In Vivo PET Detection of Lung Micrometastasis in Mice by Targeting Endothelial VCAM-1 Using a Dual-Contrast PET/MRI Probe.

Current clinical diagnostic imaging methods for lung metastases are sensitive only to large tumours (1-2 mm cross-sectional diameter), and early detection can dramatically improve treatment. We have previously demonstrated that an antibody-targeted MRI contrast agent based on microparticles of iron oxide (MPIO; 1 µm diameter) enables the imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Using a mouse model of lung metastasis, upregulation of endothelial VCAM-1 expression was demonstrated in micrometastasis-associated vessels but not in normal lung tissue, and binding of VCAM-MPIO to these vessels was evident histologically. Owing to the lack of proton MRI signals in the lungs, we modified the VCAM-MPIO to include zirconium-89 (89Zr, t1/2 = 78.4 h) in order to allow the in vivo detection of lung metastases by positron emission tomography (PET). Using this new agent (89Zr-DFO-VCAM-MPIO), it was possible to detect the presence of micrometastases within the lung in vivo from ca. 140 µm in diameter. Histological analysis combined with autoradiography confirmed the specific binding of the agent to the VCAM-1 expressing vasculature at the sites of pulmonary micrometastases. By retaining the original VCAM-MPIO as the basis for this new molecular contrast agent, we have created a dual-modality (PET/MRI) agent for the concurrent detection of lung and brain micrometastases.

Targeted opening of the blood-brain barrier using VCAM-1 functionalised microbubbles and "whole brain" ultrasound.

Metastatic tumours in the brain now represent one of the leading causes of death from cancer. Current treatments are largely ineffective owing to the combination of late diagnosis and poor delivery of therapies across the blood-brain barrier (BBB). Conjugating magnetic resonance imaging (MRI) contrast agents with a monoclonal antibody for VCAM-1 (anti-VCAM1) has been shown to enable detection of micrometastases, two to three orders of magnitude smaller in volume than those currently detectable clinically. The aim of this study was to exploit this targeting approach to enable localised and temporary BBB opening at the site of early-stage metastases using functionalised microbubbles and ultrasound. Methods: Microbubbles functionalised with anti-VCAM1 were synthesised and shown to bind to VCAM-1-expressing cells in vitro. Experiments were then conducted in vivo in a unilateral breast cancer brain metastasis mouse model using Gadolinium-DTPA (Gd-DTPA) enhanced MRI to detect BBB opening. Following injection of Gd-DTPA and targeted microbubbles, the whole brain volume was simultaneously exposed to ultrasound (0.5 MHz, 10% duty cycle, 0.7 MPa peak negative pressure, 2 min treatment time). T1-weighted MRI was then performed to identify BBB opening, followed by histological confirmation via immunoglobulin G (IgG) immunohistochemistry. Results: In mice treated with targeted microbubbles and ultrasound, statistically significantly greater extravasation of Gd-DTPA and IgG was observed in the left tumour-bearing hemisphere compared to the right hemisphere 5 min after treatment. No acute adverse effects were observed. There was no investigation of longer term bioeffects owing to the nature of the study. Conclusion: The results demonstrate the feasibility of using targeted microbubbles in combination with low intensity ultrasound to localise opening of the BBB to metastatic sites in the brain. This approach has potential application in the treatment of metastatic tumours whose location cannot be established a priori with conventional imaging methods.

Reciprocal sharing of extracellular proteases and extracellular matrix molecules facilitates Bacillus subtilis biofilm formation.

Extracellular proteases are a class of public good that support growth of Bacillus subtilis when nutrients are in a polymeric form. Bacillus subtilis biofilm matrix molecules are another class of public good that are needed for biofilm formation and are prone to exploitation. In this study, we investigated the role of extracellular proteases in B. subtilis biofilm formation and explored interactions between different public good producer strains across various conditions. We confirmed that extracellular proteases support biofilm formation even when glutamic acid provides a freely available nitrogen source. Removal of AprE from the NCIB 3610 secretome adversely affects colony biofilm architecture, while sole induction of WprA activity into an otherwise extracellular protease-free strain is sufficient to promote wrinkle development within the colony biofilm. We found that changing the nutrient source used to support growth affected B. subtilis biofilm structure, hydrophobicity and architecture. We propose that the different phenotypes observed may be due to increased protease dependency for growth when a polymorphic protein presents the sole nitrogen source. We however cannot exclude that the phenotypic changes are due to alternative matrix molecules being made. Co-culture of biofilm matrix and extracellular protease mutants can rescue biofilm structure, yet reliance on extracellular proteases for growth influences population coexistence dynamics. Our findings highlight the intricate interplay between these two classes of public goods, providing insights into microbial social dynamics during biofilm formation across different ecological niches.

Whole-Body Photobiomodulation Therapy Propels the Fibromyalgia Patient into the Recomposition Phase: A Reflexive Thematic Analysis.

BACKGROUND: Recent evidence has identified great promise for the novel whole-body photobiomodulation therapy (PBMT) for individuals with fibromyalgia (FM). However, currently no evidence has documented the experiences of participants. The objective of this study was to qualitatively assess treatment experience and response in a group of participants with FM undergoing a course of whole-body PBMT. METHODS: An interpretive hermeneutic phenomenological study situated within the worldview of pragmatism was undertaken. A convenience sample of individuals with FM were included if they had undertaken a novel 6-week trial of PBMT. Individuals undertook semi-structured interviews exploring treatment experience and multidimensional treatment responses during Week 3 and Week 6. RESULTS: Sixteen trial participants (47.3 ± 10.9 years) took part in this study. The analysis produced three overarching themes that were previously identified from a baseline study (namely, 'Body Structure & Function', 'Activities & Participation', and 'Environment') with an additional five sub-themes that highlighted the intervention experience. Subsequently, four important processes were observed and identified: increased motivation; feeling proud; improved confidence; feeling like 'old self'. This ultimately culminated in the identification of a positive spiral, which we have termed 'recomposition'. CONCLUSIONS: We believe our study is the first in the field of chronic pain management to utilise qualitative methodology to directly assess the acceptability and efficacy of a specific medical intervention in a clinical trial, and the first study to qualitatively assess whole-body PBMT experience. The findings are compelling and warrant further work to support the introduction of this device into the National Health Service (NHS).

Australian women's experiences of post-partum rectus diastasis: A qualitative study.

BACKGROUND: Post-partum rectus diastasis, or the separation of the abdominal muscles after pregnancy, occurs in conjunction with physical symptoms and impaired quality of life. In Australia, health funding for surgery to treat diastasis was ceased in 2016, but reinstated in mid-2022, providing a unique context from which women's experiences of this condition can be analysed. OBJECTIVES: The objective is to examine the experiences of Australian women with post-partum rectus diastasis. DESIGN: This is an interview-style study with qualitative content analysis. METHODS: Women diagnosed with rectus diastasis were recruited to complete a baseline questionnaire (n = 45). Twenty-three responded to invitation for one-on-one interview via Zoom® between November 2021 and May 2022. Interviews were recorded, transcribed, and analysed using qualitative content analysis to identify key themes. RESULTS: Eighteen women had undergone caesarean section and eight had twins. Thirteen had private health insurance. Women were most often diagnosed by a physiotherapist (n = 10). Key themes identified included changed physical appearance and function; issues with self-esteem and intimacy; barriers to treatment; lack of recognition as a medical condition; and overall frustration. The impact of rectus diastasis extended beyond physical and psychological symptoms to affect women's social functioning, child rearing, and return to work. There was a complex interaction between healthcare providers' knowledge of rectus the removal of funding for surgical treatment, and limitations of conservative therapy, with women's lived experiences and symptoms. The lack of an established medical definition also influenced the experiences of these women and their engagement with treatment. CONCLUSION: This study contextualizes women's experience of post-partum rectus diastasis with respect to the unique landscape of Australia's healthcare economy and provides evidence of women's absorption of health policy surrounding this condition. Our qualitative analysis provides critical knowledge for future quantitative studies, the results of which in combination could advance the definition of rectus diastasis and inform healthcare policy surrounding treatment.

The biopsychosocial factors associated with development of chronic musculoskeletal pain. An umbrella review and meta-analysis of observational systematic reviews.

AIM: The aim of this umbrella review was to establish which biopsychosocial factors are associated with development of chronic musculoskeletal pain. METHODS: Ovid Medline, Embase, Web of Science Core Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, PsycINFO, CINAHL, PEDro, PROSPERO, Google Scholar and grey literature were searched from database inception to 4th April 2023. Systematic reviews of observational prospective longitudinal studies, including populations with <3 months (not chronic) musculoskeletal pain, investigating biopsychosocial factors that contribute to development of chronic (>3 months) musculoskeletal pain. Two reviewers searched the literature, assessed risk of bias (Assessing the Methodological Quality of Systematic Reviews-2), and evaluated quality (Grading of Recommendations, Assessment, Development and Evaluation) to provide an overall statement on the certainty of evidence for each biopsychosocial factor. Data analysis was performed through random effects meta-analysis (including meta-analysis of meta-analyses where possible) and descriptive synthesis. RESULTS: 13 systematic reviews were included comprising 185 original research studies (n = 489,644 participants). Thirty-four biopsychosocial factors are associated with development of chronic musculoskeletal pain. Meta-analyses of odds and/or likelihood ratios were possible for 25 biopsychosocial factors. There is moderate certainty evidence that smoking (OR 1.24 [95%CI, 1.14-1.34), fear avoidance (LR+ 2.11 [95%CI, 1.59-2.8]; LR- 0.5 [95%CI, 0.35-0.71]) poorer support networks (OR 1.21 [95%CI, 1.14-1.29]), lower socioeconomic status (OR 2.0 [95%CI, 1.64-2.42]), and high levels of pain (OR 5.61 [95%CI, 3.74-8.43]) are associated with development of chronic musculoskeletal pain (all P<0.001). Remaining factors are of low or very low certainty evidence. CONCLUSIONS AND RELEVANCE: There is moderate certainty evidence that smoking, fear avoidance, poorer support networks, lower socioeconomic status, and high levels of pain are associated with development of chronic musculoskeletal pain. High risk of bias was evident in most included reviews; this highlights the need for higher quality systematic reviews.

Development of a high-throughput liquid chromatography-tandem mass spectrometry platform for the determination of intact natriuretic peptides in human plasma.

We present an innovative, reliable, and antibody-free analytical method to determine multiple intact natriuretic peptides in human plasma. These biomolecules are routinely used to confirm the diagnosis and monitor the evolution of heart failure, so that their determination is essential to improve diagnosis and monitor the efficacy of treatment. However, common immunoassay kits suffer from main limitations due to high cross-reactivity with structurally similar species. In our method, we pre-treated the sample by combining salting-out with ammonium sulfate with microextraction by packed sorbent technique. Analyses were then carried out by ultra-high performance liquid chromatography-electrospray ionization-tandem mass spectrometry. The use of 3-nitrobenzyl alcohol as a supercharger reagent enhanced the ESI ionization and improved the signal-to-noise ratio. The analytical protocol showed good linearity over one order of magnitude, recovery in the range of 94-105 %, and good intra- and inter-day reproducibility (RSD<20 %), and the presence of a matrix effect. Limits of detection were in the range of pg/mL for all peptides (0.2-20 pg/mL). Stability study in plasma samples demonstrated that proper protease inhibitors need to be included in blood collection tubes to avoid peptide degradation. Preliminary analyses on plasma samples from heart failure patients allow the quantification of ANP 1-28 as the most abundant species and the detection of ANP 5-28, BNP 1-32, and BNP 5-32. The method could be used to investigate how cross-reactivity issues among structurally similar species impact determinations by ELISA kits.

Bacillus subtilis Matrix Protein TasA is Interfacially Active, but BslA Dominates Interfacial Film Properties.

Microbial growth often occurs within multicellular communities called biofilms, where cells are enveloped by a protective extracellular matrix. Bacillus subtilis serves as a model organism for biofilm research and produces two crucial secreted proteins, BslA and TasA, vital for biofilm matrix formation. BslA exhibits surface-active properties, spontaneously self-assembling at hydrophobic/hydrophilic interfaces to form an elastic protein film, which renders B. subtilis biofilm surfaces water-repellent. TasA is traditionally considered a fiber-forming protein with multiple matrix-related functions. In our current study, we investigate whether TasA also possesses interfacial properties and whether it has any impact on BslA's ability to form an interfacial protein film. Our research demonstrates that TasA indeed exhibits interfacial activity, partitioning to hydrophobic/hydrophilic interfaces, stabilizing emulsions, and forming an interfacial protein film. Interestingly, TasA undergoes interface-induced restructuring similar to BslA, showing an increase in ß-strand secondary structure. Unlike BslA, TasA rapidly reaches the interface and forms nonelastic films that rapidly relax under pressure. Through mixed protein pendant drop experiments, we assess the influence of TasA on BslA film formation, revealing that TasA and other surface-active molecules can compete for interface space, potentially preventing BslA from forming a stable elastic film. This raises a critical question: how does BslA self-assemble to form the hydrophobic "raincoat" observed in biofilms in the presence of other potentially surface-active species? We propose a model wherein surface-active molecules, including TasA, initially compete with BslA for interface space. However, under lateral compression or pressure, BslA retains its position, expelling other molecules into the bulk. This resilience at the interface may result from structural rearrangements and lateral interactions between BslA subunits. This combined mechanism likely explains BslA's role in forming a stable film integral to B. subtilis biofilm hydrophobicity.

Cytogenetic Analysis of the Fish Genus Carassius Indicates Divergence, Fission, and Segmental Duplication as Drivers of Tandem Repeat and Microchromosome Evolution.

Fishes of the genus Carassius are useful experimental vertebrate models for the study of evolutionary biology and cytogenetics. Carassius demonstrates diverse biological characteristics, such as variation in ploidy levels and chromosome numbers, and presence of microchromosomes. Those Carassius polyploids with ≥150 chromosomes have microchromosomes, but the origin of microchromosomes, especially in European populations, is unknown. We used cytogenetics to study evolution of tandem repeats (U1 and U2 small nuclear DNAs and H3 histone) and microchromosomes in Carassius from the Czech Republic. We tested the hypotheses whether the number of tandem repeats was affected by polyploidization or divergence between species and what mechanism drives evolution of microchromosomes. Tandem repeats were found in tetraploid and hexaploid Carassius gibelio, and tetraploid Carassius auratus and Carassius carassius in conserved numbers, with the exception of U1 small nuclear DNA in C. auratus. This conservation indicates reduction and/or loss in the number of copies per locus in hexaploids and may have occurred by divergence rather than polyploidization. To study the evolution of microchromosomes, we used the whole microchromosome painting probe from hexaploid C. gibelio and hybridized it to tetraploid and hexaploid C. gibelio, and tetraploid C. auratus and C. carassius. Our results revealed variation in the number of microchromosomes in hexaploids and indicated that the evolution of the Carassius karyotype is governed by macrochromosome fissions followed by segmental duplication in pericentromeric areas. These are potential mechanisms responsible for the presence of microchromosomes in Carassius hexaploids. Differential efficacy of one or both of these mechanisms in different tetraploids could ensure variability in chromosome number in polyploids in general.

Inflammatory bowel disease induces pathological α-synuclein aggregation in the human gut and brain.

AIMS: According to Braak's hypothesis, it is plausible that Parkinson's disease (PD) originates in the enteric nervous system (ENS) and spreads to the brain through the vagus nerve. In this work, we studied whether inflammatory bowel diseases (IBDs) in humans can progress with the emergence of pathogenic α-synuclein (α-syn) in the gastrointestinal tract and midbrain dopaminergic neurons. METHODS: We have analysed the gut and the ventral midbrain from subjects previously diagnosed with IBD and form a DSS-based rat model of gut inflammation in terms of α-syn pathology. RESULTS: Our data support the existence of pathogenic α-syn in both the gut and the brain, thus reinforcing the potential role of the ENS as a contributing factor in PD aetiology. Additionally, we have analysed the effect of a DSS-based rat model of gut inflammation to demonstrate (i) the appearance of P-α-syn inclusions in both Auerbach's and Meissner's plexuses (gut), (ii) an increase in α-syn expression in the ventral mesencephalon (brain) and (iii) the degeneration of nigral dopaminergic neurons, which all are considered classical hallmarks in PD. CONCLUSION: These results strongly support the plausibility of Braak's hypothesis and emphasise the significance of peripheral inflammation and the gut-brain axis in initiating α-syn aggregation and transport to the substantia nigra, resulting in neurodegeneration.

Is tropical pus in the hand special? A retrospective study comparing hand infection cases in Darwin and Adelaide.

BACKGROUND: Hand infections are a common reason for presenting to hospital and can be associated with significant morbidity and prolonged antibiotic use. Factors recognized to influence patient outcomes include resistant organisms and delayed presentation. Surgeons working around Australia may assume that hand infections and appropriate treatment algorithms will be similar between sites. This is the first study to examine differences between hand infections presenting in Darwin (with its tropical climate) vs. those in a more temperate city (Adelaide). METHODS: This is a two-site retrospective study, where diagnostic discharge codes were used to identify cases for a 12-month period and patient age, sex and rurality, duration of hospital stay, microbiology results and subsequent trips to theatre were reviewed. RESULTS: Despite significant differences in rurality between FMC and RDH patients, there was no significant difference in length of hospital stay, duration of intravenous antibiotics or return trips to theatre across the two sites. RDH reported a 25% rate of MRSA, compared to 18% at FMC, as well as a statistically significant increase in uncommon microbes, with 30% compared to 12% of patients growing microbes that may not be covered by antibiotics routinely administered in metropolitan areas. A limitation of this study was that compliance with antibiotics and hospital stay were not accounted for. CONCLUSION: It is often our training years that determine our norms of everyday practice, but fewer Australian surgical training posts are located in tropical centres. The results of this study highlight the importance of not assuming that the spectrum of organisms causing hand infections are the same as that in the surgeons' state of origin.

Outcome measures for young people with adolescent idiopathic scoliosis: A qualitative exploration of healthcare professionals' perceptions and practices.

BACKGROUND: Limited knowledge exists on current use of patient reported outcome measures (PROMs) and performance measures for adolescents with idiopathic scoliosis (AIS), as well as health care professionals' (HCPs) perceived barriers and facilitators towards their use. This study's objectives were: 1) to explore current practice of HCPs when assessing outcomes for AIS 2) to understand perceived barriers and facilitators of HCPs to use PROMs 3) to understand perceived barriers and facilitators of HCPs to use performance measures. METHODS: A qualitative study recruited a purposive sample of HCPs from a tertiary hospital in the United Kingdom. Mean years of experience managing individuals with AIS was 11.8 years; and included surgeons, physiotherapists and nurses, educated at Bachelor, Masters and Doctoral level. Consent to participate and demographic information were collected in advance of the interviews. In-depth, virtual semi-structured interviews were informed by a topic guide based on current evidence. Interviews of approximately 45 minutes were audio and video recorded and transcribed verbatim alongside written field notes. Data were coded and analysed using inductive thematic analysis, involving researchers with topic and methodological expertise and input from a patient representative. RESULTS: Two themes emerged regarding current practice of using PROMs routine practice and personal evaluations. Four themes emerged as barriers to using PROMs for individuals with AIS: priority and support (e.g., HCPs focus on providing care), practical challenges (e.g., inadequate PROMs), patient-related challenges (e.g., patient preferences) and knowledge, education, and perceived value. Two themes emerged as facilitators: quality existing measure (e.g., sufficient psychometric properties), and priority and support (e.g., research department/culture). Themes for barriers to use performance measures were practicality (e.g., need physical space) and perceived value and knowledge (e.g., PROMs are more important), while the one theme for facilitators was practical consideration (e.g., acceptability). CONCLUSIONS: Although HCPs perceived the value of using outcome measures, current practice indicates limited use for individuals with AIS. The findings revealed different barriers and facilitators to implement PROMs in practice. Adopting performance measure are limited due to lack of knowledge and perceived value alongside the practicality, while considering practical factors can improve the use of these measures in practice.

Measurement properties of cervical joint position error in people with and without neck pain: a systematic review and narrative synthesis.

INTRODUCTION: Proprioception can be impaired in people with neck pain. The cervical joint position sense test, which measures joint position error (JPE), is the most common test used to assess neck proprioception. The aim of this systematic review was to assess the measurement properties of this test for the assessment of people with and without neck pain. METHODS: This systematic review was registered prospectively on Prospero (CRD42020188715). It was designed using the COSMIN guidelines and reported in line with the PRISMA checklist. Two reviewers independently searched Medline, Embase, SportDiscus, and CINAHL Plus databases from inception to the 24th July 2022 with an update of the search conducted until 14th of October 2023. The COSMIN risk of bias checklist was used to assess the risk of bias in each study. The updated criteria for good measurement properties were used to rate individual studies and then the overall pooled results. The level of evidence was rated by two reviewers independently using a modified GRADE approach. RESULTS: Fifteen studies were included in this review, 13 reporting absolute JPE and 2 reporting constant JPE. The measurement properties assessed were reliability, measurement error, and validity. The measurement of JPE showed sufficient reliability and validity, however, the level of evidence was low/very low for both measurement properties, apart from convergent validity of the constant JPE, which was high. CONCLUSION: The measure of cervical JPE showed sufficient reliability and validity but with low/very low levels of evidence. Further studies are required to investigate the reliability and validity of this test as well as the responsiveness of the measure.

The Fibromyalgia Decomposition Phenomenon: A Reflexive Thematic Analysis.

Research is needed that can provide an illustration of the different biopsychosocial and environmental experiences of people with fibromyalgia to consider how healthcare professionals can best engage with the challenges that are faced. Qualitative research is well-positioned to do this. The current study used interpretive hermeneutic phenomenology situated within a pragmatic worldview, the aim being to obtain a deeper exploration of the fibromyalgia experience prior to commencing a novel intervention. A purposive sample of individuals with fibromyalgia were selected to undertake a single interview. The interviews were analysed using a thematic analysis. The themes identified key processes of the experience. A total of 16 participants (mean age: 47.1 years) took part. Three themes and 15 sub-themes were identified, together with a process linking different experiences together. The research from this small cohort provides a clear identification of multiple components influencing the experience of fibromyalgia and the decisions around lifestyle and choices made. From this, a novel decomposition/recomposition spiral has been identified, which will benefit patients and healthcare professionals alike. An earlier diagnosis and, thus, earlier and broader treatment options can help to improve functional outcomes.

Diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain: protocol for a systematic review.

INTRODUCTION: Neuropathic pain in low back-related leg pain has gained increasing interest in contemporary research. Identification of neuropathic pain in low back-related leg pain is essential to inform precision management. Diagnostic investigations are commonly used to identify neuropathic pain in low back-related leg pain; yet the diagnostic utility of these investigations is unknown. This systematic review aims to investigate the diagnostic utility of diagnostic investigations to identify neuropathic pain in low back-related leg pain. METHODS AND ANALYSIS: This protocol has been designed and reported in accordance with the Cochrane Handbook for Diagnostic Test Accuracy studies, Centre for Reviews and Dissemination and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols checklist, respectively. The search strategy will involve two independent reviewers searching electronic databases (CINAHL, EMBASE, MEDLINE, Web of Science, Cochrane Library, AMED, Pedro), key journals (Spine, The Clinical Journal of Pain, PAIN, European Journal of Pain, The Journal of Pain, Musculoskeletal Science and Practice) and grey literature (British National Bibliography for report literature, OpenGrey, EThOS) from inception to 31 July 2023 to identify studies. Studies evaluating the diagnostic accuracy of diagnostic investigation to identify neuropathic pain in patients with low back-related leg pain will be eligible, studies not written in English will be excluded. The reviewers will extract the data from included studies, assess risk of bias (Quality Assessment of Diagnostic Accuracy Studies 2) and determine confidence in findings (Grading of Recommendations, Assessment, Development and Evaluation guidelines). Methodological heterogeneity will be assessed to determine if a meta-analysis is possible. If pooling of data is not possible then a narrative synthesis will be done. ETHICS AND DISSEMINATION: Ethical approval is not required. Findings will be published in a peer-reviewed journal, presented at relevant conferences and shared with the Patient Partner Advisor Group at Western University, Canada. PROSPERO REGISTRATION NUMBER: CRD42023438222.

Spinal mobilization force-time characteristics: A scoping literature review.

BACKGROUND: Spinal mobilization (SMob) is often included in the conservative management of spinal pain conditions as a recommended and effective treatment. While some studies quantify the biomechanical (kinetic) parameters of SMob, interpretation of findings is difficult due to poor reporting of methodological details. The aim of this study was to synthesise the literature describing force-time characteristics of manually applied SMob. METHODS: This study is reported in accordance with the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) statement. Databases were searched from inception to October 2022: MEDLINE (Ovid), Embase, CINAHL, ICL, PEDro and Cochrane Library. Data were extracted and reported descriptively for the following domains: general study characteristics, number of and characteristics of individuals who delivered/received SMob, region treated, equipment used and force-time characteristics of SMob. RESULTS: There were 7,607 records identified and of these, 36 (0.5%) were included in the analysis. SMob was delivered to the cervical spine in 13 (36.1%), the thoracic spine in 3 (8.3%) and the lumbopelvic spine in 18 (50.0%) studies. In 2 (5.6%) studies, spinal region was not specified. For SMob applied to all spinal regions, force-time characteristics were: peak force (0-128N); duration (10-120s); frequency (0.1-4.5Hz); and force amplitude (1-102N). CONCLUSIONS: This study reports considerable variability of the force-time characteristics of SMob. In studies reporting force-time characteristics, SMob was most frequently delivered to the lumbar and cervical spine of humans and most commonly peak force was reported. Future studies should focus on the detailed reporting of force-time characteristics to facilitate the investigation of clinical dose-response effects.

Lateral interactions govern self-assembly of the bacterial biofilm matrix protein BslA.

The soil bacterium Bacillus subtilis is a model organism to investigate the formation of biofilms, the predominant form of microbial life. The secreted protein BslA self-assembles at the surface of the biofilm to give the B. subtilis biofilm its characteristic hydrophobicity. To understand the mechanism of BslA self-assembly at interfaces, here we built a molecular model based on the previous BslA crystal structure and the crystal structure of the BslA paralogue YweA that we determined. Our analysis revealed two conserved protein-protein interaction interfaces supporting BslA self-assembly into an infinite 2-dimensional lattice that fits previously determined transmission microscopy images. Molecular dynamics simulations and in vitro protein assays further support our model of BslA elastic film formation, while mutagenesis experiments highlight the importance of the identified interactions for biofilm structure. Based on this knowledge, YweA was engineered to form more stable elastic films and rescue biofilm structure in bslA deficient strains. These findings shed light on protein film assembly and will inform the development of BslA technologies which range from surface coatings to emulsions in fast-moving consumer goods.

Spinal manipulation characteristics: a scoping literature review of force-time characteristics.

BACKGROUND: Spinal manipulation (SM) is a recommended and effective treatment for musculoskeletal disorders. Biomechanical (kinetic) parameters (e.g. preload/peak force, rate of force application and thrust duration) can be measured during SM, quantifying the intervention. Understanding these force-time characteristics is the first step towards identifying possible active ingredient/s responsible for the clinical effectiveness of SM. Few studies have quantified SM force-time characteristics and with considerable heterogeneity evident, interpretation of findings is difficult. The aim of this study was to synthesise the literature describing force-time characteristics of manual SM. METHODS: This scoping literature review is reported following the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) statement. Databases were searched from inception to October 2022: MEDLINE (Ovid), Embase, CINAHL, ICL, PEDro and Cochrane Library. The following search terms and their derivatives were adapted for each platform: spine, spinal, manipulation, mobilization or mobilisation, musculoskeletal, chiropractic, osteopathy, physiotherapy, naprapathy, force, motor skill, biomechanics, dosage, dose-response, education, performance, psychomotor, back, neck, spine, thoracic, lumbar, pelvic, cervical and sacral. Data were extracted and reported descriptively for the following domains: general study characteristics, number of and characteristics of individuals who delivered/received SM, region treated, equipment used and force-time characteristics of SM. RESULTS: Of 7,607 records identified, 66 (0.9%) fulfilled the eligibility criteria and were included in the analysis. Of these, SM was delivered to the cervical spine in 12 (18.2%), the thoracic spine in 40 (60.6%) and the lumbopelvic spine in 19 (28.8%) studies. In 6 (9.1%) studies, the spinal region was not specified. For SM applied to all spinal regions, force-time characteristics were: preload force (range: 0-671N); peak force (17-1213N); rate of force application (202-8700N/s); time to peak thrust force (12-938ms); and thrust duration (36-2876ms). CONCLUSIONS: Considerable variability in the reported kinetic force-time characteristics of SM exists. Some of this variability is likely due to differences in SM delivery (e.g. different clinicians) and the measurement equipment used to quantify force-time characteristics. However, improved reporting in certain key areas could facilitate more sophisticated syntheses of force-time characteristics data in the future. Such syntheses could provide the foundation upon which dose-response estimates regarding the clinical effectiveness of SM are made.

Effectiveness of thoracic spine manipulation for upper quadrant musculoskeletal disorders: protocol for a systematic review.

INTRODUCTION: Upper quadrant musculoskeletal disorders (UQMD), comprising of cranial, cervical, shoulder and upper extremity disorders, are among the most frequently reported disorders in clinical practice. Thoracic high velocity low amplitude thrust (Tx-HVLAT) manipulation is a form of conservative management recommended in systematic reviews as an effective treatment option for aspects of UQMD disorders such headache, shoulder pain and lateral elbow pain. However, no recent systematic reviews have assessed the effectiveness across UQMD. Therefore, this systematic review aims to update the current evidence on the effectiveness of Tx-HVLAT for patients with UQMD on (1) patient-reported outcomes, (2) performance measures or (3) psychosocial outcomes. METHODS AND ANALYSIS: The Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL, PEDro and Index to Chiropractic Literature will be searched from inception using Medical Subject Headings (MeSH), Thesaurus and/or free-text words. Combinations will be made based on localisation, disorder, intervention and design. Following guidelines as advised by the Cochrane Back Review Group, published randomised controlled trials will be included. Two review authors will independently assess the risk of bias (ROB) using the Cochrane Back Review Group's recommended ROB2 tool and will independently extract the data using a standardised data extraction form. Overall quality of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. For continuous data, we will calculate standardised mean differences with 95% CIs. For dichotomous outcomes, relative risks and 95% CIs will be calculated. Where possible we will present a subgroup analysis by disorder. For pooling, a random-effects model will be used. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review. The study findings will be submitted to a relevant peer-reviewed journal for dissemination and presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42023429996.

Whole-Body Photobiomodulation Therapy for Fibromyalgia: A Feasibility Trial.

Effective treatment for fibromyalgia (FM) is lacking and further treatment options are needed. Photobiomodulation therapy (PBMT) represents one potential treatment option. Whilst favourable findings have been reported using localised PBMT, no investigations have established the value of whole-body PBMT for the complete set of symptom domains in FM. A single-arm feasibility study was conducted in accordance with CONSORT (Consolidated Standards of Reporting Trials) guidelines. A non-probability sampling method was used to access individuals with FM. The primary outcome measure was identified as the Revised Fibromyalgia Impact Questionnaire (FIQR). Forty-nine participants were screened and twenty-one trial participants entered the trial. Nineteen participants completed the intervention (18 whole-body PBMT sessions over approximately six weeks). Descriptive statistics and qualitative analysis was undertaken to represent feasibility outcomes. Acceptability of the trial device and processes were established. Outcome measures towards efficacy data were guided by core and peripheral OMERACT (outcomes measures in rheumatological clinical trials) domains, utilising a combination of participant-reported and performance-based outcome measures. Data for the embedded qualitative component of the trial were captured by participant-reported experience measures and audio-recorded semi-structured interviews. Positive changes were observed for FM-specific quality of life, pain, tenderness, stiffness, fatigue, sleep disturbance, anxiety, depression and cognitive impairment. Patient global assessment revealed improvements at 6 weeks, with continued effect at 24 weeks. FM-specific quality of life at 24 weeks remained improved compared with baseline scores. The findings provided evidence to support a full-scale trial and showed promise regarding potential efficacy of this novel non-invasive treatment in an FM population.