XmoNet:a Fully Convolutional Network for Cross-Modality MR Image Inference

Magnetic resonance imaging (MRI) can generate multimodal scans with complementary contrast information, capturing various anatomical or functional properties of organs of interest. But whilst the acquisition of multiple modalities is favourable in clinical and research settings, it is hindered by a range of practical factors that include cost and imaging artefacts. We propose XmoNet, a deep-learning architecture based on fully convolutional networks (FCNs) that enables cross-modality MR image inference. This multiple branch architecture operates on various levels of image spatial resolutions, encoding rich feature hierarchies suited for this image generation task. We illustrate the utility of XmoNet in learning the mapping between heterogeneous T1- and T2-weighted MRI scans for accurate and realistic image synthesis in a preliminary analysis. Our findings support scaling the work to include larger samples and additional modalities

Внутрибольничные инфекционные осложнения у онкоурологических больных

The objective of the study was to analyze the taxonomic structure of urinary infection pathogens and determine the susceptibility of ESKAPE group microorganisms (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus spp.) isolated from cancer patients with nosocomial infections in 2018—2020 to antimicrobials.Materials and methods. 413 (71.9 %) strains of ESKAPE group bacteria from 228 patients were studied. Microorganisms were identified and antibiotic resistance was determined using Vitek-2 System (France) and MicroScan WalkAway (Germany / USA) analyzers.Results and conclusion. All gram-positive microorganisms were highly sensitive to vancomycin and teicoplanin, linezolid, tigecycline, and daptomycin, which can be used in the treatment if clinical indications are seen. Among gram-negative bacteria, the percentage of ESBL producers was 60—70 %, the percentage of carbapenem-resistant bacteria was minimalfor E. coli, rnmpared to the rest - 40—50 %, demonstrating the need to limit the use of carbapenems in the clinic.Цель исследования — анализ таксономической структуры возбудителей урологических инфекций у онкоурологических больных, сравнение чувствительности к антибиотикам микроорганизмов группы ESKAPE (Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus spp.), наиболее часто выделяемых при нозокомиальных инфекциях и обладающих наибольшей резистентностью к антибиотикам, за период 2018—2020 гг.Материалы и методы. Проанализированы результаты микробиологических исследований биологических материалов от 228 больных (574 штамма микроорганизмов). Бактерии группы ESKAPE составили 413 (71,9 %) штаммов. Идентификация выделенных микроорганизмов и установление их антибиотикочувствительности проведены на автоматических микробиологических анализаторах Vitek-2 System (Франция), MicroScan WalkAway (Германия / США).Результаты и заключение. Все грамположительные бактерии были высокочувствительны к ванкомицину и тейкопланину, линезолиду, тигециклину и даптомицину, которые могут быть использованы в терапии с учетом клинических показаний. Среди грам-отрицательных бактерий количество продуцентов бета-лактамазрасширенного спектра составило 60— 70 %, количество карбапенемрезистентных бактерий было минимальным в отношении E. coli — 6 %, для остальных — 40—50 %, что диктует необходимость ограничить использование карбапенемов в онкоурологической клинике

Нозокомиальные инфекции, вызванные Pseudomonas aeruginosa, в онкологической клинике

