The uncharacterized PA3040-3042 operon is part of the cell envelope stress response and a tobramycin resistance determinant in a clinical isolate of Pseudomonas aeruginosa.

Bacteriophages (hereafter "phages") are ubiquitous predators of bacteria in the natural world, but interest is growing in their development into antibacterial therapy as complement or replacement for antibiotics. However, bacteria have evolved a huge variety of antiphage defense systems allowing them to resist phage lysis to a greater or lesser extent. In addition to dedicated phage defense systems, some aspects of the general stress response also impact phage susceptibility, but the details of this are not well known. In order to elucidate these factors in the opportunistic pathogen Pseudomonas aeruginosa, we used the laboratory-conditioned strain PAO1 as host for phage infection experiments as it is naturally poor in dedicated phage defense systems. Screening by transposon insertion sequencing indicated that the uncharacterized operon PA3040-PA3042 was potentially associated with resistance to lytic phages. However, we found that its primary role appeared to be in regulating biofilm formation, particularly in a clinical isolate of P. aeruginosa in which it also altered tobramycin resistance. Its expression was highly growth-phase dependent and responsive to phage infection and cell envelope stress. Our results suggest that this operon may be a cryptic but important locus for P. aeruginosa stress tolerance. IMPORTANCE: An important category of bacterial stress response systems is bacteriophage defense, where systems are triggered by bacteriophage infection and activate a response which may either destroy the phage genome or destroy the infected cell so that the rest of the population survives. In some bacteria, the cell envelope stress response is activated by bacteriophage infection, but it is unknown whether this contributes to the survival of the infection. We have found that a conserved uncharacterized operon (PA3040-PA3042) of the cell envelope stress regulon in Pseudomonas aeruginosa, which has very few dedicated phage defense systems, responds to phage infection and stationary phase as well as envelope stress and is important for growth and biofilm formation in a clinical isolate of P. aeruginosa, even in the absence of phages. As homologs of these genes are found in other bacteria, they may be a novel component of the general stress response.

A Change-Point Method to Detect Meaningful Change in Return-to-Sport Progression in Athletes.

PURPOSE: To explore how the change-point method can be used to analyze complex longitudinal data and detect when meaningful changes (change points) have occurred during rehabilitation. METHOD: This design is a prospective single-case observational study of a football player in a professional club who sustained an acute lower-limb muscle injury during high-speed running in training. The rehabilitation program was entirely completed in the football club under the supervision of the club's medical team. Four wellness metrics and 5 running-performance metrics were collected before the injury and until the player returned to play. RESULTS: Data were collected over 130 days. In the univariate analysis, the change points for stress, sleep, mood, and soreness were located on days 30, 47, 50, and 50, respectively. The change points for total distance, acceleration, maximum speed, deceleration, and high-speed running were located on days 32, 34, 37, 41, and 41, respectively. The multivariate analysis resulted in a single change point for the wellness metrics and running-performance metrics, on days 50 and 67, respectively. CONCLUSIONS: The univariate approach provided information regarding the sequence and time point of the change points. The multivariate approach provided a common change point for multiple metrics, information that would benefit clinicians to have a broad overview of the changes in the rehabilitation process. Clinicians may consider the change-point method to integrate and visualize data from multiple sources to evaluate athletes' progression along the return-to-sport continuum.

Application of multiple mosaic callers improves post-zygotic mutation detection from exome sequencing data.

PURPOSE: The gold standard for identification of post-zygotic variants (PZVs) is droplet digital PCR (ddPCR) or high-depth sequencing across multiple tissues types. These approaches are yet to be systematically implemented for monogenic disorders. We developed PZV detection pipelines for correct classification of de novo variants. METHOD: Our pipelines detect PZV in parents (gonosomal mosaicism "pGoM") and children (somatic mosaicism, "M3"). We applied them to research exome sequencing (ES) data from The Australian Cerebral Palsy Biobank (ACPB, n=145 trios) and Simons Simplex Collection (SSC, n=405 families). Candidate mosaic variants were validated using deep amplicon sequencing or ddPCR. RESULTS: 69.2% (M3trio), 63.9% (M3single) and 92.7% (pGoM) of detected variants were validated, with 48.6%, 56.7% and 26.2% of variants respectively meeting strict criteria for mosaicism. In the ACPB, 16.6% of probands and 20.7% of parents had at least one true positive somatic or pGoM variant respectively. A large proportion of PZVs detected in SSC parents (79.8%) and child (94.5%) were not previously reported. We reclassified 3.7-8.0% of germline de novo variants as mosaic. CONCLUSION: Many PZVs were incorrectly classified as germline variants or missed by previous approaches. Systematic application of our pipelines could increase genetic diagnostic rate, improve estimates of recurrence risk in families, and benefit novel disease gene identification.

Thresholds for adding degraded tropical forest to the conservation estate.

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

High-level tumour methylation of BRCA1 and RAD51C is required for homologous recombination deficiency in solid cancers.

In ovarian and breast cancer, promoter methylation of BRCA1 or RAD51C is a promising biomarker for PARP inhibitor response, as high levels lead to homologous recombination deficiency (HRD). Yet the extent and role of such methylation in other cancers is not clear. This study comprehensively investigated promoter methylation of eight homologous recombination repair genes across 23 solid cancer types. Here, we showed that BRCA1 methylated cancers were associated with reduced gene expression, loss of heterozygosity (LOH), TP53 mutations and genomic features of HRD. We identified BRCA1 methylation in 3% of the copy-number high subtype of endometrial cancer, and as a rare event in six other cancer types, including lung squamous cell, pancreatic, bladder and stomach cancer. RAD51C promoter methylation was widespread across multiple cancer types, but HRD features were only observed for cases which contained high-level tumour methylation and LOH of RAD51C. While RAD51C methylation was frequent in stomach adenocarcinoma (6%) and low-grade glioma (2.5%), it was mostly detected at a low tumour level, suggestive of heterozygous methylation, and was associated with CpG island methylator phenotype. Our findings indicate that high-level tumour methylation of BRCA1 and RAD51C should be explored as a PARP inhibitor biomarker across multiple cancers.

A case for the use of chemotherapy in hereditary mitochondrial optic neuropathies: Successful administration of cisplatin/etoposide in a male patient with testicular seminoma and Leber's hereditary optic neuropathy.

We report on the successful use of chemotherapy for treatment of stage 2B testicular seminoma in a carrier of the Leber's hereditary optic neuropathy 11778 mitochondrial mutation. Neurotoxic chemotherapy may not prompt disease conversion.

Antenatal screening for fetal structural anomalies - Routine or targeted practice?

Antenatal screening with ultrasound identifies fetal structural anomalies in 3-6% of pregnancies. Identification of anomalies during pregnancy provides an opportunity for counselling, targeted imaging, genetic testing, fetal intervention and delivery planning. Ultrasound is the primary modality for imaging the fetus in pregnancy, but magnetic resonance imaging (MRI) is evolving as an adjunctive tool providing additional structural and functional information. Screening should start from the first trimester when more than 50% of severe defects can be detected. The mid-trimester ultrasound balances the benefits of increased fetal growth and development to improve detection rates, whilst still providing timely management options. A routine third trimester ultrasound may detect acquired anomalies or those missed earlier in pregnancy but may not be available in all settings. Targeted imaging by fetal medicine experts improves detection in high-risk pregnancies or when an anomaly has been detected, allowing accurate phenotyping, access to advanced genetic testing and expert counselling.

CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer.

High-grade serous ovarian cancers (HGSOCs) with homologous recombination deficiency (HRD) are initially responsive to poly (ADP-ribose) polymerase inhibitors (PARPi), but resistance ultimately emerges. HGSOC with CCNE1 amplification (CCNE1 amp) are associated with resistance to PARPi and platinum treatments. High replication stress in HRD and CCNE1 amp HGSOC leads to increased reliance on checkpoint kinase 1 (CHK1), a key regulator of cell cycle progression and the replication stress response. Here, we investigated the anti-tumor activity of the potent, highly selective, orally bioavailable CHK1 inhibitor (CHK1i), SRA737, in both acquired PARPi-resistant BRCA1/2 mutant and CCNE1 amp HGSOC models. We demonstrated that SRA737 increased replication stress and induced subsequent cell death in vitro. SRA737 monotherapy in vivo prolonged survival in CCNE1 amp models, suggesting a potential biomarker for CHK1i therapy. Combination SRA737 and PARPi therapy increased tumor regression in both PARPi-resistant and CCNE1 amp patient-derived xenograft models, warranting further study in these HGSOC subgroups.

Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine.

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection. In this study, we have engineered a range of polymer-based nanocarriers based on the poly(beta-amino ester) (PBAE) polycation platform to investigate the role that surface poly(ethylene glycol) (PEG) density has on pDNA encapsulation, formulation properties and gene transfectability both in vitro and in vivo. We achieved this by synthesising a non-PEGylated and PEGylated PBAE and produced formulations containing these PBAEs, and mixed polyplexes to tune surface PEG density. All polymers and co-formulations produced small polyplex nanoparticles with almost complete encapsulation of the cargo in all cases. Despite high gene transfection in HEK293T cells, only the fully PEGylated and mixed formulations displayed significantly higher expression of the reporter gene than the negative control in dendritic cells. Further in vivo studies with a bivalent SARS-CoV-2 pDNA vaccine revealed that only the mixed formulation led to strong antigen specific T-cell responses, however this did not translate into the presence of serum antibodies indicating the need for further studies into improving immunisation with polymer delivery systems.

Service Dogs for Veterans and Military Members With Posttraumatic Stress Disorder: A Nonrandomized Controlled Trial.

Importance: Military members and veterans (hereafter, veterans) with posttraumatic stress disorder (PTSD) increasingly seek psychiatric service dogs as a complementary intervention, yet the effectiveness of service dogs is understudied. Objective: To estimate the associations between psychiatric service dog partnership and self-reported and clinician-rated PTSD symptom severity, depression, anxiety, and psychosocial functioning after 3 months of intervention among veterans. Design, Setting, and Participants: This nonrandomized controlled trial used standardized and validated assessment instruments completed by participants and administered by blinded clinicians. Recruitment, eligibility screening, and enrollment were conducted between August 2017 and December 2019. Veterans were recruited using the database of an accredited nonprofit service dog organization with constituents throughout the US. Participants were veterans with a PTSD diagnosis; they were allocated to either the intervention group (n = 81) or control group (n = 75). Outcome assessments were performed at baseline and at the 3-month follow-up. Data analyses were completed in October 2023. Interventions: Participants allocated to the intervention group received a psychiatric service dog for PTSD, whereas those allocated to the control group remained on the waiting list based on the date of application submitted to the service dog organization. Both groups had unrestricted access to usual care. Main Outcomes and Measures: The primary outcomes were PTSD symptom severity, depression, and anxiety after 3 months, and the secondary outcomes were psychosocial functioning, such as quality of life and social health. The self-reported PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) was used to measure symptom severity, and the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) was used to assess PTSD diagnosis (score range for both instruments: 0-80, with higher scores indicating greater PTSD symptoms). Results: The 156 participants included in the trial had a mean (SD) age of 37.6 (8.3) years and included 117 males (75%), 17 Black or African American individuals (11%), 30 Hispanic individuals (19%), and 117 White individuals (76%). Compared with the control group, the intervention group had significantly lower PTSD symptom severity based on the PTSD Checklist for DSM-5 mean (SD) score (41.9 [16.9] vs 51.7 [16.1]; difference in means, -11.5 [95% CI, -16.2 to -6.6]; P < .001) and the CAPS-5 mean (SD) score (30.2 [10.2] vs 36.9 [10.2]; difference in means, -7.0 [95% CI, -10.8 to -4.5]; P < .001) at 3 months. The intervention group also had significantly lower depression scores (odds ratio [OR], 0.45 [95% CI, 0.23-0.86]; difference in means, -3.3 [95% CI, -6.8 to -0.6]), anxiety (OR, 0.25 [95% CI, 0.13-0.50]; difference in means, -4.4 [95% CI, -6.9 to -2.1]), and most areas of psychosocial functioning (eg, social isolation: OR, 0.34 [95% CI, 0.18-0.64]). Conclusions and Relevance: This nonrandomized controlled trial found that compared with usual care alone, partnership with a trained psychiatric service dog was associated with lower PTSD symptom severity and higher psychosocial functioning in veterans. Psychiatric service dogs may be an effective complementary intervention for military service-related PTSD. Trial Registration: ClinicalTrials.gov ID: NCT03245814.

RicePilaf: a post-GWAS/QTL dashboard to integrate pangenomic, coexpression, regulatory, epigenomic, ontology, pathway, and text-mining information to provide functional insights into rice QTLs and GWAS loci.

BACKGROUND: As the number of genome-wide association study (GWAS) and quantitative trait locus (QTL) mappings in rice continues to grow, so does the already long list of genomic loci associated with important agronomic traits. Typically, loci implicated by GWAS/QTL analysis contain tens to hundreds to thousands of single-nucleotide polmorphisms (SNPs)/genes, not all of which are causal and many of which are in noncoding regions. Unraveling the biological mechanisms that tie the GWAS regions and QTLs to the trait of interest is challenging, especially since it requires collating functional genomics information about the loci from multiple, disparate data sources. RESULTS: We present RicePilaf, a web app for post-GWAS/QTL analysis, that performs a slew of novel bioinformatics analyses to cross-reference GWAS results and QTL mappings with a host of publicly available rice databases. In particular, it integrates (i) pangenomic information from high-quality genome builds of multiple rice varieties, (ii) coexpression information from genome-scale coexpression networks, (iii) ontology and pathway information, (iv) regulatory information from rice transcription factor databases, (v) epigenomic information from multiple high-throughput epigenetic experiments, and (vi) text-mining information extracted from scientific abstracts linking genes and traits. We demonstrate the utility of RicePilaf by applying it to analyze GWAS peaks of preharvest sprouting and genes underlying yield-under-drought QTLs. CONCLUSIONS: RicePilaf enables rice scientists and breeders to shed functional light on their GWAS regions and QTLs, and it provides them with a means to prioritize SNPs/genes for further experiments. The source code, a Docker image, and a demo version of RicePilaf are publicly available at https://github.com/bioinfodlsu/rice-pilaf.

Judgement and Decision Making in Clinical and Return-to-Sports Decision Making: A Narrative Review.

Making return-to-sport decisions can be complex and multi-faceted, as it requires an evaluation of an individual's physical, psychological, and social well-being. Specifically, the timing of progression, regression, or return to sport can be difficult to determine due to the multitude of information that needs to be considered by clinicians. With the advent of new sports technology, the increasing volume of data poses a challenge to clinicians in effectively processing and utilising it to enhance the quality of their decisions. To gain a deeper understanding of the mechanisms underlying human decision making and associated biases, this narrative review provides a brief overview of different decision-making models that are relevant to sports rehabilitation settings. Accordingly, decisions can be made intuitively, analytically, and/or with heuristics. This narrative review demonstrates how the decision-making models can be applied in the context of return-to-sport decisions and shed light on strategies that may help clinicians improve decision quality.

SD-OCT Imaging of Macular Changes in Fabry Disease: A Case Report.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that can result in fatal end-stage renal disease, heart failure, and cerebro-occlusive events. Vague clinical symptoms and rarity often mean diagnosis and potential treatment is delayed. Ophthalmic findings in FD patients can be helpful in establishing an early diagnosis and timely treatment. Spectral domain optical coherence tomography (SD-OCT) imaging in FD patients shows hyper-reflective foci (HRF) in characteristic patterns within the inner retinal layers. We found that the HRF was localised in linear distributions at the deep and superficial borders of the retinal inner nuclear layer, likely reflecting anatomic vascular plexuses and FD-related sphingolipid deposition within the vessel walls. These results highlight the potential use of SD-OCT in FD and how it may aid diagnosis in undifferentiated patients, prognostication, and disease monitoring.

Examining the effectiveness of municipal street sweeping in removing road-deposited particles and metal(loid)s of respiratory health concern.

Road dust is a demonstrated source of urban air pollution. Given this, the implementation of street sweeping strategies that effectively limit road dust accumulation and resuspension should be a public health priority. Research examining the effectiveness of street sweeping for road dust removal in support of good air quality has been limited to date. To address this, the study aimed to assess the use of a regenerative-air street sweeper to efficiently remove road dust particles and metal(loid)s in size fractions relevant for respiratory exposure in Toronto, Canada. As part of this, the mass amounts, particle size distribution and elemental concentrations of bulk road dust before and after sweeping at five arterial sites were characterized. Sweeping reduced the total mass amount of thoracic-sized (<10 µm) road dust particles by 76 % on average. A shift in the size distribution of remaining particles toward finer fractions was observed in post-sweeping samples, together with an enrichment in many metal(loid)s such as Co, Ti and S. Overall, the mass amounts of metal(loid)s of respiratory health concern like Cu and Zn were greatly reduced with sweeping. Traffic volume and road surface quality were predictors of dust loadings and elemental concentrations. Road surface quality was also found to impact street sweeping efficiencies, with larger mass amounts per unit area collected post-sweeping where street surfaces were distressed. This study demonstrates that street sweeping using advanced technology can be highly effective for road dust removal, highlighting its potential to support air quality improvement efforts. The importance of tailoring sweeping service levels and technologies locally as per the quality of road surface and traffic patterns is emphasized. Continued efforts to mitigate non-exhaust emissions that pose a respiratory health risk at their source is essential.

Consensus methods in patellofemoral pain: how rigorous are they? A scoping review.

OBJECTIVE: Clinicians treating patients with patellofemoral pain (PFP) rely on consensus statements to make the best practice recommendations in the absence of definitive evidence on how to manage PFP. However, the methods used to generate and assess agreement for these recommendations have not been examined. Our objective was to map the methods used to generate consensus-based recommendations for PFP and apply four novel questions to assess the rigour of consensus development. DESIGN: Scoping review. DATA SOURCES: We searched Medline, SPORTDiscus, CINAHL and Embase from inception to May 2022 to identify consensus-derived statements or practice guidelines on PFP. The Joanna Briggs Institute Manual for Evidence Synthesis was followed to map the existing evidence. We measured the consensus methods based on four sets of questions addressing the panel composition, application of the consensus method chosen, agreement process and the use of evidence mapping. ELIGIBILITY CRITERIA: All consensus statements or clinical guidelines on PFP were considered. RESULTS: Twenty-two PFP consensus statements were identified. Panel composition: 3 of the 22 (14%) consensus groups reported the panellists' experience, 2 (9%) defined a desired level of expertise, 10 (45%) reported panellist sex and only 2 (9%) included a patient. Consensus method: 7 of 22 (32%) reported using an established method of consensus measurement/development. Agreement process: 10 of 22 (45%) reported their consensus threshold and 2 (9%) acknowledged dissenting opinions among the panel. Evidence mapping: 6 of 22 (27%) reported using systematic methods to identify relevant evidence gaps. CONCLUSIONS: PFP consensus panels have lacked diversity and excluded key partners including patients. Consensus statements on PFP frequently fail to use recognised consensus methods, rarely describe how 'agreement' was defined or measured and often neglect to use systematic methods to identify evidence gaps.

The Physical Demands of Wheelchair Tennis Match Play: A Systematic Review with Meta-analysis.

BACKGROUND: Wheelchair tennis, a globally popular sport, features a professional tour spanning 40 countries and over 160 tournaments. Despite its widespread appeal, information about the physical demands of wheelchair tennis is scattered across various studies, necessitating a comprehensive systematic review to synthesise available data. OBJECTIVE: The aim was to provide a detailed synthesis of the physical demands associated with wheelchair tennis, encompassing diverse factors such as court surfaces, performance levels, sport classes, and sexes. METHODS: We conducted comprehensive searches in the PubMed, Embase, CINAHL, and SPORTDiscus databases, covering articles from inception to March 1, 2023. Forward and backward citation tracking from the included articles was carried out using Scopus, and we established eligibility criteria following the Population, Exposure, Comparison, Outcome, and Study design (PECOS) framework. Our study focused on wheelchair tennis players participating at regional, national, or international levels, including both juniors and adults, and open and quad players. We analysed singles and doubles matches and considered sex (male, female), sport class (open, quad), and court surface type (hard, clay, grass) as key comparative points. The outcomes of interest encompassed play duration, on-court movement, stroke performance, and physiological match variables. The selected study designs included observational cross-sectional, longitudinal, and intervention studies (baseline data only). We calculated pooled means or mean differences with 95% confidence intervals (CIs) and employed a random-effects meta-analysis with robust variance estimation. We assessed heterogeneity using Cochrane Q and 95% prediction intervals. RESULTS: Our literature search retrieved 643 records, with 24 articles meeting our inclusion criteria. Most available information focused on international male wheelchair tennis players in the open division, primarily competing in singles on hard courts. Key findings (mean [95% CI]) for these players on hard courts were match duration 65.9 min [55.0-78.8], set duration 35.0 min [28.2-43.5], game duration 4.6 min [0.92-23.3], rally duration 6.1 s [3.7-10.2], effective playing time 19.8% [18.9-20.7], and work-to-rest ratio 1:4.1 [1:3.7-1:4.4]. Insufficient data were available to analyse play duration for female players. However, for the available data on hard court matches, the average set duration was 34.8 min [32.5-37.2]. International male players on hard court covered an average distance per match of 3859 m [1917-7768], with mean and peak average forward speeds of 1.06 m/s [0.85-1.32] and 3.55 m/s [2.92-4.31], respectively. These players executed an average of 365.9 [317.2-422.1] strokes per match, 200.6 [134.7-299.0] per set, 25.4 [16.7-38.7] per game, and 3.4 [2.6-4.6] per rally. Insufficient data were available for a meta-analysis of female players' on-court movement and stroke performance. The average and peak heart rates of international male players on hard court were 134.3 [124.2-145.1] and 166.0 [132.7-207.6] beats per minute, and the average match heart rate expressed as a percentage of peak heart rate was 74.7% [46.4-100]. We found no studies concerning regional players or juniors, and only one study on doubles match play. CONCLUSIONS: While we present a comprehensive overview of the physical demands of wheelchair tennis, our understanding predominantly centres around international male players competing on hard courts in the open division. To attain a more comprehensive insight into the sport's physical requirements, future research should prioritise the inclusion of data on female and quad players, juniors, doubles, and matches played on clay and grass court surfaces. Such endeavours will facilitate the development of more tailored and effective training programmes for wheelchair tennis players and coaches. The protocol for this systematic review was registered a priori at the International Platform of Registered Systematic Review and Meta-analysis Protocols (Registration https://doi.org/10.37766/inplasy2023.3.0060 ).

How low back pain is managed-a mixed methods study in 32 countries. Part 2 of Low Back Pain in Low- and Middle-Income Countries Series.

BACKGROUND: The Lancet Series of Low Back Pain (LBP) highlighted the lack of LBP data from low- and middle-income countries (LMICs). The study aimed to describe (1) what LBP care is currently delivered in LMICs, and (2) how that care is delivered. METHODS: An online mixed-methods study. A Consortium for LBP in LMICs (n=65) was developed with an expert panel of leading LBP researchers (>2 publications on LBP) and multidisciplinary clinicians and patient partners with five years of clinical/lived LBP experience in LMICs. Quantitative data were analyzed using descriptive statistics. Two researchers independently analyzed qualitative data using deductive and inductive coding and developed a thematic framework. FINDINGS: Forty-seven (85%) of 55 invited panel members representing 32 LMICs completed the survey (38% women; 62% men). The panel included clinicians (34%), researchers (28%), educators (6%), and patient partners (4%). Pharmacotherapies and electrophysiological agents were the most used LBP treatments. The Thematic Framework comprised of eight themes: (1) Self-management is ubiquitous; (2) Medicines are the cornerstone; (3) Traditional therapies have a place; (4) Society plays an important role; (5) Imaging use is very common; (6) Reliance on passive approaches; (7) Social determinants influence LBP care pathway; and (8) Health systems are ill-prepared to address LBP burden. INTERPRETATION: LBP care in LMICs did not consistently align with the best available evidence. Findings will help research prioritization in LMICs and guide global LBP clinical guidelines. FUNDING: The lead author's Fellowship was supported by the International Association for the Study of Pain.

How do I recognise and manage visual snow syndrome?

Visual snow syndrome (VSS) is becoming increasingly recognised by clinicians and self-diagnosed by our patients thanks to online search tools. Previously this phenomenon was overlooked or dismissed leading to increased patient anxiety. Now, however, we need to be careful with that we are not making what would seem to be an easy diagnosis of VSS when actually we are missing any underlying or mimic conditions.