Mark Laslett

Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function1-8 . These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells...

BACKGROUND: Estimating the contribution of endplate oedema known as Modic changes to lower back pain (LBP) has been the subject of multiple observational studies and reviews, some of which conclude that the evidence for an association of Modic change with LBP is uncertain while others demonstrate a clear link. The clinical trials demonstrating the benefit of basivertebral nerve ablation, a therapeutic intervention, in a tightly defined homogenous patient group with chronic LBP and Modic changes type 1 or type 2, provides further evidence for the contribution of Modic changes to LBP and shows that in these subjects, nerve ablation substantially reduces pain and disability...

BACKGROUND: A lumbar lateral shift (LLS) is a common clinical observation in patients with low back pain (LBP), and a shift contralateral to the side of pain is the most common presentation. An LLS that can rapidly alternate sides presents several treatment difficulties and has rarely been described. The purpose of the current case report was to describe the presentation and management of a patient with an alternating LLS. CASE DESCRIPTION: A 39-year-old male with a 7-week history of LBP and previous lower extremity radicular pain was referred to physical therapy...

BACKGROUND: Pelvic girdle pain (PGP) and sacroiliac joint (SIJ) dysfunction/pain are considered frequent contributors to low back pain (LBP). Like other persistent pain conditions, PGP is increasingly recognized as a multifactorial problem involving biological, psychological, and social factors. Perspectives differ between experts and a diversity of treatments (with variable degrees of evidence) have been utilized. OBJECTIVE: To develop a collaborative model of PGP that represents the collective view of a group of experts...

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BACKGROUND: Clinical examination findings are used in primary care to give an initial diagnosis to patients with low back pain and related leg symptoms. The purpose of this study was to develop best evidence Clinical Diagnostic Rules (CDR] for the identification of the most common patho-anatomical disorders in the lumbar spine; i.e. intervertebral discs, sacroiliac joints, facet joints, bone, muscles, nerve roots, muscles, peripheral nerve tissue, and central nervous system sensitization...

BACKGROUND: The diagnosis of subacromial pathology is limited by the poor accuracy of clinical tests for specific pathologies. The aim of this study was to estimate the diagnostic accuracy of clinical examination and imaging features for identifying subacromial pain (SAP) defined by a positive response to diagnostic injection, and to evaluate the influence of imaging findings on the clinical diagnosis of SAP. METHODS AND FINDINGS: In a prospective, diagnostic accuracy design, 208 consecutive patients presenting to their primary healthcare practitioner for the first time with a new episode of shoulder pain were recruited...

OBJECTIVE: To determine the reliability of patient reports of pain intensity during the application of physical tests. METHODS: A single examiner required participants to use the numeric pain rating scale (NPRS) to report the intensity of pain provoked during physical testing of the hip. Standardized versions of 14 physical tests were used on 18 people with hip pain. Tests were repeated at 1 hour and 2-7 days later. Within- and between-session reliability of reports of pain intensity was calculated using intraclass correlation coefficients (ICCs) and Lin's concordance correlation coefficients (CCCs)...

OBJECTIVE: Identify predictor variables and models for clinical outcomes for primary care shoulder pain patients to 12 months follow-up. DESIGN: A non-randomized audit with measures of pain and disability at 3 weeks, 3, 6 and 12 months. PATIENTS: Of 208 patients, 161 agreed to participate with 96.9, 98.1, 87.0 and 83.9% follow-up at 3 weeks, 3, 6 and 12 months respectively. Treatment consisted of exercise and manual therapy-based physiotherapy and corticosteroid injection under specified selection criteria...

OBJECTIVE: Measure changes in pain and disability of primary care shoulder pain patients over a 12-month period. DESIGN: A non-randomized audit with repeated measures of pain and disability at 3 weeks, 3, 6 and 12 months. PATIENTS: Of 208 patients, 161 agreed to participate with 96.9%, 98.1%, 86.3%, 83.9% follow-up at 3 weeks, at 3, 6 and 12 months, respectively. Mean age was 44 years, mean symptom duration 3.6 months. METHODS: PATIENTS were treated with protocol driven corticosteroid injection and community based care...

OBJECTIVES: Rotator cuff tears are a common and disabling complaint. The early diagnosis of medium and large size rotator cuff tears can enhance the prognosis of the patient. The aim of this study was to identify clinical features with the strongest ability to accurately predict the presence of a medium, large or multitendon (MLM) rotator cuff tear in a primary care cohort. METHODS: Participants were consecutively recruited from primary health care practices (n = 203)...

BACKGROUND: Despite numerous methodological flaws in previous study designs and the lack of validation in primary care populations, clinical tests for identifying acromioclavicular joint (ACJ) pain are widely utilised without concern for such issues. The aim of this study was to estimate the diagnostic accuracy of traditional ACJ tests and to compare their accuracy with other clinical examination features for identifying a predominant ACJ pain source in a primary care cohort. METHODS: Consecutive patients with shoulder pain were recruited prospectively from primary health care clinics...

OBJECTIVE: To compare the accuracy of combinations of clinical examination findings for predicting a positive response to injection of local anaesthetic into the subacromial bursa. DESIGN: Prospective, cohort, diagnostic validity design. SUBJECTS: Consecutive patients with shoulder pain recruited from primary care physiotherapy and general medical practices. METHODS: All subjects underwent a standardised clinical examination (index test) followed by a diagnostic injection of xylocaineTM into the subacromial bursa (reference standard test) performed under ultrasound guidance...

OBJECTIVES: Key diagnostic decisions often turn on measurement of change in pain intensity after diagnostic anesthetic blocks. This study aimed to introduce a new direct measure pain intensity change and compare it with percent change as calculated from the traditional preprocedure and postprocedure pain visual analog scales. METHODS: Shoulder pain patients enrolled in a diagnostic accuracy study comparing clinical variables with image-guided local anesthetic injections were assessed with both the traditional preprocedure and postprocedure visual analog scales and the new direct method...

PURPOSE: Over 20 years ago the term non-specific low back pain became popular to convey the limitations of our knowledge of the pathological source of most people's low back pain. Knowledge of underlying pathology has advanced little since then, despite limited improvements in outcomes for patients with low back pain. METHODS: This paper discusses potential misunderstandings related to diagnostic studies in the field of low back pain and argues that future diagnostic studies should include and investigate pathological sources of low back pain...

BACKGROUND: The prevalence of imaged pathology in primary care has received little attention and the relevance of identified pathology to symptoms remains unclear. This paper reports the prevalence of imaged pathology and the association between pathology and response to diagnostic blocks into the subacromial bursa (SAB), acromioclavicular joint (ACJ) and glenohumeral joint (GHJ). METHODS: Consecutive patients with shoulder pain recruited from primary care underwent standardised x-ray, diagnostic ultrasound scan and diagnostic injections of local anaesthetic into the SAB and ACJ...

Orthopaedic special tests (OST) are commonly used in the assessment of the painful shoulder to assist to rule-in or rule-out specific pathology. A small number of tests with high levels of diagnostic accuracy have been identified but interexaminer reliability data is variable or lacking. The aim of this study was to determine the interexaminer reliability of a group of OST with demonstrated diagnostic accuracy at primary care level. Forty consecutive subjects with shoulder pain were recruited. Six tests were performed by two examiners (physiotherapists) on the same day...

Acceptable reliability is a prerequisite for inclusion of physical examination tests in clinical examinations of the painful shoulder. The aim of this study was to establish the intraexaminer and interexaminer reliability of measures of shoulder range of motion (ROM) and muscle force using a new hand-held dynamometer with the ability to standardize overpressure force during passive ROM tests. Forty consecutive subjects with shoulder pain were recruited, and tests were performed by two physiotherapists. Tests included active ROM elevation, passive ROM glenohumeral abduction and external rotation and resisted abduction and external rotation...

BACKGROUND: Low-back pain with leg pain (sciatica) may be caused by a herniated intervertebral disc exerting pressure on the nerve root. Most patients will respond to conservative treatment, but in carefully selected patients, surgical discectomy may provide faster relief of symptoms. Primary care clinicians use patient history and physical examination to evaluate the likelihood of disc herniation and select patients for further imaging and possible surgery. OBJECTIVES: (1) To assess the performance of tests performed during physical examination (alone or in combination) to identify radiculopathy due to lower lumbar disc herniation in patients with low-back pain and sciatica;(2) To assess the influence of sources of heterogeneity on diagnostic performance...

The acute onset lumbar lateral shift, otherwise known as a list or acute scoliosis, is a common clinical observation associated with low back pain. In general orthopaedics, the presence of a lateral shift is associated with a poor prognosis; however, a manual correction method devised by McKenzie is claimed to produce rapid reversal of the deformity and reduction in pain. This single-case report presents the details of the McKenzie Mechanical Diagnosis and Treatment (MDT) management of a major right-sided lateral shift, which includes the manual correction technique, self-correction and management, prophylaxis, pain ablation, and rehabilitation to a high level of athletic function, with long-term follow-up at 9 months...