Changes in Transversus Abdominis Muscle Thickness after Lumbo-Pelvic Core Stabilization Training among Chronic Low Back Pain Individuals.

OBJECTIVE: Lumbo-pelvic core stabilization training (LPST) is one of the therapeutic exercises common in practice for rehabilitation of patients with chronic low back pain. This study was carried out to examine the therapeutic effects of LPST on the muscle thickness of transversus abdominis (TrA) at rest and during contraction among patients with chronic non-specific low back pain. MATERIALS AND METHODS: A total of 25 participants (7 males and 18 females) with chronic non-specific low back pain participated in a within-subject, repeated measures, double-blinded, placebo-controlled comparisons trial. The participants received three different types of experimental therapeutic training conditions which includes the lumbo-pelvic core stabilization training (LPST), the placebo treatment with passive cycling (PC) and a controlled intervention with rest (CI). The interventions were carried out by randomization with 48 hours between the sessions. The effectiveness of interventions was studied by measuring the changes in muscle thickness of TrA at rest and during contraction using a real time ultrasonography. RESULTS: Repeated measures ANOVA demonstrated that the LPST provided significant therapeutic benefits as measured by an increase in the muscle thickness of the TrA at rest (p<0.05) and during contraction (p<0.01). The percentage change of the muscle thickness observed during LPST was significantly higher (p<0.01) when compared to the other two experimental training conditions. CONCLUSIONS: The findings indicated that the LPST might provide therapeutic benefits by increasing the muscle thickness and function of TrA. Therefore, it is suggested that LPST technique should be considered as part of management program for treatment of low back pain.

The Internal Reliability of Family Crisis Oriented Personal Evaluation Scale (F-COPES) in Malay version among caregivers of individual with learning disabilities.

OBJECTIVES: Caregivers face challenges to adapt while handling individual with learning disabilities (LD). The Family Crisis Oriented Personal Evaluation Scale (F-COPES) is a widely used instrument to measure coping strategies among caregivers. The current study performed cross cultural translation of F-COPES in Malay language. This study aims to examine the reliability by testing internal consistency of Malay version of F-COPES which is developed through back to back translation method from original English version. MATERIALS AND METHODS: The Malay version of F-COPES was administered among 30 caregivers. RESULTS: The reliability of F-COPES in Malay version is good with Cronbach's alpha coefficient value of 0.79. The internal consistency on sub domains of F-COPES such as reframing, acquiring social support and seeking spiritual support also acceptable with Cronbach's alpha values 0.67, 0.74, and 0.80, respectively. CONCLUSIONS: The Malay version of F-COPES is a reliable tool to evaluate the coping strategies adopted by the caregivers of individual with LD.

Development and validation of non-adherence to pulmonary rehabilitation questionnaire: a clinical tool for patients with chronic obstructive pulmonary diseases.

OBJECTIVE: Non-adherence is a serious issue among the participants in pulmonary rehabilitation program (PRP). Till date, no clinical tool is available to screen participants who will show poor adherence towards PRP. This study aimed to develop and validate a tool called "Adherence to Pulmonary Rehabilitation Questionnaire (APRQ)", a self-administered questionnaire to screen the risk of non-adherence to PRP among the patients with chronic obstructive pulmonary disease. APRQ comprises of 6 main constructs such as disease management behaviour, perceived treatment benefits, emotional factors, perceived severity of disease, barriers towards treatment and coping attitude. MATERIALS AND METHODS: This was a preliminary validity study carried out in the physiotherapy department and respiratory clinic in an university teaching hospital. A total of 109 patients with average age of 58.8 ± 1 year participated in the study. The inclusion criteria for subjects were: patients diagnosed with chronic obstructive pulmonary diseases (COPD) (Stage II and III). Exclusion criteria include those COPD patients with mental problems and disabled patients. The tool was developed based on thematic analysis and in-depth interview with focus group and literature search on the factors that lead to non-adherence among the PRP's participants. Principal component analysis was carried out to examine the construct validity and content validity of APRQ. RESULTS: A total of 20 items were created under 6 constructs. However, 2 items (smoking and hospital admission) were eliminated due to poor correlations. Thus, the final version of APRQ was developed and validated with 18 items. Reliability was measured using internal consistency and achieved Cronbach's Alpha of 0.762. CONCLUSIONS: The findings from this preliminary study supports that APRQ may be a valid and reliable tool to screen adherence towards PRP among chronic lung disease patients.

Risk of mental health disorders among farmers involved in palm plantation occupation.

OBJECTIVE: The aim of this study was to define mental health status of palm plantation farmers in Muar, Johor, Malaysia. MATERIALS AND METHODS: 47 male farmers volunteered to join this study from three rural districts in southern Malaysia. Anthropometric measurements, demographic data including smoking habits and the short form of the Depression-Anxiety-Stress Scales (DASS-21) to assess mental health status were obtained in an interview. RESULTS: Mean and SD age of participants was 30.17 ± 4.86 years. Mean BMI of subjects was 22.86 ± 3.88 kg/m2. Most subjects (76.6%) were smokers. The prevalence of mild to moderate anxiety was 27.7% and Mild to moderate depression was 8.5%. CONCLUSIONS: This study revealed high prevalence of anxiety and smoking in palm plantation workers and that smoking habits can be related to their higher anxiety level.

Evaluation of postural control impairment using Balance Error Scoring System among athletes with ankle injury: an effective tool in daily clinical practice.

OBJECTIVE: The main objective of the study was to investigate postural control impairment in athletes with history of ankle injury by using Balance Error Scoring System (BESS) and to compare with the controls. PATIENTS AND METHODS: This is a case-control study that compared postural control among subjects with history of ankle injury with the matched controls. A total of sixty subjects (n = 60) were recruited from the department of physical education and sports science from a higher learning institute. Thirty athletes who had history of ankle injury were recruited for case group and the control group had an another thirty participants who were healthy athletes with no history of ankle injury. BESS was used to measure postural control by estimating the errors committed in standing between the two group of athletes. Independent sample t test was used to compare the means between two groups and the level of significance is set at level of 0.05. RESULTS: The athletes with history of ankle injury scored more number of errors in BESS with high mean value of (15.10 +/- 6.52 errors) than the control group (5.63 / 3.81 errors which was significant at p=0.01 level. CONCLUSION: Postural control impairment was identified among athletes with history of ankle injury when compared with control group.

Inverse expression states of the BRN2 and MITF transcription factors in melanoma spheres and tumour xenografts regulate the NOTCH pathway.

The use of adherent monolayer cultures have produced many insights into melanoma cell growth and differentiation, but often novel therapeutics demonstrated to act on these cells are not active in vivo. It is imperative that new methods of growing melanoma cells that reflect growth in vivo are investigated. To this end, a range of human melanoma cell lines passaged as adherent cultures or induced to form melanoma spheres (melanospheres) in stem cell media have been studied to compare cellular characteristics and protein expression. Melanoma spheres and tumours grown from cell lines as mouse xenografts had increased heterogeneity when compared with adherent cells and 3D-spheroids in agar (aggregates). Furthermore, cells within the melanoma spheres and mouse xenografts each displayed a high level of reciprocal BRN2 or MITF expression, which matched more closely the pattern seen in human melanoma tumours in situ, rather than the propensity for co-expression of these important melanocytic transcription factors seen in adherent cells and 3D-spheroids. Notably, when the levels of the BRN2 and MITF proteins were each independently repressed using siRNA treatment of adherent melanoma cells, members of the NOTCH pathway responded by decreasing or increasing expression, respectively. This links BRN2 as an activator, and conversely, MITF as a repressor of the NOTCH pathway in melanoma cells. Loss of the BRN2-MITF axis in antisense-ablated cell lines decreased the melanoma sphere-forming capability, cell adhesion during 3D-spheroid formation and invasion through a collagen matrix. Combined, this evidence suggests that the melanoma sphere-culture system induces subpopulations of cells that may more accurately portray the in vivo disease, than the growth as adherent melanoma cells.

Prolonged writing task: comparison of electromyographic analysis of upper trapezius muscle in subjects with or without neck pain.

OBJECTIVES: Work related musculoskeletal disorders represent a serious public health problem as it is a leading cause for disability and absenteeism in workers. The main purpose of the present quasi-experimental study was to compare the muscle activity of the upper trapezius in subjects with neck pain and compare it to those of normal subjects. MATERIALS AND METHODS: Fifty subjects were recruited for this study after prior screening for neck pain. A Standardized Nordic Musculoskeletal Questionnaire was used for analysis of neck pain in both symptomatic and asymptomatic groups. All the subjects were briefed about the study procedures and due consent was obtained prior to the start of the trial. The subjects were instructed to write for 30 minutes under standardized experimental conditions during which the activity of the upper trapezius was recorded using surface electromyography (EMG). RESULTS: The comparison of the results in the symptomatic and asymptomatic group showed that the mean EMG activity of upper trapezius muscle was significantly higher in the former as compared to the later group (p < 0.05). The symptomatic group showed greater increase in muscle activity as compared to the asymptomatic group. CONCLUSION: Our results depict that prolong and continuous writing tasks show overuse of upper trapezius and altered motor control pattern in symptomatic subjects as compared to the normal asymptomatic subjects.

