Methionyl-tRNA synthetase synthetic and proofreading activities are determinants of antibiotic persistence.

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site of MetRS and the other two mutants changes near the anticodon binding domain. Mutations in metG are of particular interest because MetRS is responsible for aminoacylation both initiator tRNAMet and elongator tRNAMet indicating that these mutants could impact translation initiation and/or translation elongation. We observed that all the metG mutants increased the level of antibiotic persistence as did reduced transcription levels of wild type metG. Although, the MetRS variants did not have an impact on MetRS activity itself, they did reduce translation rates. It was also observed that the MetRS variants affected the proofreading mechanism for homocysteine and that these mutants' growth is hypersensitive to homocysteine. Taken together with previous findings, our data indicate that both reductions in cellular Met-tRNAMet synthetic capacity and reduced proofreading of homocysteine by MetRS variants are positive determinants for bacterial antibiotic persistence.

Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles.

Ulcerative colitis is a chronic condition in which a dysregulated immune response contributes to the acute intestinal inflammation of the colon. Current clinical therapies often exhibit limited efficacy and undesirable side effects. Here, programmable nanomicelles were designed for colitis treatment and loaded with RU.521, an inhibitor of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. STING-inhibiting micelles (SIMs) comprise hyaluronic acid-stearic acid conjugates and include a reactive oxygen species (ROS)-responsive thioketal linker. SIMs were designed to selectively accumulate at the site of inflammation and trigger drug release in the presence of ROS. Our in vitro studies in macrophages and in vivo studies in a murine model of colitis demonstrated that SIMs leverage HA-CD44 binding to target sites of inflammation. Oral delivery of SIMs to mice in both preventive and delayed therapeutic models ameliorated colitis's severity by reducing STING expression, suppressing the secretion of proinflammatory cytokines, enabling bodyweight recovery, protecting mice from colon shortening, and restoring colonic epithelium. In vivo end points combined with metabolomics identified key metabolites with a therapeutic role in reducing intestinal and mucosal inflammation. Our findings highlight the significance of programmable delivery platforms that downregulate inflammatory pathways at the intestinal mucosa for managing inflammatory bowel diseases.

Co-designing strategies to implement long-acting injectable PrEP for sexual minority men in Chicago: a study protocol for an innovation tournament and implementation mapping.

BACKGROUND: Participatory design approaches can improve successful selection and tailoring of implementation strategies by centering the voices of key constituents. To reduce incidence of the human immunodeficiency virus (HIV) in the USA, co-design of implementation strategies is needed for long-acting injectable cabotegravir (CAB-LA), a new form of HIV pre-exposure prophylaxis, among the disproportionately impacted population of sexual minority men (SMM). This manuscript describes the protocol for participatory design approaches (i.e., innovation tournament and implementation mapping) to inform implementation of CAB-LA among SMM (≥ 12 years), particularly Black and Latino populations, in Chicago. METHODS: This research incorporates innovative methods to accomplish two objectives: (1) to crowdsource ideas for the design of implementation strategies for CAB-LA through a virtual innovation tournament and (2) to leverage the ideas from the innovation tournament to operationalize implementation strategies for CAB-LA thorough the systematic process of implementation mapping. A committee of constituents with diverse expertise and perspectives (e.g., SMM, implementation scientists, HIV clinicians, public health leadership, and community partners) will provide input throughout the design process. DISCUSSION: This research will produce a menu of co-designed implementation strategies, which can guide plans for CAB-LA integration in Chicago and provide insights for other EHE regions. Further, as the first innovation tournament focused on HIV prevention, this research can provide a framework for participatory approaches across the care continuum. Given that the co-design of implementation strategies often does not involve the participation of individuals with lived experiences, this work will center the voices of those who will benefit most.

Changes to Sexual Identity Response Options in the Youth Risk Behavior Survey.

This survey study discusses changes in the proportion of youths who selected "not sure" among other response options to questions about their sexual identity in the National Youth Risk Behavior Survey between 2019 and 2021 and recommends measures to inclusively reflect sexual identities.

Atypical Spitz tumor with SQSTM1::NTRK2 fusion: Report of a case with unique spindled cell features.

A host of signature genetic alterations have been demonstrated in Spitz neoplasms, most notably fusions of kinase genes (including BRAF, ALK, ROS1, NTRK1, NTRK3, RET, MET, MAP3K8) or variants in HRAS. While there are multiple reports of rearrangements involving NTRK1 and NTRK3 in Spitz tumors, there are very few reports of NTRK2-rearranged Spitz nevi in the literature. This report presents an NTRK2-rearranged atypical Spitz tumor with spindled cell features. The patient was a 6-year-old female with a growing pigmented papule on the back. Histopathological evaluation revealed an asymmetric, biphasic, compound proliferation of melanocytes featuring an epithelioid cell population arranged as variably sized nests and single cells along the basal layer with extension down adnexa, as well as a population of spindled melanocytes with desmoplastic features and loss of Melan-A expression in the dermis. There was partial loss of p16 expression in the epidermal component and diffuse loss in the dermal component. Immunohistochemistry for PRAME, ALK, NTRK1, HRAS Q61R, p53, and BRAF V600E were negative. A SQSTM1::NTRK2 fusion was identified by RNA sequencing. No TERT promoter hotspot variants were detected. This case report expands the known histopathologic spectrum of genetic alterations in Spitz neoplasms.

Patterns of COVID-19 related lifestyle disruptions and their associations with mental health outcomes among youth and young adults.

The COVID-19 pandemic is a socionatural disaster that has disrupted the lives of individuals, families, and communities. Youth and young adults (YYA) were uniquely vulnerable to the proximal mental health effects of the pandemic; however, few studies have examined the long-term mental health effects of the pandemic. In the present study, we sought to (a) identity distinctive profiles of COVID-related lifestyle disruptions experienced by YYA, (b) investigate sociodemographic characteristics correlates of profile membership, and (c) examine the extent to which profile membership was prospectively associated with changes in depressive and anxiety symptoms. Hypothesis were tested using latent profile analysis with data from 1055 YYA collected across two time-points, 6-months apart. Results produced a three-class model: low- (11%), moderate- (61%), and high-levels of (28%) disruption. Members of the high levels of disruption group were more likely to identify as Black or Latinx American, bisexual/pansexual, or as transgender or gender diverse in comparison to the low levels of disruption group. Inclusion in the high levels of disruption group was associated with increases in depressive and anxiety symptoms from T1 to T2. YYA from multiple marginalize communities (i. e. those who identified as both racial/ethnic and sexual/gender minorities) experienced the greatest levels of lifestyle disruption related to COVID-19. Consequently, disruptive effects of the COVID-19 pandemic prospectively eroded their mental health. YYA are in urgent need of developmentally appropriate resources to effectively recovery from the pandemic.

Changing colors and understanding: the use of mutant chromogenic protein and informational suppressor strains of Escherichia coli to explore the central dogma of molecular biology.

The central dogma of molecular biology is a key concept for undergraduate students in the life sciences as it describes the flow of information in living systems from gene-to-gene product. However, despite often being covered in many introductory life science courses, students may still have misconceptions surrounding the central dogma even as they move on to advanced courses. Active learning strategies such as laboratory activities can be useful in addressing such misconceptions. In the laboratory exercise presented here, senior undergraduate students explore the intricacies of nonsense suppressor mutations to challenge their understanding of the central dogma. The students introduce a plasmid carrying a nonfunctional chromogenic protein gene due to a nonsense mutation in a codon encoding the chromophore to various nonsense suppressor strains of Escherichia coli. Students then observe distinct chromogenic phenotypes, depending on the suppressor strain. Students showed a moderate increase in understanding of the central dogma. While the central dogma remains a challenging concept, active learning strategies like the one presented here can help reduce conceptual errors.

Changes in Sexual Behaviors Due to Mpox: a Cross-Sectional Study of Sexual and Gender Minority Individuals in Illinois.

The spread of the monkeypox virus (mpox) in 2022 primarily within the sexual networks of men who have sex with men (MSM) triggered a potentially stigmatizing public health response in the USA. Despite mpox being primarily spread through skin-to-skin contact, most messaging has promoted abstinence and/or reduction in sexual risk behaviors. More research is needed on decreases in sexual risk behaviors among sexual and gender minority (SGM) youth and young adults (YYA) related to the most recent mpox epidemic and whether there are factors associated with these decreases in sexual risk behavior. Participants within an ongoing cohort study of SGM YYA who reside in Illinois were offered the opportunity to participate in an mpox survey between September 10th and September 20th, 2022. Analyses looked at demographic factors associated with sexual activity since the start of the outbreak, as well as associations with two sexual risk reduction factors. Survey participation was 68.7% (322/469). Three-quarters of participants (82.6%) reported sexual activity since June 1st. Most sexually active participants (83.5%) adopted at least one sexual risk reduction behavior due to mpox. Black and Latinx individuals were less likely to be sexually active but more likely to report risk reduction behaviors (31.3% and 22.6%, respectively). Participants who received the mpox vaccine were more likely to report sexual activity. SGM YYA in Illinois reported that their sexual behaviors were impacted by the mpox outbreak. However, associations between vaccination and sexual behavior demonstrate that those who are vaccinated do adopt protective methods despite not decreasing sexual activity. Therefore, sex-positive communications and harm reduction messaging may be more appropriate as opposed to abstinence-only prevention, which can further stigmatize an already marginalized group.

Monkeypox-Induced Secondary Traumatic Stress: An Exploratory Analysis of Young Sexual and Gender Minority Adults Living in Illinois.

Objective: Prior epidemic literature suggests that the rapid proliferation of Monkeypox (Mpox) within the United States may trigger severe stress reactions that increase the risk of developing secondary traumatic stress among young adults most at risk of exposure. The present exploratory study aimed to investigate the degree to which proximity to Mpox (i.e. knowing people who acquired Mpox), was associated with symptoms of secondary traumatization. Method: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual and gender minority persons ages 19-39 in September 2022. A multiple linear regression was used to examine the association between proximity to Mpox and secondary traumatic stress (STS) symptoms. Results: Study findings demonstrated that Mpox morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with Mpox. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of Mpox-related STS. Results of our multiple linear regression demonstrated a positive association between an individual's indirect exposure to Mpox via their interpersonal relationships and STS symptoms. Conclusions: Findings suggest that the more adults' interpersonal relationships are saturated with people who have acquired Mpox, the more likely they are to develop symptoms of secondary traumatization. These findings provide tentative initial evidence that secondary exposure to Mpox via one's social network may undermine adults' mental health even after the conclusion of the outbreak.

Suicidality by Sexual Identity and Correlates Among American Indian and Alaska Native High School Students.

PURPOSE: This study aims to determine the prevalence of suicidality among American Indian and Alaskan Native (AI/AN) adolescents. Additionally, we measured suicidality, stratified by sex, and its association with sexual identity, sexual violence, and binge drinking. METHODS: We pooled data from the Youth Risk Behavior Survey from 2005 to 2019 to analyze the prevalence of sexual minorities, forced sex, and binge drinking, and their association with suicidality using basic descriptive statistics followed by adjusted odds ratios stratified by sex among AI/AN youth. RESULTS: 19% of AI/AN participants reported having suicidal thoughts and 14% reported having a previous suicide attempt. More than 17% of AI/AN participants identified as sexual minority youth (SMY). Compared to AI/AN heterosexual youth, AI/AN bisexual youth had significantly higher odds of reporting suicidal thoughts (aOR = 16.01), planning (aOR = 12.4), and previous attempts (aOR = 7.73). This pattern was also significantly demonstrated for AI/AN gay/lesbian youth. 43% of all AI/AN participants reported being forced into sexual intercourse. The presence of binge drinking was associated with higher odds of suicidal thoughts for both females and males compared to those who did not binge drink. DISCUSSION: At the intersection of multiple marginalization, AI/AN SMY have a high mental health burden, demonstrating the need for culturally informed, community-led, and targeted mental health support focused on SMY AI/AN. Though this study fails to capture the heterogeneity within the AI/AN community, as nuances exist at the tribal level, these results demonstrate work needs to be done to support the health burden that AI/AN youth carry.

Substance use and variation in sexual partnership rates among young MSM and young transgender women: Disaggregating between and within-person associations.

BACKGROUND: Substance use has been extensively linked to sexual behavior and HIV/STI risk among men who have sex with men (MSM) and transgender women (TW). However, the impact of specific substances and on specific partnership types is not well characterized. The current study seeks to estimate the association between specific substances and partnership rates while carefully disaggregating between and within-person associations to characterize the nature of these associations and inform prevention interventions. METHODS: Using data from a longitudinal cohort (n = 1159) of young MSM (YMSM) and young TW (YTW), we utilized a series of hybrid mixed effect models to estimate the associations between substance use (i.e., heavy episodic drinking [HED], marijuana, cocaine, ecstasy, methamphetamine, poppers, prescription stimulant, prescription painkiller, and prescription depressants) and partnerships (i.e., one-time, casual, and main). RESULTS: Results from multivariable models indicated people using substances had higher one-time (HED, poppers) and casual (HED, methamphetamine, poppers) partnership rates. In addition, participants reported higher rates of one-time (HED, ecstasy, methamphetamine, poppers) and casual partners (HED, marijuana, cocaine, methamphetamines, poppers) during periods of substance use. CONCLUSION: These findings confirm that the highest rates of sexual activity occur among YMSM-YTW using substances during periods of substance use. Yet, these findings should caution researchers against simplistic generalizations as these associations differ across substance and partnership types. Efforts to promote the health of MSM-YTW who use substances should carefully consider this complexity as interventions accounting for the unique cultural context of substance use in these populations are most likely to be successful.

Complete genome sequence of an avian pathogenic Escherichia coli strain isolated from poultry.

Avian pathogenic Escherichia coli found in the avian intestinal tract can cause systemic disease in birds and act as a foodborne zoonotic pathogen associated with human disease. Here, we report the complete genome sequence of E. coli strain H1998 isolated from a chicken with colisepticemia.

Significant Microbial Changes Are Evident in the Reproductive Tract of Pregnant Rhesus Monkeys at Mid-Gestation but Their Gut Microbiome Does Not Shift until Late Gestation.

Vaginal and rectal specimens were obtained from cycling, pregnant, and nursing rhesus monkeys to assess pregnancy-related changes in the commensal bacteria in their reproductive and intestinal tracts. Using 16S rRNA gene amplicon sequencing, significant differences were found only in the vagina at mid-gestation, not in the hindgut. To verify the apparent stability in gut bacterial composition at mid-gestation, the experiment was repeated with additional monkeys, and similar results were found with both 16S rRNA gene amplicon and metagenomic sequencing. A follow-up study investigated if bacterial changes in the hindgut might occur later in pregnancy. Gravid females were assessed closer to term and compared to nonpregnant females. By late pregnancy, significant differences in bacterial composition, including an increased abundance of 4 species of Lactobacillus and Bifidobacterium adolescentis, were detected, but without a shift in the overall community structure. Progesterone levels were assessed as a possible hormone mediator of bacterial change. The relative abundance of only some taxa (e.g., Bifidobacteriaceae) were specifically associated with progesterone. In summary, pregnancy changes the microbial profiles in monkeys, but the bacterial diversity in their lower reproductive tract is different from women, and the composition of their intestinal symbionts remains stable until late gestation when several Firmicutes become more prominent.

Partnership types and coital frequency as predictors of gonorrhea and chlamydia among young MSM and young transgender women.

BACKGROUND: Sexually transmitted infections pose a major public health challenge in the United States and this burden is especially acute in subpopulations like young men who have sex with men (YMSM) and young transgender women (YTW). Yet, the direct behavioral antecedents of these infections are not well understood making it difficult to identify the cause of recent increases in incidence. This study examines how variations in partnership rates and the number of condomless sex acts are associated with STI infections among YMSM-YTW. METHOD: This study leveraged 3 years of data from a large longitudinal cohort of YMSM-YTW. A series of generalized linear mixed models examined the association between the number of condomless anal sex acts, number of one-time partners, number of casual partners, and number of main partners and chlamydia, gonorrhea, or any STI. RESULTS: Results indicated the number of casual partners was associated with gonorrhea [aOR = 1.17 (95% CI: 1.08, 1.26)], chlamydia [aOR = 1.12 (95% CI: 1.05, 1.20)], and any STI [aOR = 1.14 (95% CI: 1.08, 1.21)] while the number of one-time partners was only associated with gonorrhea [aOR = 1.13 (95% CI: 1.02, 1.26)]. The number of condomless anal sex acts was not associated with any outcome. CONCLUSION: These findings suggest the number of casual partners is a consistent predictor of STI infection among YMSM-YTW. This may reflect the quick saturation of risk within partnerships making the number of partners, rather than the number of acts, the more relevant factor for STI risk.

Predictors of Mpox vaccine uptake among sexual and gender minority young adults living in Illinois: Unvaccinated vs. double vs. single dose vaccine recipients.

INTRODUCTION: The 2022 global outbreak of Monkeypox virus (Mpox), which has primarily spread through the sexual networks of sexual and gender minority (SGM) individuals, has introduced new public health challenges. While an efficacious Mpox vaccine is in active circulation, few Mpox vaccine studies have examined its uptake among SGM groups. The aims of this study were to investigate (a) the prevalence of Mpox vaccine uptake among SGM and (b) the contextual, Mpox-disease specific, and Mpox-vaccine specific factors associated with Mpox vaccine among SGM. METHODS: We conducted a cross-sectional survey in Illinois, USA in September 2022; 320 young SGM completed self-administered questionnaires. Multinomial logistic regression was used to assess the contextual, Mpox-disease specific, and Mpox-vaccine specific factors associated with Mpox vaccine uptake. Adjusted Odds Ratios (aORs) and 95 % Confidence Intervals (CI) are reported. RESULTS: Approximately 50 % of the SGM participants included in this study had received at least their first dose of the Mpox vaccine. Multinomial regression analysis showed that individuals who had recently experienced food insecurity, had higher degrees of fear of social rejection due to Mpox acquisition, and were more Mpox-vaccine hesitant were more likely to be unvaccinated. Conversely, knowing people who have contracted Mpox, having higher formal educational attainment, having higher degrees of Mpox-related internalized heterosexism, and being more concerned about one's safety regarding Mpox morbidity were more likely to be double-dosers. CONCLUSION: Approximately 50 % of the SGMs included in this study received at least their first dose of the Mpox vaccine; however, only one-quarter of participants completed the recommended 2-dose Mpox regimen. Our findings indicate that socioeconomic stability, fear of social rejection due to disease acquisition, and Mpox-specific vaccine hesitancy may be important structural targets to consider when developing vaccine-uptake prevention and intervention strategies tailored to the needs of sexual and gender minorities.

Mapping Community-Engaged Implementation Strategies with Transgender Scientists, Stakeholders, and Trans-Led Community Organizations.

PURPOSE OF REVIEW: Pre-exposure prophylaxis (PrEP) represents one of the most effective methods of prevention for HIV, but remains inequitable, leaving many transgender and nonbinary (trans) individuals unable to benefit from this resource. Deploying community-engaged PrEP implementation strategies for trans populations will be crucial for ending the HIV epidemic. RECENT FINDINGS: While most PrEP studies have progressed in addressing pertinent research questions about gender-affirming care and PrEP at the biomedical and clinical levels, research on how to best implement gender-affirming PrEP systems at the social, community, and structural levels remains outstanding. The science of community-engaged implementation to build gender-affirming PrEP systems must be more fully developed. Most published PrEP studies with trans people report on outcomes rather than processes, leaving out important lessons learned about how to design, integrate, and implement PrEP in tandem with gender-affirming care. The expertise of trans scientists, stakeholders, and trans-led community organizations is essential to building gender-affirming PrEP systems.

Combination therapy with simultaneous delivery of spinal cord stimulation modalities: COMBO randomized controlled trial.

Aim: The Combining Mechanisms for Better Outcomes randomized controlled trial assessed the effectiveness of various spinal cord stimulation (SCS) modalities for chronic pain. Specifically, combination therapy (simultaneous use of customized sub-perception field and paresthesia-based SCS) versus monotherapy (paresthesia-based SCS) was evaluated. Methods: Participants were prospectively enrolled (key inclusion criterion: chronic pain for ≥6 months). Primary end point was the proportion with ≥50% pain reduction without increased opioids at the 3 month follow-up. Patients were followed for 2 years. Results: The primary end point was met (n = 89; p < 0.0001) in 88% of patients in the combination-therapy arm (n = 36/41) and 71% in the monotherapy arm (n = 34/48). Responder rates at 1 and 2 years (with available SCS modalities) were 84% and 85%, respectively. Sustained functional outcomes improvement was observed out to 2 years. Conclusion: SCS-based combination therapy can improve outcomes in patients with chronic pain. Clinical Trial Registration: NCT03689920 (ClinicalTrials.gov), Combining Mechanisms for Better Outcomes (COMBO).

