Reduced salivary flow and colonization by mutans streptococci in children with Down syndrome

OBJECTIVES: Although individuals with Down syndrome have considerable oral disease, the prevalence of dental caries in this group is low. The present study aimed to compare known risk factors for dental caries development in children with Down syndrome and a matched population (siblings). In both populations, the number of acidogenic microorganisms, such as mutans streptococci, lactobacilli and Candida species, and the paraffin-stimulated pH, flow rate and IgA concentration in whole saliva were evaluated and compared. METHOD: Saliva was collected, and the caries index was evaluated in 45 sibling pairs aged between 6 and 18 years old. The salivary IgA concentration was determined by immunoturbidimetry. Salivary mutans streptococci, lactobacilli and Candida species were quantified on mitis salivarius agar containing bacitracin and 20% sucrose, rogosa agar supplemented with glacial acetic acid and sabouraud agar supplemented with chloramphenicol, respectively. RESULTS: Down syndrome children had a higher caries-free rate (p<0.05) and lower salivary mutans streptococci counts (p<0.03) compared to their siblings. Similar numbers of lactobacilli and Candida species were found in both groups. Salivary flow rates were 36% lower in Down syndrome children compared to their siblings (p<0.05). The salivary pH did not differ between Down syndrome children and controls. The Down syndrome children had an IgA secretion rate 29% lower than that of their siblings, but this difference was not statistically significant. CONCLUSIONS: In conclusion, the lower number of mutans streptococci in the saliva may be one of the factors contributing to the lower caries rate observed in Down syndrome children, despite evidence of hyposalivation

Cast versus functional brace in the rehabilitation of patients treated non-operatively for a rupture of the Achilles tendon : protocol for UK Study of Tendo Achilles Rehabilitation (UK STAR)

Introduction Achilles tendon rupture affects over 11,000 people yearly in the UK, and the incidence is increasing. Controversy remains with regards the best rehabilitation strategy for these patients. In operatively treated patients, functional bracing provides better outcomes compared with plaster casts. However, the role of functional bracing in non-operatively managed patients is unclear. This is the protocol for a multi-centre randomised trial of plaster cast immobilisation versus functional bracing for patients with a non-operatively managed Achilles tendon rupture. Methods and analysis All adults presenting with a primary rupture of the Achilles tendon will be screened. Non-operatively treated patients will be eligible to take part in the trial. Broad eligibility criteria will ensure that the results of the study can be generalised to the wider patient population. Randomisation will be on a 1:1 basis. Both rehabilitation strategies are widely used within the NHS. Standardised protocols will be followed, but details of plaster material and brace will be as per the site’s usual practice. A minimum of 330 patients will be randomised to obtain 90% power to detect a difference of 8 points in Achilles Tendon Rupture Score (ATRS) at 9 months. Quality of life and resource use will also be collected at 3, 6 and 9 months. The differences between treatment groups will be assessed on an intention-to-treat basis. Results are expected to be available in the summer of 2019. Ethics and dissemination. National Research Ethic Committee approved this study on the 18th of March 2016 (16/SC/0109). The NIHR Health Technology Assessment monograph and a manuscript to a peer-reviewed journal will be submitted upon completion of the trial. The results of this trial will substantially inform clinical practice on the clinical and cost effectiveness of the treatment of this injury

Perfeccionismo no transtorno obsessivo-compulsivo e nos transtornos alimentares

OBJETIVO: Este estudo tem dois objetivos principais. Primeiro, avaliar as dimensões do perfeccionismo no transtorno obsessivo-compulsivo e nos transtornos alimentares em comparação com duas amostras controle: psiquiátrica (depressão/ansiedade) e não clínica. Segundo, avaliar se o perfeccionismo é um traço de personalidade especificamente relacionado com estas diferentes condições clínicas. MÉTODO: 39 pacientes com transtorno obsessivo-compulsivo, 24 com transtornos alimentares, 65 com um diagnóstico de depressão e/ou ansiedade (todos estes pacientes encontravam-se em regime de ambulatório) e 70 controles não clínicos completaram a versão portuguesa da Multidimensional Perfectionism Scale. RESULTADOS: Comparativamente à amostra não clínica, todas as amostras clínicas apresentaram níveis significativamente mais elevados na Multidimensional Perfectionism Scale total, no Perfeccionismo Auto-Orientado e no Perfeccionismo-Socialmente-Prescrito. Não houve diferenças estatisticamente significativas no Perfeccionismo-Auto-Orientado e na Multidimensional Perfectionism Scale total nas três amostras clínicas. No entanto, a amostra com transtornos alimentares apresentou níveis significativamente mais elevados de Perfeccionismo-Socialmente-Prescrito, comparativamente à transtornos alimentares e à amostra psiquiátrica (depressão/ansiedade). CONCLUSÃO: O perfeccionismo revelou estar associado a uma grande variedade de condições psicopatológicas. Contudo, as diferenças encontradas entre a amostra de transtornos alimentares, de transtorno obsessivo-compulsivo e a psiquiátrica no Perfeccionismo-Socialmente-Prescrito necessitam de investigação subsequente no sentido de clarificar a especificidade desta dimensão com os transtornos alimentares

