Inhaled antibiotics: A promising drug delivery strategies for efficient treatment of lower respiratory tract infections (LRTIs) associated with antibiotic resistant biofilm-dwelling and intracellular bacterial pathogens.

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.

Changes in urinary glutathione sulfonamide (GSA) levels between admission and discharge of patients with cystic fibrosis.

There is an urgent need to develop sensitive, non-invasive biomarkers that can track airway inflammatory activity for patients with cystic fibrosis (CF). Urinary glutathione sulfonamide (GSA) levels correlate well with GSA levels in BAL samples and other markers of neutrophilic inflammation, suggesting that this biomarker may be suitable for tracking disease activity in this population. We recruited 102 children (median 11.5 years-old) and 64 adults (median 32.5 years-old) who were admitted to hospital for management of an acute pulmonary exacerbation and/or eradication of infectious agents such as Pseudomonas aeruginosa or Staphylococcus aureus. Our aim was to explore how urinary GSA levels changed across admission timepoints. Urine samples were collected at admission and discharge, and GSA measured by liquid chromatography with mass spectrometry. Paired admission-discharge results were compared using Wilcoxon signed-rank test. Paired admission-discharge samples were available for 53 children and 60 adults. A statistically significant difference was observed between admission-discharge for children and adults. Spearman's correlation analysis identified a correlation between urinary GSA levels and sex and S. aureus infection for children only. Our preliminary findings suggest that urinary GSA is responsive to the resolution of an acute pulmonary exacerbation and therefore warrants further studies in this population.

Attenuating ribosome load improves protein output from mRNA by limiting translation-dependent mRNA decay.

Developing an effective mRNA therapeutic often requires maximizing protein output per delivered mRNA molecule. We previously found that coding sequence (CDS) design can substantially affect protein output, with mRNA variants containing more optimal codons and higher secondary structure yielding the highest protein outputs due to their slow rates of mRNA decay. Here, we demonstrate that CDS-dependent differences in translation initiation and elongation rates lead to differences in translation- and deadenylation-dependent mRNA decay rates, thus explaining the effect of CDS on mRNA half-life. Surprisingly, the most stable and highest-expressing mRNAs in our test set have modest initiation/elongation rates and ribosome loads, leading to minimal translation-dependent mRNA decay. These findings are of potential interest for optimization of protein output from therapeutic mRNAs, which may be achieved by attenuating rather than maximizing ribosome load.

Mpox Diagnosis, Behavioral Risk Modification, and Vaccination Uptake among Gay, Bisexual, and Other Men Who Have Sex with Men, United Kingdom, 2022.

During the 2022 multicountry mpox outbreak, the United Kingdom identified cases beginning in May. UK cases increased in June, peaked in July, then rapidly declined after September 2022. Public health responses included community-supported messaging and targeted mpox vaccination among eligible gay, bisexual, and other men who have sex with men (GBMSM). Using data from an online survey of GBMSM during November-December 2022, we examined self-reported mpox diagnoses, behavioral risk modification, and mpox vaccination offer and uptake. Among 1,333 participants, only 35 (2.6%) ever tested mpox-positive, but 707 (53%) reported behavior modification to avoid mpox. Among vaccine-eligible GBMSM, uptake was 69% (95% CI 65%-72%; 601/875) and was 92% (95% CI 89%-94%; 601/655) among those offered vaccine. GBMSM self-identifying as bisexual, reporting lower educational qualifications, or identifying as unemployed were less likely to be vaccinated. Equitable offer and provision of mpox vaccine are needed to minimize the risk for future outbreaks and mpox-related health inequalities.

Impact of CFTR Modulation on Pseudomonas aeruginosa Infection in People With Cystic Fibrosis.

BACKGROUND: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation. METHODS: P. aeruginosa strains (n = 105) were isolated from the sputum of 11 chronically colonized pwCF at baseline and up to 21 months posttreatment with elexacaftor-tezacaftor-ivacaftor or tezacaftor-ivacaftor. Phenotypic characterization and comparative genomics were performed. RESULTS: Clonal lineages of P. aeruginosa persisted after therapy, with no evidence of displacement by alternative strains. We identified commonly mutated genes among patient isolates that may be positively selected for in the CFTR-modulated lung. However, classic chronic P. aeruginosa phenotypes such as mucoid morphology were sustained, and isolates remained just as resistant to clinically relevant antibiotics. CONCLUSIONS: Despite the clinical benefits of CFTR modulators, clonal lineages of P. aeruginosa persist that may prove just as difficult to manage in the future, especially in pwCF with advanced lung disease.

