Serum prolactin as a biomarker for the study of intracerebral dopamine effect in adult patients with phenylketonuria: a cross-sectional monocentric study

BACKGROUND: It has been previously postulated that high phenylalanine (Phe) might disturb intracerebral dopamine production, which is the main regulator of prolactin secretion in the pituitary gland. Previously, various associations between Phe and hyperprolactinemia were revealed in studies performed in phenylketonuria (PKU) children and adolescents. The aim of the present study was to clarify whether any relation between serum phenylalanine and prolactin levels can be found in adult PKU patients. PATIENTS AND METHODS: We conducted a cross-sectional, monocentric study including 158 adult patients (male n = 68, female n = 90) with PKU. All patients were diagnosed during newborn screening and were treated since birth. Serum Phe, tyrosine (Tyr), prolactin (PRL), and thyroid-stimulating hormone (TSH) levels were measured, and Phe/Tyr ratio was calculated. Males and females were analyzed separately because the serum prolactin level is gender-dependent. RESULTS: No significant correlations were found between serum phenylalanine, tyrosine, or the Phe/Tyr ratio and serum prolactin level either in the male or in the female group. CONCLUSIONS: In treated adult PKU patients, the serum prolactin level may not be significantly influenced by Phe or Tyr serum levels

Metal-responsive gene regulation and metal transport in Helicobacter species

Helicobacter species are among the most successful colonizers of the mammalian gastrointestinal and hepatobiliary tract. Colonization is usually lifelong, indicating that Helicobacter species have evolved intricate mechanisms of dealing with stresses encountered during colonization of host tissues, like restriction of essential metal ions. The recent availability of genome sequences of the human gastric pathogen Helicobacter pylori, the murine enterohepatic pathogen Helicobacter hepaticus and the unannotated genome sequence of the ferret gastric pathogen Helicobacter mustelae has allowed for comparitive genome analyses. In this review we present such analyses for metal transporters, metal-storage and metal-responsive regulators in these three Helicobacter species, and discuss possible contributions of the differences in metal metabolism in adaptation to the gastric or enterohepatic niches occupied by Helicobacter species

Remarkable genomic diversity among Escherichia isolates recovered from healthy chickens

The genus Escherichia has been extensively studied and it is known to encompass a range of commensal and pathogenic bacteria that primarily inhabit the gastrointestinal tracts of warm-blooded vertebrates. However, the presence of E. coli as a model organism and potential pathogen has diverted attention away from commensal strains and other species in the genus. To investigate the diversity of Escherichia in healthy chickens, we collected fecal samples from antibiotic-free Lohmann Brown layer hens and determined the genome sequences of 100 isolates, 81 of which were indistinguishable at the HC0 level of the Hierarchical Clustering of Core Genome Multi-Locus Sequence Typing scheme. Despite initial selection on CHROMagar Orientation medium, which is considered selective for E. coli, in silico phylotyping and core genome single nucleotide polymorphism analysis revealed the presence of at least one representative of all major clades of Escherichia, except for E. albertii, Shigella, and E. coli phylogroup B2 and cryptic clade I. The most frequent phylogenomic groups were E. coli phylogroups A and B1 and E. ruysiae (clades III and IV). We compiled a collection of reference strains isolated from avian sources (predominantly chicken), representing every Escherichia phylogroup and species, and used it to confirm the phylogeny and diversity of our isolates. Overall, the isolates carried low numbers of the virulence and antibiotic resistance genes typically seen in avian pathogenic E. coli. Notably, the clades not recovered are ones that have been most strongly associated with virulence by other studies

A critical evaluation of network and pathway based classifiers for outcome prediction in breast cancer

Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single gene classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single gene classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single gene classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single gene sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single gene classifiers for predicting outcome in breast cancer

Meningokokkenziekte in Nederland : Achtergrondinformatie voor de Gezondheidsraad

Meningococcal disease is a very serious infectious disease caused by a bacterium, the meningococcus. There are different types of meningococcus; people become ill mainly from the B, C, W and Y serogroups. Since 2002, vaccination against serogroup C meningococcal disease has been included in the National Immunisation Programme for children of 14 months. As a result, serogroup C meningococcal disease has virtually disappeared. Vaccines against serogroup B have recently become available. In addition, since 2015, there has been a rapid increase in serogroup W meningococcal disease. Multi-component vaccines are available against A, C, W and Y serogroups. Based on these developments, among others, the Health Council will advise the Minister for Health, Welfare and Sport on whether and how the current immunisation programme against meningococcal disease should be adapted. To this end, RIVM has collected background information and recent data on meningococcal disease in the Netherlands. It includes the number of people in the Netherlands who become ill each year, the efficacy and safety of the vaccines, and what the public thinks about vaccination against invasive meningococcal disease. The infection causes a severe medical condition such as meningitis or blood poisoning, which can rapidly develop into shock, frequently causing death. The disease often begins with flu-like symptoms and fever which subsequently worsen very rapidly. The infection is relatively rare in the Netherlands; there are currently 100 to 150 patients a year. Five to ten percent of these patients die despite antibiotics and intensive care. Thirty percent of the patients are left with lifelong impairments such as hearing loss, limb amputation or epilepsy. Meningococcal disease is most common in children under the age of 5, adolescents and the elderly.Meningokokkenziekte is een zeer ernstige infectieziekte die veroorzaakt wordt door een bacterie, de meningokok. Er zijn verschillende typen meningokokken; mensen worden vooral ziek van de serogroepen B, C, W en Y. Vaccinatie tegen meningokokkenziekte serogroep C is in Nederland sinds 2002 opgenomen in het Rijksvaccinatieprogramma voor kinderen van 14 maanden. Hierdoor komt meningokokkenziekte door serogroep C nauwelijks meer voor. Sinds kort zijn vaccins beschikbaar tegen serogroep B. Daarnaast is er sinds 2015 een snelle toename in meningokokkenziekte door serogroep W. Er zijn combinatievaccins beschikbaar tegen serogroep A, C, W en Y. Vanwege ondermeer deze ontwikkelingen gaat de Gezondheidsraad de minister van VWS adviseren of, en op welke manier, het huidige vaccinatieprogramma tegen meningokokkenziekte aangepast moet worden. Daartoe heeft het RIVM achtergrondinformatie en recente data over meningokokkenziekte in Nederland verzameld. Het gaat onder meer om het aantal mensen in Nederland dat jaarlijks ziek wordt, de effectiviteit en veiligheid van de vaccins, en hoe het publiek denkt over vaccinatie tegen invasieve meningokokkenziekte. De infectie geeft een ernstig ziektebeeld zoals hersenvliesontsteking of een bloedvergiftiging, die zich snel kan ontwikkelen tot een shock waar veel mensen aan overlijden. De ziekte begint vaak met griepachtige verschijnselen en koorts die vervolgens zeer snel verergeren. De infectie is in Nederland relatief zeldzaam; op dit moment zijn er 100 tot 150 patiënten per jaar. Van deze patiënten overlijdt 5-10 procent ondanks antibiotica en intensieve zorg. 30 procent van de patiënten houdt er levenslang beperkingen aan over zoals gehoorverlies, amputatie van een ledemaat of epilepsie. Meningokokkenziekte komt het meest voor bij kinderen jonger dan 5 jaar, adolescenten en ouderenMinisterie van VW

Cross-cultural adaptation and validation of the “spinal cord injury-falls concern scale” in the Italian population

Study design: Psychometrics study. Objective: The objective of this study was to develop an Italian version of the Spinal Cord Injury-Falls Concern Scale (SCI-FCS) and examine its reliability and validity. Setting: Multicenter study in spinal units in Northern and Southern Italy. The scale also was administered to non-hospitalized outpatient clinic patients. Methods: The original scale was translated from English to Italian using the “Translation and Cultural Adaptation of Patient-Reported Outcomes Measures” guidelines. The reliability and validity of the culturally adapted scale were assessed following the “Consensus-Based Standards for the Selection of Health Status Measurement Instruments” checklist. The SCI-FCS-I internal consistency, inter-rater, and intra-rater reliability were examined using Cronbach’s alpha coefficient and the intraclass correlation coefficient, respectively. Concurrent validity was evaluated using Pearson’s correlation coefficient with the Italian version of the short form of the Wheelchair Use Confidence Scale for Manual Wheelchair Users (WheelCon-M-I-short form). Results: The Italian version of the SCI-FCS-I was administered to 124 participants from 1 June to 30 September 2017. The mean ± SD of the SCI-FCS-I score was 16.73 ± 5.88. All SCI-FCS items were either identical or similar in meaning to the original version’s items. Cronbach’s α was 0.827 (p < 0.01), the inter-rater reliability was 0.972 (p < 0.01), and the intra-rater reliability was 0.973 (p < 0.01). Pearson’s correlation coefficient of the SCI-FCS-I scores with the WheelCon-M-I-short form was 0.56 (p < 0.01). Conclusions: The SCI-FCS-I was found to be reliable and a valid outcome measure for assessing manual wheelchair concerns about falling in the Italian population

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Capitate and hamate fracture in a child: the value of MRI imaging

Carpal bone fractures in children are rare, and little is known about the appropriate tools to diagnose them, particularly in toddlers. We present a 2-year-old child with a capitate and hamate fracture. Based on our experiences with this case and on a review of the literature, we discuss the value of magnetic resonance imaging in carpal trauma in children

Variants in Neuropeptide Y Receptor 1 and 5 Are Associated with Nutrient-Specific Food Intake and Are Under Recent Selection in Europeans

There is a large variation in caloric intake and macronutrient preference between individuals and between ethnic groups, and these food intake patterns show a strong heritability. The transition to new food sources during the agriculture revolution around 11,000 years ago probably created selective pressure and shaped the genome of modern humans. One major player in energy homeostasis is the appetite-stimulating hormone neuropeptide Y, in which the stimulatory capacity may be mediated by the neuropeptide Y receptors 1, 2 and 5 (NPY1R, NPY2R and NPY5R). We assess association between variants in the NPY1R, NPY2R and NPY5R genes and nutrient intake in a cross-sectional, single-center study of 400 men aged 40 to 80 years, and we examine whether genomic regions containing these genes show signatures of recent selection in 270 HapMap individuals (90 Africans, 90 Asians, and 90 Caucasians) and in 846 Dutch bloodbank controls. Our results show that derived alleles in NPY1R and NPY5R are associated with lower carbohydrate intake, mainly because of a lower consumption of mono- and disaccharides. We also show that carriers of these derived alleles, on average, consume meals with a lower glycemic index and glycemic load and have higher alcohol consumption. One of these variants shows the hallmark of recent selection in Europe. Our data suggest that lower carbohydrate intake, consuming meals with a low glycemic index and glycemic load, and/or higher alcohol consumption, gave a survival advantage in Europeans since the agricultural revolution. This advantage could lie in overall health benefits, because lower carbohydrate intake, consuming meals with a low GI and GL, and/or higher alcohol consumption, are known to be associated with a lower risk of chronic diseases

Fertilization with beneficial microorganisms decreases tomato defenses against insect pests

International audienceThe adverse effects of chemical fertilizers on agricultural fields and the environment are compelling society to move toward more sustainable farming techniques. “Effective microorganisms” is a beneficial microbial mixture that has been developed to improve soil quality and crop yield while simultaneously dramatically reducing organic chemical application. Additional indirect benefits of beneficial microorganisms application may include increased plant resistance to herbivore attack, though this has never been tested till now. Tomato plants were grown in controlled greenhouse conditions in a full-factorial design with beneficial microorganisms inoculation and commercial chemical fertilizer application as main factors. We measured plant yield and growth parameters, as well as resistance against the generalist pest Spodoptera littoralis moth larval attack. Additionally, we measured plant defensive chemistry to underpin resistance mechanisms. Overall, we found that, comparable to chemical fertilizer, beneficial microorganisms increased plant growth fruit production by 35 and 61 %, respectively. Contrary to expectations, plants inoculated with beneficial microorganisms sustained 25 % higher insect survival and larvae were in average 41 % heavier than on unfertilized plants. We explain these results by showing that beneficial microorganism-inoculated plants were impaired in the induction of the toxic glycoalkaloid molecule tomatine and the defense-related phytohormone jasmonic acid after herbivore attack. For the first time, we therefore show that biofertilizer application might endure unintended, pest-mediated negative effects, and we thus suggest that biofertilizer companies should incorporate protection attributes in their studies prior to commercialization