The emergence of SARS-CoV-2 lineages and associated saliva antibody responses among asymptomatic individuals in a large university community.

SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID monitoring program in Ohio, United States of America, and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.

Estimating seroprevalence of SARS-CoV-2 in Ohio: A Bayesian multilevel poststratification approach with multiple diagnostic tests.

Globally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 59 million people and killed more than 1.39 million. Designing and monitoring interventions to slow and stop the spread of the virus require knowledge of how many people have been and are currently infected, where they live, and how they interact. The first step is an accurate assessment of the population prevalence of past infections. There are very few population-representative prevalence studies of SARS-CoV-2 infections, and only two states in the United States-Indiana and Connecticut-have reported probability-based sample surveys that characterize statewide prevalence of SARS-CoV-2. One of the difficulties is the fact that tests to detect and characterize SARS-CoV-2 coronavirus antibodies are new, are not well characterized, and generally function poorly. During July 2020, a survey representing all adults in the state of Ohio in the United States collected serum samples and information on protective behavior related to SARS-CoV-2 and coronavirus disease 2019 (COVID-19). Several features of the survey make it difficult to estimate past prevalence: 1) a low response rate; 2) a very low number of positive cases; and 3) the fact that multiple poor-quality serological tests were used to detect SARS-CoV-2 antibodies. We describe a Bayesian approach for analyzing the biomarker data that simultaneously addresses these challenges and characterizes the potential effect of selective response. The model does not require survey sample weights; accounts for multiple imperfect antibody test results; and characterizes uncertainty related to the sample survey and the multiple imperfect, potentially correlated tests.

Acquisition of Gonococcal AniA-NorB Pathway by the Neisseria meningitidis Urethritis Clade Confers Denitrifying and Microaerobic Respiration Advantages for Urogenital Adaptation.

Neisseria meningitidis historically has been an infrequent and sporadic cause of urethritis and other urogenital infections. However, a nonencapsulated meningococcal clade belonging to the hyperinvasive clonal complex 11.2 lineage has recently emerged and caused clusters of urethritis cases in the United States and other countries. One of the genetic signatures of the emerging N. meningitidis urethritis clade (NmUC) is a chromosomal gene conversion event resulting in the acquisition of the Neisseria gonorrhoeae denitrification apparatus-the N. gonorrhoeae alleles encoding the nitrite reductase AniA, the nitric oxide (NO) reductase NorB, and the intergenic promoter region. The biological importance of the N. gonorrhoeae AniA-NorB for adaptation of the NmUC to a new environmental niche is investigated herein. We found that oxygen consumption, nitrite utilization, and NO production were significantly altered by the conversion event, resulting in different denitrifying aerobic and microaerobic growth of the clade. Further, transcription of aniA and norB in NmUC isolates differed from canonical N. meningitidis, and important polymorphisms within the intergenic region, which influenced aniA promoter activity of the NmUC, were identified. The contributions of three known meningococcal regulators (NsrR, FNR, and NarQP) in controlling the denitrification pathway and endogenous NO metabolism were distinct. Overall, transcription of aniA was dampened relative to canonical N. meningitidis, and this correlated with the lower NO accumulation in the clade. Denitrification and microaerobic respiration were bolstered, and protection against host-derived NO was likely enhanced. The acquisition of the N. gonorrhoeae denitrification pathway by the NmUC supports the clade's adaptation and survival in a microaerobic urogenital environment.

Provider Mistrust and Telemedicine Abortion Care Preferences Among Patients in Ohio, West Virginia, and Kentucky.

Objectives: The convenience and privacy provided by telemedicine medication abortion may make this service preferable to patients who mistrust their abortion provider. We assessed associations between mistrust in the abortion provider and preferences for telemedicine abortion. Study Design: From April 2020 to April 2021, we surveyed patients seeking abortion in Ohio, West Virginia, and Kentucky. Using unconditional logistic regression models, we examined unadjusted and adjusted associations between mistrust in the abortion provider and preferences for telemedicine abortion among all participants, and among only participants undergoing medication abortion. Results: Of 1,218 patients who met inclusion criteria, 546 used medication abortion services. Just more than half (56%) of all participants and many (64%) of medication abortion participants preferred telemedicine services. Only 6% of medication abortion participants received telemedicine medication dispensing services. Only 1.4% of all participants and 1% of medication abortion participants mistrusted the abortion provider. Participants who mistrusted the abortion provider were somewhat more likely to prefer telemedicine abortion (unadjusted odds ratio [OR]: 2.5, 95% CI: 0.8-7.9; adjusted OR: 2.9, 95% CI: 0.9-9), and medication abortion participants who mistrusted the abortion provider were also somewhat more likely to prefer telemedicine abortion (unadjusted OR: 3.5, 95% CI: 0.4-28.9; adjusted OR: 5.0, 95% CI: 0.6-43), although these associations were not statistically significant. Conclusions: In three abortion-restrictive states, most patients expressed preferences for telemedicine abortion, but few accessed them. Provider mistrust was rare, but those experiencing mistrust trended toward preferring telemedicine services. Telemedicine may improve access to abortion services for patients experiencing medical mistrust.

A systematic review of school-based student peer-led oral health interventions to promote the oral health of school children.

BACKGROUND: Poor oral health in children highlights the need for prevention and effective interventions. During late childhood and adolescence, peer relationships can play a vital role in adopting and maintaining positive health behaviours. AIM: To identify the oral health outcomes of school-based student peer-led delivery of oral health interventions. METHODS: A search strategy was developed, piloted, and run in four electronic databases: Medline via Ovid, Web of Science, CINAHL via EBSCO, and CENTRAL (Cochrane Central Register of Controlled Trials) using key concepts of peer, oral health and adolescent in the school context. Methodological quality was assessed using QuaDs quality assessment tool. All articles were independently screened by two researchers and data was analysed using narrative data synthesis. The PRISMA checklist complemented by aspects of the Synthesis Without Meta-analysis (SWiM) was used to report this systematic review. RESULTS: There were 7572 identified, 24 studies progressed to full-text review, ten studies met the eligibility criteria and were included in the review. Only six studies based their interventions on psychological & behavioural theory. Intervention delivered by peers showed improvements in both clinical and self-reported outcomes when compared to other delivery methods (e.g., professionals). Quality of included studies was reported according to QuaDs guidance. CONCLUSION: Peer-led interventions were more effective in improving oral health status and behaviours when compared to other modes of delivery. Future research should assess if a bi-directional impact of peer-led interventions can be seen. Specifically, if there is added value for school-based student peer-leader's including their own oral health knowledge, skills, attitude and preventative behaviours.

DEVELOPMENT AND EVALUATION OF A STANDARDIZED SYSTEM FOR THE ASSESSMENT OF LOCOMOTOR HEALTH IN ELEPHANTS UNDER HUMAN CARE.

Although lameness is a common problem in elephants (Asian elephant [Elephas maximus] and African elephants Loxodonta africana and Loxodonta cyclotis) under human care, there has not been a standardized lameness assessment system to date. This study developed and evaluated a standardized system for the assessment of locomotion in elephants under human care regardless of husbandry system. In total, 72 elephants out of a possible 73 in the United Kingdom and Ireland were filmed from behind, from in front, and from both sides. Using a questionnaire and a select panel of elephant specialists, a zoo veterinarian, and a locomotion expert, a numerical rating scoring (NRS) system was proposed. Locomotion was scored on a 4-point scale with numerical values 0-4 corresponding to specific criteria as follows: 0 = clinically sound, 1 = stiffness, 2 = abnormal tracking, and 4 = reluctance to bear weight. The intra- and interobserver repeatability of five veterinary surgeons using this system was determined and compared with a visual analog scale (VAS) expressed as a 100-mm line. Overall intraobserver reliability was moderate (Cohen's kappa [κ] = 0.676) and interobserver reliability was fair (κ = 0.37) for the presence of lameness. Interobserver agreement improved from the first scoring to second scoring from slight agreement to fair agreement for stiffness and reluctance to bear weight. Abnormal tracking had moderate intraobserver agreement for both scoring sessions. There were wide widths of agreement for the VAS interobserver (67 mm); however, they were narrower for the intraobserver (33 mm). The developed NRS can be used on freely moving elephants to evaluate elephant locomotion, regardless of husbandry methods, and has been shown to be more reliable than a VAS.

Infection With the US Neisseria meningitidis Urethritis Clade Does Not Lower Future Risk of Urethral Gonorrhea.

BACKGROUND: Cross-protective immunity between Neisseria meningitidis (Nm) and Neisseria gonorrhoeae (Ng) may inform gonococcal vaccine development. Meningococcal serogroup B (MenB) outer membrane vesicle (OMV) vaccines confer modest protection against gonorrhea. However, whether urethral Nm infection protects against gonorrhea is unknown. We examined gonorrhea risk among men with US Nm urethritis clade (US_NmUC) infections. METHODS: We conducted a retrospective cohort study of men with urethral US_NmUC (n = 128) between January 2015 and April 2018. Using diagnosis date as the baseline visit, we examined Ng status at return visits to compute urethral Ng risk. We compared these data to 3 referent populations: men with urethral Ng (n = 253), urethral chlamydia (Ct) (n = 251), and no urethral Ng or Ct (n = 255). We conducted sensitivity analyses to assess varied approaches to censoring, missing data, and anatomical site of infection. We also compared sequences of protein antigens in the OMV-based MenB-4C vaccine, US_NmUC, and Ng. RESULTS: Participants were primarily Black (65%) and heterosexual (82%). Over follow-up, 91 men acquired urethral Ng. Men with urethral US_NmUC had similar Ng risk to men with prior urethral Ng (adjusted hazard ratio [aHR]: 1.27; 95% CI: .65-2.48). Men with urethral US_NmUC had nonsignificantly increased Ng risk compared with men with urethral Ct (aHR: 1.51; 95% CI: .79-2.88), and significantly increased Ng risk compared with men without urethral Ng or Ct (aHR: 3.55; 95% CI: 1.27-9.91). Most of the protein antigens analyzed shared high sequence similarity. CONCLUSIONS: Urethral US_NmUC infection did not protect against gonorrhea despite substantial sequence similarities in shared protein antigens.

Evaluation of Urethrotropic-Clade Meningococcal Infection by Urine Metagenomic Shotgun Sequencing.

Urethral infections caused by an emerging nongroupable (NG) urethrotropic clade of Neisseria meningitidis were first reported in the United States in 2015 (the "U.S. NmNG urethritis clade"). Here, we evaluate for the presence of other urethral pathogens in men with U.S. NmNG urethritis clade infection. We evaluated 129 urine specimens collected from men at a sexual health clinic, including 33 from patients with culture-confirmed or suspected urethral N. meningitidis infection and 96 specimens in which nucleic acid amplification test detected Neisseria gonorrhoeae, Chlamydia trachomatis, both pathogens, or neither pathogen. N. meningitidis was detected first by real-time PCR, followed by metagenomic shotgun sequencing of 91 specimens to identify coinfections. N. meningitidis genomes were sequenced following selective whole-genome amplification when possible. Metagenomic sequencing detected N. meningitidis in 16 of 17 specimens from culture-confirmed N. meningitidis cases, with no coinfection by other conventional urethral pathogens. Metagenomic sequencing also detected N. meningitidis in three C. trachomatis-positive specimens, one specimen positive for both N. gonorrhoeae and C. trachomatis, and nine specimens with negative N. gonorrhoeae and C. trachomatis results, eight of which had suspected Neisseria infections. N. meningitidis from culture-confirmed N. meningitidis cases belonged to the U.S. NmNG urethritis clade, while N. meningitidis identified in other specimens belonged to multiple clonal complexes. Additional urethral pathogens were predominant in non-N. meningitidis specimens, including N. gonorrhoeae, C. trachomatis, Mycoplasma genitalium, Ureaplasma urealyticum, and herpes simplex virus 2. Coinfection with other conventional urethral pathogens is rare in men with culture-confirmed U.S. NmNG urethritis clade infection and points to the strong association of this clade with disease.

Changes in Sexual Behavior Over the COVID-19 Pandemic Among a Community-Based Cohort of Men Who Have Sex With Men in Columbus, Ohio.

BACKGROUND: The purpose was to assess COVID-19 beliefs and attitudes and examine COVID-19-related changes in sexual behavior of men who have sex with men during 3 time periods: April-July 2020 (T1), August-December 2020 (T2), January-May 2021 (T3). METHODS: Data were analyzed from 157 men who have sex with men in Ohio recruited to participate in a longitudinal multisite network study of syphilis epidemiology in 3 US cities: Columbus, Ohio; Baltimore, Maryland; and Chicago, Illinois. In April 2020, a COVID-19 module was appended to existing baseline and follow-up surveys to assess beliefs, attitudes, and changes in sexual behavior. Sample characteristics were summarized. Correlations between demographic variables (age, racial identity) and COVID-19 outcomes were examined. RESULTS: In response to COVID-19 social distancing restrictions and self-reported anxiety, some men limited sexual activity at T1, but the majority (n = 105 [67%]) continued to engage in sex. The number of men engaging in sex increased over time (T2: n = 124 [79%]; T3: n = 121 [77%]). At T1, men not in a relationship more frequently reported having less sex compared with prepandemic (n = 39 [57%]). By T3, men in a relationship more frequently reported less sex (n = 32 [54%]). Increased anxiety about sex and condom use was positively correlated with identifying as a man of color (P < 0.001). Most of the sample reported either starting or increasing online sexual activity during each time period. CONCLUSIONS: Future efforts to target sexual health during a pandemic or other health emergencies should prioritize men of color and address the unique perspective of both single and partnered men.

Housing Stability and Access to General Healthcare and Reproductive Healthcare Among Women in Ohio.

BACKGROUND: The relationship between housing instability and reproductive healthcare is understudied. We examined the association between housing insecurity and access and utilization of general healthcare, contraceptive healthcare, and abortion care. METHODS: Using data from a population-representative survey of adult reproductive-age Ohio women (N = 2,529), we assessed housing insecurity (not paying rent/mortgage on time in the past year). We examined associations between housing insecurity and the following outcomes: (1) not being able to access general healthcare in the past year; (2) experiencing delays or difficulties in accessing contraceptive healthcare in the past year; and (3) ever having an abortion. We used unadjusted and adjusted logistic regression models. We selected confounders a priori and included age, socioeconomic status, and healthcare status. RESULTS: Overall, 10.6% of Ohio women of adult reproductive age experienced housing insecurity. Approximately 27.5% of respondents were not able to access general healthcare and 10.4% experienced delays or difficulties in accessing contraceptive care. Compared to housing-secure respondents, housing-insecure women were less able to access general healthcare (adjusted odds ratio [aOR]:2.16; 95% confidence interval [CI]:1.45-3.23) and more likely to experience delays or difficulties when accessing contraceptive care (aOR:1.74; 95% CI:1.00-3.04). Insecure housing was not statistically associated with ever having an abortion (aOR:1.76; 95% CI:0.93-3.34). CONCLUSIONS: In this study, recent housing insecurity was associated with poorer access to general and contraceptive healthcare. Studies utilizing multidimensional measures of housing insecurity and other material insecurity measures are needed to further explore the relationship between material insecurity and access to general and contraceptive care.

Emergence of a novel urogenital-tropic Neisseria meningitidis.

PURPOSE OF REVIEW: Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US_NmUC). This review describes research developments that characterize this urogenital-tropic Nm. RECENT FINDINGS: The US_NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US_NmUC urethritis episodes can occur. The US_NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance. SUMMARY: The US_NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined.

Passage of abortion ban and women's accurate understanding of abortion legality.

BACKGROUND: Legislative and judicial procedures related to banning abortion after 6 weeks of gestation in Ohio occurred from November 2018 to July 2019. These activities could have increased the belief that abortion has become illegal even though the 6-week abortion ban has never been in effect to date. OBJECTIVE: We sought to determine the prevalence and correlates of holding the belief that abortion is illegal in Ohio and to evaluate whether this belief increased over the time in which the 6-week abortion ban was introduced, passed twice, and then blocked in Ohio. STUDY DESIGN: We analyzed data from the first wave of the Ohio Survey of Women, a population-based survey of adult, reproductive-aged Ohioan women conducted from October 2018 to June 2019. During each of the 8 survey months, a median of 240 women (range, 70-761) completed the survey, including the survey question "Based on what you know or have heard, is it legal to get an abortion in your state?" We used multivariable logistic regression to assess the prevalence and correlates of believing that abortion is illegal in the state of Ohio. In addition, we used multinomial logistic regression to evaluate whether this belief increased over the interval during which women completed the survey, which roughly corresponded to the interval marked by legislative and judicial activities surrounding the 6-week abortion ban. RESULTS: Most of the 2359 participants understood that abortion is legal in the state of Ohio (64.0%) with the remainder believing it to be illegal (9.8%) or being unsure (26.2%). Correlates of believing abortion to be illegal included younger age, lower socioeconomic status, never married or married status, and Black, non-Hispanic race and ethnicity. Being unsure about legality did not change over time; however, the proportion of women who believed that abortion is illegal increased from the first month (4.5%) to the last month (15.9%) of the study period. Each additional study month was associated with a 17% increase in the odds of believing abortion to be illegal, in both unadjusted and adjusted models (odds ratio, 1.17; 95% confidence interval, 1.08-1.27). CONCLUSION: Attempts to restrict abortion access could contribute to women mistakenly believing that abortion is illegal despite it being unsuccessful.

Role of temporal discounting in a conditional cash transfer (CCT) intervention to improve engagement in the prevention of mother-to-child transmission (PMTCT) cascade.

BACKGROUND: Temporal discounting, the tendency of individuals to discount future costs and benefits relative to the present, is often associated with greater engagement in risky behaviors. Incentives such as conditional cash transfers (CCTs) have the potential to counter the effects of high discount rates on health behaviors. METHODS: With data from a randomized trial of a CCT intervention among 434 HIV-positive pregnant women in the Democratic Republic of Congo, we used binomial models to assess interactions between discount rates (measured using a delay-discounting task) and the intervention. The analysis focused on two outcomes: 1) retention in HIV care, and 2) uptake of prevention of mother-to-child transmission (PMTCT) services. RESULTS: The effect of high discount rates on retention was small, and we did not observe evidence of interaction between high discount rates and CCT on retention. However, our findings suggest that CCT may mitigate the negative effect of high discount rates on uptake of PMTCT services (interaction contrast (IC): 0.18, 95% CI: - 0.09, 0.44). CONCLUSIONS: Our findings provide evidence to support the continued use of small, frequent incentives, to motivate improved uptake of PMTCT services, especially among women exhibiting high rates of temporal discounting. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01838005 , April 23, 2013.

Highly disordered histone H1-DNA model complexes and their condensates.

Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.

Environmental and Aerosolized Severe Acute Respiratory Syndrome Coronavirus 2 Among Hospitalized Coronavirus Disease 2019 Patients.

During April and May 2020, we studied 20 patients hospitalized with coronavirus disease 2019 (COVID-19), their hospital rooms (fomites and aerosols), and their close contacts for molecular and culture evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among >400 samples, we found molecular evidence of virus in most sample types, especially the nasopharyngeal (NP), saliva, and fecal samples, but the prevalence of molecular positivity among fomites and aerosols was low. The agreement between NP swab and saliva positivity was high (89.5%; κ = 0.79). Two NP swabs collected from patients on days 1 and 7 post-symptom onset had evidence of infectious virus (2 passages over 14 days in Vero E6 cells). In summary, the low molecular prevalence and lack of viable SARS-CoV-2 virus in fomites and air samples implied low nosocomial risk of SARS-CoV-2 transmission through inanimate objects or aerosols.

Heteroresistance to the model antimicrobial peptide polymyxin B in the emerging Neisseria meningitidis lineage 11.2 urethritis clade: mutations in the pilMNOPQ operon.

Clusters of Neisseria meningitidis (Nm) urethritis among primarily heterosexual males in multiple US cities have been attributed to a unique non-encapsulated meningococcal clade (the US Nm urethritis clade, US_NmUC) within the hypervirulent clonal complex 11. Resistance to antimicrobial peptides (AMPs) is a key feature of urogenital pathogenesis of the closely related species, Neisseria gonorrhoeae. The US_NmUC isolates were found to be highly resistant to the model AMP, polymyxin B (PmB, MICs 64-256 µg ml-1 ). The isolates also demonstrated stable subpopulations of heteroresistant colonies that showed near total resistant to PmB (MICs 384-1024 µg ml-1 ) and colistin (MIC 256 µg ml-1 ) as well as enhanced LL-37 resistance. This is the first observation of heteroresistance in N. meningitidis. Consistent with previous findings, overall PmB resistance in US_NmUC isolates was due to active Mtr efflux and LptA-mediated lipid A modification. However, whole genome sequencing, variant analyses and directed mutagenesis revealed that the heteroresistance phenotypes and very high-level AMP resistance were the result of point mutations and IS1655 element movement in the pilMNOPQ operon, encoding the type IV pilin biogenesis apparatus. Cross-resistance to other classes of antibiotics was also observed in the heteroresistant colonies. High-level resistance to AMPs may contribute to the pathogenesis of US_NmUC.

In Vitro Exposure of Leukocytes to HIV Preexposure Prophylaxis Decreases Mitochondrial Function and Alters Gene Expression Profiles.

The use of antiretroviral therapy (ART) as preexposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition. The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV. In this study, peripheral blood mononuclear cells (PBMCs) from people without HIV were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight. Mitochondrial mass and function were measured by flow cytometry and an Agilent XFp analyzer. Monocyte-derived macrophages (MDMs) were differentiated in 20% autologous serum for 5 days in the presence or absence of TDF or FTC, and surface markers, lipid uptake, and efferocytosis were measured by flow cytometry. MDM gene expression was measured using transcriptome sequencing (RNA-seq). Plasma lipids were measured using mass spectrometry. PBMCs exposed to TDF or FTC had decreased maximal oxygen consumption rate (OCR) and reduced mitochondrial mass. Exposure to PrEP also increased reactive oxygen species (ROS) production from monocyte subsets. Compared to MDMs cultured in medium alone, cells differentiated in the presence of TDF (829 genes) or FTC (888 genes) had significant changes in gene expression. Further, PrEP-exposed MDMs had decreased mitochondrial mass and displayed increased lipid uptake and reduced efferocytosis. Plasma biomarkers and lipid levels were also altered in vivo in individuals receiving a PrEP regimen. In conclusion, exposure of leukocytes to TDF or FTC resulted in decreased mitochondrial function and altered functional and transcriptional profiles. These findings may have important implications for the metabolic and immunologic consequences of PrEP in populations at risk for HIV acquisition.

Full Molecular Typing of Neisseria meningitidis Directly from Clinical Specimens for Outbreak Investigation.

Neisseria meningitidis is a leading cause of bacterial meningitis and sepsis worldwide and an occasional cause of meningococcal urethritis. When isolates are unavailable for surveillance or outbreak investigations, molecular characterization of pathogens needs to be performed directly from clinical specimens, such as cerebrospinal fluid (CSF), blood, or urine. However, genome sequencing of specimens is challenging because of low bacterial and high human DNA abundances. We developed selective whole-genome amplification (SWGA), an isothermal multiple-displacement amplification-based method, to efficiently enrich, sequence, and de novo assemble N. meningitidis DNA from clinical specimens with low bacterial loads. SWGA was validated with 12 CSF specimens from invasive meningococcal disease cases and 12 urine specimens from meningococcal urethritis cases. SWGA increased the mean proportion of N. meningitidis reads by 2 to 3 orders of magnitude, enabling identification of at least 90% of the 1,605 N. meningitidis core genome loci for 50% of the specimens. The validated method was used to investigate two meningitis outbreaks recently reported in Togo and Burkina Faso. Twenty-seven specimens with low bacterial loads were processed by SWGA before sequencing, and 12 of 27 were successfully assembled to obtain the full molecular typing and vaccine antigen profile of the N. meningitidis pathogen, thus enabling thorough characterization of outbreaks. This method is particularly important for enhancing molecular surveillance in regions with low culture rates. SWGA produces enough reads for phylogenetic and allelic analysis at a low cost. More importantly, the procedure can be extended to enrich other important human bacterial pathogens.

Reverse Sequence Syphilis Screening and Discordant Results in Pregnancy.

A "reverse sequence syphilis screening" algorithm is widely used for syphilis testing. This retrospective study showed that most (65%) pregnant women with discordant screening results (treponemal multiplex flow immunoassay IgG+/rapid plasma reagin-) had a nonreactive confirmatory Treponema pallidum-particle agglutination assay, likely indicative of a false-positive reaction.

For Human Papillomavirus Self-Sampling, Stated Willingness Does Not Correspond With Subsequent Uptake by Rural Malawian Women.

BACKGROUND: Human papilloma virus (HPV), the causative agent for cervical cancer, can be tested for using self-collected vaginal samples. Self-collection is promising for HPV screening in hard-to-reach populations. To assess the relationship between willingness to self-collect and subsequent uptake of self-collection, we conducted a longitudinal study of reproductive-age women in rural Malawi. METHODS: At baseline, we asked women if they would be willing to self-collect a vaginal sample for HPV testing. At follow-up (12-18 months later), we offered the same women the opportunity to self-collect a sample for HPV testing. We examined unadjusted and adjusted associations between baseline willingness to self-collect a sample for HPV testing and uptake of self-collection at follow-up using log-binomial models. RESULTS: Among 122 women who, at baseline, indicated willingness to self-collect, n = 65 (53%) agreed to self-collect a sample at follow-up. Of 64 women who stated unwillingness at baseline to self-collect, n = 30 (47%) self-collected a sample for testing at follow-up. We observed no association between women's willingness at baseline and their observed self-collection decision at follow-up (unadjusted prevalence ratio, 1.14; 95% confidence interval, 0.83-1.55). The association remained null after adjustment for age, awareness of cervical cancer, and perceived behavioral control. CONCLUSIONS: Our results suggest that evaluation of acceptability of self-collection should go beyond simply asking women if they would be willing to self-collect a vaginal sample. Given that half of this study's participants agreed to self-collect a sample when the opportunity was offered, regardless of their previously stated preferences, self-collection should be offered to everyone.