Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge.

Brown adipose tissue is a thermogenic organ that dissipates chemical energy as heat to protect animals against hypothermia and to counteract metabolic disease. However, the transcriptional mechanisms that determine the thermogenic capacity of brown adipose tissue before environmental cold are unknown. Here we show that histone deacetylase 3 (HDAC3) is required to activate brown adipose tissue enhancers to ensure thermogenic aptitude. Mice with brown adipose tissue-specific genetic ablation of HDAC3 become severely hypothermic and succumb to acute cold exposure. Uncoupling protein 1 (UCP1) is nearly absent in brown adipose tissue lacking HDAC3, and there is also marked downregulation of mitochondrial oxidative phosphorylation genes resulting in diminished mitochondrial respiration. Remarkably, although HDAC3 acts canonically as a transcriptional corepressor, it functions as a coactivator of oestrogen-related receptor α (ERRα) in brown adipose tissue. HDAC3 coactivation of ERRα is mediated by deacetylation of PGC-1α and is required for the transcription of Ucp1, Ppargc1a (encoding PGC-1α), and oxidative phosphorylation genes. Importantly, HDAC3 promotes the basal transcription of these genes independently of adrenergic stimulation. Thus, HDAC3 uniquely primes Ucp1 and the thermogenic transcriptional program to maintain a critical capacity for thermogenesis in brown adipose tissue that can be rapidly engaged upon exposure to dangerously cold temperature.

The projected degradation of subtropical coral assemblages by recurrent thermal stress.

Subtropical coral assemblages are threatened by similar extreme thermal stress events to their tropical counterparts. Yet, the mid- and long-term thermal stress responses of corals in subtropical environments remain largely unquantified, limiting our capacity to predict their future viability. The annual survival, growth and recruitment of 311 individual corals within the Solitary Islands Marine Park (Australia) was recorded over a 3-year period (2016-2018), including the 2015/2016 thermal stress event. These data were used to parameterise integral projection models quantifying the effect of thermal stress within a subtropical coral assemblage. Stochastic simulations were also applied to evaluate the implications of recurrent thermal stress scenarios predicted by four different Representative Concentration Pathways. We report differential shifts in population growth rates (λ) among coral populations during both stress and non-stress periods, confirming contrasting bleaching responses among taxa. However, even during non-stress periods, the observed dynamics for all taxa were unable to maintain current community composition, highlighting the need for external recruitment sources to support the community structure. Across all coral taxa, projected stochastic growth rates (λs ) were found to be lowest under higher emissions scenarios. Correspondingly, predicted increases in recurrent thermal stress regimes may accelerate the loss of coral coverage, species diversity and structural complexity within subtropical regions. We suggest that these trends are primarily due to the susceptibility of subtropical specialists and endemic species, such as Pocillopora aliciae, to thermal stress. Similarly, the viability of many tropical coral populations at higher latitudes is highly dependent on the persistence of up-current tropical systems. As such, the inherent dynamics of subtropical coral populations appear unable to support their future persistence under unprecedented thermal disturbance scenarios.

Unplanned ICU Admission Is Associated With Worse Clinical Outcomes in Geriatric Trauma Patients.

BACKGROUND: Geriatric trauma patients who require an unplanned ICU admission (UIA) may experience worse outcomes. As such, the American College of Surgeons initiated the Trauma Quality Improvement Program which tracks UIA as a quality benchmark. We sought to determine the overall rate and impact of UIA in our geriatric trauma population and to identify predictive risk factors. METHODS: All geriatric trauma patients (≥65) admitted to an urban, level I trauma center from January 2012 to June 2018 were identified. A retrospectively collected administrative database was queried for demographics, comorbidities, injury characteristics, and outcomes. UIA were identified and medical records were queried. Univariate analysis followed by binary logistic regression analysis were performed (P < 0.05 = significant). RESULTS: Of the 2923 geriatric patients identified, 95 (3.3%) patients experienced UIA, most commonly secondary to respiratory (34.7%) and cardiac (22.1%) events. Patients with UIA were older (81 versus 78, P = 0.04), and had higher injury severity score (10 versus 9, P < 0.01) and Charlson comorbidity indices (5 versus 4, P = 0.02). On logistic regression, age (OR 1.027, P = 0.04) and injury severity score (OR 1.032, P < 0.01) were predictive of unplanned ICU admission. Of the UIA, 69.4% were readmissions, or "bounce backs". Patients initially admitted to the ICU had 2.5 increased odds of requiring UIA. Patients with UIA experienced longer hospital stays (15 versus 5, P < 0.01), more days in the ICU (6 versus 1, P < 0.01), and higher rates of mortality (11.6% versus 5.0%, P = 0.02). CONCLUSIONS: Despite relatively low injury severity, geriatric trauma patients requiring UIA have a significant increase in morbidity and mortality. Those initially admitted to the ICU are at especially high risk for UIA, suggesting the benefit of strategies to provide an extra layer of care post-ICU.

Refugia under threat: Mass bleaching of coral assemblages in high-latitude eastern Australia.

Environmental anomalies that trigger adverse physiological responses and mortality are occurring with increasing frequency due to climate change. At species' range peripheries, environmental anomalies are particularly concerning because species often exist at their environmental tolerance limits and may not be able to migrate to escape unfavourable conditions. Here, we investigated the bleaching response and mortality of 14 coral genera across high-latitude eastern Australia during a global heat stress event in 2016. We evaluated whether the severity of assemblage-scale and genus-level bleaching responses was associated with cumulative heat stress and/or local environmental history, including long-term mean temperatures during the hottest month of each year (SSTLTMAX ), and annual fluctuations in water temperature (SSTVAR ) and solar irradiance (PARZVAR ). The most severely-bleached genera included species that were either endemic to the region (Pocillopora aliciae) or rare in the tropics (e.g. Porites heronensis). Pocillopora spp., in particular, showed high rates of immediate mortality. Bleaching severity of Pocillopora was high where SSTLTMAX was low or PARZVAR was high, whereas bleaching severity of Porites was directly associated with cumulative heat stress. While many tropical Acropora species are extremely vulnerable to bleaching, the Acropora species common at high latitudes, such as A. glauca and A. solitaryensis, showed little incidence of bleaching and immediate mortality. Two other regionally-abundant genera, Goniastrea and Turbinaria, were also largely unaffected by the thermal anomaly. The severity of assemblage-scale bleaching responses was poorly explained by the environmental parameters we examined. Instead, the severity of assemblage-scale bleaching was associated with local differences in species abundance and taxon-specific bleaching responses. The marked taxonomic disparity in bleaching severity, coupled with high mortality of high-latitude endemics, point to climate-driven simplification of assemblage structures and progressive homogenisation of reef functions at these high-latitude locations.

Quantifying Disparities in Urban Firearm Violence by Race and Place in Philadelphia, Pennsylvania: A Cartographic Study.

OBJECTIVES: To describe variability in the burden of firearm violence by race, income, and place in an urban context. METHODS: We used Philadelphia Police Department data from 2013 to 2014 to calculate firearm assault rates within census block groups for both victim residence and event locations, stratifying by race and block group income. We used cartographic modeling to determine variations in incidence of firearm assault by race, neighborhood income, and place. RESULTS: The overall rate of firearm assault was 5.0 times higher (95% confidence interval [CI] = 4.5, 5.6) for Black people compared with White people. Firearm assault rates were higher among Black people across all victim residence incomes. Relative risk of firearm assault reached 15.8 times higher (95% CI = 10.7, 23.2) for Black residents in the highest-income block groups when compared with high-income White individuals. Firearm assault events tended to occur in low-income areas and were concentrated in several "hot spot" locations with high proportions of Black residents. CONCLUSIONS: Profound disparity in exposure to firearm violence by race and place exists in Philadelphia. Black people were substantially more likely than White people to sustain firearm assault, regardless of neighborhood income.

Essential role of mitochondrial energy metabolism in Foxp3⁺ T-regulatory cell function and allograft survival.

Conventional T (Tcon) cells and Foxp3(+) T-regulatory (Treg) cells are thought to have differing metabolic requirements, but little is known of mitochondrial functions within these cell populations in vivo. In murine studies, we found that activation of both Tcon and Treg cells led to myocyte enhancer factor 2 (Mef2)-induced expression of genes important to oxidative phosphorylation (OXPHOS). Inhibition of OXPHOS impaired both Tcon and Treg cell function compared to wild-type cells but disproportionally affected Treg cells. Deletion of Pgc1α or Sirt3, which are key regulators of OXPHOS, abrogated Treg-dependent suppressive function and impaired allograft survival. Mef2 is inhibited by histone/protein deacetylase-9 (Hdac9), and Hdac9 deletion increased Treg suppressive function. Hdac9(-/-) Treg showed increased expression of Pgc1α and Sirt3, and improved mitochondrial respiration, compared to wild-type Treg cells. Our data show that key OXPHOS regulators are required for optimal Treg function and Treg-dependent allograft acceptance. These findings provide a novel approach to increase Treg function and give insights into the fundamental mechanisms by which mitochondrial energy metabolism regulates immune cell functions in vivo.

SIRT1 downregulation in pneumonia is associated with an immature neutrophil response and increased disease severity.

BACKGROUND: Pneumonia remains a common complication in trauma patients. Sirtuin 1 (SIRT1) is an anti-inflammatory NAD + -dependent deacetylase that has been shown to reduce the severity of ARDS in polymicrobial sepsis. The impact of SIRT1 in acute pneumonia, however, remains unknown. We hypothesized that SIRT1 deletion in pneumonia would worsen the inflammatory response and clinical severity, and that increased SIRT1 expression would be protective. METHODS: Ten- to 14-week-old male and female SIRT1 knockout (S1KO) mice, SIRT1 overexpressor (S1OE) mice, and their wildtype (WT) littermates underwent intra-tracheal inoculation with Pseudomonas aeruginosa . Rectal temperature was recorded, SIRT1 lung protein was quantified by western blotting, Sirt1 mRNA was measured by qPCR, and lung leukocyte subpopulations were analyzed by flow cytometry. Data were analyzed by one-way ANOVA using Prism software. RESULTS: Pneumonia created a functional SIRT1 knockdown in the lungs of WT mice by 4 hours, resulting in comparable SIRT1 levels and temperatures to the S1KO mice by 12 hours. Pneumonia also partially reduced SIRT1expression in S1OE mice, but S1OE mice still had improved thermoregulation 12 hours after pneumonia. In all groups, Sirt1 mRNA expression was not affected by infection. Sirtuin 1 deletion was associated with decreased neutrophil infiltration in the lung, as well as a shift toward a more immature neutrophil phenotype. SIRT1 deletion was also associated with decreased myeloperoxidase-positive neutrophils in the lungs following pneumonia, indicating decreased neutrophil activity. S1OE mice had no change in lung leukocyte subpopulations when compared to WT. CONCLUSION: Pneumonia creates a functional SIRT1 knockdown in mice. SIRT1 deletion altered the early inflammatory cell response to pneumonia, resulting in a neutrophil response that would be less favorable for bacterial clearance. Despite overexpression of SIRT1, S1OE mice also developed low SIRT1 levels and exhibited only minimal improvement. This suggests increasing SIRT1 transcription is not sufficient to overcome pneumonia-induced downregulation and has implications for future treatment options. Targeting SIRT1 through increasing protein stability may promote a more efficient inflammatory cell response to pneumonia, thereby preventing subsequent lung injury.

Developing a National Trauma Research Action Plan: Results from the regulatory challenges Delphi survey.

BACKGROUND: In 2016, the National Academies of Sciences, Engineering, and Medicine issued a report calling for a National Trauma Research Action Plan (NTRAP) requiring a resourced, coordinated, joint approach to trauma care research. The National Academies of Sciences, Engineering, and Medicine report recommended the identification of regulatory barriers to trauma research. The NTRAP Regulatory Challenges Panel of trauma researchers and regulatory professionals was convened to identify the most challenging aspects of regulatory processes involved in conducting research. METHODS: Trauma researchers and regulatory experts were recruited to identify and rate challenging regulatory issues in 2021 to 2022. Challenge statements were developed from a comprehensive scoping review. Panelists rated the challenge level for each statement on a 9-point Likert scale. The Delphi survey was conducted over three online rounds. Consensus was defined a priori as ≥60% agreement. Results of the Delphi survey were presented to the panel during a webinar. Panel participants then participated in breakout sessions to strategize solutions, share lessons learned, and identify where more regulatory guidance is needed. RESULTS: Thirty-eight subject matter experts rated 175 regulatory challenges, of which 141 (81%) reached the consensus threshold. Of the consensus-reaching challenge statements, 42 had a challenge rating of 6 or higher. Among the highest-rated challenges were issues pertaining to conducting prehospital research, exception from informed consent, mistrust of research among various racial and ethnic groups, and issues specific to conducting pediatric trauma research. CONCLUSION: This Delphi survey rated challenges culled from a regulatory literature scoping review. The panel identified the most challenging aspects of human subjects protection while conducting trauma research and recommended strategies and best practices to address them. The findings from this study were used to develop the NTRAP Investigator Toolkit, which is available on the internet as a resource for trauma researchers. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Altered thyroid function in severely injured patients.

