Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Iron Transport in Streptococcus pneumoniae by RitR, an Orphan Response Regulator

ABSTRACT RitR (formerly RR489) is an orphan two-component signal transduction response regulator in Streptococcus pneumoniae that has been shown to be required for lung pathogenicity. In the present study, by using the rough strain R800, inactivation of the orphan response regulator gene ritR by allele replacement reduced pathogenicity in a cyclophosphamide-treated mouse lung model but not in a thigh model, suggesting a role for RitR in regulation of tissue-specific virulence factors. Analysis of changes in genome-wide transcript mRNA levels associated with the inactivation of ritR compared to wild-type cells was performed by the use of high-density DNA microarrays. Genes with a change in transcript abundance associated with inactivation of ritR included piuB, encoding an Fe permease subunit, and piuA, encoding an Fe carrier-binding protein. In addition, a dpr ortholog, encoding an H2O2 resistance protein that has been shown to reduce synthesis of reactive oxygen intermediates, was activated in the wild-type (ritR+) strain. Microarray experiments suggested that RitR represses Fe uptake in vitro by negatively regulating the Piu hemin-iron transport system. Footprinting experiments confirmed site-specific DNA-binding activity for RitR and identified three binding sites that partly overlap the +1 site for transcription initiation upstream of piuB. Transcripts belonging to other gene categories found to be differentially expressed in our array studies include those associated with (i) H2O2 resistance, (ii) repair of DNA damage, (iii) sugar transport and capsule biosynthesis, and (iv) two-component signal transduction elements. These observations suggest that RitR is an important response regulator whose primary role is to maintain iron homeostasis in S. pneumoniae. The name ritR (repressor of iron transport) for the orphan response regulator gene, rr489, is proposed.
Chronic obstructive pulmonary disease exacerbation and inhaler device handling: real-life assessment of 2935 patients

Acute exacerbations of chronic obstructive pulmonary disease (COPD) can be prevented by inhaled treatment. Errors in inhaler handling, not taken into account in clinical trials, could impact drug delivery and minimise treatment benefit. We aimed to assess real-life inhaler device handling in COPD patients and its association with COPD exacerbations. To this end, 212 general practitioners and 50 pulmonologists assessed the handling of 3393 devices used for continuous treatment of COPD in 2935 patients. Handling errors were observed in over 50% of handlings, regardless of the device used. Critical errors compromising drug delivery were respectively made in 15.4%, 21.2%, 29.3%, 43.8%, 46.9% and 32.1% of inhalation assessment tests with Breezhaler® (n=876), Diskus® (n=452), Handihaler® (n=598), pressurised metered-dose inhaler (pMDI) (n=422), Respimat® (n=625) and Turbuhaler® (n=420). The proportion of patients requiring hospitalisation or emergency room visits in the past 3 months for severe COPD exacerbation was 3.3% (95% CI 2.0–4.5) in the absence of error and 6.9% (95% CI 5.3–8.5) in the presence of critical error (OR 1.86, 95% CI 1.14–3.04, p<0.05). Handling errors of inhaler devices are underestimated in real life and are associated with an increased rate of severe COPD exacerbation. Training in inhaler use is an integral part of COPD management. Inhaler mishandling is frequent and associated with increased severe COPD exacerbation http://ow.ly/rRvU3069S0Y
Epidemiologic study of odontogenic and non-odontogenic cysts in children and adolescents of a Brazilian population

Background The objective of this study was to describe the frequency of cystic lesions in a Brazilian population of patients histopathologically diagnosed in the first and second decade of life. Material and Methods Retrospective descriptive cross-sectional study was performed. Biopsy records were obtained from the archives of a Brazilian referral center between 1980 and 2016. Results A total of 2.114 biopsy records of pediatric patients were analyzed with oral and maxillofacial lesions. Data such as gender, age, anatomical location, and histopathological diagnosis were collected and categorized. Among all oral and maxillofacial lesions (n=2.114), were diagnosed 294 cases of odontogenic cysts (13.9%) and 16 cases of non-odontogenic cysts (0.8%). The most frequent lesions in each group were, respectively: radicular cyst (n=145) and epidermoid cyst (n=4). These lesions were most common in female (n=158), with a mean age of 14 years. For intraosseous lesions, the mandible (n=148) was the most affected anatomic site; moreover, the floor of the mouth (n=6) was most affected by cysts in soft tissues. Conclusions Odontogenic cysts were relatively common in population studied, but non-odontogenic cysts were rare in these patients. Key words:Odontogenic cysts, non-odontogenic cysts, cysts in children, cysts in adolescents.
Effects of a parental exposure to diuron on Pacific oyster spat methylome

Abstract Environmental epigenetic is an emerging field that studies the cause–effect relationship between environmental factors and heritable trait via an alteration in epigenetic marks. This field has received much attentions since the impact of environmental factors on different epigenetic marks have been shown to be associated with a broad range of phenotypic disorders in natural ecosystems. Chemical pollutants have been shown to affect immediate epigenetic information carriers of several aquatic species but the heritability of the chromatin marks and the consequences for long term adaptation remain open questions. In this work, we investigated the impact of the diuron herbicide on the DNA methylation pattern of spat from exposed Crassotrea gigas genitors. This oyster is one of the most important mollusk species produced worldwide and a key coastal economic resource in France. The whole genome bisulfite sequencing (WGBS, BS-Seq) was applied to obtain a methylome at single nucleotide resolution on DNA extracted from spat issued from diuron exposed genitors comparatively to control spat. We showed that the parental diuron exposure has an impact on the DNA methylation pattern of its progeny. Most of the differentially methylated regions occurred within coding sequences and we showed that this change in methylation level correlates with RNA level only in a very small group of genes. Although the DNA methylation profile is variable between individuals, we showed conserved DNA methylation patterns in response to parental diuron exposure. This relevant result opens perspectives for the setting of new markers based on epimutations as early indicators of marine pollutions.
Title Equity in the utilisation of health care in Ireland

This paper analyses the extent of equity of health service delivery across the income distribution in Ireland – that is the extent to which there is equal treatment for equal need irrespective of income. We find that almost all services, apart from dental and optician services, are used more by those at the lower end of the income distribution, but that this group also have the greatest need for health care. The comparison of health need to health care delivery across the income distribution without standardising for confounding factors suggests that those in higher income groups receive more health care for a given health status indicating inequity. However, need for health care is highest among the elderly and this group also tend to be at the bottom of the income distribution. Once we standardise for age, sex and location we find that hospital services are distributed equitably across the income distribution, whereas GP and prescription services tend to be pro-poor (used more by those with lower incomes for a given health status) and dental and optician services tend to be pro-rich (used more by those with higher incomes for a given health status).
Neural Correlates of Feedback Processing in Toddlers

External feedback provides essential information for successful learning. Feedback is especially important for learning in early childhood, as toddlers strongly rely on external signals to determine the consequences of their actions. In adults, many electrophysiological studies have elucidated feedback processes using a neural marker called the feedback-related negativity (FRN). The neural generator of the FRN is assumed to be the ACC, located in medial frontal cortex. As frontal brain regions are the latest to mature during brain development, it is unclear when in early childhood a functional feedback system develops. Is feedback differentiated on a neural level in toddlers and in how far is neural feedback processing related to children's behavioral adjustment? In an EEG experiment, we addressed these questions by measuring the brain activity and behavioral performance of 2.5-year-old toddlers while they played a feedback-guided game on a touchscreen. Electrophysiological results show differential brain activity for feedback with a more negative deflection for incorrect than correct outcomes, resembling the adult FRN. This provides the first neural evidence for feedback processing in toddlers. Notably, FRN amplitudes were predictive of adaptive behavior: the stronger the differential brain activity for feedback, the better the toddlers' adaptive performance during the game. Thus, already in early childhood toddlers' feedback-guided performance directly relates to the functionality of their neural feedback processing. Implications for early feedback-based learning as well as structural and functional brain development are discussed.
Humoral and Innate Antiviral Immunity as Tools to Clear Persistent HIV Infection

