Combination Breeding and Marker-Assisted Selection to Develop Late Blight Resistant Potato Cultivars

(1) Background: Although resistance to pathogens and pests has been researched in many potato cultivars and breeding lines with DNA markers, there is scarce evidence as to the efficiency of the marker-assisted selection (MAS) for these traits when applied at the early stages of breeding. A goal of this study was to estimate the potential of affordable DNA markers to track resistance genes that are effective against the pathogen Phytophthora infestans (Rpi genes), as a practical breeding tool on a progeny of 68 clones derived from a cross between the cultivar Sudarynya and the hybrid 13/11-09. (2) Methods: this population was studied for four years to elucidate the distribution of late blight (LB) resistance and other agronomical desirable or simple to phenotype traits such as tuber and flower pigmentation, yield capacity and structure. LB resistance was phenotypically evaluated following natural and artificial infection and the presence/absence of nine Rpi genes was assessed with 11 sequence-characterized amplified region (SCAR) markers. To validate this analysis, the profile of Rpi genes in the 13/11-09 parent was established using diagnostic resistance gene enrichment sequencing (dRenSeq) as a gold standard. (3) Results: at the early stages of a breeding program, when screening the segregation of F1 offspring, MAS can halve the workload and selected SCAR markers for Rpi genes provide useful tools

South American species <i>Solanum alandiae</i> Card. and <i>S. okadae</i> Hawkes et Hjerting as potential sources of genes for potato late blight resistance

For several decades, wild species of Solanum L. section Petota Dumort. have been involved in potato cultivar breeding for robust resistance to pests and diseases. Potato late blight (LB) is caused by oomycete Phytophthora infestans (Mont.) de Bary, and the genes for race-specific resistance to P. infestans (Rpi genes) have been introgressed into cultivated potatoes by remote crosses and trans- or cisgenesis, first from S. demissum Buk. and, more recently, from other wild species, such as S. bulbocastanum Dun., S. stoloniferum Schlechtd. et Bché, and S. venturii Hawkes et Hjerting (according to the nomenclature by Hawkes, 1990). Most wild species already involved in breeding for LB resistance came from North and Central Americas: series Bulbocastana (Rydb.) Hawkes, Demissa Buk. and Longipedicellata Buk., and some Rpi genes of these species have been already characterized in much detail. Rpi genes of South American species, including the series Tuberosa (Rydb.) Hawkes, have not been sufficiently investigated. Among the latter, this study focuses on the Rpi genes of S. alandiae Card. and S. okadae Hawkes et Hjerting. Four accessions of S. alandiae, one accession of S. okadae and 11 clones of interspecific potato hybrids comprising S. alandiae germplasm from the VIR collection were PCR-screened using specific SCAR (Sequence Characterized Amplified Region) markers for eight Rpi genes. SCAR amplicons of five Rpi genes registered in this study were validated by comparing their sequences with those of prototype genes deposited in the NCBI Genbank. Among the structural homologues of Rpi genes found in S. alandiae and S. okadae, of special interest are homologues of CC-NB-LRR resistance genes with broad specificity towards P. infestans races, in particular R2=Rpi-blb3, R8, R9a, Rpi-vnt1 and Rpi-blb2 (94–99, 94–99, 86–89, 92–98 and 91% identity with the prototype genes, respectively). Our data may help to better understand the process of Rpi gene divergence along with the evolution of tuberbearing Solanum species, particularly in the series Tuberosa

Advanced liver disease in Russian children and adolescents with chronic hepatitis C

Russia has one of the highest prevalences of paediatric chronic hepatitis C infection (CHC). Our aim was to provide a detailed characterization of children and adolescents with CHC including treatment outcomes.Thus, an observational study of children with CHC aged <18 years was conducted in three hepatology centres from November 2014 to May 2017. Of 301 children(52% male), 196(65%) acquired HCV vertically, 70(23%) had a history of blood transfusion or invasive procedures, 1 injecting drug use and 34(11%) had no known risk factors. Median age at HCV diagnosis was 3.1[IQR 1.1,8.2] and 10.8[7.4,14.7] at last follow-up. The most common genotype was 1b(51%), followed by 3(31%). Over a quarter of patients (84,28%) had raised liver transaminases. Of 92 with liver biopsy, 38(41%) had bridging fibrosis (median age 10.4[7.1,14.1]). Of 223 evaluated by transient elastography (TE), 67(30%) had liver stiffness ≥5.0kPa. For each year increase in age mean stiffness increased by 0.09kPa(95%CI 0.05,0.13, p<0.001). There was significant correlation between liver stiffness and biopsy results (Tau-b=0.29, p=0.042). Of 205 treated with IFN-based regimens, 100(49%) had SVR24. Most children (191,93%) experienced adverse reactions, leading to treatment discontinuation in 6(3%). In conclusion, a third of children acquired HCV via non-vertical routes and a substantial proportion of those with liver biopsy had advanced liver disease. Only half of children achieved SVR24 with IFN-based regimens highlighting the need for more effective and better tolerated treatments with direct-acting antivirals. Further studies are warranted in Russia on causes and prevention of non-vertical transmission of HCV in children. This article is protected by copyright. All rights reserved

A Model-Based Methodology for Spray-Drying Process Development

Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales

Advanced liver disease in Russian children and adolescents with chronic hepatitis C.

Russia has one of the highest prevalences of paediatric chronic hepatitis C infection (CHC). Our aim was to provide a detailed characterization of children and adolescents with CHC including treatment outcomes. Thus, an observational study of children with CHC aged <18 years was conducted in three hepatology centres from November 2014 to May 2017. Of 301 children (52% male), 196 (65%) acquired HCV vertically, 70 (23%) had a history of blood transfusion or invasive procedures, 1 injecting drug use and 34 (11%) had no known risk factors. Median age at HCV diagnosis was 3.1 [interquartile range, IQR 1.1, 8.2] and 10.8 [7.4, 14.7] at last follow-up. The most common genotype was 1b (51%), followed by 3 (37%). Over a quarter of patients (84, 28%) had raised liver transaminases. Of 92 with liver biopsy, 38 (41%) had bridging fibrosis (median age 10.4 [7.1, 14.1]). Of 223 evaluated by transient elastography, 67 (30%) had liver stiffness ≥5.0 kPa. For each year, increase in age mean stiffness increased by 0.09 kPa (95% CI 0.05, 0.13, P < 0.001). There was significant correlation between liver stiffness and biopsy results (Tau-b = 0.29, P = 0.042). Of 205 treated with IFN-based regimens, 100 (49%) had SVR24. Most children (191, 93%) experienced adverse reactions, leading to treatment discontinuation in 6 (3%). In conclusion, a third of children acquired HCV via nonvertical routes and a substantial proportion of those with liver biopsy had advanced liver disease. Only half of children achieved SVR24 with IFN-based regimens highlighting the need for more effective and better-tolerated treatments with direct-acting antivirals. Further studies are warranted in Russia on causes and prevention of nonvertical transmission of HCV in children

ПОСЛЕОПЕРАЦИОННЫЕ ОСЛОЖНЕНИЯ РЕКОНСТРУКТИВНО-ВОССТАНОВИТЕЛЬНЫХ ОПЕРАЦИЙ У БОЛЬНЫХ ОПУХОЛЯМИ ГОЛОВЫ И ШЕИ

The main goal of reconstructive surgery is to improve the quality of life of patients who have undergone surgery. However, recurrences and postoperative complications after such surgeries pose a serious challenge.The purpose of the study was to evaluate immediate surgical outcomes in head and neck cancer patients who underwent reconstructive surgery following tumor resection, as well as to analyze the causes of postoperative complications.Material and Methods. Immediate treatment outcomes were analyzed in 272 head and neck cancer patients, who were treated from 2008 to 2018. All patients were divided into 2 groups. Group I consisted of 172 patients, who underwent radical surgery and reconstruction. Group II comprised 100 patients, who underwent radical surgery alone. The groups were matched by stage, gender, age, previous treatment, and tumor location.Results. The incidence of recurrence was lower in Group I than in Group II (19 % versus 32 %, p&gt;0,05). Postoperative complications occurred in 14 % of patients who underwent reconstruction of postoperative defects with rotation flaps and in 35 % of patients who underwent reconstruction with free revascularized flaps (p&lt;0,05). The rate of complications was higher in patients undergoing maxillary and mandibular reconstructions (39,6 %) than in patients undergoing reconstructions of the other parts of the head and neck (23,7 %) (p&lt;0,05). Patients who received chemoradiotherapy had higher rate of postoperative complications than those who had no neoadjuvant treatment (37 % versus 22 %, p&gt;0,05).Conclusion. Knowledge of the factors that have a significant impact on the likelihood of developing postoperative complications after reconstructive surgeries makes it possible to take measures to prevent  them. Основной целью реконструктивно-пластических операций является улучшение качества жизни прооперированных больных. Однако возникающие рецидивы и  послеоперационные осложнения при подобных операциях являются значимой проблемой и требуют дальнейшего изучения. Целью исследования явились оценка непосредственных результатов хирургического лечения больных злокачественными новообразованиями головы и шеи с реконструктивно-пластическим компонентом и анализ причин возникновения  послеоперационных осложнений. Материал и методы. Проведен анализ непосредственных результатов лечения 272 больных злокачественными опухолями головы и шеи за период с 2008 по 2018 г., которые были разделены на 2 группы. В первую группу (n=172) вошли больные,  которым вместе с радикальным удалением опухоли был выполнен реконструктивно- пластический этап; во вторую группу (n=100) – пациенты, которым проведена радикальная операция без пластического этапа. Группы были сопоставимы по стадии, полу, возрасту, предшествующему лечению и локализации опухолевого процесса. Результаты. По данным исследования отмечена меньшая частота продолженного роста опухоли в группе с реконструктивно-пластическим этапом – 19 % больных, по  сравнению с контрольной группой – 32 % (p&gt;0,05). Установлено, что при использовании ротированных лоскутов послеоперационные осложнения возникли в 14  %, а свободных реваскуляризированных лоскутов – в 35 % случаев (p&lt;0,05). Реконструкция верхней и нижней челюсти сопровождается более частым развитием осложнений (39,6 %), чем устранение дефектов в других областях головы и шеи (23,7 %) (p&lt;0,05). У больных, получивших химиолучевое лечение, послеоперационные  осложнения наблюдались чаще, чем у пациентов без неоадъювантного лечения, – в 37 % и 22 % случаев соответственно (p&gt;0,05). Заключение. Знание факторов, оказывающих значимое влияние на вероятность развития послеоперационных осложнений при реконструктивно-пластических операциях, дает возможность проводить эффективные мероприятия по их профилактике

stocktaking OF STATE PROPERTY on DEPOSITS IN THE SPHERE OF OIL AND GAS

The article views the criteria for oil extraction taking into account the modern conditions. The author makes differentiation between the position of a deposit user as a deposit leaseholder and the state as an owner

Psychogenic eating disorders in infants and ways of their correction

Eating disorder is observed in infants at different developmental stages. This condition may be caused by comorbidities, organic diseases, or psychogenic causes. After birth, a child’s eating behavior evolves, which largely depends on the relations arising between him, his mother, and other family members. Eating disorders may be caused by an impaired child-mother relationship: inadequate maternal behavior, excessive or poor parenteral attention. The treatment of eating disorders involves a comprehensive approach, including behavioral and dietary correction that is considered in this paper