BACKGROUND: Hemorrhagic shock profoundly affects the neuroendocrine profile of trauma patients, and we hypothesized that massive resuscitation would negatively impact thyroid function. METHODS: A prospective, observational study investigating thyroid function in hypotensive trauma patients (systolic blood pressure <90 mm Hg × 2) who survived >48 h was conducted at a Level I center over a 6-mo period. Blood samples for thyroid function were collected at time of presentation to the trauma bay and serially for 48 h. Collected data included demographics, injury data, vital signs, transfusion needs, crystalloid use, and vasopressor requirements. Patients receiving >5 units packed red blood cells (PRBC) within 12 h were compared with those receiving ≤5 units. RESULTS: Patients who required >5 units of PRBC/12 h had significantly lower total and free T4 levels on initial presentation, and levels remained significantly depressed over the next 48 h when compared with patients who required a less aggressive resuscitative effort. T3 values were markedly suppressed during the initial 48 h post trauma in all patients, but were significantly lower in patients requiring >5 units PRBC. TSH levels remained within the normal range for all time points. Lower trauma admission T4 levels were associated with the need for greater crystalloid resuscitation within the first 24 h. CONCLUSION: Measurements of thyroid function are significantly altered in severely injured patients on initial presentation, and low T4 levels predict the need for large resuscitation. Further research investigating the profile and impact of thyroid function in trauma patients during resuscitation and recovery is warranted.

Mineralocorticoid deficiency in hemorrhagic shock.

BACKGROUND: In the critically ill, mineralocorticoid deficiency (MD) is associated with greater disease severity, the development of acute renal insufficiency, and increased mortality. We hypothesized that severely injured trauma patients presenting with hemorrhagic shock would demonstrate a high degree of MD. We also hypothesized that MD in these patients would be associated with increased length of stay, hypotension, fluid requirements, and acute kidney injury (AKI). MATERIALS AND METHODS: Thirty-two trauma patients in hemorrhagic shock on admission to the trauma bay (SBP <90 mm Hg × 2) were enrolled. Blood samples were obtained on ICU admission and 8, 16, 24, and 48 hours later. Plasma aldosterone (PA) and renin (PR) were assayed by radioimmunoassay. MD was defined as a ratio of PA/PR ≤2. Demographic data, injury severity score, ICU and hospital length of stay, fluid requirements, mean arterial pressure, serum sodium, hypotension, and risk for AKI were compared for patients with and without MD. RESULTS: At ICU admission, 48% of patients met criteria for MD. Patients with MD were significantly more likely to experience hypotension (MAP ≤60 mm Hg) during the study period. MD patients required significantly more units of blood in 48 h than non-MD patients (13 [7-22] versus 5 [2-7], P = 0.015) and had increased crystalloid requirements (18L [14-23] versus 9L [6-10], P < 0.001). MD patients were at higher risk for AKI according to RIFLE and AKIN criteria. CONCLUSIONS: MD is a common entity in trauma patients presenting in hemorrhagic shock. Patients with MD required a more aggressive resuscitative effort, were more likely to experience hypotension, and had a higher risk of AKI than non-MD patients. Future studies are needed to fully understand the impact of MD following trauma and the potential role for hormonal replacement therapy.

Penetrating trauma in urban women: patterns of injury and violence.

BACKGROUND: Penetrating trauma is known to occur with less frequency in women than in men, and this difference has resulted in a lack of characterization of penetrating injury patterns involving women. We hypothesized that the nature of penetrating injury differs significantly by gender and that these injuries in women are associated with important psychosocial and environmental factors. MATERIALS AND METHODS: A level 1 urban trauma center registry was queried for all patients with penetrating injuries from 2002-2010. Patient and injury variables (demographics and mechanism of injury) were abstracted and compared between genders; additional social and psychiatric histories and perpetrator information were collected from the records of admitted female patients. RESULTS: Injured women were more likely to be Caucasian, suffer stab wounds instead of gunshot wounds, and present with a higher blood alcohol level than men. Compared with women with gunshot wounds, those with stab wounds were three times more likely to report a psychiatric or intimate partner violence history. Women with self-inflicted injuries had a significantly greater incidence of prior penetrating injury and psychiatric and criminal history. Male perpetrators outnumbered female perpetrators; patients frequently not only knew their perpetrator but also were their intimate partners. Intimate partner violence and random cross-fire incidents each accounted for about a quarter of injuries observed. CONCLUSIONS: Penetrating injuries in women represent a nonnegligible subset of injuries seen in urban trauma centers. Psychiatric and social risk factors for violence play important roles in these cases, particularly when self-infliction is suspected. Resources allocated for urban violence prevention should proportionately reflect the particular patterns of violence observed in injured women.

Practitioner perceptions of trauma video review.

PURPOSE: Multidisciplinary trauma team education through trauma video review (TVR) is a useful performance improvement tool, but video recording resuscitations may cause providers anxiety. We examined perceptions of educational value and anxiety associated with being reviewed in TVR. METHODS: Trauma team members were asked to complete an anonymous online survey. Educational scores (E scores) and anxiety scores (A score) were calculated from survey responses. Respondents were divided into groups by roles: trainees (T; medical students, residents, and fellows), attending surgeons (A), and nurses (N). Kruskal-Wallis test was used for statistical testing. FINDINGS: A total of 39 subjects completed the survey (T = 17, 43%; A = 8, 23%; N = 14, 35%). TVR scored high in educational value (median E score 90; IQR = 78-96) but provoked moderate anxiety (median A score 27; IQR = 20-36). No significant differences in E scores were seen between groups. A scores were not significantly different between groups N and T (20 vs 33; P = .11) or groups T and A (33 vs. 35; P = 1.0) but were significantly higher in group A than in group N (36 vs 20; P = .04). CONCLUSIONS: Despite perceptions of educational value, TVR is associated with anxiety among providers, which is different between groups. Continued assessment of perceptions regarding TVR may allow for modifications to maintain educational value while decreasing anxiety.

Sirt3 Deletion Increases Inflammation and Mortality in Polymicrobial Sepsis.

Background: Sirtuin 3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that confers resilience to cellular stress by promoting mitochondrial activity. Mitochondrial dysfunction is a major driver of inflammation during sepsis. We hypothesize that Sirt3 expression improves survival in polymicrobial sepsis by mitigating the inflammatory response. Materials and Methods: Sirt3 knockout (S3KO) and wild-type (WT) mice underwent cecal ligation and puncture (CLP) or sham surgery. mRNA expression was quantified using quantitative polymerase chain reaction (qPCR) and protein expression was quantified using enzyme-linked immunosorbent assay (ELISA). Spectrophotometric assays were used to quantify serum markers of organ dysfunction. For in vitro studies, bone marrow-derived macrophages (BMDMs) were harvested from S3KO and WT mice and treated with lipopolysaccharide (LPS). Results: After CLP, hepatic Sirt3 levels decreased from baseline by nine hours and remained depressed at 24 hours. Peak serum interleukin-6 (IL-6) protein levels were higher in S3KO mice. In LPS-treated BMDMs, IL-6 mRNA levels peaked earlier in S3KO cells, although peak levels were comparable to WT. Although S3KO mice had decreased median survival after CLP compared with WT, there was no difference in five-day survival or organ dysfunction. Conclusions: Although S3KO mice initially had increased inflammation and mortality, this difference abated with time, and overall survival was comparable between the groups. This pattern is consistent with the timeline of sepsis-induced Sirt3 downregulation in WT mice, and suggests that Sirt3 downregulation occurring in sepsis is at least partially responsible for the initial hyperinflammatory response and subsequent mortality. Our data support upregulation of Sirt3 as a promising therapeutic strategy for further research in sepsis.

Fatal opioid overdoses geospatially cluster with level 1 trauma centers in Ohio.

OBJECTIVE: Ohio is consistently ranked as one of the worst states for opioid overdose deaths. Traumatic injury has been linked to opioid overdose deaths, yet the location of trauma centers has not been explored. We examined whether geospatial clustering occurred between county-level opioid overdose deaths (OODs) and trauma center levels. METHODS: We obtained 2019 county-level data from the Ohio Department of Health for fatal overdoses from prescription opioids. We obtained the total number of opioid doses prescribed in 2019 per county from the Ohio Automated Rx Reporting System and American College of Surgeons designated trauma center locations within Ohio from their website. We used geospatial analysis to assess if clustering occurred between trauma center level and prescription opioid overdose deaths at a county level. RESULTS: There were 42 trauma centers located within 21 counties: 7 counties had level 1, and 14 counties had only level 2/level 3. There was no difference in rates of opioid doses prescribed per 100,000 people between counties with level 1 trauma centers and only level 2/level 3. However, prescription OODs rates were significantly higher in counties with level 1 trauma centers (37.6 vs 20, P = .02). Geospatial clustering was observed between level 1 trauma centers and prescription opioid overdose deaths at the county level (P < .01). CONCLUSION: Geospatial clustering exists between prescription OODs and level 1 trauma center locations in Ohio. Improved at-risk patient identification and targeted community outreach represent opportunities for trauma providers to tackle the opioid epidemic.

Regulatory challenges in conducting human subjects research in emergency settings: the National Trauma Research Action Plan (NTRAP) scoping review.

The complexity of the care environment, the emergent nature, and the severity of patient injury make conducting clinical trauma research challenging. These challenges hamper the ability to investigate potentially life-saving research that aims to deliver pharmacotherapeutics, test medical devices, and develop technologies that may improve patient survival and recovery. Regulations intended to protect research subjects impede scientific advancements needed to treat the critically ill and injured and balancing these regulatory priorities is challenging in the acute setting. This scoping review attempted to systematically identify what regulations are challenging in conducting trauma and emergency research. A systematic search of PubMed was performed to identify studies published between 2007 and 2020, from which 289 articles that address regulatory challenges in conducting research in emergency settings were included. Data were extracted and summarized using descriptive statistics and a narrative synthesis of the results. The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Most articles identified were editorial/commentary (31%) and published in the USA (49%). Regulatory factors addressed in the papers were categorized under 15 regulatory challenge areas: informed consent (78%), research ethics (65%), institutional review board (55%), human subjects protection (54%), enrollment (53%), exception from informed consent (51%), legally authorized representative (50%), patient safety (41%), community consultation (40%), waiver of informed consent (40%), recruitment challenges (39%), patient perception (30%), liability (15%), participant incentives (13%), and common rule (11%). We identified several regulatory barriers to conducting trauma and emergency research. This summary will support the development of best practices for investigators and funding agencies.

Coral assemblages at higher latitudes favor short-term potential over long-term performance.

The persistent exposure of coral assemblages to more variable abiotic regimes is assumed to augment their resilience to future climatic variability. Yet, while the determinants of coral population resilience across species remain unknown, we are unable to predict the winners and losers across reef ecosystems exposed to increasingly variable conditions. Using annual surveys of 3171 coral individuals across Australia and Japan (2016-2019), we explore spatial variation across the short- and long-term dynamics of competitive, stress-tolerant, and weedy assemblages to evaluate how abiotic variability mediates the structural composition of coral assemblages. We illustrate how, by promoting short-term potential over long-term performance, coral assemblages can reduce their vulnerability to stochastic environments. However, compared to stress-tolerant, and weedy assemblages, competitive coral taxa display a reduced capacity for elevating their short-term potential. Accordingly, future climatic shifts threaten the structural complexity of coral assemblages in variable environments, emulating the degradation expected across global tropical reefs.

Mutualism with sea anemones triggered the adaptive radiation of clownfishes.

BACKGROUND: Adaptive radiation is the process by which a single ancestral species diversifies into many descendants adapted to exploit a wide range of habitats. The appearance of ecological opportunities, or the colonisation or adaptation to novel ecological resources, has been documented to promote adaptive radiation in many classic examples. Mutualistic interactions allow species to access resources untapped by competitors, but evidence shows that the effect of mutualism on species diversification can greatly vary among mutualistic systems. Here, we test whether the development of obligate mutualism with sea anemones allowed the clownfishes to radiate adaptively across the Indian and western Pacific oceans reef habitats. RESULTS: We show that clownfishes morphological characters are linked with ecological niches associated with the sea anemones. This pattern is consistent with the ecological speciation hypothesis. Furthermore, the clownfishes show an increase in the rate of species diversification as well as rate of morphological evolution compared to their closest relatives without anemone mutualistic associations. CONCLUSIONS: The effect of mutualism on species diversification has only been studied in a limited number of groups. We present a case of adaptive radiation where mutualistic interaction is the likely key innovation, providing new insights into the mechanisms involved in the buildup of biodiversity. Due to a lack of barriers to dispersal, ecological speciation is rare in marine environments. Particular life-history characteristics of clownfishes likely reinforced reproductive isolation between populations, allowing rapid species diversification.

Hyperbaric oxygen therapy in necrotizing soft tissue infections.

BACKGROUND: Surgical debridement and antibiotics are the mainstays of therapy for patients with necrotizing soft tissue infections (NSTIs), but hyperbaric oxygen therapy (HBO) is often used as an adjunctive measure. Despite this, the efficacy of HBO remains unclear. We hypothesized that HBO would have no effect on mortality or amputation rates. METHODS: We performed a retrospective analysis of our institutional experience from 2005 to 2009. Inclusion criteria were age > 18 y and discharge diagnosis of NSTI. We abstracted baseline demographics, physiology, laboratory values, and operative course from the medical record. The primary endpoint was in-hospital mortality; the secondary endpoint was extremity amputation rate. We compared baseline variables using Mann-Whitney, chi-square, and Fisher's exact test, as appropriate. Significance was set at P < 0.05. RESULTS: We identified 80 cases over the study period. The cohort was 54% male (n = 43) and 53% white (n = 43), and had a mean age of 55 ± 16 y. There were no significant differences in demographics, physiology, or comorbidities between groups. In-hospital mortality was not different between groups (16% in the HBO group versus 19% in the non-HBO group; P = 0.77). In patients with extremity NSTI, the amputation rate did not differ significantly between patients who did not receive HBO and those who did (17% versus 25%; P = 0.46). CONCLUSIONS: Hyperbaric oxygen therapy does not appear to decrease in-hospital mortality or amputation rate after in patients with NSTI. There may be a role for HBO in treatment of NSTI; nevertheless, consideration of HBO should never delay operative therapy. Further evidence of efficacy is necessary before HBO can be considered the standard of care in NSTI.

Risk Factors for Unplanned ICU Readmission Among Trauma Patients: Age Matters.

To determine the frequency of unplanned ICU readmission (UIR) among adult (18-64) and elderly (65+) trauma patients and to compare the risk factors for UIR and its clinical impact between age groups. DESIGN: Retrospective cohort study using clinical data from a statewide trauma registry. SETTING: All accredited trauma centers in Pennsylvania. PATIENTS: Consecutive adult and elderly trauma patients requiring admission from the emergency department to the ICU between 2012 and 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 48,340 included in the analysis, 49.5% were elderly and 3.8% experienced UIR. UIR was 1.7 times more likely among elderly patients and was associated with increased hospital length of stay in both age groups. UIR was associated with an absolute increased risk of hospital mortality of 6.1% among adult patients and 16.9% among elderly patients experiencing UIR. In addition to overall injury severity and burden of preexisting medical conditions, specific risk factors for UIR were identified in each age group. In adult but not elderly patients, UIR was significantly associated with history of stroke, peptic ulcer disease, cirrhosis, diabetes, and malignancy. In elderly but not adult patients, UIR was also significantly associated with chronic kidney disease. CONCLUSIONS: UIR is associated with worse clinical outcomes in both adult and elderly trauma patients, but risk factors and the magnitude of impact differ between age groups. Interventions to mitigate the risk of UIR that take into account patients' age group and specific risk factors may improve outcomes.