Correction: Guo et al. A Siamese Transformer Network for Zero-Shot Ancient Coin Classification. J. Imaging 2023, 9, 107.

Jochen Büttner was not included as an author in the original publication [...].

Genomic analyses of Burkholderia respiratory isolates indicates two evolutionarily distinct B. anthina clades.

Introduction: The Burkholderia cepacia complex (BCC) encompasses a group of at least 22 genetically distinct gram-negatives bacterial species ubiquitous in nature. Recognised as a group of genetically and phenotypically flexible species, the BCC inhabits diverse ecological niches causing both plant and human diseases. Comparative genomic analysis provides an in depth understanding into the population biology, phylogenetic relationship, and genomic architecture of species. Methods: Here, we genomically characterise Burkholderia anthina isolated from patients with chronic lung infections, an understudied pathogen within the Burkholderia cepacia complex. Results: We demonstrate that B. anthina is polyphyletic and constitutes two distinct evolutionary lineages. Core- and pan-genome analyses demonstrated substantial metabolic diversity, with B. anthina Clade I enriched in genes associated with microbial metabolism in diverse environments, including degradation of aromatic compounds and metabolism of xenobiotics, while B. anthina Clade II demonstrated an enhanced capability for siderophore biosynthesis. Discussion: Based on our phylogenetic and comparative genomic analyses, we suggest stratifying B. anthina to recognise a distinct species harbouring increased potential for iron metabolism via siderophore synthesis, for which we propose the name Burkholderia anthinoferum (sp. nov.).

Development and Validation of a Brief Measure of Sexual Wellbeing for Population Surveys: The Natsal Sexual Wellbeing Measure (Natsal-SW).

Sexual wellbeing is an important aspect of population health. Addressing and monitoring it as a distinct issue requires valid measures. Our previous conceptual work identified seven domains of sexual wellbeing: security; respect; self-esteem; resilience; forgiveness; self-determination; and comfort. Here, we describe the development and validation of a measure of sexual wellbeing reflecting these domains. Based on the analysis of 40 semi-structured interviews, we operationalized domains into items, and refined them via cognitive interviews, workshops, and expert review. We tested the items via two web-based surveys (n = 590; n = 814). Using data from the first survey, we carried out exploratory factor analysis to assess and eliminate poor performing items. Using data from the second survey, we carried out confirmatory factor analysis to examine model fit and associations between the item reduced measure and external variables hypothesized to correlate with sexual wellbeing (external validity). A sub-sample (n = 113) repeated the second survey after 2 weeks to evaluate test-retest reliability. Confirmatory factor analysis indicated that a "general specific model" had best fit (RMSEA: 0.064; CFI: 0.975, TLI: 0.962), and functioned equivalently across age group, gender, sexual orientation, and relationship status. The final Natsal-SW measure comprised 13 items (from an initial set of 25). It was associated with external variables in the directions hypothesized (all p < .001), including mental wellbeing (0.454), self-esteem (0.564), body image (0.232), depression (-0.384), anxiety (-0.340), sexual satisfaction (0.680) and sexual distress (-0.615), and demonstrated good test-retest reliability (ICC = 0.78). The measure enables sexual wellbeing to be quantified and understood within and across populations.

Paraquat ingestion in an adult with cystic fibrosis (CF): Diagnostic and management dilemmas.

N,N'-dimethyl-4,4'bipyridinium dichloride (Paraquat) is a potent herbicide used widely in agriculture. We report the effects of an ingestion of paraquat by a 28 year old male with cystic fibrosis and the diagnostic and management challenges this posed in both the acute and longer term setting. We describe the effects of direct paraquat toxicity on the lung tissue secondary to aspiration and review the long-term sequelae of paraquat, namely osteonecrosis. Our case is the first to describe osteonecrosis of the knee in the context of paraquat toxicity. Survival following ingestion remains poor with a high associated mortality. However, timely treatment with NAC and immunosuppression may impact on survival. In those patients who do survive the acute phase post ingestion, follow-up over years may be required to detect the long-term effects of paraquat on bone health.

Temporally specific gene expression and chromatin remodeling programs regulate a conserved Pdyn enhancer.

Neuronal and behavioral adaptations to novel stimuli are regulated by temporally dynamic waves of transcriptional activity, which shape neuronal function and guide enduring plasticity. Neuronal activation promotes expression of an immediate early gene (IEG) program comprised primarily of activity-dependent transcription factors, which are thought to regulate a second set of late response genes (LRGs). However, while the mechanisms governing IEG activation have been well studied, the molecular interplay between IEGs and LRGs remain poorly characterized. Here, we used transcriptomic and chromatin accessibility profiling to define activity-driven responses in rat striatal neurons. As expected, neuronal depolarization generated robust changes in gene expression, with early changes (1 hr) enriched for inducible transcription factors and later changes (4 hr) enriched for neuropeptides, synaptic proteins, and ion channels. Remarkably, while depolarization did not induce chromatin remodeling after 1 hr, we found broad increases in chromatin accessibility at thousands of sites in the genome at 4 hr after neuronal stimulation. These putative regulatory elements were found almost exclusively at non-coding regions of the genome, and harbored consensus motifs for numerous activity-dependent transcription factors such as AP-1. Furthermore, blocking protein synthesis prevented activity-dependent chromatin remodeling, suggesting that IEG proteins are required for this process. Targeted analysis of LRG loci identified a putative enhancer upstream of Pdyn (prodynorphin), a gene encoding an opioid neuropeptide implicated in motivated behavior and neuropsychiatric disease states. CRISPR-based functional assays demonstrated that this enhancer is both necessary and sufficient for Pdyn transcription. This regulatory element is also conserved at the human PDYN locus, where its activation is sufficient to drive PDYN transcription in human cells. These results suggest that IEGs participate in chromatin remodeling at enhancers and identify a conserved enhancer that may act as a therapeutic target for brain disorders involving dysregulation of Pdyn.

Antimicrobial and in silico studies of the triterpenoids of Dichapetalum albidum.

Here we report a new polyhydroxylated triterpene, 2ß,6ß,21α-trihydroxyfriedelan-3-one (4) isolated from the root and stem bark of Dichapetalum albidum A. Chev (Dichapetalaceae), along with six known triterpenoids (1-3, 5, 6, 8), sitosterol-3ß-O-D-glucopyranoside (9), a dipeptide (7), and a tyramine derivative of coumaric acid (10). Friedelan-3-one (2) showed an antimicrobial activity (IC50) of 11.40 µg/mL against Bacillus cereus, while friedelan-3α-ol (1) gave an IC50 of 13.07 µg/mL against Staphylococcus aureus with ampicillin reference standard of 19.52 µg/mL and 0.30 µg/mL respectively. 3ß-Acetyl tormentic acid (5) showed an IC50 of 12.50 µg/mL against Trypanosoma brucei brucei and sitosterol-3ß-O-d-glucopyranoside (9) showed an IC50 of 5.06 µg/mL against Leishmania donovani with respective reference standards of IC50 5.02 µg/mL for suramin and IC50 0.27 µg/mL for amphotericin B. Molecular docking of the isolated compounds on the enzyme glucose-6-phosphate dehydrogenase (G6PDH) suggested 3ß-acetyl tormentic acid (5) and sitosterol-3ß-O-D-glucopyranoside (9) as plausible inhibitors of the enzyme in accordance with the experimental biological results observed.

Examining SRP pathway function in mRNA localization to the endoplasmic reticulum.

Signal recognition particle (SRP) pathway function in protein translocation across the endoplasmic reticulum (ER) is well established; its role in RNA localization to the ER remains, however, unclear. In current models, mRNAs undergo translation- and SRP-dependent trafficking to the ER, with ER localization mediated via interactions between SRP-bound translating ribosomes and the ER-resident SRP receptor (SR), a heterodimeric complex comprising SRA, the SRP-binding subunit, and SRB, an integral membrane ER protein. To study SRP pathway function in RNA localization, SR knockout (KO) mammalian cell lines were generated and the consequences of SR KO on steady-state and dynamic mRNA localization examined. CRISPR/Cas9-mediated SRPRB KO resulted in profound destabilization of SRA. Pairing siRNA silencing of SRPRA in SRPRB KO cells yielded viable SR KO cells. Steady-state mRNA compositions and ER-localization patterns in parental and SR KO cells were determined by cell fractionation and deep sequencing. Notably, steady-state cytosol and ER mRNA compositions and partitioning patterns were largely unaltered by loss of SR expression. To examine SRP pathway function in RNA localization dynamics, the subcellular trafficking itineraries of newly exported mRNAs were determined by 4-thiouridine (4SU) pulse-labeling/4SU-seq/cell fractionation. Newly exported mRNAs were distinguished by high ER enrichment, with ER localization being SR-independent. Intriguingly, under conditions of translation initiation inhibition, the ER was the default localization site for all newly exported mRNAs. These data demonstrate that mRNA localization to the ER can be uncoupled from the SRP pathway function and reopen questions regarding the mechanism of RNA localization to the ER.

Pattern forming mechanisms of color vision.

While our understanding of the way single neurons process chromatic stimuli in the early visual pathway has advanced significantly in recent years, we do not yet know how these cells interact to form stable representations of hue. Drawing on physiological studies, we offer a dynamical model of how the primary visual cortex tunes for color, hinged on intracortical interactions and emergent network effects. After detailing the evolution of network activity through analytical and numerical approaches, we discuss the effects of the model's cortical parameters on the selectivity of the tuning curves. In particular, we explore the role of the model's thresholding nonlinearity in enhancing hue selectivity by expanding the region of stability, allowing for the precise encoding of chromatic stimuli in early vision. Finally, in the absence of a stimulus, the model is capable of explaining hallucinatory color perception via a Turing-like mechanism of biological pattern formation.

Substance use, socio-demographic characteristics, and self-rated health of people seeking alcohol and other drug treatment in New South Wales: baseline findings from a cohort study.

OBJECTIVE: To investigate the demographic characteristics, substance use, and self-rated health of people entering treatment in New South Wales public health services for alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use, by principal drug of concern. DESIGN: Baseline findings of a cohort study; analysis of data in patient electronic medical records and NSW minimum data set for drug and alcohol treatment services. SETTING, PARTICIPANTS: People completing initial Australian Treatment Outcomes Profile (ATOP) assessments on entry to publicly funded alcohol and other drug treatment services in six NSW local health districts/networks, 1 July 2016 - 30 June 2019. MAIN OUTCOME MEASURES: Socio-demographic characteristics, and substance use and self-rated health (psychological, physical, quality of life) during preceding 28 days, by principal drug of concern. RESULTS: Of 14 087 people included in our analysis, the principal drug of concern was alcohol for 6051 people (43%), opioids for 3158 (22%), amphetamine-type stimulants for 2534 (18%), cannabis for 2098 (15%), and cocaine for 246 (2%). Most people commencing treatment were male (9373, 66.5%), aged 20-39 years (7846, 50.4%), and were born in Australia (10 934, 86.7%). Polysubstance use was frequently reported, particularly by people for whom opioids or amphetamine-type stimulants were the principal drugs of concern. Large proportions used tobacco daily (53-82%, by principal drug of concern group) and reported poor psychological health (47-59%), poor physical health (32-44%), or poor quality of life (43-52%). CONCLUSIONS: The prevalence of social disadvantage and poor health is high among people seeking assistance with alcohol, amphetamine-type stimulants, cannabis, cocaine, or opioids use problems. Given the differences in these characteristics by principal drug of concern, health services should collect comprehensive patient information during assessment to facilitate more holistic, tailored, and person-centred care.

Temporally specific gene expression and chromatin remodeling programs regulate a conserved Pdyn enhancer.

Neuronal and behavioral adaptations to novel stimuli are regulated by temporally dynamic waves of transcriptional activity, which shape neuronal function and guide enduring plasticity. Neuronal activation promotes expression of an immediate early gene (IEG) program comprised primarily of activity-dependent transcription factors, which are thought to regulate a second set of late response genes (LRGs). However, while the mechanisms governing IEG activation have been well studied, the molecular interplay between IEGs and LRGs remain poorly characterized. Here, we used transcriptomic and chromatin accessibility profiling to define activity-driven responses in rat striatal neurons. As expected, neuronal depolarization generated robust changes in gene expression, with early changes (1 h) enriched for inducible transcription factors and later changes (4 h) enriched for neuropeptides, synaptic proteins, and ion channels. Remarkably, while depolarization did not induce chromatin remodeling after 1 h, we found broad increases in chromatin accessibility at thousands of sites in the genome at 4 h after neuronal stimulation. These putative regulatory elements were found almost exclusively at non-coding regions of the genome, and harbored consensus motifs for numerous activity-dependent transcription factors such as AP-1. Furthermore, blocking protein synthesis prevented activity-dependent chromatin remodeling, suggesting that IEG proteins are required for this process. Targeted analysis of LRG loci identified a putative enhancer upstream of Pdyn (prodynorphin), a gene encoding an opioid neuropeptide implicated in motivated behavior and neuropsychiatric disease states. CRISPR-based functional assays demonstrated that this enhancer is both necessary and sufficient for Pdyn transcription. This regulatory element is also conserved at the human PDYN locus, where its activation is sufficient to drive PDYN transcription in human cells. These results suggest that IEGs participate in chromatin remodeling at enhancers and identify a conserved enhancer that may act as a therapeutic target for brain disorders involving dysregulation of Pdyn.

A Siamese Transformer Network for Zero-Shot Ancient Coin Classification.

Ancient numismatics, the study of ancient coins, has in recent years become an attractive domain for the application of computer vision and machine learning. Though rich in research problems, the predominant focus in this area to date has been on the task of attributing a coin from an image, that is of identifying its issue. This may be considered the cardinal problem in the field and it continues to challenge automatic methods. In the present paper, we address a number of limitations of previous work. Firstly, the existing methods approach the problem as a classification task. As such, they are unable to deal with classes with no or few exemplars (which would be most, given over 50,000 issues of Roman Imperial coins alone), and require retraining when exemplars of a new class become available. Hence, rather than seeking to learn a representation that distinguishes a particular class from all the others, herein we seek a representation that is overall best at distinguishing classes from one another, thus relinquishing the demand for exemplars of any specific class. This leads to our adoption of the paradigm of pairwise coin matching by issue, rather than the usual classification paradigm, and the specific solution we propose in the form of a Siamese neural network. Furthermore, while adopting deep learning, motivated by its successes in the field and its unchallenged superiority over classical computer vision approaches, we also seek to leverage the advantages that transformers have over the previously employed convolutional neural networks, and in particular their non-local attention mechanisms, which ought to be particularly useful in ancient coin analysis by associating semantically but not visually related distal elements of a coin's design. Evaluated on a large data corpus of 14,820 images and 7605 issues, using transfer learning and only a small training set of 542 images of 24 issues, our Double Siamese ViT model is shown to surpass the state of the art by a large margin, achieving an overall accuracy of 81%. Moreover, our further investigation of the results shows that the majority of the method's errors are unrelated to the intrinsic aspects of the algorithm itself, but are rather a consequence of unclean data, which is a problem that can be easily addressed in practice by simple pre-processing and quality checking.

COVID-19 infection and vaccination uptake in men and gender-diverse people who have sex with men in the UK: analyses of a large, online community cross-sectional survey (RiiSH-COVID) undertaken November-December 2021.

BACKGROUND: Men and gender-diverse people who have sex with men are disproportionately affected by health conditions associated with increased risk of severe illness due to COVID-19 infection. METHODS: An online cross-sectional survey of men and gender-diverse people who have sex with men in the UK recruited via social networking and dating applications from 22 November-12 December 2021. Eligible participants included self-identifying men, transgender women, or gender-diverse individuals assigned male at birth (AMAB), aged ≥ 16, who were UK residents, and self-reported having had sex with an individual AMAB in the last year. We calculated self-reported COVID-19 test-positivity, proportion reporting long COVID, and COVID-19 vaccination uptake anytime from pandemic start to survey completion (November/December 2021). Logistic regression was used to assess sociodemographic, clinical, and behavioural characteristics associated with SARS-CoV-2 (COVID-19) test positivity and complete vaccination (≥ 2 vaccine doses). RESULTS: Among 1,039 participants (88.1% white, median age 41 years [interquartile range: 31-51]), 18.6% (95% CI: 16.3%-21.1%) reported COVID-19 test positivity, 8.3% (95% CI: 6.7%-10.1%) long COVID, and 94.5% (95% CI: 93.3%-96.1%) complete COVID-19 vaccination through late 2021. In multivariable models, COVID-19 test positivity was associated with UK country of residence (aOR: 2.22 [95% CI: 1.26-3.92], England vs outside England) and employment (aOR: 1.55 [95% CI: 1.01-2.38], current employment vs not employed). Complete COVID-19 vaccination was associated with age (aOR: 1.04 [95% CI: 1.01-1.06], per increasing year), gender (aOR: 0.26 [95% CI: 0.09-0.72], gender minority vs cisgender), education (aOR: 2.11 [95% CI: 1.12-3.98], degree-level or higher vs below degree-level), employment (aOR: 2.07 [95% CI: 1.08-3.94], current employment vs not employed), relationship status (aOR: 0.50 [95% CI: 0.25-1.00], single vs in a relationship), COVID-19 infection history (aOR: 0.47 [95% CI: 0.25-0.88], test positivity or self-perceived infection vs no history), known HPV vaccination (aOR: 3.32 [95% CI: 1.43-7.75]), and low self-worth (aOR: 0.29 [95% CI: 0.15-0.54]). CONCLUSIONS: In this community sample, COVID-19 vaccine uptake was high overall, though lower among younger age-groups, gender minorities, and those with poorer well-being. Efforts are needed to limit COVID-19 related exacerbation of health inequalities in groups who already experience a greater burden of poor health relative to other men who have sex with men.

Sexual behaviour, STI and HIV testing and testing need among gay, bisexual and other men who have sex with men recruited for online surveys pre/post-COVID-19 restrictions in the UK.

OBJECTIVES: We examined sexual behaviour, sexually transmitted infection (STI) and HIV testing and testing need, and identified associated factors, among gay, bisexual and other men who have sex with men (GBMSM) in the UK after COVID-19 restrictions ended, and compared these with 'pre-pandemic' estimates. METHODS: We analysed survey data from GBMSM (N=1039) recruited via social media and Grindr in November-December 2021. We then compared Grindr-recruited 2021 participants (N=437) with those from an equivalent survey fielded in March-May 2017 (N=1902). Questions on sexual behaviour and service use had lookback periods of 3-4 months in both surveys. Unmet testing need was defined as reporting any new male and/or multiple condomless anal sex (CAS) partners without recent STI/HIV testing. Participants were UK residents, GBMSM, aged ≥16 years who reported sex with men in the last year. Multivariable logistic regression identified associated sociodemographic and health-related factors with unmet STI/HIV testing need in 2021, and then for 2017/2021 comparative analyses, adjusting for demographic differences. RESULTS: In 2021, unmet STI and HIV testing need were greater among older GBMSM (aged ≥45 years vs 16-29 years; adjusted OR (aOR): 1.45 and aOR: 1.77, respectively), and lower for pre-exposure prophylaxis (PrEP) users (vs non-PrEP users; aOR: 0.32 and aOR: 0.23, respectively). Less unmet STI testing need was observed among HIV-positive participants (vs HIV-negative/unknown; aOR: 0.63), and trans and non-binary participants (vs cisgender male; aOR: 0.34). Between 2017 (reference) and 2021, reported sexual risk behaviours increased: ≥1 recent new male sex partner (72.1%-81.1%, aOR: 1.71) and ≥2 recent CAS partners (30.2%-48.5%, aOR: 2.22). Reporting recent STI testing was greater in 2021 (37.5%-42.6%, aOR: 1.34) but not recent HIV testing, and there was no significant change over time in unmet STI (39.2% vs 43.7%) and HIV (32.9% vs 39.0%) testing need. DISCUSSION: Comparable community surveys suggest that UK resident GBMSM may have engaged in more sexual risk behaviours in late 2021 than pre-pandemic. While there was no evidence of reduced STI/HIV service access during this time, there remained considerable unmet STI/HIV testing need.

Carcinoma en Cuirasse.

This case report describes hyperpigmented, indurated, and sclerotic plaques on the anterior trunk and upper abdomen with overlying scale that were studded with firm, erythematous papules.