A guide to barley mutants.

BACKGROUND: Mutants have had a fundamental impact upon scientific and applied genetics. They have paved the way for the molecular and genomic era, and most of today's crop plants are derived from breeding programs involving mutagenic treatments. RESULTS: Barley (Hordeum vulgare L.) is one of the most widely grown cereals in the world and has a long history as a crop plant. Barley breeding started more than 100 years ago and large breeding programs have collected and generated a wide range of natural and induced mutants, which often were deposited in genebanks around the world. In recent years, an increased interest in genetic diversity has brought many historic mutants into focus because the collections are regarded as valuable resources for understanding the genetic control of barley biology and barley breeding. The increased interest has been fueled also by recent advances in genomic research, which provided new tools and possibilities to analyze and reveal the genetic diversity of mutant collections. CONCLUSION: Since detailed knowledge about phenotypic characters of the mutants is the key to success of genetic and genomic studies, we here provide a comprehensive description of mostly morphological barley mutants. The review is closely linked to the International Database for Barley Genes and Barley Genetic Stocks ( bgs.nordgen.org ) where further details and additional images of each mutant described in this review can be found.

Parents' experiences of sham feeding their child with esophageal atresia at home while awaiting reconstructive surgery. A qualitative interview study.

PURPOSE: This study aimed to explore parents' experience of sham feeding their baby born with esophageal atresia at home, waiting for reconstructive surgery. METHOD: Semi-structured interviews were conducted with parents of six children born with esophageal atresia waiting for delayed reconstruction. The interviews were analyzed using qualitative content analysis. RESULTS: Parents experienced that sham feed reinforced the healthy abilities in their baby. They had faith in their own ability as parents to care for their child as well as to see to their baby's strength to cope with difficulties. Parents expressed that the health care system can hinder as well as be a major support on their way to a more normal life at home while waiting for reconstructive surgery. CONCLUSION: The experience of sham feeding at home while waiting for reconstructive surgery is characterized by positive aspects both for children born with esophageal atresia and their parents.

Endoscopic Chemocauterization with Trichloroacetic Acid for Congenital or Recurrent Tracheoesophageal Fistula in Children with Esophageal Atresia: Experience from a Tertiary Center.

BACKGROUND: Recurrent tracheoesophageal fistula (rTEF) is a well-known complication after surgery of EA, occurring in roughly 3-10% of the patients. Recent studies have highlighted safety and efficacy of endoscopic management of recurrent TEF. The aim of this study was to evaluate the efficacy of chemocauterization with trichloroacetic acid (TCA) in rTEF and congenital tracheoesophageal fistula (cTEF). METHODS: Retrospective chart review of consecutive patients with recurrent or congenital TEF who underwent endoscopic chemo-cauterization between 2018 and 2022 at a tertiary center. Children diagnosed with TEF who underwent primary or secondary endoscopic treatment were included. Median follow up time was 19 months for rTEF and 33 months for cTEF. RESULTS: During the study period, 18 patients were treated endoscopically by chemocatuerization with TCA at our institution. Treatment of recurrent TEF was successful in 13 of 14 patients (93%) Treatment of congenital TEF was successful in 2 of 4 patients (50%). In 14 patients, closure was seen after 1-2 treatments. There were no serious adverse reactions or complications to the endoscopic treatment of TEF. CONCLUSION: Endoscopic chemocauterization is a minimal invasive technique with low morbidity and high success rate and may be considered as primary treatment for recurrent TEF. LEVEL OF EVIDENCE: III.

Long-Term Outcome of Nonoperative Treatment of Appendicitis.

This cohort study uses registry data to report the long-term outcomes of patients who participated in randomized clinical trials of antibiotics vs surgery in Sweden in the 1990s.

Incidence and antiviral treatment of cytomegalovirus infection in infants with biliary atresia.

PURPOSE: Patients with biliary atresia (BA) and cytomegalovirus (CMV) infection may have poorer outcomes after Kasai portoenterostomy (KPE) than uninfected patients, suggesting a rationale for antiviral treatment (AVT). We aimed to describe the incidence of CMV infection and of AVT in BA patients, and to detect any differences between infected and uninfected patients to conclude if AVT is of use. METHODS: Data on BA patients who underwent KPE 2004-2020 were retrospectively collected, and the outcome was analyzed with regard to CMV status. RESULTS: Fifteen out of forty-six (33%) BA patients had signs of ongoing CMV infection. They did not differ significantly from the CMV-negative patients regarding rate of prematurity, birth weight, or biochemical markers but were slightly older at KPE. All patients received steroids postoperatively and all patients with ongoing CMV infection received AVT with very good effect on viremia and without major side effects. The AVT consisted of oral valganciclovir (10-40 (- 58) mg/kg/d) or intravenous ganciclovir (5.3-11 mg/kg/d). CONCLUSION: Ongoing CMV infection is common in this group of patients. The viremia can effectively be treated with AVT without any major side effects. Larger, randomized studies are needed to clarify the possible effect on clinical outcome.

