57 Publication(s) found
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Rheumatology, Rheumatoid Arthritis
8. May 2018

Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis

OBJECTIVES:
The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular…

Osteoarthritis
17. Jan 2018

Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis

BACKGROUND:
Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinica…

Rheumatology, Osteoarthritis, Clinical Data Quality
9. Jan 2018

Gender Differences in Knee Joint Congruity Quantified from MRI: A Validation Study with Data from Center for Clinical and Basic Research and Osteoarthritis Initiative.

Objective Gender is a risk factor in the onset of osteoarthritis (OA). The aim of the study was to investigate gender differences in contact area (CA) and congruity index (CI) in the medial tibiofemoral (MTF) joint in 2 different cohorts, quantified automatically from magnetic resonance imaging (MRI…

Chronic Obstructive Pulmonary Disease, Respiratory System
4. Dec 2017

Biomarkers of collagen turnover are related to annual change in FEV1 in patients with chronic obstructive pulmonary disease within the ECLIPSE study

BACKGROUND:
Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1.

METHODS:
One thousand COPD subjects from the observatio…

Rheumatology, Rheumatoid Arthritis
28. Aug 2017

Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis

OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…

Oncology
26. Oct 2016

Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study

The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are the key fac…

Hepatic System, Type 2-Diabetes
20. Oct 2016

Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy

There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…

Extracellular Matrix Research, Respiratory System
4. Oct 2016

High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study

BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…

Bone, Osteoporosis
1. Oct 2016

A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D …

Type 2-Diabetes
8. Sep 2016

Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes

AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…

Rheumatology, Rheumatoid Arthritis
20. Jan 2016

Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study

BACKGROUND:
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection r…

Endocrinology
7. Dec 2015

Collagen Type III and VI Turnover in Response to Long-Term Immobilization

BACKGROUND:
Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarker…

Alzheimer’s Disease, Central Nervous System
11. Jun 2015

Relationship between serum levels of tau fragments and clinical progression of Alzheimer's disease

Enzyme-generated fragments of tau have been linked to neuronal death and may serve as serum biomarkers of cognitive loss. Two competitive ELISAs detecting an ADAM10-generated fragment (Tau-A) or a caspase-3-generated fragment (Tau-C) were measured in baseline serum samples from patients with mild to…

Extracellular Matrix Research
30. Apr 2015

Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women

Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…

Clinical Data Quality
1. Apr 2015

Impact of source data verification on data quality in clinical trials: an empirical post hoc analysis of three phase 3 randomized clinical trials

AIM:
The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.

METHODS:
We used data from three randomized phase I…

Rheumatology, Osteoarthritis
1. Apr 2015

OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA

BACKGROUND/PURPOSE:
The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Art…

Rheumatology, Osteoarthritis
1. Apr 2015

Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials

PURPOSE:
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural d…

Clinical Data Quality
19. Oct 2014

Impact of Source Data Verification on data quality in clinical trials: An empirical post-hoc analysis of three phase 3 randomised clinical trials

AIM:
The aim of this project was to perform an empirical evaluation of the impact of on site source data verification (SDV) on the data quality in a clinical trial database to guide an informed decision on selection of the monitoring approach.

METHODS:
We used data from three randomized phase I…

Hepatic System, Hepatitis B/C
29. Sep 2014

PRO-C3-levels in patients with HIV/HCV-Co-infection reflect fibrosis stage and degree of portal hypertension

BACKGROUND:
Liver-related deaths represent the leading cause of mortality among patients with HIV/HCV-co-infection, and are mainly related to complications of fibrosis and portal hypertension. In this study, we aimed to evaluate the structural changes by the assessment of extracellular matrix (ECM)…

Rheumatology, Rheumatoid Arthritis
20. Sep 2014

Serological biomarkers of joint tissue turnover predict tocilizumab response at baseline

Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarticular joint inflammation resulting in massive tissue turnover. The turnover is partly mediated by an up-regulation of proteolytic enzymes, such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMP…

1. Sep 2014

Combined antiretroviral therapy attenuates hepatic extracellular matrix remodeling in HIV patients assessed by novel protein fingerprint markers

OBJECTIVES:
Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade ex…

Rheumatology, Rheumatoid Arthritis
5. Feb 2014

Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study

OBJECTIVE:
We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.

METHODS:
The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early …

Rheumatology, Osteoarthritis
14. Aug 2013

Serological identification of fast progressors of structural damage with rheumatoid arthritis

INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…

Rheumatology, Spondyloarthropathies
1. Aug 2013

Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis

Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural prote…

Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013

A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease

Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …

Bone
3. Mar 2013

Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis

CONTEXT:
Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1-34) or rhPTH(1-84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance.

OB…

Hepatic System, Alcoholic Liver Disease
3. Mar 2013

Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis--a serological evaluation

BACKGROUND/AIM:
We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis.

METHODS:
Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red stainin…

Rheumatology, Rheumatoid Arthritis
4. Oct 2012

IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522)

OBJECTIVE:
To evaluate changes in biochemical markers of bone metabolism in response to tocilizumab in patients with anti-tumor necrosis factor-refractory rheumatoid arthritis (RA).

METHODS:
RADIATE was a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. C-reactive pro…

Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012

Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker

BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…

Endocrinology, Type 2-Diabetes
27. May 2011

Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy

BACKGROUND:
Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a cl…

Rheumatology, Osteoarthritis
19. Apr 2011

Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover

OBJECTIVES:
Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a trauma…

Bone, Osteoporosis
14. Apr 2011

Strontium ranelate effect in postmenopausal women with different clinical levels of osteoarthritis

OBJECTIVE:
The objective of this post hoc analysis was to investigate the effect of strontium ranelate on a cartilage degradation marker in postmenopausal women who participated in a randomized, placebo-controlled osteoporosis study. Women were stratified according to reported symptoms of osteoarth…

Rheumatology, Osteoarthritis
13. Apr 2011

Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis

OBJECTIVES:
In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.

METHODS:
A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against…

Bone
5. Apr 2011

Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials

Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the…

Oncology, Bone
3. Mar 2011

Serum N-Terminal Propeptide of Collagen Type I is Associated with the Number of Bone Metastases in Breast and Prostate Cancer and Correlates to Other Bone Related Markers

BACKGROUND:
A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the …

Bone, Osteoporosis
5. Oct 2010

Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)--assessment of corresponding epitopes

OBJECTIVES:
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP epitopes in the rat- and human species.

METHODS:
Monoclonal antibodies were raised again…

Rheumatology, Osteoarthritis
17. Jun 2010

Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation

BACKGROUND:
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass In…

Cardiovascular System, Atherosclerosis
21. Apr 2010

Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes

BACKGROUND:
Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular mat…

Bone
18. Feb 2010

The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study

BACKGROUND:
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA).

MATERIALS AND METHODS:
The study was a phase-I, 2-week, placebo-controlled, do…

Bone
16. Jan 2010

Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy

AIMS:
The aims of the study were to investigate interindividual variations in the bioavailability of salmon calcitonin (sCT) following single oral 0.8 mg doses at three different times of the day, and intraindividual variation in sCT bioavailability at each end of a 14-day treatment period. We also…

Bone
10. Dec 2009

PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women

BACKGROUND:
Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1) locus. Carriers …

Bone, Osteoporosis
20. Sep 2009

Is bone quality associated with collagen age?

The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not…

Endocrinology, Type 2-Diabetes
15. Aug 2009

A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats

Agonists of Perioxisome Proliferator-Activator Receptor gamma (PPARgamma), which work as insulin sensitizers, are approved for type 2 diabetes. However, adverse effects, such as oedemas, infarctions, and increased fracture rates, limit their applicability. We performed a head-to-head comparison of e…

Rheumatology, Osteoarthritis
24. Jul 2009

Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers

INTRODUCTION:
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations…

Extracellular Matrix Research
14. May 2009

Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of prote…

Bone
4. Apr 2009

Influence of food intake on the bioavailability and efficacy of oral calcitonin

AIMS:
To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT).

METHODS:
A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62-74 years. The influence of f…

Bone
2. Feb 2009

A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin

The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 year…

Bone
4. Dec 2008

Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin

BACKGROUND:
Bone resorption displays marked diurnal variation. Reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks. The aim of the study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral salmon calcitonin …

Bone, Osteoporosis
18. Nov 2008

Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation

BACKGROUND:
Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would h…

Bone
19. Sep 2008

The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality

Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality.

INTRODUCTIO…

Bone
8. Sep 2008

Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of Salmon Calcitonin

BACKGROUND:
To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT).

METHODS:
The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I …

Oncology, Bone
27. Jun 2008

Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

BACKGROUND:
Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in br…

Bone, Osteoporosis
17. May 2008

Biochemical markers for monitoring response to therapy: evidence for higher bone specificity by a novel marker compared with routine markers

The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node …

Bone, Osteoporosis
19. Mar 2008

Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies

Bone collagen maturation may be important for anti-fracture efficacy as the reduction in risk is only partly explained by a concomitant increase in BMD during anti-resorptive therapy. Different treatments caused diverse profiles in bone collagen degradation products, which may have implications for …

Bone
18. Jun 2007

Osteoclasts prefer aged bone

We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of age…

Rheumatology, Osteoarthritis
15. Mar 2007

Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen

The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.

DESIGN:
Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis fac…

Oncology, Bone
15. Jul 2006

Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion

We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localiz…