Lactobacillus-dominated vaginal microbiotas are associated with reproductive health and STI resistance in women, whereas altered microbiotas are associated with bacterial vaginosis (BV), STI risk and ...poor reproductive outcomes. Putative vaginal taxa have been observed in male first-catch urine, urethral swab and coronal sulcus (CS) specimens but the significance of these observations is unclear. We used 16 S rRNA sequencing to characterize the microbiota of the CS and urine collected from 18 adolescent men over three consecutive months. CS microbiotas of most participants were more stable than their urine microbiotas and the composition of CS microbiotas were strongly influenced by circumcision. BV-associated taxa, including Atopobium, Megasphaera, Mobiluncus, Prevotella and Gemella, were detected in CS specimens from sexually experienced and inexperienced participants. In contrast, urine primarily contained taxa that were not abundant in CS specimens. Lactobacilllus and Streptococcus were major urine taxa but their abundance was inversely correlated. In contrast, Sneathia, Mycoplasma and Ureaplasma were only found in urine from sexually active participants. Thus, the CS and urine support stable and distinct bacterial communities. Finally, our results suggest that the penis and the urethra can be colonized by a variety of BV-associated taxa and that some of these colonizations result from partnered sexual activity.
BackgroundRepeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined MethodsAdolescent ...women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use ResultsWe observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced ⩾1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use ConclusionsMost repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies
The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical ...countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing, and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources, and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data, the authors have generated dose response data in adult male mice maintained under identical conditions and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow, and lung) in the surviving mice. Lethal dose (LD(30), LD(50), and LD(70)) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. These data can be used to aid the design of good laboratory practice (GLP)-compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure.
Some athletes experience a slow recovery after sport-related concussion (SRC). There is little agreement on what constitutes slow recovery, however, and minimal data on the prevalence, predictors, or ...prognosis for this group. The objectives of this study were to apply an operationalized definition of slow recovery and characterize predictors and long-term prognosis of these individuals.
This is a prospective multisite observational study of collegiate athletes. Participants underwent multimodal assessments preseason and 5 additional time points after SRC. Time from injury to initiation of return to play progression (asymptomatic timepoint) and from injury to return to play (RTP) were the primary markers of recovery.
One thousand seven hundred fifty-one concussed male and female collegiate athletes were studied. Eighty percent of participants reached the asymptomatic and/or RTP time points by days 14 and 24, respectively. Slow recovery was thus defined as exceeding 1 or both of those intervals (n = 399). This group was statistically more likely to be female (41.1% vs 35.6%,
= 0.05), have higher initial postinjury SCAT symptom severity scores (mean SD: 36.6 23.4 vs 25.4 19.9,
< 0.001), lower postinjury Standardized Assessment of Concussion scores (mean SD:25.74 2.98 vs 26.26 2.85,
= 0.004), perform worse on the postinjury Balance Error Scoring System (mean SD: 17.8 8.9 vs 15.9 8.5,
< 0.01), have fewer assessments in the first 14 days after injury (mean SD: 48.8 29.7 vs 67.9 24.6,
< 0.01), and be injured in practice (70.7% vs 65.1%,
= 0.04). 77.6% of the slow recovery group returned to play within 60 days of injury, and 83.4% (n = 349) returned to play within 90 days of injury. Only 10.6% had not returned to play 6 months postinjury.
This study suggests an overall favorable prognosis for slowly recovering athletes and provides data for athletes and medical teams to consider in calibrating RTP expectations and making decisions about medical disqualification vs ongoing engagement in their sport.
Background
Concussion diagnosis is typically made through clinical examination and supported by performance on clinical assessment tools. Performance on commonly implemented and emerging assessment ...tools is known to vary between administrations, in the absence of concussion.
Objective
To evaluate the test-retest reliability of commonly implemented and emerging concussion assessment tools across a large nationally representative sample of student-athletes.
Methods
Participants (
n
= 4874) from the Concussion Assessment, Research, and Education Consortium completed annual baseline assessments on two or three occasions. Each assessment included measures of self-reported concussion symptoms, motor control, brief and extended neurocognitive function, reaction time, oculomotor/oculovestibular function, and quality of life. Consistency between years 1 and 2 and 1 and 3 were estimated using intraclass correlation coefficients or Kappa and effect sizes (Cohen’s
d
). Clinical interpretation guidelines were also generated using confidence intervals to account for non-normally distributed data.
Results
Reliability for the self-reported concussion symptoms, motor control, and brief and extended neurocognitive assessments from year 1 to 2 ranged from 0.30 to 0.72 while effect sizes ranged from 0.01 to 0.28 (i.e., small). The reliability for these same measures ranged from 0.34 to 0.66 for the year 1–3 interval with effect sizes ranging from 0.05 to 0.42 (i.e., small to less than medium). The year 1–2 reliability for the reaction time, oculomotor/oculovestibular function, and quality-of-life measures ranged from 0.28 to 0.74 with effect sizes from 0.01 to 0.38 (i.e., small to less than medium effects).
Conclusions
This investigation noted less than optimal reliability for most common and emerging concussion assessment tools. Despite this finding, their use is still necessitated by the absence of a gold standard diagnostic measure, with the ultimate goal of developing more refined and sound tools for clinical use. Clinical interpretation guidelines are provided for the clinician to apply with a degree of certainty in application.
The authors have developed a murine model of the Hematopoietic Syndrome of the Acute Radiation Syndrome (H-ARS) for efficacy testing of medical countermeasures (MCM) against radiation according to ...the FDA Animal Rule. Ten- to 12-wk-old male and female C57BL/6 mice were exposed to the LD50/30-LD70/30 dose of total body irradiation (TBI, (137)Cs, 0.62-0.67 Gy min(-1)) in the morning hours when mice were determined to be most radiosensitive, and they were assessed for 30-d survival and mean survival time (MST). Antibiotics were delivered in drinking water on days 4-30 post-TBI at a concentration based on the amount of water that lethally-irradiated mice were found to consume. The fluoroquinolones, ciprofloxacin and levofloxacin, as well as the tetracycline doxycycline, and aminoglycoside neomycin, all significantly increased MST of decedent mice, while ciprofloxacin (p = 0.061) and doxycycline + neomycin (p = 0.005) showed at least some efficacy to increase 30-d survival. Blood sampling (30 μL/mouse every fifth day) was found to negatively impact 30-d survival. Histopathology of tissues harvested from nonmoribund mice showed expected effects of lethal irradiation, while moribund mice were largely septicemic with a preponderance of enteric organisms. Kinetics of loss and recovery of peripheral blood cells in untreated mice and those treated with two MCM, granulocyte-colony stimulating factor and Amifostine further characterized and validated this model for use in screening studies and pivotal efficacy studies of candidate MCM for licensure to treat irradiated individuals suffering from H-ARS.
Sport-related concussion and repetitive head impact exposure in contact sports continue to receive increased attention in public and medical spheres. The Concussion Assessment, Research and Education ...(CARE) Consortium, a multicenter cooperative, was established to study the natural history of concussion in National Collegiate Athletic Association (NCAA) collegiate student-athletes across 29 colleges and universities in the United States. The purpose of this investigation is to provide normative data from the CARE Consortium and evaluate for differences between sport categories.
NCAA student-athletes were evaluated annually for general demographics and sport-specific characteristics before the start of the competitive season. We collected demographic and medical history information and evaluated each student-athlete's neurocognitive function, neurological status, postural stability, and self-reported symptoms. Sports were categorized by the amount of contact typically associated with the sport (i.e., contact, limited contact, non-contact). Comparisons between the three sport categories for the evaluated variables were made using linear or zero inflated negative binomial regression models adjusted for gender, concussion history, and household income.
Over a 2-year period (August 2014-July 2016), 15,681 NCAA athletes completed preseason evaluations. Overall, 53% of the athletes were in the contact sport group, 31% were in the limited contact group and 17% were in the non-contact group. After adjusting for covariates, there were statistically significant differences found between athlete groups, although the differences and effect sizes were small and not clinically significant. The contact sport group had better scores on Immediate Post-Concussion Assessment Testing (ImPACT
) visual and verbal memory, Sport Concussion Assessment Tool (SCAT) symptom checklist, and Brief Symptom Inventory-18 (BSI-18), but slower ImPACT reaction time and worse scores on Standardized Assessment of Concussion (SAC). Further, the data indicate that some ImPACT score distributions were noticeably different from those presented in the technical manual.
In this large, racially and socio-economically diverse cohort of male and female college athletes, we found no evidence that student-athletes participating in contact sports have clinically meaningful deficits in pre-season cognitive and balance testing. They also did not report significantly more symptoms of psychological distress when compared with student-athletes in non-contact or limited contact sports. In addition, the data suggest potential limitations when using published ImPACT norms when evaluating injured athletes.
ObjectivesTo examine sex differences in sport-related concussion (SRC) across comparable sports.MethodsProspective cohort of collegiate athletes enrolled between 2014 and 2017 in the Concussion ...Assessment, Research and Education Consortium study.ResultsAmong 1071 concussions (females=615; 57.4%), there was no difference in recovery (median days to full return to play) (females=13.5 (IQR 9.0, 23.1) vs males=11.8 (IQR 8.1, 19.0), p=0.96). In subgroup analyses, female recovery was longer in contact (females=12.7 days (IQR 8.8, 21.4) vs males=11.0 days (IQR 7.9, 16.2), p=0.0021), while male recovery was longer in limited contact sports (males=16.9 days (IQR 9.7, 101.7) vs females=13.8 days (IQR 9.1, 22.0), p<0.0001). There was no overall difference in recovery among Division I schools (females=13.7 (IQR 9.0, 23.1) vs males=12.2 (IQR 8.2 19.7), p=0.5), but females had longer recovery at the Division II/III levels (females=13.0 (IQR 9.2, 22.7) vs males=10.6 (IQR 8.1, 13.9), p=0.0048).ConclusionOverall, no difference in recovery between sexes across comparable women’s and men’s sports in this collegiate cohort was found. However, females in contact and males in limited contact sports experienced longer recovery times, while females had longer recovery times at the Division II/III level. These disparate outcomes indicate that, while intrinsic biological sex differences in concussion recovery may exist, important, modifiable extrinsic factors may play a role in concussion outcomes.
causes the genital ulcer disease chancroid and painful cutaneous ulcers in children who live in the tropics. To acquire heme from the host,
expresses a TonB-dependent hemoglobin receptor, HgbA, which ...is necessary and sufficient for
to progress to the pustular stage of disease in a controlled human infection model. HgbA transports hemoglobin across the outer membrane; how heme is transported across the cytoplasmic membrane is unclear. In previous studies, transcripts encoding the YfeABCD heme transporter were upregulated in experimental lesions caused by
in human volunteers, suggesting the latter may have a role in virulence. Here we constructed a double deletion mutant, 35000HPΔ
Δ
, which exhibited growth defects relative to its parent 35000HP in media containing human hemoglobin as an iron source. Five human volunteers were inoculated at three sites on the skin overlying the deltoid with each strain. The results of the trial showed that papules formed at 100% (95% CI, 71.5, 100) at both 35000HP and 35000HPΔ
Δ
-inoculated sites (
= 1.0). Pustules formed at 60% (95% CI, 25.9, 94.1) at parent-inoculated sites and 53% (95% CI, 18.3, 88.4) at mutant-inoculated sites (
= 0.79). Thus, the ABC transporter encoded by
and
was dispensable for
virulence in humans. In the absence of YfeABCD,
likely utilizes other periplasmic binding proteins and ABC-transporters such as HbpA, SapABCDF, and DppBCDF to shuttle heme from the periplasm into the cytoplasm, underscoring the importance of redundancy of such systems in gram-negative pathogens.
Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase ...survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD50/60) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n = 22) or filgrastim-treated (n = 24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality 20.8% (5/24) compared to the controls 59.1% (13/22). Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome.
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