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

Rugoscopy in human identification: a study in a sample of twins

Palatal rugae patterns can be useful for forensic identification purposes. However, some doubts persist in concerning the pattern singularity in twins. The purpose of this study was to assess palatal rugae pattern singularity in a sample of twins. To do this, the palatal rugae patterns of 19 pairs of monozygotic twins and 47 pairs of dizygotic twins were studied. Our results showed that in monozygotic twins, no statistical significant differences were found, either in the form or number of palatal rugae. However, in dizygotic twins, differences were found in the number or shape of all palatal rugae (except for the shape of the first two right ones), suggesting that the palatal rugae pattern can be useful for identification purposes of dizygotic, but not of monozygotic, twins.Generation XXI was funded by Programa Operacional de Saúde (Regional Department of Ministry of Health). It has support from the Portuguese Foundation for Science and Technology (FCT) and from the Calouste Gulbenkian Foundation.An individual grant to Braga S (SFRH/BD/120500/2016) by the Portuguese Foundation for Science and Technology (FCT) is gratefully acknowledged.This work was financed by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 – Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/MEC-MCI/29777/2017/POCI-01-0145-FEDER-029777

Development of a framework for metabolic pathway analysis-driven strain optimization methods

Genome-scale metabolic models (GSMMs) have become important assets for rational design of compound overproduction using microbial cell factories. Most computational strain optimization methods (CSOM) using GSMMs, while useful in metabolic engineering, rely on the definition of questionable cell objectives, leading to some bias. Metabolic pathway analysis approaches do not require an objective function. Though their use brings immediate advantages, it has mostly been restricted to small scale models due to computational demands. Additionally, their complex parameterization and lack of intuitive tools pose an important challenge towards making these widely available to the community. Recently, MCSEnumerator has extended the scale of these methods, namely regarding enumeration of minimal cut sets, now able to handle GSMMs. This work proposes a tool implementing this method as a Java library and a plugin within the OptFlux metabolic engineering platform providing a friendly user interface. A standard enumeration problem and pipeline applicable to GSMMs is proposed, making use by the community simpler. To highlight the potential of these approaches, we devised a case study for overproduction of succinate, providing a phenotype analysis of a selected strategy and comparing robustness with a selected solution from a bi-level CSOM.The authors thank the project “DeYeastLibrary—Designer yeast strain library optimized for metabolic engineering applications”, Ref. ERA-IB-2/0003/2013, funded by national funds through “Fundação para a Ciência e Tecnologia / Ministério da Ciência, Tecnologia e Ensino Superior”.info:eu-repo/semantics/publishedVersio

Does oral hygiene prevents nosocomial infections in hospitalized patients? A systematic review and meta-analysis

This study aimed to evaluate the impact of oral hygiene (OH) with chlorhexidine (CHX) on the evolution of nosocomial infections (NI). Electronic searches were carried out in PubMed, Scopus, Cochrane Library, Web of Science, VHL, and Grey Literature databases. Randomized clinical trials were included. Methodological quality and risk of bias were assessed using RoB 2.0. Meta-analyses were carried out comparing patients who did or did not receive OH with CHX (0.05%, 0.12% and 2%) for NI, Ventilator-Associated Pneumonia (VAP), S. aureus infection (SA), duration of mechanical ventilation (MV), length of hospital stay and Intensive Care Unit (ICU). The certainty of evidence (CE) was evaluated with GRADE approach. Thirteen studies were selected for quantitative and qualitative synthesis. The risk for VAP (RR 0.72 [0.58, 0.90], p=0.003) and NI (RR 0.70 [0.58, 0.83], p<0.001) were lower in patients of the CHX groups compared to controls, independently for [CHX] used for NI (RR≥0.49, p≤0.03). Patients who received CHX 2×/day presented similar risk to control (RR 0.98 [0.75, 1.30], p=0.91); while 3 and 4×/day or more (RR≥0.52, p≤0.002) presented lower risk for NI. Similar risk for SA was observed among groups (RR 0.42 [0.14, 1.26], p=0.12). The average days of hospitalization (p=0.67), ICU stay (p=0.37) and MV (p=0.57) did not differ between the groups. CE ranged from very low to moderate. OH with CHX reduced NI, regardless of concentration, when used 3×/day or more. However, it had no effect against AS and did not reduce length of hospital stay

Citrullination regulates pluripotency and histone H1 binding to chromatin.

Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.Cancer Research UKThis is the author accepted manuscript. The final version is available from the Nature Publishing Group via http://dx.doi.org/10.1038/nature1294

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta