DODGE: Automated point source bacterial outbreak detection using cumulative long term genomic surveillance.

SUMMARY: The reliable and timely recognition of outbreaks is a key component of public health surveillance for foodborne diseases. Whole genome sequencing (WGS) offers high resolution typing of foodborne bacterial pathogens and facilitates the accurate detection of outbreaks. This detection relies on grouping WGS data into clusters at an appropriate genetic threshold, however, methods and tools for selecting and adjusting such thresholds according to the required resolution of surveillance and epidemiological context are lacking. Here we present DODGE (Dynamic Outbreak Detection for Genomic Epidemiology), an algorithm to dynamically select and compare these genetic thresholds. DODGE can analyse expanding datasets over time and clusters that are predicted to correspond to outbreaks (or 'investigation clusters') can be named with the established genomic nomenclature systems to facilitate integrated analysis across jurisdictions. DODGE was tested in two real-world genomic surveillance datasets of different duration, two months from Australia and nine years from the UK. In both cases only a minority of isolates were identified as investigation clusters. Two known outbreaks in the UK dataset were detected by DODGE and were recognised at an earlier timepoint than the outbreaks were reported. These findings demonstrated the potential of the DODGE approach to improve the effectiveness and timeliness of genomic surveillance for foodborne diseases and the effectiveness of the algorithm developed. AVAILABILITY: DODGE is freely available at https://github.com/LanLab/dodge and can easily be installed using Conda. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Patterns of inpatient acute care and emergency department utilization within one year post-initial amputation among individuals with dysvascular major lower extremity amputation in Ontario, Canada: A population-based retrospective cohort study.

INTRODUCTION: Lower extremity amputation (LEA) is a life altering procedure, with significant negative impacts to patients, care partners, and the overall health system. There are gaps in knowledge with respect to patterns of healthcare utilization following LEA due to dysvascular etiology. OBJECTIVE: To examine inpatient acute and emergency department (ED) healthcare utilization among an incident cohort of individuals with major dysvascular LEA 1 year post-initial amputation; and to identify factors associated with acute care readmissions and ED visits. DESIGN: Retrospective cohort study using population-level administrative data. SETTING: Ontario, Canada. POPULATION: Adults individuals (18 years or older) with a major dysvascular LEA between April 1, 2004 and March 31, 2018. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Acute care hospitalizations and ED visits within one year post-initial discharge. RESULTS: A total of 10,905 individuals with major dysvascular LEA were identified (67.7% male). There were 14,363 acute hospitalizations and 19,660 ED visits within one year post-discharge from initial amputation acute stay. The highest common risk factors across all the models included age of 65 years or older (versus less than 65 years), high comorbidity (versus low), and low and moderate continuity of care (versus high). Sex differences were identified for risk factors for hospitalizations, with differences in the types of comorbidities increasing risk and geographical setting. CONCLUSION: Persons with LEA were generally more at risk for acute hospitalizations and ED visits if higher comorbidity and lower continuity of care. Clinical care efforts might focus on improving transitions from the acute setting such as coordinated and integrated care for sub-populations with LEA who are more at risk.

Eligibility for antiamyloid treatment: preparing for disease-modifying therapies for Alzheimer's disease.

BACKGROUND: Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) have early evidence of efficacy. Widespread delivery of DMTs will require major service reconfiguration. Treatment pathways will need to include triaging for eligibility, regular infusions and baseline and follow-up MRI scanning. A critical step in planning is provision of real-world estimates of patients likely to be eligible for triaging, but these are challenging to obtain. METHODS: We performed a retrospective service evaluation of patients attending five memory services across North and East London and a national specialist cognitive disorders service. We examined the likely proportion of patients who would (1) be referred for triaging for DMTs and (2) potentially be suitable for treatments. RESULTS: Data from a total of 1017 patients were included, 517 of whom were seen in community memory services and 500 in a specialist clinic. In the memory services, 367/517 (71%) were diagnosed with possible AD. After exclusions of those in whom cognitive and frailty scores, MRI contraindications or anticoagulant use indicated they would be unlikely to be suitable, an estimated 32% would be eligible for triaging. In the specialist cognitive clinic, where additional investigations are available, 14% of those seen (70/500) would be potentially eligible for treatment. CONCLUSIONS: While a sizeable proportion of patients attending memory clinics may be referred for triaging for DMTs for AD, only a minority are likely to be suitable for these, as demonstrated in patients seen in specialist cognitive services. This will need to be considered when designing pathways for DMT delivery.

Neurophysiology of Resilience in Juvenile Fibromyalgia.

Objective: Juvenile fibromyalgia (JFM) is a chronic pain syndrome predominantly affecting adolescent girls. Resilience may be a protective factor in coping with pain, reducing affective burden, and promoting positive outlooks. Brain regions affected in JFM overlap with those linked to resilience, particularly in the default-mode network (DMN). We investigate the role of resilience on core somatic and affective symptoms in JFM and assess the neurophysiological substrates for the first time. Methods: Forty-one girls with JFM and 40 pain-free adolescents completed a resting-state fMRI assessment and self-report questionnaires. We used clustering analyses to group JFM participants based on resilience, and principal component analyses to summarize core somatic and affective symptoms. We estimated whole-brain and within-DMN connectivity and assessed differences between higher and lower resilience JFM groups and compared their connectivity patterns to pain-free participants. Results: The higher resilience JFM group had less affective (T=4.03; p<.001) but similar core somatic symptoms (T=1.05; p=.302) than the lower resilience JFM group. They had increased whole-brain (T's>3.90, pFDR's<.03) and within-DMN (T=2.20, p=.03) connectivity strength, and higher connectivity between DMN nodes and self-referential, regulatory, and reward-processing regions. Conversely, higher DMN-premotor connectivity was observed in the lower resilience group. Conclusion: JFM participants with higher resilience were protected affectively but not in core somatic symptoms. Greater resilience was accompanied by higher signal integration within the DMN, a network central to internally oriented attention and flexible attention shifting. Crucially, the connectivity pattern in highly resilient patients resembled that of pain-free adolescents, which was not the case for the lower resilience group.

SaLTy: a novel Staphylococcus aureus Lineage Typer.

Staphylococcus aureus asymptomatically colonises 30 % of humans but can also cause a range of diseases, which can be fatal. In 2017 S. aureus was associated with 20 000 deaths in the USA alone. Dividing S. aureus isolates into smaller sub-groups can reveal the emergence of distinct sub-populations with varying potential to cause infections. Despite multiple molecular typing methods categorising such sub-groups, they do not take full advantage of S. aureus genome sequences when describing the fundamental population structure of the species. In this study, we developed Staphylococcus aureus Lineage Typing (SaLTy), which rapidly divides the species into 61 phylogenetically congruent lineages. Alleles of three core genes were identified that uniquely define the 61 lineages and were used for SaLTy typing. SaLTy was validated on 5000 genomes and 99.12 % (4956/5000) of isolates were assigned the correct lineage. We compared SaLTy lineages to previously calculated clonal complexes (CCs) from BIGSdb (n=21 173). SALTy improves on CCs by grouping isolates congruently with phylogenetic structure. SaLTy lineages were further used to describe the carriage of Staphylococcal chromosomal cassette containing mecA (SCCmec) which is carried by methicillin-resistant S. aureus (MRSA). Most lineages had isolates lacking SCCmec and the four largest lineages varied in SCCmec over time. Classifying isolates into SaLTy lineages, which were further SCCmec typed, allowed SaLTy to describe high-level MRSA epidemiology. We provide SaLTy as a simple typing method that defines phylogenetic lineages (https://github.com/LanLab/SaLTy). SaLTy is highly accurate and can quickly analyse large amounts of S. aureus genome data. SaLTy will aid the characterisation of S. aureus populations and ongoing surveillance of sub-groups that threaten human health.

Melting curve analysis reveals false-positive norovirus detection in a molecular syndromic panel.

BACKGROUND: Molecular syndromic panels can improve rapidity of results and ease clinical laboratory workflow, although caution has been raised for potential false-positive results. Upon implementation of a new panel for infectious diarrhea (BioFire® FilmArray® Gastrointestinal [GI] Panel, bioMérieux) in our clinical laboratory, a higher than expected number of stool samples with norovirus were detected. OBJECTIVES: The goal of this study was to investigate positive percent agreement and the false-positive rate of norovirus detected by the multiplex BioFire GI panel compared to a singleplex commercial assay. STUDY DESIGN: From October 2023 to January 2024, all prospective stool samples with a positive norovirus result by BioFire had melting curves reviewed manually using the BioFire FilmArray Torch System. Stool samples further underwent testing by a supplementary real-time RT-PCR assay (Xpert® Norovirus, Cepheid) for comparative analysis. RESULTS: Of the 50 stool samples with norovirus detected by BioFire, 18 (36 %) tested negative by Xpert (deemed "false-positives"). Furthermore, melting curve analysis revealed nearly all of these samples had atypical melting curve morphologies for the "Noro-1" target on BioFire (16/18, 89 %), which was statistically significant (Odds Ratio 173.2, 95 % CI [22.2, 5326.9], p < 0.0001). Stool samples with multiple pathogens detected by BioFire including norovirus were not more likely to produce false-positive norovirus results (Odds Ratio 1, 95 % CI [0.3, 3.3], p = 1). CONCLUSIONS: Although not described in the manufacturer's Instructions for Use, we propose routine manual review of melting curves for the BioFire GI panel prior to reporting, to mitigate potential false-positive norovirus results.

A Multilocus Sequence Typing Scheme for Rapid Identification of Xanthomonas citri Based on Whole-Genome Sequencing Data.

Xanthomonas citri is a plant-pathogenic bacterium associated with a diverse range of host plant species. It has undergone substantial reclassification and currently consists of 14 different subspecies or pathovars that are responsible for a wide range of plant diseases. Whole-genome sequencing (WGS) provides a cutting-edge advantage over other diagnostic techniques in epidemiological and evolutionary studies of X. citri because it has a higher discriminatory power and is replicable across laboratories. WGS also allows for the improvement of multilocus sequence typing (MLST) schemes. In this study, we used genome sequences of Xanthomonas isolates from the NCBI RefSeq database to develop a seven-gene MLST scheme that yielded 19 sequence types (STs) that correlated with phylogenetic clades of X. citri subspecies or pathovars. Using this MLST scheme, we examined 2,911 Xanthomonas species assemblies from NCBI GenBank and identified 15 novel STs from 37 isolates that were misclassified in NCBI. In total, we identified 545 X. citri assemblies from GenBank with 95% average nucleotide identity to the X. citri type strain, and all were classified as one of the 34 STs. All MLST classifications correlated with a phylogenetic position inferred from alignments using 92 conserved genes. We observed several instances where strains from different pathovars formed closely related monophyletic clades and shared the same ST, indicating that further investigation of the validity of these pathovars is required. Our MLST scheme described here is a robust tool for rapid classification of X. citri pathovars using WGS and a powerful method for further comprehensive taxonomic revision of X. citri pathovars.

How has body image been evaluated among people with lower limb loss? A scoping review.

PURPOSE: Lower limb loss can result in an altered body image, leading to changes in self-esteem, mental health and quality of life. This scoping review explored how body image has been evaluated among people with lower limb loss. MATERIALS AND METHODS: Five databases (Embase, Medline, PsychINFO, CINHAL, and Nursing and Allied Health Database) were searched from inception until March 19, 2023. Inclusion criteria: 1) people with lower limb loss; 2) evaluated a body image outcome or theme; and 3) a qualitative, quantitative or mixed methods design. RESULTS: Twenty-four quantitative (n = 19 cross-sectional, n = 3 intervention cohort and n = 2 prospective cohort), 2 qualitative and 1 mixed methods design studies were included. The definition of body image varied across studies, with 59% of studies not reporting a conceptual or theoretical definition. People with lower limb loss perceived a more negative body image compared to control groups. In prospective cohort studies, changes in body image over time were inconclusive. CONCLUSION: People with lower limb loss report a negative body image when compared to other populations. Definitions and understanding of body image changed overtime and varied among studies which may impact introducing interventions to promote positive body image during rehabilitation and beyond in this population.

People with lower limb loss experience altered body image following limb amputation, at the initiation, during and after prosthetic rehabilitation, and re-integrating into the community.Clinicians are encouraged to use this study's proposed lower limb loss-specific definition of body image.The proposed definition incorporates common terminology used in past research in the field and amputee-specific situations when referring to altered body image among this patient population.To better support the psychological adjustment of people with lower limb loss in rehabilitation programs and beyond, clinicians and researchers should evaluate body image at multiple time points (e.g., admission and discharge to rehabilitation, follow-up) using an outcome measure that asks about both with and without a prosthesis on the residual limb.

Botulinum toxin therapy for management of phantom and residual limb pain following amputation: A systematic review.

Chronic pain following amputation is debilitating. Due to its mechanisms in modulating muscle contraction and pain, botulinum toxin has been investigated as a treatment option for phantom limb pain (PLP) and residual limb pain (RLP). The objective of this study was to determine the efficacy of botulinum toxin injection in the management of PLP and RLP following major limb amputation using a systematic review of the literature. The databases Medline, CINAHL, EMBASE, Scopus, Web of Science, and Cochrane were searched from inception through October 30, 2023. The search identified 50 articles; 37 underwent full-text review, and 11 were included in the final review. Eighty-nine individuals with pain were investigated by the included studies; 53 had RLP and 63 had PLP. There was significant variation in botulinum toxin type, injection method, and dosage. Twenty-one (53.9%) and 27 (64.3%) participants had improvement in PLP and RLP following botulinum toxin injection, respectively. Therefore, there is potential for use of botulinum toxin for the treatment of PLP and RLP. However, due to the minimal number of studies, small sample sizes, and heterogenous methodologies, our ability to conclude with certainty the efficacy of botulinum toxin injection on the treatment of PLP and RLP following amputation is limited.

Uncovering the boundaries of Campylobacter species through large-scale phylogenetic and nucleotide identity analyses.

Campylobacter species are typically helical shaped, Gram-negative, and non-spore-forming bacteria. Species in this genus include established foodborne and animal pathogens as well as emerging pathogens. The accumulation of genomic data from the Campylobacter genus has increased exponentially in recent years, accompanied by the discovery of putative new species. At present, the lack of a standardized species boundary complicates distinguishing established and novel species. We defined the Campylobacter genus core genome (500 loci) using publicly available Campylobacter complete genomes (n = 498) and constructed a core genome phylogeny using 2,193 publicly available Campylobacter genomes to examine inter-species diversity and species boundaries. Utilizing 8,440 Campylobacter genomes representing 33 species and 8 subspecies, we found species delineation based on an average nucleotide identity (ANI) cutoff of 94.2% is consistent with the core genome phylogeny. We identified 60 ANI genomic species that delineated Campylobacter species in concordance with previous comparative genetic studies. All pairwise ANI genomic species pairs had in silico DNA-DNA hybridization scores of less than 70%, supporting their delineation as separate species. We provide the tool Campylobacter Genomic Species typer (CampyGStyper) that assigns ANI genomic species to query genomes based on ANI similarities to medoid genomes from each ANI genomic species with an accuracy of 99.96%. The ANI genomic species definitions proposed here allow consistent species definition in the Campylobacter genus and will facilitate the detection of novel species in the future.IMPORTANCEIn recent years, Campylobacter has gained recognition as the leading cause of bacterial gastroenteritis worldwide, leading to a substantial rise in the collection of genomic data of the Campylobacter genus in public databases. Currently, a standardized Campylobacter species boundary at the genomic level is absent, leading to challenges in detecting emerging pathogens and defining putative novel species within this genus. We used a comprehensive representation of genomes of the Campylobacter genus to construct a core genome phylogenetic tree. Furthermore, we found an average nucleotide identity (ANI) of 94.2% as the optimal cutoff to define the Campylobacter species. Using this cutoff, we identified 60 ANI genomic species which provided a standardized species definition and nomenclature. Importantly, we have developed Campylobacter Genomic Species typer (CampyGStyper), which can robustly and accurately assign these ANI genomic species to Campylobacter genomes, thereby aiding pathogen surveillance and facilitating evolutionary and epidemiological studies of existing and emerging pathogens in the genus Campylobacter.

Emergence of Poultry-Associated Human Salmonella enterica Serovar Abortusovis Infections, New South Wales, Australia.

Salmonella enterica serovar Abortusovis is a ovine-adapted pathogen that causes spontaneous abortion. Salmonella Abortusovis was reported in poultry in 2009 and has since been reported in human infections in New South Wales, Australia. Phylogenomic analysis revealed a clade of 51 closely related isolates from Australia originating in 2004. That clade was genetically distinct from ovine-associated isolates. The clade was widespread in New South Wales poultry production facilities but was only responsible for sporadic human infections. Some known virulence factors associated with human infections were only found in the poultry-associated clade, some of which were acquired through prophages and plasmids. Furthermore, the ovine-associated clade showed signs of genome decay, but the poultry-associated clade did not. Those genomic changes most likely led to differences in host range and disease type. Surveillance using the newly identified genetic markers will be vital for tracking Salmonella Abortusovis transmission in animals and to humans and preventing future outbreaks.

What are relevant predictors of physical activity in older adults with lower limb loss (LLL)? Results of a retrospective analysis.

BACKGROUND: People with lower limb loss (LLL) have reduced physical activity (PA). There is evidence of physical and psychosocial predictors of PA in older adults with limb loss. However, these 2 areas (physical/psychosocial) have not been evaluated in the same analysis. OBJECTIVES: To describe and identify predictors of PA in individuals with LLL. STUDY DESIGN: Cross-sectional study. METHODS: Secondary analysis of data from a multisite Canadian randomized control trial involving community-dwelling prosthetic ambulators with unilateral transtibial or transfemoral amputation (N = 72). The dependent variable was the Physical Activity Scale for the Elderly. Potential predictors were four step square test, 2-minute walk test, Short Physical Performance Battery, Life Space Assessment, walking while talking test, and Activities-specific Balance Confidence scale. RESULTS: Seventy-two community-dwelling lower limb prosthesis users were enrolled. The sample included 62 male participants (86%), and 58 participants (81%) had transtibial amputation. The average age of participants was 65 (8.9) years, and for 49 participants (70%), the amputation was over 24 months ago. The total mean Standard Deviation (SD) Physical Activity Scale for the Elderly score was 153.2 (88.3), with scores of 148.1 (11.4) and 184.5 (24.7) for male and female participants, respectively. Regression analysis identified Life Space Assessment (ß = 1.15, p = 0.007) and Short Physical Performance Battery (ß = 3.51, p = 0.043) as statistically significant predictors accounting for 25% of the variance in PA. CONCLUSIONS: Community mobility and physical performance are the most meaningful predictors of PA. Future research should examine additional factors (e.g., environment, motivation). Understanding the predictors for PA after LLL would improve clinical practice as clinicians would have increased knowledge to modify and improve training.

Optimizing Temporal Summation of Heat Pain Using a Constant Contact Heat Stimulator.

Purpose: Temporal summation (TS) of pain occurs when pain increases over repeated presentations of identical noxious stimuli. TS paradigms can model central sensitization, a state of hyperexcitability in nociceptive pathways that promotes chronic pain onset and maintenance. Many experimenters use painful heat stimuli to measure TS (TS-heat); yet, TS-heat research faces unresolved challenges, including difficulty evoking summation in up to 30-50% of participants. Moreover, substantial variability exists between laboratories regarding the methods for evoking and calculating TS-heat. Patients and Methods: To address these limitations, this study sought to identify optimal parameters for evoking TS-heat in healthy participants with a commercially available constant contact heat stimulator, the Medoc TSA-II. Working within constraints of the TSA-II, stimulus trains with varying parameters (eg, stimulus frequency, baseline temp, peak temp, peak duration, testing site) were tested in a sample of 32 healthy, chronic pain-free participants to determine which combination best evoked TS-heat. To determine whether TS scoring method altered results, TS-heat was scored using three common methods. Results: Across all methods, only two trains successfully evoked group-level TS-heat. These trains shared the following parameters: site (palmar hand), baseline and peak temperatures (44°C and 50°C, respectively), and peak duration (0.5 s). Both produced summation that peaked at moderate pain (~50 out of 100 rating). Conclusion: Future TS-heat investigations using constant contact thermodes and fixed protocols may benefit from adopting stimulus parameters that include testing on the palmar hand, using 44°C baseline and 50°C peak temperatures, at ≥0.33 Hz stimulus frequency, and peak pulse durations of at least 0.5 seconds.

The effect of exercise interventions on gait outcomes in subacute and chronic rehabilitation from lower-limb amputation: A systematic review and meta-analysis.

Successful walking is a substantial contributor to quality of life in people with lower-limb amputation (PLLA), yet gait difficulties are common. Evidence-based exercise guidelines are necessary for PLLA with different clinical characteristics and at different phases of recovery. To systematically review the literature evaluating effects of exercise interventions on gait outcomes in PLLA at subacute and chronic stages of recovery. Databases MEDLINE, EMBASE, CINAHL, SPORTDiscus, Scopus, and the Cochrane Library were searched (inception to May 10, 2022). Inclusion criteria: randomized controlled trials assessing gait outcomes following exercise intervention; subjects were PLLA ≥18 years of age and used a prosthesis for walking. Meta-analysis using random effects with inverse variance to generate standardized mean differences (SMDs) was completed for primary gait outcomes. Subgroup analysis was conducted for the recovery phase (i.e., subacute and chronic) and level of amputation (e.g., transfemoral and transtibial). Of 16 included articles, 4 studies examined the subacute phase of recovery, whereas 12 examined the chronic phase. Subacute interventions were 30 minutes, 1-7 times/week, for 2-12 weeks. Chronic interventions were 15-60-minutes, 2-3 times/week, for 4-16 weeks. Low-moderate level evidence was shown for a small improvement in the subacute phase (SMD = 0.42, 95% confidence interval [0.06-0.79], I 2 = 46.0%) and a moderate improvement in the chronic phase (SMD = 0.67, 95% confidence interval [0.40-0.94], I 2 = 0.0%) in favor of exercise intervention groups. Multicomponent exercise programs consisting of gait, balance, and strength training are effective at improving gait outcomes in PLLA at subacute and chronic phases of recovery. The optimal duration and frequency of exercise is unclear because of variation between interventions, highlighting an area for future work.

Reduced Cortico-Cortical Resting-State Connectivity in Sensory Systems Related to Bodily Pain in Juvenile Fibromyalgia.

OBJECTIVE: Juvenile-onset fibromyalgia (JFM) is a paradigmatic chronic pain condition for which the underlying neurobiological substrates are poorly understood. This study examined, for the first time, data-driven resting-state functional connectivity (rsFC) alterations in 37 female adolescents with JFM compared with 43 healthy female adolescents and identified associations with bodily pain. METHODS: Whole-brain voxel-wise rsFC alterations were assessed using the intrinsic connectivity contrast, a measure of node centrality at each voxel, and seed-based analyses for interpretability. We studied the relationship between rsFC alterations in somatosensory systems and the location and extension of bodily pain. RESULTS: Adolescents with JFM had voxel-wise rsFC reductions in the paracentral lobule (PCL)/primary somatosensory cortex (S1) (T = 4.89, family-wise error corrected p-value (pFWE) < 0.001) and left midcingulate cortex (T = 4.67, pFWE = 0.043). Post hoc analyses revealed reduced rsFC spanning major cortical sensory hubs (T > 4.4, pFWE < 0.030). Cortico-cortical rsFC reductions within PCL/S1 in JFM occurred in locations innervated by bodily areas where the pain was most frequent (F = 3.15; positive false discovery rate = 0.029) and predicted widespread pain (T > 4.4, pFWE < 0.045). Conversely, adolescents with JFM had increases in PCL/S1-thalamus (T = 4.75, pFWE = 0.046) and PCL/S1-anterior insula rsFC (T = 5.13, pFWE = 0.039). CONCLUSION: Reduced cortico-cortical sensory integration involving PCL/S1 and spanning the sensory systems may underly critical pain sensory features in youth with JFM. Reduced sensory integration is paralleled by augmented cross-talk between sensory and affective/salience-processing regions, potentially indicating a shift toward more affectively colored sensory experiences to the detriment of specific sensory discrimination.

Efficiently Differentiating Agonists and Competitive Antagonists for Weak Allosteric Protein-Ligand Interactions with Linear Response Theory.

What makes an agonist and a competitive antagonist? In this work, we aim to answer this question by performing parallel tempering Monte Carlo simulations on the serotonin type 3A (5-HT3A) receptor. We use linear response theory to predict conformational changes in the 5-HT3A receptor active site after weak perturbations are applied to its allosteric binding sites. A covariance tensor is built from conformational sampling of its apo state, and a harmonic approximation allows us to substitute the calculation of ligand-induced forces with the binding site's displacement vector. Remarkably, our study demonstrates the feasibility of effectively discerning between agonists and competitive antagonists for multiple ligands, requiring computationally expensive calculations only once per protein.

Migration and health study: a socio-ecological analysis of sexual health among migrants in Manitoba, Canada.

BACKGROUND: To develop effective public health policies, programs, and services tailored to the unique sexual health needs of migrant populations, it is essential to understand the myriad socio-ecological factors that influence their sexual health. This qualitative community-based participatory study aimed to explore factors influencing migrants' sexual health at different socio-ecological levels in a Canadian setting. METHODS: Participants (n = 34) from African, Caribbean, Black; Latin American; South Asian; Middle Eastern, as well as East and Southeast Asian communities were recruited across Manitoba using printed flyers, community organizations, and social media. Individual interviews, conducted in English, French, Mandarin, Cantonese, Tagalog, Arabic, Swahili, and Tigrinya languages, explored questions relating to sexual health and experiences with service providers. Data were analyzed using reflexive thematic analysis and socio-ecological systems theory. RESULTS: The study uncovered a range of individual, interpersonal, institutional, and socio-structural factors that affect the sexual health of migrants in Manitoba. Individual factors such as sexual health knowledge and testing practices, interpersonal factors like the type of sexual partnerships, institutional factors such as sexual health information needs, language, and service access barriers, and structural-level factors like gender norms and HIV stigma exerted a significant influence on the sexual health practices of study respondents. Sexual health awareness was influenced by various factors including length of time in Canada and involvement in community-based services. Study respondents identified issues related to access to HIV testing and sexual health information, as well as language barriers, racism in healthcare, and HIV stigma. Gender and social norms played a significant role in discouraging communication about sex and safer sex practices. CONCLUSIONS: The study highlights the complex interplay of factors that influence the sexual health of migrants, and the need for targeted sexual health awareness campaigns and provision of sexual health information in languages spoken by migrants. Public health interventions focused on improving the sexual health outcomes for migrants should consider the socio-ecological elements identified in this study. These findings can inform public health campaigns to increase access to services and address sexual health inequities among migrant communities in Canada.

Emergence and genomic insights of non-pandemic O1 Vibrio cholerae in Zhejiang, China.

IMPORTANCE: It is well recognized that only Vibrio cholerae O1 causes cholera pandemics. However, not all O1 strains cause pandemic-level disease. In this study, we analyzed non-pandemic O1 V. cholerae isolates from the 1960s to the 1990s from China and found that they fell into three lineages, one of which shared the most recent common ancestor with pandemic O1 strains. Each of these non-pandemic O1 lineages has unique properties that contribute to their capacity to cause cholera. The findings of this study enhanced our understanding of the emergence and evolution of both pandemic and non-pandemic O1 V. cholerae.

Rheumatoid arthritis and older age are associated with lower humoral and cellular immune response to primary series COVID-19 mRNA vaccine.

OBJECTIVE: People with autoimmune disease have worse COVID-19 infection-related outcomes, lower antibody responses to COVID-19 vaccine, and higher rates of breakthrough infection. Immunosuppressive medications used to treat rheumatoid arthritis (RA) are associated with lower COVID-19 vaccine responses, though independent contributions of comorbidities, T-cell immunity, and age are less clear. We sought to test the hypothesis that RA, immunosuppressive medications used to treat RA, and older age, contribute to reduced B and T cell response to COVID-19 vaccine. METHODS: We evaluated serum samples, taken the day of 1st vaccine dose, the day of 2nd dose, 2-6 weeks after 2nd dose, 7-12 weeks after 2nd dose, 13-24 weeks after 2nd dose, and 2-6 weeks after the 3rd dose, for anti-spike IgG and neutralizing antibody levels to Wuhan and Omicron BA.1 and peripheral blood mononuclear cells (PBMC) for spike-specific IFN-γ and IL-2 production by ELISPOT assay in 46 RA and 101 non-autoimmune control participants before and after the primary series COVID-19 mRNA vaccination. RESULTS: RA participants had lower spike-specific IgG and Wuhan-strain neutralizing antibody levels 2-6 weeks compared to controls after the second dose of primary vaccine series. Neutralizing antibody levels against Omicron BA.1 were low in both groups. IFN-γ production correlated with Wuhan neutralizing antibody levels, while older age negatively correlated with spike-specific IL-2, IFN-γ and IgG. Lower antibody levels were associated with older age, RA status, and medication usage, while lower T cell responses were associated primarily with older age. CONCLUSIONS: These data indicate lower COVID-19 mRNA vaccine-induced antibody levels in persons with RA compared to individuals without RA, likely partially attributable to immune suppressive medications. At the same time, older age is associated with lower antibody and cellular immune response to COVID-19 vaccines.

Social and structural barriers and facilitators to HIV healthcare and harm reduction services for people experiencing syndemics in Manitoba: study protocol.

INTRODUCTION: In Manitoba, Canada, there has been an increase in the number of people newly diagnosed with HIV and those not returning for regular HIV care. The COVID-19 pandemic resulted in increased sex and gender disparities in disease risk and mortalities, decreased harm reduction services and reduced access to healthcare. These health crises intersect with increased drug use and drug poisoning deaths, houselessness and other structural and social factors most acutely among historically underserved groups. We aim to explore the social and structural barriers and facilitators to HIV care and harm reduction services experienced by people living with HIV (PLHIV) in Manitoba. METHODS AND ANALYSIS: Our study draws on participatory action research design. Guiding the methodological design are the lived experiences of PLHIV. In-depth semi-structured face-to-face interviews and quantitative questionnaires will be conducted with two groups: (1) persons aged ≥18 years living or newly diagnosed with HIV and (2) service providers who work with PLHIV. Data collection will include sex, gender, sociodemographic information, income and housing, experiences with the criminal justice system, sexual practices, substance use practices and harm reduction access, experiences with violence and support, HIV care journey (since diagnosis until present), childhood trauma and a decision-making questionnaire. Data will be analysed intersectionally, employing grounded theory for thematic analysis, sex-based and gender-based analysis and social determinants of health and syndemic framework to understand the experiences of PLHIV in Manitoba. ETHICS AND DISSEMINATION: We received approval from the University of Manitoba Health Ethics Research Board (HS25572; H2022:218), First Nations Health and Social Secretariat of Manitoba, Nine Circles Community Health Centre, Shared Health Manitoba (SH2022:194) and 7th Street Health Access Centre. Findings will be disseminated using community-focused knowledge translation strategies identified by participants, peers, community members and organisations, and reported in conferences, peer-reviewed journals and a website (www.alltogether4ideas.org).