Prevalence of Mental Health Problems, Associated Factors, and Health-Related Quality of Life in Children with Long-Gap Esophageal Atresia in Sweden.

BACKGROUND: Children with long-gap esophageal atresia (LGEA) face a high risk of digestive and respiratory morbidity, but their mental health outcomes have not been investigated. We aimed to identify the prevalence of mental health problems in children with LGEA, associated factors and health-related quality of life (HRQOL). METHODS: Twenty-six children with LGEA aged 3-17 were recruited nationwide in Sweden. One of their parents and adolescents aged 11-17 completed information on the child's mental health (Strength and Difficulties Questionnaire), generic (PedsQL 4.0) and condition-specific HRQOL (EA-QOL). Parents gave information on current child symptomatology. Mental health level was determined using validated norms; abnormal≥90 percentile/borderline≥80 percentile/normal. Elevated levels were considered borderline/abnormal. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05. RESULTS: Twelve children with LGEA aged 3-17 (46%) had elevated scores of ≥1 mental health domain in parent-reports, whereas 2 adolescents (15%) in self-reports. In parent-reports, 31% of the children had elevated levels of peer relationship problems, with associated factors being child sex male (p = 0.037), airway infections (p = 0.002) and disturbed night sleep (p = 0.025). Similarly, 31% showed elevated levels of hyperactivity/inattention, and associated factors were male sex (p = 0.005), asthma (p = 0.028) and disturbed night sleep (p = 0.036). Elevated levels of emotional symptoms, seen in 20%, were related to swallowing difficulties (p = 0.038) and vomiting problems (p = 0.045). Mental health problems correlated negatively with many HRQOL domains (p < 0.05). CONCLUSIONS: Children with LGEA risk mental health difficulties according to parent-reports, especially peer relationship problems and hyperactivity/inattention, with main risk factors being male sex, airway problems and sleep disturbances. This should be considered in follow-up care and research, particularly since their mental health problems may impair HRQOL. LEVELS OF EVIDENCE: Prognosis study, LEVEL II.

Postoperative morbidity and health-related quality of life in children with delayed reconstruction of esophageal atresia: a nationwide Swedish study.

BACKGROUND: In 10-15% of children with esophageal atresia (EA) delayed reconstruction of esophageal atresia (DREA) is necessary due to long-gap EA and/or prematurity/low birth weight. They represent a patient subgroup with high risk of complications. We aimed to evaluate postoperative morbidity and health-related quality of life (HRQOL) in a Swedish national cohort of children with DREA. METHODS: Postoperative morbidity, age-specific generic HRQOL (PedsQL™ 4.0) and condition-specific HRQOL (The EA-QOL questionnaires) in children with DREA were compared with children with EA who had primary anastomosis (PA). Factors associated with the DREA group's HRQOL scores were analyzed using Mann-Whitney U-test and Spearman's rho. Clinical data was extracted from the medical records. Significance level was p < 0.05. RESULTS: Thirty-four out of 45 families of children with DREA were included and 30 returned the questionnaires(n = 8 children aged 2-7 years; n = 22 children aged 8-18 years). Compared to children with PA(42 children aged 2-7 years; 64 children aged 8-18 years), there were no significant differences in most early postoperative complications. At follow-up, symptom prevalence in children aged 2-7 with DREA ranged from 37.5% (heartburn) to 75% (cough). Further digestive and respiratory symptoms were present in ≥ 50%. In children aged 8-18, it ranged from 14.3% (vomiting) to 40.9% (cough), with other digestive and airway symptoms present in 19.0-27.3%. Except for chest tightness (2-7 years), there were no significant differences in symptom prevalence between children with DREA and PA, nor between their generic or condition-specific HRQOL scores (p > 0.05). More children with DREA underwent esophageal dilatations (both age groups), gastrostomy feeding (2-7 years), and antireflux treatment (8-18 years), p < 0.05. Days to hospital discharge after EA repair and a number of associated anomalies showed a strong negative correlation with HRQOL scores (2-7 years). Presence of cough, airway infection, swallowing difficulties and heartburn were associated with lower HRQOL scores (8-18 years), p < 0.05. CONCLUSIONS: Although children with DREA need more treatments, they are not a risk group for postoperative morbidity and impaired HRQOL compared with children with PA. However, those with a long initial hospital stay, several associated anomalies and digestive or respiratory symptoms risk worse HRQOL. This is important information for clinical practice, families and patient stakeholders.

Incidence, Impact and Treatment of Ongoing CMV Infection in Patients with Biliary Atresia in Four European Centres.

Cytomegalovirus (CMV) infection has been suggested to be of importance for the development and outcome of biliary atresia (BA). However, most data are only available from single centre studies. We retrospectively collected data on rates, outcomes, and treatments for ongoing CMV infection at the time of Kasai portoenterostomy (KPE) from four different tertiary centres in Europe. The rate of ongoing CMV infection varied between 10-32% in the four centres. CMV positive patients were significantly older and had higher levels of several liver biochemistries at the time of KPE (p < 0.05 for all comparisons). In the largest centre, CMV infection was more common in non-Caucasians, and CMV infected patients had poorer long-term survival with native liver than CMV negative patients (p = 0.0001). In contrast, survival with native liver in the subgroup of CMV infected patients who had received antiviral treatment was similar to the CMV negative group. We conclude that ongoing CMV infection at the time of KPE occurs in a significant proportion of BA patients and that these patients seem to differ from CMV negative patients regarding age and biochemistry at the time of KPE as well as long-term survival with native liver. The latter difference may be reduced by antiviral treatment, but randomized, controlled trials are needed before such treatment can be recommended routinely.

International Core Outcome Set for Acute Simple Appendicitis in Children: Results of a Systematic Review, Delphi Study, and Focus Croups With Young People.

OBJECTIVE: To develop an international core outcome set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children. SUMMARY OF BACKGROUND DATA: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS. METHODS: The development process consisted of 4 phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a 2-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS. RESULTS: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (8 countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with 10 outcomes emerging with consensus. After 2 young peoples' focus groups, 2 additional outcomes were added to the final COS (12): mortality, bowel obstruction, intraabdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications. CONCLUSION: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment ofsimple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

Fibrin Network Porosity and Endo-/Exogenous Thrombin Cross-talk.

The earliest assessment of fibrin network porosity used a liquid permeation system and confocal 3D microscopy, which was later replaced by scanning electron microscopy. Although the methods have extensively been applied in studies of health or disease, there remains debate on the choice of a proper clotting trigger. In this review, we assess published data and convey our opinions with regard to several issues. First, when the coagulation process is initiated by recombinant tissue factor (rTF) and phospholipids, the fibrin network porosity is regulated by the endogenous thrombin based on enzymatic activations of multiple coagulants. If purified thrombin (1.0 IU/mL) is employed as the clotting trigger, fibrin network porosity may be affected by exogenous thrombin, which directly polymerizes fibrinogen in plasma, and additionally by endogenous thrombin stemming from a "positive feedback loop" action of the added thrombin. Second, with use of either endogenous or exogenous thrombin, the concentration and clotting property of available fibrinogen both influence the fibrin network porosity. Third, in the assay systems in vitro, exogenous thrombin but not rTF-induced endogenous thrombin seems to be functional enough to activate factor XIII, which then contributes to a decrease in the fibrin network porosity. Fourth, fibrin network porosity determines the transport of fibrinolytic components into/through the clots and therefore serves as an indicator of the fibrinolysis potential in plasma.

Genome-Wide Association Analysis and Genomic Prediction for Adult-Plant Resistance to Septoria Tritici Blotch and Powdery Mildew in Winter Wheat.

Septoria tritici blotch (STB) caused by the fungal pathogen Zymoseptoria tritici and powdery mildew (PM) caused by Blumeria graminis f.sp tritici (Bgt) are among the forefront foliar diseases of wheat that lead to a significant loss of grain yield and quality. Resistance breeding aimed at developing varieties with inherent resistance to STB and PM diseases has been the most sustainable and environment-friendly approach. In this study, 175 winter wheat landraces and historical cultivars originated from the Nordic region were evaluated for adult-plant resistance (APR) to STB and PM in Denmark, Estonia, Lithuania, and Sweden. Genome-wide association study (GWAS) and genomic prediction (GP) were performed based on the adult-plant response to STB and PM in field conditions using 7,401 single-nucleotide polymorphism (SNP) markers generated by 20K SNP chip. Genotype-by-environment interaction was significant for both disease scores. GWAS detected stable and environment-specific quantitative trait locis (QTLs) on chromosomes 1A, 1B, 1D, 2B, 3B, 4A, 5A, 6A, and 6B for STB and 2A, 2D, 3A, 4B, 5A, 6B, 7A, and 7B for PM adult-plant disease resistance. GP accuracy was improved when assisted with QTL from GWAS as a fixed effect. The GWAS-assisted GP accuracy ranged within 0.53-0.75 and 0.36-0.83 for STB and PM, respectively, across the tested environments. This study highlights that landraces and historical cultivars are a valuable source of APR to STB and PM. Such germplasm could be used to identify and introgress novel resistance genes to modern breeding lines.

Long-term Follow-up for Missed Cases of Eosinophilic Esophagitis in Children With Previous Foreign Body in the Esophagus.

OBJECTIVES: A foreign body impacted in the esophagus could be a sign of eosinophilic esophagitis (EoE). Our aim was to investigate if children previously diagnosed with a foreign body in the esophagus had a missed diagnosis of EoE. METHODS: In this population-based longitudinal study, all children (0-18 years) diagnosed with a foreign body in the esophagus in Stockholm, Sweden 2006 to 2016, were identified. In addition to a review of medical files, each family was contacted (n = 325) and asked standardized questions. Children with symptoms indicating EoE were offered esophagogastroduodenoscopy (EGD). RESULTS: We found 325 pediatric cases of foreign body. Two hundred and seven (64%) underwent an endoscopy at the event, 3 of these had biopsies taken, whereby 2 were diagnosed with EoE. Six additional patients were diagnosed with EoE between the initial event and the study follow-up. Children with persisting symptoms suggestive of EoE at the follow-up (n = 21), were offered EGD whereof 7 accepted. Four new cases of EoE were found. Hence, 12 (3.7%) of the children with a previous foreign body, either spontaneously released or endoscopically removed, were diagnosed with EoE. In the structured interview, dysphagia, food impactions and drinking excessively with meals, as well as food allergies, were significantly more common in EoE patients. CONCLUSIONS: Children with a foreign body in the esophagus are at risk of having EoE. Biopsies should be taken during foreign body removal and questions about swallowing problems and allergic diseases should be carefully explored also in children who do not need EGD because of spontaneous release.

The Clotting Trigger Is an Important Determinant for the Coagulation Pathway In Vivo or In Vitro-Inference from Data Review.

Blood coagulation comprises a series of enzymatic reactions leading to thrombin generation and fibrin formation. This process is commonly illustrated in a waterfall-like manner, referred to as the coagulation cascade. In vivo, this "cascade" is initiated through the tissue factor (TF) pathway, once subendothelial TF is exposed and bound to coagulation factor VII (FVII) in blood. In vitro, a diminutive concentration of recombinant TF (rTF) is used as a clotting trigger in various global hemostasis assays such as the calibrated automated thrombogram, methods that assess fibrin turbidity and fibrin viscoelasticity tests such as rotational thromboelastometry. These assays aim to mimic in vivo global coagulation, and are useful in assessing hyper-/hypocoagulable disorders or monitoring therapies with hemostatic agents. An excess of rTF, a sufficient amount of negatively charged surfaces, various concentrations of exogenous thrombin, recombinant activated FVII, or recombinant activated FIXa are also used to initiate activation of specific sub-processes of the coagulation cascade in vitro. These approaches offer important information on certain specific coagulation pathways, while alterations in pro-/anticoagulants not participating in these pathways remain undetectable by these methods. Reviewing available data, we sought to enhance our knowledge of how choice of clotting trigger affects the outcome of hemostasis assays, and address the call for further investigations on this topic.

Thoracoscopy or Thoracotomy for Esophageal Atresia: A Systematic Review and Meta-analysis.

OBJECTIVE: This systematic review with meta-analysis compares health- and provider-based outcomes of thoracoscopic to thoracotomy repair of esophageal atresia. SUMMARY OF BACKGROUND DATA: Thoracoscopic surgery has become a routine operation for esophageal atresia repair. However, large studies comparing the safety and efficacy of thoracoscopy to thoracotomy are scarce. Current reviews are obscured with institutional experiences or pool small samples. METHODS: PRISMA-compliant search in Medline/PubMed, EMBASE, Web of Science, and Cochrane Library (PROSPERO #CRD42019121862) for original studies comparing thoracoscopy to thoracotomy for esophageal atresia. Quality assessments were performed using the Joanna Briggs Institute Critical Appraisal Tool. Meta-analyses were presented as odds ratios and standardized mean differences. RESULTS: This is the largest published meta-analysis, including 17 studies and 1043 patients. Thoracoscopy produce shorter hospital stay [standardized mean differences (SMD) -11.91; 95% confidence interval (CI) 23.49-6.10; P = 0.0440], time until extubation (SMD -3.22; 95% CI 5.93-0.51; P = 0.0198), time until first oral feeding (SMD -2.84; 95% CI 4.62-1.07; P = 0.0017), and fewer musculoskeletal complications [odds ratio (OR) 0.08; 95% CI 0.01-0.58; P = 0.0133). Thoracoscopy is as safe as thoracotomy regarding leakage (OR -1.92; 95% CI 0.97-3.80; P = 0.0622), stricture formation (OR 2.66; 95% CI 0.86-3.23; P = 0.1339), stricture dilatation (OR 1.90; 95% CI 0.16-3.88; P = 0.0767), and mortality (OR 1.18; 95% CI 0.34-4.16; P = 0.7934). However, thoracoscopy take longer (SMD +27.69; 95% CI 12.06-43.32; P = 0.0005) and necessitate more antireflux surgery (OR 2.12; 95% CI 1.06-4.24; P = 0.0343). CONCLUSION: Thoracoscopy is effective and safe, with similar or better outcomes than thoracotomy for patients and providers. The only significant drawback is the need for antireflux surgery in the first years of life. Comparative randomized long-term studies are needed.

ERNICA Consensus Conference on the Management of Patients with Long-Gap Esophageal Atresia: Perioperative, Surgical, and Long-Term Management.

INTRODUCTION: Evidence supporting best practice for long-gap esophageal atresia is limited. The European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) organized a consensus conference on the management of patients with long-gap esophageal atresia based on expert opinion referring to the latest literature aiming to provide clear and uniform statements in this respect. MATERIALS AND METHODS: Twenty-four ERNICA representatives from nine European countries participated. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing items on perioperative, surgical, and long-term management, and literature review. The 2-day conference was held in Berlin in November 2019. Anonymous voting was conducted via an internet-based system using a 1 to 9 scale. Consensus was defined as ≥75% of those voting scoring 6 to 9. RESULTS: Ninety-seven items were generated. Complete consensus (100%) was achieved on 56 items (58%), e.g., avoidance of a cervical esophagostomy, promotion of sham feeding, details of delayed anastomosis, thoracoscopic pouch mobilization and placement of traction sutures as novel technique, replacement techniques, and follow-up. Consensus ≥75% was achieved on 90 items (93%), e.g., definition of long gap, routine pyloroplasty in gastric transposition, and avoidance of preoperative bougienage to enable delayed anastomosis. Nineteen items (20%), e.g., methods of gap measurement were discussed controversially (range 1-9). CONCLUSION: This is the first consensus conference on the perioperative, surgical, and long-term management of patients with long-gap esophageal atresia. Substantial statements regarding esophageal reconstruction or replacement and follow-up were formulated which may contribute to improve patient care.

Partial Biliary Diversion May Promote Long-Term Relief of Pruritus and Native Liver Survival in Children with Cholestatic Liver Diseases.

INTRODUCTION: Rare cholestatic liver diseases may cause debilitating pruritus in children. Partial biliary diversion (PBD) may relieve pruritus and postpone liver transplantation which is the only other alternative when conservative treatment fails. The aim was to report long-term outcome after PBD in a population of 26 million people during a 25-year period. MATERIALS AND METHODS: This is an international, multicenter retrospective study reviewing medical journals. Complications were graded according to the Clavien-Dindo classification system. RESULTS: Thirty-three patients, 14 males, underwent PBD at a median of 1.5 (0.3-13) years at four Nordic pediatric surgical centers. Progressive familial intrahepatic cholestasis was the most common underlying condition. Initially, all patients got external diversion, either cholecystojejunostomy (25 patients) or button placed in the gallbladder or a jejunal conduit. Early complications occurred in 14 (42%) patients, of which 3 were Clavien-Dindo grade 3. Long-term stoma-related complications were common (55%). Twenty secondary surgeries were performed due to stoma problems such as prolapse, stricture, and bleeding, or conversion to another form of PBD. Thirteen children have undergone liver transplantation, and two are listed for transplantation due to inefficient effect of PBD on pruritus. Serum levels of bile acids in the first week after PBD construction were significantly lower in patients with good relief of pruritus than in those with poor effect (13 [2-192] vs. 148 [5-383] µmol/L; p = 0.02). CONCLUSION: PBD may ensure long-term satisfactory effect on intolerable pruritus and native liver survival in children with cholestatic liver disease. However, stoma-related problems and reoperations are common.