Spinal cord stimulation (SCS) is a device-based therapy for chronic pain that delivers electrical impulses to the spinal cord, disrupting pain signals to the brain. Pain relief can be achieved using different SCS techniques that use or do not use paresthesia (stimulation that produces a tingling sensation). These approaches affect patients in different ways, suggesting that different biological processes are involved in enabling pain relief. Research also suggests that better long-term results occur when patients can choose the therapy that is best for their own needs. This clinical study compared pain relief and other functional activities in those receiving combination therapy (simultaneous use of SCS that does and does not produce tingling sensation) against those receiving monotherapy (only SCS therapy producing tingling sensation) for 3 months. In the study, 88% of those receiving combination therapy and 71% with monotherapy alone reported a 50% (or greater) decrease in overall pain (the 'responder rate') without an increased dose of opioid drugs at 3 months after the start of therapy. This responder rate was found to be 84% at 1 year and 85% at 2 years (with all SCS therapy options available). Analysis of functional activities or disability showed that patients improved from 'severely disabled' at study start to 'moderately disabled' after 2 years, indicating that effective long-term (2 year) improvement can be achieved using SCS-based combination therapy for chronic pain.

Network canvas: an open-source tool for capturing social and contact network data.

MOTIVATION: Social influence and contact networks are extremely important for understanding health behaviour and the spread of disease. Yet, most traditional software tools are not optimized to capture these data, making measurement of personal networks challenging. Our team developed Network Canvas to provide an end-to-end workflow with intuitive interfaces to enable researchers to design and conduct network interviews. IMPLEMENTATION: Network Canvas consists of three applications (Architect, Interviewer and Server). All applications are written in JavaScript and run on Windows, macOS and Linux; Interviewer also runs on Android and iOS. GENERAL FEATURES: Network Canvas substantially reduces the complexity and technical knowledge required to collect network data via three point-and-click applications. The tool has wide applicability for measuring contact and social influence networks in epidemiology. AVAILABILITY: Network Canvas is open source and freely available [networkcanvas.com] under the GNU General Public License 3.

Instability in Housing and Medical Care Access: The Inequitable Impacts of the COVID-19 Pandemic on U.S. Transgender Populations.

Purpose: To assess whether the COVID-19 pandemic has inequitably impacted key social determinants of health (SDoH), specifically employment, housing, and health care, for U.S. transgender populations. Methods: Between April 13, 2020 and August 3, 2020, we conducted a national, cross-sectional online survey of sexual and gender minority individuals (N=870). We used logistic regression to calculate both unadjusted and adjusted odds of unemployment, homelessness/housing instability, and interruptions in medical care owing to the pandemic by gender and gender modality. Adjusted models controlled for age, race/ethnicity, and region. Results: In adjusted models, transgender and gender diverse people had 2.12 times the odds of reporting homelessness/housing instability and 2.88 times the odds of reporting medical care interruptions compared with cisgender peers. Transgender men, women, and nonbinary people had 4.12, 3.29, and 3.48 times the adjusted odds of interruptions in medical care compared with cisgender men, respectively. We did not observe significant differences in employment. Conclusions: Findings add empirical support to the hypothesis that socioeconomic consequences of COVID-19 are inequitably impacting transgender people. To contextualize our results and support future research in this area, we present a conceptual model of the short- and long-term impacts of COVID-19 on transgender populations using a framework of stigma as a fundamental cause of health inequities. Our findings emphasize that public health professionals must urgently consider-and intervene to address-the pandemic's SDoH-related impacts on transgender populations.

The E. coli pathobiont LF82 encodes a unique variant of σ70 that results in specific gene expression changes and altered phenotypes.

LF82, an adherent invasive Escherichia coli pathobiont, is associated with ileal Crohn's disease, an inflammatory bowel disease of unknown etiology. Although LF82 contains no virulence genes, it carries several genetic differences, including single nucleotide polymorphisms (SNPs), that distinguish it from nonpathogenic E. coli. We have identified and investigated an extremely rare SNP that is within the highly conserved rpoD gene, encoding σ70, the primary sigma factor for RNA polymerase. We demonstrate that this single residue change (D445V) results in specific transcriptome and phenotypic changes that are consistent with multiple phenotypes observed in LF82, including increased antibiotic resistance and biofilm formation, modulation of motility, and increased capacity for methionine biosynthesis. Our work demonstrates that a single residue change within the bacterial primary sigma factor can lead to multiple alterations in gene expression and phenotypic changes, suggesting an underrecognized mechanism by which pathobionts and other strain variants with new phenotypes can emerge.