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The gut microbiome consists of the trillions of bacteria, fungi, and viruses that inhabit the digestive tract. These communities are sensitive to disruption from environmental exposures ranging from diet changes to illness. Disruption of the community of lactic acid producing bacteria,Lactobaccillacea, has been well documented in mood disorders and stress exposure. In fact, oral supplement with manyLactobacillusspecies can ameliorate these effects, preventing depression- and anxiety-like behavior. Here, for the first time, we utilize a gnotobiotic mouse colonized with the Altered Schaedler Flora to remove the two native species ofLactobaccillacea. Using this novel microbial community, we found that theLactobacillusspecies themselves, and not the disrupted microbial communities are protective from environmental stressors. Further, we determine thatLactobaccillaceaare maintaining homeostatic IFNγ levels which are mediating these behavioral and circuit level responses. By utilizing the Altered Schaedler Flora, we have gained new insight into how probiotics influence behavior and give novel methods to study potential therapies developed to treat mood disorders.

Background Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown. Methods From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test. Results The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P P = 0.36). Conclusions In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline. Trial registration ClinicalTrials.gov number: NCT02444988. Date registered: May 15, 2015.

Objective Linezolid and vancomycin-resistant Enterococcus faecium (LRVREF) is globally emerging as a urinary nosocomial pathogen. A decrease in the amount of successful treatment options has created a necessity for the development of novel antimicrobial therapies. Combination therapy may provide an effective alternative for treatment. Fosfomycin and doxycyclin are currently used individually for the treatment of urinary tract infections. Fosfomycin has recently seen increased use because of its persistent activity against a large spectrum of multidrug-resistant organisms. The purpose of this study was to investigate the interaction of fosfomycin plus doxycyclin against LRVREF isolates. Methods MICs for fosfomycin and doxycyclin were determined for 24 unique clinical LRVREF isolates (4%, fosfomycin-susceptible; 92%, doxycyclin-susceptible). In vitro synergy testing with the combination of fosfomycin and doxycyclin was performed using an Etest method and time-kill assay. Results The combination of fosfomycin and doxycyclin demonstrated synergy with the Etest method in 11/24 (46%) isolates and in 10/24 (42%) isolates by the time-kill assay. Results from the Etest method and time-kill assay were in agreement for 7/24 (29.2%) of isolates. No antagonism was found. Conclusions The combination of fosfomycin and doxycyclin should be evaluated further with additional LRVREF isolates. In vivo studies should also be performed before use in clinical situations.

Background Spousal bereavement can lead to adverse health outcomes; however, not all widow(er)s experience the same degree of health problems. Thus, it is important to understand the contribution of disparities (e.g., childhood maltreatment and subjective social status) that may underlie adverse health outcomes that arise following bereavement. Methods We collected data from 130 spousally bereaved individuals at 3-time points (3 months post-loss, 4 months post-loss, and 6 months post-loss). Using mixed models, we assessed the interaction of childhood maltreatment, subjective social status, and time to predict changes in proinflammatory cytokine production, depressive symptoms, grief symptoms. Results We found a significant interaction between childhood maltreatment, subjective social status, and time predicting proinflammatory cytokine production (beta > -0.01, p = 0.048), depressive symptoms (beta = 0.008, p =.010), and grief symptoms (beta = 0.001 p =.001). Conclusion This study highlights the role of disparities related to childhood maltreatment and subjective social status on adverse health outcomes following spousal bereavement.

Terrestrial carnivores are among the most imperiled species worldwide, yet some species are resilient and are recovering in human-dominated landscapes after decades or centuries of absence. Bobcat (Lynx rufus) populations were extirpated from much of Midwestern US in the mid-1800’s, and are currently expanding and recolonizing their former range. In this study, we investigated multi-scale habitat selection for Ohio’s expanding bobcat population, and examined habitat connectivity in order to evaluate the conduits for dispersal statewide. We used citizen observations collected between 1978 and 2019 and logistic regression to evaluate population-level habitat selection, and GPS telemetry data for 20 individuals collected between 2012 and 2014 and a distribution-weighted exponential Resource Selection Function to evaluate individual-level habitat selection within home ranges. At the population level, bobcats selected for higher amounts of forest and pasture (at a 50 km2 scale) and herbaceous vegetation (at 15–50 50 km2 scales), thus overall heterogeneous forested habitat. At individual (home range) level, bobcats selected for forested habitats with low road density and farther away from high traffic roads; they also showed weak selection for open habitat at the home range level. Male home ranges were significantly greater than female home ranges. Lastly, we used the population-level spatial outputs (i.e. habitat suitability map) to parameterize habitat connectivity models using circuit theory in the program Circuitscape. We tested three relationships between habitat suitability and resistance to movement and used a subset of data on potential dispersing individuals to evaluate which relationship performed best. All three relationships performed almost equally well, and we calculated a weighted averaged connectivity map as our final map. Habitat was highly permeable to movements between core areas of two genetically distinct subpopulations located in southeastern Ohio. We also identified potential dispersal corridors from the core areas to other regions of Ohio dominated by agriculture and suburban development via forested riparian corridors. Overall, our analysis offers new information on habitat selection and connectivity in a rebounding felid population and offers important ecological information for wildlife management strategies. We recommend that the suitability and connectivity models should be periodically updated until the population reaches an equilibrium, and be integrated with data from neighboring states for a comprehensive assessment of a conservation success story.

Childhood adversity is associated with a host of mental and physical health problems across the lifespan. Individuals who have experienced childhood adversity (e.g., child abuse and neglect, family conflict, poor parent/child relationships, low socioeconomic status or extreme poverty) are at a greater risk for morbidity and premature mortality than those not exposed to childhood adversity. Several mechanisms likely contribute to the relationship between childhood adversity and health across the lifespan (e.g., health behaviors, cardiovascular reactivity). In this paper, we review a large body of research within the field of psychoneuroimmunology, demonstrating the relationship between early life stress and alterations of the immune system. We first review the literature demonstrating that childhood adversity is associated with immune dysregulation across different indices, including proinflammatory cytokine production (and its impact on telomere length), illness and infection susceptibility, latent herpesvirus reactivation, and immune response to a tumor. We then summarize the growing literature on how childhood adversity may alter epigenetic processes. Finally, we propose future directions related to this work that have basic and applied implications.

The microbial communities that live in symbiosis with the mucosal surfaces of animals provide the host with defense strategies against pathogens. These microbial communities are largely shaped by the environment and the host genetics. Triploid Atlantic salmon (Salmo salar) are being considered for aquaculture as they are reproductively sterile and thus cannot contaminate the natural gene pool. It has not been previously investigated how the microbiome of triploid salmon compares to that of their diploid counterparts. In this study, we compare the steady-state skin and gill microbiome of both diploid and triploid salmon, and determine the effects of salmonid alphavirus 3 experimental infection on their microbial composition. Our results show limited differences in the skin-associated microbiome between triploid and diploid salmon, irrespective of infection. In the gills, we observed a high incidence of the bacterial pathogen Candidatus Branchiomonas, with higher abundance in diploid compared to triploid control fish. Diploid salmon infected with SAV3 showed greater histopathological signs of epitheliocystis compared to controls, a phenomenon not observed in triploid fish. Our results indicate that ploidy can affect the alpha diversity of the gills but not the skin-associated microbial community. Importantly, during a natural outbreak of Branchiomonas sp. the gill microbiome of diploid Atlantic salmon became significantly more dominated by this pathogen than in triploid animals. Thus, our results suggest that ploidy may play a role on Atlantic salmon gill health and provide insights into co-infection with SAV3 and C. Branchiomonas in Atlantic salmon.

The loss of a spouse is associated with a host of negative health outcomes. While bereaved individuals commonly report somatic symptoms, no investigations exist of the association between reactivation of latent Epstein–Barr virus (EBV) and somatic symptoms among this population. Further, how an individual perceives the quality of their lost relationship in retrospect may impact loss outcomes. Among 99 bereaved spouses, elevated EBV antibody titers were associated with somatic symptoms for those who retrospectively reported high or mean levels of relationship satisfaction (RS), but not among those less satisfied. Further, higher RS was associated with greater grief symptoms. This study identifies higher retrospective RS as a possible risk factor for negative physical and mental health outcomes during bereavement.

Healthy development of ovarian follicles depends on appropriate interactions and function between oocytes and their surrounding granulosa cells. Previously, we showed that double knockout of Irx3 and Irx5 (Irx3/5 DKO) in mice resulted in abnormal follicle morphology and follicle death. Further, female mouse models of individual Irx3 or Irx5 knockouts were both subfertile but with distinct defects. Notably, the expression profile of each gene suggests independent roles for each; first, they are colocalized in pre-granulosa cells during development that then progresses to include oocyte expression during germline nest breakdown and primordial follicle formation. Thereafter, their expression patterns diverge between oocytes and granulosa cells coinciding with the formulation and maturation of intimate oocyte–granulosa cell interactions. The objective of this study was to investigate the contributions of Irx5 and somatic cell-specific expression of Irx3 during ovarian development. Our results show that Irx3 and Irx5 contribute to female fertility through different mechanisms and that Irx3 expression in somatic cells is important for oocyte quality and survival. Based on evaluation of a series of genetically modified mouse models, we conclude that IRX3 and IRX5 collaborate in the same cells and then in neighboring cells to foster a healthy and responsive follicle. Long after these two factors have extinguished, their legacy enables these intercellular connections to mature and respond to extracellular signals to promote follicle maturation and ovulation.

Objectives American Indian/Alaska Native (AI/AN) youth are a high-risk group for sleep problems and associated chronic conditions. Urban AI/AN youth may face certain challenges, including specific psychosocial stressors (e.g., discrimination) and environmental factors (e.g., noise, light) that render them particularly vulnerable to poor sleep health. However, few studies have explored AI/AN adolescent sleep. To our knowledge, this is the first study to use systematic qualitative methods with AI/AN youth to explore their sleep environment and sleep behaviors. Design In-depth interviews with 26 youth. Setting Two urban areas in Central and Southern California. Participants Urban-dwelling AI/AN youth, age 12-16 years. Intervention N/A. Measurement N/A. Results We identified five main themes, each with subthemes: sleep patterns and desired sleep, sleep barriers inside the home, environmental factors, sleep facilitators, and cultural dimensions. Key concerns discussed were poor sleep hygiene, excessive use of electronics prior to bedtime, issues with temperature regulation, and noise both within and outside the home. Parents can be an important vehicle for messaging around sleep health and for behavior management. Participating adolescents also indicated differing levels of attachment to Native identity, suggesting that culturally-targeted sleep interventions should build in openness and flexibility to a range of identity starting points. Further, we identified cultural practices, such as sweat lodges and dreamcatchers, that could be incorporated in future sleep interventions for this population. Conclusion Findings increase our understanding of urban AI/AN youth's sleep environments and behaviors, thus potentially informing program development around sleep health for this vulnerable population.

Rationale: Administration of intravenous crystalloid solutions is a fundamental therapy for sepsis, but the effect of crystalloid composition on patient outcomes remains unknown. Objectives: To compare the effect of balanced crystalloids versus saline on 30-day in-hospital mortality among critically ill adults with sepsis. Methods: Secondary analysis of patients from SMART (Isotonic Solutions and Major Adverse Renal Events Trial) admitted to the medical ICU with an International Classification of Diseases, 10th Edition, Clinical Modification System code for sepsis, using multivariable regression to control for potential confounders. Measurements and Main Results: Of 15,802 patients enrolled in SMART, 1,641 patients were admitted to the medical ICU with a diagnosis of sepsis. A total of 217 patients (26.3%) in the balanced crystalloids group experienced 30-day in-hospital morality compared with 255 patients (31.2%) in the saline group (adjusted odds ratio [aOR], 0.74; 95% confidence interval [CI], 0.59–0.93; P = 0.01). Patients in the balanced group experienced a lower incidence of major adverse kidney events within 30 days (35.4% vs. 40.1%; aOR, 0.78; 95% CI, 0.63–0.97) and a greater number of vasopressor-free days (20 ± 12 vs. 19 ± 13; aOR, 1.25; 95% CI, 1.02–1.54) and renal replacement therapy–free days (20 ± 12 vs. 19 ± 13; aOR, 1.35; 95% CI, 1.08–1.69) compared with the saline group. Conclusions: Among patients with sepsis in a large randomized trial, use of balanced crystalloids was associated with a lower 30-day in-hospital mortality compared with use of saline. Clinical trial registered with www.clinicaltrials.gov (NCT02444988).

Following exposure to the common cold (i.e., rhinovirus), locally produced nasal cytokines (rather than the infection itself) drive the progression of one's symptoms (Hendley et al., 1973; Cohen et al., 1999). Stress-induced local inflammation exacerbates local cytokine production (e.g., marital hostility; Kiecolt-Glaser et al., 2005). An individual's ability to effectively manage their emotions is a critical component of positive health and well-being. Here, we evaluated whether one's self-reported frequency of cognitive reappraisal, an adaptive emotion regulation strategy, predicts nasal cytokine production following experimental rhinovirus exposure. Emotion regulation strategies were assessed at baseline prior to experimental infection. After the baseline assessment, each participant was exposed to a strain of rhinovirus (RV-39) and followed for 5 days in quarantine. Nasal interleukin (IL)-1β, IL-6, and IL-8 and subjective symptoms were assessed at baseline and on each of the 5 days of quarantine. A multilevel analysis of the data for 159 participants with documented infection demonstrated that less frequent use of cognitive reappraisal predicted heightened production of the nasal cytokine composite. Those who self-reported using cognitive reappraisal strategies less frequently displayed elevated nasal IL-6 and IL-8. Among the 63 participants with clinical cold, less frequent use of cognitive reappraisal was associated with heightened production of nasal IL-1β, IL-6, and IL-8. In ancillary analyses, the composite of nasal cytokines was associated with the severity of one's subjective symptoms across the 5 days. Findings suggest that emotion regulation strategies, particularly cognitive reappraisal, influence illness trajectories during rhinovirus infection.

IntroductionFollowing extubation from invasive mechanical ventilation, nearly one in seven critically ill adults requires reintubation. Reintubation is independently associated with increased mortality. Postextubation respiratory support (non-invasive ventilation or high-flow nasal cannula applied at the time of extubation) has been reported in small-to-moderate-sized trials to reduce reintubation rates among hypercapnic patients, high-risk patients without hypercapnia and low-risk patients without hypercapnia. It is unknown whether protocolised provision of postextubation respiratory support to every patient undergoing extubation would reduce the overall reintubation rate, compared with usual care.Methods and analysisThe Protocolized Post-Extubation Respiratory Support (PROPER) trial is a pragmatic, cluster cross-over trial being conducted between 1 October 2017 and 31 March 2019 in the medical intensive care unit of Vanderbilt University Medical Center. PROPER compares usual care versus protocolized post-extubation respiratory support (a respiratory therapist-driven protocol that advises the provision of non-invasive ventilation or high-flow nasal cannula based on patient characteristics). For the duration of the trial, the unit is divided into two clusters. One cluster receives protocolised support and the other receives usual care. Each cluster crosses over between treatment group assignments every 3 months. All adults undergoing extubation from invasive mechanical ventilation are enrolled except those who received less than 12 hours of mechanical ventilation, have ‘Do Not Intubate’ orders, or have been previously reintubated during the hospitalisation. The anticipated enrolment is approximately 630 patients. The primary outcome is reintubation within 96 hours of extubation.Ethics and disseminationThe trial was approved by the Vanderbilt Institutional Review Board. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.Trial registration numberNCT03288311.

American Indian and Alaska Native (AI/AN) youth exhibit multiple health disparities, including high rates of alcohol and other drug (AOD) use, violence and delinquency, and mental health problems. Approximately 70% of AI/AN youth reside in urban areas, where negative outcomes on behavioral health and well-being are often high. Identity development may be particularly complex in urban settings, where youth may face more fragmented and lower density AI/AN communities, as well as mixed racial-ethnic ancestry and decreased familiarity with AI/AN lifeways. This study examines racial-ethnic and cultural identity among AI/AN adolescents and associations with behavioral health and well-being by analyzing quantitative data collected from a baseline assessment of 185 AI/AN urban adolescents from California who were part of a substance use intervention study. Adolescents who identified as AI/AN on their survey reported better mental health, less alcohol and marijuana use, lower rates of delinquency, and increased happiness and spiritual health.

BACKGROUND: Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial. METHODS: In a multicenter, randomized trial conducted in seven intensive care units in the United States, we randomly assigned adults undergoing tracheal intubation to receive either ventilation with a bag-mask device or no ventilation between induction and laryngoscopy. The primary outcome was the lowest oxygen saturation observed during the interval between induction and 2 minutes after tracheal intubation. The secondary outcome was the incidence of severe hypoxemia, defined as an oxygen saturation of less than 80%. RESULTS: Among the 401 patients enrolled, the median lowest oxygen saturation was 96% (interquartile range, 87 to 99) in the bag-mask ventilation group and 93% (interquartile range, 81 to 99) in the no-ventilation group (P = 0.01). A total of 21 patients (10.9%) in the bag-mask ventilation group had severe hypoxemia, as compared with 45 patients (22.8%) in the no-ventilation group (relative risk, 0.48; 95% confidence interval [CI], 0.30 to 0.77). Operator-reported aspiration occurred during 2.5% of intubations in the bag-mask ventilation group and during 4.0% in the no-ventilation group (P = 0.41). The incidence of new opacity on chest radiography in the 48 hours after tracheal intubation was 16.4% and 14.8%, respectively (P = 0.73). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, patients receiving bag-mask ventilation had higher oxygen saturations and a lower incidence of severe hypoxemia than those receiving no ventilation. (Funded by Vanderbilt Institute for Clinical and Translational Research and others; PreVent ClinicalTrials.gov number, NCT03026322.)

Identification of defined epithelial cell populations with progenitor properties is critical for understanding prostatic development and disease. Here, we demonstrate that Sox2 expression is enriched in the epithelial cells of the proximal prostate adjacent to the urethra. We use lineage tracing of Sox2-positive cells during prostatic development, homeostasis, and regeneration to show that the Sox2 lineage is capable of self-renewal and contributes to prostatic regeneration. Persisting luminal cells express Sox2 after castration, highlighting a potential role for Sox2 in cell survival and castration-resistance. In addition to revealing a novel progenitor population in the prostate, these data implicate Sox2 as a regulatory factor of adult prostate epithelial stem cells. Stem Cells 2019;37:690–700

Commensal microorganisms present at mucosal surfaces play a vital role in protecting the host organism from bacterial infection. There are multiple factors that contribute to selecting for the microbiome, key of which are host genetics. Flavobacterium psychrophillum, the causative agent of Bacterial Cold Water Disease in salmonids, accounts for acute losses in wild and farmed Rainbow Trout (Oncorhynchus mykiss). The U.S. National Center for Cool and Cold Water Aquaculture has used family-based selective breeding to generate a line of rainbow trout with enhanced resistance to F. psychrophilum. The goal of this study is to determine whether selective breeding impacts the gut and gill microbiome of the F. psychrophilum-resistant as compared to a background matched susceptible trout line. Mid-gut and gill samples were collected from juvenile fish (mean bwt 118g) and microbial diversity assessed by 16S rDNA amplicon sequencing. Results indicate that alpha diversity was significantly higher in the mid-gut of the susceptible line compared to the resistant line, while no significant differences in alpha diversity were observed in the gills. Mycoplasma sp. was the dominant taxon in the mid-gut of both groups, although it was present at a decreased abundance in the susceptible line. We also observed an increased abundance of taxa that could potentially be pathogenic in the susceptible line, including Brevinema sp. and Enterobacteriaceae members. Within the gills, both lines exhibited similar microbial profiles, with Candidatus Branchiomonas being the dominant taxon. Together, these results suggest that selectively bred Flavobacterium psychrophillum-resistant trout may harness a more resilient gut microbiome, attributing to the disease resistant phenotype, providing a framework for future experiments.

PURPOSE OF THE REVIEW: Intravenous fluid administration is a fundamental therapy in critical care, yet key questions remain unanswered regarding optimal fluid composition and dose. This review evaluates recent evidence regarding the effects of fluid resuscitation on pathophysiology, organ function, and clinical outcomes for critically ill patients. RECENT FINDINGS: Recent findings suggest that intravenous fluid composition affects risk of kidney injury and death for critically ill adults. Generally, the risk of kidney injury and death appears to be greater with semisyntheic colloids compared to crystalloids, and with saline compared to balanced crystalloids. Whether a liberal, restrictive, or hemodynamic responsiveness-guided approach to fluid dosing improves outcomes during sepsis or major surgery remains uncertain. SUMMARY: As evidence on fluid resuscitation evolves, a reasonable approach would be to use primarily balanced crystalloids, consider 2–3 liters for initial fluid resuscitation of hypovolemic or distributive shock, and use measures of anticipated hemodynamic response to guide further fluid administration.

Background Youth health risk behaviors, including substance use (psychoactive substances including alcohol and illicit drugs), have been the subject of relatively limited study to date in Middle Eastern countries. This study provides insights into the perceived prevalence and patterns of alcohol and drug use among Palestinian youth. Methods The study was based on ten focus groups and 17 individual interviews with youth aged 16–24 years (n = 83), collected as part of the formative phase of a cross-sectional, population representative study of risk taking behaviors among Palestinian youth in the West Bank in 2012. Qualitative analysis was used to code detailed notes of focus groups and interviews. Results Most participants reported that substance use exists, even in socially conservative communities. Almost all participants agreed that alcohol consumption is common and that alcohol is easily available. The top alcoholic drinks referred to by the study participants were vodka, whisky, beer, and wine. Most participants claimed that they drink alcohol to cope with stress, for fun, out of curiosity, to challenge society, and due to the influence of the media. Participants were familiar with illicit drugs and knew of youth who engaged in drug use: marijuana, cocaine, and heroin were mentioned most frequently. Study participants believed that youth use drugs as a result of stress, the Israeli occupation, inadequate parental control, lack of awareness, unhappiness, curiosity, and for entertainment. Many participants were unaware of any local institutions to support youth with substance use problems. Others expressed their distrust of any such institution as they assumed them to be inefficient, profit-driven, and posing the risk of potential breaches of confidentiality. Conclusions Although this study uses a purposive sample, the results suggest that substance use exists among Palestinian youth. Risk behaviors are a concern given inadequate youth-friendly counseling services and the strong cultural constraints on open discussion or education about the impact of high risk behaviors. These barriers to treatment and counseling can exacerbate the health and social consequences of alcohol abuse and illicit drug use.

Among critically ill adults, sepsis remains both common and lethal. In addition to antibiotics and source control, fluid resuscitation is a fundamental sepsis therapy. The physiology of fluid resuscitation for sepsis, however, is complex. A landmark trial found early goal-directed sepsis resuscitation reduced mortality, but 3 recent multicenter trials did not confirm this benefit. Multiple trials in resource-limited settings have found increased mortality with early fluid bolus administration in sepsis, and the optimal approach to early sepsis resuscitation across settings remains unknown. After initial resuscitation, excessive fluid administration may contribute to edema and organ dysfunction. Using dynamic variables such as passive leg raise testing can predict a patient’s hemodynamic response to fluid administration better than static variables such as central venous pressure. Whether using measures of “fluid responsiveness” to guide fluid administration improves patient outcomes, however, remains unknown. New evidence suggests improved patient outcomes with the use of balanced crystalloids compared to saline in sepsis. Albumin may be beneficial in septic shock, but other colloids such as starches, dextrans, and gelatins appear to increase the risk of death and acute kidney injury. For the clinician caring for patients with sepsis today, the initial administration of 20 mL/kg of intravenous balanced crystalloid, followed by consideration of the risks and benefits of subsequent fluid administration represents a reasonable approach. Additional research is urgently needed to define the optimal dose, rate, and composition of intravenous fluid during the management of patients with sepsis and septic shock.

Relatively little is known about patterns of health risk behaviors among Middle Eastern youth, including how these behaviors are related to perceived peer norms. In a sample of approximately 2,500 15–24 year old Palestinian youth, perceived engagement of general peers in alcohol consumption, drug use and sexual activity was substantially greater than youths’ own (self-reported) engagement in these activities, suggesting a tendency to overestimate the prevalence of risk-taking behavior among peers. Individual participation in a risk behavior strongly covaries with the perceived levels of both friends’ and peers’ engagement in that behavior (p = 0.00 in each case). In addition, significant clustering of risk behaviors is found: youth who participate in one risk behavior are more likely to participate in others. These findings for a rare representative sample of Middle Eastern youth are strikingly similar to those in the US and Europe. The clustering of behaviors suggests that prevention programs should be structured to deal with a range of connected risk behaviors for which certain youth may be at risk. The findings also suggest that adjusting expectations about peers’ behavior may reduce young Palestinians’ engagement in risk taking.

Background Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation. Methods A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation. Results The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79-98) in the checklist group vs 93% (IQR, 84-100) with usual care ( P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94-133) in the checklist group vs 108 mm Hg (IQR, 90-132) in the usual care group ( P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life-threatening procedural complications (40.8% vs 32.6%; P = .20). Conclusions The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care. Trial Registry ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Introduction: Automated electronic sniffers may be useful for early detection of acute respiratory distress syndrome (ARDS) for institution of treatment or clinical trial screening. Methods: In a prospective cohort of 2929 critically ill patients, we retrospectively applied published sniffer algorithms for automated detection of acute lung injury to assess their utility in diagnosis of ARDS in the first 4 ICU days. Radiographic full-text reports were searched for “edema” OR (“bilateral” AND “infiltrate”) and a more detailed algorithm for descriptions consistent with ARDS. Patients were flagged as possible ARDS if a radiograph met search criteria and had a PaO2/FiO2 or SpO2/FiO2 of 300 or 315, respectively. Test characteristics of the electronic sniffers and clinical suspicion of ARDS were compared to a gold standard of 2-physician adjudicated ARDS. Results: Thirty percent of 2841 patients included in the analysis had gold standard diagnosis of ARDS. The simpler algorithm had sensitivity for ARDS of 78.9%, specificity of 52%, positive predictive value (PPV) of 41%, and negative predictive value (NPV) of 85.3% over the 4-day study period. The more detailed algorithm had sensitivity of 88.2%, specificity of 55.4%, PPV of 45.6%, and NPV of 91.7%. Both algorithms were more sensitive but less specific than clinician suspicion, which had sensitivity of 40.7%, specificity of 94.8%, PPV of 78.2%, and NPV of 77.7%. Conclusions: Published electronic sniffer algorithms for ARDS may be useful automated screening tools for ARDS and improve on clinical recognition, but they are limited to screening rather than diagnosis because their specificity is poor.

Background Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. Methods Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. Results The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position ( P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. Conclusions In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. Trial Registry ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov

The term “birth trauma” is one that is well ingrained into the lexicon of medical providers. There is ample information of the types of injuries that are incurred during the birth process. However, there is no uniformed term for the process of an unforeseen act that leads to a precipitous birth. We would like to show a case report of such an act. The infant's injuries were sustained while in utero and the trauma induced a medical team to deliver the infant due to non-reassuring heart tones. Also, we would like to introduce the term of “trauma-induced delivery” into the medical literature as a way to describe similar types of deliveries that are influenced by factors related to physical forces applied to the mother's body, either intentional or unintentional., Highlights • Introduction of the term “trauma-induced delivery(ies)” into the literature • Leading cause of non-obstetric maternal deaths has been from trauma. • Around 7% of all pregnancies may have been affected by a traumatic event. • Trauma-induced deliveries can be set off by accidents, physical abuse, or self-inflicted.

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span. © The Author 2015.

Advances in genomic sequencing technologies in the past decade have revolutionized the field of genomics, resulting in faster and less expensive sequencing. Holding back the potential for innovation, however, is a widespread lack of understanding of genomics and sequencing by the general public. In an attempt to remedy this problem, this paper presents an introduction to the fields of genomics, bioinformatics, and proteomics using the blueberry genome as a model case study of the plant genomics field. The blueberry (Vaccinium sect. Cyanococcus) is often cited as a “super food” in the media due to its nutritional benefits and global economic importance. There have been a number of related genomic publications in the past 20 years; however, a completed genome and a full analysis into the health-related pathways are still needed. As exemplified by this blueberry case study, there are opportunities for future genomic research into numerous beneficial plant species. The solid background presented in this paper provides future researchers the foundation to explore these uncharted areas.

HIV is a serious public health problem for homeless populations. Homeless men who have sex with women have received less attention in the HIV risk literature than other homeless populations. This research uses multi-level modeling to investigate the context of unprotected sex among heterosexually active homeless men in the Skid Row area of Los Angeles. Based on interviews with 305 randomly selected men who discussed 665 of their recent female sexual relationships, this project investigates the correlates of unprotected sex during the past 6 months at the partnership, individual, and social network levels. Several different measures of relationship closeness and lack of communication about HIV/condoms were associated with unprotected sex. Controlling for relationship factors, men’s negative attitudes towards condoms, mental health, and higher number of male sex partners also were associated with having unprotected sex with female partners. We discuss the implications of these findings for health interventions.

Background The INNER NO OUTER (INO) gene, which encodes a YABBY-type transcription factor, specifies and promotes the growth of the outer integument of the ovule in Arabidopsis. INO expression is limited to the abaxial cell layer of the developing outer integument of the ovule and is regulated by multiple regions of the INO promoter, including POS9, a positive element that when present in quadruplicate can produce low-level expression in the normal INO pattern. Results Significant redundancy in activity between different regions of the INO promoter is demonstrated. For specific regulatory elements, multimerization or the addition of the cauliflower mosaic virus 35S general enhancer was able to activate expression of reporter gene constructs that were otherwise incapable of expression on their own. A new promoter element, POS6, is defined and is shown to include sufficient positive regulatory information to reproduce the endogenous pattern of expression in ovules, but other promoter regions are necessary to fully suppress expression outside of ovules. The full-length INO promoter, but not any of the INO promoter deletions tested, is able to act as an enhancer-blocking insulator to prevent the ectopic activation of expression by the 35S enhancer. Sequence conservation between the promoter regions of Arabidopsis thaliana, Brassica oleracea and Brassica rapa aligns closely with the functional definition of the POS6 and POS9 regions, and with a defined INO minimal promoter. The B. oleracea INO promoter is sufficient to promote a similar pattern and level of reporter gene expression in Arabidopsis to that observed for the Arabidopsis promoter. Conclusions At least two independent regions of the INO promoter contain sufficient regulatory information to direct the specific pattern but not the level of INO gene expression. These regulatory regions act in a partially redundant manner to promote the expression in a specific pattern in the ovule and suppress expression outside of ovules. Establishment of this pattern requires cooperation and competition between multiple positive and negative regulatory elements.

Declines in self-reported sleep quotas with globalizing lifestyle changes have focused attention on their possible role in rising global health problems such as obesity or depression. Cultural factors that act across the life course and support sleep sufficiency have received scant attention, nor have the potential interactions of cultural and biological factors in age-related changes in sleep behavior been systematically investigated. This study examines the effects of cultural norms for napping and sleeping arrangements along with sleep schedules, age, and gender on sleep budgets among Egyptian households. Data were collected in 2000 from 16 households with 78 members aged 3–56 years at two sites in Egypt (Cairo and an agrarian village). Each participant provided one week of continuous activity records and details of each sleep event. Records showed that nighttime sleep onsets were late and highly variable. Napping was common and, along with wake time flexibility, played a key role in maintaining sleep sufficiency throughout the life course into later middle age. Cosleeping was prevalent and exhibited contrasting associations with reduced duration and sufficiency of both nocturnal and total sleep, and with earlier, more regular, and less disrupted sleep. Daily sleep quotas met published guidelines and showed age-related changes similar to existing reports, but differed in how they were achieved. Cultural norms organizing sleep practices by age and gender appear to tap their intrinsic biological properties as well. Moreover, flexibility in how sleep was achieved contributed to sleep sufficiency. The findings suggest how biocultural dynamics can play key roles in sleep patterns that sustain favorable sleep quotas from infancy onwards in populations pursuing globalizing contemporary lifestyles.

Homeless men in the U.S. represent a large and growing population, and have elevated rates of HIV/AIDS and sexual risk behaviors, including unprotected sex with women. We conducted qualitative interviews (n = 30) with homeless men using shelters and meal lines in downtown Los Angeles (Skid Row) to better understand how such men view the risks of sexual encounters with female partners. Men living on Skid Row perceived multiple risks, including HIV and unwanted pregnancy as well as emotional trauma, loss of resources, exacerbation of drug addiction, and physical attack. Respondents described using visual and behavioral cues, social reputation, geographical location, feelings of trust, perceived relationship seriousness, and medically inaccurate “folk” beliefs to judge whether partners were risky and/or condom use was warranted. Medically inaccurate beliefs suggest the potential utility of evidence-based interventions to change such beliefs. We also consider implications for relationships on the street and housing interventions.

This paper details a facile approach for the synthesis of stable and monodisperse silver nanoparticles performed at ambient/low temperature, whereAllium sativum(garlic) extract functions as the silver salt reducing agent during nanoparticle synthesis as well as the postsynthesis stabilizing ligands. Varying the synthesis conditions provides control of particle size, size-distribution, and kinetics of particle formation. Infrared spectroscopy, energy dispersive X-ray chemical analysis, and high-performance liquid chromatography indicated that allicin and other carbohydrates in the garlic extract are the primary nanoparticle stabilizing moieties. The synthesized silver nanoparticles also demonstrate potential for biomedical applications, owing to (1) enhanced stability in biological media, (2) resistance to oxidation by the addition of H2O2, (3) ease and scalability of synthesis, and (4) lack of harsh chemicals required for synthesis. Cytotoxicity assays indicated no decrease in cellular proliferation for vascular smooth muscle cells and 3T3 fibroblasts at a concentration of 25 μg/mL, confirming that silver nanoparticles synthesized with garlic extract are potential candidates for future experimentation and implementation in the biomedical field.

This article examines the life and work of South African journalist Nat Nakasa (1937-1965), a writer for the popular news magazine Drum, the first black columnist for the Johannesburg newspaper the Rand Daily Mail, and the founding editor of the African literary journal The Classic. He has long lurked on the fringes of South African historiography, never playing more than a bit part in studies of early apartheid-era journalism, literature and intellectual culture. Indeed, the specifics of his life have been overshadowed in both popular memory and academic study by the potent symbolism of his death, frequently evoked as a marker of the destruction wrought on black intellectuals by National Party rule. Nakasa committed suicide in exile in the United States at the age of only 28. Drawing on interviews, newspapers and magazines, memoirs, government surveillance documents, and personal papers, this article aims to fill in but also to complicate this legacy. In a broader sense, it also seeks to show how biographical narrative can be employed to cut across time periods, movements, perspectives, and geography, providing an important reminder that every history is peopled by the sprawled and frequently contradictory lives of individuals.