A polymorphism in the agouti signalling protein (ASIP) is associated with decreased levels of mRNA.

To date, a role for agouti signalling protein (ASIP) in human pigmentation has not been well characterized. It is known that agouti plays a pivotal role in the pigment switch from the dark eumelanin to the light pheomelanin in the mouse. However, because humans do not have an agouti banded hair pattern, its role in human pigmentation has been questioned. We previously identified a single polymorphism in the 3'-untranslated region (UTR) of ASIP that was found at a higher frequency in African-Americans compared with other population groups. To compare allele frequencies between European-Australians and indigenous Australians, the g.8818A --> G polymorphism was genotyped. Significant differences were seen in allele frequencies between these groups (P < 0.0001) with carriage of the G allele highest in Australian Aborigines. In the Caucasian sample set a strong association was observed between the G allele and dark hair colour (P = 0.004) (odds ratio 4.6; 95% CI 1.4-15.27). The functional consequences of this polymorphism are not known but it was postulated that it might result in message instability and premature degradation of the transcript. To test this hypothesis, ASIP mRNA levels were quantified in melanocytes carrying the variant and non-variant alleles. Using quantitative real-time polymerase chain reaction the mean ASIP mRNA ratio of the AA genotype to the AG genotype was 12 (P < 0.05). This study suggests that the 3'-UTR polymorphism results in decreased levels of ASIP and therefore less pheomelanin production.

Genetic association and cellular function of MC1R variant alleles in human pigmentation.

We have examined MC1R variant allele frequencies in the general population of South East Queensland and in a collection of adolescent dizygotic and monozygotic twins and family members to define statistical associations with hair and skin color, freckling, and mole count. Results of these studies are consistent with a linear recessive allelic model with multiplicative penetrance in the inheritance of red hair. Four alleles, D84E, R151C, R160W, and D294H, are strongly associated with red hair and fair skin with multinomial regression analysis showing odds ratios of 63, 118, 50, and 94, respectively. An additional three low-penetrance alleles V60L, V92M, and R163Q have odds ratios 6, 5, and 2 relative to the wild-type allele. To address the cellular effects of MC1R variant alleles in signal transduction, we expressed these receptors in permanently transfected HEK293 cells. Measurement of receptor activity via induction of a cAMP-responsive luciferase reporter gene found that the R151C and R160W receptors were active in the presence of NDP-MSH ligand, but at much reduced levels compared with that seen with the wild-type receptor. The ability to stimulate phosphorylation of the cAMP response element binding protein (CREB) transcription factor was also apparent in all stimulated MC1R variant allele-expressing HEK293 cell extracts as assessed by immunoblotting. In contrast, human melanoma cell lines showed wide variation in the their ability to undergo cAMP-mediated CREB phosphorylation. Culture of human melanocytes of known MC1R genotype may provide the best experimental approach to examine the functional consequences for each MC1R variant allele. With this objective, we have established more than 300 melanocyte cell strains of defined MC1R genotype.

CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin.

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

Frequent allelic loss at 10q23 but low incidence of PTEN mutations in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, highly metastatic skin tumor of neuroectodermal origin. The disease shares clinical and histopathological features with small cell lung carcinoma (SCLC). The genetic mechanisms underlying the development and tumor progression of MCC are poorly understood. We recently showed by comparative genomic hybridization (CGH) that the pattern of chromosomal abnormalities in MCC resembles that of SCLC. One of the most frequently observed losses involved the entire chromosome 10 or partial loss of the chromosome 10 long arm (33% of examined MCC cases). The PTEN tumor-suppressor gene has been mapped to 10q23.3 and was shown to be mutated in a variety of human cancers including SCLC. Germline PTEN mutations have been observed in familial predisposing cancer syndromes including Cowden disease. Interestingly, an association between Cowden syndrome and Merkel cell carcinoma has been reported. To study the possible role of PTEN in MCC oncogenesis, loss of heterozygosity (LOH) analysis for the 10q23 region was performed on 26 MCC tumor samples from 23 MCC patients. The PTEN locus was deleted in 9 of 21 (43%) informative MCC tumor samples [7 of 18 (39%) MCC patients]. Despite this high frequency of LOH at 10q23, mutation and homozygous deletion screening of the PTEN gene revealed only one tumor with a nonsense mutation and a second with a homozygous deletion of exon 9. These data suggest that either alternative mechanisms lead to inactivation of the PTEN gene or that other tumor-suppressor genes at chromosome 10 are implicated in the development of MCC.

Mutation analysis of P73 and TP53 in Merkel cell carcinoma.

The p73 gene has been mapped to 1p36.33, a region which is frequently deleted in a wide variety of neoplasms including tumours of neuroectodermal origin. The p73 protein shows structural and functional homology to p53. For these reasons, p73 was considered as a positional and functional candidate tumour suppressor gene. Thus far, mutation analysis has provided no evidence for involvement of p73 in oligodendrogliomas, lung carcinoma, oesophageal carcinoma, prostatic carcinoma and hepatocellular carcinoma. In neuroblastoma, two mutations have been observed in a series of 140 tumours. In view of the occurrence of 1p deletions in Merkel cell carcinoma (MCC) and the location of p73 we decided to search for mutations in the p73 gene in five MCC cell lines and ten MCC tumours to test potential tumour suppressor function for this gene in MCC. In view of the possible complementary functions of p73 and TP53 we also examined the status of the TP53 gene. Sequence analysis of the entire coding region of the p73 gene revealed previously reported polymorphisms in four MCCs. In one MCC tumour, a mis-sense mutation located in the NH2-terminal transactivation region of the p73 gene was found. These results show that p73, analogous to neuroblastoma, is infrequently mutated in MCC. This is also the first report in which the role of TP53 in MCC has been investigated by sequencing the entire coding region of TP53. TP53 mis-sense mutations and one non-sense mutation were detected in three of 15 examined MCCs, suggesting that TP53 mutations may play a role in the pathogenesis or progression of a subset of MCCs. Moreover, typical UVB induced C to T mutations were found in one MCC cell line thus providing further evidence for sun-exposure in the aetiology of this rare skin cancer.

Deletion mapping on the short arm of chromosome 1 in Merkel cell carcinoma.

Twenty-two Merkel cell carcinoma (MCC) biopsies and six cell lines from 24 patients were examined for loss of heterozygosity (LOH) at 11 loci on 1p and one on 1q, to determine LOH regions on chromosome 1p. Sixteen (73%) tumors had LOH for at least one locus; 14 demonstrated LOH at more than one locus, and 7 (29%) samples had more than one region of loss, with 4 of these having loss at all informative loci on 1p. Three common regions of loss (SRO) were defined by LOH in multiple tumors. Eight samples demonstrated LOH between D1S214 and D1S160 (1p36), seven between D1S234 and D1S186 (1p35), and 11 for the region centromeric of D1S211 and D1S220 (1p32-1p33). Seven samples (29%) demonstrated more than one region of loss. LOH on 1p occurs frequently in MCC and more than one tumor suppressor gene on 1p is likely to play a role in the development of this tumor type.

Molecular analysis of 1p36 breakpoints in two Merkel cell carcinomas.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine tumor of the skin. Only little information is available on the genetic alterations occurring in this tumor. Cytogenetic studies thus far have not shown recurrent chromosomal changes, although various structural chromosome 1 rearrangements, including deletions, often leading to loss of distal 1p material appear to be frequent. We report on fluorescence in situ hybridization and loss of heterozygosity analyses of an MCC tumor and MCC cell line UISO. The present study has shown that two distinct regions in the most distal band 1p36 on the short arm of chromosome 1 can be implicated in MCC. One region at 1p36.3 was delineated by a distal deletion in the MCC tumor as a result of an unbalanced translocation, resulting in loss of all markers distal to ENO1. This region was previously shown to be deleted in different tumor types including neuroblastoma. In cell line UISO an insertion in 1p36.2 was identified. The insertion breakpoint indicates a second, more proximal, region on 1p involved in MCC. The insertion breakpoint was mapped within a cluster of repetitive tRNA and snRNA genes and thus could coincide with the constitutional 1p36 breakpoint previously reported in a patient with neuroblastoma.

Characteristic pattern of chromosomal gains and losses in Merkel cell carcinoma detected by comparative genomic hybridization.

Merkel cell carcinoma or small cell carcinoma of the skin is a rare skin cancer seen in increasing numbers in Queensland, Australia. In its clinical course and histopathology, it resembles small cell lung carcinoma (SCLC). Little is known of the genetic basis of this disease except for a number of cytogenetic studies and three loss of heterozygosity studies. Therefore, comparative genomic hybridization was performed to determine the characteristic DNA gains and losses that occur in this tumor. Comparative genomic hybridization analysis of 34 specimens from 24 patients revealed a pattern of gains and losses that closely resembles that seen in SCLC. Overall frequent loss was seen for chromosomes 3p (46%), 5q (21%), 8p (21%), 10 (33%), 11q (17%), 13q (33%), and 17p (25%). Significant gains were seen for chromosomes 1 (63%), 3q (33%), 5p (38%), 8q (38%), 19 (63%), and X (41%), with smaller numbers having gains for chromosomes 6, 7, 20, and 21. In contrast to SCLC, amplification in Merkel cell carcinoma is a rare event.

Loss of heterozygosity of chromosome 13 in Merkel cell carcinoma.

We have examined a series of 24 Merkel cell carcinoma (MCC) DNAs for loss of heterozygosity (LOH) at eight loci on chromosome 13. All patients were heterozygous for at least one locus. Overall, 18 of 24 (75%) patients showed LOH, among whom 10 patients demonstrated LOH at all informative loci. A single common region of loss was identified in all cases and included the marker D13S233 (13q14.3), which maps close to the retinoblastoma susceptibility gene RB1. The RB1 protein was not detected by Western blot analysis in any of nine MCC cell lines tested. These data indicate that 13q losses are the most common chromosomal losses observed to date in MCC and the likely target of these deletions is the RB1 locus.

Insights into the Merkel cell phenotype from Merkel cell carcinoma cell lines.

Merkel cell carcinoma (MCC) of the skin is an aggressive form of skin cancer and is being seen with increasing incidence in Queensland. We have recently established a number of MCC cell lines and characterized these for growth, morphology, expression of neuroendocrine markers and radiation sensitivity. As a result, cell lines were grouped into four classes by their morphology in a similar way to small cell lung cancer (SCLC) cell lines. Types I and II cell lines grew slowly as tight spherical clusters suspended in the medium, with Type II cell lines less densely packed than the Type I cell lines. Type III cell lines grew as flat 2-dimensional clusters and had shorter doubling times and Type IV cell lines grew as adherent monolayers and had the shortest doubling times. Expression of neuroendocrine markers distinguished those with a classic phenotype from those with a variant one. Mainly morphological Types I and II retained the classic phenotype while Classes III and IV had a variant phenotype. The range of surviving fraction at 2 Gray (SF2 0.2-0.45) seen in MCC cell lines was not as high as seen in SCLC cell lines but the variant ones tended to be more radiation resistant. Examination of POU proteins showed that neuroendocrine phenotype was linked with expression of brn-2, and growth in suspension with brn-3c.

Loss of heterozygosity studies in squamous cell carcinomas of the head and neck.

BACKGROUND: Loss of heterozygosity (LOH) studies have been pivotal in identifying tumor suppressor genes involved in the pathogenesis of a number of cancers. In squamous cell carcinomas of the head and neck region (SCCHN), LOH studies using the Southern blot technique are scarce. METHODS: SCCHNs were obtained immediately after surgical resection from 78 patients. Histologic confirmation was made by frozen section and tumors with less than 50% malignant cells were excluded. DNA was digested with restriction enzymes, and after Southern blotting the membranes were hybridized with radio-labeled probes. Chromosome arms analyzed included 1p, 3p, 4p, Sq, 8p, lOp, 11p, 11q, 13q, 17p, 17q, 18q, 21q, and 22q. RESULTS: The average rate LOH was 25% per chromosome arm. Significantly higher rates of LOH were observed for chromosome arms 5q (56%) and 17p (45%). Other investigators have reported high rates of LOH for the H- ras-1 locus, and chromosome arms 11p, 11q, and 13q. However, these results were not confirmed in this study. For patients with stage 1 or 2 tumors, the overall LOH rate was 13%, and for patients with stage 3 or 4 disease the rate was 23%. This difference was statistically significant (p < 0.025). CONCLUSIONS: tumors progress to higher stages, they appear to accumulate an increasing number of genetic abnormalities. Chromosome arms 5q and 17p contain tumor suppressor genes which are likely to be involved in the pathogenesis of SCCHN: