Identifying spring barley cultivars with differential response to tillage

Cultivars and some cultivar mixtures of spring barley were grown under inversion and non-inversion tillage conditions for three or four years and assessed for disease and yield in order to obtain genotypes that can be used to determine the mechanisms of cultivation adaptation. In general, the higher-yielding cultivars under inversion tillage conditions gave lower yields under non-inversion tillage, whereas low-yielding older cultivars showed relatively smaller reductions in yield under non-inversion tillage. A few cultivars showed preferential yield performance for either inversion or non-inversion tillage and this was irrespective of their overall yield performance. There was no pedigree or breeding programme link between these cultivars and no above-ground gross morphological trait observed was associated with tillage adaptation. Root hairs may contribute to inversion tillage adaptation as a root hair absence mutant was associated with non-inversion adaptation and it is likely that other root-associated traits are responsible also for tillage adaptation. There was no overall cultivar or tillage interaction with rhynchosporium symptoms but a differential tillage interaction may occur in individual years. We have identified clearly contrasting cultivars and tested their across-season robustness with respect to tillage treatment for further detailed mechanistic studies and identification of tillage adaptation traits

Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis

L-selectin ligands might be relevant for inflammatory cell trafficking into the small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc mice). Immunoblockade of peripheral node addressin or mucosal addressin cell adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and small intestine by immunohistochemistry and confirmed by real-time reverse transcription polymerase chain reaction and flow cytometry. In addition, reconstitution of wild-type mice with PSGL-1−/− bone marrow demonstrated that PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium, localized within mesenteric lymph node and small intestine. Endothelial PSGL-1 bound P-selectin–IgG and its blockade or genetic deletion altered the recruitment of lymphocytes to the small intestine, as revealed by intravital microscopy and homing studies. Endothelial expression of PSGL-1 adds a new dimension to the various cellular interactions involved in small intestinal recruitment. Thus, the multiple roles of PSGL-1 may explain why targeting this single adhesion molecule results in attenuation of chronic murine ileitis, a disease previously resistant to antiadhesion molecule strategies

Differential Genotype Dependent Inhibition of CYP2C9 in Humans

ABSTRACT: The effects of genetic polymorphisms in drug-metabolizing enzymes (e.g., CYP2C9*3) on drug clearance have been well characterized but much less is known about whether these polymorphisms alter susceptibility to drug-drug interactions. Previous in vitro work has demonstrated that genotype-dependent inhibition of CYP2C9 mediated flurbiprofen metabolism, suggesting the possibility of genotype-dependent inhibition interactions in vivo. In the current study, flurbiprofen was used as a probe substrate and fluconazole as a prototypical inhibitor to investigate whether genotype-dependent inhibition of CYP2C9 occurs in vivo. From 189 healthy volunteers who were genotyped for CYP2C9 polymorphisms, 11 control subjects (CYP2C9*1/*1), 9 heterozygous and 2 homozygous for the CYP2C9*3 allele participated in the pharmacokinetic drug interaction study. Subjects received a single 50-mg oral dose of flurbiprofen alone or after administration of either 200 or 400 mg of fluconazole for 7 days using an open, randomized, crossover design. Flurbiprofen and fluconazole plasma concentrations along with flurbiprofen and 4-hydroxyflurbiprofen urinary excretion were monitored. Flurbiprofen apparent oral clearance differed significantly among the three genotype groups (p < 0.05) at baseline but not after pretreatment with 400 mg of fluconazole for 7 days. Changes in flurbiprofen apparent oral clearance after fluconazole coadministration were gene dose-dependent, with virtually no change occurring in *3/*3 subjects. Analysis of fractional clearances suggested that the fraction metabolized by CYP2C9, as influenced by genotype, determined the degree of drug interaction observed. In summary, the presence of CYP2C9*3 alleles (either one or two alleles) can alter the degree of drug interaction observed upon coadministration of inhibitors. The cytochrome P450 (P450) superfamily of enzymes plays an important role in the oxidation of numerous xenobiotics, with CYP2C9 accounting for 10 to 20% of the P450 protein content in human liver. CYP2C9 has been reported to catalyze approximately 20% of P450-mediated drug oxidation reactions Certain diseases or the presence of comorbid conditions may necessitate coadministration of multiple medications, increasing the chances of drug-drug interactions. However, genetic polymorphisms in drug-metabolizing enzymes are not routinely evaluated for their impact on drug interactions during clinical studies. Genotype-dependent inhibition has been demonstrated with CYP2D6 and CYP2C19 genetic polymorphism

Teen perception of texting and driving in rural West Virginia

In the last decade, texting and driving has evolved into a serious problem among the adolescent population. The goal of this study was to determine if education can effectively raise awareness of the dangers of texting and driving and positively influence the behavior of rural West Virginia teens. A 25 question survey designed to asses teen driving behavior was administered to 143 rural West Virginia high school students before and after and educational session. The educational session was designed to explain how texting and driving impairs driving ability and show graphic images of accidents and injuries that resulted from this behavior. Pre and post-lecture survey responses were then analyzed. The survey results revealed that texting and driving is highly prevalent among rural West Virginia teens, with 57% of teens admitting to this behavior. Around 73% of teens agreed that texting and driving was very dangerous, but many continued to do so regardless. Additionally, 59% admitted to talking on the phone while driving, and 11% admitted to drinking and driving. A single lecture was not observed to reduce texting and driving behavior among the study population. More research is needed to establish an effective method to reduce this dangerous behavior

MicroRNA profiling reveals marker of motor neuron disease in ALS models

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p

Antimicrobial Resistance Distribution Differs Among Methicillin Resistant Staphylococcus aureus Sequence Type (ST) 5 Isolates From Health Care and Agricultural Sources

Antimicrobial resistance (AMR) is an expanding public health concern and methicillin resistant Staphylococcus aureus (MRSA) is a notable example. Since the discovery of livestock associated MRSA (LA-MRSA), public health concerns have arisen surrounding the potential of LA-MRSA isolates to serve as a reservoir for AMR determinants. In this study, we compare swine associated LA-MRSA ST5 and human clinical MRSA ST5 isolates for phenotypic antimicrobial susceptibilities determined via broth microdilution and genotypic determinants of AMR using whole genome sequencing and comparative genomic analysis to identify AMR elements. Swine associated LA-MRSA ST5 isolates exhibited phenotypic resistance to fewer antibiotics than clinical MRSA ST5 isolates from humans with no swine contact. Distinct genomic AMR elements were harbored by each subgroup, with little overlap in shared AMR genes between swine associated LA-MRSA ST5 and clinical MRSA ST5 isolates. Our results demonstrate that phenotypic antimicrobial susceptibilities and genotypic determinants of AMR among swine associated LA-MRSA ST5 and clinical MRSA ST5 isolates are separate and distinct

Angiographic findings and clinical correlates in patients with cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry

AbstractObjectivesWe sought to delineate the angiographic findings, clinical correlates and in-hospital outcomes in patients with cardiogenic shock (CS) complicating acute myocardial infarction.BackgroundPatients with CS complicating acute myocardial infarction carry a grave prognosis. Detailed angiographic findings in a large, prospectively identified cohort of patients with CS are currently lacking.MethodsWe compared the clinical characteristics, angiographic findings, and in-hospital outcomes of 717 patients selected to undergo angiography and 442 not selected, overall and by shock etiology: left or right ventricular failure versus mechanical complications.ResultsPatients who underwent angiography had lower baseline risk and a better hemodynamic profile than those who did not. Overall, 15.5% of the patients had significant left main lesions on angiography, and 53.4% had three-vessel disease, with higher rates of both for those with ventricular failure, compared with patients who had mechanical complications. Among patients who underwent angiography, those with ventricular failure had significantly lower in-hospital mortality than patients with mechanical complications (45.2% vs. 57.0%; p = 0.021). Importantly, for patients with ventricular failure, in-hospital mortality also correlated with disease severity: 35.0% for no or single-vessel disease versus 50.8% for three-vessel disease. Furthermore, mortality was associated with the culprit lesion location (78.6% in left main lesion, 69.7% in saphenous vein graft lesions, 42.4% in circumflex lesions, 42.3% in left anterior descending lesions, and 37.4% in right coronary artery lesions), and Thrombolysis In Myocardial Infarction (TIMI) flow grade (46.5% in TIMI 0/1, 49.4% in TIMI 2 and 26% in TIMI 3).ConclusionsPatients who underwent angiographic study in the SHOCK Trial Registry had a more benign cardiac risk profile, more favorable hemodynamic findings and lower in-hospital mortality than those for whom angiograms were not obtained. Patients with CS caused by ventricular failure had more severe atherosclerosis, and a different distribution of culprit vessel involvement but lower in-hospital mortality, than those with mechanical complications. Overall in-hospital survival correlates with the extent of coronary artery obstructions, location of culprit lesion and baseline coronary TIMI flow grade

White Matter Network Architecture Guides Direct Electrical Stimulation Through Optimal State Transitions

Electrical brain stimulation is currently being investigated as a therapy for neurological disease. However, opportunities to optimize such therapies are challenged by the fact that the beneficial impact of focal stimulation on both neighboring and distant regions is not well understood. Here, we use network control theory to build a model of brain network function that makes predictions about how stimulation spreads through the brain's white matter network and influences large-scale dynamics. We test these predictions using combined electrocorticography (ECoG) and diffusion weighted imaging (DWI) data who volunteered to participate in an extensive stimulation regimen. We posit a specific model-based manner in which white matter tracts constrain stimulation, defining its capacity to drive the brain to new states, including states associated with successful memory encoding. In a first validation of our model, we find that the true pattern of white matter tracts can be used to more accurately predict the state transitions induced by direct electrical stimulation than the artificial patterns of null models. We then use a targeted optimal control framework to solve for the optimal energy required to drive the brain to a given state. We show that, intuitively, our model predicts larger energy requirements when starting from states that are farther away from a target memory state. We then suggest testable hypotheses about which structural properties will lead to efficient stimulation for improving memory based on energy requirements. Our work demonstrates that individual white matter architecture plays a vital role in guiding the dynamics of direct electrical stimulation, more generally offering empirical support for the utility of network control theoretic models of brain response to stimulation

Motorcycle Helmet Effectiveness in Reducing Head, Face and Brain Injuries by State and Helmet Law

Background: Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S. Methods: We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet. Data were combined in the Crash Outcome Data Evaluation System\u27s General Use Model and included motorcycle crash records probabilistically linked to emergency department and inpatient discharges for years 2005-2008. Medical outcomes were compared between partial and universal helmet law settings. We estimated adjusted relative risks (RR) and 95 % confidence intervals (CIs) for head, facial, traumatic brain, and moderate to severe head/facial injuries associated with helmet use within each helmet law setting using generalized log-binomial regression. Results: Reported helmet use was higher in universal law states (88 % vs. 42 %). Median charges, adjusted for inflation and differences in state-incomes, were higher in partial law states (emergency department $1987 vs.$1443; inpatient $31,506 vs.$25,949). Injuries to the head and face, including traumatic brain injuries, were more common in partial law states. Effectiveness estimates of helmet use were higher in partial law states (adjusted-RR (CI) of head injury: 2.1 (1.9-2.2) partial law single vehicle; 1.4 (1.2, 1.6) universal law single vehicle; 1.8 (1.6-2.0) partial law multi-vehicle; 1.2 (1.1-1.4) universal law multi-vehicle). Conclusions: Medical charges and rates of head, facial, and brain injuries among motorcyclists were lower in universal law states. Helmets were effective in reducing injury in both helmet law settings; lower effectiveness estimates were observed in universal law states

Teen perception of texting and driving in rural West Virginia

In the last decade, texting and driving has evolved into a serious problem among the adolescent population. The goal of this study was to determine if education can effectively raise awareness of the dangers of texting and driving and positively influence the behavior of rural West Virginia teens. A 25 question survey designed to asses teen driving behavior was administered to 143 rural West Virginia high school students before and after and educational session. The educational session was designed to explain how texting and driving impairs driving ability and show graphic images of accidents and injuries that resulted from this behavior. Pre and post-lecture survey responses were then analyzed. The survey results revealed that texting and driving is highly prevalent among rural West Virginia teens, with 57% of teens admitting to this behavior. Around 73% of teens agreed that texting and driving was very dangerous, but many continued to do so regardless. Additionally, 59% admitted to talking on the phone while driving, and 11% admitted to drinking and driving. A single lecture was not observed to reduce texting and driving behavior among the study population. More research is needed to establish an effective method to reduce this dangerous behavior