Orbital period change of Dimorphos due to the DART kinetic impact.

The Double Asteroid Redirection Test (DART) spacecraft successfully performed the first test of a kinetic impactor for asteroid deflection by impacting Dimorphos, the secondary of near-Earth binary asteroid (65803) Didymos, and changing the orbital period of Dimorphos. A change in orbital period of approximately 7 min was expected if the incident momentum from the DART spacecraft was directly transferred to the asteroid target in a perfectly inelastic collision1, but studies of the probable impact conditions and asteroid properties indicated that a considerable momentum enhancement (ß) was possible2,3. In the years before impact, we used lightcurve observations to accurately determine the pre-impact orbit parameters of Dimorphos with respect to Didymos4-6. Here we report the change in the orbital period of Dimorphos as a result of the DART kinetic impact to be -33.0 ± 1.0 (3σ) min. Using new Earth-based lightcurve and radar observations, two independent approaches determined identical values for the change in the orbital period. This large orbit period change suggests that ejecta contributed a substantial amount of momentum to the asteroid beyond what the DART spacecraft carried.

Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 ± 0.10 mm s-1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m-3, we find that the expected value of the momentum enhancement factor, ß, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m-3, [Formula: see text]. These ß values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

Catastrophic Health Care Expenditure Following Brachial Plexus Injury.

PURPOSE: Brachial plexus injuries (BPIs) are devastating to patients not only functionally but also financially. Like patients experiencing other traumatic injuries and unexpected medical events, patients with BPIs are at risk of catastrophic health expenditure (CHE) in which out-of-pocket health spending exceeds 40% of postsubsistence income (income remaining after food and housing expenses). The individual financial strain after BPIs has not been previously quantified. The purpose of this study was to assess the proportion of patients with BPIs who experience risk of CHE after reconstructive surgery. METHODS: Administrative databases were used from 8 states to identify patients who underwent surgery for BPIs. Demographics including age, sex, race, and insurance payer type were obtained. Inpatient billing records were used to determine the total surgical and inpatient facility costs within 90 days after the initial surgery. Due to data constraints, further analysis was only conducted for privately-insured patients. The proportion of patients with BPIs at risk of CHE was recorded. Predictors of CHE risk were determined from a multivariable regression analysis. RESULTS: Among 681 privately-insured patients undergoing surgery for BPIs, nearly one-third (216 [32%]) were at risk of CHE. Black race and patients aged between 25 and 39 years were significant risk factors associated with CHE. Sex and the number of comorbidities were not associated with risk of CHE. CONCLUSIONS: Nearly one-third of privately-insured patients met the threshold for being at risk of CHE after BPI surgery. CLINICAL RELEVANCE: Identifying those patients at risk of CHE can inform strategies to minimize long-term financial distress after BPIs, including detailed counseling regarding anticipated health care expenditures and efforts to optimize access to appropriate insurance policies for patients with BPIs.

Altered synaptic glutamate homeostasis contributes to cognitive decline in young APP/PSEN1 mice.

Non-convulsive epileptiform activity is a common and under-studied comorbidity of Alzheimer's disease that may significantly contribute to onset of clinical symptoms independently of other neuropathological features such as ß-amyloid deposition. We used repeated treatment with low dose kainic acid (KA) to trigger sub-threshold epileptiform activity in young (less than 6 months) wild-type (WT) and APP/PSEN1 mice to test the role of disruption to the glutamatergic system in epileptiform activity changes and the development of memory deficits. Short-term repeated low-dose KA (five daily treatments with 5 mg/kg, IP) impaired long-term potentiation in hippocampus of APP/PSEN1 but not WT mice. Long-term repeated low-dose KA (fourteen weeks of bi-weekly treatment with 7.5-10 mg/kg) led to high mortality in APP/PSEN1 mice. KA treatment also impaired memory retention in the APP/PSEN1 mice in a Morris water maze task under cognitively challenging reversal learning conditions where the platform was moved to a new location. Four weeks of bi-weekly treatment with 5 mg/kg KA also increased abnormal spike activity in APP/PSEN1 and not WT mice but did not impact sleep/wake behavioral states. These findings suggest that hyperexcitability in Alzheimer's disease may indeed be an early contributor to cognitive decline that is independent of heavy ß-amyloid-plaque load, which is absent in APP/PSEN1 mice under 6 months of age.

The management of clenched fist injuries with local anaesthesia and field sterility.