Abstract Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells. On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions. HIV-1 Env-specific antibodies have the potential to bind HIV-1 cell surface Env and promote elimination of infected CD4+ T cells by recruiting cytotoxic effector cells, such as natural killer cells, monocytes, and polymorphonuclear cells. Harnessing humoral and innate cellular responses has become one focus of research to develop innovative strategies to recruit and redirect cytotoxic effector cells to eliminate the HIV-1 latently infected CD4+ T-cell reservoir.
Metagenomic analysis of orange colored protrusions from the muscle of Queen Conch Lobatus gigas (Linnaeus, 1758)

The endangered marine gastropod, Lobatus gigas, is an important fishery resource in the Caribbean region. Microbiological and parasitological research of this species have been poorly addressed despite its role in ecological fitness, conservation status and prevention of potential pathogenic infections. This study identified taxonomic groups associated with orange colored protrusions in the muscle of queen conchs using histological analysis, 454 pyrosequencing, and a combination of PCR amplification and automated Sanger sequencing. The molecular approaches indicate that the etiological agent of the muscle protrusions is a parasite belonging to the subclass Digenea. Additionally, the scope of the molecular technique allowed the detection of bacterial and fungi clades in the assignment analysis. This is the first evidence of a digenean infection in the muscle of this valuable Caribbean resource.
Factors associated with professional satisfaction in primary care: Results from EUprimecare project

Abstract Background: Given the importance of primary care to healthcare systems and population health, it seems crucial to identify factors that contribute to the quality of primary care. Professional satisfaction has been linked with quality of primary care. Physician dissatisfaction is considered a risk factor for burnout and leaving medicine. Objectives: This study explored factors associated with professional satisfaction in seven European countries. Methods: A survey was conducted among primary care physicians. Estonia, Finland, Germany and Hungary used a web-based survey, Italy and Lithuania a telephone survey, and Spain face to face interviews. Sociodemographic information (age, sex), professional experience and qualifications (years since graduation, years of experience in general practice), organizational variables related to primary care systems and satisfaction were included in the final version of the questionnaire. A logistic regression analysis was performed to assess the factors associated with satisfaction among physicians. Results: A total of 1331 primary care physicians working in primary care services responded to the survey. More than half of the participants were satisfied with their work in primary care services (68.6%). We found significant associations between satisfaction and years of experience (OR = 1.01), integrated network of primary care centres (OR = 2.8), patients having direct access to specialists (OR = 1.3) and professionals having access to data on patient satisfaction (OR = 1.3). Public practice, rather than private practice, was associated with lower primary care professional satisfaction (OR = 0.8). Conclusion: Elements related to the structure of primary care are associated with professional satisfaction. At the individual level, years of experience seems to be associated with higher professional satisfaction.
Phenotypic and Genotypic Characterization of Klebsiella pneumoniae Isolated From Retail Foods in China

Klebsiella pneumoniae is not only a major hospital-acquired pathogen but also an important food-borne pathogen that can cause septicaemia, liver abscesses, and diarrhea in humans. The phenotypic and genotypic characteristics of K. pneumoniae in retail foods have not been thoroughly investigated in China. The objective of this study was to characterize K. pneumoniae isolates through biotyping, serotyping, determination of virulence factors, antibiotic resistance testing, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR), and (GTG)5-PCR molecular typing. From May 2013 to April 2014, a total of 61 K. pneumoniae isolates were collected from retail foods in China. Using API 20E test strips, five different biotype profiles were identified among these isolates. The majority of isolates belonged to biochemical profile “5215773” (50 isolates, 80.6%). The capsular serotypes of the 61 K. pneumoniae isolates and one reference strain were determined by PCR. Of the seven capsular serotypes tested, four different capsular serotypes were identified. Serotypes K1, K20, K57, and K2 were detected in two, three, two, and one isolates, respectively. Serotypes K3, K5, and K54 were not detected. The presence of 11 virulence genes was assessed by PCR. The most common virulence genes were fimH (85.5%), ureA (79.0%), wabG (77.4%), uge (56.5%), and kfuBC (29.0%). ERIC-PCR and (GTG)5-PCR molecular typing indicated high genetic diversity among K. pneumoniae isolates. We identified 60 different ERIC patterns and 56 distinct (GTG)5 patterns. Genotypic results indicated that isolates carrying similar virulence factors were generally genetically related. Some isolates from the same geographic area have a closer relationship. The isolates showed high levels of resistance to ampicillin (51/62, 82.2%). Resistance to streptomycin (11/62, 17.7%) and piperacillin (10/62, 16.1%) was also common. The presence of virulent and antibiotic-resistant K. pneumoniae in foods poses a potential health hazard for consumers. Our findings highlight the importance of surveillance of K. pneumoniae in foods.
Occupational group, educational level, marital status and deleterious habits among individuals with maxillofacial fractures: retrospective study

Background To investigate the occupational profile, educational level, marital status and deleterious habits to the health of patients with maxillofacial fractures of a population of northeastern Brazil. Material and Methods A retrospective study of patients records admitted to the Division of Oral and Maxillofacial Surgery at the Walter Cantídio University Hospital (Fortaleza, Brazil) who sustained maxillofacial fractures was conducted in the period between 2006 and 2015. Results A total of 338 patients rendered 355 fractures. Males were the most affected (p<0.001), with prevalence in the third decade of life (p<0.001). There was a predominance of motorcycle accidents (p<0.001), home workers (p<0.001), low educational status (p = 0.032), and no cigarette use (p<0.001) or alcohol (p = 0.023). Fractures of the zygomatic-orbital complex were the most prevalent in the sample (p<0.001). Conclusions The sociodemographic profile exerted a significant influence on the epidemiological profile of maxillofacial fractures in a Brazilian population during the study period. Key words:Epidemiological studies, trauma, facial bones.
A General Model for Estimating Macroevolutionary Landscapes

&NA; The evolution of quantitative characters over long timescales is often studied using stochastic diffusion models. The current toolbox available to students of macroevolution is however limited to two main models: Brownian motion and the Ornstein‐Uhlenbeck process, plus some of their extensions. Here, we present a very general model for inferring the dynamics of quantitative characters evolving under both random diffusion and deterministic forces of any possible shape and strength, which can accommodate interesting evolutionary scenarios like directional trends, disruptive selection, or macroevolutionary landscapes with multiple peaks. This model is based on a general partial differential equation widely used in statistical mechanics: the Fokker‐Planck equation, also known in population genetics as the Kolmogorov forward equation. We thus call the model FPK, for Fokker‐Planck‐Kolmogorov. We first explain how this model can be used to describe macroevolutionary landscapes over which quantitative traits evolve and, more importantly, we detail how it can be fitted to empirical data. Using simulations, we show that the model has good behavior both in terms of discrimination from alternative models and in terms of parameter inference. We provide R code to fit the model to empirical data using either maximum‐likelihood or Bayesian estimation, and illustrate the use of this code with two empirical examples of body mass evolution in mammals. FPK should greatly expand the set of macroevolutionary scenarios that can be studied since it opens the way to estimating macroevolutionary landscapes of any conceivable shape. [Adaptation; bounds; diffusion; FPK model; macroevolution; maximum‐likelihood estimation; MCMC methods; phylogenetic comparative data; selection. ]
Can Limited Education of Lung Ultrasound Be Conducted to Medical Students Properly? A Pilot Study

Objectives. Lung ultrasonography (LUS) is a useful examination to identify lung problems. Unfortunately, there are currently no LUS educational programs for medical students. We designed a brief LUS training course for medical students during the ED rotation. The purpose of training was improving cognitive and psychomotor learning domains, knowledge of ultrasound, knowledge of LUS, image acquisition, and image interpretation. Methods. Forty students in their fourth year of medical school were enrolled in this study. Student achievement was evaluated through examinations of cognitive and psychomotor skills. A survey was administered following the training. Results. The average test result was 42.1 ± 13.7 before training and 82.6 ± 10.7 after training. With respect to the assessment of LUS performance, the acceptable rates for right and left anterior chest wall scanning and right and left posterolateral scanning were 95%, 97.5%, 92.5%, and 100%, respectively. The students felt a high level of confidence in their ability to administer LUS to patients after training and they agreed that inclusion of LUS training in the medical school curriculum is necessary. Conclusion. This study showed that, among the medical students without ultrasound experience, limited LUS education to improve their knowledge, image acquisition, and interpretation ability was successful.
Improvements in fitness are not obligatory for exercise training‐induced improvements in CV risk factors

The purpose of this study was to assess whether changes in physical fitness relate to changes in cardiovascular risk factors following standardized, center‐based and supervised exercise training programs in subjects with increased cardiovascular risk. We pooled data from exercise training studies of subjects with increased cardiovascular risk (n = 166) who underwent 8–52 weeks endurance training. We determined fitness (i.e., peak oxygen uptake) and traditional cardiovascular risk factors (body mass index, blood pressure, total cholesterol, high‐density lipoprotein cholesterol), before and after training. We divided subjects into quartiles based on improvement in fitness, and examined whether these groups differed in terms of risk factors. Associations between changes in fitness and in cardiovascular risk factors were further tested using Pearson correlations. Significant heterogeneity was apparent in the improvement of fitness and individual risk factors, with nonresponder rates of 17% for fitness, 44% for body mass index, 33% for mean arterial pressure, 49% for total cholesterol, and 49% for high‐density lipoprotein cholesterol. Neither the number, nor the magnitude, of change in cardiovascular risk factors differed significantly between quartiles of fitness change. Changes in fitness were not correlated with changes in cardiovascular risk factors (all P > 0.05). Our data suggest that significant heterogeneity exists in changes in peak oxygen uptake after training, while improvement in fitness did not relate to improvement in cardiovascular risk factors. In subjects with increased cardiovascular risk, improvements in fitness are not obligatory for training‐induced improvements in cardiovascular risk factors.
Paraproteinemic keratopathy in monoclonal gammopathy of undetermined significance treated with primary keratoprosthesis

Rationale: We report a case of paraproteinemic keratopathy associated with monoclonal gammopathy of undetermined significance, treated with keratoprosthesis as a primary penetrating procedure. Histopathological findings and a world literature review are presented. Patient concerns: A 74 year old female recently diagnosed with monoclonal gammopathy undetermined significance presented with progressive blurry vision bilaterally. Diagnoses: Examination revealed corneal opacities consistent with paraproteinemic keratopathy. Interventions: Corneal transplantation with the Boston Type I keratoprosthesis was performed on the right and, a year later, on the left. Outcomes: Visual outcomes were good. Histopathological staining of host corneal buttons were consistent with monoclonality, and electron microscopy revealed fibrillar extracellular aggregates within intervening normal stroma. Lessons: Corneal deposits may be the only manifestation of monoclonal gammopathy of undetermined significance in patients who are otherwise systemically asymptomatic. Ophthalmologists who encounter corneal opacities may order the appropriate diagnostic studies to determine the presence of occult systemic disease. Risk of graft failure after penetrating keratoplasty from recurring opacities is high, so keratoprosthesis as a primary penetrating procedure may afford superior long-term outcomes. Host corneal buttons retrieved from penetrating keratoplasty or corneal biopsy may be sent for histopathological examination to confirm the diagnosis.