iac May 03 FX Commentary: Bob Iaccino By link.brightcove.com Published On :: Fri, 03 May 2019 13:25:24 -0700 Bob Iaccino, Path Trading Partners Full Article
iac May 06 FX Commentary: Bob Iaccino By link.brightcove.com Published On :: Mon, 06 May 2019 12:22:00 -0700 Bob Iaccino, Path Trading Partners Full Article
iac MAY 09 FX Commentary: Bob Iaccino By link.brightcove.com Published On :: Thu, 09 May 2019 12:36:42 -0700 Bob Iaccino, Path Trading Partners Full Article
iac May 10 FX Commentary: Bob Iaccino By link.brightcove.com Published On :: Fri, 10 May 2019 13:51:08 -0700 Bob Iaccino, Path Trading Partners Full Article
iac May 13 FX Commentary: Bob Iaccino By link.brightcove.com Published On :: Mon, 13 May 2019 13:37:20 -0700 Bob Iaccino, Path Trading Partners Full Article
iac Influence of Birth Hospital on Outcomes of Ductal-Dependent Cardiac Lesions By pediatrics.aappublications.org Published On :: 2010-11-22T10:58:39-08:00 It is not known whether birth at a pediatric cardiac specialty center or at a hospital with a higher neonatal level of care affects mortality for infants with ductal-dependent congenital heart disease. For infants with ductal-dependent congenital heart disease, there is no difference in 90-day mortality for those born at specialty centers versus other centers in the state of Washington. (Read the full article) Full Article
iac Cardiac Screening Prior to Stimulant Treatment of ADHD: A Survey of US-Based Pediatricians By pediatrics.aappublications.org Published On :: 2012-01-16T00:06:48-08:00 Over the past decade, drug oversight committees and professional organizations have debated the evidence regarding cardiac screening to identify undiagnosed disorders associated with sudden cardiac death in youth with attention-deficit/hyperactivity disorder before beginning treatment with stimulants.How practicing pediatricians have responded to this controversy is not known. We present results from a national sample of pediatricians regarding current attitudes, barriers, and practices for cardiac screening in youth with attention-deficit/hyperactivity disorder before prescribing stimulants. (Read the full article) Full Article
iac Effect of Acculturation and Distance From Cardiac Center on Congenital Heart Disease Mortality By pediatrics.aappublications.org Published On :: 2012-05-07T00:07:48-07:00 Disparities in outcomes of ethnic minority children have been reported, and have been ascribed to having barriers to access to health care. Minority parents have indicated that difficulties in access are because of problems with transportation and being non-English speaking.This population-based study of Texas infants with severe congenital heart disease reports that neither home distance from a cardiac center nor Hispanic children having a Latin American–born parent were risk factors for first-year mortality. (Read the full article) Full Article
iac Early Vaccinations Are Not Risk Factors for Celiac Disease By pediatrics.aappublications.org Published On :: 2012-06-25T00:07:30-07:00 Celiac disease is an immunologic disorder with autoimmune features. Sweden experienced an epidemic of celiac disease in infants (1984–1996). Early vaccinations might influence the risk for autoimmune diseases, and could potentially have contributed to celiac disease risk and the epidemic.Early vaccinations within the national Swedish program are not risk factors for celiac disease, nor do changes over time contribute to explaining the Swedish epidemic. A protective effect by vaccination against tuberculosis (bacillus Calmette-Guérin) is suggested. (Read the full article) Full Article
iac Economic Evaluation of Strategies to Reduce Sudden Cardiac Death in Young Athletes By pediatrics.aappublications.org Published On :: 2012-07-02T00:07:33-07:00 Sudden cardiac death in young athletes is an uncommon but devastating event. Addition of routine electrocardiogram (ECG) screening to standard preparticipation care may reduce the number of sudden deaths. Lack of data regarding effectiveness and costs has prevented widespread implementation.Adding ECG screening to current preparticipation evaluation is not cost-effective. Cost is driven primarily by the evaluation of the large number of false-positive findings. An ECG-only screening strategy is more cost-effective. (Read the full article) Full Article
iac Continuous Versus Bolus Infusion of Doxorubicin in Children With ALL: Long-term Cardiac Outcomes By pediatrics.aappublications.org Published On :: 2012-11-19T00:08:01-08:00 Doxorubicin therapy, effective against many malignancies, is limited by cardiotoxicity. Continuous-infusion doxorubicin, compared with bolus-infusion, reduces early cardiotoxicity in adults. Its effectiveness in reducing late cardiotoxicity in children remains uncertain.This multicenter randomized trial assessed whether continuous-infusion of doxorubicin in pediatric patients provides long-term cardioprotection or improvement in event-free survival over bolus-infusion in acute lymphoblastic leukemia. Continuous-infusion of doxorubicin provided no cardioprotection or improvement in event-free survival. (Read the full article) Full Article
iac Prevalence of Childhood Celiac Disease and Changes in Infant Feeding By pediatrics.aappublications.org Published On :: 2013-02-18T00:06:40-08:00 Celiac disease is increasing in several countries and has emerged as a public health problem. Infant feeding has been suggested to affect celiac disease development and/or clinical expression. However, evidence-based complementary feeding strategies are limited.Significant difference in celiac disease prevalence between 2 cohorts of 12-year-olds indicates an option for disease prevention. The cohorts differed in infant feeding, and our findings suggest that gradual introduction of gluten in small amounts during ongoing breastfeeding is favorable. (Read the full article) Full Article
iac The Rising Incidence of Celiac Disease in Scotland By pediatrics.aappublications.org Published On :: 2013-09-09T00:07:21-07:00 The overall incidence of pediatric celiac disease (CD) is rising, as are other autoimmune conditions. Additionally, increasing numbers of children are older at the point of diagnosis and are diagnosed with CD through active screening.Accounting for screened and nonclassic cases, there is an independent 2.5-fold rise in the incidence of classically presenting cases of pediatric CD (Oslo definitions). Thus, indicating a true rise in pediatric CD incidence in southeast Scotland in 20 years. (Read the full article) Full Article
iac Early Feeding and Risk of Celiac Disease in a Prospective Birth Cohort By pediatrics.aappublications.org Published On :: 2013-10-07T00:07:05-07:00 Lower risk of early celiac disease (CD) has been observed with breastfeeding and low dose of gluten at introduction. Gluten introduction before 4 or after 6 months has been associated with increased risk. For CD diagnosed after 2 years, the association is unclear.Gluten introduction delayed to >6 months as well as breastfeeding >12 months was associated with a modest increase in CD in this first population-based birth cohort study, and gluten introduction under continued breastfeeding was not protective. (Read the full article) Full Article
iac Usefulness of Symptoms to Screen for Celiac Disease By pediatrics.aappublications.org Published On :: 2014-01-13T00:06:58-08:00 Celiac disease (CD) often goes undiagnosed. Current guidelines suggest intensified active case-finding, with liberal testing of children with CD-associated symptoms and/or conditions. However, methods for also finding undiagnosed CD cases in the general population should be explored and evaluated.In a population-based CD screening, information on CD-associated symptoms and conditions, obtained before knowledge of CD status, was not useful in discriminating undiagnosed CD cases from non-CD children. The majority of screening-detected CD cases had no CD-associated symptoms or conditions. (Read the full article) Full Article
iac Psychiatric Functioning and Quality of Life in Young Patients With Cardiac Rhythm Devices By pediatrics.aappublications.org Published On :: 2014-03-24T00:06:22-07:00 Initial studies in children and young adults have identified higher levels of anxiety and lower quality of life scores in patients with implantable cardioverter–defibrillators. Few studies are available looking at the same questions in young patients with pacemakers.Anxiety is highly prevalent in young patients with ICDs, but the higher rates can be attributed to medical disease severity and age at implantation rather than type of device. Patients with pacemakers have depression and anxiety but at lower rates. (Read the full article) Full Article
iac Age at Gluten Introduction and Risk of Celiac Disease By pediatrics.aappublications.org Published On :: 2015-01-19T00:05:33-08:00 Both early and late introduction to gluten has been associated with increased risk for celiac disease (CD) and being breastfed at time of gluten introduction has been associated with a lower risk for CD.In this prospective multinational study, time to first introduction to gluten-containing cereals is not an independent risk factor for developing CD, by a 5-year follow-up, neither on an overall level nor on country-level comparison. (Read the full article) Full Article
iac Clinical Features of Celiac Disease: A Prospective Birth Cohort By pediatrics.aappublications.org Published On :: 2015-03-02T00:05:26-08:00 Celiac disease (CD) may develop at any age. Young children with CD are at particular risk for malabsorption and failure to thrive. HLA-DR3-DQ2 homozygotes are at the highest genetic risk and develop CD very early in life.Most children with CD detected in screening by 4 years of age have no symptoms and normal growth. Symptoms are unrelated to HLA genotype. Autoantibody levels correlate higher with severity of mucosal lesions in symptomatic as compared to asymptomatic children. (Read the full article) Full Article
iac Cardiac Biomarkers and Acute Kidney Injury After Cardiac Surgery By pediatrics.aappublications.org Published On :: 2015-03-09T00:05:24-07:00 Acute kidney injury (AKI) occurs in up to 50% of children after cardiopulmonary bypass and is associated with adverse outcomes. Renal biomarkers have been shown to predict postoperative AKI, but few studies have examined cardiac biomarkers for risk classification.Preoperative levels of creatine kinase-MB and heart-type fatty acid binding protein are strongly associated with the development of postoperative AKI after pediatric cardiac surgery and can be used to improve preoperative clinical risk prediction. (Read the full article) Full Article
iac Neurodevelopmental Outcomes After Cardiac Surgery in Infancy By pediatrics.aappublications.org Published On :: 2015-04-27T00:05:20-07:00 Neurodevelopmental disabilities are the most common, and potentially the most damaging, sequelae of congenital heart defects. Children with congenital heart defects undergoing surgery in infancy have problems with reasoning, learning, executive function, inattention and impulsive behavior, language skills, and social skills.Early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk infants with congenital heart defects survive cardiac surgery, a growing population will require significant societal resources. (Read the full article) Full Article
iac Unrecognized Celiac Disease in Children Presenting for Rheumatology Evaluation By pediatrics.aappublications.org Published On :: 2015-06-15T00:06:46-07:00 Associations have been reported between celiac disease (CD) and numerous autoimmune conditions in adults and children. However, current screening guidelines do not consider patients with rheumatic diseases to be at high risk for CD.The prevalence of CD in children presenting for rheumatology evaluation was found to be 2% by routine serologic screening. The majority of screening-detected CD cases had no CD-associated symptoms. Gluten restriction was found to relieve some musculoskeletal complaints. (Read the full article) Full Article
iac Chronic Neuromotor Disability After Complex Cardiac Surgery in Early Life By pediatrics.aappublications.org Published On :: 2015-09-21T00:07:35-07:00 Neurodevelopmental outcomes after cardiac surgery in early life provide critical information for understanding and improving care. Studies show these children are at risk for arterial ischemic stroke and acquired brain injury; further characterization of motor impairment is needed.This study focuses on the presence of chronic neuromotor disabilities including cerebral palsy and motor impairments after acquired brain injury in children surviving early complex cardiac surgery, providing information on the frequency, characteristics, and predictors that may assist in prevention. (Read the full article) Full Article
iac Complex response of the CpxAR two-component system to {beta}-lactams on antibiotic resistance and envelop homeostasis in Enterobacteriaceae [Mechanisms of Resistance] By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 The Cpx stress response is widespread among Enterobacteriaceae. We have previously reported a mutation in cpxA in a multidrug resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields to a single amino acid substitution (Y144N) located in the periplasmic sensor domain of CpxA. In this work, we sought to characterize this mutation in Escherichia coli by using genetic and biochemical approaches. Here, we show that cpxAY144N is an activated allele that confers resistance to β-lactams and aminoglycosides in a CpxR-dependent manner, by regulating the expression of the OmpF porin and the AcrD efflux pump, respectively. We also demonstrate the intimate interconnection between Cpx system and peptidoglycan integrity on the expression of an exogenous AmpC β-lactamase by using imipenem as a cell wall active antibiotic or inactivation of penicillin-binding proteins. Moreover, our data indicate that the Y144N substitution abrogates the interaction between CpxA and CpxP and increase phosphotransfer activity on CpxR. Because the addition of a strong AmpC inducer such as imipenem is known to causes abnormal accumulation of muropeptides (disaccharide-pentapeptide, N-acetylglucosamyl-1,6-anhydro-N-acetylmuramyl-l-alanyl-d-glutamy-meso-diaminopimelic-acid-d-alanyl-d-alanine) in the periplasmic space, we propose these molecules activate the Cpx system by displacing CpxP from the sensor domain of CpxA. Altogether, these data could explain why large perturbations to peptidoglycan caused by imipenem lead to mutational activation of the Cpx system and bacterial adaptation through multidrug resistance. These results also validate the Cpx system, in particular the interaction between CpxA and CpxP, as a promising therapeutic target. Full Article
iac The Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultra-Broad-Spectrum Beta-lactamase Inhibitor of Serine and Metallo Beta-Lactamases in Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii. [Mechanisms of Resis By aac.asm.org Published On :: 2020-03-30T10:04:32-07:00 QPX7728 is an ultra-broad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo beta-lactamases at a nano molar range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impact of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3 producing isogenic strains of K. pneumoniae and P. aeruginosa and OXA-23-producing strains of A. baumannii with various combinations of efflux and porin mutations. QPX7728 was minimally affected by multi-drug resistance efflux pumps in either Enterobacteriaceae, or in non-fermenters such as P. aeruginosa or A. baumannii. In P. aeruginosa, the potency of QPX7728 was further enhanced when the outer membrane is permeabilized. The potency of QPX7728 in P. aeruginosa is not affected by inactivation of the carbapenem porin OprD. While changes in OmpK36 (but not OmpK35) reduced the potency of QPX7728 (8-16-fold), QPX7728 (4 μg/ml) nevertheless completely reversed KPC-mediated meropenem resistance in strains with porin mutations, consistent with a lesser effect of these mutations on the potency of QPX7728 compared to other agents. The ultra-broad-spectrum beta-lactamase inhibition profile combined with enhancement of the activity of multiple beta-lactam antibiotics with varying sensitivity to the intrinsic resistance mechanisms of efflux and permeability indicate QPX7728 is a useful inhibitor for use with multiple beta-lactam antibiotics. Full Article
iac Effect of the Lysin, Exebacase, on Cardiac Vegetation Progression in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus (MRSA) Endocarditis as Determined by Echocardiography [Pharmacology] By aac.asm.org Published On :: 2020-04-27T08:14:56-07:00 Background: MRSA pose significant therapeutic challenges, related to their: frequency in clinical infections; innate virulence properties; and propensity for multi-antibiotic resistance. MRSA are among the most common causes of endovascular infections, including infective endocarditis (IE).Objective: To employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE.Study Design: TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (vs daptomycin alone). Primary intravegetation outcomes were: maximum size; weights at sacrifice; and MRSA counts at infection baseline vs after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment Day 1).Results: A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase + daptomycin vs the daptomycin-alone therapy groups (p = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower vs daptomycin-alone (p < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (p = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower vs untreated controls (p<0.0001) and the daptomycin-alone group (p<0.0001).Conclusion: This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size and weight. Moreover, TTE appears to be an efficient non-invasive tool to assess therapeutic efficacies in experimental MRSA IE. Full Article
iac Combination Therapy Using Benznidazole and Aspirin During the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase [Clinical Therapeutics] By aac.asm.org Published On :: 2020-05-04T08:49:24-07:00 Chagas disease, caused by the protozoan Trypanosoma cruzi, is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy, and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (NFX) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against T. cruzi infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than that in BZ-treated mice. These results were associated with an increase in the number of eosinophils and reticulocytes and level of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the LXA4 receptor antagonist, Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of acute phase of Chagas disease that are beneficial for chronic patients. Full Article
iac Arsenal v Olympiacos facts By www.uefa.com Published On :: Fri, 21 Feb 2020 12:00:00 GMT Alexandre Lacazette's late goal in Greece has given Arsenal the advantage, although Olympiacos won their last game away to the Gunners. Full Article comp_matches
iac Olympiacos v Wolves facts By www.uefa.com Published On :: Mon, 02 Mar 2020 21:00:00 GMT Olympiacos's reward for a dramatic victory against 2019 runners-up Arsenal is another tie against English opposition, Wolverhampton Wanderers. Full Article comp_matches
iac Wolves v Olympiacos facts By www.uefa.com Published On :: Fri, 13 Mar 2020 18:55:00 GMT After a 1-1 draw in Piraeus, Wolverhampton Wanderers and Olympiacos meet at Molineux to decide their round of 16 tie. Full Article comp_matches
iac Viacom and CBS to finally reunite By www.financialexpress.com Published On :: 2019-08-16T00:31:00+05:30 The deal will combine the CBS television network, CBS News, Showtime cable networks with MTV Networks, Nickelodeon, Comedy Central and Paramount Pictures. Full Article Industry
iac Know who is the inspiration of Viacom18 Studios’ Ajit Andhare By www.financialexpress.com Published On :: 2019-09-27T00:39:00+05:30 Elon Musk for his sheer audacity of dreaming unabashedly and then making those impossible dreams come true, says Ajit Andhare, COO, Viacom18 Studios. Full Article Industry
iac Ajit Jogi Suffers Cardiac Arrest, Put On Ventilator, Condition "Serious" By www.ndtv.com Published On :: May 9, 2020 03:47 PM Former Chhattisgarh Chief Minister Ajit Jogi has been admitted to a hospital in Raipurafter he suffered a cardiac arrest at his home this afternoon. His condition is said to be "serious" and is on... Full Article india-news
iac Child Support Begins Sending Payments to New ReliaCard® By news.delaware.gov Published On :: Fri, 14 Feb 2020 20:28:35 +0000 NEW CASTLE (Feb. 14, 2020) – On Monday, Feb. 10, the Delaware Division of Child Support Services successfully began sending payments to the new prepaid debit card, issued by U.S. Bank ReliaCard, for child support recipients. New applicants of the ReliaCard will have payments sent to their card on Feb. 17, 2020. The Division of […] Full Article Delaware Health and Social Services Division of Child Support Services News ReliaCard
iac Ajit Jogi, former Chhattisgarh CM, suffers cardiac arrest; critical By www.financialexpress.com Published On :: 2020-05-09T17:22:00+05:30 Former Chhattisgarh chief minister Ajit Jogi, 74, was admitted in a private hospital here on Saturday after he suffered a cardiac arrest, doctors said, adding that his condition is critical. Full Article India
iac La doctrina de la expiación real, 1ª Parte By feeds.gracia.org Published On :: Mon, 14 Oct 2019 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día. Full Article
iac La Doctrina de la Expiación Real, 2ª Parte By feeds.gracia.org Published On :: Tue, 15 Oct 2019 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día. Full Article
iac La Doctrina de la Expiación Real, 2ª Parte B By feeds.gracia.org Published On :: Wed, 16 Oct 2019 00:00:00 PST La enseñanza bíblica en profundidad de John MacArthur lleva la verdad transformadora de la Palabra de Dios a millones de personas cada día. Full Article
iac Noncardiac Chest Pain May Warrant More Management: Study By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Noncardiac Chest Pain May Warrant More Management: StudyCategory: Health NewsCreated: 4/24/2010 12:10:00 PMLast Editorial Review: 4/26/2010 12:00:00 AM Full Article
iac Migraines More Likely for People With Celiac Disease, Study Says By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Migraines More Likely for People With Celiac Disease, Study SaysCategory: Health NewsCreated: 5/3/2012 4:05:00 PMLast Editorial Review: 5/4/2012 12:00:00 AM Full Article
iac Dispatcher-Assisted CPR Boosts Cardiac Arrest Survival in Kids: Study By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Dispatcher-Assisted CPR Boosts Cardiac Arrest Survival in Kids: StudyCategory: Health NewsCreated: 4/30/2014 4:36:00 PMLast Editorial Review: 5/1/2014 12:00:00 AM Full Article
iac COPD Tied to Raised Risk for Sudden Cardiac Death By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: COPD Tied to Raised Risk for Sudden Cardiac DeathCategory: Health NewsCreated: 4/29/2015 12:00:00 AMLast Editorial Review: 4/29/2015 12:00:00 AM Full Article
iac Cardiac Rehab Boosts Quality of Life After Heart Attack: Study By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Cardiac Rehab Boosts Quality of Life After Heart Attack: StudyCategory: Health NewsCreated: 4/27/2020 12:00:00 AMLast Editorial Review: 4/28/2020 12:00:00 AM Full Article
iac Out-of-Hospital Cardiac Arrests On the Rise During COVID-19 Crisis By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Out-of-Hospital Cardiac Arrests On the Rise During COVID-19 CrisisCategory: Health NewsCreated: 4/30/2020 12:00:00 AMLast Editorial Review: 5/1/2020 12:00:00 AM Full Article
iac Multisociety Roadmap for Restarting Elective Cardiac Cases By www.webmd.com Published On :: Wed, 06 May 2020 12:57:05 EST A new consensus document provides guidance on the safe reintroduction of cardiovascular procedures and testing derailed by the COVID-19 pandemic. Full Article
iac Compensatory Guaiacyl Lignin Biosynthesis at the Expense of Syringyl Lignin in 4CL1-Knockout Poplar By www.plantphysiol.org Published On :: 2020-05-08T08:30:48-07:00 The lignin biosynthetic pathway is highly conserved in angiosperms, yet pathway manipulations give rise to a variety of taxon-specific outcomes. Knockout of lignin-associated 4-coumarate:CoA ligases (4CLs) in herbaceous species mainly reduces guaiacyl (G) lignin and enhances cell wall saccharification. Here we show that CRISPR-knockout of 4CL1 in poplar (Populus tremula x alba) preferentially reduced syringyl (S) lignin, with negligible effects on biomass recalcitrance. Concordant with reduced S-lignin was downregulation of ferulate 5-hydroxylases (F5Hs). Lignification was largely sustained by 4CL5, a low-affinity paralog of 4CL1 typically with only minor xylem expression or activity. Levels of caffeate, the preferred substrate of 4CL5, increased in line with significant upregulation of caffeoyl shikimate esterase1. Upregulation of caffeoyl-CoA O-methyltransferase1 and downregulation of F5Hs are consistent with preferential funneling of 4CL5 products toward G-lignin biosynthesis at the expense of S-lignin. Thus, transcriptional and metabolic adaptations to 4CL1-knockout appear to have enabled 4CL5 catalysis at a level sufficient to sustain lignification. Finally, genes involved in sulfur assimilation, the glutathione-ascorbate cycle, and various antioxidant systems were upregulated in the mutants, suggesting cascading responses to perturbed thioesterification in lignin biosynthesis. Full Article
iac Cerebral venous thrombosis: Associations between disease severity and cardiac markers By cp.neurology.org Published On :: 2020-04-06T12:45:20-07:00 Background Plasma cardiac troponin (cTn) elevation occurs in acute ischemic stroke and intracranial hemorrhage and can suggest a poor prognosis. Because acute cerebral venous thrombosis (CVT) might lead to venous stasis, which could result in cardiac stress, it is important to evaluate whether cTn elevation occurs in patients with CVT. Methods Inpatients at Johns Hopkins Hospital from 2005 to 2015 meeting the following criteria were included: CVT (ICD-9 codes with radiologic confirmation) and available admission electrocardiogram (ECG) and cTn level. In regression models, presence of ECG abnormalities and cTn elevation (>0.06 ng/mL) were evaluated as dependent variables in separate models, with location and severity of CVT involvement as independent variables, adjusted for age, sex, and hypertension. Results Of 81 patients with CVST, 53 (66%) met the inclusion criteria. Participants were, on average, aged 42 years, white (71%), and female (66%). The left transverse sinus was most commonly thrombosed (47%), with 66% having >2 veins thrombosed. Twenty-two (41%) had cTn elevation. Odds of cTn elevation increased per each additional vein thrombosed (adjusted OR 2.79, 95% CI [1.08–7.23]). Of those with deep venous involvement, 37.5% had cTn elevation compared with 4.4% without deep clots (p = 0.02). Venous infarction (n = 15) was associated with a higher mean cTn (0.14 vs 0.02 ng/mL, p = 0.009) and was predictive of a higher cTn in adjusted models (β = 0.15, 95% CI [0.06–0.25]). Conclusions In this single-center cohort study, markers of CVT severity were associated with increased odds of cTn elevation; further investigation is needed to elucidate causality and significance. Full Article
iac The Antiactivator of Type III Secretion, OspD1, Is Transcriptionally Regulated by VirB and H-NS from Remote Sequences in Shigella flexneri [Article] By jb.asm.org Published On :: 2020-04-27T08:00:23-07:00 Shigella species, the causal agents of bacillary dysentery, use a type III secretion system (T3SS) to inject two waves of virulence proteins, known as effectors, into the colonic epithelium to subvert host cell machinery. Prior to host cell contact and secretion of the first wave of T3SS effectors, OspD1, an effector and antiactivator protein, prevents premature production of the second wave of effectors. Despite this important role, regulation of the ospD1 gene is not well understood. While ospD1 belongs to the large regulon of VirB, a transcriptional antisilencing protein that counters silencing mediated by the histone-like nucleoid structuring protein H-NS, it remains unclear if VirB directly or indirectly regulates ospD1. Additionally, it is not known if ospD1 is regulated by H-NS. Here, we identify the primary ospD1 transcription start site (+1) and show that the ospD1 promoter is remotely regulated by both VirB and H-NS. Our findings demonstrate that VirB regulation of ospD1 requires at least one of the two newly identified VirB regulatory sites, centered at –978 and –1270 relative to the ospD1 +1. Intriguingly, one of these sites lies on a 193-bp sequence found in three conserved locations on the large virulence plasmids of Shigella. The region required for H-NS-dependent silencing of ospD1 lies between –1120 and –820 relative to the ospD1 +1. Thus, our study provides further evidence that cis-acting regulatory sequences for transcriptional antisilencers and silencers, such as VirB and H-NS, can lie far upstream of the canonical bacterial promoter region (i.e., –250 to +1). IMPORTANCE Transcriptional silencing and antisilencing mechanisms regulate virulence gene expression in many important bacterial pathogens. In Shigella species, plasmid-borne virulence genes, such as those encoding the type III secretion system (T3SS), are silenced by the histone-like nucleoid structuring protein H-NS and antisilenced by VirB. Previous work at the plasmid-borne icsP locus revealed that VirB binds to a remotely located cis-acting regulatory site to relieve transcriptional silencing mediated by H-NS. Here, we characterize a second example of remote VirB antisilencing at ospD1, which encodes a T3SS antiactivator and effector. Our study highlights that remote transcriptional silencing and antisilencing occur more frequently in Shigella than previously thought, and it raises the possibility that long-range transcriptional regulation in bacteria is commonplace. Full Article
iac Exceptionally well-preserved Permocalculus cf. tenellus (Pia) (Gymnocodiaceae) from Upper Permian Khuff Formation limestones, Saudi Arabia By jm.lyellcollection.org Published On :: 2017-08-10T08:29:35-07:00 An exceptionally well-preserved specimen of the articulated rhodophyte Permocalculus, compared with P. tenellus sensu Elliott, 1955, is described from fine-grained Upper Permian limestones of the Khuff Formation of Saudi Arabia. Longitudinal medullary and sheaf-like cortical filaments extend through the uniserial series of elongate-globular, concave- and convex-terminating, interlocking segments for which they are interpreted to have functioned in articulation. The filaments tend to splay and branch laterally into the cortex where they terminate at the pores. At the terminal aperture, the filaments extend as bifurcating and possibly trifurcating branches and may serve as the origin of a new segment. Numerous elongate-globular chambers, up to five in each row and intimately involved with the filaments, are developed in the outer medulla and are considered to represent reproductive sporangia. The specimen is considered to have occupied predominantly low-energy, normal to slightly elevated salinity, shallow conditions within the subtidal regime of a lagoon. Full Article
iac Facility-Level Variation in Cardiac Stress Test Use Among Patients With Diabetes: Findings From the Veterans Affairs National Database By care.diabetesjournals.org Published On :: 2020-04-20T12:00:33-07:00 Full Article
iac Cardiac biomarkers are prognostic in systemic light chain amyloidosis with no cardiac involvement by standard criteria By www.haematologica.org Published On :: 2020-05-01T00:05:42-07:00 Patients with systemic immunoglobulin light chain amyloidosis (AL) with no evidence of cardiac involvement by consensus criteria have excellent survival, but 20% will die within 5 years of diagnosis and prognostic factors remain poorly characterised. We report the outcomes of 378 prospectively followed Mayo stage I patients (N-terminal pro b-type natriuretic peptide <332 ng/L, high sensitivity cardiac troponin <55 ng/L). The median presenting N-terminal pro b-type natriuretic peptide was 161 ng/L, high sensitivity cardiac troponin 10 ng/L, creatinine 76 μmol/L and mean left ventricular septal wall thickness, 10 mm. Median follow up was 42 (1-117 months), with 71 deaths; median overall survival was not reached (78% survival at 5 years). Although no patients had cardiac involvement by echocardiogram, a proportion (n=25/90, 28%) had cardiac involvement by cardiac magnetic resonance imaging. Age, autonomic nervous system involvement, N-terminal pro b-type natriuretic peptide >152 ng/L, high sensitivity cardiac troponin >10 ng/L and cardiac involvement by magnetic resonance imaging were predictive for survival; on multivariate analysis only N-terminal pro b-type natriuretic peptide >152 ng/L (P<0.008, hazard ratio [HR] 3.180, confidence interval [CI]: 1.349-7.495) and cardiac involvement on magnetic resonance imaging (P=0.026, HR=5.360, CI: 1.219-23.574) were prognostic. At 5 years, 70% of patients with N-terminal pro b-type natriuretic peptide >152 ng/L were alive. In conclusion, N-terminal pro b-type natriuretic peptide is prognostic for survival in patients with no cardiac involvement by consensus criteria and cardiac involvement is detected by magnetic resonance imaging in such cases. This suggests that N-terminal pro b-type natriuretic peptide thresholds for cardiac involvement in AL may need to be redefined. Full Article