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Objectives: To compare clinical, neurological, treatment and outcome of recurrent Guillian-Barré Syndrome (GBS) with non-recurrent GBS. Also, to compare different episodes of recurrent GBS., Methods: The patient's case records were retrieved retrospectively from the electronic database and case record files. Clinical profile, nerve conduction study, treatment, and outcome details of children with a diagnosis of GBS admitted in Pediatric Intensive Care Unit (PICU) from 2010 to March 2022 were screened. Recurrent GBS cases, as defined by the National Institute of Neurological and Communicative Diseases and Strokes (NINCDS) criteria, were analysed separately. The comparison was made between the first episode of recurrent GBS with non-recurrent GBS, and predictors of recurrence were identified. A comparison of course and outcome was also done between different episodes of GBS in recurrent cases., Results: Recurrent GBS was observed in 11 (4.7%) out of 234 cases during the study period. The presence of respiratory (p 0.015) and gastrointestinal illness (p 0.007) as preceding illnesses were associated with recurrence. No difference was noted between the first episode of recurrent GBS and non-recurrent GBS. The first and second episodes of GBS in 11 recurrent cases were similar in course and outcome., Conclusions: Recurrent GBS is underreported but a known entity. No difference was seen between the two episodes of recurrent GBS. However, more data is required to find the features of recurrent GBS so that limited PICU resources can be used judiciously and intervention planned accordingly., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Objective: Multisystem inflammatory syndrome (MIS-C) in children is a febrile illness that has overlapping presentation with other locally prevalent illnesses. Clinicolaboratory profile of children admitted with MIS-C and dengue were compared to understand their presentation at the outset., Methods: This was a retrospective study of children ≤ 12 y admitted with MIS-C (WHO definition) or laboratory-confirmed dengue between August 2020 and January 2021 at a tertiary center in North India., Results: A total of 84 children (MIS-C - 40; dengue - 44) were included. The mean (SD) age [83.5 (39) vs. 91.6 (35) mo] was comparable. Rash (72.5% vs. 22.7%), conjunctival injection (60% vs. 2.3%), oral mucocutaneous changes (27.5% vs. 0) and gallop rhythm (15% vs. 0) were seen more frequently with MIS-C, while petechiae [29.5% vs. 7.5%], myalgia (38.6% vs. 10%), headache (22.7% vs. 2.5%), and hepatomegaly (68.2% vs. 27.5%) were more common with dengue. Children with MIS-C had significantly higher C-reactive protein (124 vs. 3.2 mg/L) and interleukin 6 (95.3 vs. 20.7 ng/mL), while those with dengue had higher hemoglobin (12 vs. 10.2 g/dL) lower mean platelet count (26 vs. 140 × 10 9 /L), and greater elevation in aspartate (607 vs. 44 IU/L) and alanine (235.5 vs. 56 IU/L) aminotransferases. The hospital stay was longer with MIS-C; however, PICU stay and mortality were comparable., Conclusion: In hospitalized children with acute febrile illness, the presence of mucocutaneous features and highly elevated CRP could distinguish MIS-C from dengue. The presence of petechiae, hepatomegaly, and hemoconcentration may favor a diagnosis of dengue., (© 2022. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Most children with Guillain-Barré syndrome (GBS) recover but may suffer from long-term sequelae, interfering with development and quality of life. Owing to the lack of published data, we aimed to assess the long-term neurological, behavioral, functional, quality of life, and school performance outcomes them., Methods: Design: Cross-sectional observational., Setting: Pediatric intensive care unit., Patients: Children, aged one to 12 years, with GBS admitted over five years (July 2012 to June 2017) were enrolled during one year (July 2017 to June 2018). These children were assessed for the following outcomes: neurological (Hughes disability score, Pediatric Cerebral Performance Category [PCPC], Pediatric Overall Performance Category [POPC], and Glasgow Outcome Scale-Extended Pediatric version [GOS-E Peds] scales), behavioral (Childhood Psychopathology Measurement Schedule [CPMS]), functional (Vineland Social Maturity Scale [VSMS]-Indian Adaptation), quality of life (Pediatric Quality of Life [PedsQL]), and school performance (Parent-Directed Questionnaire)., Results: Eighty children were enrolled after a median of 3.0 (1.3-4.2) years from discharge. The majority (95%) had favorable neurological recovery (Hughes disability score 0 to 1). Favorable outcome was noted in 95% of children on PCPC, 87.5% on POPC, 60% on GOS-E Peds, 86.2% on CPMS, 92.5% on VSMS, and 98% on PedsQL. The majority (97.5%) of childre were attending schools, and 57.7% had satisfactory school performance. The presence of quadriparesis at admission, mechanical ventilation, tracheostomy requirement, poor ambulatory status at discharge, and longer pediatric intensive care unit and hospital stay predicted unfavorable neurological outcome on different tools. Absence of quadriparesis at admission and no requirement of mechanical ventilation predicted a favorable result on all outcome measures., Conclusions: On long-term follow-up, most children with severe GBS showed favorable neurological, behavioral, functional, and quality of life outcomes. Severe clinical presentation and prolonged intensive care unit stay predict poor long-term outcome., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Exogenous melatonin (EMT) application has been used to reduce postharvest senescence and improve the quality and antioxidant enzyme activities of papaya fruits during cold storage., Methods: The effects of exogenous melatonin application (1. 5 mM) were investigated on papaya fruits during cold storage (10°C ± 2°C) for 28 days in the present study., Results and Discussion: The EMT treatment delayed postharvest senescence significantly with lower maturing status compared with untreated papaya fruits (control). In addition, EMT treatment maintained substantially higher titratable acidity values and ascorbic acid content but significantly lower soluble solids content and lower weight loss compared with the untreated fruits. Concerning the antioxidant capacity, the EMT-treated papaya fruit exhibited markedly higher total phenolic content and, consequently, higher DPPH-radical scavenging activity than the control group. The EMT treatment not only kept a higher enzyme activity of superoxide dismutase, peroxidase, and catalase but also significantly inhibited the accumulation of hydrogen peroxide and malondialdehyde, along with satisfying sensory attributes., Conclusion: The findings of this study indicated that EMT application could be commercially used as an eco-friendly strategy to reduce postharvest senescence and maintain the fresh-like quality traits of papaya fruit during cold storage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Randhawa, Azam, Liu, Ejaz, Ilahy, Qadri, Khan, Umer, Khan and Wang.)

Background: Staphylococcus aureus co-infection is seldom reported in children with severe dengue., Methodology: In this retrospective study, we reported five children with severe dengue and S. aureus co-infection admitted to pediatric intensive care unit (PICU) during July-December 2021., Results: All children had prolonged fever, persistence of bilateral pleural effusion beyond the critical phase, thrombocytopenia and raised inflammatory markers [C-reactive protein (CRP) and procalcitonin]. S. aureus was isolated from pleural fluid (n = 2, 40%), blood (n = 2, 40%) and endotracheal aspirate (n = 1, 20%). Four children (80%) grew methicillin-sensitive S. aureus, while 1 (20%) had methicillin-resistant S. aureus. Two children (40%) had septic thromboemboli in skin, and 1 (20%) had limb cellulitis. One child required anterior thoracotomy, pericardiectomy and bilateral pleural decortication, while all other children required intercostal chest tube drainage. All children required prolonged targeted antibiotics, invasive mechanical ventilation and had prolong stay in PICU and all of them survived., Conclusion: In children with severe dengue, persistence of fever, persistence of pleural effusion beyond critical phase and raised CRP and procalcitonin should raise suspicion of bacterial/S. aureus co-infection., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Developing wheat varieties with durable resistance is a core objective of the International Maize and Wheat Improvement Center (CIMMYT) and many other breeding programs worldwide. The CIMMYT advanced wheat line "Mucuy" displayed high levels of resistance to stripe rust (YR) and leaf rust (LR) in field evaluations in Mexico and several other countries. To determine the genetic basis of YR and LR resistance, 138 F 5 recombinant inbred lines (RILs) derived from the cross of Apav#1× Mucuy were phenotyped for YR responses from 2015 to 2020 at field sites in India, Kenya, and Mexico, and LR in Mexico. Seedling phenotyping for YR and LR responses was conducted in the greenhouse in Mexico using the same predominant races as in field trials. Using 12,681 polymorphic molecular markers from the DArT, SNP, and SSR genotyping platforms, we constructed genetic linkage maps and QTL analyses that detected seven YR and four LR resistance loci. Among these, a co-located YR/LR resistance loci was identified as Yr29/Lr46 , and a seedling stripe rust resistance gene YrMu was mapped on the 2AS/2NS translocation. This fragment also conferred moderate adult plant resistance (APR) under all Mexican field environments and in one season in Kenya. Field trial phenotyping with Lr37 -virulent Puccinia triticina races indicated the presence of an APR QTL accounting for 18.3-25.5% of the LR severity variation, in addition to a novel YR resistance QTL, QYr.cim-3DS , derived from Mucuy. We developed breeder-friendly KASP and indel molecular markers respectively for Yr29 / Lr46 and YrMu . The current study validated the presence of known genes and identified new resistance loci, a QTL combination effect, and flanking markers to facilitate accelerated breeding for genetically complex, durable rust resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yuan, Singh, Randhawa, Bhavani, Kumar, Huerta-Espino, Lagudah and Lan.)

Acute encephalitis is a syndromic diagnosis. In the last two decades, a unique clinico-radiological entity, named acute encephalopathy with biphasic seizures and late restricted diffusion (AESD), has been reported in children from Asia. It is characterised by an acute febrile illness with seizures and encephalopathy, with some initial improvement followed by a second flurry of seizures and deep encephalopathy, 3-4 days later. MRI may show a pattern of 'bright tree appearance'. An aetiological agent may not always be identified but an infectious trigger is proposed. Immunomodulatory therapy has been tried with variable results. The prognosis is variable, and children are usually left with neurological sequelae including epilepsy and cognitive impairment. We describe a female infant who presented with the typical clinico-radiological syndrome of AESD and human bocavirus was identified in the stool. She received steroids and antiepileptic drugs. She has persistent cognitive impairment at follow-up but remained seizure free., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To analyze the clinical features associated with the need for mechanical ventilation (MV) in children with Guillain-Barré syndrome (GBS)., Design: Retrospective cohort study, 2010-2019., Setting: PICU., Patients: All children, 1 month to 12 years old, diagnosed with GBS in our single-center PICU., Intervention: Retrospective chart and data review., Measurements and Main Results: Out of 189 children identified with a diagnosis of GBS, 130 were boys (69%). The median (interquartile range [IQR]) age was 6 years (3-9 yr). At admission, the Hughes disability score was 5 (4-5), and cranial nerve palsies were present in 81 children (42%). Autonomic instability subsequently occurred in a total of 97 children (51%). In the 159 children with nerve conduction studies, the axonal variant of GBS (102/159; 64%) predominated, followed by the demyelinating variant (38/189; 24%). All children received IV immunoglobulins as first-line therapy at the time of admission. The median (IQR) length of PICU stay was 12 days (3-30.5 d). Ninety-nine children (52%) underwent invasive MV, and median duration of MV was 25 days (19-37 d). At admission, upper limb power less than or equal to 3 (p = 0.037; odds ratio (OR), 3.5 [1.1-11.5]), lower limb power less than or equal to 2 (p = 0.008; OR, 3.5 [1.4-8.9]), and cranial nerve palsy (p = 0.001; OR, 3.2 [1.6-6.1]) were associated with subsequent need for MV. Prolonged (> 21 d) MV was associated with more severe examination findings at admission: upper limb power less than or equal to 2 (p < 0.0001; OR, 4.2 [2.5-6.9]) and lower limb power less than or equal to 1 (p < 0.0001; OR, 4.5 [2.6-7.9])., Conclusions: In children with GBS, referred to our center in North India, severe neuromuscular weakness at admission was associated with the need for MV. Furthermore, greater severity of this examination was associated with need for prolonged (> 21 d) MV. Identification of these signs may help in prioritizing critical care needs and early PICU transfer., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Polycythaemia vera (PV) is a clonal proliferative disorder of the bone marrow characterised by autonomous haematopoiesis, which results in a panmyelosis in the peripheral blood. It is typically characterised by an acquired mutation in JAK-2 V617F. Progression to myelofibrosis (MF), characterised by worsening cytopenias and the development of constitutional symptoms, is seen in up to 10% of cases. Extramedullary haematopoiesis (EMH) in the spleen is a common finding in myelofibrotic transformation, but elsewhere in the body it is extremely unusual. We report the case of a 69-year-old male whose PV progressed to secondary MF and who presented with compression of the thoracic spinal cord directly as a result of EMH. Cytogenetic and molecular findings in the bone marrow were in keeping with evolving myeloid disease. He was managed by surgical laminectomy with an excellent outcome. Extramedullary haematopoiesis may be seen in both PV and on transformation to MF. This very rare complication should be borne in mind when managing patients with myeloproliferative disorders.

Competing Interests: The authors declare no conflict of interest.

Bread wheat (Triticum aestivum L.) cultivars adapted to specific environments and resistant to prevalent pathogens are preferred for obtaining high yield. This study aimed to identify wheat genotypes with superior grain yield (GY) and yield associated traits from 168 genotypes of International Maize and Wheat Improvement Center's 13th Stem Rust Resistance Screening Nursery evaluated over two seasons during 2019 and 2020 under high disease pressure of both stem rust (SR) and yellow rust (YR) in a 21 × 8 α-lattice design with 3 replications in Kenya. Effects due to seasons were significant for YR Aud , SR Aud , 1000-kernel weight (TKW), days to heading (DH), plant height (PH) and number of spikelets spike -1 (SS), while genotypes and genotypes × season interaction effects were significant for all traits except number of kernels spike -1 . Respectively, heritability values of 0.95, 0.93, 0.87, 0.86, 0.77 and 0.75 were observed for area under disease progress curve for SR (SR Aud ), YR (YR Aud ), TKW, DH, biomass (BM) and GY. Path analysis showed positive direct effects on GY via PH, SS, BM, and TKW. Biplot analysis identified 16 genotypes with superior desirable traits GY, BM and harvest index. The SR contributed the highest reduction in GY and TKW while YR contributed the most reduction in BM. These identified genotypes with superior GY combined with adequate resistance to both SR and YR are potentially valuable resources for improvement of locally adapted wheat cultivars., (© 2021. The Author(s).)

In 2020, a considerable overlap occurred between the COVID-19 pandemic and seasonal dengue transmission in India. This study aimed to evaluate the effects of acute or recent infection with SARS-CoV-2 on the course and outcomes of dengue fever in children. We prospectively enrolled 44 children with a clinical and laboratory diagnosis of dengue fever. Assessment of acute and recent SARS-CoV-2 infection was done using reverse transcription-polymerase chain reaction and IgG antibody through ELISA. Children were grouped based on evidence of SARS-CoV-2 exposure and clinical severity, and outcomes were compared. The median age of the study cohort was 96 months (interquartile range [IQR]: 69-129 months). Fever (98%), vomiting (78%), abdominal pain (68%), hepatomegaly (68%), and edema (32%) were the common features. About two-thirds (N = 30) had severe dengue; 20 (45%) had dengue shock. Liver dysfunction (58%) and acute kidney injury (25%) were other major organ dysfunctions. Nineteen (43%) children stayed in the pediatric intensive care unit for a median duration of 5 days (IQR: 2-11 days). None had acute SARS-CoV2 infection; however, IgG against SARS-CoV-2 was detected in 15 (34%) cases. Children with recent exposure to SARS-CoV-2 showed a trend toward a lower incidence of acute kidney injury, fewer organ dysfunctions, and a lower frequency of invasive ventilation. Four children (9%) died; none of the deaths were in the SARS-CoV-2-exposed group. The present study exposes preliminary evidence that dengue fever might follow a less severe course in children with recent exposure to SARS-CoV-2 infection. However, it is pertinent to understand the antigenic similarity and cross-protective antibody response between the two viruses and their clinical relevance.

Objectives: To describe the intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C)., Methodology: This retrospective study was conducted in the pediatric emergency, pediatric intensive care unit (PICUs) and the coronavirus disease 2019 (COVID 19) hospital of a tertiary teaching and referral hospital in North India over a period of 5 months (September 2020 to January 2021). Clinical details, laboratory investigations, intensive care needs, treatment and short-term outcome were recorded., Results: Forty children with median interquartile range age of 7 (5-10) years were enrolled. The common clinical features were fever (97.5%), mucocutaneous involvement (80%), abdominal (72.5%) and respiratory (50%) symptoms. Shock was noted in 80% children. Most cases (85%) required PICU admission where they received nasal prong oxygen (40%), non-invasive (22.5%) and invasive (22.5%) ventilation and vasoactive drug support (72.5%). The confirmation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) exposure was in the form of positive serology (66.7%), reverse transcriptase polymerase chain reaction (10%), and contact with SARS-CoV-2 positive case (12.5%). The common echocardiographic findings included myocardial dysfunction (ejection fraction <55%; 72.5%), and coronary artery dilatation or aneurysm (22.5%). The immunomodulatory treatment included intravenous immunoglobulin (2 g/kg) (100%) and steroids (methylprednisolone 10-30 mg/kg/day for 3-5 days) (85%). Aspirin was used in 80% and heparin (low molecular weight) in 7.5% cases. Two children died (5%) and median duration of PICU and hospital stay in survivors were 5 (2-8) and 7 (4-9) days, respectively. Children with shock showed higher total leucocyte count and higher rates of myocardial dysfunction., Conclusion: Cardiovascular involvement and shock are predominant features in severe disease. Early diagnosis can be challenging given the overlapping features with other diagnoses. A high index of suspicion is warranted in children with constellation of fever, mucocutaneous, gastrointestinal and cardiovascular involvement alongwith evidence of systemic inflammation and recent or concurrent SARS-CoV-2 infection. The short-term outcome is good with appropriate organ support therapies and immunomodulation., (© The Author(s) [2021]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A 79-year-old woman presented with new-onset heart failure. She had pleural effusion, pericardial effusion, and an ejection fraction of 35% on echocardiogram. Her coronary angiogram revealed mild coronary artery disease (CAD). However, initially unexplained extravasation of the contrast was also seen in the cranial view during angiogram. The decision was made to medically manage CAD, but she remained tachycardic, with borderline low blood pressure. After a series of complications and tests, clearance of contrast from the stomach was confirmed. This represents an unusual case in which fluoroscopy revealed active gastric bleeding with contrast extravasation during coronary angiography.

Pediatric Advanced Life Support (PALS) guidelines are updated every five years and the new 2020 guidelines were issued recently. We briefly review the important changes in terms of rates of rescue breaths, timing of epinephrine, resuscitation in septic shock, use of extracorporeal therapies, and the new component in the chain of survival - recovery.

Stem rust caused by Puccinia graminis f. sp. tritici ( Pgt ) remains a constraint to wheat production in East Africa. In this study, we characterized the genetics of stem rust resistance, identified QTLs, and described markers associated with stem rust resistance in the spring wheat line CI 14275. The 113 recombinant inbred lines, together with their parents, were evaluated at the seedling stage against Pgt races TTKSK, TRTTF, TPMKC, TTTTF, and RTQQC. Screening for resistance to Pgt races in the field was undertaken in Kenya, Ethiopia, and the United States in 2016, 2017, and 2018. One gene conferred seedling resistance to race TTTTF, likely Sr7a . Three QTL were identified that conferred field resistance. QTL QSr.cdl-2BS.2 , that conferred resistance in Kenya and Ethiopia, was validated, and the marker Excalibur&#95;c7963&#95;1722 was shown to have potential to select for this QTL in marker-assisted selection. The QTL QSr.cdl-3B.2 is likely Sr12 , and QSr.cdl-6A appears to be a new QTL. This is the first study to both detect and validate an adult plant stem rust resistance QTL on chromosome arm 2BS. The combination of field QTL QSr.cdl-2BS.2 , QSr.cdl-3B.2 , and QSr.cdl-6A has the potential to be used in wheat breeding to improve stem rust resistance of wheat varieties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kosgey, Edae, Dill-Macky, Jin, Bulbula, Gemechu, Macharia, Bhavani, Randhawa and Rouse.)

Stem rust of wheat caused by Puccinia graminis Pers. f.sp. trtici Eriks and E. Henn., is the most damaging fungal disease of both common ( Triticum aestivum L.) and durum ( Triticum turgidum L., ssp. Durum) wheat. Continuously emerging races virulent to many of the commercially deployed qualitative resistance genes have caused remarkable loss worldwide and threaten global wheat production. The objectives of this study were to evaluate the response of a panel of 283 durum wheat lines assembled by the International Maize and Wheat Improvement Center (CIMMYT) to multiple races of stem rust in East Africa at the adult plant stage and map loci associated with field resistance. The lines were evaluated in Debre Zeit, Ethiopia and Njoro, Kenya from 2018 to 2019 in five environments (year × season). The panel was genotyped using genotyping-by-sequencing. After filtering, 26,439 Single Nucleotide Polymorphism (SNP) markers and 280 lines and three checks were retained for analysis. Population structure was assessed using principal component analysis. Genome-wide association analysis (GWAS) was conducted using Genomic Association and Prediction Integrated Tool (GAPIT). The broad-sense heritability of the phenotype data revealed that 64-83% of the variation in stem rust response explained by the genotypes and lines with multiple race resistance were identified. GWAS analysis detected a total of 160 significant marker trait associations representing 42 quantitative trait loci. Of those, 21 were potentially novel and 21 were mapped to the same regions as previously reported loci. Known stem rust resistance genes/alleles were postulated including Sr8a , Sr8155B1, SrWeb/Sr9h, Sr11, Sr12, Sr13/Sr13 alleles, Sr17, Sr28/Sr16 , Sr22 , and Sr49. Lines resistant to multiple races in East Africa can be utilized as parents in durum wheat breeding programs. Further studies are needed to determine if there are new alleles at the Sr13 locus and potential markers for the known Sr13 alleles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Megerssa, Ammar, Acevedo, Brown-Guedira, Ward, Degete, Randhawa and Sorrells.)

Stripe or yellow rust (YR) caused by Puccinia striiformis Westend. f. sp. tritici Erikss. is a persistent biotic-stress threatening global wheat production. To broaden our understanding of the shared genetic basis of YR resistance across multi-site and multi-year evaluations, we performed a large genome-wide association study using 43,706 YR observations on 23,346 wheat lines from the International Maize and Wheat Improvement Center evaluated between 2013 and 2019 at sites in India, Kenya and Mexico, against predominant races prevalent in the countries. We identified 114 repeatable markers tagging 20 quantitative trait loci (QTL) associated with YR on ten chromosomes including 1D, 2A, 2B, 2D, 3A, 4A, 4D, 5A, 5B and 6B, among which four QTL, QYr.cim-2DL.2, QYr.cim-2AS.1, QYr.cim-2BS.2 and QYr.cim-2BS.3 were significant in more than ten datasets. Furthermore, we report YR-associated allelic fingerprints for the largest panel of wheat breeding lines (52,067 lines) till date, creating substantial opportunities for YR favorable allele enrichment using molecular markers. Overall, the markers and fingerprints reported in this study provide excellent insights into the genetic architecture of YR resistance in different geographical regions, time-periods and wheat germplasm and are a huge resource to the global wheat breeding community for accelerating YR resistance breeding efforts.

Leaf (brown) rust (LR) and stripe (yellow) rust (YR), caused by Puccinia triticina and P. striiformis f. sp. tritici , respectively, significantly reduce wheat production worldwide. Disease-resistant wheat varieties offer farmers one of the most effective ways to manage these diseases. The common wheat ( Triticum aestivum L.) Arableu#1, developed by the International Maize and Wheat Improvement Center and released as Deka in Ethiopia, shows susceptibility to both LR and YR at the seedling stage but a high level of adult plant resistance (APR) to the diseases in the field. We used 142 F 5 recombinant inbred lines (RILs) derived from Apav#1 × Arableu#1 to identify quantitative trait loci (QTLs) for APR to LR and YR. A total of 4,298 genotyping-by-sequencing markers were used to construct a genetic linkage map. The study identified four LR resistance QTLs and six YR resistance QTLs in the population. Among these, QLr.cim-1BL.1/QYr.cim-1BL.1 was located in the same location as Lr46/Yr29 , a known pleiotropic resistance gene. QLr.cim-1BL.2 and QYr.cim-1BL.2 were also located on wheat chromosome 1BL at 37 cM from Lr46/Yr29 and may represent a new segment for pleiotropic resistance to both rusts. QLr.cim-7BL is likely Lr68 given its association with the tightly linked molecular marker cs7BLNLRR . In addition, QLr.cim-3DS , QYr.cim-2AL , QYr.cim-4BL , QYr.cim-5AL , and QYr.cim-7DS are probably new resistance loci based on comparisons with published QTLs for resistance to LR and YR. Our results showed the diversity of minor resistance QTLs in Arableu#1 and their role in conferring near-immune levels of APR to both LR and YR, when combined with the pleiotropic APR gene Lr46 / Yr29 .

The durum wheat lines Heller#1 and Dunkler from the International Maize and Wheat Improvement Center Global Wheat Program showed moderate and stable adult plant resistance to leaf rust under high disease pressure over field environments in northwestern Mexico. Leaf rust phenotyping was performed on two recombinant inbred line (RIL) populations derived from crosses of Heller#1 and Dunkler with the susceptible parent Atred#2, conducted under artificially induced Puccinia triticina epidemics in 2013, 2014, 2015, and 2016. The Atred#2 × Heller#1 and Atred#2 × Dunkler populations were genotyped by single nucleotide polymorphism (SNP) platforms and diversity arrays technology markers, respectively. Four leaf rust resistance quantitative trait loci were detected simultaneously in the two RIL populations: Lr46 , QLr.cim-2BC , QLr.cim-5BL , and QLr.cim-6BL based on phenotypic data across all four crop seasons. They explained 11.7 to 46.8%, 7.2 to 26.1%, 8.4 to 24.1%, and 12.4 to 28.5%, respectively, of the phenotypic variation for leaf rust resistance in Atred#2 × Heller#1 and 16.3 to 56.6%, 6.7 to 15.7%, 4.1 to 10.1%, and 5.1 to 20.2% of the variation in the Atred#2 × Dunkler population. Only the resistance allele of QLr.cim-2BC was from the susceptible parent Atred#2, and resistance alleles at other loci came from the resistant parents Heller#1 and Dunkler. The SNP markers closely linked to Lr46 and QLr.cim-2BC were converted to kompetitive allele specific PCR markers for use in marker-assisted selection to improve leaf rust resistance through crosses with Heller#1 and Dunkler sources.

Importance: Several studies have examined the role of warfarin in preventing strokes in patients with atrial fibrillation and end-stage renal disease; however, the results remain inconclusive., Objective: To assess recently published studies to examine the outcomes of the use of warfarin among patients with atrial fibrillation and end-stage renal disease., Data Sources: A literature search was performed using the terms warfarin and atrial fibrillation and end-stage renal disease and warfarin and atrial fibrillation and dialysis in the MEDLINE, Embase, and Google Scholar databases from January 1, 2008, to February 28, 2019., Study Selection: The studies included were those with patients with end-stage renal disease and atrial fibrillation who were receiving warfarin and with hazard ratios (HRs) of at least 1 primary outcome. The studies excluded were those with a lack of information on outcomes and unreliable 95% CIs of the results., Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in selecting studies. Collected data were also scrutinized for reliable 95% CIs. Finally, studies were examined for perceived biases, their limitations, and the definitions of the outcomes., Main Outcomes and Measures: The HRs and 95% CIs were calculated for the incidence of ischemic stroke, hemorrhagic stroke, major bleeding, and mortality among patients receiving anticoagulants and those not receiving anticoagulants., Results: Study selection yielded 15 studies with a total of 47 480 patients with atrial fibrillation and end-stage renal disease. Of these patients, 10 445 (22.0%) were taking warfarin. With a mean (SD) follow-up period of 2.6 (1.4) years, warfarin use was associated with no significant change for the risk of ischemic stroke (HR, 0.96; 95% CI, 0.82-1.13), with a significantly higher risk of hemorrhagic stroke (HR, 1.49; 95% CI, 1.03-1.94), with no significant difference in the risk of major bleeding (HR, 1.20; 95% CI, 0.99-1.47), and with no change in overall mortality (HR, 0.95; 95% CI, 0.83-1.09)., Conclusions and Relevance: In the studies reviewed, warfarin use appears to have been associated with no change in the incidence of ischemic stroke in patients with atrial fibrillation and end-stage renal disease. However, from the studies reviewed, it does appear to be associated with a significantly higher risk of hemorrhagic stroke, with no significant difference in the risk of major bleeding, and with no change in mortality.

Bread wheat improvement using genomic tools is essential for accelerating trait genetic gains. Here we report the genomic predictabilities of 35 key traits and demonstrate the potential of genomic selection for wheat end-use quality. We also performed a large genome-wide association study that identified several significant marker-trait associations for 50 traits evaluated in South Asia, Africa and the Americas. Furthermore, we built a reference wheat genotype-phenotype map, explored allele frequency dynamics over time and fingerprinted 44,624 wheat lines for trait-associated markers, generating over 7.6 million data points, which together will provide a valuable resource to the wheat community for enhancing productivity and stress resilience.

Barrett's esophagus (BE) is the only known precursor of esophageal adenocarcinoma (EAC) and is amenable to treatment. However, more than 90 percent of EAC patients are never diagnosed with antecedent BE. Identification of molecular markers for BE is needed to improve detection of BE through efficient non-endoscopic methods that are cost-effective, sensitive and can be used to cater to a larger group of the population at risk. Alterations in mitochondria and mitochondrial DNA have been shown to be associated with various cancers, including esophageal cancer. Mitochondrial response to oxidative stress, alterations in mitochondrial metabolism, changes in mitochondrial membrane potential and mitochondrial genetic mutations have been found to be associated with BE pathogenesis. This mini-review focuses on the role of mitochondria in the pathogenesis of BE and EAC and the prospects of using that knowledge to develop effective strategies for the improved detection and risk-stratification in BE patients.

Stripe rust is a major disease constraint of wheat production worldwide. Resistance to stripe rust was analyzed using 131 F 6 recombinant inbred lines (RILs) derived from a cross between synthetic derived wheat line Soru#1 and wheat cultivar Naxos. The phenotype was evaluated in Mexico and Norway at both seedling and adult plant stages. Linkage groups were constructed based on 90K single-nucleotide polymorphism (SNP), sequence-tagged site, and simple sequence repeat markers. Two major resistance loci conferred by Soru#1 were detected and located on chromosomes 1BL and 4DS. The 1BL quantitative trait loci explained 15.8 to 40.2 and 51.1% of the phenotypic variation at adult plant and seedling stages, respectively. This locus was identified as Yr24/Yr26 based on the flanking markers and infection types. Locus 4DS was flanked by molecular markers D&#95;GB5Y7FA02JMPQ0&#95;238 and BS00108770&#95;51. It explained 8.4 to 27.8 and 5.5% of stripe rust variation at the adult plant and seedling stages, respectively. The 4DS locus may correspond to known resistance gene Yr28 based on the resistance source. All RILs that combine Yr24/Yr26 and Yr28 showed significantly reduced stripe rust severity in all four environments compared with the lines with only one of the genes. SNP marker BS00108770&#95;51 was converted into a breeder-friendly kompetitive allele-specific polymerase chain reaction marker that will be useful to accelerate Yr28 deployment in wheat breeding programs.

Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare.

Races belonging to Ug99 lineage of stem rust fungus Puccinia graminis f. sp. tritici ( Pgt ) continue to pose a threat to wheat ( Triticum aestivum L.) production in various African countries. Growing resistant varieties is the most economical and environmentally friendly control measure. Recombinant inbred line (RIL) populations from the crosses of susceptible parent 'Cacuke' with the resistant parents 'Huhwa' and 'Yaye' were phenotyped for resistance at the seedling stage to Pgt race TTKSK (Ug99) and in adult plants in field trials at Njoro, Kenya for two seasons in 2016. Using the Affymetrix Axiom breeders SNP array, two stem rust resistance genes, temporarily designated as SrH and SrY , were identified and mapped on chromosome arm 2BL through selective genotyping and bulked segregant analysis (BSA), respectively. Kompetitive allele specific polymorphism (KASP) markers and simple sequence repeat (SSR) markers were used to saturate chromosome arm 2BL in both RIL populations. SrH mapped between markers cim109 and cim114 at a distance of 0.9 cM proximal, and cim117 at 2.9 cM distal. SrY was flanked by markers cim109 and cim116 at 0.8 cM proximal, and IWB45932 at 1.9 cM distal. Two Ug99-effective stem rust resistance genes derived from bread wheat, Sr9h and Sr28 , have been reported on chromosome arm 2BL. Infection types and map position in Huhwa and Yaye indicated that Sr28 was absent in both the parents. However, susceptible reactions produced by resistant lines from both populations against Sr9h -virulent race TTKSF+ confirmed the presence of a common resistance locus Sr9h in both lines. Test of allelism is required to establish genetic relationships between genes identified in present study and Sr9h . Marker cim117 linked to SrH was genotyped on set of wheat lines with Huhwa in the pedigree and is advised to be used for marker assisted selection for this gene, however, a combination of phenotypic and genotypic assays is desirable for both genes especially for selection of Sr9h in breeding programs.

Competing Interests: Competing interests: None declared.

Since 1984, the 'Chilero' spring wheat line developed by CIMMYT has proven to be highly resistant to leaf rust and stripe rust. Amid efforts to understand the basis of resistance of this line, a recombinant inbred line (RIL) population derived from a cross between Avocet and Chilero was studied. The parents and RILs were characterized in field trials for leaf rust and stripe rust in three locations in Mexico between 2012 and 2015 and genotyped with DArT-array, DArT-GBS, and SSR markers. A total of 6,168 polymorphic markers were used to construct genetic linkage maps. Inclusive composite interval mapping detected four colocated resistance loci to both rust diseases and two stripe rust resistant loci in the Avocet × Chilero population. Among these, the quantitative trait locus (QTL) on chromosome 1BL was identified as a pleotropic adult plant resistance gene Lr46/Yr29, whereas QLr.cim-5DS/QYr.cim-5DS was a newly discovered colocated resistance locus to both rust diseases in Chilero. Additionally, one new stripe rust resistance locus on chromosome 7BL was mapped in the current population. Avocet also contributed two minor colocated resistance QTLs situated on chromosomes 1DL and 4BS. The flanking SNP markers can be converted to breeder friendly Kompetitive Allele Specific PCR (KASP) markers for wheat breeding programs.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Growing resistant wheat varieties is a key method of minimizing the extent of yield losses caused by the globally important wheat leaf rust (LR) and stripe rust (YR) diseases. In this study, a population of 186 F 8 recombinant inbred lines (RILs) derived from a cross between a synthetic wheat derivative (PI610750) and an adapted common wheat line (cv. "UC1110") were phenotyped for LR and YR response at both seedling and adult plant stages over multiple seasons. Using a genetic linkage map consisting of single sequence repeats and diversity arrays technology markers, in combination with inclusive composite interval mapping analysis, we detected a new LR adult plant resistance (APR) locus, QLr.cim-2DS , contributed by UC1110. One co-located resistance locus to both rusts, QLr.cim-3DC/QYr.cim-3DC , and the known seedling resistance gene Lr26 were also mapped. QLr.cim-2DS and QLr.cim-3DC showed a marginally significant interaction for LR resistance in the adult plant stage. In addition, two previously reported YR APR loci, QYr.ucw-3BS and Yr48 , were found to exhibit stable performances in rust environments in both Mexico and the United States and showed a highly significant interaction in the field. Yr48 was also observed to confer intermediate seedling resistance against Mexican YR races, thus suggesting it should be re-classified as an all-stage resistance gene. We also identified 5 and 2 RILs that possessed all detected YR and LR resistance loci, respectively. With the closely linked molecular markers reported here, these RILs could be used as donors for multiple resistance loci to both rusts in wheat breeding programs.

Background: Approximately 20% of patients undergoing ankle brachial index testing for critical limb ischemia have noncompressible vessels because of tibial artery calcification. This represents a clinical challenge in determining tibial artery patency. We sought to identify the prevalence of tibial artery and pedal arch patency by angiography in these patients., Methods and Results: One hundred twenty-five limbs (of 89 patients) with critical limb ischemia and ankle brachial index ≥1.4 who underwent lower extremity angiograms within 1 year were included. Reviewers of angiography were blinded to results of physiological testing. Tibial artery vessels were classified as completely occluded, significantly stenosed (≥50%), or patent (<50% stenosis). The sensitivity of toe brachial index and pulse volume recording to predict tibial artery disease was also determined. Of 125 limbs with noncompressible ankle brachial index, 72 (57.6%) anterior tibial and 80 (64%) posterior tibial arteries were occluded. Another 23 (18.4%) anterior tibial and 13 (10.4%) posterior tibial arteries had ≥50% stenosis. Pulse volume recording was moderate to severely dampened in 54 of 119 (45.4%) limbs. Toe brachial index <0.7 was found in 75 of 83 (90.4%) limbs. Moderate to severe pulse volume recording dampening was 43.6% sensitive, whereas toe brachial index <0.7 was 89.7% sensitive in diagnosing occluded or significantly stenotic tibial artery disease. The pedal arch was absent or incomplete in 86 of 103 (83.5%) limbs., Conclusions: Among patients with critical limb ischemia and noncompressible ankle brachial index results, the prevalence of occlusive tibial and pedal arch disease is very high. Toe brachial index <0.7 is more sensitive in diagnosing occluded and significantly stenotic tibial artery disease in these patients compared with ankle pulse volume recording., (© 2017 American Heart Association, Inc.)

Key Message: New leaf rust adult plant resistance (APR) QTL QLr.cim - 6BL was mapped and confirmed the known pleotropic APR gene Lr46 effect on leaf rust in durum wheat line Bairds. CIMMYT-derived durum wheat line Bairds displays an adequate level of adult plant resistance (APR) to leaf rust in Mexican field environments. A recombinant inbred line (RIL) population developed from a cross of Bairds with susceptible parent Atred#1 was phenotyped for leaf rust response at Ciudad Obregon, Mexico, during 2013, 2014, 2015 and 2016 under artificially created epidemics of Puccinia triticina (Pt) race BBG/BP. The RIL population and its parents were genotyped with the 50 K diversity arrays technology (DArT) sequence system and simple sequence repeat (SSR) markers. A genetic map comprising 1150 markers was used to map the resistance loci. Four significant quantitative trait loci (QTLs) were detected on chromosomes 1BL, 2BC (centromere region), 5BL and 6BL. These QTLs, named Lr46, QLr.cim-2BC, QLr.cim-5BL and QLr.cim-6BL, respectively, explained 13.5-60.8%, 9.0-14.3%, 2.8-13.9%, and 11.6-29.4%, respectively, of leaf rust severity variation by the inclusive composite interval mapping method. All of these resistance loci were contributed by the resistant parent Bairds, except for QLr.cim-2BC, which came from susceptible parent Atred#1. Among these, the QTL on chromosome 1BL was the known pleiotropic APR gene Lr46, whereas QLr.cim-6BL, a consistently detected locus, should be a new leaf rust resistance locus in durum wheat. The mean leaf rust severity of RILs carrying all four QTLs ranged from 8.0 to 17.5%, whereas it ranged from 10.9 to 38.5% for three QTLs (Lr46 + 5BL + 6BL) derived from the resistant parent Bairds. Two RILs with four QTLs combinations can be used as sources of complex APR in durum wheat breeding.

Leaf rust, stripe rust, and stem rust pose a significant threat to global wheat production. Growing rust resistant cultivars is the most efficient and environment friendly method to reduce yield losses. Genetic analysis is undertaken to identify genes and study their roles in conferring rust resistance in a given wheat background. This chapter summarizes the protocol for genetic analysis of rust resistance at both seedling and adult plant stages. Additionally, it examines statistical analysis and related software to characterize quantitative trait loci (QTL) linked with rust resistance.

Objective: Due to their unique pathophysiological profile, patients with hypertrophic cardiomyopathy (HCM) undergoing non-cardiac surgery require additional attention to perioperative management. We sought to compare perioperative outcomes of patients with HCM undergoing non-cardiac surgery with a matched group patients without HCM., Methods: This observational cohort study conducted at a tertiary care centre included patients with HCM (n=92, age 67 years, 54% men) undergoing intermediate-risk and high-risk non-cardiac surgeries between 1/2007 and 12/2013 (excluding <18 years, prior septal myectomy/alcohol ablation, low-risk surgery) who were 1:2 matched (based on age, gender, type and time of non-cardiac surgery) with patients without HCM (n=184, median age 65 years, 53% men). A composite endpoint (30-day postoperative death, myocardial infarction, stroke, in-hospital decompensated congestive heart failure (CHF) and rehospitalisation within 30 days) and postoperative atrial fibrillation (AF) were recorded., Results: There was a significantly lower incidence of intraoperative hypotension/tachycardia in patients with HCM versus those without HCM (p<0.001). At 30 days postoperatively, 42 (15%) patients had composite events. Rates of 30-day death, MI or stroke were very low in patients with HCM (5%). However, a significantly higher proportion of patients with HCM met the composite endpoint versus patients without HCM (20 (22%) vs 22 (12%), p=0.03), driven by decompensated CHF. On logistic regression, HCM, high-risk non-cardiac surgery, high anaesthesia risk score and intraoperative duration of hypotension were independently associated with 30-day composite events (p<0.05)., Conclusions: Patients with HCM undergoing high-risk and intermediate-risk non-cardiac surgeries have a low perioperative event rate, at an experienced centre. However, they have a higher risk of composite events versus matched patients without HCM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Takotsubo cardiomyopathy (TC) mimics acute myocardial infarction (AMI). We postulated that ventricular dysfunction in TC in the absence of significant myocardial necrosis would produce higher B-type natriuretic peptide (BNP)/troponin T (TnT) and BNP/creatine kinase MB fraction (CKMB) ratios than in AMI.Methods and Results: We studied 58 consecutive TC (age 65.8 +/- 12.9) and 97 AMI patients (age 59.8 +/-13.4). The ratios of BNP/TnT and BNP/CKMB were calculated with the use of first simultaneously drawn laboratory values. Receiver operating characteristic curves were used to distinguish TC from AMI with 95% specificity based on cardiac biomarker ratios. Median BNP/TnT and BNP/CKMB ratios were, respectively,1,292 [interquartile range 443.4-2,657.9] and 28.44 [13.7-94.8] in the TC group and 226.9[69.91-426.32] and 3.63 [1.07-10.02] in the AMI group (P <.001). TC can be distinguished from AMI with 95% specificity with the use of BNP/TnT ratio ≥1,272 (sensitivity 52%) and BNP/CKMB ratio ≥29.9 (sensitivity 50%).Conclusions: The value of BNP is significantly higher in TC than in AMI. Early BNP/TnT and BNP/CKMB ratios help to differentiate TC from AMI with greater accuracy than BNP alone.

Background: Takotsubo cardiomyopathy (TC) mimics acute myocardial infarction (AMI). We postulated that ventricular dysfunction in TC in the absence of significant myocardial necrosis would produce higher B-type natriuretic peptide (BNP)/troponin T (TnT) and BNP/creatine kinase MB fraction (CKMB) ratios than in AMI., Methods and Results: We studied 58 consecutive TC (age 65.8 ± 82.9) and 97 AMI patients (age 59.8 ± 83.4). The ratios of BNP/TnT and BNP/CKMB were calculated with the use of first simultaneously drawn laboratory values. Receiver operating characteristic curves were used to distinguish TC from AMI with 95% specificity based on cardiac biomarker ratios. Median BNP/TnT and BNP/CKMB ratios were, respectively, 1,292 [interquartile range 443.4-2,657.9] and 28.44 [13.7-94.8] in the TC group and 226.9 [69.91-426.32] and 3.63 [1.07-10.02] in the AMI group (P < .001). TC can be distinguished from AMI with 95% specificity with the use of BNP/TnT ratio ≥ 1,272 (sensitivity 52%) and BNP/CKMB ratio ≥ 29.9 (sensitivity 50%)., Conclusions: The value of BNP is significantly higher in TC than in AMI. Early BNP/TnT and BNP/CKMB ratios help to differentiate TC from AMI with greater accuracy than BNP alone., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Bleeding is a significant morbidity associated with percutaneous nephrolithotomy. This study was conducted to evaluate the safety and efficacy of the antifibrinolytic agent tranexamic acid in reducing blood loss in patients undergoing percutaneous nephrolithotomy., Materials and Methods: A total of 200 patients undergoing percutaneous nephrolithotomy were randomized into 2 equal groups. Patients in the tranexamic acid group received 1 gm tranexamic acid at induction followed by 3 oral doses of 500 mg during 24 hours, while those in the control group did not receive tranexamic acid. The patient demographics and clinical data of the 2 groups were compared., Results: Baseline patient demographics were similar in both groups. Mean hemoglobin decrease in the tranexamic acid group was significantly lower than that of the control group (1.39 vs 2.31 gm/dl, p <0.0001). Mean operative time in the tranexamic acid group was significantly lower than that in the control group (48.3 vs 70.8 minutes, p <0.0001). The stone clearance rate was similar in both groups (91% vs 82%, p = 0.06). The blood transfusion rate was lower in the tranexamic acid group (2% vs 11%, p = 0.018), as was the complication rate (33% vs 59%, p <0.0001). Two patients with a solitary functioning kidney in the tranexamic acid group required ureteral stenting to relieve anuria due to clot obstruction., Conclusions: The use of tranexamic acid in percutaneous nephrolithotomy is safe, and is associated with reduced blood loss and a lower complication rate., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Atrioventricular (AV) junction ablation for treatment of refractory atrial fibrillation is a well defined, standardized procedure and the simplest of commonly performed radiofrequency ablations in the field of cardiac electrophysiology. We report successful AV junction ablation using an inferior approach in a case of inferior vena cava interruption. Inability during the procedure to initially pass the ablation catheter into the right ventricle, combined with low amplitude electrograms, led to suspicion of an anatomic abnormality. This was determined to be a heterotaxy syndrome with inferior vena cava interruption and azygos continuation, draining in turn into the superior vena cava. Advancing Schwartz right 0 (SRO) sheath through the venous abnormality into the right atrium allowed adequate catheter stability to successfully induce complete AV block with radiofrequency energy.