FOXG1 targets BMP repressors and cell cycle inhibitors in human neural progenitor cells.

FOXG1 is a critical transcription factor in human brain where loss-of-function mutations cause a severe neurodevelopmental disorder, while increased FOXG1 expression is frequently observed in glioblastoma. FOXG1 is an inhibitor of cell patterning and an activator of cell proliferation in chordate model organisms but different mechanisms have been proposed as to how this occurs. To identify genomic targets of FOXG1 in human neural progenitor cells (NPCs), we engineered a cleavable reporter construct in endogenous FOXG1 and performed chromatin immunoprecipitation (ChIP) sequencing. We also performed deep RNA sequencing of NPCs from two females with loss-of-function mutations in FOXG1 and their healthy biological mothers. Integrative analyses of RNA and ChIP sequencing data showed that cell cycle regulation and Bone Morphogenic Protein (BMP) repression gene ontology categories were over-represented as FOXG1 targets. Using engineered brain cell lines, we show that FOXG1 specifically activates SMAD7 and represses CDKN1B. Activation of SMAD7 which inhibits BMP signaling may be one way that FOXG1 patterns the forebrain, while repression of cell cycle regulators such as CDKN1B may be one way that FOXG1 expands the NPC pool to ensure proper brain size. Our data reveal novel mechanisms on how FOXG1 may control forebrain patterning and cell proliferation in human brain development.

Kabuki syndrome stem cell models reveal locus specificity of histone methyltransferase 2D (KMT2D/MLL4).

Kabuki syndrome is frequently caused by loss-of-function mutations in one allele of histone 3 lysine 4 (H3K4) methyltransferase KMT2D and is associated with problems in neurological, immunological and skeletal system development. We generated heterozygous KMT2D knockout and Kabuki patient-derived cell models to investigate the role of reduced dosage of KMT2D in stem cells. We discovered chromosomal locus-specific alterations in gene expression, specifically a 110 Kb region containing Synaptotagmin 3 (SYT3), C-Type Lectin Domain Containing 11A (CLEC11A), Chromosome 19 Open Reading Frame 81 (C19ORF81) and SH3 And Multiple Ankyrin Repeat Domains 1 (SHANK1), suggesting locus-specific targeting of KMT2D. Using whole genome histone methylation mapping, we confirmed locus-specific changes in H3K4 methylation patterning coincident with regional decreases in gene expression in Kabuki cell models. Significantly reduced H3K4 peaks aligned with regions of stem cell maps of H3K27 and H3K4 methylation suggesting KMT2D haploinsufficiency impact bivalent enhancers in stem cells. Preparing the genome for subsequent differentiation cues may be of significant importance for Kabuki-related genes. This work provides a new insight into the mechanism of action of an important gene in bone and brain development and may increase our understanding of a specific function of a human disease-relevant H3K4 methyltransferase family member.

Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons.

We identified individuals with variations in ACTL6B, a component of the chromatin remodeling machinery including the BAF complex. Ten individuals harbored bi-allelic mutations and presented with global developmental delay, epileptic encephalopathy, and spasticity, and ten individuals with de novo heterozygous mutations displayed intellectual disability, ambulation deficits, severe language impairment, hypotonia, Rett-like stereotypies, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Nine of these ten unrelated individuals had the identical de novo c.1027G>A (p.Gly343Arg) mutation. Human-derived neurons were generated that recaptured ACTL6B expression patterns in development from progenitor cell to post-mitotic neuron, validating the use of this model. Engineered knock-out of ACTL6B in wild-type human neurons resulted in profound deficits in dendrite development, a result recapitulated in two individuals with different bi-allelic mutations, and reversed on clonal genetic repair or exogenous expression of ACTL6B. Whole-transcriptome analyses and whole-genomic profiling of the BAF complex in wild-type and bi-allelic mutant ACTL6B neural progenitor cells and neurons revealed increased genomic binding of the BAF complex in ACTL6B mutants, with corresponding transcriptional changes in several genes including TPPP and FSCN1, suggesting that altered regulation of some cytoskeletal genes contribute to altered dendrite development. Assessment of bi-alleic and heterozygous ACTL6B mutations on an ACTL6B knock-out human background demonstrated that bi-allelic mutations mimic engineered deletion deficits while heterozygous mutations do not, suggesting that the former are loss of function and the latter are gain of function. These results reveal a role for ACTL6B in neurodevelopment and implicate another component of chromatin remodeling machinery in brain disease.

Neuron-derived extracellular vesicles enriched from plasma show altered size and miRNA cargo as a function of antidepressant drug response.

Previous work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEV) to circumvent these limitations and investigate neuronal miRNA changes associated with antidepressant response. Samples were collected at two time points (baseline and after 8 weeks of follow-up) from depressed patients who responded (N = 20) and did not respond (N = 20) to escitalopram treatment, as well as controls (N = 20). Total extracellular vesicles (EVs) were extracted from plasma, and then further enriched for NDEV by immunoprecipitation with L1CAM. EVs and NDEVs were characterized, and NDEV miRNA cargo was extracted and sequenced. Subsequently, studies in cell lines and postmortem tissue were conducted. Characterization of NDEVs revealed that they were smaller than other EVs isolated from plasma (p < 0.0001), had brain-specific neuronal markers, and contained miRNAs enriched for brain functions (p < 0.0001) Furthermore, NDEVs from depressed patients were smaller than controls (p < 0.05), and NDEV size increased with ADT response (p < 0.01). Finally, changes in NDEV cargo, specifically changes in miR-21-5p, miR-30d-5p, and miR-486-5p together (p < 0.01), were associated with ADT response. Targets of these three miRNAs were altered in brain tissue from depressed individuals (p < 0.05). Together, this study indicates that changes in peripherally isolated NDEV can act as both a clinically accessible and informative biomarker of ADT response specifically through size and cargo.

miR-323a regulates ERBB4 and is involved in depression.

Major depressive disorder (MDD) is a complex and debilitating illness whose etiology remains unclear. Small RNA molecules, such as micro RNAs (miRNAs) have been implicated in MDD, where they display differential expression in the brain and the periphery. In this study, we quantified miRNA expression by small RNA sequencing in the anterior cingulate cortex and habenula of individuals with MDD and psychiatrically-healthy controls. Thirty-two miRNAs showed significantly correlated expression between the two regions (False Discovery Rate < 0.05), of which four, miR-204-5p, miR-320b, miR-323a-3p, and miR-331-3p, displayed upregulated expression in MDD. We assessed the expression of predicted target genes of differentially expressed miRNAs in the brain, and found that the expression of erb-b2 receptor tyrosine kinase 4 (ERBB4), a gene encoding a neuregulin receptor, was downregulated in both regions, and was influenced by miR-323a-3p in vitro. Finally, we assessed the effects of manipulating miRNA expression in the mouse ACC on anxiety- and depressive-like behaviors. Mice in which miR-323-3p was overexpressed or knocked-down displayed increased and decreased emotionality, respectively. Additionally, these mice displayed significantly downregulated and upregulated expression of Erbb4, respectively. Overall, our findings indicate the importance of brain miRNAs in the pathology of MDD, and emphasize the involvement of miR-323a-3p and ERBB4 in this phenotype. Future studies further characterizing miR-323a-3p and neuregulin signaling in depression are warranted.

Cocaine-related DNA methylation in caudate neurons alters 3D chromatin structure of the IRXA gene cluster.

Epigenetic mechanisms, like those involving DNA methylation, are thought to mediate the relationship between chronic cocaine dependence and molecular changes in addiction-related neurocircuitry, but have been understudied in human brain. We initially used reduced representation bisulfite sequencing (RRBS) to generate a methylome-wide profile of cocaine dependence in human post-mortem caudate tissue. We focused on the Iroquois Homeobox A (IRXA) gene cluster, where hypomethylation in exon 3 of IRX2 in neuronal nuclei was associated with cocaine dependence. We replicated this finding in an independent cohort and found similar results in the dorsal striatum from cocaine self-administering mice. Using epigenome editing and 3C assays, we demonstrated a causal relationship between methylation within the IRX2 gene body, CTCF protein binding, three-dimensional (3D) chromatin interaction, and gene expression. Together, these findings suggest that cocaine-related hypomethylation of IRX2 contributes to the development and maintenance of cocaine dependence through alterations in 3D chromatin structure in the caudate nucleus.

Integrative DNA Methylation and Gene Expression Analysis in the Prefrontal Cortex of Mexicans Who Died by Suicide.

BACKGROUND: Suicide represents a major health concern, especially in developing countries. While many demographic risk factors have been proposed, the underlying molecular pathology of suicide remains poorly understood. A body of evidence suggests that aberrant DNA methylation and expression is involved. In this study, we examined DNA methylation profiles and concordant gene expression changes in the prefrontal cortex of Mexicans who died by suicide. METHODS: In collaboration with the coroner's office in Mexico City, brain samples of males who died by suicide (n = 35) and age-matched sudden death controls (n = 13) were collected. DNA and RNA were extracted from prefrontal cortex tissue and analyzed with the Infinium Methylation480k and the HumanHT-12 v4 Expression Beadchips, respectively. RESULTS: We report evidence of altered DNA methylation profiles at 4430 genomic regions together with 622 genes characterized by differential expression in cases vs controls. Seventy genes were found to have concordant methylation and expression changes. Metacore-enriched analysis identified 10 genes with biological relevance to psychiatric phenotypes and suicide (ADCY9, CRH, NFATC4, ABCC8, HMGA1, KAT2A, EPHA2, TRRAP, CD22, and CBLN1) and highlighted the association that ADCY9 has with various pathways, including signal transduction regulated by the cAMP-responsive element modulator, neurophysiological process regulated by the corticotrophin-releasing hormone, and synaptic plasticity. We therefore went on to validate the observed hypomethylation of ADCY9 in cases vs control through targeted bisulfite sequencing. CONCLUSION: Our study represents the first, to our knowledge, analysis of DNA methylation and gene expression associated with suicide in a Mexican population using postmortem brain, providing novel insights for convergent molecular alterations associated with suicide.

A Dual Noradrenergic Mechanism for the Relief of Neuropathic Allodynia by the Antidepressant Drugs Duloxetine and Amitriptyline.

In addition to treating depression, antidepressant drugs are also a first-line treatment for neuropathic pain, which is pain secondary to lesion or pathology of the nervous system. Despite the widespread use of these drugs, the mechanism underlying their therapeutic action in this pain context remains partly elusive. The present study combined data collected in male and female mice from a model of neuropathic pain and data from the clinical setting to understand how antidepressant drugs act. We show two distinct mechanisms by which the selective inhibitor of serotonin and noradrenaline reuptake duloxetine and the tricyclic antidepressant amitriptyline relieve neuropathic allodynia. One of these mechanisms is acute, central, and requires descending noradrenergic inhibitory controls and α2A adrenoceptors, as well as the mu and delta opioid receptors. The second mechanism is delayed, peripheral, and requires noradrenaline from peripheral sympathetic endings and ß2 adrenoceptors, as well as the delta opioid receptors. We then conducted a transcriptomic analysis in dorsal root ganglia, which suggested that the peripheral component of duloxetine action involves the inhibition of neuroimmune mechanisms accompanying nerve injury, including the downregulation of the TNF-α-NF-κB signaling pathway. Accordingly, immunotherapies against either TNF-α or Toll-like receptor 2 (TLR2) provided allodynia relief. We also compared duloxetine plasma levels in the animal model and in patients and we observed that patients' drug concentrations were compatible with those measured in animals under chronic treatment involving the peripheral mechanism. Our study highlights a peripheral neuroimmune component of antidepressant drugs that is relevant to their delayed therapeutic action against neuropathic pain.SIGNIFICANCE STATEMENT In addition to treating depression, antidepressant drugs are also a first-line treatment for neuropathic pain, which is pain secondary to lesion or pathology of the nervous system. However, the mechanism by which antidepressant drugs can relieve neuropathic pain remained in part elusive. Indeed, preclinical studies led to contradictions concerning the anatomical and molecular substrates of this action. In the present work, we overcame these apparent contradictions by highlighting the existence of two independent mechanisms. One is rapid and centrally mediated by descending controls from the brain to the spinal cord and the other is delayed, peripheral, and relies on the anti-neuroimmune action of chronic antidepressant treatment.

Medium throughput bisulfite sequencing for accurate detection of 5-methylcytosine and 5-hydroxymethylcytosine.

BACKGROUND: Epigenetic modifications of DNA, such as 5-methylcytosine and 5-hydroxymethycytosine, play important roles in development and disease. Here, we present a cost-effective and versatile methodology for the analysis of DNA methylation in targeted genomic regions, which comprises multiplexed, PCR-based preparation of bisulfite DNA libraries followed by customized MiSeq sequencing. RESULTS: Using bisulfite and oxidative bisulfite conversion of DNA, we have performed multiplexed targeted sequencing to analyse several kilobases of genomic DNA in up to 478 samples, and achieved high coverage data of 5-methylcytosine and 5-hydroxymethycytosine at single-base resolution. Our results demonstrate the ability of this methodology to detect all levels of cytosine modifications at greater than 100× coverage in large sample sets at low cost compared to other targeted methods. CONCLUSIONS: This approach can be applied to multiple settings, from candidate gene to clinical studies, and is especially useful for validation of differentially methylated or hydroxymethylated regions following whole-genome analyses.

Spinal Manipulative Therapy for Adolescent Idiopathic Scoliosis: A Systematic Review.

OBJECTIVE: The purpose of this study was to perform a systematic review of clinical trials of spinal manipulative therapy for adolescent idiopathic scoliosis. METHODS: Search strategies were developed for PubMed, CINHAL, and CENTRAL databases. Studies were included through June 2016 if they were prospective trials that evaluated spinal manipulative therapy (eg, chiropractic, osteopathic, physical therapy) for adolescent idiopathic scoliosis. Data were extracted and assessed by 2 independent reviewers. Cochrane risk of bias tools were used to assess the quality of the included studies. Data were reported qualitatively because heterogeneity prevented statistical pooling. RESULTS: Four studies satisfied the inclusion criteria and were critically appraised. The findings of the included studies indicated that spinal manipulative therapy might be effective for preventing curve progression or reducing Cobb angle. However, the lack of controls and small sample sizes precluded robust estimation of the interventions' effect sizes. CONCLUSION: There is currently insufficient evidence to establish whether spinal manipulative therapy may be beneficial for adolescent idiopathic scoliosis. The results of the included studies suggest that spinal manipulative therapy may be a promising treatment, but these studies were all at substantial risk of bias. Further high-quality studies are warranted to conclusively determine if spinal manipulative therapy may be effective in the management of adolescent idiopathic scoliosis.

Investigation of genes important in neurodevelopment disorders in adult human brain.

Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

Guided Imagery for Adolescent Post-spinal Fusion Pain Management: A Pilot Study.

Orthopedic surgery for adolescent idiopathic scoliosis entails anxiety and severe postoperative pain. The aim of this pilot study was to investigate an intervention for adolescent post-spinal fusion pain management in patients from a tertiary care hospital in Montreal, Canada. Participants were adolescents and young adults ages 11 to 20 years undergoing spinal fusion. Participants were randomized to standard care or standard care with adjunct intervention. The intervention consisted of a DVD with information and guided imagery/relaxation exercises to practice at least three times a week at home. A nurse screened the DVD with the patient preoperatively and at discharge (T1) and telephoned 2 weeks post-discharge (T2) to reinforce the technique. Both groups completed questionnaires at T1, T2, and T3 (1-month postoperative follow-up). Outcome measures included pain intensity, anxiety, coping mechanisms, and daily activities. From March 2010 to June 2011, we enrolled 40 of 45 eligible participants (n = 20 per group), average age 15 ± 2.1 years, 7 participants were male. Compared with the control group, the experimental group experienced significantly less overall pain at all time points, with moderate to large effect sizes at T2, T3 (p ≤ .007). Worst pain in 24 hours was moderately decreased at T2 (p = .01). State-trait anxiety remained high. On a 10-point scale, a median 2.5-point benefit was seen in eating and sleeping (Mann-Whitney test, p = .002), and 2 points in walking (Mann-Whitney test, p = .003). Coping strategies showed no significant differences. Addition of a guided imagery and relaxation exercise DVD for home use was more effective than standard care alone for postoperative pain. Our nonpharmacologic adjunct looks promising. Larger sample size and longer (6-9 months) follow-up will permit refinement.

Frequency and indication of non-musculoskeletal examinations: a cross-sectional survey of Quebec chiropractors.

BACKGROUND: Approximately 1% of low back pain is estimated to be caused by serious systemic diseases, including cancer, infection, or abdominal aortic dissection. This study aimed to determine the frequency of execution of non-MSK physical examination procedures among Quebec chiropractors and to identify the clinical context that prompts them to use these physical examination procedures. METHODS: Cross-sectional survey containing 44 questions administered to a random sample of Quebec chiropractors using a succession of online, postal and phone questionnaires. The 4-part survey questionnaire contained six demographic questions, 28 single-choice questions to determine the frequency of execution of non-MSK physical examination procedures, seven short clinical vignettes for which the respondents had to select the non-MSK examinations that would be required, and two questions inquiring about the proportion of new patients for which participants' felt non-MSK examinations were necessary and whether appropriate assessments were performed. The questionnaire was pilot tested, and feedback received integrated prior to administration. We conducted descriptive statistics, Pearson correlations, and an ANOVA. RESULTS: The survey was completed by 182 chiropractors (response rate: 36.4%). The most commonly non-musculoskeletal examination performed daily were blood pressure (12.1%) and cranial nerves (4.9%). The most common tests never performed were oxygen saturation (68.7%), cardiac auscultation (69.2%), tibio-brachial index (71.4%), breast (86.8%), rectal (96.7%), testicular (95.6%), and vaginal (99.9%) exams. Female chiropractors and Quebec University in Trois-Rivières graduates reported that a significantly higher proportion of their new patients required a non-musculoskeletal physical examination compared to male participants (37.2% vs 28.3%) or Canadian Memorial Chiropractic College graduates (33.9% vs 19.9%). Reason for not performing a physical examination included the belief that another healthcare professional was better positioned to perform and/or interpret the related tests (76.4%). CONCLUSIONS: Vital signs and cranial nerve examinations were the most frequency performed non-musculoskeletal examinations reported by chiropractors. Apart from the genitourinary exam almost never performed, most participants chose non-musculoskeletal examinations deemed appropriate for the patient's presentation.

Spinal degeneration and lumbar multifidus muscle quality may independently affect clinical outcomes in patients conservatively managed for low back or leg pain.

Few non-surgical, longitudinal studies have evaluated the relations between spinal degeneration, lumbar multifidus muscle (LMM) quality, and clinical outcomes. None have assessed the potential mediating role of the LMM between degenerative pathology and 12-month clinical outcomes. This prospective cohort study used baseline and 12-month follow-up data from 569 patients conservatively managed for low back or back-related leg pain to estimate the effects of aggregate degenerative lumbar MRI findings and LMM quality on 12-month low back and leg pain intensity (0-10) and disability (0-23) outcomes, and explored the mediating role of LMM quality between degenerative findings and 12-month clinical outcomes. Adjusted mixed effects generalized linear models separately estimated the effect of aggregate spinal pathology and LMM quality. Mediation models estimated the direct and indirect effects of pathology on leg pain, and pathology and LMM quality on leg pain, respectively. Multivariable analysis identified a leg pain rating change of 0.99 [0.14; 1.84] (unstandardized beta coefficients [95% CI]) in the presence of ≥ 4 pathologies, and a disability rating change of - 0.65 [- 0.14; - 1.16] for each 10% increase in muscle quality, but no effect on back pain intensity. Muscle quality had a non-significant mediating role (13.4%) between pathology and leg pain intensity. The number of different pathologies present demonstrated a small effect on 12-month leg pain intensity outcomes, while higher LMM quality had a direct effect on 12-month disability ratings but no mediating effect between pathology and leg pain. The relations between degenerative pathology, LMM quality, and pain-related outcomes appear complex and may include independent pathways.

Creating and testing a questionnaire to predict immediate and strong positive responders to spinal manipulative therapy for non-specific low back pain. A pilot study.

BACKGROUND: Many chiropractors use spinal manipulative techniques (SMT) to treat spinal pain. A recent Delphi study posited 18 items across five domains as predictors of patients experiencing non-specific low back pain most likely to experience a strong and immediate positive response to SMT. We sought to create a 'pen and paper' questionnaire that would measure these items and then pilot its use in a clinical setting to determine its 'usability' for a larger study. Knowing this information would inform a more efficacious use of SMT. METHOD: Of the 18 items identified in the Delphi study, 13 were deemed historical in nature and readily provided by the chiropractor and patient. A literature search revealed reliable and valid measures for two more items. The remaining three items were generated by creating descriptive questions matched to an appropriate Likert scale. A panel of six chiropractors who had used SMT for at least 7 years when treating non-specific low back pain was formed to evaluate the items for clarity and relevance. Ten Western Australian chiropractors were then recruited to pilot the questionnaire on ten consecutive patients with non-specific low back pain where SMT was used from March to June 2020. Ethics approval was obtained from Murdoch University. RESULTS: COVID-19 restrictions impacted on practitioner recruitment and delayed the data collection. Of the intended 100 participants, only 63 could be recruited over a 3-month period from seven chiropractors. Time constraints forced the closure of the data collection. The measures of all predictor items demonstrated ceiling effects. Feedback from open-ended practitioner questions was minimal, suggesting an ease of use. CONCLUSION: The length of time and level of participation required to collect the calculated sample size was inadequate and suggested that incentivization may be required for a larger investigation. Significant ceiling effects were found and suggested that participants did so because of a positive bias toward chiropractic care and the use of SMT. The questionnaires in this pilot study require alternative measures and further validation before use in a larger study.

Exploring 1st- and 2nd-year chiropractic students' willingness and attitudes toward peer physical examination.

OBJECTIVE: This study aimed to explore chiropractic students' perceptions and attitudes about the appropriateness of peer physical examination as a teaching tool and their willingness and comfort with it. METHODS: A modified version of a validated questionnaire was used. First- and 2nd-year chiropractic students at Murdoch University were approached during their practical sessions. The responses were analyzed using descriptive statistics reporting frequencies and percentages. Comparison between classes, age, and sex was evaluated by cross-tabulation. RESULTS: A total of 184 questionnaires were completed with a response rate of 76.6%. Our results demonstrated that most students were comfortable with and willing to participate in peer physical examination as well as trusted it as an appropriate part of their training and a valuable learning experience. Nevertheless, a small percentage were uncomfortable with peer physical examination and regarded it as an unprofessional activity. In addition, it was revealed that younger females (≤20 years) reported feeling unnecessarily exposed and therefore significantly less comfortable with peer physical examination. They were also less comfortable when examined in the inguinal area by a student of the opposite sex. CONCLUSION: Although peer physical examination appears to be a very popular training tool, it still has a few areas of concern that need to be investigated and addressed to improve students' attitude, perception, and comfort with this teaching technique. Further studies could investigate how other factors such as religious beliefs contribute toward students' perception and attitudes regarding peer physical examination.

The impact of pregnancy on women with adolescent idiopathic scoliosis: a scoping review.

INTRODUCTION: Adolescent idiopathic scoliosis is the most common spinal deformity encountered in adolescents and larger curves are more prevalent in girls. For females with scoliosis, women's health issues are of particular concern, especially pregnancy. The aim of this review was to summarise the best available evidence to determine the influence of pregnancy on scoliosis-related outcomes in women with scoliosis and whether scoliosis affects maternal-health outcomes, differentiating between patients who have been managed conservatively and/or surgically. EVIDENCE ACQUISITION: A search was conducted using CINAHL, Scopus, Cochrane Database, MEDLINE, and EMBASE from inception to May 2023 to identify relevant articles in any language. The scoping review followed the PRISMA-ScR guidelines. Studies were eligible if they included pregnant women (primiparous or multiparous) with a diagnosis of scoliosis of unknown aetiology. The results were summarized by outcomes, including pregnancy and scoliosis-related outcomes and type of management. EVIDENCE SYNTHESIS: Our comprehensive search strategy identified 6872 articles, of which 50 articles were eligible for this review. Back pain appears to be more prevalent in this population during pregnancy and associated with the major curve and the decrease of lumbar lordosis. There have been reports of failed attempted spinal anaesthesia among patients with instrumented scoliosis correction and minor complications related to epidural anaesthesia at a higher rate compared to non-instrumented patients and healthy controls, however successful spinal analgesia can be achieved in patients with instrumented scoliosis correction. Overall, the caesarean section rate was similar in scoliosis patients compared to controls without scoliosis and to national averages. Curve progression occurs in some but not all patients during pregnancy, and this phenomenon occurs irrespective of the treatment received. CONCLUSIONS: Higher-quality prospective longitudinal research is needed to understand the relationship between pregnancy and adolescent idiopathic scoliosis. Further, the patient's perspective, concerns and fears surrounding pregnancy with scoliosis are yet to be explored. Exploring the impact of pregnancy on women with adolescent idiopathic scoliosis would have clinically relevant outcomes and could help provide pertinent answers to patients and healthcare workers and help guide future research.

Lumbar multifidus muscle morphology is associated with low back-related pain duration, disability, and leg pain: A cross-sectional study in secondary care.

BACKGROUND: Systematic reviews and studies exploring associations between morphologic change of paraspinal muscles and low back pain or related outcomes such as disability, radiculopathy, and physical workload, have reported conflicting results. This study explores the associations between lumbar multifidus muscle quality and clinical outcomes relating to low back pain. METHODS: Cross-sectional study of spinal clinic outpatients presenting with a primary complaint of low back and/or leg symptoms. Univariable and multivariable regression models were used to investigate associations between MRI-based multifidus muscle cross-sectional area at L4 and L5 and clinical outcomes for low back pain, leg pain, disability, restricted motion, and strenuous nature of work. Results were reported with ß-coefficients, odds ratios (OR), or incidence rate ratios (IRR) and their corresponding 95% confidence intervals, based on a 10% difference in muscle quality for each clinical variable. Multivariable analyses were adjusted for age, sex, and BMI. RESULTS: 875 patients [487 females; mean (SD) age: 43.6 (10.2) years] were included. In the multivariable analyses, muscle quality was significantly associated with disability (0-23 scale) [ß: -0.74, 95% CI: -1.14, -0.34], leg pain intensity (0-10 scale) [ß: -0.25, 95% CI: -0.46, -0.03], and current pain duration of more than 12 months [OR: 1.27, 95% CI: 1.03, 1.55]. No associations were found for low back pain intensity, morning stiffness, painful active range of motion, or work nature. CONCLUSIONS: Patients with higher lumbar multifidus muscle quality reported lower levels of low back pain-related disability and leg pain intensity, indicating that muscle quality may play a role in the etiology of lumbar spine disorders. However, the clinical importance of these associations is uncertain due to the low magnitude of identified associations. Future longitudinal studies are needed to understand the effect of lumbar multifidus muscle quality on lumbar-related pain and disability.

Understanding patient preferences for student clinician attire: a cross-sectional study of a student chiropractic clinic in Australia.

Objectives: Previous studies have investigated the role of clinical attire in establishing patient-held perceptions of professionalism and knowledgeability across various healthcare settings. This study aimed to understand patients' preferences for chiropractic student attire. Methods: Three hundred and twenty patients were recruited from a university chiropractic clinic and asked to complete an online questionnaire. The patients' preferences for five different attires were rated and calculated as the composite score of five domains (knowledgeable, trustworthy, caring, professional, and comfortable). Results: While 71.9% of participants indicated that how students dress was important to them, most (63.4%) disagreed that wearing a white coat was essential for chiropractic student clinicians. The most preferred form of attire was the current clinic shirt. Conclusion: The attire worn by chiropractic student clinicians at a single institution was found to be an influential attribute. Student chiropractic clinicians should dress professionally to make a good first impression. This study provided some guidance with the ongoing debate around students' dress code.

Objectif: Des études antérieures ont examiné le rôle de la tenue vestimentaire en clinique dans l'établissement des perceptions des patients quant au professionnalisme et à la compétence dans divers environnements de soins de santé. Cette étude visait à comprendre les préférences des patients en matière de tenue vestimentaire des étudiants en chiropratique. Méthodologie: Trois cent vingt patients ont été recrutés dans une clinique chiropratique universitaire et invités à remplir un questionnaire en ligne. Les préférences des patients pour cinq tenues différentes ont été évaluées et calculées en tant que score composite de cinq domaines (bien informé, digne de confiance, attentionné, professionnel et confortable). Résultats: Si 71,9 % des participants ont indiqué que la tenue vestimentaire des étudiants était importante pour eux, la plupart (63,4 %) n'étaient pas d'accord avec le fait que le port d'une blouse blanche était essentiel pour les étudiants cliniciens en chiropratique. La tenue vestimentaire la plus appréciée était la chemise de clinique actuelle. Conclusion: La tenue vestimentaire des étudiants cliniciens en chiropratique d'un même établissement s'est révélée être un attribut influent. Les étudiants en chiropratique doivent s'habiller de manière professionnelle pour faire une bonne première impression. Cette étude a permis d'éclairer le débat en cours sur le code vestimentaire des étudiants.