ADHD and eating disorders in childhood and adolescence: An updated minireview.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders with overactivity, inattention, and impulsivity as core characteristics. Recent studies suggest that 20 % of children with ADHD also develop eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge eating disorder. However, little is still known about the association between ADHD and EDs through childhood and adolescence. Therefore, in the present work, we aimed at summarizing the studies investigating ADHD and EDs in childhood and adolescence over the last 10 years. METHODS: A bibliographic search on PubMed was performed and only studies that considered participants with a clinical diagnosis of ADHD, patients with an additional diagnosis of EDs and patients under 18 years old were included. A total of 7 studies were retrieved and included in the review. RESULTS: The majority of the reviewed studies (N = 5) found an association between ADHD and EDs, while the remaining, which focused on EDs symptomatology, reported either lower ED symptoms in ADHD sample or no association between ADHD and EDs. LIMITATIONS: the majority of studies were cross-sectional and therefore did not allow to explore the longitudinal casual relation between ADHD and EDs in the developmental age range considered. CONCLUSIONS: This review suggests that children and adolescents with ADHD should be monitored for EDs. However, more work is still needed to better understand the clinical implications of the comorbidity between ADHD and EDs and its prospective impact on the life of children and adolescents with ADHD.

Laboratory evidence that dinotefuran, pyriproxyfen and permethrin combination abrogates Leishmania infantum transmissibility by sick dogs.

Dogs are reservoir hosts of leishmaniasis caused by Leishmania infantum and transmitted by phlebotomine vectors. The effect of dinotefuran, pyriproxyfen and permethrin spot-on solution (Vectra®3D, Ceva Santé Animale, Libourne, France) on Leishmania transmissibility by naturally infected dogs via reared Phlebotomus perniciosus, was assessed. Dogs affected by leishmaniasis were submitted to xenodiagnosis and 6 infecting >10% of insects were treated topically on day 0. Antifeeding, insecticidal and anti-transmissibility effects were evaluated through xenodiagnoses performed on days 1, 7 and 28, using individual pre-treatment parameters as control. Feeding and mortality rates were assessed at 24 h, whereas promastigote infection, maturation and burden were assessed up to 96 h post blood meal (potentially infectious rate). On day 1, the anti-feeding efficacy was >95% in 4 dogs, insecticidal efficacy 100% in 4 dogs, and anti-transmissibility effect 100% in 6 dogs. Efficacy rates recorded on day 7 were very similar to day 1. On day 28, anti-feeding and insecticidal efficacy values were much broader, ranging 32.6-100% and 7.7-94.4%, respectively. Potentially infectious insects were recorded from two dogs, with sharp decrease in transmissibility rate as compared with pre-treatment condition. Altogether, Vectra®3D abrogated by >98% the potential Leishmania transmissibility by the examined pool of infected dogs over 1 month.

Permanence of de novo segmental aneuploidy in sequential embryo biopsies.

