Extragenital Sexually Transmitted Infections Among High-Risk Men Who Have Sex With Men in Johannesburg, South Africa.

BACKGROUND: In South Africa, extragenital etiological sexually transmitted infection (STI) screening among men who have sex with men (MSM) is not routinely available. We aimed to determine the prevalence of STI pathogens at rectal and pharyngeal sites, syphilis seroprevalence, and associated risk factors among a selection of high-risk MSM without symptomatic urethritis attending a men's health clinic in Johannesburg, South Africa. METHODS: A cross-sectional study was conducted in 2022. Enrolled clients self-reported demographic, sexual behavioral risks, and clinical information. Client or clinician-collected rectal and pharyngeal swabs were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis. C. trachomatis-positive rectal samples were reflex tested for lymphogranuloma venereum. Blood specimens were screened for syphilis. Univariate and multivariate regression models were used to determine factors independently associated with the presence of an extragenital STI or syphilis. RESULTS: Among the 97 participants (median age, 29 years), 24.7% had an extragenital STI and 9.4% had high nontreponemal antibody titers (rapid plasma reagin ≥1:16). Rectal STIs were detected in 26.4% participants: N. gonorrhoeae (14.3%), C. trachomatis (9.9%), and M. genitalium (5.5%). Pharyngeal STIs were less prevalent (4.1%). Overall, the prevalence of any STI was 41%. Sex under the influence of drugs (adjusted odds ratio, 4.94; 95% confidence interval, 1.56-15.69) and engaging in condomless receptive anal intercourse with a casual partner (adjusted odds ratio, 8.36; 95% confidence interval, 1.73-40.28) were independent risk factors for having an extragenital STI. CONCLUSIONS: The high burden of extragenital STIs and active syphilis in asymptomatic MSM underscores the importance of routine etiological screening in this key population, as the syndromic approach would not enable detection or treatment of these infections.

Emergence of high-level azithromycin-resistant Neisseria gonorrhoeae causing male urethritis in Johannesburg, South Africa, 2021.

BACKGROUND: In South Africa, Neisseria gonorrhoeae , which is the predominant cause of male urethritis, is treated syndromically using dual ceftriaxone and azithromycin therapy. We determined antimicrobial susceptibilities of N. gonorrhoeae isolates from urethral discharge specimens, and genetically characterised those with elevated minimum inhibitory concentrations (MICs) for first-line antimicrobials. METHODS: Routine antimicrobial susceptibility testing (AST) of N. gonorrhoeae isolates included E-test for ceftriaxone, cefixime and gentamicin and agar dilution for azithromycin and spectinomycin. Neisseria gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) was performed for isolates with elevated MICs to identify antimicrobial resistance (AMR) determinants, and Neisseria gonorrhoeae Multi-Antigen Sequence Typing (NG-MAST) was used to determine strain relatedness. RESULTS: N. gonorrhoeae was cultured from urethral discharge swab specimens obtained from 196 of 238 (82.4%) men presenting to a primary healthcare facility in Johannesburg in 2021. All viable isolates were susceptible to extended-spectrum cephalosporins. Four isolates had high azithromycin MICs ranging from 32mg/L to >256mg/L and grouped into two novel NG-MAST and NG-STAR groups. Two isolates from Group 1 (NG-MAST ST20366, NG-STAR ST4322) contained mutated mtrR (G45D) and 23S rRNA (A2059G) alleles, while the two isolates from Group 2 (NG-MAST ST20367, NG-STAR ST4323) had different mutations in mtrR (A39T) and 23S rRNA (C2611T). CONCLUSIONS: We report the first cases of high-level azithromycin resistance in N. gonorrhoeae from South Africa. Continued AMR surveillance is critical to detect increasing azithromycin resistance prevalence in N. gonorrhoeae , which may justify future modifications to the STI syndromic management guidelines.

Risk of Injury-Related Readmission Varies by Initial Presenting-Hospital Type Among Children at High Risk for Physical Abuse.

OBJECTIVES: Children experiencing physical abuse may initially present to hospitals with underappreciated minor injuries, only to experience more severe injuries in the future. The objectives of this study were to 1) describe young children presenting with high-risk diagnoses for physical abuse, 2) characterize the hospitals to which they initially presented, and 3) evaluate associations of initial presenting-hospital type with subsequent admission for injury. METHODS: Patients aged younger than 6 years from the 2009-2014 Florida Agency for Healthcare Administration database with high-risk diagnoses (codes previously associated with >70% risk of child physical abuse) were included. Patients were categorized by the hospital type to which they initially presented: community hospital, adult/combined trauma center, or pediatric trauma center. Primary outcome was subsequent injury-related hospital admission within 1 year. Association of initial presenting-hospital type with outcome was evaluated with multivariable logistic regression, adjusting for demographics, socioeconomic status, preexisting comorbidities, and injury severity. RESULTS: A total of 8626 high-risk children met inclusion criteria. Sixty-eight percent of high-risk children initially presented to community hospitals. At 1 year, 3% of high-risk children had experienced subsequent injury-related admission. On multivariable analysis, initial presentation to a community hospital was associated with higher risk of subsequent injury-related admission (odds ratio, 4.03 vs level 1/pediatric trauma center; 95% confidence interval, 1.83-8.86). Initial presentation to a level 2 adult or combined adult/pediatric trauma center was also associated with higher risk for subsequent injury-related admission (odds ratio, 3.19; 95% confidence interval, 1.40-7.27). CONCLUSIONS: Most children at high risk for physical abuse initially present to community hospitals, not dedicated trauma centers. Children initially evaluated in high-level pediatric trauma centers had lower risk of subsequent injury-related admission. This unexplained variability suggests stronger collaboration is needed between community hospitals and regional pediatric trauma centers at the time of initial presentation to recognize and protect vulnerable children.

Molecular Characterization and Detection of Macrolide and Fluoroquinolone Resistance Determinants in Mycoplasma genitalium in South Africa, 2015 to 2018.

BACKGROUND: Antimicrobial resistance in Mycoplasma genitalium is a global concern, as therapeutic options are limited. We aimed to determine the prevalence of macrolide and fluoroquinolone resistance-associated genetic determinants and strain diversity in M. genitalium-positive surveillance specimens from symptomatic primary health care center attendees in South Africa (2015-2018). A secondary objective was to investigate for an association between M. genitalium strain type, HIV serostatus, and antimicrobial resistance. METHODS: A total of 196 M. genitalium-positive specimens from adult males and females presenting with genital discharge to primary health care centers were tested for resistance-associated mutations in 23S rRNA, parC and gyrA. A dual-locus sequence type (DLST) was assigned to M. genitalium strains based on the detection of single nucleotide polymorphisms in the semiconserved 5' region of the mgpB gene (MG191-sequence typing) as well as the enumeration of short tandem repeats within the lipoprotein gene (MG309 short tandem repeat typing). RESULTS: The A2059G mutation in 23S rRNA, associated with macrolide resistance, was detected in 3 of 182 specimens (1.7%; 95% confidence interval, 0.3-4.7). We did not detect gyrA or parC mutations associated with fluoroquinolone resistance in specimens that could be sequenced. Molecular typing with DLST revealed genetic heterogeneity, with DLST 4-11 being the most common M. genitalium strain type detected. There were no associations between DLST and macrolide resistance or HIV infection. CONCLUSIONS: We found a low prevalence of M. genitalium strains with macrolide resistance-associated mutations over a 4-year surveillance period. Ongoing antimicrobial resistance surveillance is essential for informing genital discharge syndromic treatment guidelines.

Treponema pallidum Macrolide Resistance and Molecular Epidemiology in Southern Africa, 2008 to 2018.

Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral therapeutic alternatives to benzathine penicillin G for syphilis or for other clinical indications. Macrolides are not included in the South African syndromic management guidelines for genital ulcer disease; however, in 2015, a 1-g dose of azithromycin was incorporated into treatment algorithms for genital discharge. We determined the prevalence of 23S rRNA macrolide resistance-associated point mutations in 135 T. pallidum-positive surveillance specimens from Botswana, Zimbabwe, and South Africa between 2008 and 2018. Additionally, we investigated the association between macrolide resistance, T. pallidum strain type, and HIV coinfection. A significant increase in the prevalence of the A2058G macrolide resistance-associated point mutation was observed in specimens collected after 2015. There was a high level of molecular heterogeneity among T. pallidum strains circulating in the study communities, with strain type 14d/f being the most predominant in South Africa. Fourteen novel strain types, derived from three new tpr gene restriction fragment length polymorphism patterns and seven new tp0548 gene sequence types, were identified. There was an association between A2058G-associated macrolide resistance and T. pallidum strain types 14d/f and 14d/g but no association between T. pallidum macrolide resistance and HIV coinfection. The majority of T. pallidum strains, as well as strains containing the A2058G mutation, belonged to the SS14-like clade. This is the first study to extensively detail the molecular epidemiology and emergence of macrolide resistance in T. pallidum in southern Africa.

The changing epidemiology of genital ulcer disease in South Africa: has donovanosis been eliminated?

OBJECTIVES: We used an in-house molecular assay for the detection of Klebsiella granulomatis in ulcer specimens collected over a 12-year surveillance period in order to determine whether a diagnosis of donovanosis could be ascribed to genital ulcer disease (GUD) of unknown aetiology in our setting. METHODS: Between 2007 and 2018, a total of 974 genital ulcer specimens with no previously identified sexually transmitted (STI) pathogens were selected from STI aetiological surveys conducted in all nine provinces of South Africa. Giemsa-stained ulcer smears from the same participants had previously been routinely analysed for the presence of typical Donovan bodies within large mononuclear cells. A Klebsiella screening assay targeting the phoE (phosphate porin) gene was used in combination with restriction digest analysis and sequencing to confirm the presence of K. granulomatis. RESULTS: The Klebsiella screening assay tested positive in 19/974 (2.0%) genital ulcer specimens. Restriction digest analysis and nucleotide sequencing of the phoE gene confirmed that none of these specimens was positive for K. granulomatis DNA. Similarly, Donovan bodies were not identified in the Giemsa stained ulcer smears of these specimens. CONCLUSIONS: This is the first study to assess K. granulomatis as a cause of genital ulceration in South Africa over a 12-year surveillance period using molecular methods. The results demonstrate that K. granulomatis is no longer a prevalent cause of GUD in our population.

Added Cost and Time Spent by Patients With History of Abuse in Florida Emergency Departments.

Interpersonal violence is known to lead to both short- and long-term health effects. Victims of sexual abuse tend to have higher healthcare costs and higher rates of physical and mental health issues than nonvictims. In this study, we investigate whether the comorbidity of mental illness and a personal history of adult physical and sexual abuse (HAPSA) results in higher healthcare costs and length of emergency department (ED) stay among Florida residents. A Negative Binomial and Log-Linear Regression Analysis suggest increased ED visit duration for those with a history of abuse, Hispanics, the uninsured, and those with multiple comorbidities. In addition, increased costs were found to be associated with White race, the uninsured, those with multiple comorbidities, and the facility type (for-profit hospitals).

Prevalence and Antimicrobial Resistance of Mycoplasma genitalium Infection Among Women Living With Human Immunodeficiency Virus in South Africa: A Prospective Cohort Study.

This prospective cohort study of 622 women living with human immunodeficiency virus (HIV) from Johannesburg (2012) detected Mycoplasma genitalium in 7.4% (95% confidence interval [CI]: 5.5-9.7, 46/622), with detection more likely with lower CD4 counts(adjusted odds ratio [AOR] 1.02 per 10 cells/µL decrease, 95% CI: 1.00-1.03) and higher plasma HIV-1 RNA (AOR 1.15 per log copies/mL increase, 95% CI: 1.03-1.27). No mutations for macrolide/quinolone resistance was detected.

The Prevalence of Mycoplasma genitalium and Association With Human Immunodeficiency Virus Infection in Symptomatic Patients, Johannesburg, South Africa, 2007-2014.

BACKGROUND: Mycoplasma genitalium is associated with genital discharge syndrome, but limited prevalence data are available in South Africa. The prevalence rates of M. genitalium infection and human immunodeficiency virus (HIV) coinfection were determined in urogenital specimens collected from male and female patients presenting with genital discharge syndrome to a primary health care center in Johannesburg, South Africa from 2007 through 2014. METHODS: Genital specimens from 4731 patients were tested by a validated in-house multiplex real-time polymerase chain reaction assay for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and M. genitalium. Sera were tested for HIV infection using the Determine HIV 1/2 and Unigold assays. RESULTS: The relative prevalence of M. genitalium in males and females was 8.9% and 10.6%, respectively. The prevalence of HIV infection in those infected with M. genitalium, without other sexually transmitted infections (STIs), was significantly higher than in those without M. genitalium infection (48.9% vs. 40.5%, P = 0.014). This significant difference in HIV seroprevalence was particularly observed among females in the study cohort. CONCLUSIONS: The relative prevalence of M. genitalium and its association with prevalent HIV among females with vaginal discharge syndrome (VDS) calls for further research on the potential role of M. genitalium in the transmission and acquisition of HIV.

Incidence, Persistence, Clearance, and Correlates of Genital Human Papillomavirus Infection and Anogenital Warts in a Cohort of Men Living With Human Immunodeficiency Virus in South Africa.

OBJECTIVE: To estimate the incidence; persistence and correlates of human papillomavirus (HPV) infection and anogenital warts (AGW) among men living with human immunodeficiency virus (MLHIV). METHODS: Overall, 304 MLHIV 18 years or older were enrolled and attended follow-up visits at 6, 12, and 18 months. Clinicians examined for AGW, collected blood, and penile swabs for HPV testing (Roche Linear Array) at each visit. Time to AGW incidence or clearance was estimated by Kaplan-Meier method. Factors associated with persistent HPV infection and AGW clearance were evaluated with generalized estimating equations and Cox regression, respectively. RESULTS: Mean age of participants was 38 years (standard deviation, 8 years); 25% reported more than 1 sexual partner in the past 3 months. Most (65%) participants were on antiretroviral treatment (ART) with a median CD4 count of 445 cells/µL (interquartile range, 328-567). Prevalence of HPV infection and AGW at enrolment were 79% (224 of 283) and 12% (36 of 304), respectively. Two hundred fifty-nine men were followed up for a median (interquartile range) 1.4 years (0.5-1.7 years). Incidence of any-genital HPV infection was 2.9 (95% confidence interval, 1.5-5.5) per 100 person-years. Persistence of any-genital HPV infection was 35% (68 of 192) and was higher among MLHIV with low CD4 count (adjusted odds ratio, 3.54; 95% confidence interval, 2.07-6.05). Incidence of AGW was 1.4 per 100 person-years. Men living with human immunodeficiency virus with high CD4 count were more likely to clear AGW than those with low CD4 count (adjusted hazard ratio, 3.69; 95% confidence interval, 1.44-9.47). No associations were observed between persistent genital HPV infection, AGW clearance with enrolment ART status or duration. CONCLUSIONS: Human immunodeficiency virus-positive men have a high burden of genital HPV infection and AGW. The ART and HPV vaccine could reduce this burden.

Clinical Characteristics of Mycoplasma genitalium and the Usefulness of Syndromic Management Among Women Living With Human Immunodeficiency Virus.

We report the clinical symptoms and examination findings of Mycoplasma genitalium (MG) in women living with human immunodeficiency virus in South Africa. If we relied on syndromic management alone to treat MG, only 15 of 46 MG-infected women would have received. appropriate treatment: sensitivity of 32.6% (95% confidence interval, 19.5-48.0) and specificity of 67.4% (95% confidence interval, 63.4-71.2).

Macrolide and fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Johannesburg, South Africa, 2007-2014.

BACKGROUND: Antimicrobial resistance in Mycoplasma genitalium is rising globally with resultant clinical treatment failure. We investigated the prevalence of mutations in the macrolide and fluoroquinolone resistance-determining regions of M. genitalium in Johannesburg, South Africa, and ascertained their association with HIV serostatus. METHODS: Stored M. genitalium positive specimens, collected from STI and HIV patients enrolled in the Gauteng STI National Microbiological Surveillance programme (2007-2014) and a large HIV outpatient clinic-based study (2007) in Johannesburg, were tested for antimicrobial resistance. RESULTS: We determined the prevalence of 23S rRNA gene mutations conferring macrolide resistance and mutations in the quinolone resistance-determining regions (QRDR) of the gyrA and parC genes in 266 M. genitalium positive DNA extracts. No macrolide resistance-associated mutations were detected in any of the specimens analysed. QRDR mutations with known M. genitalium-associated fluoroquinolone resistance were not detected in gyrA, however, one specimen (0.4%) contained a D87Y amino acid alteration in parC, which has been linked to fluoroquinolone treatment failure. The most common parC amino acid change detected, of unknown clinical significance, was P62S (18.8%). We found no significant association between QRDR mutations in M. genitalium and HIV-infection. CONCLUSIONS: Ongoing antimicrobial resistance surveillance in M. genitalium is essential, as macrolide resistance may emerge given the recent incorporation of azithromycin into the 2015 South African national STI syndromic management guidelines.

Comparison of an in-house real-time duplex PCR assay with commercial HOLOGIC® APTIMA assays for the detection of Neisseria gonorrhoeae and Chlamydia trachomatis in urine and extra-genital specimens.

BACKGROUND: Extra-genital Neisseria gonorrhoeae and Chlamydia trachomatis infections are mostly asymptomatic, and important reservoir sites of infection as they often go undetected and may be more difficult to eradicate with recommended therapeutic regimens. Commercial nucleic acid amplification tests (NAATs) have not received regulatory approval for the detection of N. gonorrhoeae and C. trachomatis in extra-genital specimens. The HOLOGIC® APTIMA Combo2 assay for N. gonorrhoeae and C. trachomatis has performed well in evaluations using extra-genital specimens. METHODS: We assessed the performance of an in-house real-time duplex PCR assay for the detection of N. gonorrhoeae and C. trachomatis in urine and extra-genital specimens using the HOLOGIC® APTIMA assays as gold standard comparators. Urine, oropharyngeal and ano-rectal specimens were collected from each of 200 men-who-have-sex-with-men (MSM) between December 2011 and July 2012. RESULTS: For N. gonorrhoeae detection, the in-house PCR assay showed 98.5-100% correlation agreement with the APTIMA assays, depending on specimen type. Sensitivity for N. gonorrhoeae detection was 82.4% for ano-rectal specimens, 83.3% for oropharyngeal specimens, and 85.7% for urine; and specificity was 100% with all specimen types. The positive predictive value (PPV) for N. gonorrhoeae detection was 100% and the negative predictive value (NPV) varied with sample type, ranging from 98.5-99.5%. For C. trachomatis detection, correlation between the assays was 100% for all specimen types. The sensitivity, specificity, PPV and NPV of the in-house PCR assay was 100% for C. trachomatis detection, irrespective of specimen type. CONCLUSION: The in-house duplex real-time PCR assay showed acceptable performance characteristics in comparison with the APTIMA® assays for the detection of extra-genital N. gonorrhoeae and C. trachomatis.

Cav2.3 (R-Type) Calcium Channels are Critical for Mediating Anticonvulsive and Neuroprotective Properties of Lamotrigine In Vivo.

BACKGROUND/AIMS: Lamotrigine (LTG) is a popular modern antiepileptic drug (AED), however, its mechanism of action has yet to be fully understood, as it is known to modulate many members of several ion channel families. In heterologous systems, LTG inhibits Cav2.3 (R-type) calcium currents, which contribute to kainic-acid- (KA) induced epilepsy in vivo. To gain insight into the role of R-type currents in LTG drug action in vivo, we compared the effects of LTG to topiramate and lacosamide in Cav2.3-deficient mice and controls on KA-induced seizures. METHODS: Behavioral seizure rating and quantitative electrocorticography were performed after injection of 20 mg/kg [and 30 mg/kg] KA. One hour before KA injection, mice were pretreated with either 30 mg/kg LTG, 50 mg/kg topiramate (TPM) or 30 mg/kg lacosamide (LSM). RESULTS: Ablation of Cav2.3 reduced total seizure scores by 28.6% (p=0.0012) and pretreatment with LTG reduced seizure activity of control mice by 23.2% (p=0.02). In Cav2.3-deficient mice LTG pretreatment increased seizure activity by 22.1% (p=0.018) and increased the percentage of degenerated CA1 pyramidal neurons (p=0.02). All three tested AEDs reduced seizure activity in control mice, however only the non-calcium channel modulating AED, LSM had an anticonvulsive effect in Cav2.3-deficient mice. Furthermore LTG altered electrocorticographic parameters differently in the two genotypes, decreasing relative power of ictal spikes in control mice compared to Cav2.3-defcient mice. CONCLUSION: These findings give first in vivo evidence for an essential role for Cav2.3 in LTG pharmacology and shed light on a paradoxical effect of LTG in their absence. Furthermore, LTG appears to promote ictal activity in Cav2.3-deficient mice resulting in increased neurotoxicity in the CA1 region. This paradoxical mechanism, possibly reflecting rebound hyperexcitation of pyramidal CA1 neurons after increased inhibition, may be key in understanding LTG-induced seizure aggravation, observed in clinical practice.

Multiple nickel-sensitive targets elicit cardiac arrhythmia in isolated mouse hearts after pituitary adenylate cyclase-activating polypeptide-mediated chronotropy.

The pituitary adenylate cyclase-activating polypeptide (PACAP)-27 modulates various biological processes, from the cellular level to function specification. However, the cardiac actions of this neuropeptide are still under intense studies. Using control (+|+) and mice lacking (-|-) either R-type (Cav2.3) or T-type (Cav3.2) Ca2+ channels, we investigated the effects of PACAP-27 on cardiac activity of spontaneously beating isolated perfused hearts. Superfusion of PACAP-27 (20nM) caused a significant increase of baseline heart frequency in Cav2.3(+|+) (156.9±10.8 to 239.4±23.4 bpm; p<0.01) and Cav2.3(-|-) (190.3±26.4 to 270.5±25.8 bpm; p<0.05) hearts. For Cav3.2, the heart rate was significantly increased in Cav3.2(-|-) (133.1±8.5 bpm to 204.6±27.9 bpm; p<0.05) compared to Cav3.2(+|+) hearts (185.7±11.2 bpm to 209.3±22.7 bpm). While the P wave duration and QTc interval were significantly increased in Cav2.3(+|+) and Cav2.3(-|-) hearts following PACAP-27 superfusion, there was no effect in Cav3.2(+|+) and Cav3.2(-|-) hearts. The positive chronotropic effects observed in the four study groups, as well as the effect on P wave duration and QTc interval were abolished in the presence of Ni2+ (50µM) and PACAP-27 (20nM) in hearts from Cav2.3(+|+) and Cav2.3(-|-) mice. In addition to suppressing PACAP's response, Ni2+ also induced conduction disturbances in investigated hearts. In conclusion, the most Ni2+-sensitive Ca2+ channels (R- and T-type) may modulate the PACAP signaling cascade during cardiac excitation in isolated mouse hearts, albeit to a lesser extent than other Ni2+-sensitive targets.

Prevalence of anogenital HPV infection, related disease and risk factors among HIV-infected men in inner-city Johannesburg, South Africa: baseline findings from a cohort study.

BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is associated with the development of anogenital cancers, particularly in men living with HIV (MLWH). We describe the prevalence of anogenital HPV infection, abnormal anal cytology and anogenital warts (AGWs) in MLWH in Johannesburg, and explore whether HPV infection and receipt of antiretroviral treatment is associated with detection of abnormal anal cytology and AGWs. METHODS: We enrolled a cohort of 304 sexually-active MLWH ≥18 years, who completed a questionnaire and physical examination. Genital swabs were collected from all men and intra-anal swabs from 250 (82%). Swabs were tested for HPV DNA and genotypes, and anal smears graded using the Bethesda classification. Factors associated with anogenital disease were assessed by logistic regression models. RESULTS: Two thirds were receiving antiretroviral treatment, for a median 33 months (IQR = 15-58) and 54% were HIV-virologically suppressed. Only 5% reported ever having sex with men. Among 283 genital swabs with valid results, 79% had any HPV, 52% had HR-HPV and 27% had >1 HR-HPV infection. By comparison, 39% of the 227 valid intra-anal swabs had detectable HPV, 25% had any HR-HPV and 7% >1 HR infection. While most anal smears were normal (51%), 20% had ASCUS and 29% were LSIL. No cases had HSIL or cancer. Infection with >1 HR type (adjusted OR [aOR] = 2.39; 95%CI = 1.02-5.58) and alpha-9 types (aOR = 3.98; 95%CI = 1.42-11.16) were associated with having abnormal cytology. Prevalence of AGWs was 12%. Infection with any LR type (aOR = 41.28; 95%CI = 13.57-125.62), >1 LR type (aOR = 4.14; 95%CI = 1.60-10.69), being <6 months on antiretroviral treatment (aOR = 6.90; 95%CI = 1.63-29.20) and having a CD4+ count <200 cells/µL (aOR = 5.48; 95%CI: 1.60-18.78) were associated with having AGWs. CONCLUSIONS: In this population, anogenital HR-HPV infection and associated low-grade disease is common, but severe anal dysplasia was not detected. Findings reinforce the need for HPV vaccination in men for preventing both AGWs and HR-HPV infection. Given the absence of anal HSILs, however, the findings do not support the use of anal screening programmes in this population.

SimLabel: a graphical user interface to simulate continuous wave EPR spectra from site-directed spin labeling experiments.

Site-directed spin labeling (SDSL) combined with continuous wave electron paramagnetic resonance (cw EPR) spectroscopy is a powerful technique to reveal, at the residue level, structural transitions in proteins. SDSL-EPR is based on the selective grafting of a paramagnetic label on the protein under study, followed by cw EPR analysis. To extract valuable quantitative information from SDSL-EPR spectra and thus give reliable interpretation on biological system dynamics, numerical simulations of the spectra are required. Such spectral simulations can be carried out by coding in MATLAB using functions from the EasySpin toolbox. For non-expert users of MATLAB, this could be a complex task or even impede the use of such simulation tool. We developed a graphical user interface called SimLabel dedicated to run cw EPR spectra simulations particularly coming from SDSL-EPR experiments. Simlabel provides an intuitive way to visualize, simulate, and fit such cw EPR spectra. An example of SDSL-EPR spectra simulation concerning the study of an intrinsically disordered region undergoing a local induced folding is described and discussed. We believe that this new tool will help the users to rapidly obtain reliable simulated spectra and hence facilitate the interpretation of their results. Copyright © 2017 John Wiley & Sons, Ltd.

Cardiac functions of voltage-gated Ca(2+) channels: role of the pharmacoresistant type (E-/R-Type) in cardiac modulation and putative implication in sudden unexpected death in epilepsy (SUDEP).

Voltage-gated Ca(2+) channels (VGCCs) are ubiquitous in excitable cells. These channels play key roles in many physiological events like cardiac regulation/pacemaker activity due to intracellular Ca(2+) transients. In the myocardium, the Cav1 subfamily (L-type: Cav1.2 and Cav1.3) is the main contributor to excitation-contraction coupling and/or pacemaking, whereas the Cav3 subfamily (T-type: Cav3.1 and Cav3.2) is important in rhythmically firing of the cardiac nodal cells. No established cardiac function has been attributed to the Cav2 family (E-/R-type: Cav2.3) despite accumulating evidence of cardiac dysregulation observed upon deletion of the Cav2.3 gene, the only member of this family so far detected in cardiomyocytes. In this review, we summarize the pathophysiological changes observed after ablation of the E-/R-type VGCC and propose a cardiac mechanism of action for this channel. Also, considering the role played by this channel in epilepsy and its reported sensitivity to antiepileptic drugs, a putative involvement of this channel in the cardiac mechanism of sudden unexpected death in epilepsy is also discussed.

Acute appendicitis: variation in outcomes by insurance status.

BACKGROUND: Acute appendicitis (AA) is often studied as a surrogate for acute care surgery. Previous studies have shown differences in outcomes based on insurance status, but associated costs to health care systems are in need of further study. The purpose of the present study was to investigate how treatment, outcomes, and health care resource utilization differ between the uninsured and commercially insured in the setting of AA. METHODS: Patients with AA were identified by International Classification of Diseases, ninth edition, codes using the Agency for Health Care Administration Florida Hospital inpatient discharge data sets for 2002-2011. The outcomes studied were admission with complicated versus uncomplicated appendicitis, receiving laparoscopic versus open appendectomy and experiencing a perioperative complication, length of stay, and overall hospital cost. Data were analyzed using logistic, negative binomial, and least squares multivariate regression. A P value <0.05 was considered significant. All equations controlled for patient demographics, comorbidities, and year and hospital-fixed effects. RESULTS: The uninsured were more likely to present with complicated appendicitis (odds ratio = 1.31, P < 0.01), less likely to receive laparoscopic appendectomy (odds ratio = 0.70, P < 0.01), had longer length of stay, greater costs but had similar rates of perioperative complications in comparison to the commercially insured. CONCLUSIONS: Insurance status is known to affect health care utilization. The uninsured may delay seeking medical assistance, causing greater incidence of complicated disease and increased costs of treatment. Increasing the number of insured via the Affordable Care Act may improve patient outcomes and decrease costs related to AA. These findings may also apply to other acute care surgery conditions.