Improvement of lower extremity electrodiagnostic findings following a trial of spinal manipulation and motion-based therapy

BACKGROUND: Lumbar disc herniation is a problem frequently encountered in manual medicine. While manual therapy has shown reasonable success in symptomatic management of these cases, little information is known how manual therapy may affect the structure and function of the lumbar disc itself. In cases where lumbar disc herniation is accompanied by radicular symptoms, electrodiagnostic testing has been used to provide objective clinical information on nerve function. This report examines the treatment rendered for a patient with lower extremity neurological deficit, as diagnosed on electrodiagnostic testing. Patient was treated using spinal manipulation and exercises performed on a Pettibon Wobble Chair™, using electrodiagnostic testing as the primary outcome assessment. CASE PRESENTATION: An elderly male patient presented to a private spine clinic with right-sided foot drop. He had been prescribed an ankle-foot orthosis for this condition. All sensory, motor, and reflex findings in the right leg and foot were absent. This was validated on prior electromyography and nerve conduction velocity testing, performed by a board certified neurologist. Patient was treated using spinal manipulation twice-weekly and wobble chair exercises three times daily for 90 days total. Following this treatment, the patient was referred for follow-up electrodiagnostic studies. Significant improvements were made in these studies as well as self-rated daily function. CONCLUSION: Motion-based therapies, as part of a comprehensive rehabilitation program, may contribute to the restoration of daily function and the reversal of neurological insult as detected by electrodiagnostic testing. Electrodiagnostic testing may be a useful clinical tool to evaluate the progress of chiropractic patients with lumbar disc herniation and radicular pain syndromes

General practitioners apply the usual care for shoulder complaints better than expected – analysis of videotaped consultations

BACKGROUND: The education and activation program (EAP) is a newly developed intervention to prevent the development of chronic shoulder complaints (SCs). Trained general practitioners (GPs) administer the EAP. The EAP addresses inadequate cognitions and maladaptive behavior related to the SCs. The effect of the EAP is evaluated in a randomized clinical trial. The aim of the present study is to use videotaped consultations to study (1) the performance of trained GPs administering the EAP and (2) the presence of key features of the EAP already embedded in usual care (UC). METHODS: Five trained GPs were videotaped while treating a standardized patient with EAP. Additionally, five GPs administering UC were videotaped. Two blinded observers evaluated the videotapes in relation to key features of the EAP which were scored on the EAP checklist. RESULTS: The mean total score on the EAP checklist was 4.7 (SD = 2.9) for the UC group and 7.1 (SD = 2.1) for the EAP group. Neither group reached a score higher than 8, which was considered to reflect an acceptable number of key EAP features. CONCLUSION: Our comparison of the presence of key features of EAP shows that the UC and EAP groups differed less than was expected. GPs in the UC group performed above expectation, with a mean total score of 4.7. Moreover, the low number of key features present in the EAP group may very well have led to a reduced effectiveness of the EAP. The results of this study can be used to optimize the training of GPs using the EAP

Was Wright Right? The Canonical Genetic Code is an Empirical Example of an Adaptive Peak in Nature; Deviant Genetic Codes Evolved Using Adaptive Bridges

The canonical genetic code is on a sub-optimal adaptive peak with respect to its ability to minimize errors, and is close to, but not quite, optimal. This is demonstrated by the near-total adjacency of synonymous codons, the similarity of adjacent codons, and comparisons of frequency of amino acid usage with number of codons in the code for each amino acid. As a rare empirical example of an adaptive peak in nature, it shows adaptive peaks are real, not merely theoretical. The evolution of deviant genetic codes illustrates how populations move from a lower to a higher adaptive peak. This is done by the use of “adaptive bridges,” neutral pathways that cross over maladaptive valleys by virtue of masking of the phenotypic expression of some maladaptive aspects in the genotype. This appears to be the general mechanism by which populations travel from one adaptive peak to another. There are multiple routes a population can follow to cross from one adaptive peak to another. These routes vary in the probability that they will be used, and this probability is determined by the number and nature of the mutations that happen along each of the routes. A modification of the depiction of adaptive landscapes showing genetic distances and probabilities of travel along their multiple possible routes would throw light on this important concept

Perfusion by Arterial Spin Labelling following Single Dose Tadalafil in Small Vessel Disease (PASTIS): study protocol for a randomized controlled trial

Background Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. Methods/design Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. Sample size: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p < 0.05, 90% power). Primary outcomes are cerebral blood flow in subcortical white matter and deep grey nuclei. Secondary outcomes are cortical grey matter cerebral blood flow and performance on cognitive tests (reaction time, information processing speed, digit span forwards and backwards, semantic fluency). Discussion Recruitment started on 4th September 2015 and 36 participants have completed to date (19th April 2017). No serious adverse events have occurred. All participants have been recruited from one centre, St George’s University Hospitals NHS Foundation Trust. Trial registration European Union Clinical Trials Register: EudraCT number 2015-001235-20. Registered on 13 May 2015

Flexion Relaxation and Its Relation to Pain and Function over the Duration of a Back Pain Episode

BACKGROUND: Relaxation of the erector spinae often occurs in healthy individuals as full trunk flexion is achieved when bending forward from standing. This phenomenon, referred to as flexion relaxation is often absent or disrupted (EMG activity persists) in individuals reporting low back pain (LBP). METHODS AND RESULTS: Self-reported pain and disability scores were compared to EMG measures related to the flexion relaxation (FR) phenomenon by 33 participants with LBP at up to eight sessions over a study period of up to eight weeks. Fourteen participants served as a control group. In the protocol, starting from standing participants bent forward to a fully flexed posture, and then extended the trunk to return to standing position. A thoracic inclinometer was used to measure trunk posture. Surface electrodes located at the L2 and L5 levels recorded EMG amplitudes of the erector spinae. Ratios of EMG amplitudes recorded during forward bending to amplitudes at full flexion, and ratios of extension to full flexion were calculated. EMG amplitudes and their ratios were compared between control and LBP groups at the initial visit. No significant differences between groups were found except at the L5 location at full flexion. Correlations of the ratios to pain and function scores recorded in repeated sessions over the LBP episode also were compared between LBP group participants classified as having transient, recurrent or chronic symptoms. In another analysis participants were grouped by whether their symptoms resolved over the study period. CONCLUSIONS: The transient LBP group had significantly stronger correlations between pain and function to both ratios, than did those with more chronic LBP symptoms. Participants who experienced symptom resolution generally had stronger correlations of ratios to both pain and function than those with partial or no resolution. Improved understanding of these relationships may provide insight in clinical management of LBP

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth

Distinct physiological and behavioural functions for parental alleles of imprinted Grb10

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development1, but also postnatal functions including energy homeostasis2 and behaviour3, 4. When the two parental alleles are unequally represented within a social group (when there is sex bias in dispersal and/or variance in reproductive success)5, 6, imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules7. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10-deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue-specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus Grb10 is, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues

Structure and evolution of the mouse pregnancy-specific glycoprotein (Psg) gene locus

BACKGROUND: The pregnancy-specific glycoprotein (Psg) genes encode proteins of unknown function, and are members of the carcinoembryonic antigen (Cea) gene family, which is a member of the immunoglobulin gene (Ig) superfamily. In rodents and primates, but not in artiodactyls (even-toed ungulates / hoofed mammals), there have been independent expansions of the Psg gene family, with all members expressed exclusively in placental trophoblast cells. For the mouse Psg genes, we sought to determine the genomic organisation of the locus, the expression profiles of the various family members, and the evolution of exon structure, to attempt to reconstruct the evolutionary history of this locus, and to determine whether expansion of the gene family has been driven by selection for increased gene dosage, or diversification of function. RESULTS: We collated the mouse Psg gene sequences currently in the public genome and expressed-sequence tag (EST) databases and used systematic BLAST searches to generate complete sequences for all known mouse Psg genes. We identified a novel family member, Psg31, which is similar to Psg30 but, uniquely amongst mouse Psg genes, has a duplicated N1 domain. We also identified a novel splice variant of Psg16 (bCEA). We show that Psg24 and Psg30 / Psg31 have independently undergone expansion of N-domain number. By mapping BAC, YAC and cosmid clones we described two clusters of Psg genes, which we linked and oriented using fluorescent in situ hybridisation (FISH). Comparison of our Psg locus map with the public mouse genome database indicates good agreement in overall structure and further elucidates gene order. Expression levels of Psg genes in placentas of different developmental stages revealed dramatic differences in the developmental expression profile of individual family members. CONCLUSION: We have combined existing information, and provide new information concerning the evolution of mouse Psg exon organization, the mouse Psg genomic locus structure, and the expression patterns of individual Psg genes. This information will facilitate functional studies of this complex gene family

Many LINE1 elements contribute to the transcriptome of human somatic cells

Over 600 LINE 1 elements are shown to be transcribed in humans; 400 of these are full-length elements in the reference genome