Clenched fist injury is associated with a high risk of infectious complications and is commonly managed with formal irrigation and debridement in the operating theatre. The purpose of this study was to determine outcomes associated with irrigation and debridement of clenched fist injuries under local anaesthesia using field sterility outside the operative theatre. In this single centre study, 232 patients were identified with clenched fist injury and 210 were treated with a standard protocol beginning with administration of intravenous antibiotics and then irrigation and debridement at the bedside. Primary outcome measures were the need for repeat debridement and complications. Secondary outcome measures included factors associated with the need for repeat debridement. Fifteen of the 210 patients (7%) required repeat debridement. Patients with cultures positive for gram-negative organisms had a significantly increased risk of repeat debridement. Irrigation and debridement under local anaesthesia using field sterility results in an acceptably low risk of complications or need for repeat debridement.Level of evidence: IV.

Proximal Row Carpectomy Versus 4-Corner Fusion: Incidence, Conversion to Fusion, and Cost.

PURPOSE: The primary objective of this study was to compare incidence, demographic trends, and rates of subsequent fusion between proximal row carpectomy (PRC) and 4-corner fusion (4CF) among patients in the United States. METHODS: A total of 3,636 patients who underwent PRC and 5,047 who underwent 4CF were identified from the years 2005 through 2014 among enrollees in the PearlDiver database. Regional distribution, demographic characteristics, annual incidence, comorbidities, and subsequent wrist fusion were compared between the 2 groups. Of the patients identified, 3,512 from each group were age- and sex-matched and subsequently compared for rates of converted fusion, 30- and 90-day readmission rates, and average direct cost. RESULTS: Patients undergoing 4CF and PRC did not have statistically significant differences in comorbidities. The incidence of the procedures among all subscribers increased for both PRC (1.8 per 10,000 to 2.6 per 10,000) and 4CF (1.2 per 10,000 to 2.0 per 10,000) from 2005 to 2014. Comparing the matched cohorts, patients who underwent 4CF had a higher rate of subsequent fusion than those who underwent PRC (2.67% vs 1.79%). Readmission rates were not significantly different at 30 or 90 days. Average direct cost was significantly greater for 4CF than for PRC. CONCLUSIONS: Both PRC and 4CF have been utilized at increasing rates in the past decade. Wrist fusion rates and average costs are higher in the 4CF group without a significant difference in readmission rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Effects of Far-Infrared Emitting Ceramic Materials on Recovery During 2-Week Preseason of Elite Futsal Players.

Nunes, RFH, Cidral-Filho, FJ, Flores, LJF, Nakamura, FY, Rodriguez, HFM, Bobinski, F, De Sousa, A, Petronilho, F, Danielski, LG, Martins, MM, Martins, DF, and Guglielmo, LGA. Effects of far-infrared emitting ceramic materials on recovery during 2-week preseason of elite futsal players. J Strength Cond Res 34(1): 235-248, 2020-We investigated the effects of far-infrared emitting ceramic materials (cFIR) during overnight sleep on neuromuscular, biochemical and perceptual markers in futsal players. Twenty athletes performed a 2-week preseason training program and during sleep wore bioceramic (BIO; n = 10) or placebo pants (PL; n = 10). Performance (countermovement jump [CMJ]; squat jump [SJ]; sprints 5, 10, and 15-m) and biochemical markers (tumor necrosis factor alpha-TNF-α, interleukin 10-IL-10, thiobarbituric acid-reactive species [TBARS], carbonyl, superoxide dismutase [SOD], catalase [CAT]) were obtained at baseline and after the 1st and 2nd week of training. Delayed-onset muscle soreness (DOMS) and training strain were monitored throughout. Changes in ΔCMJ and ΔSJ were possibly (60/36/4 [week-1]) and likely (76/22/2 [week-2]) higher in BIO. Both groups were faster in 5-m sprint in week 2 compared with baseline (p = 0.015), furthermore, BIO was likely faster in 10-m sprint (3/25/72 [week 1]). Significant group × time interaction in %ΔTNF-α were observed (p = 0.024 [week-1]; p = 0.021 [week-2]) with values possibly (53/44/3 [week 1]) and likely (80/19/1 [week 2]) higher in BIO. The %ΔIL-10 decreased across weeks compared with baseline (p = 0.019 [week-1]; p = 0.026 [week-2]), showing values likely higher in BIO (81/16/3 [week-1]; 80/17/3 [week-2]). Significant weekly increases in %ΔTBARS (p = 0.001 [week-1]; p = 0.011 [week-2]) and %ΔCarbonyl (p = 0.002 [week-1]; p < 0.001 [week-2]) were observed compared with baseline, showing likely (91/5/4 [week-1]) and possibly (68/30/2 [week-2]) higher changes in BIO. Significant weekly decreases in %ΔSOD were observed compared with baseline (p = 0.046 [week 1]; p = 0.011 [week-2]), and between week 2 and week 1 (p = 0.021), in addition to significant decreases in %ΔCAT compared with baseline (p = 0.070 [week 1]; p = 0.012 [week 2]). Training strain (p = 0.021; very -likely [0/2/98]; week 1) and DOMS was lower in BIO (likely; 7 sessions) with differences over time (p = 0.001). The results suggest that the daily use of cFIR clothing could facilitate recovery, especially on perceptual markers during the early phases of an intensive training period.

Epidemiological and Treatment Trends of Distal Radius Fractures across Multiple Age Groups.

Background The purpose of this study is to assess the epidemiology, population-specific treatment trends, and complications of distal radius fractures in the United States. Methods The PearlDiver database (Humana [2007-2014], Medicare [2005-2014]) was used to access US inpatient and outpatient data for all patients who had undergone operative and nonoperative treatment for a distal radius fracture in the United States. Epidemiologic analysis was performed followed by age-based stratification, to assess prevalence, treatment trends, and rates of complications. Results A total of 1,124,060 distal radius treatment claims were captured. The incidence of distal radius fractures follows a bimodal distribution with distinct peaks in the pediatric and elderly population. Fractures in the pediatric population occurred predominately in males, whereas fractures in the elderly population occurred more frequently in females. The most commonly used modality of treatment was nonoperative; however, the use of internal fixation increased significantly during the study period, from 8.75 to 20.02%, with a corresponding decrease in percutaneous fixation. The overall complication rate was 8.3%, with mechanical symptoms most frequently reported. Conclusions The last decade has seen a significant increase in the use of internal fixation as treatment modality for distal radius fractures. The impetus for this change is likely multifactorial and partly related to recent innovations including volar locking plates and an increasingly active elderly population. The implicated financial cost must be weighed against the productivity cost of maintaining independent living to determine the true burden to the healthcare system.

Are Low Patient Satisfaction Scores Always Due to the Provider?: Determinants of Patient Satisfaction Scores During Spine Clinic Visits.

STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to investigate the impact of various components on patient satisfaction scores SUMMARY OF BACKGROUND DATA.: Patient satisfaction has become an important component of quality assessments. However, with many of these sources collecting satisfaction data reluctant to disclose detailed information, little remains known about the potential determinants of patient satisfaction. METHODS: Two hundred patients were contacted via phone within 3 weeks of new patient encounter with 11 spine providers. Standardized patient satisfaction phone survey consisting of 25 questions (1-10 rating scale) was administered. Questions inquired about scheduling, parking, office staff, teamwork, wait-time, radiology, provider interactions/behavior, treatment, and follow-up communication. Potential associations between these factors and three main outcome measures were investigated: (1) provider satisfaction, (2) overall clinic visit satisfaction, and (3) quality of care. RESULTS: Significant associations (P < 0.0001) with provider satisfaction, overall clinic visit satisfaction, and perceived overall quality of care were found with appointment scheduling, parking, office staff, teamwork, wait time, radiology, provider interactions/behavior, treatment, and follow-up communication. Nurse-practitioner/resident involvement was positively associated with scores (P ≤ 0.03). A "candy-man" effect was not noted, as pain medication prescribing did not play a significant role in satisfaction (P > 0.05).In multivariate regression analysis, explanation of medical condition/treatment (P = 0.002) and provider empathy (P = 0.04) were significantly associated with provider satisfaction scores, while the amount of time spent with the provider was not. Conversely, teamwork of staff/provider and follow-up communication were significantly associated with both overall clinic visit satisfaction and quality of care (P ≤ 0.03), while provider behaviors or satisfaction were not. CONCLUSION: Satisfaction with the provider was associated with better explanations of the spine condition/treatment plan and provider empathy, but was not a significant factor in either overall clinic visit satisfaction or perceived quality of care. Patients' perception of teamwork between staff and providers along with reliable follow-up communication were found to be significant determinants of overall patient satisfaction and perceived quality of care. LEVEL OF EVIDENCE: 3.

Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.

With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counterpart of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).

Illuminating gravitational waves: A concordant picture of photons from a neutron star merger.

Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.

Ejection of the Massive Hydrogen-rich Envelope Timed with the Collapse of the Stripped SN 2014C.

We present multi-wavelength observations of SN 2014C during the first 500 days. These observations represent the first solid detection of a young extragalactic stripped-envelope SN out to high-energy X-rays ~40 keV. SN 2014C shows ordinary explosion parameters (Ek ~ 1.8 × 1051 erg and Mej ~ 1.7 M⊙). However, over an ~1 year timescale, SN 2014C evolved from an ordinary hydrogen-poor supernova into a strongly interacting, hydrogen-rich supernova, violating the traditional classification scheme of type-I versus type-II SNe. Signatures of the SN shock interaction with a dense medium are observed across the spectrum, from radio to hard X-rays, and revealed the presence of a massive shell of ~1 M⊙of hydrogen-rich material at ~6 × 1016 cm. The shell was ejected by the progenitor star in the decades to centuries before collapse. This result challenges current theories of massive star evolution, as it requires a physical mechanism responsible for the ejection of the deepest hydrogen layer of H-poor SN progenitors synchronized with the onset of stellar collapse. Theoretical investigations point at binary interactions and/or instabilities during the last nuclear burning stages as potential triggers of the highly time-dependent mass loss. We constrain these scenarios utilizing the sample of 183 SNe Ib/c with public radio observations. Our analysis identifies SN 2014C-like signatures in ~10% of SNe. This fraction is reasonably consistent with the expectation from the theory of recent envelope ejection due to binary evolution if the ejected material can survive in the close environment for 103-104 years. Alternatively, nuclear burning instabilities extending to core C-burning might play a critical role.

Impact of Discharge Disposition on 30-Day Readmissions Following Elective Spine Surgery.

BACKGROUND: Readmissions are a significant economic burden on the health care system and increasingly being utilized as a metric of quality. Patients discharged to home vs an inpatient facility have different characteristics, which might influence the readmissions following spine surgery. OBJECTIVE: To determine the effect of discharge disposition on readmission rates and causes of readmission after spine surgery. METHODS: Patients enrolled in a prospective registry and undergoing elective spine surgery were analyzed. Readmissions (30 d), demographic, clinical variables, and baseline patient-reported outcomes were recorded. Patients were dichotomized as discharged home vs inpatient facility. RESULTS: Of total 1631 patients, 1444 (89%) patients were discharged home and 187 (11%) discharged to an inpatient facility. Sixty-five (4%) patients were readmitted at 30 d. There was no significant difference in readmissions between patients discharged to a facility 10 (5%) vs home 55 (4%; P = .210). In a multivariable analysis, adjusting for all the comorbidities, the discharge destination was not associated with readmission within 30 d. The medical complications (80%) were the most common cause of readmission in those discharged to a facility. Patients discharged home had significantly higher readmissions related to surgical wound issues (67%; P = .034). CONCLUSION: Despite the older age and higher comorbidities in patients discharged to an inpatient facility, the proportion of readmissions was comparable to those discharged home. Patients discharged home had a higher proportion of readmissions related to surgical wound complications and those discharged to facility had higher readmissions associated with medical complications. Understanding causes of readmission based on discharge destination may allow targeted intervention to reduce the readmission rates following spine surgery.

Oxidative stress, serotonergic changes and decreased ultrasonic vocalizations in a mouse model of Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz syndrome is an inherited monogenic disorder in which mutations to the 7-dehydrocholesterol (7-DHC) reductase (Dhcr7) gene lead to deficits in cholesterol synthesis. As a result, many patients suffer from gross physiological and neurological deficits. The purpose of this study was to identify a potential abnormal behavioral phenotype in a compound mutant mouse model for Smith-Lemli-Opitz disease (Dhcr7 Δ3-5/T93M ) to further validate the model and to provide potential targets for future therapeutic interventions. We also sought to identify some of the underlying changes in brain function that may be responsible for behavioral differences among groups. The Dhcr7 compound mutant mice were smaller than their single mutant littermates. Both single and compound heterozygous mice made fewer ultrasonic vocalizations when separated from the dam, which may suggest a communication deficit in these animals. Striking increases of the highly oxidizable 7-DHC were observed in the compound mutant mice. 7-Dehydrocholesterol is the precursor to cholesterol and builds up because of decreased function of the mutated Dhcr7 enzyme. Additionally, several differences were noted in the serotonergic system including increased expression of the serotonin transporter and increased uptake of serotonin by isolated synaptosomes. We propose that changes to the oxidative environment during development can have a significant impact on the development of serotonergic function and that this contributes to behavioral differences observed in the mutant mice.

Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform.

We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms. A number of shared differentially expressed genes and pathways between subAR and cAR in both platforms strongly suggest that these two clinical phenotypes form a continuum of alloimmune activation. SubAR is associated with fewer or less expressed genes than cAR in blood, whereas in biopsy tissues, this clinical phenotype demonstrates a more robust molecular signature for both platforms. The discovery work done in this study confirms a clear ability to detect gene expression profiles for sTx, subAR, and cAR in both blood and biopsy tissue, yielding equivalent predictive performance that is agnostic to both technology and platform. Our data also provide strong biological insights into the molecular mechanisms underlying these signatures, underscoring their logistical potential as molecular diagnostics to improve clinical outcomes following kidney transplantation.

Impact of old age on patient-report outcomes and cost utility for anterior cervical discectomy and fusion surgery for degenerative spine disease.

PURPOSE: With growing older population and increasing rates of cervical spinal surgery, it is vital to understand the value of cervical surgery in this population. We set forth to determine the cost utility following anterior cervical decompression and fusion (ACDF) for degenerative disease in older patients. METHODS: Patients undergoing ACDF for degenerative diseases were enrolled into prospective longitudinal registry. Patient-reported outcomes (PROs) were recorded at baseline, 1-year, and 2-year postoperatively. Two-year medical resource utilization, missed work, and health-state values [quality-adjusted life years (QALYs)] were assessed to compute cost per QALY gained. Patients were dichotomized based on age: <65 years (younger) and ≥65 years (older) to compare the cost utility in these age groups. RESULTS: Total 218 (87%) younger patients and 33 (13%) older patients who underwent ACDF were analyzed. Both the groups demonstrated a significant improvement in PROs 2-year following surgery. The older patients had a lower mean cumulative gain in QALYs compared to younger patients at 1 year (0.141 vs. 0.28, P = 0.05) and 2 years (0.211 vs. 0.424, P = 0.04). There was no significant difference in the mean total 2-year cost between older [$21,041 (95% CI $18,466-$23,616)] and younger [$22,669 (95% CI $$21,259-$24,079)] patients (P = 0.27). Two-year cost per QALY gained in older vs. younger patients was ($99,720/QALYs gained vs. ($53,464/QALYs gained, P = 0.68). CONCLUSION: ACDF surgery provided a significant gain in health-state utility in older patients with degenerative cervical pathology, with a mean cumulative 2-year cost per QALY gained of $99,720/QALY. While older patients have a slightly higher cost utility compared to their younger counterparts, surgery in the older cohort does provide a significant improvement in pain, disability, and quality-of-life outcomes.

Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies.

An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We hypothesized that developing IFTA correlates with altered urinary tract microbiomes (UMBs). UMBs at two serial time points, 1 and 6-8 months posttransplant, were assessed by 16S microbial ribosomal gene sequencing in 25 patients developing biopsy-proven IFTA compared to 23 transplant patients with normal biopsies and excellent function (TX) and 20 healthy nontransplant controls (HC). Streptococcus, the dominant genera in HC males, was lower in IFTA and TX males at 1 month compared to HCs. At 6-8 months, Streptococcus was further decreased in IFTA males, but normalized in TX. IFTA males and females had increases in number of genera per sample at 6-8 months. UMB composition varied substantially between individuals in all groups. Despite the wide variation in UMBs between individuals, IFTA was associated with a loss in dominant resident urinary microbes in males, and a parallel increase in nonresident, pathogenic bacteria in males and females. UMB changes may contribute to IFTA development by alteration of the host immune response.

The fitness burden imposed by synthesising quorum sensing signals.

It is now well established that bacterial populations utilize cell-to-cell signaling (quorum-sensing, QS) to control the production of public goods and other co-operative behaviours. Evolutionary theory predicts that both the cost of signal production and the response to signals should incur fitness costs for producing cells. Although costs imposed by the downstream consequences of QS have been shown, the cost of QS signal molecule (QSSM) production and its impact on fitness has not been examined. We measured the fitness cost to cells of synthesising QSSMs by quantifying metabolite levels in the presence of QSSM synthases. We found that: (i) bacteria making certain QSSMs have a growth defect that exerts an evolutionary cost, (ii) production of QSSMs negatively correlates with intracellular concentrations of QSSM precursors, (iii) the production of heterologous QSSMs negatively impacts the production of a native QSSM that shares common substrates, and (iv) supplementation with exogenously added metabolites partially rescued growth defects imposed by QSSM synthesis. These data identify the sources of the fitness costs incurred by QSSM producer cells, and indicate that there may be metabolic trade-offs associated with QS signaling that could exert selection on how signaling evolves.