Search

Overwhelming data indicate that individuals with even mildly elevated blood pressure (BP) are at great risk for developing clinical hypertension and future cardiovascular disease (CVD). There remains a lack of consensus regarding treatment strategies for mildly elevated BP, termed prehypertension, and the knowledge of pathophysiology and mechanisms of its clinical outcomes remains limited. Our primary aim was to investigate βAR-mediated inflammation control (BARIC) responses of blood monocytes to isoproterenol (Iso) in relation to BP and CVD risk factors, including obesity, depressive mood, fasting glucose, triglycerides, and cholesterol levels in the 64 prehypertensive compared to 84 individuals with normal BP. BARIC was determined by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by ex vivo Iso treatment (10(-8)M). Depressive mood was assessed by Beck Depression Inventory (BDI). Fasting metabolic and lipid panels were assessed, and plasma levels of inflammatory cytokines TNF, IL-1β, IL-6 were measured in a subset to confirm proinflammatory state of prehypertensive participants. Prehypertensive participants were older, heavier, included more men, and presented higher levels of fasting glucose, triglycerides, cholesterol, and plasma TNF compared to normotensive participants (p's<.05). BARIC was significantly attenuated in the prehypertensive compared to normotensive group (p<.05). BARIC was negatively associated with systolic BP, diastolic BP, age, BMI, fasting glucose, triglycerides, total and low density cholesterol levels, and somatic depressive symptoms in all participants (p's<.0001 to .05). However, among the prehypertensive individuals BARIC was positively associated with SBP even after controlling for the covariates (age, gender, race, BMI, glucose and lipid panel, somatic BDI scores) (p<.05). This differing nature of the BARIC-SBP relationship between the two BP groups may be attributed to moderating factors such as cardiorespiratory fitness or depressive symptoms that could not be clearly deciphered in this current study. Nonetheless, our findings indicate the associations between inflammation dysregulation mediated by sympathoadrenal activation and BP that is observable even among individuals with normal to mildly elevated BP. BARIC may be a useful and sensitive indicator of elevated risk for vascular inflammatory disease that can be detected even at lower BP levels, especially given its associations with traditional CVD risk factors and the critical role of monocytes in atherogenic processes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries and the underlying cause of cardiovascular disease, a major cause of mortality worldwide. The over-accumulation of modified cholesterol-containing low-density lipoproteins (e.g. oxLDL) in the artery wall and the subsequent recruitment and activation of macrophages contributes to the development of atherosclerosis. The excessive uptake of modified-LDL by macrophages leads to a lipid-laden "foamy" phenotype and pro-inflammatory cytokine production. Modified-LDLs promote foam cell formation in part by stimulating de novo lipid biosynthesis. However, it is unknown if lipid biosynthesis directly regulates foam cell pro-inflammatory mediator production. Lipin-1, a phosphatidate phosphohydrolase required for the generation of diacylglycerol during glycerolipid synthesis has recently been demonstrated to contribute to bacterial-induced pro-inflammatory responses by macrophages. In this study we present evidence demonstrating the presence of lipin-1 within macrophages in human atherosclerotic plaques. Additionally, reducing lipin-1 levels in macrophages significantly inhibits both modified-LDL-induced foam cell formation in vitro, as observed by smaller/fewer intracellular lipid inclusions, and ablates modified-LDL-elicited production of the pro-atherogenic mediators tumor necrosis factor-α, interleukin-6, and prostaglandin E2. These findings demonstrate a critical role for lipin-1 in the regulation of macrophage inflammatory responses to modified-LDL. These data begin to link the processes of foam cell formation and pro-inflammatory cytokine production within macrophages., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Although ergogenic, acute caffeine ingestion may increase urine volume, prompting concerns about fluid balance during exercise and sport events. This meta-analysis evaluated caffeine induced diuresis in adults during rest and exercise., Design: Meta-analysis., Methods: A search of three databases was completed on November 1, 2013. Only studies that involved healthy adults and provided sufficient information concerning the effect size (ES) of caffeine ingestion on urine volume were included. Sixteen studies met the inclusion criteria, providing a total of 28 ESs for the meta-analysis. Heterogeneity was assessed using a random-effects model., Results: The median caffeine dosage was 300 mg. The overall ES of 0.29 (95% confidence interval (CI) = 0.11-0.48, p = 0.001) corresponds to an increase in urine volume of 109 ± 195 mL or 16.0 ± 19.2% for caffeine ingestion vs. non-caffeine conditions. Subgroup meta-analysis confirmed exercise as a strong moderator: active ES = 0.10, 95% CI = -0.07 to 0.27, p = 0.248 vs. resting ES = 0.54, 95% CI = 0.22-0.85, p = 0.001 (Cochran's Q, p = 0.019). Females (ES = 0.75, 95% CI = 0.38-1.13, p < 0.001) were more susceptible to diuretic effects than males (ES = 0.13, 95% CI = -0.05 to 0.31, p = 0.158) (Cochran's Q, p = 0.003)., Conclusions: Caffeine exerted a minor diuretic effect which was negated by exercise. Concerns regarding unwanted fluid loss associated with caffeine consumption are unwarranted particularly when ingestion precedes exercise., (Copyright © 2014 Sports Medicine Australia. All rights reserved.)

This study examined the effects of dehydration on intermittent sprint performance and perceptual responses. Eight male collegiate baseball players completed intermittent sprints either dehydrated (DEHY) by 3% body mass or euhydrated (EU). Body mass was reduced through exercise in the heat with controlled fluid restriction occurring 1 day before the trial. Participants completed twenty-four 30-m sprints divided into 3 bouts of 8 sprints with 45 seconds of rest between each sprint and 3 minutes between each bout. Perceived recovery status (PRS) scale was recorded before the start of each trial. Heart rate (HR), ratings of perceived exertion (RPE) (0-10 OMNI scale), and perceived readiness (PR) scale were recorded after every sprint, and session RPE (SRPE) was recorded 20 minutes after completing the entire session. A 2 (condition) × 3 (bout of sprints) repeated-measures ANOVA revealed a significant main effect of condition on mean sprint time (p = 0.03), HR (p < 0.01), RPE (p = 0.01), and PR (p = 0.02). Post hoc tests showed significantly faster mean sprint times for EU vs. DEHY during the second (4.87 ± 0.29 vs. 5.03 ± 0.33 seconds; p = 0.01) and third bouts of sprints (4.91 ± 0.29 vs. 5.12 ± 0.44 seconds; p = 0.02). Heart rate was also significantly lower (p ≤ 0.05) for EU during the second and third bouts. Post hoc measures also showed significantly impaired (p ≤ 0.05) feelings of recovery (PRS) before exercise and increased (p ≤ 0.05) perceptual strain before each bout (PR) during the second and third bouts of repeated sprint work (i.e., RPE and PR) and after the total session (SRPE) in the DEHY condition. Dehydration impaired sprint performance, negatively altered perception of recovery status before exercise, and increased RPE and HR response.

Sweat production is crucial for thermoregulation. However, sweating can be problematic for individuals with spinal cord injuries (SCI), as they display a blunting of sudomotor and vasomotor responses below the level of the injury. Sweat gland density and eccrine gland metabolism in SCI are not well understood. Consequently, this study examined sweat lactate (S-LA) (reflective of sweat gland metabolism), active sweat gland density (SGD), and sweat output per gland (S/G) in 7 SCI athletes and 8 able-bodied (AB) controls matched for arm ergometry VO2peak. A sweat collection device was positioned on the upper scapular and medial calf of each subject just prior to the beginning of the trial, with iodine sweat gland density patches positioned on the upper scapular and medial calf. Participants were tested on a ramp protocol (7 min per stage, 20 W increase per stage) in a common exercise environment (21±1°C, 45-65% relative humidity). An independent t-test revealed lower (p<0.05) SGD (upper scapular) for SCI (22.3 ±14.8 glands · cm(-2)) vs. AB. (41.0 ± 8.1 glands · cm(-2)). However, there was no significant difference for S/G between groups. S-LA was significantly greater (p<0.05) during the second exercise stage for SCI (11.5±10.9 mmol · l(-1)) vs. AB (26.8±11.07 mmol · l(-1)). These findings suggest that SCI athletes had less active sweat glands compared to the AB group, but the sweat response was similar (SLA, S/G) between AB and SCI athletes. The results suggest similar interglandular metabolic activity irrespective of overall sweat rate.

The Surgical Care Improvement Project (SCIP) is a national program aimed at reducing perioperative complications and is a quality benchmark metric for Centers for Medicare and Medicaid Services. This study evaluates whether a multidisciplinary program improved an institution's compliance with SCIP measures. Analysis of the facility's performance data identified three key areas of SCIP noncompliance: 1) timely discontinuation of perioperative antibiotics and urinary catheters, 2) initiation of venous thromboembolism prophylaxis, and 3) perioperative beta blocker administration. Multidisciplinary teams collaborated with providers and department chairs in reviewing and enable SCIP compliance. Anesthesia staff managed preoperative antibiotics. SCIP-compliant order sets, venous thromboembolism pop-up alerts, and progress note templates were added to the electronic medical record. Standardized education was provided to explain SCIP requirements, review noncompliant cases, and update teams on SCIP performance. Data were captured from January 2009 to March 2014. Ten SCIP fallouts were reported for general surgery specialties in January 2013, when the SCIP compliance project launched. Specifically, colon-related surgery achieved 100 per cent compliance. Six months after implementation, overall SCIP compliance at our institution improved by 65 per cent (from 90.7-98.6% compliance).

Visceral injury from cardiac arrest resuscitation is a rare but potentially life-threatening complication. We describe and review 2 cases of hepatic laceration complicated by major abdominal hemorrhage manifested as delayed shock following cardiopulmonary resuscitation after cardiac arrest. Two patients enrolled in our institutional post cardiac arrest resuscitation clinical pathway had evidence of major liver laceration presenting as delayed shock due to massive hemoperitoneum. Case analysis revealed coagulopathy due to systemic anticoagulation as a risk factor for major hemorrhage. Both cases were successfully managed via hepatic artery embolization. Visceral abdominal injuries are an uncommon but important complication of cardiopulmonary resuscitation.Coagulopathy, including therapeutic systemic anticoagulation, is a risk factor for clinically significant hemorrhage.

In health, long-lived plasma cells (LLPC) are essential for durable protective humoral immunity, and, conversely, in disease are a major source of pathogenic Abs in autoimmunity, graft rejection, and allergy. However, the molecular basis for their longevity is largely unknown. We have recently found that CD28 signaling in plasma cells (PC) is essential for sustaining Ab titers, by supporting the survival of LLPC, but not short-lived PC (SLPC). We now find that, unlike SLPC, CD28 activation in LLPC induces prosurvival downstream Vav signaling. Knockin mice with CD28 cytoplasmic tail mutations that abrogate Vav signaling (CD28-AYAA) had significantly fewer LLPC but unaffected SLPC numbers, whereas mice with mutations that abrogate PI3K signaling (CD28-Y170F) were indistinguishable from wild-type controls. This was consistent with the loss of CD28's prosurvival effect in LLPC from CD28-AYAA, but not CD28-Y170F, mice. Furthermore, the CD28 Vav motif in the B lineage was essential for the long-term maintenance of Ag-specific LLPC populations and Ab titers in vivo. Signaling downstream of the CD28 Vav motif induced previously undescribed transcriptional regulation of B lymphocyte-induced maturation protein-1, a key mediator of PC differentiation and maintenance. These findings suggest CD28 signaling in LLPC modulates the central B lymphocyte-induced maturation protein-1 transcriptional nexus involved in long-term survival and function., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Hematopoietic stem cells (HSCs) emerge from aortic endothelium via the endothelial-to-hematopoietic transition (EHT). The molecular mechanisms that initiate and regulate EHT remain poorly understood. Here, we show that adenosine signaling regulates hematopoietic stem and progenitor cell (HSPC) development in zebrafish embryos. The adenosine receptor A2b is expressed in the vascular endothelium before HSPC emergence. Elevated adenosine levels increased runx1(+)/cmyb(+) HSPCs in the dorsal aorta, whereas blocking the adenosine pathway decreased HSPCs. Knockdown of A2b adenosine receptor disrupted scl(+) hemogenic vascular endothelium and the subsequent EHT process. A2b adenosine receptor activation induced CXCL8 via cAMP-protein kinase A (PKA) and mediated hematopoiesis. We further show that adenosine increased multipotent progenitors in a mouse embryonic stem cell colony-forming assay and in embryonic day 10.5 aorta-gonad-mesonephros explants. Our results demonstrate that adenosine signaling plays an evolutionary conserved role in the first steps of HSPC formation in vertebrates., (© 2015 Jing et al.)

Despite remarkable advances in the knowledge of infection and human response to it, sepsis continues to be one of the most common challenges surgeons and critical care providers face. Surgeons confront the problem of infection every day, in treating established infections or reacting to a consequence of surgical intervention. Infections after surgery continue to be a problem despite massive efforts to prevent them. Patients rely on the surgeon's ability to recognize infection and treat it. Also, preventing nosocomial infection and antibiotic resistance is a primary responsibility. This article describes diagnostic and therapeutic measures for sepsis in the perioperative surgical patient., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Sepsis remains a major cause of morbidity and mortality in most intensive care units. Protracted sepsis can evolve into a state of profound immunosuppression characterized by secondary infections, frequently with opportunistic-type pathogens. Immunoadjuvant therapy is currently being evaluated as a novel treatment for patients with sepsis. Two of the most promising immunoadjuvants are interleukin-7 (IL-7) and anti-programmed cell death 1 antibody (anti-PD-1). Both IL-7 and anti-PD-1 have been reported to boost host immunity and improve outcomes in patients with viral infections and cancer. The purpose of this study was to define the immunological mechanisms of action of IL-7 and anti-PD-1 in the two-hit sepsis model of cecal ligation and puncture followed by Candida albicans. In addition, we examined whether combined treatment with IL-7 and anti-PD-1 provided any additive beneficial effects in reversing immune dysfunction. The present findings demonstrated that IL-7 and anti-PD-1 had differing effects on innate and adaptive immune functions. Compared with anti-PD-1, IL-7 increased lymphocyte proliferation; expression of lymphocyte adhesion molecules, lymphocyte function-associated antigen 1, and very late antigen-4; interferon-γ production; and CD28 expression on splenic CD8 T cells. In contrast, anti-PD-1 seemed to have a greater effect on major histocompatibility complex class II expression on splenic macrophages and dendritic cells than IL-7. Combined treatment with IL-7 and anti-PD-1 produced additive effects on CD28 expression, lymphocyte proliferation, and splenic secretion of interferon-γ. In conclusion, the present study shows differences in immunomodulatory actions between IL-7 and anti-PD-1 and provides a potential rationale for combining IL-7 and anti-PD-1 in the therapy of sepsis.

Aims: In the recent Iraq and Afghanistan conflicts, survival rates from complex battlefield injuries have continued to improve. The resulting war-related wounds are challenging, with confounding issues making assessment of tissue perfusion subjective and variable. This review discusses the utility of intraoperative fluorescence angiography, and its usefulness as an objective tool to evaluate the perfusion of tissues in the face of complex war-related injuries., Methods: A retrospective review of all war-related traumatic and reconstructive cases employing intraoperative indocyanine green laser angiography (ICGLA) was performed. Data analyzed included indication for use, procedure success/failure rates, modifications performed, and perfusion-related complications. Anatomical regions assessed were extremity, head and neck, truncal, and intra-abdominal viscera. The endpoint of specific interest involved the decision for additional debridement of poorly perfused tissue, as based on the ICGLA findings., Results: Over a 3-year period, this study examined 123 extremity soft tissue flaps, 41 extremity injuries including amputation and/or amputation revision cases, 13 craniofacial flaps, and 9 truncal/abdomen/gastrointestinal cases in which ICGLA was utilized to assess tissue perfusion and viability. A total of 35 (18.8%) of cases employing ICGLA required intraoperative modifications to address perfusion-related issues., Conclusions: Intraoperative fluorescent angiography is an objective, useful tool to assess various war-related traumatic injuries. This study expands on prior cited indications for ICGLA to include (1) guiding debridement in heavily contaminated wounds, (2) providing improved assessment of avulsion soft tissue injuries, (3) allowing for rapid detection of vascular and/or microvascular compromise in soft tissue and osseous flap reconstructions, (4) reducing and preventing perfusion-related complications in trauma, amputation closures, and reconstruction procedures, (5) contributing to better outcomes in certain complex orthopedic and composite tissue injuries, and (6) enabling improved postoperative wound and reconstruction assessment in those cases of perfusion-related issues that arise within a delayed setting., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)

Objective: to integrate findings of individual studies in order to broaden the understanding of first-time mothers' experiences of early labour., Design: the methodology was metasynthesis which is based on the interpretive meta-ethnography described by Noblit and Hare (1988). Metasynthesis is research on research which synthesises the findings of previous qualitative studies, and the focus is on interpretation and the creation of new knowledge., Setting: all included studies originated from high resource countries (USA 2, UK 4, and Scandinavia 5) and all were carried out in a context of hospital based maternity care., Participants: a total of 231 women participated in the studies., Findings: 11 articles were included. The main results are presented with the metaphor a balancing act in an unknown territory. The 'unknown territory' has a double meaning: as the personal experience of going into labour for the first time and as encountering the maternity care system. On both levels women have to make significant decisions: whether labour really has started and subsequently when to go to the hospital. A key challenge is to balance the arrival on the labour ward at the 'right' time, not too early and not too late. Arriving at the 'right' time leads to a positive path, while arriving 'too soon' might lead to a cascade of negative experiences. The results are further presented with five central themes: 'Finding out if labour has started is absorbing'; 'Dealing with labour at home'; 'Trying to arrive at the labour ward at the right time'; 'There is always a risk of being sent home'; 'Encountering health professionals arouses strong emotions'., Conclusions: the metasynthesis broadens the understanding of first-time mothers' experiences of early labour, and suggests that women's needs when planning a hospital birth are not being adequately met at this stage in the labour process. Three areas of future research are suggested: how to support and strengthen women during pregnancy in order to cope with early labour; women's experiences of early labour when planning a birth in contexts other than hospital; and to continue to investigate new ways of giving care during early labour., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

How often do people visit the world's protected areas (PAs)? Despite PAs covering one-eighth of the land and being a major focus of nature-based recreation and tourism, we don't know. To address this, we compiled a globally-representative database of visits to PAs and built region-specific models predicting visit rates from PA size, local population size, remoteness, natural attractiveness, and national income. Applying these models to all but the very smallest of the world's terrestrial PAs suggests that together they receive roughly 8 billion (8 x 109) visits/y-of which more than 80% are in Europe and North America. Linking our region-specific visit estimates to valuation studies indicates that these visits generate approximately US $600 billion/y in direct in-country expenditure and US $250 billion/y in consumer surplus. These figures dwarf current, typically inadequate spending on conserving PAs. Thus, even without considering the many other ecosystem services that PAs provide to people, our findings underscore calls for greatly increased investment in their conservation.

The prevalence of drug resistance in both clinical and community settings as a consequence of alterations of biosynthetic pathways, enzymes or cell wall architecture is a persistent threat to human health. We have designed, synthesized, and tested a novel class of non-transpeptidase, β-lactamase resistant monocyclic β-lactams that carry an arylthio group at C4. These thioethers exhibit inhibitory and cidal activity against serine β-lactamase producing Mycobacterium tuberculosis wild type strain (Mtb) and multiple (n=8) β-lactamase producing Moraxella catarrhalis clinical isolates., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Our objective was to assess the effect of implementing an electronic health record (EHR) on surgical resident work flow, duty hours, and operative experience at a large teaching hospital. In May 2012, an EHR was put into effect at our institution replacing paper documentation and orders. Resident time to complete patient documentation, average duty hours, and operative experience before EHR and afterward (at 1, 4, 6, 8, and 24 weeks) were surveyed. We obtained 100 per cent response rate from 15 surgical residents at all time intervals. The average time spent documenting before EHR was 9 ± 2 minutes per patient document and at Weeks 1, 4, 6, 8, and 24 after EHR implementation was 22 ± 10, 15 ± 7, 15 ± 7, 14 ± 8, and 12 ± 4 minutes, respectively. Repeated measures analysis of variance demonstrated a difference among the means (P < 0.0001). Discharge summary and operative note remained significantly longer to complete at Week 24 compared with paper documentation (P < 0.05). Average resident work hours and operative cases per week before EHR were 77 ± 5 hours and 12 ± 5 cases, respectively, which were similar at all time points after EHR implementation (P > 0.05). At 24 weeks after EHR, 74 per cent of residents felt their risk of performing a medical error using electronic documentation and order entry was higher compared with paper charting and orders. Transition to EHR led to a significant doubling in resident time spent performing documentation for each patient. It improved over 6 months after implementation but never reached the pre-EHR baseline for operative notes and discharge summaries. Average resident work hours and case logs remained similar during this transition.

The use of transgenics in fish is a relatively recent development for advancing understanding of genetic mechanisms and developmental processes, improving aquaculture, and for pharmaceutical discovery. Transgenic fish have also been applied in ecotoxicology where they have the potential to provide more advanced and integrated systems for assessing health impacts of chemicals. The zebrafish (Daniorerio) is the most popular fish for transgenic models, for reasons including their high fecundity, transparency of their embryos, rapid organogenesis and availability of extensive genetic resources. The most commonly used technique for producing transgenic zebrafish is via microinjection of transgenes into fertilized eggs. Transposon and meganuclease have become the most reliable methods for insertion of the genetic construct in the production of stable transgenic fish lines. The GAL4-UAS system, where GAL4 is placed under the control of a desired promoter and UAS is fused with a fluorescent marker, has greatly enhanced model development for studies in ecotoxicology. Transgenic fish have been developed to study for the effects of heavy metal toxicity (via heat-shock protein genes), oxidative stress (via an electrophile-responsive element), for various organic chemicals acting through the aryl hydrocarbon receptor, thyroid and glucocorticoid response pathways, and estrogenicity. These models vary in their sensitivity with only very few able to detect responses for environmentally relevant exposures. Nevertheless, the potential of these systems for analyses of chemical effects in real time and across multiple targets in intact organisms is considerable. Here we illustrate the techniques used for generating transgenic zebrafish and assess progress in the development and application of transgenic fish (principally zebrafish) for studies in environmental toxicology. We further provide a viewpoint on future development opportunities.

Actin microridges form labyrinth like patterns on superficial epithelial cells across animal species. This highly organized assembly has been implicated in mucus retention and in the mechanical structure of mucosal surfaces, however the mechanisms that regulate actin microridges remain largely unknown. Here we characterize the composition and dynamics of actin microridges on the surface of zebrafish larvae using live imaging. Microridges contain phospho-tyrosine, cortactin and VASP, but not focal adhesion kinase. Time-lapse imaging reveals dynamic changes in the length and branching of microridges in intact animals. Transient perturbation of the microridge pattern occurs before cell division with rapid re-assembly during and after cytokinesis. Microridge assembly is maintained with constitutive activation of Rho or inhibition of myosin II activity. However, expression of dominant negative RhoA or Rac alters microridge organization, with an increase in distance between microridges. Latrunculin A treatment and photoconversion experiments suggest that the F-actin filaments are actively treadmilling in microridges. Accordingly, inhibition of Arp2/3 or PI3K signaling impairs microridge structure and length. Taken together, actin microridges in zebrafish represent a tractable in vivo model to probe pattern formation and dissect Arp2/3-mediated actin dynamics in vivo.

Objective: To evaluate and provide a real-life view of the operation of the Healthy Start vitamins scheme., Setting: The study took place in primary care and community settings that served rural, urban and ethnically diverse populations, in two sentinel sites: London, and Yorkshire and the Humber. An online consultation and stakeholder workshops elicited views from across England., Participants: 669 health and social care practitioners including health visitors, midwives, public health practitioners, general practitioners, paediatricians and support staff participated in focus group discussions (n=49) and an online consultation (n=620). 56 participants representing health and social care practitioners, policymakers, service commissioners, and voluntary and independent sectors took part in stakeholder workshops., Methods: Three-phase multimethod study comprising focus group discussions, an online consultation and stakeholder workshops. Qualitative data were analysed thematically and quantitative data from the online survey were analysed using descriptive statistics., Results: Study participants were concerned about the low uptake of Healthy Start vitamin supplements and the consequences of this for health outcomes for women and young children. They experienced Healthy Start vitamin distribution as logistically complex, requiring the time, resources and creative thinking of a range of local and regional practitioners from senior strategists to administrative support workers. In the light of this, many participants argued that moving to universal provision of vitamin supplements would be more cost-effective than the current system., Conclusions: There is consistency of views of health practitioners that the current targeted system of providing free vitamin supplements for low-income childbearing women and young children via the Healthy Start programme is not fulfilling its potential to address vitamin deficiencies. There is wide professional and voluntary sector support for moving from the current targeted system to provision of free vitamin supplements for all pregnant and new mothers, and children up to their fifth birthday., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Large segmental bone and composite tissue defects often require vascularized osseous flaps for definitive reconstruction. However, failed osseous flaps due to inadequate perfusion can lead to significant morbidity. Utilization of indocyanine green (ICG) fluorescence angiography has been previously shown to reliably assess soft tissue perfusion. Our group will outline the application of this useful intraoperative tool in evaluating the perfusion of vascularized osseous flaps., Methods: A retrospective review was performed to identify those osseous and/or osteocutaneous bone flaps, where ICG angiography was employed. Data analyzed included flap types, success and failure rates, and perfusion-related complications. All osseous flaps were evaluated by ICG angiography to confirm periosteal and endosteal perfusion., Results: Overall 16 osseous free flaps utilizing intraoperative ICG angiography to assess vascularized osseous constructs were performed over a 3-year period. The flaps consisted of the following: nine osteocutaneous fibulas, two osseous-only fibulas, two scapular/parascapular with scapula bone, two quadricep-based muscle flaps, containing a vascularized femoral bone component, and one osteocutaneous fibula revision. All flap reconstructions were successful with the only perfusion-related complication being a case of delayed partial skin flap loss., Conclusions: Intraoperative fluorescence angiography is a useful adjunctive tool that can aid in flap design through angiosome mapping and can also assess flap perfusion, vascular pedicle flow, tissue perfusion before flap harvest, and flap perfusion after flap inset. Our group has successfully extended the application of this intraoperative tool to assess vascularized osseous flaps in an effort to reduce adverse outcomes related to preventable perfusion-related complications., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Hydration affects multiple aspects of basketball performance, but few investigations have examined the hydration profiles of collegiate basketball players. We examined multiday prepractice hydration status of 11 male and 11 female NCAA (National Collegiate Athletic Association) Division II basketball players' sweat losses, fluid intake, and how accurately players estimated their sweat losses. Urine-specific gravity (USG) was spontaneously assessed before 2 practices. Sweat losses and fluid intakes were measured during a conditioning practice (CP) and sport-specific practice (SP). After practices, players filled 1,030 ml practice bottles to estimate their sweat losses. Urine-specific gravity between practices exhibited a moderate correlation (r = 0.54; p = 0.012) and were consistently high (17% of samples = USG >1.030) with no difference in mean USG between men (1.026 ± 0.004) and women (1.022 ± 0.008). Athletes' estimations of their sweat loss volumes between CP and the longer SP were strongly correlated (r = 0.88; p < 0.001). Estimation error was high (absolute error for both practices = 71 ± 52%) and error direction varied greatly within men. Women consistently underestimated sweat losses by 63 ± 28% and 65 ± 20% during CP and SP. Sweat losses during SP equaled 2,471 ± 495 ml and 1,910 ± 441 ml for men and women, respectively, but high practice fluid intake limited body mass losses to 1.1 ± 0.6% by the end of practice. It is plausible that hypohydration is related to poor conceptualization of sweat losses. Simulating the methodology of this study could help identify chronically hypohydrated athletes and be used to educate on between-practice fluid needs.

Introduction: The purpose of this study was to analyze the effect of residents on patient outcomes in laparoscopic ventral hernia repair (LVHR).We hypothesized that increasing postgraduate year (PGY) level would correlate with better outcomes., Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried from 2005 to 2011 for elective LVHR. Attending only cases were used as the control, and resident cases were stratified into junior (PGY 1-3), chief (4-5), and fellow (6+) cases. Standard statistical tests and multivariate regression controlling for age, body mass index, Charlson comorbidity index, smoking, functional status, and inpatient cases were performed for trainee involvement and PGY level., Results: There were 6,841 ventral hernia repairs that met inclusion criteria: 2,773 attending and 4,068 resident cases. There were 1,644 junior, 1,983 chief, and 441 fellow cases. Patients were similar between the attending and resident groups. The resident group had a higher rate of inpatient cases, general complications, longer operative time, and hospital length of stay. After controlling for confounders in multivariate analysis, only operative time was significantly different; resident cases were 17.7 min longer (CI 15.0-20.6; p < 0.001). There was no significant difference in the rate of wound or major complications, readmission, reoperation, or mortality between attending and resident cases. Demographics were not significantly different between the PGY level strata. On multivariate regression by PGY level with attending alone as the reference, only operative time was significantly different. Juniors (15.7 min, CI 12.2-19.2), chiefs (18.0 min, CI 14.7-21.3), and fellows (24.9 min, CI 19.1-30.7) had significantly longer cases than attending alone; all p < 0.001., Conclusion: Trainee involvement during LVHR does not change the clinical outcomes for patients as compared to those performed by an attending only. Operative time is significantly longer with increasing PGY level, perhaps indicating the complexity of the operation or increasing trainee involvement as primary surgeon. However, patient care does not suffer, affirming the current surgical training curriculum is appropriate.

With an optimized expression cassette consisting of the soybean (Glycine max) native promoter modified for enhanced expression driving a chimeric gene coding for the soybean native amino-terminal 86 amino acids fused to an insensitive shuffled variant of maize (Zea mays) 4-hydroxyphenylpyruvate dioxygenase (HPPD), we achieved field tolerance in transgenic soybean plants to the HPPD-inhibiting herbicides mesotrione, isoxaflutole, and tembotrione. Directed evolution of maize HPPD was accomplished by progressively incorporating amino acids from naturally occurring diversity and novel substitutions identified by saturation mutagenesis, combined at random through shuffling. Localization of heterologously expressed HPPD mimicked that of the native enzyme, which was shown to be dually targeted to chloroplasts and the cytosol. Analysis of the native soybean HPPD gene revealed two transcription start sites, leading to transcripts encoding two HPPD polypeptides. The N-terminal region of the longer encoded peptide directs proteins to the chloroplast, while the short form remains in the cytosol. In contrast, maize HPPD was found almost exclusively in chloroplasts. Evolved HPPD enzymes showed insensitivity to five inhibitor herbicides. In 2013 field trials, transgenic soybean events made with optimized promoter and HPPD variant expression cassettes were tested with three herbicides and showed tolerance to four times the labeled rates of mesotrione and isoxaflutole and two times the labeled rates of tembotrione., (© 2014 American Society of Plant Biologists. All Rights Reserved.)

Current herbicide and herbicide trait practices are changing in response to the rapid spread of glyphosate-resistant weeds. Growers urgently needed glyphosate when glyphosate-resistant crops became available because weeds were becoming widely resistant to most commonly used selective herbicides, making weed management too complex and time consuming for large farm operations. Glyphosate made weed management easy and efficient by controlling all emerged weeds at a wide range of application timings. However, the intensive use of glyphosate over wide areas and concomitant decline in the use of other herbicides led eventually to the widespread evolution of weeds resistant to glyphosate. Today, weeds that are resistant to glyphosate and other herbicide types are threatening current crop production practices. Unfortunately, all commercial herbicide modes of action are over 20 years old and have resistant weed problems. The severity of the problem has prompted the renewal of efforts to discover new weed management technologies. One technology will be a new generation of crops with resistance to glyphosate, glufosinate and other existing herbicide modes of action. Other technologies will include new chemical, biological, cultural and mechanical methods for weed management. From the onset of commercialization, growers must now preserve the utility of new technologies by integrating their use with other weed management technologies in diverse and sustainable systems., (© 2014 Society of Chemical Industry.)

Ligation of erythropoietin (EPO) receptor (EPOR) JAK2 kinase complexes propagates signals within erythroid progenitor cells (EPCs) that are essential for red blood cell production. To reveal hypothesized novel EPOR/JAK2 targets, a phosphotyrosine (PY) phosphoproteomics approach was applied. Beyond known signal transduction factors, 32 new targets of EPO-modulated tyrosine phosphorylation were defined. Molecular adaptors comprised one major set including growth factor receptor-bound protein 2 (GRB2)-associated binding proteins 1-3 (GAB1-3), insulin receptor substrate 2 (IRS2), docking protein 1 (DOK1), Src homology 2 domain containing transforming protein 1 (SHC1), and sprouty homologue 1 (SPRY1) as validating targets, and SPRY2, SH2 domain containing 2A (SH2D2A), and signal transducing adaptor molecule 2 (STAM2) as novel candidate adaptors together with an ORF factor designated as regulator of human erythroid cell expansion (RHEX). RHEX is well conserved in Homo sapiens and primates but absent from mouse, rat, and lower vertebrate genomes. Among tissues and lineages, RHEX was elevated in EPCs, occurred as a plasma membrane protein, was rapidly PY-phosphorylated >20-fold upon EPO exposure, and coimmunoprecipitated with the EPOR. In UT7epo cells, knockdown of RHEX inhibited EPO-dependent growth. This was associated with extracellular signal-regulated kinase 1,2 (ERK1,2) modulation, and RHEX coupling to GRB2. In primary human EPCs, shRNA knockdown studies confirmed RHEX regulation of erythroid progenitor expansion and further revealed roles in promoting the formation of hemoglobinizing erythroblasts. RHEX therefore comprises a new EPO/EPOR target and regulator of human erythroid cell expansion that additionally acts to support late-stage erythroblast development., (© 2014 Verma et al.)

Background: Pregnancy and the first years of life are important times for future child well-being. Early identification of families and children who might be likely to experience poorer outcomes could enable health professionals and parents to work together to promote each child's well-being. Little is known about the acceptability and feasibility of such an approach to parents., Objective: To investigate parents' views about how health professionals should identify and work with families who may benefit from additional input to maximize their children's future health and well-being., Design: A qualitative study using focus groups., Setting and Participants: Eleven focus groups were conducted with a total of 54 parents; 42 mothers and 12 fathers living in the north of England., Results: Parents welcomed the idea of preventive services. They strongly believed that everyone should have access to services to enhance child well-being whilst recognizing that some families need additional support. Making judgements about who should receive additional services based on specific criteria evoked powerful emotions because of the implication of failure. Parents projected a belief in themselves as 'good parents' even in adverse circumstances., Conclusions: Targeted additional preventive services can be acceptable and welcome if health professionals introduce them sensitively, in the context of an existing relationship, providing parents are active participants., (© 2012 John Wiley & Sons Ltd.)

Introduction: The open abdominal (OA) approach is a management strategy used in the most severely injured trauma patients. In addition to the morbidity and mortality, a major challenge is the gradual development of dense adhesions that make reoperations progressively more difficult. This randomized, prospective, proof-of-concept study was conducted to determine the effect of carboxymethylcellulose sodium hyaluronate adhesion barrier (CMHAB; Seprafilm, Genzyme Biosurgery, Bridgewater, NJ) on abdominal adhesions and wound characteristics in trauma open abdomens., Methods: A prospective, randomized, controlled study of wound and adhesion characteristics with or without CMHAB was conducted at 5 level I trauma centers. Consenting patients were randomized to either CMHAB or no adhesion barrier (NAB) groups. We evaluated patient demographics, injury characteristics/severity, reason for OA management, wound sizes (transverse/longitudinal), Zuhlke adhesion score, abdominal contamination score, hospital/intensive care durations of stay, morbidity, and mortality., Results: Thirty patients were enrolled (17 randomized to CMHAB; 13 randomized to NAB) with mean age of 40.3, Injury Severity Score of 30, Abbreviated Injury Score (AIS)-abdomen of 3.68, APACHE II score of 14.4, and 67% blunt trauma mechanism. The groups were well-matched with regard to age, sex, Injury Severity Score/abdominal AIS, penetrating/blunt injury rates, initial lactate/base deficit, mortality, OA indications, and contamination scores. There were no differences in nonabdominal or abdominal complications (ie, fistula, abscess, wound related) between the groups. Patients with CMHAB had shorter intensive care unit durations of stay (15 vs 22 days; P < .05). Intraoperative adhesion scores were not different during the first four operations but diverged significantly at the 5th operative intervention or after about 1 week of OA therapy. After the 5th operation, adhesion scores in the NAB group were 67% greater (approximately 1 Zuhlke point) than the CMHAB group. We did not note differences between wound sizes over time, closure types, or wound closure characteristics between CMHAB and NAB., Conclusion: Although CMHAB did not eliminate adhesions in this proof-of-concept study, it limited their severity, particularly in abdomens left open >9 days or requiring ≥5 operations. There was no difference in wound sizes, overall or abdominal complications, or mortality between the groups. Further research is warranted to better delineate potential benefits of CMHAB, especially in the setting of reoperations in post-OA patients., (Copyright © 2014 Mosby, Inc. All rights reserved.)

First described in 1924, necrotizing fasciitis (NF) is a rapidly progressing, severe suppurative infection of the superficial fascia, often associated with vascular thrombosis and necrosis of the overlying skin. Despite advances in medical therapy, the mortality remains high, with rates exceeding 25 to 50% in some studies. Early diagnosis and treatment is paramount in the management of this serious infection and should include wide surgical debridement and drainage of all necrotic tissues, coupled with aggressive parenteral antibiotics. This infectious process has been commonly associated with traumatic events in patients with compromised immune systems, diabetes, chronic steroid use, and alcoholism. The common microbacterial organisms associated with necrotizing fasciitis include Streptococcus pyogenes and Staphylococcus aureus and less commonly, facultative and anaerobic microorganisms. Most cases typically present in the extremities, trunk, and/or groin regions. Although this virulent soft tissue infection can occur within the face and neck areas, cases of isolated periorbital NF have been relatively uncommon. However, head and neck cases of NF have had high associated morbidity and mortality rates. In recent publications, the reported mortality rate for isolated periorbital NF was not insignificant, ranging from 8.5 to 12.5%. The prognosis, morbidity, and mortality rates will be greatly increased in those patients who present late in the infectious phase, have a delay in diagnosis and/or treatment, or who demonstrate extension of this virulent infection into the face, cervical, or sternal/mediastinal regions. An aggressive multimodal approach is required in treating periorbital necrotizing infection, with the main tenant remaining wide and adequate surgical debridement of affected tissues. This difficult clinical situation can create a subsequent challenge with respect to achieving good functional and cosmetic outcomes in those patients with periorbital NF. Delayed reconstruction of the eyelids with skin grafts and/or facial flaps is often required to avoid late complications such as cicatricial lid retraction, lid malposition, exposure keratopathy, and potential loss of vision. We describe a patient who presented to a military combat hospital with a virulent periorbital soft tissue infection. We have outlined his treatment course from the initial presentation through definitive reconstruction., (Published by Elsevier Inc.)

Session ratings of perceived exertion (SRPE) are sensitive to changes in total work volume and work rate during resistance training. This study examined the influence of work distribution (varied load, set, and repetitions [reps]) on SRPE in 2 resistance exercise trials matched for total work volume (sets × reps × percentage of 1 repetition maximum [% 1RM]) and work rate (total work volume/time). Participants completed a low load/high rep (LLHR) trial (2 sets × 12 reps × 3-minute recovery at ∼60% 1RM) and a high load/low rep (HLLR) trial (3 sets × 6 reps × 1.5-minute recovery at ∼80% 1RM) of the bench press, lat pull-down, overhead press, upright row, triceps extension, and biceps curl. A 2-minute recovery separated each exercise in both trials. Session ratings of perceived exertion and recovery heart rate (HR) were recorded 20 minutes after exercise. Preset and postset RPE and HR were higher for HLLR vs. LLHR (3.1 ± 1.6; 104 ± 15 b·min-1 vs. 2.1 ± 1.3; 98 ± 10 b·min-1) and (5.5 ± 0.9; 139 ± 14 b·min-1 vs. 4.4 ± 0.9; 131 ± 12 b·min-1), respectively. Session RPE was higher for HLLR (5.7 ± 1.4) vs. LLHR (4.3 ± 1.4) with no difference in recovery HR. Session ratings of perceived exertion was greater with higher load despite matched total volumes and work rates. Higher preset acute RPE and HR in HLLR may indicate differences in recovery between sets. Higher postset acute RPE and HR in HLLR indicated increased difficulty of individual sets in HLLR, which likely contributed to SRPE differences. Practitioners can be confident that SRPE accurately reflects changes in training load when the number of sets, reps, and loads are altered within routine training.

A current controversy is whether patients with sepsis progress to an immunosuppressed state. We hypothesized that reactivation of latent viruses occurred with prolonged sepsis thereby providing evidence of clinically-relevant immunosuppression and potentially providing a means to serially-monitor patients' immune status. Secondly, if viral loads are markedly elevated, they may contribute to morbidity and mortality. This study determined if reactivation of herpesviruses, polyomaviruses, and the anellovirus TTV occurred in sepsis and correlated with severity. Serial whole blood and plasma samples from 560 critically-ill septic, 161 critically-ill non-septic, and 164 healthy age-matched patients were analyzed by quantitative-polymerase-chain-reaction for cytomegalovirus (CMV), Epstein-Barr (EBV), herpes-simplex (HSV), human herpes virus-6 (HHV-6), and TTV. Polyomaviruses BK and JC were quantitated in urine. Detectable virus was analyzed with respect to secondary fungal and opportunistic bacterial infections, ICU duration, severity of illness, and survival. Patients with protracted sepsis had markedly increased frequency of detectable virus. Cumulative viral DNA detection rates in blood were: CMV (24.2%), EBV (53.2%), HSV (14.1%), HHV-6 (10.4%), and TTV (77.5%). 42.7% of septic patients had presence of two or more viruses. The 50% detection rate for herpesviruses was 5-8 days after sepsis onset. A small subgroup of septic patients had markedly elevated viral loads (>104-106 DNA copies/ml blood) for CMV, EBV, and HSV. Excluding TTV, DNAemia was uncommon in critically-ill non-septic patients and in age-matched healthy controls. Compared to septic patients without DNAemia, septic patients with viremia had increased fungal and opportunistic bacterial infections. Patients with detectable CMV in plasma had higher 90-day mortality compared to CMV-negative patients; p<0.05. Reactivation of latent viruses is common with prolonged sepsis, with frequencies similar to those occurring in transplant patients on immunosuppressive therapy and consistent with development of an immunosuppressive state. Whether reactivated latent viruses contribute to morbidity and mortality in sepsis remains unknown.

This study examined the separate effects of caffeine and menthol on cognition and mood during simulated firefighting in the heat. Participants (N = 10) performed three trials in a counterbalanced order, either with 400 mg caffeine, menthol lozenges, or placebo. The simulated firefighting consisted of 2 bouts of 20-min treadmill exercise and one bout of 20-min stepping exercise in the heat with two brief 15-min rest periods between each exercise phase. Exercise induced significant dehydration (>3%) and elevated rectal temperature (>38.9 °C), for all three conditions. Neither caffeine nor menthol reduced perceived exertion compared to placebo (p > 0.05). Mood ratings (i.e., alertness, hedonic tone, tension) significantly deteriorated over time (p < 0.05), but there was no difference among the three conditions. Simple reaction time, short-term memory, and retrieval memory did not alter with treatments or repeated evaluations. Reaction accuracy from a math test remained unchanged throughout the experimental period; reaction time from the math test was significantly faster after exposure to the heat (p < 0.05). It is concluded that, exhaustive exercise in the heat severely impacted mood, but minimally impacted cognition. These treatments failed to show ergogenic benefits in a simulated firefighting paradigm in a hot environment., (Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

Regulatory T cells (Treg cells) express members of the tumor-necrosis factor (TNF) receptor superfamily (TNFRSF), but the role of those receptors in the thymic development of Treg cells is undefined. We found here that Treg cell progenitors had high expression of the TNFRSF members GITR, OX40 and TNFR2. Expression of those receptors correlated directly with the signal strength of the T cell antigen receptor (TCR) and required the coreceptor CD28 and the kinase TAK1. The neutralization of ligands that are members of the TNF superfamily (TNFSF) diminished the development of Treg cells. Conversely, TNFRSF agonists enhanced the differentiation of Treg cell progenitors by augmenting responsiveness of the interleukin 2 receptor (IL-2R) and transcription factor STAT5. Costimulation with the ligand of GITR elicited dose-dependent enrichment for cells of lower TCR affinity in the Treg cell repertoire. In vivo, combined inhibition of GITR, OX40 and TNFR2 abrogated the development of Treg cells. Thus, expression of members of the TNFRSF on Treg cell progenitors translated strong TCR signals into molecular parameters that specifically promoted the development of Treg cells and shaped the Treg cell repertoire.

Background: The carbon stored in vegetation varies across tropical landscapes due to a complex mix of climatic and edaphic variables, as well as direct human interventions such as deforestation and forest degradation. Mapping and monitoring this variation is essential if policy developments such as REDD+ (Reducing Emissions from Deforestation and Forest Degradation) are to be known to have succeeded or failed., Results: We produce a map of carbon storage across the watershed of the Tanzanian Eastern Arc Mountains (33.9 million ha) using 1,611 forest inventory plots, and correlations with associated climate, soil and disturbance data. As expected, tropical forest stores more carbon per hectare (182 Mg C ha(-1)) than woody savanna (51 Mg C ha(-1)). However, woody savanna is the largest aggregate carbon store, with 0.49 Pg C over 9.6 million ha. We estimate the whole landscape stores 1.3 Pg C, significantly higher than most previous estimates for the region. The 95% Confidence Interval for this method (0.9 to 3.2 Pg C) is larger than simpler look-up table methods (1.5 to 1.6 Pg C), suggesting simpler methods may underestimate uncertainty. Using a small number of inventory plots with two censuses (n = 43) to assess changes in carbon storage, and applying the same mapping procedures, we found that carbon storage in the tree-dominated ecosystems has decreased, though not significantly, at a mean rate of 1.47 Mg C ha(-1) yr(-1) (c. 2% of the stocks of carbon per year)., Conclusions: The most influential variables on carbon storage in the region are anthropogenic, particularly historical logging, as noted by the largest coefficient of explanatory variable on the response variable. Of the non-anthropogenic factors, a negative correlation with air temperature and a positive correlation with water availability dominate, having smaller p-values than historical logging but also smaller influence. High carbon storage is typically found far from the commercial capital, in locations with a low monthly temperature range, without a strong dry season, and in areas that have not suffered from historical logging. The results imply that policy interventions could retain carbon stored in vegetation and likely successfully slow or reverse carbon emissions.

CD28 is a critical regulator of T cell function, augmenting proliferation, cytokine secretion, and cell survival. Our previous work using knockin mice expressing point mutations in CD28 demonstrated that the distal proline motif was primarily responsible for much of CD28 function, whereas in marked contrast to prior studies, mutation of the PI3K-binding motif had little discernible effect. In this study, we examined the phenotype of mice in which both motifs are simultaneously mutated. We found that mutation of the PYAP motif unmasks a critical role for the proximal tyrosine motif in regulating T cell proliferation and expression of Bcl-xL but not cytokine secretion. In addition, we demonstrated that, although function is more severely impaired in the double mutant than in either single mutant, there remained residual CD28-dependent responses, definitively establishing that additional motifs can partially mediate CD28 function.

Much of the biodiversity-related climate change impacts research has focused on the direct effects to species and ecosystems. Far less attention has been paid to the potential ecological consequences of human efforts to address the effects of climate change, which may equal or exceed the direct effects of climate change on biodiversity. One of the most significant human responses is likely to be mediated through changes in the agricultural utility of land. As farmers adapt their practices to changing climates, they may increase pressure on some areas that are important to conserve (conservation lands) whereas lessening it on others. We quantified how the agricultural utility of South African conservation lands may be altered by climate change. We assumed that the probability of an area being farmed is linked to the economic benefits of doing so, using land productivity values to represent production benefit and topographic ruggedness as a proxy for costs associated with mechanical workability. We computed current and future values of maize and wheat production in key conservation lands using the DSSAT4.5 model and 36 crop-climate response scenarios. Most conservation lands had, and were predicted to continue to have, low agricultural utility because of their location in rugged terrain. However, several areas were predicted to maintain or gain high agricultural utility and may therefore be at risk of near-term or future conversion to cropland. Conversely, some areas were predicted to decrease in agricultural utility and may therefore prove easier to protect from conversion. Our study provides an approximate but readily transferable method for incorporating potential human responses to climate change into conservation planning., (© 2013 Society for Conservation Biology.)

This study examined sex-specific responses during self-paced, high-intensity interval training (HIIT). Sixteen (8 men and 8 women) individuals completed a peak oxygen uptake test and 3 treadmill HIIT sessions on separate days. The HIIT sessions consisted of six 4-minute intervals performed at the highest self-selected intensity individuals felt they could maintain. Recovery between intervals was counterbalanced and consisted of 1-, 2-, or 4-minute recovery during each trial. Relative measures of intensity, including percentage of velocity at VO2peak (vVO2peak), %VO2peak, %HRmax, and blood lactate concentration ([La]), were observed during the trials. Perceived readiness was recorded immediately before and ratings of perceived exertion (RPE) were recorded at the end of each interval with session RPE recorded after each trial. Results revealed a significant effect of sex on %vVO2peak (p < 0.01) and %HRmax (p < 0.01). Data show that across trials, men self-select higher %vVO2peak (84.5 vs. 80.7%), whereas women produce higher %HRmax (96.9 vs. 92.1%) and %VO2peak (89.6 vs. 86.1%) with no difference in [La] or perceptual responses. These findings support the notion that women may demonstrate improved recovery during high-intensity exercise, as they will self-select intensities resulting in greater cardiovascular strain. Moreover, results confirm previous findings suggesting that a 2:1 work-to-rest ratio is optimal during HIIT for both men and women.

Reduced folic acid derivatives support biosynthesis of DNA, RNA and amino acids in bacteria as well as in eukaryotes, including humans. While the genes and steps for bacterial folic acid synthesis are known, those associated with folic acid catabolism are not well understood. A folate catabolite found in both humans and bacteria is p -aminobenzoyl-glutamate (PABA-GLU). The enzyme p -aminobenzoyl-glutamate hydrolase (PGH) breaks down PABA-GLU and is part of an apparent operon, the abg region, in E. coli . The subunits of PGH possess sequence and catalytic similarities to carboxypeptidase enzymes from Pseudomonas species. A comparison of the subunit sequences and activity of PGH, relative to carboxypeptidase enzymes, may lead to a better understanding of bacterial physiology and pathway evolution. We first compared the amino acid sequences of AbgA, AbgB and carboxypeptidase G 2 from Pseudomonas sp. RS-16, which has been crystallized. Then we compared the enzyme activities of E. coli PGH and commercially available Pseudomonas carboxypeptidase G using spectrophotometric assays measuring cleavage of PABA-GLU, folate, aminopterin, methotrexate, 5-formyltetrahydrofolate, and 5-methyltetrahydrofolate. The K m and V max values for the folate and anti-folate substrates of PGH could not be determined, because the instrument reached its limit before the enzyme was saturated. Therefore, activity of PGH was compared to the activity of CPG, or normalized to PABA-GLU (nmole/min/µg). Relative to its activity with 10 µM PABA-GLU (100%), PGH cleaved glutamate from methotrexate (48%), aminopterin (45%) and folate (9%). Reduced folates leucovorin (5-formyltetrahydrofolate) and 5-methyltetrahydrofolate were not cleaved by PGH. Our data suggest that E. coli PGH is specific for PABA-GLU as its activity with natural folates (folate, 5-methyltetrahydrofolate, and leucovorin) was very poor. It does, however, have some ability to cleave anti-folates which may have clinical applications in treatment of chemotherapy overdose.

Background: Children in care often have poor outcomes. There is a lack of evaluative research into intervention options., Aims: To examine the efficacy of Multidimensional Treatment Foster Care for Adolescents (MTFC-A) compared with usual care for young people at risk in foster care in England., Method: A two-arm single (assessor) blinded randomised controlled trial (RCT) embedded within an observational quasi-experimental case-control study involving 219 young people aged 11-16 years (trial registration: ISRCTN 68038570). The primary outcome was the Child Global Assessment Scale (CGAS). Secondary outcomes were ratings of educational attendance, achievement and rate of offending., Results: The MTFC-A group showed a non-significant improvement in CGAS outcome in both the randomised cohort (n = 34, adjusted mean difference 1.3, 95% CI -7.1 to 9.7, P = 0.75) and in the trimmed observational cohort (n = 185, adjusted mean difference 0.95, 95% CI -2.38 to 4.29, P = 0.57). No significant effects were seen in secondary outcomes. There was a possible differential effect of the intervention according to antisocial behaviour., Conclusions: There was no evidence that the use of MTFC-A resulted in better outcomes than usual care. The intervention may be more beneficial for young people with antisocial behaviour but less beneficial than usual treatment for those without.

Background: Good nutrition is important during pregnancy, breastfeeding and early life to optimise the health of women and children. It is difficult for low-income families to prioritise spending on healthy food. Healthy Start is a targeted United Kingdom (UK) food subsidy programme that gives vouchers for fruit, vegetables, milk, and vitamins to low-income families. This paper reports an evaluation of Healthy Start from the perspectives of women and health practitioners., Methods: The multi-method study conducted in England in 2011/2012 included focus group discussions with 49 health practitioners, an online consultation with 620 health and social care practitioners, service managers, commissioners, and user and advocacy groups, and qualitative participatory workshops with 85 low-income women. Additional focus group discussions and telephone interviews included the views of 25 women who did not speak English and three women from Traveller communities., Results: Women reported that Healthy Start vouchers increased the quantity and range of fruit and vegetables they used and improved the quality of family diets, and established good habits for the future. Barriers to registration included complex eligibility criteria, inappropriate targeting of information about the programme by health practitioners and a general low level of awareness among families. Access to the programme was particularly challenging for women who did not speak English, had low literacy levels, were in low paid work or had fluctuating incomes. The potential impact was undermined by the rising price of food relative to voucher value. Access to registered retailers was problematic in rural areas, and there was low registration among smaller shops and market stalls, especially those serving culturally diverse communities., Conclusions: Our evaluation of the Healthy Start programme in England suggests that a food subsidy programme can provide an important nutritional safety net and potentially improve nutrition for pregnant women and young children living on low incomes. Factors that could compromise this impact include erosion of voucher value relative to the rising cost of food, lack of access to registered retailers and barriers to registering for the programme. Addressing these issues could inform the design and implementation of food subsidy programmes in high income countries.

Session ratings of perceived exertion (SRPE) during resistance training may be influenced by specific exercise parameters. The purpose of this study was to examine the influence of work rate (total work per unit time) and recording time on SRPE. Participants performed 3 exercise bouts of bench press, lat pull-down, overhead press, upright row, triceps extension, and biceps curl at 60% of predetermined 1 repetition maximum according to these protocols: (a) 3 sets × 8 repetitions (reps) × 1.5 minutes of recovery, (b) 3 sets × 8 reps × 3 minutes of recovery, and (c) 2 sets × 12 reps × 3 minutes of recovery. Session ratings of perceived exertion for the 3 × 8 × 1.5-minute recovery (5.3 ± 1.8) and 2 × 12 × 3-minute recovery trials (6.2 ± 1.7) were significantly greater vs. 3 × 8 × 3-minute recovery trial (4.2 ± 1.8). The difference approached significance between work rate-matched protocols (p = 0.08). No difference was observed between SRPE at 15 minutes (5.1 ± 1.8) vs. 30 minutes (5.2 ± 1.9) post exercise. Post-set in-task ratings of perceived exertion were higher for the 2 × 12 × 3-minute recovery trial (5.9 ± 1.4) vs. 3 × 8 × 1.5-minute recovery trial (4.8 ± 1.2) and 3 × 8 × 3-minute recovery trial (4.0 ± 1.6). The difference approached significance (p = 0.07) for the 3 × 8 × 3-minute recovery trial vs. 3 × 8 × 1.5-minute recovery trial. Session ratings of perceived exertion responded to changes in work rate with no significant difference at matched work rates, indicating that SRPE is responsive to training load. Results indicated that more proximal monitoring (15 minutes post exercise) yielded reliable estimates of SRPE increasing the practical utility of the measure.

Sepsis remains the leading cause of death in most intensive care units. Advances in understanding the immune response to sepsis provide the opportunity to develop more effective therapies. The immune response in sepsis can be characterized by a cytokine-mediated hyper-inflammatory phase, which most patients survive, and a subsequent immune-suppressive phase. Patients fail to eradicate invading pathogens and are susceptible to opportunistic organisms in the hypo-inflammatory phase. Many mechanisms are responsible for sepsis-induced immuno-suppression, including apoptotic depletion of immune cells, increased T regulatory and myeloid-derived suppressor cells, and cellular exhaustion. Currently in clinical trial for sepsis are granulocyte macrophage colony stimulating factor and interferon gamma, immune-therapeutic agents that boost patient immunity. Immuno-adjuvants with promise in clinically relevant animal models of sepsis include anti-programmed cell death-1 and interleukin-7. The future of immune therapy in sepsis will necessitate identification of the immunologic phase using clinical and laboratory parameters as well as biomarkers of innate and adaptive immunity.

Current American College of Sports Medicine (ACSM) guidelines recommend replacing 150% of sweat losses between training bouts separated by ≤12 hours, but little evidence exists concerning the implications of this strategy for runners. Participants (n = 13) in this study replaced 75% (1637 ± 372 mL) or 150% (3099 ± 850 mL) of sweat losses following an outdoor evening run (∼75 minutes; Wet-bulb-globe temperature (WBGT) = ∼27°C) and consumed a standardised evening meal and breakfast before completing an outdoor (WBGT = ∼23°C) 10-km time-trial the following morning. Urine was collected between runs and urine specific gravity (USG) was assessed pre-run. Significant differences were found in pre-run body mass (75% = 69.6 ± 9.2; 150% = 70.1 ± 9.3 kg; P = 0.02) and USG (75% = 1.026 ± 0.005; 150% = 1.014 ± 0.007; P < 0.001). Heart rate during 10-km run (168 ± 14 versus 168 ± 12 beats min(-1)) and post-run intestinal temperature (39.08 ± 0.52 versus 39.00 ± 0.70 °C) did not differ for 75% and 150%, respectively, despite an ∼3% performance improvement (75% = 47.28 ± 6.64; 150% = 45.93 ± 6.04 minutes; P = 0.001) due to a faster pace in the second half of the run with 150% replacement. Session rate of perceived exertion (RPE) was lower (P = 0.02) during 150% (7.5 ± 1.3) versus 75% (8.4 ± 0.9). Reluctant drinkers potentially hinder training quality between evening and morning runs in the heat, but copious urine production and difficulty in consuming recommended fluid volumes suggest fluid replacement <150% may be more ideal.

Background: Management of destructive colon injuries during damage control (DC) laparotomy is debated. The authors reviewed a single institution's experience with destructive colon injuries to identify risk factors for anastomotic failure after colon reconstruction., Methods: The authors identified all trauma patients sustaining destructive colon injuries between 2002 and 2011 from their medical center's trauma registry. Anastomotic leak was defined as suture or staple line disruption or enteral fistula formation., Results: Of 171 identified patients, 68 had DC procedures, 41 (60%) had subsequent anastomoses performed during the same hospitalization, and 27 (40%) were diverted. The colon anastomotic leak rate in patients who underwent DC laparotomy was higher than in patients who were reconstructed at the primary operation in a non-DC setting (17% vs 6%, P = .09). The use of vasopressors after the initial DC operation more than quadrupled the leak rate to 50% (P = .02)., Conclusions: Colonic anastomotic disruptions yield deadly consequences, and diversion rather than anastomosis should be used in patients who require vasopressor support after the initial DC procedure., (Copyright © 2013 Elsevier Inc. All rights reserved.)