight into the recovery after ATR. Secondarily this study aims to explore factors contributing to recovery and gain insight into the cost-effectiveness of ATR management.MethodsThis multicenter prospective cohort study will include all adult ( 18years) patients with an ATR treated at the three main hospitals in the Northern Netherlands: University Medical Center Groningen, Martini Hospital Groningen and Medical Center Leeuwarden. All subjects will be invited for three visits at 3, 6 and 12months post-injury. The following data will be collected: patient-reported outcome measures (PROMs), physical tests, imaging and economic questionnaires. At 3months post-injury personal, injury, and treatment data will be collected through a baseline questionnaire and assessment of the medical file. The PROMs concern the Dutch version of the Achilles Tendon Total Rupture Score, EQ-5D-5L, Oslo Sport Trauma Research Center Overuse Injury Questionnaire, Injury Psychological Readiness Return to Sport Scale, Tampa Scale of Kinesiophobia, Expectations, Motivation and Satisfaction questionnaire and a ranking of reasons for not returning to sport. The administered physical tests are the heel-rise test, standing dorsiflexion range of motion, resting tendon length and single leg hop for distance. Ultrasound Tissue Characterization will be used for imaging. Finally, economic data will be collected using the Productivity Cost Questionnaire and Medical Consumption Questionnaire.DiscussionThis prospective cohort study will contribute to optimal decision making in the primary treatment and rehabilitation of ATRs by providing insight into (1) ATR recovery (2) novel imaging for monitoring recovery (3) (barriers to) return to sport and (4) cost-effectiveness of management. The analysis of these data strives to give a broad insight into the recovery after ATR as well as provide data on novel imaging and costs, contributing to individualized ATR management.Trial registrationTrialregister.nl. NTR6484. 20/06/2017. 20/07/2017

Correction to: Being active with a total hip or knee prosthesis: a systematic review into physical activity and sports recommendations and interventions to improve physical activity behavior

Objectives: Regular physical activity (PA) is considered important after total hip and knee arthroplasty (THA/TKA). Objective was to systematically assess literature on recommendations given by healthcare professionals to persons after THA and TKA and to provide an overview of existing interventions to stimulate PA and sports participation. Methods: A systematic review with a narrative synthesis including articles published between January 1995 and January 2021 reporting on recommendations and interventions. The PubMed, Embase, CINAHL and PsycInfo databases were systematically searched for original articles reporting on physical activity and sports recommendations given by healthcare professionals to persons after THA and TKA, and articles reporting on interventions/programs to stimulate a physically active lifestyle after rehabilitation or explicitly defined as part of the rehabilitation. Methodological quality was assessed with the Mixed Methods Appraisal Tool (MMAT). The review was registered in Prospero (PROSPERO:CRD42020178556). Results: Twenty-one articles reported on recommendations. Low-impact activities were allowed. Contact sports, most ball sports, and martial arts were not recommended. One study informed on whether health-enhancing PA recommendations were used to stimulate persons to become physically active. No studies included recommendations on sedentary behavior. Eleven studies reported on interventions. Interventions used guidance from a coach/physiotherapist; feedback on PA behavior from technology; and face-to-face, education, goal-setting, financial incentives and coaching/financial incentives combined, of which feedback and education seem to be most effective. For methodological quality, 18 out of 21 (86%) articles about recommendations and 7 out of 11 (64%) articles about interventions scored yes on more than half of the MMAT questions (0–5 score). Conclusion: There is general agreement on what kind of sports activities can be recommended by healthcare professionals like orthopedic surgeons and physiotherapists. No attention is given to amount of PA. The same is true for limiting sedentary behavior. The number of interventions is limited and diverse, so no conclusions can be drawn. Interventions including provision of feedback about PA, seem to be effective and feasible