The purpose of the study was to evaluate the frequency of isolation of multi-resistant Pseudomonas aeruginosa and identify the mechanisms of resistance to carbapenems.Material and methods. We analyzed 866 strains of Pseudomonos aeruginosaisolated from clinical samples from cancer patients in the period 2014–2016. the level of resistance to piperacillin/tazobactam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, amikacin in dynamics was determined. carbapenem-resistant (car-R) strains were examined for the presence of enzymes.Results. Between 2014 and 2016, the number of strains resistant to piperacillin/tazobactam was 20.1–12.9 %, to ceftazidime – 33.0–32.9 %, to cefepime – 25.6–32.9 %, ciprofloxacin – 36.8–43.8 %, amikacin – 23.8–24.9 %. No statistically significant differences were found (p>0.05). However, an increase in the number of car-R strains from 31.7 to 43.8 % was observed (p<0.05). of 7 strains of P. aeruginosainvestigated for the presence of acquired carbapenemases, the production of metal-beta-lactamase of group Vimwas detected in 2 strains, and class acarbapenemases of the gEs-5 group in one strain.Conclusion. P. aeruginosaresistance to all antibiotic groups did not exceed 50 % and remained almost unchanged for 3 years, with the exception of the increase in car-R strains. three out of 7 (42.9 %) carbapenem-resistant strains were genetically stable.Цель исследования – оценить частоту выделения мультирезистентных Pseudomonas aeruginosaи выявить механизмы резистентности к карбапенемам.Материал и методы. Проанализировано 866 штаммов синегнойных палочек, выделенных из патологических материалов от онкологических больных в 2014–16 гг. Определен уровень резистентности к пиперациллину/тазобактаму, цефтазидиму, цефепи-му, имипенему, меропенему, ципрофлоксацину, амикацину в динамике. Резистентные к карбапенемам (car-R) штаммы исследовали на наличие ферментов.Результаты. Число штаммов, резистентных к пиперациллину/тазобактаму в период 2014–2016 гг., составляло 20,1 % и 12,9 %, цефтазидиму – 33,0–32,9 %, цефепиму – 25,6–32,9 %, ципрофлоксацину – 36,8–43,8 %, амикацину – 23,8–24,9 %. Разница во всех случаях недостоверна (p>0,05). В то же время наблюдалось увеличение числа car-R штаммов с 31,7 до 43,8 % (p<0,05). Анализ 7 штаммов в отношении приобретенных карбапенемаз выявил продукцию металло-бета-лактамаз группы Vimу 2 штаммов, gEs-5 – у 1 штамма.Заключение. Резистентность P. aeruginosaко всем группам антибиотиков не превышала 50 % и практически не изменялась в течение 3 лет, за исключением нарастания car-R штаммов. Из 7 (42,9 %) изученных карбапенем-резистентных штаммов 3 были устойчивы генетически

Effect and process evaluation of a kindergarten-based, family-involved cluster randomised controlled trial in six European countries on four- to six-year-old children's steps per day: The ToyBox-study

Background: The ToyBox-intervention is a theory- and evidence-based intervention delivered in kindergartens to improve four- to six-year-old children''s energy balance-related behaviours and prevent obesity. The current study aimed to (1) examine the effect of the ToyBox-intervention on increasing European four- to six-year-old children'' steps per day, and (2) examine if a higher process evaluation score from teachers and parents was related to a more favourable effect on steps per day. Methods: A sample of 2438 four- to six-year-old children (51.9% boys, mean age 4.75±0.43years) from 6 European countries (Belgium, Bulgaria, Germany, Greece, Poland and Spain) wore a motion sensor (pedometer or accelerometer) for a minimum of two weekdays and one weekend day both at baseline and follow-up to objectively measure their steps per day. Kindergarten teachers implemented the physical activity component of the ToyBox-intervention for 6 weeks in total, with a focus on (1) environmental changes in the classroom, (2) the child performing the actual behaviour and (3) classroom activities. Children''s parents received newsletters, tip cards and posters. To assess intervention effects, multilevel repeated measures analyses were conducted for the total sample and the six intervention countries separately. In addition, process evaluation questionnaires were used to calculate a total process evaluation score (with implementation and satisfaction as a part of the overall score) for teachers and parents which was then linked with the physical activity outcomes. Results: No significant intervention effects on four- to six-year-old children'' steps per weekday, steps per weekend day and steps per average day were found, both in the total sample and in the country-specific samples (all p>0.05). In general, the intervention effects on steps per day were least favourable in four- to six-year-old children with a low teachers process evaluation score and most favourable in four- to six-year-old children with a high teachers process evaluation score. No differences in intervention effects were found for a low, medium or high parents'' process evaluation score. Conclusion: The physical activity component of the ToyBox-intervention had no overall effect on four- to six-year-old children'' steps per day. However, the process evaluation scores showed that kindergarten teachers that implemented the physical activity component of the ToyBox-intervention as planned and were satisfied with the physical activity component led to favourable effects on children''s steps per day. Strategies to motivate, actively involve and engage the kindergarten teachers and parents/caregivers are needed to induce larger effects

Differences in energy balance-related behaviours in European preschool children: The ToyBox-study

Background: The aim of the current study was to compare levels of energy balance-related behaviours (physical activity, sedentary behaviour, and dietary behaviours (more specifically water consumption, sugar-sweetened beverage consumption and unhealthy snacking)) in four- to six-year-old preschoolers from six European countries (Belgium, Bulgaria, Germany, Greece, Poland, and Spain) within the ToyBox cross-sectional study. Methods: A sample of 4,045 preschoolers (4.77 ± 0.43 years; 52.2% boys) had valid physical activity data (steps per day), parents of 8,117 preschoolers (4.78 ± 0.46 years; 53.0% boys) completed a parental questionnaire with questions on sedentary behaviours (television viewing, computer use, and quiet play), and parents of 7,244 preschoolers (4.77 ± 0.44 years; 52.0% boys) completed a food frequency questionnaire with questions on water consumption, sugar-sweetened beverage consumption and unhealthy snacking. Results: The highest levels of physical activity were found in Spain (12,669 steps/day on weekdays), while the lowest levels were found in Bulgaria and Greece (9,777 and 9,656 steps/day on weekdays, respectively). German preschoolers spent the least amount of time in television viewing (43.3 min/day on weekdays), while Greek preschoolers spent the most time in television viewing (88.5 min/day on weekdays). A considerable amount of time was spent in quiet play in all countries, with the highest levels in Poland (104.9 min/day on weekdays), and the lowest levels in Spain (60.4 min/day on weekdays). Belgian, German, and Polish preschoolers had the lowest intakes of water and the highest intakes of sugar-sweetened beverages. The intake of snacks was the highest in Belgian preschoolers (73.1 g/day) and the lowest in Greek preschoolers (53.3 g/day). Conclusions: Across six European countries, differences in preschoolers'' energy balance-related behaviours were found. Future interventions should target European preschoolers '' energy balance- related behaviours simultaneously, but should apply country-specific adaptations

CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation

Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity. The sporadic nature of the syndrome and lack of clear inheritance patterns pointed to a genetic heterogeneity. Here, we report a genetic analysis of a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Karyotyping revealed a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21. Fluorescence in situ hybridization analysis narrowed down the region around the breakpoints, and the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was found to be expressed in a diverse range of tissues including fetal eye and fetal brain. Quantitative PCR of the CDK19 transcript from Epstein–Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene. cdk8, the closest orthologue of human CDK19 in Drosophila has been shown to play a major role in eye development. Conditional knock-down of Drosophila cdk8 in multiple dendrite (md) neurons resulted in 35% reduced dendritic branching and altered morphology of the dendritic arbour, which appeared to be due in part to a loss of small higher order branches. In addition, Cdk8 mutant md neurons showed diminished dendritic fields revealing an important role of the CDK19 orthologue in the developing nervous system of Drosophila. This is the first time the CDK19 gene, a component of the mediator co-activator complex, has been linked to a human disease

Adult Type 3 Adenylyl Cyclase–Deficient Mice Are Obese

Background: A recent study of obesity in Swedish men found that polymorphisms in the type 3 adenylyl cyclase (AC3) are associated with obesity, suggesting the interesting possibility that AC3 may play a role in weight control. Therefore, we examined the weight of AC3 mice over an extended period of time. Methodology/Principal Findings: We discovered that AC3 2/2 mice become obese as they age. Adult male AC3 2/2 mice are about 40 % heavier than wild type male mice while female AC3 2/2 are 70 % heavier. The additional weight of AC3 2/2 mice is due to increased fat mass and larger adipocytes. Before the onset of obesity, young AC3 2/2 mice exhibit reduced physical activity, increased food consumption, and leptin insensitivity. Surprisingly, the obesity of AC3 2/2 mice is not due to a loss of AC3 from white adipose and a decrease in lipolysis. Conclusions/Significance: We conclude that mice lacking AC3 exhibit obesity that is apparently caused by low locomotor activity, hyperphagia, and leptin insensitivity. The presence of AC3 in primary cilia of neurons of the hypothalamus suggests that cAMP signals generated by AC3 in the hypothalamus may play a critical role in regulation of body weight

Mutations in a Guanylate Cyclase GCY-35/GCY-36 Modify Bardet-Biedl Syndrome–Associated Phenotypes in Caenorhabditis elegans

Ciliopathies are pleiotropic and genetically heterogeneous disorders caused by defective development and function of the primary cilium. Bardet-Biedl syndrome (BBS) proteins localize to the base of cilia and undergo intraflagellar transport, and the loss of their functions leads to a multisystemic ciliopathy. Here we report the identification of mutations in guanylate cyclases (GCYs) as modifiers of Caenorhabditis elegans bbs endophenotypes. The loss of GCY-35 or GCY-36 results in suppression of the small body size, developmental delay, and exploration defects exhibited by multiple bbs mutants. Moreover, an effector of cGMP signalling, a cGMP-dependent protein kinase, EGL-4, also modifies bbs mutant defects. We propose that a misregulation of cGMP signalling, which underlies developmental and some behavioural defects of C. elegans bbs mutants, may also contribute to some BBS features in other organisms

The dynamic cilium in human diseases

Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified