The biomechanical fingerprint of hip and knee osteoarthritis patients during activities of daily living.

Background: Osteoarthritis is a highly prevalent disease affecting the hip and knee joint and is characterized by load-mediated pain and decreased quality of life. Dependent on involved joint, patients present antalgic movement compensations, aiming to decrease loading on the involved joint. However, the associated alterations in mechanical loading of the ipsi- and contra-lateral lower limb joints, are less documented.

Can the Output of a Learned Classification Model Monitor a Person's Functional Recovery Status Post-Total Knee Arthroplasty?

Osteoarthritis is a common musculoskeletal disorder. Classification models can discriminate an osteoarthritic gait pattern from that of control subjects. However, whether the output of learned models (probability of belonging to a class) is usable for monitoring a person's functional recovery status post-total knee arthroplasty (TKA) is largely unexplored.

Movement Quality Parameters during Gait Assessed by a Single Accelerometer in Subjects with Osteoarthritis and Following Total Joint Arthroplasty.

This study's aim is threefold: (I) Evaluate movement quality parameters of gait in people with hip or knee osteoarthritis (OA) compared to asymptomatic controls from a single trunk-worn 3D accelerometer. (II) Evaluate the sensitivity of these parameters to capture changes at 6-weeks, 3-, 6-, and 12-months following total knee arthroplasty (TKA). (III) Investigate whether observed changes in movement quality from 6-weeks and 12-months post-TKA relates to changes in patient-reported outcome measures (PROMs).

Joint kinematics alone can distinguish hip or knee osteoarthritis patients from asymptomatic controls with high accuracy.

Osteoarthritis (OA) is one of the leading musculoskeletal disabilities worldwide, and several interventions intend to change the gait pattern in OA patients to more healthy patterns. However, an accessible way to follow up the biomechanical changes in a clinical setting is still missing. Therefore, this study aims to evaluate whether we can use biomechanical data collected from a specific activity of daily living to help distinguish hip OA patients from controls and knee OA patients from controls using features that potentially could be measured in a clinical setting.

Functional movement assessment by means of inertial sensor technology to discriminate between movement behaviour of healthy controls and persons with knee osteoarthritis.

Background: Apart from biomechanical alterations in movement patterns, it is known that movement limitations in persons with knee osteoarthritis (PwKOA) are related to an individual's perception and belief regarding pain and disability. To gain more insights into the functional movement behaviour of PwKOA in a clinical setting, inertial sensor technology can be applied. This study first aims to evaluate the ability of inertial sensors to discriminate between healthy controls (HC) and PwKOA.

Discriminant validity of 3D joint kinematics and centre of mass displacement measured by inertial sensor technology during the unipodal stance task.

Background: The unipodal stance task is a clinical task that quantifies postural stability and alignment of the lower limb joints, while weight bearing on one leg. As persons with knee osteoarthritis (KOA) have poor postural and knee joint stability, objective assessment of this task might be useful.

Objective: To investigate the discriminant validity of three-dimensional joint kinematics and centre of mass displacement (COM) between healthy controls and persons with knee KOA, during unipodal stance using inertial sensors.

Assessment of Scapulothoracic, Glenohumeral, and Elbow Motion in Adhesive Capsulitis by Means of Inertial Sensor Technology: A Within-Session, Intra-Operator and Inter-Operator Reliability and Agreement Study.

Adhesive capsulitis (AC) is a glenohumeral (GH) joint condition, characterized by decreased GH joint range of motion (ROM) and compensatory ROM in the elbow and scapulothoracic (ST) joint. To evaluate AC progression in clinical settings, objective movement analysis by available systems would be valuable. This study aimed to assess within-session and intra- and inter-operator reliability/agreement of such a motion capture system.

Effects of Visually Augmented Gait Training on Foot-Ground Clearance: An Intervention to Reduce Tripping-Related Falls.

Minimum toe clearance (MTC ∼10-30 mm) is a hazardous mid-swing gait event, characterized by high-foot velocity (∼4.60 m·s-1) and single-foot support. This experiment tested treadmill-based gait training effects on MTC.

Reliability and Agreement of 3D Trunk and Lower Extremity Movement Analysis by Means of Inertial Sensor Technology for Unipodal and Bipodal Tasks.

This study evaluates the reliability and agreement of the 3D range of motion (ROM) of trunk and lower limb joints, measured by inertial measurement units (MVN BIOMECH Awinda, Xsens Technologies), during a single leg squat (SLS) and sit to stand (STS) task. Furthermore, distinction was made between movement phases, to discuss the reliability and agreement for different phases of both movement tasks. Twenty healthy participants were measured on two testing days.

Reliability of 3D Lower Extremity Movement Analysis by Means of Inertial Sensor Technology during Transitional Tasks.

This study assesses the reliability and agreement of trunk and lower limb joints' 3D kinematics, measured by inertial measurement units, during walking and more demanding movement tasks. For data analysis, tasks were divided in open and closed chain phases. Twenty healthy participants were included.

Mobile assessment of the lower limb kinematics in healthy persons and in persons with degenerative knee disorders: A systematic review.

Inertial sensor systems are increasingly used in the assessment of persons with knee osteoarthritis (KOA) and total knee replacement (TKR). This systematic review aims to (1) investigate the application of inertial sensor systems and kinematics derived from these systems, and (2) assess if current assessment protocols consist of tasks which are, according to the International Classification of Functioning, Disability and Health (ICF) for KOA, relevant for persons with KOA and TKR. A search was conducted in six electronic databases (ACM, CINAHL, EMBASE, IEEE, PubMed, Web of Science) to include papers assessing the knee and one or more adjacent joints by means of inertial sensors in healthy persons or persons with KOA or TKR.

Shoulder assessment according to the international classification of functioning by means of inertial sensor technologies: A systematic review.

This review investigates current protocols using Inertial Measurement Units (IMUs) in shoulder research, and outlines future paths regarding IMU use for shoulder research. Different databases were searched for relevant articles. Criteria for study selection were (1) research in healthy persons or persons with shoulder problems, (2) IMUs applied as assessment tool for the shoulder (in healthy subjects and shoulder patients) or upper limb (in shoulder patients), (3) peer-reviewed, full-text papers in English or Dutch.

Clinical validation study of genetic markers for capecitabine efficacy in metastatic colorectal cancer patients.

Background And Aim: Pharmacogenetic studies continue to search for pretreatment predictors of chemotherapeutic efficacy and toxicity in metastatic colorectal cancer. Both genome-wide association studies and candidate gene studies have yielded potential genetic markers for chemosensitivity. We conducted a clinical association study, validating the effect of specific genetic markers cited in recently published papers on the efficacy of the oral 5-fluoro-uracil prodrug capecitabine.

Brostallicin versus doxorubicin as first-line chemotherapy in patients with advanced or metastatic soft tissue sarcoma: an European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group randomised phase II and pharmacogenetic study.

Aim: Brostallicin is a DNA minor groove binder that has shown activity in patients with soft tissue sarcoma (STS) failing first-line therapy. The present study assessed the safety and efficacy of first-line brostallicin in patients with advanced or metastatic STS >60 years or not fit enough to receive combination chemotherapy. A prospective explorative pharmacogenetic analysis was undertaken in parallel.

Differences in 5-hydroxytryptamine-3B haplotype frequencies between Asians and Caucasians.

Background: The 5-hydroxytryptamine (5-HT3) receptor is a ligand-operated ion channel with five different receptor subunits (5-HT3A, B, C, D, and E) found in humans. Activation of 5-HT3 receptors influences various effects such as drug-induced emesis and causes behavioral problems such as anxiety, depression and cognitive disorders. To explore interethnic differences in the response to 5-HT3 antagonists, we studied haplotype frequencies in the gene encoding the 5-HT3B receptor in Asians and Caucasians.

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Objective: Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

Methods: We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m(2) as monotherapy or as combined chemotherapy.

Clinical and pharmacogenetic determinants for the discontinuation of non-ergoline dopamine agonists in Parkinson's disease.

Objective: To identify determinants for the discontinuation of non-ergoline dopamine agonist (DA) treatment in patients with Parkinson’s disease (PD) and to identify genetic determinants in genes encoding dopamine receptor (DR)D2 and DRD3 in a exploratory analysis.

Methods: Patients included were first-time users of the non-ergoline DA ropinirole or pramipexole who had been diagnosed with PD before 2005. Treatment discontinuation was defined as a gap of 180 days or more between two refills of the DA.

Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis.

Objective: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients.

Comparative toxicity of arsenite metabolites in wild type CHO cells and in cells deficient in excision repair cross-complementing 1 and 2.

Arsenic (As) has been shown to alter one or more DNA repair processes. Excision repair cross-complementing 1 and 2 (ERCC1 and ERCC2) have shown to be associated with arsenic-induced toxicity and carcinogenicity. In this study, we investigated cytotoxic effects of various As metabolites in relation to two nucleotide excision repair genes: ERCC1 and ERCC2.

Mechanism of arsenic-induced neurotoxicity may be explained through cleavage of p35 to p25 by calpain.

In recent studies we have demonstrated that arsenic (As) metabolites change the composition of neuronal cytoskeletal proteins in vivo and in vitro. To further examine the mechanism of arsenic-induced neurotoxicity with various arsenate metabolites (iAsV, MMAV and DMAV) and arsenite metabolites (iAsIII, MMAIII and DMAIII), we investigated the role of the proteolytic enzyme calpain and its involvement in the cleavage of p35 protein to p25, and also mRNA expression levels of calpain, cyclin-dependent kinase 5 (cdk5) and glycogen synthase kinase 3 beta (gsk3ss). A HeLa cell line transfected with a p35 construct (HeLa-p35) was used as a model, since all other proteins such as calpain, CDK5 and GSK3beta are already present in HeLa cells as they are in neuronal cells.

Pharmacokinetics of riluzole: evidence for glucuronidation as a major metabolic pathway not associated with UGT1A1 genotype.

Pharmacokinetic studies of riluzole show a large inter-individual variability of the drug's clearance and serum concentrations. Optimizing the individual dosage of riluzole may have the potential to improve the effect of riluzole treatment on survival of patients with amyotrophic lateral sclerosis (ALS). Limited data are available on the in vivo metabolic elimination of riluzole.

Arsenic metabolites affect expression of the neurofilament and tau genes: an in-vitro study into the mechanism of arsenic neurotoxicity.

Neurological studies indicate that the central (CNS) and peripheral nervous system (PNS) may be affected by arsenic (As). As-exposed patients show significantly lower nerve conduction velocities (NCVs) in their peripheral nerves in comparison to healthy subjects. As may play a role in the disruption of neuroskeletal integrity, but the mechanisms by which it exerts a toxic effect on the peripheral and central nervous system are still unclear.

Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients.

The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. The glutamates are released from MTX by activity of the enzyme gamma-glutamyl-hydrolase (GGH), thereby allowing the efflux of MTX. GGH 452C>T has been associated with decreased catalytic activity and higher accumulation of long-chain MTX-polyglutamate.