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.

Macrophage maturation from blood monocytes is altered in people with HIV, and is linked to serum lipid profiles and activation indices: A model for studying atherogenic mechanisms.

People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Proportions of vascular homing monocytes are enriched in PWH; however, little is known regarding monocyte-derived macrophages (MDMs) that may drive atherosclerosis in this population. We isolated PBMCs from people with and without HIV, and cultured these cells for 5 days in medium containing autologous serum to generate MDMs. Differential gene expression (DGE) analysis of MDMs from PWH identified broad alterations in innate immune signaling (IL-1ß, TLR expression, PPAR ßδ) and lipid processing (LXR/RXR, ACPP, SREBP1). Transcriptional changes aligned with the functional capabilities of these cells. Expression of activation markers and innate immune receptors (CD163, TLR4, and CD300e) was altered on MDMs from PWH, and these cells produced more TNFα, reactive oxygen species (ROS), and matrix metalloproteinases (MMPs) than did cells from people without HIV. MDMs from PWH also had greater lipid accumulation and uptake of oxidized LDL. PWH had increased serum levels of free fatty acids (FFAs) and ceramides, with enrichment of saturated FAs and a reduction in polyunsaturated FAs. Levels of lipid classes and species that are associated with CVD correlated with unique DGE signatures and altered metabolic pathway activation in MDMs from PWH. Here, we show that MDMs from PWH display a pro-atherogenic phenotype; they readily form foam cells, have altered transcriptional profiles, and produce mediators that likely contribute to accelerated ASCVD.

Repeat Episodes of Symptomatic Urethritis Due to a Uropathogenic Meningococcal Clade.

In 2015, we identified a non-groupable clade of Neisseria meningitidis that causes urethritis in men (the US_NmUC). Because repeat infection is common with Neisseria gonorrhoeae, we examined whether reinfection also occurs with the US_NmUC. We provide evidence that men are susceptible to repeat episodes of urethritis from the US_NmUC.

The Effects of Multiple Sets of Squats and Jump Squats on Mechanical Variables.

Rossetti, ML, Munford, SN, Snyder, BW, Davis, SE, and Moir, GL. The effects of multiple sets of squats and jump squats on mechanical variables. J Strength Cond Res 34(4): 1017-1023, 2020-The mechanical responses to 2 nonballistic squat and 2 ballistic jump squat protocols performed over multiple sets were investigated. One protocol from each of the 2 nonballistic and ballistic conditions incorporated a pause between the eccentric and concentric phases of the movements in order to determine the influence of the coupling time on the mechanical variables and postactivation potentiation (PAP). Eleven men (age: 21.9 ± 1.8 years; height: 1.79 ± 0.05 m; mass: 87.0 ± 7.4 kg) attended 4 sessions where they performed multiple sets of squats and jump squats with a load equivalent to 30% 1-repetition maximum under one of the following conditions: (a) 3 × 4 repetitions of nonballistic squats (30N-B); (b) 3 × 4 repetitions of nonballistic squats with a 3-second pause between the eccentric and concentric phases of each repetition (30PN-B); (c) 3 × 4 repetitions of ballistic jump squats (30B); (d) 3 × 4 repetitions of ballistic jump squats with a 3-second pause between the eccentric and concentric phases of each repetition (30PB). Force plates were used to calculate variables including average vertical velocity, average vertical force (GRF), and average power output (PO). Vertical velocities during the ballistic conditions were significantly greater than those attained during the nonballistic conditions (mean differences: 0.21-0.25 m·s, p < 0.001, effect sizes [ES]: 1.70-1.89) as were GRFs (mean differences: 478-526 N, p < 0.001, ES: 1.61-1.63), and PO (mean differences: 711-869 W, p < 0.001, ES: 1.66-1.73). Moreover, the increase in PO across the 3 sets in 30B was significantly greater than the changes observed during 30N-B, 30PN-B, and 30PB (p ≤ 0.015). The pause reduced the mechanical variables during both the nonballistic and ballistic conditions, although the differences were not statistically significant (p > 0.05). Ballistic jump squats may be an effective exercise for developing PO given the high velocities and forces generated in these exercises. Furthermore, the completion of multiple sets of jump squats may induce PAP to enhance PO. The coupling times between the eccentric and concentric phases of the jump squats should be short in order to maximize the GRF and PO across the sets.

Digital Breast Tomosynthesis: Cost-Effectiveness of Using Private and Medicare Insurance in Community-Based Health Care Facilities.

OBJECTIVE: The purpose of this study was to determine whether digital breast tomosynthesis (DBT) is a cost-effective alternative to full-field digital mammography (FFDM) for both Medicare and privately insured patients undergoing screening mammography. MATERIALS AND METHODS: A retrospective data analysis was performed between July 15, 2013, and July 14, 2014, with data on women presenting for screening mammography that included any additional radiologic workup (n = 6319). Patients chose to undergo DBT or FFDM on the basis of personal preference, physician suggestion, and cost difference. The summation of findings over the 1-year period were used to calculate recall rates, cancer detection rates, and billing costs for a regional private insurer and Medicare. RESULTS: Data from the 6319 patients who participated were divided: 3655 patients underwent DBT, and 2664 underwent FFDM during the year of screening. Private insurance billing cost $2.9 million, and Medicare cost $1.2 million for screening, follow-up imaging, and radiologic procedures. Per-person costs were approximately $40 higher for the DBT group using both forms of insurance. However, cost per cancer detected was lower in the DBT group for both private and governmental insurance, leading to potentially $3.7 million and $899,000 saved per 100 cancers found. After standardization of the difference in cancer detection rates between the two groups, DBT was a cost-equivalent alternative to FFDM for private insurance billing but was a cost-inefficient alternative with respect to Medicare costs. CONCLUSION: In a community-based setting, DBT is a cost-equivalent or potentially cost-effective alternative to FFDM and has the capacity for improving cancer detection and recall rates.

High levels of self-reported prescription opioid use by HIV-positive individuals.

Prescription medication use (other than antiretroviral therapy (ART)) is highly prevalent among people living with HIV. Prescription medications may be used medically or non-medically: non-medical use includes using more medication than prescribed, using medication prescribed to someone else, or using medication for a purpose other than its prescribed use. During 12 weeks in 2014-2015, we characterized medical and non-medical prescription medication use among HIV-positive patients attending an academic medical center (n = 149) and a community clinic (n = 105). Separately for the past year and the past month, these 254 participants self-reported their use of prescription opioids, sedatives, stimulants, anti-anxiety medications, antipsychotic medications, and erectile dysfunction medications. Respondents were largely male (91%), aged 40 or older (61%), identified as gay or bisexual (79%), and were men who have sex with men (85%). ART use was nearly universal (95%). Nearly half (43%) of participants reported medical use of prescription opioids; 11% of the opioid use was reported as non-medical use. Anti-anxiety medication use was also frequent, and differed by site: 41% of community-clinic responders reported medical use of anti-anxiety medications compared to 23% of hospital clinic respondents who reported medical use. Prescription sedative use was also approximately twice as high among community-clinic participants, with medical use reported by 43% of respondents and non-medical use by 12%; in comparison, at the hospital clinic, sedative use was reported by 18% (medical) and 7% (non-medical) of participants. Stimulant use was rare in both sites. No demographic characteristic was significantly associated with medical or non-medical use of any prescription medication. The current focus of many studies on only non-medical prescription medication use not only underestimates the widespread exposure of HIV-positive individuals to these drugs, but may also underestimate potential adverse effects of prescription medications in this population.

Antibiotic Susceptibility Profile for the US Neisseria meningitidis Urethritis Clade.

The US Neisseria meningitidis urethritis clade (US_NmUC) harbors gonococcal deoxyribonucleic acid alleles and causes gonorrhea-like urogenital tract disease. A large convenience sample of US_NmUC isolates (N = 122) collected between January 2015 and December 2019 in Columbus, Ohio demonstrated uniform susceptibility to antibiotics recommended for gonorrhea treatment and meningococcal chemoprophylaxis.

Using Drop Jumps and Jump Squats to Assess Eccentric and Concentric Force-Velocity Characteristics.

The purpose of this study was to investigate the eccentric and concentric force-velocity (Fv) characteristics recorded during drop jumps (DJ) from different heights and loaded jump squats (JS) and to determine the number of jumps required to accurately model the eccentric and concentric Fv relationships. Fourteen resistance-trained men (age: 21.9 ± 1.8 years) performed a countermovement jump (CMJ) and DJ from heights of 0.40, 0.60, and 0.80 m. JS with loads equivalent to 0%, 27%, 56%, and 85% 1-repetition maximum were performed in a separate session. Force platforms and a 3-D motion analysis system were used to record the average force ( F ¯ ) and velocity ( v ¯ ) during the absorption (CMJ, DJ40, DJ60, DJ80) and propulsion (JS0, JS27, JS56, JS85) phases of the jumps. Eccentric (absorption phase) and concentric (propulsion phase) Fv characteristics were then calculated and linear regression equations were determined when the number of jumps included was varied. F ¯ during the absorption phase significantly increased from CMJ to DJ60 while v ¯ increased significantly from CMJ to DJ80. The two-point method (CMJ, DJ80) resulted in a significantly lower y-intercept (mean difference [MD]: 0.7 N/kg) and a greater slope (MD: 0.7 Ns/m) for the eccentric Fv characteristics compared to the multiple-point method. F ¯ increased significantly and v ¯ decreased significantly with increasing external load in the JS conditions. The two-point method (JS0, JS85) resulted in a significantly greater y-intercept (MD: 1.1 N/kg) compared to the multiple-point method for the concentric Fv characteristics. Both DJ and loaded JS may provide means of assessing the eccentric and concentric Fv characteristics with only two jumps being required.

Assessing Plyometric Ability during Vertical Jumps Performed by Adults and Adolescents.

The purpose of this study was to compare different methods for assessing plyometric ability during countermovement (CMJ) and drop jumps (DJ) in a group of adults and adolescents. Ten resistance-trained adult men (age: 22.6 ± 1.6 years) and ten adolescent male basketball players (age: 16.5 ± 0.7 years) performed a CMJ and a DJ from a height of 0.40 m. Jump height (JH), contact time, normalized work (WNORM), and power output (PONORM) during the absorption and propulsion phases were calculated from force platforms and 3-D motion analysis data. Plyometric ability was assessed using the modified reactive strength index (RSIMOD during CMJ) and the reactive strength index (RSI during DJ) as well as three indices using propulsion time, propulsion work (PWI), and propulsion power. Adults jumped significantly higher than adolescents (mean difference [MD]: 0.05 m) while JH (MD: 0.05 m) and ground contact time (MD: 0.29 s) decreased significantly from CMJ to DJ. WNORM (MD: 4.2 J/kg) and PONORM (MD: 24.2 W/kg) during the absorption phase of CMJ were significantly less than these variables during the propulsion phases of the jumps. The reactive strength index variants increased significantly from the CMJ to DJ (MD: 0.23) while all other plyometric indices decreased significantly. Neither RSIMOD nor RSI contributed significantly to the prediction of JH during CMJ and DJ, respectively, while PWI was able to explain ≥68% of the variance in JH. Variants of the reactive strength index do not reflect the changes in mechanical variables during the ground contact phase of CMJ and DJ and may not provide an accurate assessment of plyometric ability during different vertical jumps.

Prospective Analysis of Lipid Composition Changes with Antiretroviral Therapy and Immune Activation in Persons Living with HIV.

BACKGROUND: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described. METHODS: Plasma lipid concentrations and their fatty acid composition were measured by differential mobility spectroscopy in samples from 35 treatment-naive HIV+ participants beginning raltegravir (RAL)-based ART and from HIV- individuals (n = 13) matched for age and sex. RESULTS: The levels of SaFA, including palmitic (16:0) and stearic (18:0) acid were enriched in HIV+ participants (pre- and post-ART), and SaFA levels were often positively correlated with levels of immune activation (ie, IL-6, sCD14, and TNFR1) at baseline and week 48. Levels of PUFAs (including 18:3, 20:4, and 20:5) were lower in HIV+ participants at baseline compared to levels in HIV- participants (P < 0.01), and levels of these PUFAs were increased following 48 weeks of ART. Levels of PUFAs were often inversely related to immune activation. Levels of LPC were increased in HIV+ participants, both pre- and post-ART vs HIV- participants, and the composition of LPC was enriched for SaFAs among HIV+ individuals. At week 48, several LPC molecules containing SaFAs were positively correlated with levels of sCD14, D-dimer, and TNFR1 (P < 0.01), and levels of PUFA-containing LPC (18:3, 20:5, 22:5, 22:6) were positively correlated with CD4+ T cell counts and inversely correlated with sCD14 and IL-6 (P < 0.01). CONCLUSIONS: The composition of the lipidome is altered in HIV infection and changes when ART is administered. Alterations in SaFAs were generally associated with inflammatory markers and may contribute to comorbid disease pathogenesis.