STUDY QUESTION: Is de novo segmental aneuploidy (SA) a biological event or an artifact that is erroneously interpreted as partial chromosome imbalance? SUMMARY ANSWER: The detection of de novo SA in sequential biopsies of preimplantation embryos supports the biological nature of SA. WHAT IS KNOWN ALREADY: Although some SAs are detected in oocytes and in blastocysts, the highest incidence is observed in cleavage-stage embryos. Based on these findings, we can postulate that the majority of cells affected by SAs are eliminated by apoptosis or that affected embryos mainly undergo developmental arrest. STUDY DESIGN, SIZE, DURATION: This retrospective study includes 342 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed between January 2014 and December 2018. Chromosome analysis was performed on 331 oocytes, 886 cleavage-stage embryos and 570 blastocysts (n = 1787). From 268 expanded blastocysts, the blastocoelic fluid (BF) was also analyzed (resulting in 2025 samples in total). In cases of SAs involving loss or gain in excess of 15 Mb, embryos were not considered for transfer and sequential biopsies were performed at following stages. This resulted in 66 sets where the initial diagnosis of SAs (4 made in polar bodies, 25 in blastomeres and 37 in trophectoderm (TE) cells) was followed up. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 2082 samples (2025 + 27 whole embryos) were processed by whole genome amplification followed by array comparative genomic hybridization. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of SAs was 6.3% in oocytes, increased to 16.6% in cleavage-stage embryos (P < 0.001) and decreased to 11.2% in blastocysts (P < 0.025 versus oocytes; P < 0.01 versus cleavage-stage embryos). The highest incidence of SAs was found in BFs (26.1%, P < 0.001). The analysis of 66 sets of sequential biopsies revealed that the initial finding was confirmed in all following samples from 39 sets (59.1% full concordance). In 12 additional sets, SAs were detected in some samples while in others the interested chromosome had full aneuploidy (18.2%). In three more sets, there was a partial concordance with the initial diagnosis in some samples, but in all TE samples the interested chromosome was clearly euploid (4.5%). In the remaining 12 sets, the initial SA was not confirmed at any stage and the corresponding chromosomes were euploid (18.2% no concordance). The pattern of concordance was not affected by the number of SAs in the original biopsy (single, double or complex) or by the absence or presence of concomitant aneuploidies for full chromosomes. LIMITATIONS, REASONS FOR CAUTION: Chromosome analyses were performed on biopsies that might not be representative of the true constitution of the embryo itself due to the occurrence of mosaicism. WIDER IMPLICATIONS OF THE FINDINGS: The permanence of SAs throughout the following stages of embryo development in more than half of the analyzed sets suggests for this dataset a very early origin of this type of chromosome imbalance, either at meiosis or at the first mitotic divisions. Since SAs remained in full concordance with the initial diagnosis until the blastocyst stage, a corrective mechanism seems not to be in place. In the remaining cases, it is likely that, as for full chromosome aneuploidy, mosaicism derived from mitotic errors could have occurred. In following cell divisions, euploid cell lines could prevail preserving the embryo chances of implantation. Due to the scarcity of data available, the transfer of embryos with SAs should be strictly followed up to establish possible clinical consequences related to this condition. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained. There are no conflicts of interest.

Gate-reflectometry dispersive readout and coherent control of a spin qubit in silicon.

Silicon spin qubits have emerged as a promising path to large-scale quantum processors. In this prospect, the development of scalable qubit readout schemes involving a minimal device overhead is a compelling step. Here we report the implementation of gate-coupled rf reflectometry for the dispersive readout of a fully functional spin qubit device. We use a p-type double-gate transistor made using industry-standard silicon technology. The first gate confines a hole quantum dot encoding the spin qubit, the second one a helper dot enabling readout. The qubit state is measured through the phase response of a lumped-element resonator to spin-selective interdot tunneling. The demonstrated qubit readout scheme requires no coupling to a Fermi reservoir, thereby offering a compact and potentially scalable solution whose operation may be extended above 1 K.

Video modeling for the development of personal hygiene skills in youth with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder mainly characterised by deficits in social communication as well as by narrow patterns of behaviour and interests (American Psychiatric Association, 2013), often accompanied by language, intellectual and sensory impairments. The severity of these impairments may lead to deficits in the development of daily living activities such as simple meal preparation and feeding, community skills (e.g. buying groceries), personal care (e.g. dressing) and personal hygiene skills (bathing, toileting, hand washing, teeth brushing) needed for independence. Among others, the lack of independence in personal hygiene skills increases the burden of the caregiver and makes children with ASD more dependent (Flynn & Healy, 2012). Therefore, it is important to develop tools for helping individuals with ASD in increasing their ability to perform these basic life activities which will lead to savings that can be invested in other critical areas of needs.

Analytical comparison between two hematological analyzer systems: CAL-8000 vs. XN-9000.

INTRODUCTION: This study was aimed to compare the analytical performance of traditional and new parameters and morphological flags of CAL-8000 and XN-9000. The automated differential leukocyte count (DIFF profile) and morphological flags were compared with optical microscopy (OM). METHODS: A total of 1025 peripheral blood samples, collected in K3 EDTA tubes, were analyzed by CAL-8000, by XN-9000, and by OM. Within-run imprecision was performed in low cellularity samples. The comparison was made using Spearman's correlation, Passing-Bablok regression, Bland-Altman bias, and Cohen's K test. RESULTS: Within-run imprecision in low cellularity samples yielded reproducible data between the instruments (imprecision was higher than 10% on samples with platelet count <21 × 109 /L using impedance technology). Passing-Bablok regression (CAL-8000 vs. XN-9000) yielded slopes ranging between 0.2 to 1.16 and intercepts from -6.54 to 21.63. The bias for leukocytes parameters ranged from -1.8% to -82.2%, the red blood cell parameters from -2.9% to 3.1%, platelets parameters from -27.8% to 26%, and reticulocyte parameters from -115.3% to 4.5%. The comparison of morphological flags yielded a K value always <0.55. The DIFF profile vs. OM had a Passing-Bablok regression with slopes ranging between 0.34 to 1.00 and intercepts from -0.01% to 0.11 and bias ranging from -42.9% to 2.6% for XN-9000 parameters and from -2.7% to 35.0% for CAL-8000 parameters. The comparison of morphological flags showed a K value ranging from 0.35 to 0.77 for XN-9000 and from 0.17 to 0.54 for CAL-8000. CONCLUSION: Differences exist between the two analyzers, especially in the generation of morphology flags, thus emphasizing the need of pursuing a major degree of harmonization and/or adopting instrument-specific reference ranges.

Mindray BC-6800 body fluid mode, performance of nucleated cells, and differential count in ascitic and pleural fluids.

INTRODUCTION: An accurate and rapid analysis of cells in body fluids (BFs) is important for diagnosis and follow-up in many pathological conditions. We evaluated the analytical performance of the module BF Mindray BC-6800 (BC-6800-BF) for cytometric analysis of ascitic and pleural fluids. METHODS: A total of 99 ascitic and 45 pleural samples were collected and assessed with BC-6800-BF and optical microscopy. This study also includes the evaluation of limit blank (LoB), limit detection (LoD), limit quantitation, (LoQ), carryover, linearity, and diagnostic concordance between the two methods. RESULTS: For TC-BF, LoB was 1 × 10(6) cells/L, LoD was 3 × 10(6) cells/L, and LoQ was 4 × 10(6) cells/L. Linearity was excellent (r(2) = 0.99) and carryover was negligible. TC-BF performed with the two methods showed Pearson's correlation of 0.99 (P < 0.0001), Passing-Bablok regression y = 1.04x - 1.17, and bias 33.7 cells. In ascitic fluids, polymorphonuclear cells (PMN) showed an area under curve (AUC) of 0.98 (P < 0.0001). In pleural fluids, mononuclear cells (MN) and PMN % displayed an AUC of 0.79 (P < 0.0001) and 0.93 (P < 0.0001), respectively. CONCLUSIONS: BC-6800-BF in ascitic and pleural fluids offers rapid and accurate cell and differential counts in clinically relevant concentration ranges. The use of BC-6800-BF may allow to replace routine optical counting, except for samples displaying abnormal cell counts or abnormal DIFF scattergram.

First Report of a Successful Pregnancy in an Everolimus-Treated Heart-Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs.

The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy.

Chromosome analysis in embryos from young patients with previous parity.

This study included 173 young couples of proven fertility who had previously undergone preimplantation genetic screening for chromosomes X and Y for family balancing. Several months later, when the outcome of the pregnancies was already known, the blastomeres from the corresponding embryos transferred were reanalysed by fluorescence in-situ hybridization (FISH) for chromosomes 13, 16, 18, 21, 22 with the aim of investigating correlation with embryo viability and the level of FISH sensitivity (embryos confirmed to be euploid). According to the results, informative in 152 couples, the proportion of euploid embryos was significantly lower in 53 nonpregnant women when compared with 99 women with term pregnancy (49% versus 75% respectively, P < 0.001). In addition, in 21 nonpregnant patients, all embryos transferred were found to be chromosomally abnormal. The level of FISH sensitivity was calculated in the group of term pregnancies where the number of euploid embryos was expected to exceed or match with the number of babies born. The resulting false-negative rate was 4.0% per patient and 1.9% per embryo. These findings confirmed the limited prediction power of embryo morphology on implantation but also the relevance of chromosomal abnormalities in causing embryo demise.

Predicting aneuploidy in human oocytes: key factors which affect the meiotic process.

BACKGROUND: To estimate the incidence of aneuploidy in relation to patients' characteristics, the type of hormonal stimulation and their response to induction of multiple follicular growth, 4163 first polar bodies (PB1s) were analyzed. METHODS: Five hundred and forty four infertile couples underwent 706 assisted conception cycles (640 with poor prognosis indications and 66 controls) in which chromosomal analysis of PB1 for the chromosomes 13, 15, 16, 18, 21 and 22 was performed. Results were evaluated in a multivariate analysis. RESULTS: The proportion of normal oocytes was directly correlated (P < 0.01) with (i) the number of mature oocytes and (ii) the establishment of a clinical pregnancy; and inversely correlated (P < 0.01) with (i) female age, (ii) causes of female infertility (endometriosis, abortions, ovulatory factor), (iii) poor prognosis indications (female age, number of previous cycles, multiple poor prognosis indications), (iv) number of FSH units per oocyte and (v) number of FSH units per metaphase II oocyte. There was a weak significance of frequency (P < 0.05) between type of abnormality (originated by chromatid predivision, chromosome non-disjunction or combined mechanisms in the same oocyte) and groups of the studied variables, rather than to a specific abnormality or a specific chromosome. CONCLUSIONS: The type of infertility had a significant effect on errors derived from the first meiotic division, whose incidence was significantly higher in the presence of endometriosis or of an ovulatory factor, and in women that experienced repeated abortions. Each aneuploidy event was found to be dependent not on a specific variable, but on groups of variables. In addition, the tendency of chromosomal abnormalities to occur simultaneously implies that the deriving aneuploidies can be of any type.

Paternal contribution to aneuploidy in preimplantation embryos.

The association between sperm indices and the chromosomal status of preimplantation embryos was assessed in 230 couples with a female partner younger than 36 years undergoing 295 cycles of preimplantation diagnosis for aneuploidy: 105 cycles had normozoospermic samples, 134 cycles presented with oligoasthenoteratozoospermia (OAT), while the remaining cycles had spermatozoa retrieved from the seminal tract due to obstructive (29 cycles) or non-obstructive azoospermia (NOA, 27 cycles). One blastomere was biopsied from day-3 embryos and analysed for chromosomes XY, 13, 15, 16, 17, 18, 21, and 22. From the testing of 1549 embryos, the proportion of chromosomally abnormal embryos was significantly lower in normozoospermic patients (55%) than in OAT (62%, P < 0.025) and NOA patients (69%, P < 0.005). Complex abnormalities were the most frequent defect in NOA (68%), which also demonstrated the highest incidence of gonosomal aneuploidy (12%). From the re-analysis of all blastomeres in 493 non-transferred embryos, 95% of NOA embryos were chaotic mosaics. In conclusion, a severe male infertility condition could contribute to the generation of chromosomal abnormalities in the resulting embryos. This might occur especially in NOA patients in which the high incidence of chromosomal abnormalities is mainly due to mosaicism and gonosomal aneuploidy.

Capillary blood viscosity in microcirculation.

As known, at the arteriolar level there is the highest resistance to the flow due to the section and to the velocity with an average pressure fall of 50 mmHg (from 85 to 35 mmHg). This resistance is expressed in sec(-1) by the ratio W/2r. This ratio is very high with an average value of 332 sec(-1) and viscosity at this high shear-rate is negligible. At the capillary level the pressure fall is 11.5 mmHg but the vascular resistance W/2r is much lower, on average 32 sec(-1). We can say that if a resistance of 333 sec(-1) corresponds with a pressure fall of 50 mmHg, then a resistance of 32 sec(-1) should correspond with a pressure fall of 4.8 mmHg. The highest pressure fall is due to another kind of resistance which we can define as "Capillary Blood Viscosity" because it depends on the rheological and structural characteristics of the blood. Our instrument reproduces the structure of the capillary district in an experimental model and measures the General Blood Viscosity (GBV) and the Capillary Blood Viscosity (CBV) at the same shear-rate and in particular at the low shear-rate when in non-Newtonian fluids the highest increase in viscosity appears. Consequently, at the capillary, viscosity is dominant with respect to the other geometric and physical resistances. Moreover, the percentage ratio between the GBV and the CBV gives a physical measure of erythrocyte deformability. Knowing viscosity at shear-rate present in the circulatory system, we can obtain the size of RBCs aggregates in the different circulatory districts and their characteristics expressed like "aggregation bond". Changes in CBV are the only possibility in clinical practice to improve the circulatory flow in the capillary district because it is not sure that changes in the arteriolar section can improve the capillary flow or rather open arterio-venous anastomosis. Moreover, in the systemic circulation the aggregate size allows us to point out the phenomenon of cell adhesion because the presence of several receptors involves also the other blood cells. Finally the size and the stability of the RBCs aggregates can modify the endothelial thrombo-resistance.

Do static or dynamic AFOs improve balance?

OBJECTIVE: To verify if partial or total limitation of degrees of freedom at ankle joints could help patients with balance disorders in standing and walking. DESIGN: A cross-over design was chosen. Patients with multiple sclerosis (MS) were tested in three experimental conditions: barefooted, wearing ankle foot orthoses (AFOs), and wearing AFOs that allowed plantar flexion. SETTING: Neurorehabilitation unit in a rehabilitation centre. SUBJECTS: Fourteen patients suffering from MS with mild strength problems and balance disorders that required them to use walking aids outside. MAIN OUTCOME MEASURES: Tests inferring static and dynamic skills were carried out in the three experimental conditions described above. RESULTS: Improvements were obtained in static balance tests especially wearing dynamic AFOs; the number of patients who were able to pass tasks on balance in upright position such as 'standing with feet together, head extended' increased from three to nine. Dynamic balance was impaired especially with static AFOs; the time spent walking 10 metres with these orthoses increased by 172% with respect to barefoot; less difference (113%) has been reported wearing dynamic AFOs. CONCLUSION: Static and dynamic AFOs improved static balance, while dynamic balance was impaired especially by static AFOs; less negative influence on dynamic balance has been found while wearing dynamic AFOs.

Possible interchromosomal effect in embryos generated by gametes from translocation carriers.

BACKGROUND: The incidence of abnormal pregnancies in carriers of balanced translocations depends strictly on the chromosomes involved in the translocations. The aim of this study was to verify whether conventional aneuploidy screening could be advantageously combined with preimplantation genetic diagnosis (PGD) for translocations. METHODS: Twenty-eight carriers of Robertsonian and reciprocal translocations underwent 43 PGD cycles; specific probes were used to screen the translocation in 172 embryos generated by 35 cycles; most of these embryos were also screened for chromosomes 13, 16, 18, 21, 22 (n = 166), XY (n = 107), 1 (n = 17) and 15 (n = 88). For the remaining eight cycles (carriers of reciprocal translocations) only the chromosomes involved in common aneuploidy screening were investigated on the 40 embryos generated in vitro. RESULTS: In Robertsonian translocations, the proportion of embryos with abnormalities due to the translocation was 21%, common aneuploidies contributed 31% of total abnormalities, whereas the remaining 36% of embryos had abnormalities due to both types of chromosome. For reciprocal translocations, the chromosomes involved in the translocation were responsible for 65% of total abnormalities; only 6% of the embryos were abnormal for common aneuploidies and 16% carried abnormalities due to both the chromosomes involved in the translocation and those not related to the translocation. CONCLUSIONS: An interchromosomal effect seems to play a role in the case of Robertsonian translocations, where the relevant contribution of aneuploidy exposes the couple to an additional risk of abnormal pregnancy.

Induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor RPR-115135: role of gene mutations.

To investigate the relationship between oncogene activation and induction of micronuclei by a new non-peptidic mimetic farnesyltransferase inhibitor, RPR-115135, two isogenic cell lines, human colon cancer line HCT-116, which harbors a K-ras mutation, and spontaneously immortalized human breast epithelial cell line MCF-10A, were utilized. HCT-116 cells were transfected with an empty control pCMV vector (clone CMV-2) or with a dominant negative mutated p53 transgene (clone Mu-p53-2) to disrupt p53 function. In both clones RPR-115135 induced a significant increase in the frequency of micronucleation at concentrations that did not affect cell membrane integrity. RPR-115135 produced a significant increase in the ratio of CREST+ to CREST- micronuclei. MCF-10A cells were stably transfected with either c-Ha-ras or c-erbB-2 or both H-ras + c-erbB-2. No induction of micronuclei was observed. No induction of micronuclei was reported in human lymphocytes and in primary spinal cells obtained from 7-day chick embryos. In conclusion, RPR-115135 acts as an aneugenic agent in a complex manner, dependent upon the complement of mutations in cell regulatory genes in tumour cells and this activity may be independent of ras genotype.

Learning disabilities: analysis of 69 children.

With this article we intend to demonstrate the importance of evaluation and follow up of children with learning disabilities, through a multidisciplinary team. As well as to establish the need of intervention. We evaluate 69 children, from Aline Picheth Public School, in Curitiba, attending first or second grade of elementary school, through general and evolutionary neurological examination, pediatric checklist symptoms, and social, linguistic and psychological (WISC-III, Bender Infantile and WPPSI-figures) evaluation. The incidence was higher in boys (84,1%), familiar history of learning disabilities was found in 42%, and writing abnormalities in 56,5%. The most frequent diagnosis was attention deficit and hyperactivity disorder, in 39,1%. With this program, we aimed to reduce the retention taxes and stress the importance of this evaluation, and, if necessary, multidisciplinary intervention in the cases of learning disabilities.

RPR-115135, a new non peptidomimetic farnesyltransferase inhibitor, induces G0/G1 arrest only in serum starved cells.

A new non peptidomimetic farnesyltransferase inhibitor, RPR-115135, was studied in an isogenic cell model system consisting of human colon cancer HCT-116 line. HCT-116 cells were transfected with an empty control pCMV vector or with a dominant-negative mutated p53 transgene to disrupt p53 function. Growth inhibitory effects of RPR-115135 were evaluated on cells growing under different conditions (serum starvation, serum starvation and recovery, nocodazole treatment). The cytotoxic activity of RPR-115135 was independent of the cell cycle status of the target cells. Addition of RPR-115135 only to cells exposed to reduced serum conditions (0.1% FCS) resulted in an enhanced ability of HCT-116 cells to arrest in the G0/G1 phase. This arrest response appeared independent of p53/p21cip1/waf-1 function. A reduction of Cyclin A protein amount by RPR-115135 was observed in both clones. These latter results suggest that RPR-115135 might down-regulate the cell cycle factor that would normally impede G0/G1 arrest.