Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of medication for attention-deficit/hyperactivity disorder and risk of unintentional injuries in children and adolescents with co-occurring neurodevelopmental disorders.

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is often associated with other neurodevelopmental disorders (NDs) and with risky behaviors and adverse health outcomes, including injuries. Treatment with ADHD medication has been associated with reduced risk of injuries. However, it is unknown whether the association is present in individuals with co-occurring NDs. The aim of the present study was to estimate the association between ADHD medication use and unintentional injuries in Sweden in children and adolescents with ADHD, including those with co-occurring NDs. METHODS Using a linkage of several national registers via the unique personal identification number, we identified individuals with a diagnosis of ADHD and of other NDs, including autism spectrum disorder, intellectual disability, communication disorders, learning disorders and motor disorders. The primary outcome was unintentional injuries. Secondary outcome was traumatic brain injury (TBI). Individuals were followed from January 1st 2006 or their 5th birthday or the date of the first unintentional injury, whichever came last, to December 31st 2013 or their 18th birthday or death, whichever came first. We compared the rate of injuries during periods on-treatment with the rate of injuries during periods off-treatment within the same individual using stratified Cox regression to calculate hazard ratio (HR) with 95% confidence intervals (CIs). RESULTS For children and adolescents with ADHD (N = 9,421) the rate of any unintentional injuries (HR = 0.85; 95% CI = 0.78-0.92) and TBIs (HR = 0.27; 95% CIs = 0.20-0.38) during medicated periods was lower than during non-medicated periods. Similar results were found among individuals with co-occurring NDs (N = 2,986), for unintentional injuries (HR = 0.88; 95% CI = 0.77-1.01) and for TBIs (HR = 0.27; 95% CI = 0.16-0.44). CONCLUSIONS Beneficial effects of ADHD medication may extend beyond reduction of ADHD core symptoms to prevention of unintentional injuries in children and adolescents, including individuals with co-occurring NDs.
Sensory cutaneous papillae in the sea lamprey (Petromyzon marinus L.): II. Ontogeny and immunocytochemical characterization of solitary chemosensory cells

Solitary chemosensory cells (SCCs) and their innervating fibers are located in the respiratory system of many vertebrates, including papillae on lamprey gill pores. In order to gain stronger insight for the role of these chemosensory cells, we examined immunocytochemical and innervation characteristics, as well as abundance at the different stages of the lamprey life cycle. The SCCs were distinguished from the surrounding epithelial cells by calretinin and phospholipase C140 immunoreactivity. Nerve fibers extended into the gill pore papillae, as far as the SCCs and serotonergic fibers extended from the underlying dermis into the papillar base. Gill pore papillae were absent and SCCs were sparse during the larval stage and in newly transformed lamprey. Few SCCs were located on small nub‐like papillae during the parasitic juvenile stage, but SCCs were abundant on prominent papillae in migrating and in spawning adults. These findings show similarities between the SCCs in lampreys and other vertebrates and suggest that gill SCC function may be important during the feeding juvenile and the adult stages of the lamprey life cycle.
Antibiotics for secondary prevention of coronary heart disease

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of antibiotics for the secondary prevention of coronary heart disease. As a secondary objective, we plan to assess the effects of individual types of antibiotics for the secondary prevention of coronary heart disease.
Adolescents living with HIV are at higher risk of death and loss to follow up from care: Analysis of cohort data from eight health facilities in Ethiopia

Background There are limited data on the treatment outcomes of adolescents living with HIV. Our objective was to compare mortality and loss to follow up (LTFU) rates between adolescent and younger age groups at enrollment in care. Methods This was a retrospective cohort study carried out in eight health facilities in two regions of Ethiopia. Adolescents (age 10–14 and 15–19 year) and children (age 0–9 year) enrolled in chronic HIV care between 2005 and 2013 constituted the study population. We reviewed the individual patient charts between March and June 2014 and updated the data on the status of each patient through December 2015. We used death and loss-to-follow up as primary endpoints and used the Cox-regression analysis where age, categorized as adolescent versus child, was the main predictor variable. Results Of 2058 participants studied, 52.1% were adolescents. The cohort contributed 2422 person-years of observation (PYO) during the pre-ART follow-up, whereas 1531 patients put on ART contributed 5984 PYO. Of those put on ART, 209 (13.7%) LTFU and 92 (6%) deaths were reported. Adolescents in age group 15–19 yr had the highest risk of LTFU [adjusted hazard ratio, aHR (95% CI) = 3.1 2.1, 5.0 ] followed by those in age group 10–14 yr (aHR = 1.5 [0.9, 2.3]) compared with children aged 0–9 yr. Mortality hazard was significantly higher among younger adolescents (aHR = 2.8 [1.4, 5.4]) and older adolescents (aHR = 2.3 [1.1, 4.9]) compared with children. Conclusions Adolescents are at higher risk of mortality and LTFU as compared to children ages 0–9. Younger adolescents and children had similar LTFU rates. Narrow age band disaggregated analysis can serve as useful guide for tailoring interventions to the specific needs of different age groups.
Genetic mapping of distal femoral, stifle, and tibial radiographic morphology in dogs with cranial cruciate ligament disease

Cranial cruciate ligament disease (CCLD) is a complex trait. Ten measurements were made on orthogonal distal pelvic limb radiographs of 161 pure and mixed breed dogs with, and 55 without, cranial cruciate partial or complete ligament rupture. Dogs with CCLD had significantly smaller infrapatellar fat pad width, higher average tibial plateau angle, and were heavier than control dogs. The first PC weightings captured the overall size of the dog’s stifle and PC2 weightings reflected an increasing tibial plateau angle coupled with a smaller fat pad width. Of these dogs, 175 were genotyped, and 144,509 polymorphisms were used in a genome-wide association study with both a mixed linear and a multi-locus model. For both models, significant (pgenome <3.46×10−7 for the mixed and< 6.9x10-8 for the multilocus model) associations were found for PC1, tibial diaphyseal length and width, fat pad base length, and femoral and tibial condyle width at LCORL, a known body size-regulating locus. Other body size loci with significant associations were growth hormone 1 (GH1), which was associated with the length of the fat pad base and the width of the tibial diaphysis, and a region on CFAX near IRS4 and ACSL4 in the multilocus model. The tibial plateau angle was associated significantly with a locus on CFA10 in the linear mixed model with nearest candidate genes BET1 and MYH9 and on CFA08 near candidate genes WDHD1 and GCH1. MYH9 has a major role in osteoclastogenesis. Our study indicated that tibial plateau slope is associated with CCLD and a compressed infrapatellar fat pad, a surrogate for stifle osteoarthritis. Because of the association between tibial plateau slope and CCLD, and pending independent validation, these candidate genes for tibial plateau slope may be tested in breeds susceptible to CCLD before they develop disease or are bred.
Immune Dysfunctions and Immunotherapy in Colorectal Cancer: The Role of Dendritic Cells

Colorectal cancer (CRC), a multi-step malignancy showing increasing incidence in today’s societies, represents an important worldwide health issue. Exogenous factors, such as lifestyle, diet, nutrition, environment and microbiota, contribute to CRC pathogenesis, also influencing non neoplastic cells, including immune cells. Several immune dysfunctions were described in CRC patients at different disease stages. Many studies underline the role of microbiota, obesity-related inflammation, diet and host reactive cells, including dendritic cells (DC), in CRC pathogenesis. Here, we focused on DC, the main cells linking innate and adaptive anti-cancer immunity. Variations in the number and phenotype of circulating and tumor-infiltrating DC have been found in CRC patients and correlated with disease stages and progression. A critical review of DC-based clinical studies and of recent advances in cancer immunotherapy leads to consider new strategies for combining DC vaccination strategies with check-point inhibitors, thus opening perspectives for a more effective management of this neoplastic disease.
Evolution & Development

Correspondence Frietson Galis, Naturalis Biodiversity Center, 2333 CR Leiden, The Netherlands. Email: frietson.galis@naturalis.nl Abstract The absence of a paternal contribution in an unfertilized ovum presents two developmental constraints against the evolution of parthenogenesis. We discuss the constraint caused by the absence of a centrosome and the one caused by the missing set of chromosomes and how they have been broken in specific taxa. They are examples of only a few well‐underpinned examples of developmental constraints acting at macro‐evolutionary scales in animals. Breaking of the constraint of the missing chromosomes is the best understood and generally involves rare occasions of drastic changes of meiosis. These drastic changes can be best explained by having been induced, or at least facilitated, by sudden cytological events (e.g., repeated rounds of hybridization, endosymbiont infections, and contagious infections). Once the genetic and developmental machinery is in place for regular or obligate parthenogenesis, shifts to other types of parthenogenesis can apparently rather easily evolve, for example, from facultative to obligate parthenogenesis, or from pseudoarrhenotoky to haplodiploidy. We argue that the combination of the two developmental constraints forms a near‐absolute barrier against the gradual evolution from sporadic to obligate or regular facultative parthenogenesis, which can probably explain why the occurrence of the highly advantageous mode of regular facultative parthenogenesis is so rare and entirely absent in vertebrates.
RILP Restricts Insulin Secretion Through Mediating Lysosomal Degradation of Proinsulin

Insulin secretion is tightly regulated by membrane trafficking. RILP (Rab7 interacting lysosomal protein) regulates the endocytic trafficking, but its role in insulin secretion has not been investigated. In this study, we found that overexpression of RILP inhibited insulin secretion in both the β-cell lines and freshly isolated islets. Consequently, the expression of RILP in islets suppressed the ability to recover the glucose homeostasis in type 1 diabetes mice upon transplantation. Of physiological relevance is that RILP expression was upregulated in the diabetic mouse islets. Mechanistically, overexpression of RILP induced insulin granule clustering, decreased the number of proinsulin-containing granules in β-cells, and significantly promoted proinsulin degradation. Conversely, RILP depletion sustained proinsulin and increased insulin secretion. The proinsulin degradation induced by RILP expression was inhibited by lysosomal inhibitors and was Rab7-dependent. Finally, we showed that RILP interacts with insulin granule–associated Rab26 to restrict insulin secretion. This study presents a new pathway regulating insulin secretion and mechanically demonstrates a novel function of RILP in modulating insulin secretion through mediating the lysosomal degradation of proinsulin.
16 T high static magnetic field inhibits receptor activator of nuclear factor kappa‐Β ligand‐induced osteoclast differentiation by regulating iron metabolism in Raw264.7 cells

High static magnetic fields (HiSMFs) are usually defined as those SMFs with intensities ≥1 T. Although many studies have indicated that SMFs have positive effects on bone tissue, there were limited studies that investigate the effects of cells, including osteoclasts, to illustrate the effect of HiSMF on osteoclast differentiation, and whether iron involve in the altered osteoclast formation and resorption ability under HiSMF. 16 T HiSMF generated from a superconducting magnet was used. Osteoclastogenesis, bone resorption, acting ring formation, messenger ribonucleic acid expression, and protein expression were determined by tartrate‐resistant acid phosphatase staining, pits formation assay, rhodamine‐conjugated phalloidine staining, quantitative real‐time polymerase chain reaction, and western blot, respectively. The changes induced by HiSMF in the level of iron and the concentration of mitochondrial protein, adenosine triphosphate, reactive oxygen species, malonaldehyde, and glutathione were examined by atomic absorption spectrometry and corresponding commercial kits, respectively. The results showed that HiSMF significantly inhibited osteoclastic formation and resorption ability and reduced cellular iron content during osteoclast differentiation. Mitochondrial concentration and oxidative stress levels in osteoclasts were decreased under HiSMF. Mechanistically, HiSMF markedly blocked the expression of osteoclast‐associated transcription factors and osteoclast marker genes and inhibited iron absorption and iron storage‐related protein expression. These findings demonstrated that the effect of HiSMF on iron metabolism of osteoclasts was involved in the inhibition of HiSMF on osteoclast differentiation.
Limites e possibilidades do idoso frente à aposentadoria.

This qualitative study whose objective was identify the vision of elderly facing retirement through structured interviews with 15 elderly retirees participating in the Program of Geriatrics and Gerontology at the Universidade Federal Fluminense in Niteroi-RJ, with CEP approved by the Institution under number 125. 294 project interview. It was concluded that both limits considered negatives, as the possibilities are taken as positive points associated with a prior retirement planning associated with better quality of life of the elderly.
Pharmacodynamics OF TNF α inhibitors for the treatment of psoriasis

ABSTRACT Introduction: The treatment of psoriasis with conventional topical therapies and disease-modifying anti-rheumatic drugs (DMARDs) is often linked to unsatisfactory outcomes and the risk of serious adverse events. Over the last decades, research advances in understanding the role of tumor necrosis factor alpha (TNF α) and other cytokines in the pathogenesis of psoriasis have driven the introduction of biologic agents targeting specific immune mediators in everyday clinical practice. TNF α inhibitors are a consolidated treatment option for patients with moderate-to-severe disease with remarkable efficacy and a reassuring safety profile. Areas covered: The PubMed database was searched using combinations of the following keywords: psoriasis, TNF α inhibitors, biologic therapy, pharmacodynamics, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, adverse effects. The aim of this review is to describe the pharmacodynamic profile of anti-TNF α inhibitors, currently approved by the European Medicines Agency (EMA) for the treatment of psoriasis, focusing on related clinical implications, also in comparison to the new generation biological therapies targeting the interleukin 23/interleukin 17 axis. Expert opinion: Pharmacodynamics of TNF α inhibitors should be fully considered in planning patient’s therapy strategies, especially in case of secondary failures, poor adherence to treatment, instable psoriasis, high risk of infection, pregnant or lactating women, metabolic comorbidities, coexistence of other immune-mediated inflammatory diseases.
Kinetics of mean platelet volume predicts mortality in patients with septic shock

Introduction Thrombocytopenia is well recognized as a poor prognosis sign associated with increased mortality and prolonged Intensive Care Unit (ICU) stay, particularly in septic patients. Mean platelet volume (MPV) could represent a relevant predictive marker of mortality. Here we investigated whether MPV kinetics during the first 15 days after hospital admission has a potential prognostic value for clinical outcome in septic shock. Methods We performed a retrospectively analysis of a cohort of 301 septic patients admitted in ICU. Three-month mortality was the primary endpoint. The prognostic value of the covariates of interest was ascertained by multidimensional analysis. We proposed a classification and regression trees analysis to predict survival probability. Results MPV kinetics was significantly different between 90-day survivors and non-survivors when followed during 15 days (except on day 3). 10-day MPV >11.6fL was an independent predictive factor of 90-day mortality (Hazard Ratio (HR) 3.796, 95% Confidence Interval (CI) [1.96–7.35], p = 0.0001) in multivariate analysis. Base excess on day 4 <1.9mmol/L was also a predictive factor of mortality (HR 2.972, 95%CI [1.38–6.40], p = 0.0054. Conclusion MPV increase during the first 15 days after ICU admission in non-survivors was observed during septic shock and 10-day MPV >11.6fL was an independent predictive factor of 90-day mortality. This could be explained by the emergent response to acute platelet loss during septic shock, leading to megakaryocyte rupture to produce new but potentially immature platelets in the circulation. Therefore, continuous monitoring of MPV may be a useful parameter to stratify mortality risk in septic shock.
Experimental characterization of two archaeal inosine 5'-monophosphate cyclohydrolases

There is variability as to how archaea catalyze the final step of de novo purine biosynthesis to form inosine 5’-monophosphate (IMP) from 5-formamidoimidazole-4-carboxamide ribonucleotide (FAICAR). Although non-archaea almost uniformly use the bifunctional PurH protein, which has an N-terminal IMP cyclohydrolase (PurH2) fused to a C-terminal folate-dependent aminoimidazole-4-carboxamide ribonucleotide (AICAR) formyltransferase (PurH1) domain, a survey of the genomes of archaea reveals use of PurH2 (with or without fusion to PurH1), the “euryarchaeal signature protein” PurO, or an unidentified crenarchaeal IMP cyclohydrolase. In this report, we present the cloning and functional characterization of two representatives of the known IMP cyclohydrolase families. The locus TK0430 in Thermococcus kodakarensis encodes a PurO-type IMP cyclohydrolase with demonstrated activity despite its position in a cluster of apparently redundant biosynthetic genes, the first functional characterization of a PurO from a non-methanogen. Kinetic characterization reveals a Km for FAICAR of 1.56 ± 0.39 μM and a kcat of 0.48 ± 0.04 s-1. The locus AF1811 from Archaeoglobus fulgidus encodes a PurH2-type IMP cyclohydrolase. This Archaeoglobus fulgidus PurH2 has a Km of 7.8 ± 1.8 μM and kcat of 1.32 ± 0.14 s-1, representing the first characterization of an archaeal PurH2 and the first characterization of PurH2 that naturally occurs unfused to an AICAR formyltransferase domain. Each of these two characterized IMP cyclohydrolases converts FAICAR to IMP in vitro, and each cloned gene allows the growth on purine-deficient media of an E. coli purine auxotroph lacking the purH2 gene.
Identification of social relation within pedestrian dyads

This study focuses on social pedestrian groups in public spaces and makes an effort to identify the type of social relation between the group members. As a first step for this identification problem, we focus on dyads (i.e. 2 people groups). Moreover, as a mutually exclusive categorization of social relations, we consider the domain-based approach of Bugental, which precisely corresponds to social relations of colleagues, couples, friends and families, and identify each dyad with one of those relations. For this purpose, we use anonymized trajectory data and derive a set of observables thereof, namely, inter-personal distance, group velocity, velocity difference and height difference. Subsequently, we use the probability density functions (pdf) of these observables as a tool to understand the nature of the relation between pedestrians. To that end, we propose different ways of using the pdfs. Namely, we introduce a probabilistic Bayesian approach and contrast it to a functional metric one and evaluate the performance of both methods with appropriate assessment measures. This study stands out as the first attempt to automatically recognize social relation between pedestrian groups. Additionally, in doing that it uses completely anonymous data and proves that social relation is still possible to recognize with a good accuracy without invading privacy. In particular, our findings indicate that significant recognition rates can be attained for certain categories and with certain methods. Specifically, we show that a very good recognition rate is achieved in distinguishing colleagues from leisure-oriented dyads (families, couples and friends), whereas the distinction between the leisure-oriented dyads results to be inherently harder, but still possible at reasonable rates, in particular if families are restricted to parent-child groups. In general, we establish that the Bayesian method outperforms the functional metric one due, probably, to the difficulty of the latter to learn observable pdfs from individual trajectories.
Epidemiology of Neonatal Sepsis at Johannesburg Hospital

AbstractWe evaluated sepsis in the neonatal unit at Johannesburg Hospital including the time of onset, clinical features, outcome of the treatment of patients, pathogens isolated, and antimicrobial sensitivity to provide site-specific guidelinesfor empiric antibiotic therapy. This was a retrospective study conducted in the neonatal unit of the Johannesburg Hospital between 1 July 2002 and 30 June 2003. All neonates with growth on blood cultures were included. Demographic, clinical, laboratory and microbiological data were reviewed. Of a total of l03 infants with l40 positive blood cultures, eight isolates were most likely to be contaminants. There were thus 132 significant isolates in 96 patients: five presented with early onset sepsis(EOS) and 91 withlate onset sepsis (LOS). Gram-negative bacilli werethe predominant isolatesin EOS and coagulL-negative staphylococci(CoNS)the predominantisolates(63)in LOS (40/63 considered significant, CoNS were not speciated as Staphylococcus epidermidis). Theremaining is.