Assessing externalizing and internalizing behaviour in children: use of the motor behaviour checklist in a typical school-age Polish sample

The study was designed to investigate externalizing and internalizing behaviours in a typical school-aged sample of children (N=112) using the Polish version of the Motor Behaviour Checklist for Children. The instrument was translated into Polish and teachers observed and recorded the motor behaviour of their students in school settings during physical education and free play situations. Findings demonstrated a psychometrically robust application of the MBC in a Polish sample as well as gender differences in total externalizing scores. In addition, age was found to be significant correlated with internalizing scores and especially with the social interaction factor. Teachers reported boys as more inattentive and more hyperactive/impulsive than girls and more likely to display externalising symptoms connected with ADHD particularly in school settings. Findings underscore the importance of early diagnosis and have practical implications when designing behavioural management programs and educational interventions in school settings

Metabolomika i proteomika w diagnostyce nieswoistych chorób zapalnych jelit

Ulcerative colitis and Crohn’s disease belong to the group of inflammatory bowel diseases and are characterized by chronic inflammation of gastrointestinal tract. The pathogenesis of these conditions is multifactorial and not fully understood. The diagnostic process of inflammatory bowel diseases is often time consuming and involves many different diagnostic tests. Researchers are looking for novel diagnostic tools, that would lead to early and correct diagnosis, optimal treatment and would be possibly least invasive. Novel technolog ies, such as metabolomics and proteomics show great promise for future clinical use. Meta bolomics involves analysis of metabolites in cells and tissues, whereas proteomics is based on the analysis protein and peptide profile, that are changing depending on underlying disease.Wrzodziejące zapalenie jelita grubego i choroba Leśniowskiego-Crohna to przewlekłe choroby zapalne przewodu pokarmowego, których patogeneza jest wieloczynnikowa i nie do końca zbadana. Proces diagnostyczny prowadzący do właściwego leczenia jest często czasochłonny. Od lat trwają badania zmierzające do odkrycia wiarygodnych i minimalnie inwazyjnych testów diagnostycznych, służących do szybkiego rozpoznawania tych chor ób i poprawy opieki nad pacjentami. Duże nadzieje niosą ze sobą nowe dziedziny nauki, takie jak metabolomika i proteomika, które mogą prowadzić do odkr ycia nowych biomarkerów tych schor zeń. Zajmują się oceną metabolitów (metabolomika) oraz białek i peptydów (pr oteomika) w komórkach i tkankach, których skład zmienia się w zależności od stanu chorobowego

Routine gastric residual volume measurement to guide enteral feeding in mechanically ventilated infants and children : the GASTRIC feasibility study

Background The routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding, is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it. Objective(s) To answer the question: Is it feasible to conduct a trial of not measuring gastric residual volume on clinical outcomes in mechanically ventilated infants and children in the UK? Design A mixed methods study involving five linked work packages in two parallel arms, neonatal units and paediatric intensive care units. 1. A survey of units to establish current UK practice. 2. qualitative interviews with healthcare professionals and caregivers of children admitted to either setting. 3. A modified two-round e-Delphi survey to investigate health care professionals’ opinions on trial design issues and to obtain consensus on outcomes. 4. National databases were examined to determine the potential eligible populations. 5. Two consensus meetings, of health care professionals and parents to review the data and agreed consensus on outcomes that had not reached consensus in the e-Delphi. Participants and setting Parents of children with experience of ventilation and tube feeding in both neonatal units and in paediatric intensive care units, and health care professionals working in neonatal units and paediatric intensive care units. Results Baseline surveys showed the practice of gastric residual volume measurement was very common: 96% PICUs and 65% in neonatal units. Ninety percent of parents both from neonatal units and paediatric intensive care units supported a future trial, whilst highlighting concerns around possible delays in detecting complications. Health care professionals also indicated a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes were addressed by developing a simple flowchart and education package. The trial design survey and e-Delphi study gained consensus on trial 12 PICU and 9 neonatal unit outcome measures and identified acceptable inclusion and exclusion criteria. Given the differences in physiology, disease processes, environments, staffing and outcomes of interest, two different trials are required in the two settings. Database analyses subsequently showed trials were feasible in both settings in terms of patient numbers. Of 16222 children who met the inclusion criteria in PICU 12 629 stayed > 3 days. In neonatal units, 15 375 neonates <32 weeks age. Finally, the two consensus meetings demonstrated ‘buy in’ from the wider UK neonatal communities and paediatric intensive care units and enabled us to discuss and vote on the outcomes that did not achieve consensus in the e-Delphi study. Conclusions and future work Two separate UK trials (one in neonatal units and one in paediatric intensive care units) are feasible to conduct, but they cannot be combined due to differences in outcome measures and treatment protocols, reflecting the distinctness of the two specialties

Origins left, right and centre: increasing the number of initiation sites in the Escherichia coli chromosome

© 2018 by the authors. The bacterium Escherichia coli contains a single circular chromosome with a defined architecture. DNA replication initiates at a single origin called oriC. Two replication forks are assembled and proceed in opposite directions until they fuse in a specialised zone opposite the origin. This termination area is flanked by polar replication fork pause sites that allow forks to enter, but not to leave. Thus, the chromosome is divided into two replichores, each replicated by a single replication fork. Recently, we analysed the replication parameters in E. coli cells, in which an ectopic origin termed oriZ was integrated in the right-hand replichore. Two major obstacles to replication were identified: (1) head-on replication–transcription conflicts at highly transcribed rrn operons, and (2) the replication fork trap. Here, we describe replication parameters in cells with ectopic origins, termed oriX and oriY, integrated into the left-hand replichore, and a triple origin construct with oriX integrated in the left-hand and oriZ in the right-hand replichore. Our data again highlight both replication–transcription conflicts and the replication fork trap as important obstacles to DNA replication, and we describe a number of spontaneous large genomic rearrangements which successfully alleviate some of the problems arising from having an additional origin in an ectopic location. However, our data reveal additional factors that impact efficient chromosome duplication, highlighting the complexity of chromosomal architecture

The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends.

Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies

The Hsc70 disaggregation machinery removes monomer units directly from α-synuclein fibril ends

Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as alpha-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study alpha-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse alpha-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies. Molecular chaperones from the Hsp70 family can break up protein aggregates, including amyloids. Here, the authors utilize microfluidic diffusional sizing to assess the mechanism of alpha-synuclein (alpha S) disaggregation by the Hsc70-DnaJB1-Apg2 system, and show that single alpha S molecules are removed directly from the fibril ends

One-pot hydrogen peroxide and hydrohalic acid induced ring closure and selective aromatic halogenation to give new ring-fused benzimidazoles

A new series of selectively dichlorinated and dibrominated five to eight-membered ring [1,2-a] fused benzimidazoles and [1,4]oxazino[4,3-a]benzimidazoles are synthesized in mostly high yields of >80% using the reaction of hydrogen peroxide and hydrohalic acid with commercially available o-cyclic amine substituted anilines. Domestic bleach with HCl is also capable of a one-pot ring-closure and chlorination

Novel and promising compounds to treat Cryptosporidium parvum infections

No fully effective approved drug therapy exists for Cryptosporidium infections of immunocompetent and immunocompromised patients. Here, we investigated 11 benzimidazole derivatives carrying substituted thioalkyl and thiobenzyl groups at position 2 of benzimidazole nucleus and additional substituents at the benzene part of benzimidazole for inhibition of the in vitro growth of the intestinal protozoan parasite, Cryptosporidium parvum. Three of them, i.e., 5-carboxy-2-(4-nitrobenzylthio)-1H-benzimidazole, 5,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, and 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, (compounds 5, 7, and 8) were the most active (IC50 28–31 μM). The concentration of compounds 5, 7, and 8 that caused 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was comparable with those obtained for paromomycin

Controlled ultraviolet (UV) photoinitiated fabrication of monolithic porous layer open tubular (monoPLOT) capillary columns for chromatographic applications

An automated column fabrication technique that is based on a ultraviolet (UV) light-emitting diode (LED) array oven, and provides precisely controlled "in-capillary" ultraviolet (UV) initiated polymerization at 365 nm, is presented for the production of open tubular monolithic porous polymer layer capillary (monoPLOT) columns of varying length, inner diameter (ID), and porous layer thickness. The developed approach allows the preparation of columns of varying length, because of an automated capillary delivery approach, with precisely controlled and uniform layer thickness and monolith morphology, from controlled UV power and exposure time. The relationships between direct exposure times, intensity, and layer thickness were determined, as were the effects of capillary delivery rate (indirect exposure rate), and multiple exposures on the layer thickness and axial distribution. Layer thickness measurements were taken by scanning electron microscopy (SEM), with the longitudinal homogeneity of the stationary phase confirmed using scanning capacitively coupled contactless conductivity detection (sC(4)D). The new automated UV polymerization technique presented in this work allows the fabrication of monoPLOT columns with a very high column-to-column production reproducibility, displaying a longitudinal phase thickness variation within ±0.8% RSD (relative standard deviation)

Novel and promising compounds to treat Cryptosporidium parvum infections

No fully effective approved drug therapy exists for Cryptosporidium infections of immunocompetent and immunocompromised patients. Here, we investigated 11 benzimidazole derivatives carrying substituted thioalkyl and thiobenzyl groups at position 2 of benzimidazole nucleus and additional substituents at the benzene part of benzimidazole for inhibition of the in vitro growth of the intestinal protozoan parasite, Cryptosporidium parvum. Three of them, i.e., 5-carboxy-2-(4-nitrobenzylthio)-1H-benzimidazole, 5,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, and 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole, (compounds 5, 7, and 8) were the most active (IC50 28–31 μM). The concentration of compounds 5, 7, and 8 that caused 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was comparable with those obtained for paromomycin