The US federal regulation "Exception from Informed Consent for Emergency Research," 21 Code of Federal Regulations 50.24, permits emergency research without informed consent under limited conditions. Additional safeguards to protect human subjects include requirements for community consultation and public disclosure prior to starting the research. Because the regulations are vague about these requirements, Institutional Review Boards determine the adequacy of these activities at a local level. Thus, there is potential for broad interpretation and practice variation.
We tested the hypothesis that reduced root cortical cell file number (CCFN) would improve drought tolerance in maize (Zea mays L.) by reducing the metabolic costs of soil exploration. Maize genotypes with contrasting CCFN were grown under well-watered and water-stressed conditions in greenhouse mesocosms and in the field in the USA and Malawi. CCFN ranged from 6 to 19 among maize genotypes. In mesocosms reduced CCFN was correlated with 57% reduction of root respiration per unit root length. Under water stress in the mesocosms, genotypes with reduced CCFN had between 15% and 60% deeper rooting (D95), 78% greater stomatal conductance, 36% greater leaf CO2 assimilation, and between 52% to 139% greater shoot biomass than genotypes with many cell files. Under water stress in the field, genotypes with reduced CCFN had between 33% to 40 %deeper rooting (D95), 28% lighter stem water ?18O signature signifying deeper water capture, between 10% to 35% greater leaf relative water content, between 35% and 70% greater shoot biomass at flowering, and between 33% and 114% greater yield than genotypes with many cell files. These results support the hypothesis that reduced CCFN improves drought tolerance by reducing the metabolic costs of soil exploration, enabling deeper soil exploration, greater water acquisition, and improved growth and yield under water stress. The large genetic variation for CCFN in maize germplasm suggest that CCFN merits attention as a breeding target to improve the drought tolerance of maize and possibly other cereal crops.
ABSTRACT Mantle cell lymphoma (MCL) is a rare B-cell malignancy that carries a relatively poor prognosis compared to other forms of non-Hodgkin's lymphoma. Standardized preclinical tools are desperately required to hasten the discovery and translation of promising new treatments for MCL. Through an initiative organized through the Mantle Cell Lymphoma Consortium and the Lymphoma Research Foundation, we gathered MCL cell lines from laboratories around the world to create a characterized MCL cell bank at the American Type Culture Collection (ATCC). Initiated in 2006, this collection now contains 8 cell lines, all of which have been rigorously characterized and are now stored and available for distribution to the general scientific community. We believe the awareness and use of these standardized cell lines will decrease variability between investigators, harmonize international research efforts, improve our understanding of the pathogenesis of the disease, and hasten the development of novel treatment strategies.
The objective of this study was to test the hypothesis that large cortical cell size would improve drought tolerance by reducing root metabolic costs. Maize lines contrasting in root cortical cell size (CCS) measured as cross-sectional area were grown under well-watered and water-stressed conditions in greenhouse mesocosms and in the field in the USA and in Malawi. CCS varied among genotypes, ranging from 101 to 533 µm2.In mesocosms large CCS reduced respiration per unit root length by 59%.Under water stress in mesocosms, lines with large CCS had between 21% and 27% deeper rooting (D95), 50% greater stomatal conductance, 59% greater leaf CO2 assimilation, and between34% and44% greater shoot biomass than lines with small CCS. Under water stress in the field, lines with large CCS had between 32% and 41%deeper rooting (D95), 32% lighter stem water ?18O signature signifying deeper water capture, between 22%and30% greater leaf relative water content, between 51% and 100% greater shoot biomass at flowering, and between 99% and 145% greater yield than lines with small cells. Our results are consistent with the hypothesis that large CCS improves drought tolerance by reducing the metabolic cost of soil exploration, enabling deeper soil exploration, greater water acquisition, and improved growth and yield under water stress. These results coupled with the substantial genetic variation for CCS in diverse maize germplasm suggest that CCS merits attention as a potential breeding target to improve the drought tolerance of maize and possibly other cereal crops.
Occupational stress is a major physical and mental hazard for many workers and has been found to contribute to cardiovascular disease, musculoskeletal disorders, mood disturbances, workplace injuries, and mental health problems. Health care utilization related to these physical and mental health problems costs employers billions of dollars annually. To combat this problem, employers should adopt a preventive approach and institute organizational and administrative changes that require the participation of both management and workers. This article reviews policies that could impact the quality of work life and influence organizational changes needed to achieve occupational health and safety. Occupational health nurses play a vital role in designing and implementing policies to improve work environments and reduce occupational stress. [Workplace Health Saf 2014;62(10):432-438.].
The dietary compound capsaicin is responsible for the "hot and spicy" taste of chili peppers and pepper extracts. It is a valuable pharmacological agent with several therapeutic applications in controlling pain and inflammation. Emerging studies show that it displays potent anti-tumor activity in several human cancers. On a more basic research level, capsaicin has been used as a ligand to activate several types of ion-channel receptors. The pharmacological activity of capsaicin-like compounds is dependent on several factors like the dose, the route of administration and most importantly on its concentration at target tissues. The present review describes the current knowledge involving the metabolism and bioavailability of capsaicinoids in rodents and humans. Novel drug delivery strategies used to improve the bioavailability and therapeutic index of capsaicin are discussed in detail. The generation of novel capsaicin-mimetics and improved drug delivery methods will foster the hope of innovative applications of capsaicin in human disease.
Exposure to hypoxia elicits an increase in minute ventilation (VM) that diminishes during continued exposure (roll-off). Brainstem N-methyl-D-aspartate receptors (NMDAR) and neuronal nitric oxide synthase (nNOS) contribute to the initial hypoxia-induced increases in VM. Roll off is regulated by platelet-derived growth factor receptor-? (PDGFR-?) and S-nitrosoglutathione reductase (GSNOR). S-nitrosylation inhibits activities of NMDAR and nNOS but enhances GSNOR activity. The importance of S-nitrosylation in the hypoxic ventilatory response (HVR) is unknown. This study confirms that ventilatory roll-off is virtually absent in female GSNOR+/- and GSNO-/- mice and evaluated the location of GSNOR in female mouse brainstem, and temporal changes in GSNOR activity, protein expression and S-nitrosylation status of GSNOR, NMDAR (1, 2A, 2B), nNOS and PDGFR-? during hypoxic challenge. GSNOR-positive neurons were present throughout the brainstem including the nucleus tractus solitarius. Protein abundances for GSNOR, nNOS, all NMDAR subunits and PDGFR-? were not altered by hypoxia. GSNOR activity and S-nitrosylation status temporally increased with hypoxia. In addition, nNOS S-nitrosylation increased with 3 min and 15 min of hypoxia. Changes in NMDAR S-nitrosylation were detected in NMDAR 2B at 15 min of hypoxia. No hypoxia-induced changes in PDGFR-? S-nitrosylation were detected. However, PDGFR-? phosphorylation increased in the brainstems of wild-type mice during hypoxic exposure (consistent with roll-off) whereas it did not rise in GSNOR+/- mice (consistent with lack of roll-off). These data suggest that (a) S-nitrosylation events regulate HVR, (b) increases in S-nitrosylation of NMDAR 2B, nNOS, and GSNOR may contribute to ventilatory roll-off and (c) GSNOR regulates PDGFR-? phosphorylation.
Root anatomical trait variation is described for three maize RIL populations. Six quantitative trait loci (QTL) are presented for anatomical traits: root cross-sectional area, % living cortical area, aerenchyma area, and stele area. Root anatomy is directly related to plant performance, influencing resource acquisition and transport, the metabolic cost of growth, and the mechanical strength of the root system. Ten root anatomical traits were measured in greenhouse-grown plants from three recombinant inbred populations of maize [intermated B73 × Mo17 (IBM), Oh43 × W64a (OhW), and Ny821 × H99 (NyH)]. Traits included areas of cross section, stele, cortex, aerenchyma, and cortical cells, percentages of the cortex occupied by aerenchyma, and cortical cell file number. Significant phenotypic variation was observed for each of the traits, with maximum values typically seven to ten times greater than minimum values. Means and ranges were similar for the OhW and NyH populations for all traits, while the IBM population had lower mean values for the majority of traits, but a 50 % greater range of variation for aerenchyma area. A principal component analysis showed a similar trait structure for the three families, with clustering of area and count traits. Strong correlations were observed among area traits in the cortex, stele, and cross-section. The aerenchyma and percent living cortical area traits were independent of other traits. Six QTL were identified for four of the traits. The phenotypic variation explained by the QTL ranged from 4.7 % (root cross-sectional area, OhW population) to 12.0 % (percent living cortical area, IBM population). Genetic variation for root anatomical traits can be harnessed to increase abiotic stress tolerance and provide insights into mechanisms controlling phenotypic variation for root anatomy.
Suboptimal nitrogen (N) availability is a primary constraint for crop production in developing nations, while in rich nations, intensive N fertilization carries substantial environmental and economic costs. Therefore, understanding root phenes that enhance N acquisition is of considerable importance. Structural-functional modeling predicts that root cortical aerenchyma (RCA) could improve N acquisition in maize (Zea mays). We evaluated the utility of RCA for N acquisition by physiological comparison of maize recombinant inbred lines contrasting in RCA grown under suboptimal and adequate N availability in greenhouse mesocosms and in the field in the United States and South Africa. N stress increased RCA formation by 200% in mesocosms and by 90% to 100% in the field. RCA formation substantially reduced root respiration and root N content. Under low-N conditions, RCA formation increased rooting depth by 15% to 31%, increased leaf N content by 28% to 81%, increased leaf chlorophyll content by 22%, increased leaf CO2 assimilation by 22%, increased vegetative biomass by 31% to 66%, and increased grain yield by 58%. Our results are consistent with the hypothesis that RCA improves plant growth under N-limiting conditions by decreasing root metabolic costs, thereby enhancing soil exploration and N acquisition in deep soil strata. Although potential fitness tradeoffs of RCA formation are poorly understood, increased RCA formation appears be a promising breeding target for enhancing crop N acquisition.
Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1-6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.
Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication.
Several root anatomical phenes affect water acquisition from drying soil, and may therefore have utility in breeding more drought-tolerant crops. Anatomical phenes that reduce the metabolic cost of the root cortex ('cortical burden') improve soil exploration and therefore water acquisition from drying soil. The best evidence for this is for root cortical aerenchyma; cortical cell file number and cortical senescence may also be useful in this context. Variation in the number and diameter of xylem vessels strongly affects axial water conductance. Reduced axial conductance may be useful in conserving soil water so that a crop may complete its life cycle under terminal drought. Variation in the suberization and lignification of the endodermis and exodermis affects radial water conductance, and may therefore be important in reducing water loss from mature roots into dry soil. Rhizosheaths may protect the water status of young root tissue. Root hairs and larger diameter root tips improve root penetration of hard, drying soil. Many of these phenes show substantial genotypic variation. The utility of these phenes for water acquisition has only rarely been validated, and may have strong interactions with the spatiotemporal dynamics of soil water availability, and with root architecture and other aspects of the root phenotype. This complexity calls for structural-functional plant modelling and 3D imaging methods. Root anatomical phenes represent a promising yet underexplored and untapped source of crop breeding targets.
Many interventions to reduce allergen levels in the home are recommended to asthma and allergy patients. One that is readily available and can be highly effective is the use of high performing filters in forced air ventilation systems.
Imaging is paramount in the setting of blunt trauma and is now the standard of care at any trauma center. Although anteroposterior radiography has inherent limitations, the ability to acquire a radiograph in the trauma bay with little interruption in clinical survey, monitoring, and treatment, as well as radiography's accepted role in screening for traumatic aortic injury, supports the routine use of chest radiography. Chest CT or CT angiography is the gold-standard routine imaging modality for detecting thoracic injuries caused by blunt trauma. There is disagreement on whether routine chest CT is necessary in all patients with histories of blunt trauma. Ultimately, the frequency and timing of CT chest imaging should be site specific and should depend on the local resources of the trauma center as well as patient status. Ultrasound may be beneficial in the detection of pneumothorax, hemothorax, and pericardial hemorrhage; transesophageal echocardiography is a first-line imaging tool in the setting of suspected cardiac injury. In the blunt trauma setting, MRI and nuclear medicine likely play no role in the acute setting, although these modalities may be helpful as problem-solving tools after initial assessment. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
QTL were identified for root architectural traits in maize. Root architectural traits, including the number, length, orientation, and branching of the principal root classes, influence plant function by determining the spatial and temporal domains of soil exploration. To characterize phenotypic patterns and their genetic control, three recombinant inbred populations of maize were grown for 28 days in solid media in a greenhouse and evaluated for 21 root architectural traits, including length, number, diameter, and branching of seminal, primary and nodal roots, dry weight of embryonic and nodal systems, and diameter of the nodal root system. Significant phenotypic variation was observed for all traits. Strong correlations were observed among traits in the same root class, particularly for the length of the main root axis and the length of lateral roots. In a principal component analysis, relationships among traits differed slightly for the three families, though vectors grouped together for traits within a given root class, indicating opportunities for more efficient phenotyping. Allometric analysis showed that trajectories of growth for specific traits differ in the three populations. In total, 15 quantitative trait loci (QTL) were identified. QTL are reported for length in multiple root classes, diameter and number of seminal roots, and dry weight of the embryonic and nodal root systems. Phenotypic variation explained by individual QTL ranged from 0.44 % (number of seminal roots, NyH population) to 13.5 % (shoot dry weight, OhW population). Identification of QTL for root architectural traits may be useful for developing genotypes that are better suited to specific soil environments.
Abstract Objective. The objective of this guideline is to recommend evidence-based practices for timely prehospital pediatric seizure cessation while avoiding respiratory depression and seizure recurrence. Methods. A multidisciplinary panel was chosen based on expertise in pediatric emergency medicine, prehospital medicine, and/or evidence-based guideline development. The panel followed the National Prehospital EBG Model using the GRADE methodology to formulate questions, retrieve evidence, appraise the evidence, and formulate recommendations. The panel members initially searched the literature in 2009 and updated their searches in 2012. The panel finalized a draft of a patient care algorithm in 2012 that was presented to stakeholder organizations to gather feedback for necessary revisions. Results. Five strong and ten weak recommendations emerged from the process; all but one was supported by low or very low quality evidence. The panel sought to ensure that the recommendations promoted timely seizure cessation while avoiding respiratory depression and seizure recurrence. The panel recommended that all patients in an active seizure have capillary blood glucose checked and be treated with intravenous (IV) dextrose or intramuscular (IM) glucagon if <60 mg/dL (3 mmol/L). The panel also recommended that non-IV routes (buccal, IM, or intranasal) of benzodiazepines (0.2 mg/kg) be used as first-line therapy for status epilepticus, rather than the rectal route. Conclusions. Using GRADE methodology, we have developed a pediatric seizure guideline that emphasizes the role of capillary blood glucometry and the use of buccal, IM, or intranasal benzodiazepines over IV or rectal routes. Future research is needed to compare the effectiveness and safety of these medication routes.
Abstract Background. The management of acute traumatic pain is a crucial component of prehospital care and yet the assessment and administration of analgesia is highly variable, frequently suboptimal, and often determined by consensus-based regional protocols. Objective. To develop an evidence-based guideline (EBG) for the clinical management of acute traumatic pain in adults and children by advanced life support (ALS) providers in the prehospital setting. Methods. We recruited a multi-stakeholder panel with expertise in acute pain management, guideline development, health informatics, and emergency medical services (EMS) outcomes research. Representatives of the National Highway Traffic Safety Administration (sponsoring agency) and a major childrens research center (investigative team) also contributed to the process. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to guide the process of question formulation, evidence retrieval, appraisal/synthesis, and formulation of recommendations. The process also adhered to the National Prehospital Evidence-Based Guideline (EBG) model process approved by the Federal Interagency Council for EMS and the National EMS Advisory Council. Results. Four strong and three weak recommendations emerged from the process; two of the strong recommendations were linked to high- and moderate-quality evidence, respectively. The panel recommended that all patients be considered candidates for analgesia, regardless of transport interval, and that opioid medications should be considered for patients in moderate to severe pain. The panel also recommended that all patients should be reassessed at frequent intervals using a standardized pain scale and that patients should be re-dosed if pain persists. The panel suggested the use of specific age-appropriate pain scales. Conclusion. GRADE methodology was used to develop an evidence-based guideline for prehospital analgesia in trauma. The panel issued four strong recommendations regarding patient assessment and narcotic medication dosing. Future research should define optimal approaches for implementation of the guideline as well as the impact of the protocol on safety and effectiveness metrics.
Abstract Background. Decisions about the transportation of trauma patients by helicopter are often not well informed by research assessing the risks, benefits, and costs of such transport. Objective. The objective of this evidence-based guideline (EBG) is to recommend a strategy for the selection of prehospital trauma patients who would benefit most from aeromedical transportation. Methods. A multidisciplinary panel was recruited consisting of experts in trauma, EBG development, and emergency medical services (EMS) outcomes research. Representatives of the Federal Interagency Committee on Emergency Medical Services (FICEMS), the National Highway Traffic Safety Administration (NHTSA) (funding agency), and the Childrens National Medical Center (investigative team) also contributed to the process. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to guide question formulation, evidence retrieval, appraisal/synthesis, and formulate recommendations. The process followed the National Evidence-Based Guideline Model Process, which has been approved by the Federal Interagency Committee on EMS and the National EMS Advisory Council. Results. Two strong and three weak recommendations emerged from the process, all supported only by low or very low quality evidence. The panel strongly recommended that the 2011 CDC Guideline for the Field Triage of Injured Patients be used as the initial step in the triage process, and that ground emergency medical services (GEMS) be used for patients not meeting CDC anatomic, physiologic, and situational high-acuity criteria. The panel issued a weak recommendation to use helicopter emergency medical services (HEMS) for higher-acuity patients if there is a time-savings versus GEMS, or if an appropriate hospital is not accessible by GEMS due to systemic/logistical factors. The panel strongly recommended that online medical direction should not be required for activating HEMS. Special consideration was given to the potential need for local adaptation. Conclusions. Systematic and transparent methodology was used to develop an evidence-based guideline for the transportation of prehospital trauma patients. The recommendations provide specific guidance regarding the activation of GEMS and HEMS for patients of varying acuity. Future research is required to strengthen the data and recommendations, define optimal approaches for guideline implementation, and determine the impact of implementation on safety and outcomes including cost.
Abstract Background. The burgeoning literature in prehospital care creates an opportunity to improve care through evidence-based guidelines (EBGs). Previously, an established process for the creation of such guidelines and adoption and implementation at the local level was lacking. This has led to great variability in the content of prehospital protocols in different jurisdictions across the globe. Recently the Federal Interagency Committee on Emergency Medical Services (FICEMS) and the National EMS Advisory Council (NEMSAC) approved a National Prehospital Evidence-based Guideline Model Process for the development, implementation, and evaluation of EBGs. The Model Process recommends the use of established guideline development tools such as Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Objective. To describe the process of development of three prehospital EBGs using the National Prehospital EBG Model Process (EBG Model Process) and the GRADE EBG development tool. Methods. We conducted three unique iterations of the EBG Model Process utilizing the GRADE EBG development tool. The process involved 6 distinct and essential steps, including 1) assembling the expert panel and providing GRADE training; 2) defining the evidence-based guideline (EBG) content area and establishing the specific clinical questions to address in patient, intervention, comparison, and outcome (PICO) format; 3) prioritizing outcomes to facilitate systematic literature searches; 4) creating GRADE tables, or evidence profiles, for each PICO question; 5) vetting and endorsing GRADE evidence tables and drafting recommendations; and 6) synthesizing recommendations into an EMS protocol and visual algorithm. Feedback and suggestions for improvement were solicited from participants and relevant stakeholders in the process. Results. We successfully used the process to create three separate prehospital evidence-based guidelines, formatted into decision tree algorithms with levels of evidence and graded recommendations assigned to each decision point. However, the process revealed itself to be resource intensive, and most of the suggestions for improvement would require even more resource utilization. Conclusions. The National Prehospital EBG Model Process can be used to create credible, transparent, and usable prehospital evidence-based guidelines. We suggest that a centralized or regionalized approach be used to create and maintain a full set of prehospital EBGs as a means of optimizing resource use.
Background and Aims Formation of root cortical aerenchyma (RCA) can be induced by nutrient deficiency. In species adapted to aerobic soil conditions, this response is adaptive by reducing root maintenance requirements, thereby permitting greater soil exploration. One trade-off of RCA formation may be reduced radial transport of nutrients due to reduction in living cortical tissue. To test this hypothesis, radial nutrient transport in intact roots of maize (Zea mays) was investigated in two radiolabelling experiments employing genotypes with contrasting RCA. Methods In the first experiment, time-course dynamics of phosphate loading into the xylem were measured from excised nodal roots that varied in RCA formation. In the second experiment, uptake of phosphate, calcium and sulphate was measured in seminal roots of intact young plants in which variation in RCA was induced by treatments altering ethylene action or genetic differences. Key Results In each of three paired genotype comparisons, the rate of phosphate exudation of high-RCA genotypes was significantly less than that of low-RCA genotypes. In the second experiment, radial nutrient transport of phosphate and calcium was negatively correlated with the extent of RCA for some genotypes. Conclusions The results support the hypothesis that RCA can reduce radial transport of some nutrients in some genotypes, which could be an important trade-off of this trait.
Abstract Objective. To describe pediatric patients transported by the Pediatric Emergency Care Applied Research Networks (PECARNs) affiliated emergency medical service (EMS) agencies and the process of submitting and aggregating data from diverse agencies. Methods. We conducted a retrospective analysis of electronic patient care data from PECARNs partner EMS agencies. Data were collected on all EMS runs for patients less than 19 years old treated between 2004 and 2006. We conducted analyses only for variables with usable data submitted by a majority of participating agencies. The investigators aggregated data between study sites by recoding it into categories and then summarized it using descriptive statistics. Results. Sixteen EMS agencies agreed to participate. Fourteen agencies (88%) across 11 states were able to submit patient data. Two of these agencies were helicopter agencies (HEMS). Mean time to data submission was 378 days (SD 175). For the 12 ground EMS agencies that submitted data, there were 514,880 transports, with a mean patient age of 9.6 years (SD 6.4); 53% were male, and 48% were treated by advanced life support (ALS) providers. Twenty-two variables were aggregated and analyzed, but not all agencies were able to submit all analyzed variables and for most variables there were missing data. Based on the available data, median response time was 6 minutes (IQR: 4-9), scene time 15 minutes (IQR: 11-21), and transport time 9 minutes (IQR: 6-13). The most common chief complaints were traumatic injury (28%), general illness (10%), and respiratory distress (9%). Vascular access was obtained for 14% of patients, 3% received asthma medication, <1% pain medication, <1% assisted ventilation, <1% seizure medication, <1% an advanced airway, and <1% CPR. Respiratory rate, pulse, systolic blood pressure, and GCS were categorized by age and the majority of children were in the normal range except for systolic blood pressure in those under one year old. Conclusions. Despite advances in data definitions and increased use of electronic databases nationally, data aggregation across EMS agencies was challenging, in part due to variable data collection methods and missing data. In our sample, only a small proportion of pediatric EMS patients required prehospital medications or interventions.
Abstract Background. In 2008, the National Highway Traffic Safety Administration funded the development of a model process for the development and implementation of evidence-based guidelines (EBGs) for emergency medical services (EMS). We report on the implementation and evaluation of an evidence-based prehospital pain management protocol developed using this model process. Methods. An evidence-based protocol for prehospital management of pain resulting from injuries and burns was reviewed by the Protocol Review Committee (PRC) of the Maryland Institute for Emergency Medical Services Systems (MIEMSS). The PRC recommended revisions to the Maryland protocol that reflected recommendations in the EBG: weight-based dosing and repeat dosing of morphine. A training curriculum was developed and implemented using Marylands online Learning Management System and successfully accessed by 3,941 paramedics and 15,969 BLS providers. Field providers submitted electronic patient care reports to the MIEMSS statewide prehospital database. Inclusion criteria were injured or burned patients transported by Maryland ambulances to Maryland hospitals whose electronic patient care records included data for level of EMS provider training during a 12-month preimplementation period and a 12-month postimplementation period from September 2010 through March 2012. We compared the percentage of patients receiving pain scale assessments and morphine, as well as the dose of morphine administered and the use of naloxone as a rescue medication for opiate use, before and after the protocol change. Results. No differences were seen in the percentage of patients who had a pain score documented or the percent of patients receiving morphine before and after the protocol change, but there was a significant increase in the total dose and dose in mg/kg administered per patient. During the postintervention phase, patients received an 18% higher total morphine dose and a 14.9% greater mg/kg dose. Conclusions. We demonstrated that the implementation of a revised statewide prehospital pain management protocol based on an EBG developed using the National Prehospital Evidence-based Guideline Model Process was associated with an increase in dosing of narcotic pain medication consistent with that recommended by the EBG. No differences were seen in the percentage of patients receiving opiate analgesia or in the documentation of pain scores.
Nicotine, the addictive component of cigarettes, promotes lung cancer proliferation via the ?7-nicotinic acetylcholine receptor (?7-nAChR) subtype. The present manuscript explores the effect of nicotine exposure on ?7-nAChR levels in squamous cell carcinoma of the lung (SCC-L) in vitro and in vivo. Nicotine (at concentrations present in the plasma of average smokers) increased ?7-nAChR levels in human SCC-L cell lines. Nicotine-induced up-regulation of ?7-nAChR was confirmed in vivo by chicken chorioallantoic membrane models. We also observed that the levels of ?7-nAChR in human SCC-L tumors (isolated from patients who are active smokers) correlated with their smoking history. Nicotine increased the levels of ?7-nAChR mRNA and ?7-nAChR transcription in human SCC-L cell lines and SCC-L tumors. Nicotine-induced up-regulation of ?7-nAChR required GATA4 and GATA6. ChIP assays showed that nicotine induced the binding of GATA4 or GATA6 to Sp1 on the ?7-nAChR promoter, thereby inducing its transcription and increasing its levels in human SCC-L. Our data are clinically relevant because SCC-L patients smoked for decades before being diagnosed with cancer. It may be envisaged that continuous exposure to nicotine (in such SCC-L patients) causes up-regulation of ?7-nAChRs, which facilitates tumor growth and progression. Our results will also be relevant to many SCC-L patients exposed to nicotine via second-hand smoke, electronic cigarettes, and patches or gums to quit smoking.
Dyspnea, described as breathlessness or shortness of breath, is usually caused by cardiopulmonary disease. The role of imaging in chronic dyspnea (>1 mo in duration) with suspected pulmonary origin is reviewed as suggested by the American College of Radiology Appropriateness Criteria Expert Panel on Thoracic Imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
The solitary pulmonary nodule (SPN) is a common medical problem for which management can be quite complex. Imaging remains at the center of management of SPNs, and computed tomography is the primary modality by which SPNs are characterized and followed up for stability. This manuscript summarizes the American College of Radiology Appropriateness Criteria for radiographically detected solitary pulmonary nodules and briefly reviews the various imaging techniques available. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Pulmonary hypertension (PH) may be idiopathic or related to a variety of diseases. The diagnosis, accurate assessment of etiology and severity, prognosis, treatment response, and follow-up of PH can be achieved using a diverse set of diagnostic examinations. In this review, the role of imaging in the evaluation of PH as suggested by the American College of Radiology Appropriateness Criteria Expert Panel on Thoracic Imaging has been discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The development and review of the guidelines include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Root cortical aerenchyma (RCA) increases water and nutrient acquisition by reducing the metabolic costs of soil exploration. In this study the hypothesis was tested that living cortical area (LCA; transversal root cortical area minus aerenchyma area and intercellular air space) is a better predictor of root respiration, soil exploration and, therefore, drought tolerance than RCA formation or root diameter.
Daily routine chest radiographs in the intensive care unit (ICU) have been a tradition for many years. Anecdotal reports of misplacement of life support items, acute lung processes, and extra pulmonary air collections in a small number of patients served as a justification for routine chest radiographs in the ICU. Having analyzed this practice, the ACR Appropriateness Criteria Expert Panel on Thoracic Imaging has made the following recommendations: • When monitoring a stable patient or a patient on mechanical ventilation in the ICU, a portable chest radiograph is appropriate for clinical indications only. • It is appropriate to obtain a chest radiograph after placement of an endotracheal tube, central venous line, Swan-Ganz catheter, nasogastric tube, feeding tube, or chest tube. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The strongest data contributing to these recommendations were derived from a meta-analysis of 8 trials comprising 7,078 ICU patients by Oba and Zaza .
The National Lung Screening Trial (NLST) has provided compelling evidence of the efficacy of lung cancer screening using low-dose helical computed tomography (LDCT) to reduce lung cancer mortality. The NLST randomized 53,454 older current or former heavy smokers to receive LDCT or chest radiography (CXR) for three annual screens. Participants were observed for a median of 6.5 years for outcomes. Vital status was available in more than 95% of participants. LDCT was positive in 24.2% of screens, compared with 6.9% of CXRs; more than 95% of all positive LDCT screens were not associated with lung cancer. LDCT detected more than twice the number of early-stage lung cancers and resulted in a stage shift from advanced to early-stage disease. Complications of LDCT screening were minimal. Lung cancer-specific mortality was reduced by 20% relative to CXR; all-cause mortality was reduced by 6.7%. The major harms of LDCT are radiation exposure, high false-positive rates, and the potential for overdiagnosis. This review discusses the risks and benefits of LDCT screening as well as an approach to LDCT implementation that incorporates systematic screening practice with smoking cessation programs and offers opportunities for better determination of appropriate risk cohorts for screening and for better diagnostic prediction of lung cancer in the setting of screen-detected nodules. The challenges of implementation are considered for screening programs, for primary care clinicians, and across socioeconomic strata. Considerations for future research to complement imaging-based screening to reduce the burden of lung cancer are discussed.
Although short in duration, air pollutant exposures occurring in non-residential microenvironments (MEs), including restaurants, vehicles and commercial locations, can represent a large fraction of total personal exposures. For the Sources and Composition of Particulate Exposures study, a novel compact sampling system was developed, facilitating simultaneous measurement of highly speciated PM(2.5) mass in a range of commercial and residential locations. This sampler also included 1-min measurements of PM(2.5) mass and ultrafine particle (UFP) counts. Sampling was conducted in a number of MEs (retail stores, restaurants and vehicles) throughout Atlanta. Chemically resolved particulate measurements in these locations are of interest for both exposure scientists and epidemiologists but have typically not been conducted because of logistical constraints associated with sampling these trace constituents. We present measurements from a non-random sample of locations that are limited in their generalizability but provide several promising hypothesis-generating results. PM(2.5) mass concentrations greater than 100? ?g/m(3), and UFPs>10(5) particles /cm(3) were measured during several events in the restaurant and vehicle. Somewhat unexpectedly, the grocery store ME, along with the restaurant and vehicle, also had the highest levels of elemental carbon (EC), organic carbon (OC) and most elements. In-vehicle concentrations of soil-related elements (Al, Ca, Fe, K and Ti) and auto-related elements (EC, OC, Zn and Cu) were higher than those measured at a central ambient site. The lowest concentrations for most pollutants were found in the hospital and retail locations. It is questionable whether periodic, high PM concentrations in the grocery store and restaurant pose health risks for customers; however, individuals working in these locations may be exposed to levels of concern.
Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the ?7-nicotinic acetylcholine receptor (?7-nAChR) on endothelial cells. Therefore, we conjectured that ?7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule ?7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation of primary human microvascular endothelial cells of the lung (HMEC-Ls). Furthermore, MG624 displayed robust anti-angiogenic activity in the Matrigel, rat aortic ring and rat retinal explant assays. The anti-angiogenic activity of MG624 was assessed by two in vivo models, namely the chicken chorioallantoic membrane model and the nude mice model. In both of these experimental models, MG624 inhibited angiogenesis of human SCLC tumors. Most importantly, the administration of MG624 was not associated with any toxic side effects, lethargy or discomfort in the mice. The anti-angiogenic activity of MG624 was mediated via the suppression of nicotine-induced FGF2 levels in HMEC-Ls. MG624 decreased nicotine-induced early growth response gene 1 (Egr-1) levels in HMEC-Ls, and reduced the levels of Egr-1 on the FGF2 promoter. Consequently, this process decreased FGF2 levels and angiogenesis. Our findings suggest that the anti-angiogenic effects of MG624 could be useful in anti-angiogenic therapy of human SCLCs.
Several studies linking alterations in differential placental methylation with pregnancy disorders have implicated (de)regulation of the placental epigenome with fetal programming and later-in-life disease. We have previously demonstrated that maternal tobacco use is associated with alterations in promoter methylation of placental CYP1A1 and that these changes are correlated with CYP1A1 gene expression and fetal growth restriction. In this study we sought to expand our analysis of promoter methylation by correlating it to gene expression on a genome-wide scale. Employing side-by-side IlluminaHG-12 gene transcription with Infinium27K methylation arrays, we interrogated correlative changes in placental gene expression and DNA methylation associated with maternal tobacco smoke exposure at an epigenome-wide level and in consideration of signature gene pathways. We observed that the expression of 623 genes and the methylation of 1024 CpG dinucleotides are significantly altered among smokers, with only 38 CpGs showing significant differential methylation (differing by a methylation level of ?10%). We identified a significant Pearson correlation (?0.7 or ?-0.7) between placental transcriptional regulation and differential CpG methylation in only 25 genes among non-smokers but in 438 genes among smokers (18-fold increase, p < 0.0001), with a dominant effect among oxidative stress pathways. Differential methylation at as few as 6 sites was attributed to maternal smoking-mediated birth weight reduction in linear regression models with Bonferroni correction (p < 1.8 × 10(-6)). These studies suggest that a common perinatal exposure (such as maternal smoking) deregulates placental methylation in a CpG site-specific manner that correlates with meaningful alterations in gene expression along signature pathways.
Accurate staging of lung cancer is necessary to describe and communicate disease extent, predict prognosis, determine therapy, and evaluate the results of clinical trials. The Union Internationale Contre le Cancer and the American Joint Committee on Cancer published the seventh edition of tumor, node, and metastasis in lung cancer in 2009. Changes to the sixth edition have been based on the analysis of a large database of patients with lung cancer by the International Staging Committee of the International Association for the Study of Lung Cancer. This study reviews the new seventh edition of the tumor, node, and metastasis lung cancer staging system and discusses the radiologic and therapeutic implications.
Acute respiratory illness is defined as one or more of the following: cough, sputum production, chest pain, or dyspnea (with or without fever). The workup of these patients depends on many factors, including clinical presentation and the suspected etiology. This study reviews the literature on the indications and usefulness of radiologic studies for the evaluation of acute respiratory illness in the immunocompetent patient. The following recommendations are the result of evidence-based consensus by the American College of Radiology Appropriateness Criteria Expert Panel on Thoracic Radiology. Chest radiographs are usually appropriate in (1) patients with positive physical examination or risk factors for pneumonia, (2) for the assessment of complicated pneumonia, or (3) in cases of emerging infections and biological warfare agents such as severe acute respiratory syndrome, H1N1, and anthrax. Computed tomography, although having a more limited role, is usually appropriate (1) in the assessment of complicated pneumonia and (2) in patients with suspected severe acute respiratory syndrome, H1N1, or anthrax and a normal radiograph.
Although organ transplants have been applied for decades, outcomes of somatic cell transplants remain disappointing, presumably due to lack of appropriate supporting stromal cells. Thus, cotransplantation with liver stromal cells, hepatic stellate cells (HSC), achieves long-term survival of islet allografts in mice by way of induction of effector T cell apoptosis and generation of regulatory T (Treg) cells. In this study we provide evidence both in vitro and in vivo that HSC can promote generation of myeloid-derived suppressor cells (MDSC). HSC-induced MDSC demonstrate potent immune inhibitory activity. Induction of MDSC is dependent on an intact interferon gamma signaling pathway in HSC and is mediated by soluble factors, suggesting that the specific tissue stromal cells, such as HSC, play a crucial role in regulating immune response by way of inflammation-induced generation of MDSC. Large amounts of MDSC can be propagated in vitro from bone marrow-derived myeloid precursor cells under the influence of HSC.
Vertical placement of roots within the soil determines their efficiency of acquisition of heterogeneous belowground resources. This study quantifies the architectural traits of seedling basal roots of bean (Phaseolus vulgaris), and shows that the distribution of root tips at different depths results from a combined effect of both basal root growth angle (BRGA) and root length. Based on emergence locations, the basal roots are classified in three zones, upper, middle, and lower, with each zone having distinct architectural traits. The genotypes characterized as shallow on BRGA alone produced basal roots with higher BRGA, greater length, and more vertically distributed roots than deep genotypes, thereby establishing root depth as a robust measure of root architecture. Although endogenous indole-3-acetic acid (IAA) levels were similar in all genotypes, IAA and 1-N-naphthylphthalamic acid treatments showed different root growth responses to auxin because shallow and deep genotypes tended to have optimal and supraoptimal auxin levels, respectively, for root growth in controls. While IAA increased ethylene production, ethylene also increased IAA content. Although differences in acropetal IAA transport to roots of different zones can account for some of the differences in auxin responsiveness among roots of different emergence positions, this study shows that mutually dependent ethylene-auxin interplay regulates BRGA and root growth differently in different genotypes. Root length inhibition by auxin was reversed by an ethylene synthesis inhibitor. However, IAA caused smaller BRGA in deep genotypes, but not in shallow genotypes, which only responded to IAA in the presence of an ethylene inhibitor.
Screening for pulmonary metastatic disease is an important step for staging a patient with a known or recently discovered malignancy. Here we present our recommendations for screening for metastatic disease based on recommendations from the literature and experiences of pulmonary radiologists. In short, chest computed tomographic (CT) screening is the most appropriate tool for evaluation of pulmonary metastasis in the majority of cases. Chest computed tomographic screening is also recommended for follow-up and to determine response to therapy. Other modalities such as chest radiography, magnetic resonance imaging, and scintigraphy will also be discussed. Please note that this study is a summary of the complete version of this topic, which is available on the ACR website at www.acr.org. Practitioners are encouraged to refer to the complete version.
Efficiency and effectiveness are often used as quality indicators in emergency departments. With an aim to improve patient throughput and departmental efficiency while decreasing left-without-being-seen (LWBS) rates, this two-group, pre-intervention, post-intervention study in a pediatric emergency department evaluated the outcomes of implementing rapid triage on arrival-to-triage time, fast track utilization, and LWBS.
Up to 3 million US children are cared for by emergency medical services (EMSs) annually. Limited research exists on pediatric prehospital care. The Pediatric Emergency Care Applied Research Network (PECARN) mission is to perform high-quality research for children, including prehospital research. Our objective was to develop a pediatric-specific prehospital research agenda.
Supernumerary, derivative, and ring X chromosomes are relatively common in Turner syndrome females but have been reported rarely in males. To date, less than 10 cases have been published, of which only 2 have been partially characterized in defining the breakpoints and genetic content of the derivative X chromosome. We describe a male with mosaicism for a supernumerary X chromosome (46,XY/47,XY, r(X)) who has multiple congenital anomalies, including features of craniofrontonasal dysplasia (Mendelian Inheritance in Man 304110) and the presence of ectopic female reproductive organs. Using comparative genomic hybridization array mapping, we determined that the derivative X is composed of a 24-Mb fragment that contains the regions Xp11.3 through Xq13.1 and lacks the XIST gene. This is the first report to describe a detailed molecular characterization of a ring X chromosome in a male by comparative genomic hybridization array analysis. We compare the clinical and molecular findings in this patient to other 46,XY, r(X) patients reported in the literature and discuss the potential role of disomy for known genes contained on the ring X chromosome.
Lung cancer is the leading cause of cancer-related deaths worldwide, with a dismal 5-year survival rate of 15%. The TNM (tumor-node-metastasis) classification system for lung cancer is a vital guide for determining treatment and prognosis. Despite the importance of accuracy in lung cancer staging, however, correct staging remains a challenging task for many radiologists. The new 7th edition of the TNM classification system features a number of revisions, including subdivision of tumor categories on the basis of size, differentiation between local intrathoracic and distant metastatic disease, recategorization of malignant pleural or pericardial disease from stage III to stage IV, reclassification of separate tumor nodules in the same lung and lobe as the primary tumor from T4 to T3, and reclassification of separate tumor nodules in the same lung but not the same lobe as the primary tumor from M1 to T4. Radiologists must understand the details set forth in the TNM classification system and be familiar with the changes in the 7th edition, which attempts to better correlate disease with prognostic value and treatment strategy. By recognizing the relevant radiologic appearances of lung cancer, understanding the appropriateness of staging disease with the TNM classification system, and being familiar with potential imaging pitfalls, radiologists can make a significant contribution to treatment and outcome in patients with lung cancer.
Hemoptysis is defined as the expectoration of blood originating from the tracheobronchial tree or pulmonary parenchyma, ranging from 100 mL to 1 L in volume over a 24-hour period. This article reviews the literature on the indications and usefulness of radiologic studies for the evaluation of hemoptysis. The following recommendations are the result of evidence-based consensus by the American College of Radiology Appropriateness Criteria Expert Panel on Thoracic Radiology: (1) Initial evaluation of patients with hemoptysis should include a chest radiograph; (2) Patients at high risk for malignancy (>40 y old, >40 pack-year smoking history) with negative chest radiograph, computed tomography (CT) scan, and bronchoscopy can be followed with observation for the following 3 years. Radiography and CT are recommended imaging modalities for follow-up. Bronchoscopy may complement imaging during the period of observation; (3) In patients who are at high risk for malignancy and have suspicious chest radiograph findings, CT is suggested for initial evaluation; CT should also be considered in patients who are active or exsmokers, despite a negative chest radiograph; and (4) Massive hemoptysis can be effectively treated with either surgery or percutaneous embolization. Contrast-enhanced multidetector CT before embolization or surgery can define the source of hemoptysis as bronchial systemic, nonbronchial systemic, and/or pulmonary arterial. Percutaneous embolization may be used initially to halt the hemorrhage before definitive surgery.
The purpose of this study was to explore factors that may help explain the mortality differences between African Americans and Whites. This study was a retrospective analysis of data from Tennessees 95 counties. Standardized mortality ratios (SMRs) for African Americans were determined based on White, all-cause, age-specific mortality rates, and served as the dependent variable. Potential explanatory variables included measures of demography, socioeconomic status, and social environment. Bivariate and multivariate analyses showed a significant association between SMR and population density (t=2.18, p=.037) among 36 counties, with more than 20 African American deaths per year, and between SMR and the proportion of the population that is African American (t=2.23, p=.033) in an analysis that included all 95 counties. Mortality differences based on demographic characteristics, rather than on the usual social determinants of health, raise further questions about the root causes of health inequities.
We compare emergency department (ED) patient flow during the fall 2009 novel H1N1-associated surge in patient volumes at an urban, tertiary care, pediatric medical center to that in the previous winter virus season.
Osteoporosis is a common complication of aging. Alternatives to pharmacologic treatment are needed for older adults. Nonpharmacologic treatment with low magnitude, high frequency mechanical stimulation has been shown to prevent bone loss in animal and human studies.
Root cortical aerenchyma (RCA) reduces root respiration in maize by converting living cortical tissue to air volume. We hypothesized that RCA increases drought tolerance by reducing root metabolic costs, permitting greater root growth and water acquisition from drying soil. To test this hypothesis, recombinant inbred lines with high and low RCA were observed under water stress in the field and in soil mesocosms in a greenhouse. In the field, lines with high RCA had 30% more shoot biomass at flowering compared with lines with low RCA under water stress. Root length density in deep soil was significantly greater in the high RCA lines compared with the low RCA lines. Mid-day leaf relative water content in the high RCA lines was 10% greater than in the low RCA lines under water stress. The high RCA lines averaged eight times the yield of the low RCA lines under water stress. In mesocosms, high RCA lines had less seminal root respiration, deeper rooting, and greater shoot biomass compared with low RCA lines under water stress. These results support the hypothesis that RCA is beneficial for drought tolerance in maize by reducing the metabolic cost of soil exploration.
The purpose of this study was to determine the incidence and distribution of catheter-related problems in long-term indwelling urinary catheter users. We also sought to assess appropriateness of catheter use and examine relationships among catheter complications and catheter care practices.
S-nitrosothiols have been implicated in the etiology of various pulmonary diseases. Many of these diseases display gender preferences in presentation or altered severity that occurs with puberty, the mechanism by which is unknown. Estrogen has been shown to influence the expression and activity of endothelial nitric oxide synthase (eNOS) which is associated with increased S-nitrosothiol production. The effects of gender hormones on the expression and activity of the de-nitrosylating enzyme S-nitrosoglutathione reductase (GSNO-R) are undefined. This report evaluates the effects of gender hormones on the activity and expression of GSNO-R and its relationship to N-acetyl cysteine (NAC)-induced pulmonary hypertension (PH). GSNO-R activity was elevated in lung homogenates from female compared to male mice. Increased activity was not due to changes in GSNO-R expression, but correlated with GSNO-R S-nitrosylation: females were greater than males. The ability of GSNO-R to be activated by S-nitrosylation was confirmed by: 1) the ability of S-nitrosoglutathione (GSNO) to increase the activity of GSNO-R in murine pulmonary endothelial cells and 2) reduced activity of GSNO-R in lung homogenates from eNOS(-/-) mice. Gender differences in GSNO-R activity appear to explain the difference in the ability of NAC to induce PH: female and castrated male animals are protected from NAC-induced PH. Castration results in elevated GSNO-R activity that is similar to that seen in female animals. The data suggest that GSNO-R activity is modulated by both estrogens and androgens in conjunction with hormonal regulation of eNOS to maintain S-nitrosothiol homeostasis. Moreover, disruption of this eNOS-GSNO-R axis contributes to the development of PH.
Cervical spine injuries in children are rare. However, immobilization and imaging for potential cervical spine injury after trauma are common and are associated with adverse effects. Risk factors for cervical spine injury have been developed to safely limit immobilization and radiography in adults, but not in children. The purpose of our study is to identify risk factors associated with cervical spine injury in children after blunt trauma.
The prostate gland represents a multifaceted system in which prostate epithelia and stroma have distinct physiological roles. To understand the interaction between stroma and glandular epithelia, it is essential to delineate the gene expression profiles of these two tissue types in prostate cancer. Most studies have compared tumor and normal samples by performing global expression analysis using a mixture of cell populations. This report presents the first study of prostate tumor tissue that examines patterns of differential expression between specific cell types using laser capture microdissection (LCM).
This study examined how sleep deprivation influenced psychomotor performance of nurses who worked the night shift. Psychomotor performance was measured with the d2 Test of Attention, which quantifies attention, concentration, processing speed, and quality of performance. A sample of 289 licensed nurses was tested with the instrument. Fifty-six percent of the sample was sleep deprived. Mean psychomotor performance scores (26.6 for men and 11.4 for women) were above the normative means (44.4 for men and 41.03 for women). A significant (p<.001) inverse relationship was found between psychomotor performance and hours of sleep. Nurses reported more hours of sleep on a general self-report sleep item than in a sleep diary.
Work environment stress, a salient health and safety issue for secondary school teachers, school administrators, parents, and students, was examined in 168 teachers from two urban and five suburban high schools. The purpose of this study was to examine relationships between ongoing and episodic stressors and anxiety and depression, as well as the extent to which anxiety and depression may be predicted by stressors and coworker and supervisor support. The Ongoing Stressor Scale (OSS) and the Episodic Stressor Scale (ESS), the Coworker and Supervisor Contents of Communication Scales (COCS), the State Anxiety inventory (S-Anxiety), and the Center for Epidemiological Studies Depression Scale (CES-D) were used to measure the variables. Ongoing and episodic stressors were significantly and positively associated with anxiety and depression. Ongoing stressors and coworker support were significant in explaining anxiety and depression among secondary school teachers. Coworker support had an inverse relationship to anxiety and depression.
Pioglitazone is prescribed to improve insulin sensitivity in type 2 diabetes mellitus patients and has been discussed as a therapy for metabolic syndrome. Pioglitazone and other thiazolidinediones are associated with fluid retention and edema that may exacerbate existing or developing congestive heart failure, which is often present in these patients. Using a nonhuman primate model, our aims were to evaluate (1) whether fluid shifts were detectable in normoglycemic monkeys, (2) which fluid compartment changed, and (3) whether fluid retention was dose dependent. Seventeen adult male cynomolgus macaques (Macaca fascicularis) were studied in a Latin square design such that all animals received 0, 1, 2, and 5 mg/kg pioglitazone for 6 weeks with 2 weeks of washout between dosing intervals. Doses approximated human exposures achieved with 30, 45, and 60 mg. At the end of each period, animals were weighed and underwent dual-absorption x-ray absorption scanning for body composition measurements. Fluid volumes were quantitated by Evans blue dilution for plasma volume, equilibration of sodium bromide for extracellular water, and deuterated water for total body water. Significant (P < .05) effects were seen with expansion of PV at both the 2- and 5-mg/kg doses, along with reduced plasma sodium at 5 mg/kg; however, surrogate end points used to indicate fluid retention (body weight, hematocrit, total protein, and albumin) did not change significantly. Significant trends toward increases in interstitial fluid and extracellular water with increasing dose were apparent. Pioglitazone effectively improved metabolic status by significantly decreasing fasting glucose and triglycerides and increasing adiponectin. We conclude that thiazolidinedione-related plasma volume expansion occurs in nondiabetic primates and that fluid retention is detectable when compartments are directly measured.
The existing family presence literature indicates that implementation of a family presence policy can result in positive outcomes. The purpose of our evidence-based practice project was to evaluate a family presence intervention using the 6 As of the evidence cycle (ask, acquire, appraise, apply, analyze, and adopt/adapt). For step 1 (ask), we propose the following question: Is it feasible to implement a family presence intervention during trauma team activations and medical resuscitations in a pediatric emergency department using national guidelines to ensure appropriate family member behavior and uninterrupted patient care?
Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti-proliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.
The liver is considered to be an immune-privileged organ that favors the induction of tolerance. The underlying mechanisms are not completely understood. Interestingly, liver transplants are spontaneously accepted in several animal models, but hepatocyte transplants are acutely rejected, suggesting that liver nonparenchymal cells may effectively protect the parenchymal cells from immune attack. We have shown the profound T cell inhibitory activity of hepatic stellate cells (HSCs). Thus, cotransplantation with HSCs effectively protects islet allografts from rejection in mice. In this study, using T cell receptor transgenic and gene knockout approaches, we provided definitive evidence that HSCs protected cotransplanted islet allografts by exerting comprehensive inhibitory effects on T cells, including apoptotic death in graft-infiltrating antigen-specific effector T cells and marked expansion of CD4(+) Forkhead box protein (Foxp)3(+) T regulatory (Treg) cells. All these effects required an intact interferon-gamma (IFN-gamma) signaling in HSCs, demonstrated by using HSCs isolated from IFN-gamma receptor 1 knockout mice. B7-H1 expression on HSCs, a product molecule of IFN-gamma signaling, was responsible for induction of T cells apoptosis, but had no effect on expansion of Treg cells, suggesting that undetermined effector molecules produced by IFN-gamma signaling is involved in this process.
This analysis examines differences between measured ambient indoor, and personal sulfate concentrations across cities, seasons, and individuals to elucidate how these differences may impact PM2.5 exposure measurement error. Data were analyzed from four panel studies conducted in Atlanta, Baltimore, Boston, and Steubenville (OH). Among the study locations, 1912 person-days of personal sulfate data were collected over 396 days involving 245 individual sampling sessions. Long-term differences in ambient and personal levels averaged over time are examined. Differences between averaged ambient and personal sulfate among and within cities were observed, driven by between subject and city differences in sulfate infiltration, F(inf), from outdoors to indoors. Neglecting this source of variability in associations may introduce bias in studies examining long-term exposures and chronic health. Indoor sulfate was highly correlated with and similar in magnitude to personal sulfate, suggesting indoor PM monitoring may be another means of characterizing true exposure variability.
PPARgamma agonists are synthetic ligands for the peroxisome proliferator-activated receptor-gamma (PPARgamma). These agents have insulin-sensitizing properties but can cause fluid retention, thereby limiting their usefulness in patients at risk for cardiovascular disease. The side effect etiology is unknown, but the nature of presentation suggests modulation of renal salt and water homeostasis. In a well-characterized cell culture model of the principal cell type [Madin-Darby canine kidney (MDCK)-C7], PPARgamma agonists inhibit vasopressin-stimulated Cl(-) secretion with agonist dose-response relationships that mirror receptor transactivation profiles. Analyses of the components of the vasopressin-stimulated intracellular signaling pathway indicated no PPARgamma agonist-induced changes in basolateral membrane conductances, intracellular cAMP, protein kinase A, or total cellular adenine nucleotides. The PPARgamma agonist-induced decrease in anion secretion is the result of decreased mRNA of the final effector in the pathway, the apically located cystic fibrosis transmembrane regulator (CFTR). These data showing that CFTR is a target for PPARgamma agonists may provide new insights into the physiology of PPARgamma agonist-induced fluid retention.
Cigarette smoking bears a strong etiological association with many neovascularization-related diseases like cancer, cardiovascular disease and macular degeneration. Although cigarette smoke is a complex mixture of many compounds, nicotine is the major active and addictive component of tobacco. Recent studies have shown that nicotine can enhance angiogenesis and arteriogenesis in several experimental systems and animal models. The pro-angiogenic activity of nicotine is mediated by nicotinic acetylcholine receptors, which have been found to be expressed on several types of cells in the vasculature like endothelial cells, smooth muscle cells and immune cells. The present review summarizes the pro-angiogenic activity of nicotine in neoplastic and non-neoplastic disease. The present article focuses on the role of nAChRs, particularly alpha7-nAChR in mediating the pro-angiogenic effects of nicotine. The expression patterns of nAChRs on various components of the vasculature are discussed. The complex signaling pathways underlying the angiogenic effect of nAChRs are described. The review also takes a look at the therapeutic potential of nAChR agonists and antagonists in angiogenesis-related diseases. More basic research as well as patient-oriented clinical studies is needed to firmly establish the clinical potential of nAChR ligands in angiogenesis-based therapies. Also the side effects of targeting nAChRs remain to be established in patients. The development of selective nAChR agonists and antagonists with improved specificity may represent novel therapeutic regimens in the treatment of angiogenesis-related diseases.
Obesity is an epidemic in the United States. The relationship between traumatic injury and obesity in children is not well-studied. We hypothesized that overweight children suffer more severe injuries, different distributions of injuries and improper use of restraints in motor vehicle collisions.
Acute gastroenteritis is characterized by diarrhea, which may be accompanied by nausea, vomiting, fever, and abdominal pain.
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