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Abstract Background Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M. Methods We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing. Results We verified three mutations - c.542delC in SOX2, resulting in p.Pro181Argfs*22, p.Glu105X in OTX2 and p.Cys240X in FOXE3. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in CRYBA4, p.Val201Met in FOXE3 and p.Asp291Asn in VSX2. Our analysis methodology gave one false positive result comprising a mutation in PAX6 (c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in SOX2. Conclusions Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.

Abstract Background Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25–50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient. Methods This paper describes the protocol of a randomised clinical trial comparing the effects of motor control exercises with a graded activity program in the treatment of chronic non specific low back pain. Further analysis will identify clinical features that may predict a patient's response to each treatment. One hundred and seventy two participants will be randomly allocated to receive either a program of motor control exercises or graded activity. Measures of outcome will be obtained at 2, 6 and 12 months after randomisation. The primary outcomes are: pain (average pain intensity over the last week) and function (patient-specific functional scale) at 2 and 6 months. Potential treatment effect modifiers will be measured at baseline. Discussion This trial will not only evaluate which exercise approach is more effective in general for patients will chronic low back pain, but will also determine which exercise approach is best for an individual patient. Trial registration number ACTRN12607000432415

Background: Chronic low back pain remains a major health problem in Australia and around the world. Unfortunately the majority of treatments for this condition produce small effects because not all patients respond to each treatment. It appears that only 25-50% of patients respond to exercise. The two most popular types of exercise for low back pain are graded activity and motor control exercises. At present however, there are no guidelines to help clinicians select the best treatment for a patient. As a result, time and money are wasted on treatments which ultimately fail to help the patient.Methods: This paper describes the protocol of a randomised clinical trial comparing the effects of motor control exercises with a graded activity program in the treatment of chronic non specific low back pain. Further analysis will identify clinical features that may predict a patient's response to each treatment. One hundred and seventy two participants will be randomly allocated to receive either a program of motor control exercises or graded activity. Measures of outcome will be obtained at 2, 6 and 12 months after randomisation. The primary outcomes are: pain (average pain intensity over the last week) and function (patient-specific functional scale) at 2 and 6 months. Potential treatment effect modifiers will be measured at baseline.Discussion: This trial will not only evaluate which exercise approach is more effective in general for patients will chronic low back pain, but will also determine which exercise approach is best for an individual patient.Trial Registration Number: ACTRN12607000432415. [ABSTRACT FROM AUTHOR]

Introduction: Although a number of contraception methods exist, long-acting reversible contraceptives have been recommended for female adolescents owing to their low failure rates. However, concern exists that the increasing use of long-acting reversible contraceptive among female adolescents may have unintended consequences of decreasing condom use for the prevention of sexually transmitted infections. Despite this concern, few studies have directly explored the relationship between the use of long-acting reversible contraceptive versus other forms of contraception and diagnosis of sexually transmitted infections in female adolescents. This study compares the rates of sexually transmitted infection diagnosis following various forms of contraceptive use., Methods: This study was an archival data analysis of single state Medicaid claims retrieved for female adolescents, aged 14-19 years, who received a contraceptive prescription and had 1 year of follow-up data available (n=62,550) between 2011 and 2015. Incidence of sexually transmitted infections was the outcome of interest. Data analysis was conducted in 2018., Results: Compared with the contraceptive pill, hormonal implant (a form of long-acting reversible contraceptives) was associated with significantly lower risk of sexually transmitted infections (hazard ratio=0.81; 95% CI=0.70, 0.93; p=0.004), and hormonal injection was associated with higher risk of sexually transmitted infections (hazard ratio=1.08; 95% CI=1.00, 1.16; p=0.040)., Conclusions: This analysis provides strong evidence that the risk for the acquisition of sexually transmitted infections is no higher for long-acting reversible contraceptives than for other forms of contraception. These results support the use of long-acting reversible contraceptive in female adolescents, as proposed and reaffirmed by the American College of Obstetricians and Gynecologists and American Academy of Pediatrics., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Motor control exercises to improve control and coordination of trunk muscles and graded activity under the principles of cognitive-behavioral therapy are 2 commonly used exercise therapies, yet there is little evidence to support the use of one intervention over the other., Objective: The objective of this study was to compare the effectiveness of motor control exercises and graded activity for patients with chronic nonspecific low back pain., Design: This study was a prospectively registered randomized controlled trial with outcome assessment and statistical analyses conducted blind to group., Setting: The study was conducted in primary care settings., Patients: The participants were 172 patients with chronic (>12 weeks) nonspecific low back pain., Interventions: Patients were randomly assigned to receive either motor control exercises or graded activity. There was no attempt to subclassify patients to match them to a treatment. Patients in both groups received 14 sessions of individualized, supervised exercise therapy., Measurements: Primary outcomes were average pain over the previous week (numeric rating scale) and function (Patient-Specific Functional Scale); secondary outcomes were disability (24-item Roland-Morris Disability Questionnaire), global impression of change (Global Perceived Effect Scale), and quality of life (36-Item Short-Form Health Survey questionnaire [SF-36]). Outcome measures were collected at baseline and at 2, 6, and 12 months after intervention., Results: A linear mixed models analysis showed that there were no significant differences between treatment groups at any of the time points for any of the outcomes studied. For example, the effect for pain at 2 months was 0.0 (-0.7 to 0.8)., Limitations: Clinicians could not be blinded to the interventions., Conclusion: results of this study suggest that motor control exercises and graded activity have similar effects for patients with chronic nonspecific low back pain.

Self-management of chronic illnesses has been widely recognised as an important goal on quality of life, health service utilisation and cost grounds. This study describes the first published account on the application of this approach to people suffering from chronic pain conditions in a Southeast Asian country, Malaysia. A heterogeneous sample of chronic pain patients in Malaysia attended a 2-week cognitive-behavioural pain management programme (PMP) aimed at improving daily functional activities and general psychological well-being. Complete datasets from 70 patients out of 102 patients who attended 11 programmes conducted from 2002 to 2007, as well as the 1-month and 1-year follow-up sessions at the hospital clinic, are reported. The pre- to post-treatment results on self-report measures indicate that significant gains were achieved on the dimensions of pain, disability and psychological well-being. These gains were maintained at both 1-month and 1-year follow-ups. The results mirror those reported from similar interventions in Europe and North America and indicate the concept of self-management of a chronic illness is acceptable and meaningful to Asian patients. Importantly, the achieved outcomes were independent of gender and ethnic group status.

Background: Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M., Methods: We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing., Results: We verified three mutations - c.542delC in SOX2, resulting in p.Pro181Argfs*22, p.Glu105X in OTX2 and p.Cys240X in FOXE3. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in CRYBA4, p.Val201Met in FOXE3 and p.Asp291Asn in VSX2. Our analysis methodology gave one false positive result comprising a mutation in PAX6 (c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in SOX2., Conclusions: Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.

Background: Stretch is commonly prescribed as part of physical rehabilitation in pain management programs, yet little is known about its effectiveness., Objective: A randomized controlled trial was conducted to investigate the effects of a 3-week stretch program on muscle extensibility and stretch tolerance in patients with chronic musculoskeletal pain., Design: A within-subject design was used, with one leg of each participant randomly allocated to an experimental (stretch) condition and the other leg randomly allocated to a control (no-stretch) condition., Patients and Setting: Thirty adults with pain of musculoskeletal origin persisting for at least 3 months were recruited from patients enrolled in a multidisciplinary pain management program at a hospital in Sydney, Australia., Intervention: The hamstring muscles of the experimental leg were stretched daily for 1 minute over 3 weeks; the control leg was not stretched. This intervention was embedded within a pain management program and supervised by physical therapists., Measurements: Primary outcomes were muscle extensibility and stretch tolerance, which were reflected by passive hip flexion angles measured with standardized and nonstandardized torques, respectively. Initial measurements were taken before the first stretch on day 1, and final measurements were taken 1 to 2 days after the last stretch. A blinded assessor was used for testing., Results: Stretch did not increase muscle extensibility (mean between-group difference in hip flexion was 1 degrees , 95% confidence interval=-2 degrees to 4 degrees ), but it did improve stretch tolerance (mean between-group difference in hip flexion was 8 degrees , 95% confidence interval=5 degrees to 10 degrees )., Conclusion: Three weeks of stretch increases tolerance to the discomfort associated with stretch but does not change muscle extensibility in patients with chronic musculoskeletal pain.

Research suggests that a combination of a somatic and a psychosocial intervention for chronic noncancer pain should be associated with a better outcome than either alone. This study presents data on a series of 31 patients who underwent sequential treatment with an implantable device targeting pain relief and a cognitive-behavioral pain management program that targeted improved function. A combination of treatments was used as there was a suboptimal response to the initial treatment. There were improvements in a range of outcomes at a long-term follow-up. Significant improvements were found in disability, affective distress, self-efficacy, and catastrophizing, but not in average pain severity. Further analyses failed to demonstrate an order effect. These results support the view that combined somatic and psychosocial interventions can achieve better outcomes than either alone in selected chronic pain patients. This approach requires that psychological assessment is essential before the use of an implantable device. This may not only improve patient selection, but also identify psychosocial factors that may be modified to enhance the effectiveness of invasive interventions. In addition, consideration for an implantable device following a suboptimal response to treatment in a cognitive-behavioral pain management program should include a re-evaluation of the patients' beliefs and use of self-management (coping) strategies before deciding on further treatment options.

We have identified and cloned a cDNA encoding a new member of the monooxygenase family of enzymes. This novel enzyme, which we call MOX (monooxygenase X; unknown substrate) is a clear sequence homologue of the enzyme dopamine beta-hydroxylase (DBH). MOX maintains many of the structural features of DBH, as evidenced by the retention of most of the disulfide linkages and all of the peptidyl ligands to the active site copper atoms. Unlike DBH, MOX lacks a signal peptide sequence and therefore is unlikely to be a secreted molecule. The steady-state mRNA levels of MOX are highest in the kidney, lung, and adrenal gland, indicating that the tissue distribution of MOX is broader than that of DBH. Antisera raised to a fusion protein of MOX identifies a single band of the expected mobility by Western blot analysis. MOX mRNA levels are elevated in some fibroblast cell strains at replicative senescence, through this regulation is not apparent in all primary cell strains. The gene for MOX resides on the q arm of chromosome 6 and the corresponding mouse homolog has been identified.

Recently, a novel PCR-based technique, differential display (DD), has facilitated the study of differentially expressed genes at the mRNA level. We report here an improved version of DD, which we call Enhanced Differential Display (EDD). We have modified the technique to enhance reproducibility and to facilitate sequencing and cloning. Using EDD, we have generated and verified a catalog of genes that are differentially expressed between young and senescent human diploid fibroblasts (HDF). From 168 genetags that were identified initially, 84 could be sequenced directly from PCR amplified bands. These sequences represent 27 known genes and 37 novel genes. By Northern blot analysis we have confirmed the differential expression of a total of 23 genes (12 known, 11 novel), while 19 (seven known, 12 novel) did not show differential expression. Several of the known genes were previously observed by others to be differentially expressed between young and senescent fibroblasts, thereby validating the technique.