Diuresis renography and ultrasonography in children with antenatally detected hydronephrosis can support diagnoses and suggest related surgery treatment.

OBJECTIVE: Prenatal ultrasound (US) screening detects the hydronephrosis (HN)-dilatation of fetal renal collecting system in 1%-5% of all pregnancies. In most children, HN is detected by prenatal US screening between 18-20 gestational week. Pelvi- ureteric junction (PUJ) stenosis is the most common etiological factor of prenatal HN and requires postnatal follow-up. Diuresis renography plays important role in the follow-up by complementing morphological information obtained by US with the data about differential renal function (DRF) and drainage. We studied the association between ultrasound parameters and results of diuresis renography in first diagnosed PUJ stenosis and the predictive factors of pyeloplasty in order to evaluate the usefulness of diuresis renography in these children postnatally. PATIENTS AND METHODS: Children with antenatally detected HN attributed to presumed PUJ stenosis were investigated with mercapto-acetyltriglycine (MAG3) diuresis renography. Parents gave informed consent for the procedure. The inclusion criteria were: age up to 4 years, diagnosis of prenatal HN determined by US during pregnancy based on the antero-posterior diameter (APD) of renal pyelon and at least one post-natal US which confirmed diagnosis. Exclusion criteria were: APD of pyelon <10mm, previous surgical treatment of HN, vesicoureteral reflux excluded by micturating cystourethrography, and patients having any anomaly of the contralateral kidney. Sixty two patients 43 boys, 19 girls, median age 16 months were selected. They were divided into three groups based on the size of pyelon, three groups based on the calyceal size and two groups according to thickness of parenchyma. Renography was performed for 24 minutes after the iv. application of 99mTc MAG3, 144 ten-sec images were applied. Furosemide was administered after 2 min. (F+2). Post-void static images were acquired at 60min. The non-commercial software developed by International Atomic Energy Agency was applied to process the studies. The criteria for pathological findings (poor or no drainage) were the renographic curve maintaining a plateau, Normalized Residual Activity (NORA) at 20. min.>1.62, Output efficiency (OE) at 20. min.<71%, postmicturating NORA >0.11. The DRF was considered normal within the range of 45%-55%. RESULTS: Good drainage had 74% of children, partial drainage 11%, and poor 15%. There was a clear association between the size of pyelon, calyces, parenchyma thickness and drainage. There was also a clear association between the calyceal size, parenchyma thickness and DRF. Differential renal function was <45% in 18% of children. A relation between the type of drainage and DRF was not determined. Thus, 66.7% of those with poor drainage had preserved DRF. Seven out of nine children with poor drainage underwent pyeloplasty. The threshold for pyeloplasty was the pyelon of 18mm and calyces of 10mm. The model of the multivariate logistic regression which included ultrasound parameters (APD of pyelon, calyces size and parenchymal thickness), drainage and DRF, which were significant predictors in univariate analysis, showed that only drainage was an independent predictor for the need of pyeloplasty. CONCLUSION: Antero-posterior diameter of the pyelon <15mm indicates a favorable course of congenital HN in most children. Pattern of drainage obtained by diuresis renography was the only independent predictor for the need of pyeloplasty.

SUCCESSFUL TREATMENT OF PULMONARY AND LYMPHATIC MANIFESTATIONS OF LYMPHANGIOLEIOMYOMATOSIS WITH SIROLIMUS.

Lymphangioleiomyomatosis (LAM) is a rare, progressive, diffuse cystic lung disease predominantly affecting women of child bearing age. Recently treatment with sirolimus was shown to stabilize lung function decline and improve quality of life in patients with LAM. We treated three premenopausal women suffering from LAM manifesting as diffuse cystic lung disease, chylous effusions, and lymphangioleioyomas with sirolimus (1-3 mg a day; sirolimus trough levels 2.9-8.5 ng/ml). All three patients had a remarkable response to sirolimus, with resolution of effusions, improvement in lung function and shrinking of abdominal lymphangioleiomyomas. Our case series further complements the literature in that sirolimus is a safe and effective treatment for LAM and its lymphatic manifestations.

Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood.

Cardiac Time Intervals under Motion Using Bimodal Chest E-Tattoos and Multistage Processing.

GOAL: We present a thin, soft, and chest conformable bimodal sensor, known as the chest e-tattoo, coupled with an advanced signal processing framework to accurately identify various cardiac events, and thereby extract cardiac time intervals even during body motion. METHODS: We built a wireless electronic tattoo that features synchronous electrocardiography (ECG) and seismocardiography (SCG). The SCG measures chest vibrations due to heartbeat, providing information on cardiovascular health that is complementary to the ECG. However, the efficacy of the SCG is compromised by motion-induced artifacts. The slim and stretchy design of the e-tattoo allows it to be strategically placed near the xiphoid process, facilitating high-quality monitoring of the ECG and SCG for increased signal quality. Nine participants were measured during walking and cycling. We propose a multistage signal processing framework, integrating an adaptive Normalized Least Mean Squares (NLMS) filter, ensemble averaging, and Empirical Mode Decomposition (EMD), together named the FAD framework, to accurately extract cardiac time intervals (CTIs).

Short term priming effect of brain-actuated muscle stimulation using bimanual movements in stroke.

OBJECTIVE: Brain-computer interface triggered-functional electrical stimulation (BCI-FES) is an emerging neurorehabilitation therapy post stroke, mostly for the affected hand. We explored the feasibility of a bimanual BCI-FES and its short-term priming effects, i.e. stimuli-induced behaviour change. We compared EEG parameters between unimanual and bimanual movements and differentiated the effect of age from the effect of stroke. METHODS: Ten participants with subacute stroke, ten age-matched older healthy adults, and ten younger healthy adults underwent unimanual and bimanual BCI-FES sessions. Delta alpha ratio (DAR) and brain symmetry index (BSI) were derived from the pre- and post- resting-state EEG. Event-related desynchronization (ERD) and laterality index were derived from movement- EEG. RESULTS: Participants were able to control bimanual BCI-FES. ERD was predominantly contralateral for unimanual movements and bilateral for bimanual movements. DAR and BSI only changed in healthy controls. Baseline values indicated that DAR was affected by stroke while BSI was affected by both age and stroke. CONCLUSIONS: Bimanual BCI control offers a larger repertoire of movements, while causing the same short-term changes as unimanual BCI-FES. Prolonged practice may be required to achieve a measurable effect on DAR and BSI for stroke. SIGNIFICANCE: Bimanual BCI-FES is feasible in people affected by stroke.

Tracking of airborne radionuclides from the damaged Fukushima Dai-ichi nuclear reactors by European networks.

Radioactive emissions into the atmosphere from the damaged reactors of the Fukushima Dai-ichi nuclear power plant (NPP) started on March 12th, 2011. Among the various radionuclides released, iodine-131 ((131)I) and cesium isotopes ((137)Cs and (134)Cs) were transported across the Pacific toward the North American continent and reached Europe despite dispersion and washout along the route of the contaminated air masses. In Europe, the first signs of the releases were detected 7 days later while the first peak of activity level was observed between March 28th and March 30th. Time variations over a 20-day period and spatial variations across more than 150 sampling locations in Europe made it possible to characterize the contaminated air masses. After the Chernobyl accident, only a few measurements of the gaseous (131)I fraction were conducted compared to the number of measurements for the particulate fraction. Several studies had already pointed out the importance of the gaseous (131)I and the large underestimation of the total (131)I airborne activity level, and subsequent calculations of inhalation dose, if neglected. The measurements made across Europe following the releases from the Fukushima NPP reactors have provided a significant amount of new data on the ratio of the gaseous (131)I fraction to total (131)I, both on a spatial scale and its temporal variation. It can be pointed out that during the Fukushima event, the (134)Cs to (137)Cs ratio proved to be different from that observed after the Chernobyl accident. The data set provided in this paper is the most comprehensive survey of the main relevant airborne radionuclides from the Fukushima reactors, measured across Europe. A rough estimate of the total (131)I inventory that has passed over Europe during this period was <1% of the released amount. According to the measurements, airborne activity levels remain of no concern for public health in Europe.

Grandiose and vulnerable narcissism, identity integration and self-control related to criminal behavior.

BACKGROUND: Although systematic research on narcissism has been conducted for over 100 years, researchers have only recently started to distinguish between grandiose and vulnerable narcissism in relation to criminal behavior. In addition, there is some evidence suggesting that identity integration and self-control may underlie this association. Therefore, the present study aimed to develop a theory-driven hypothetical model that investigates the complex associations between grandiose and vulnerable narcissism, identity integration, self-control, and criminal behavior using structural equation modeling (SEM). METHODS: The total sample (N = 222) included 65 (29.3%) individuals convicted of criminal behavior and 157 (70.7%) participants from the community, with a mean age of 37.71 years (SD = 13.25). Criminal behavior was a grouping variable used as a categorical outcome, whereas self-report questionnaires were used to assess grandiose and vulnerable narcissism, self-control, and identity integration. RESULTS: The overall SEM model yielded good fit indices. Grandiose narcissism negatively predicted criminal behavior above and beyond the influence of identity integration and self-control. In contrast, vulnerable narcissism did not have a direct significant effect on criminal behavior, but it was indirectly and positively associated with criminal behavior via identity integration and self-control. Moreover, grandiose narcissism was positively, whereas vulnerable narcissism was negatively associated with identity integration. However, identity integration did not have a direct significant effect on criminal behavior, but it was indirectly and negatively associated with criminal behavior via self-control. Finally, self-control was, in turn, negatively related to criminal behavior. CONCLUSIONS: We propose that both subtypes of narcissism should be carefully considered in clinical assessment and current intervention practices.

Surrogate or conventional light chains are required for membrane immunoglobulin mu to activate the precursor B cell transition.

To examine the role of light chains in early B cell development we combined RAG-1 and lambda 5 mutations to produce mice that expressed neither conventional nor surrogate light chains (RAG-1-/-, lambda 5-/-). Unique heavy and light chain genes were then introduced into the double and single mutant backgrounds. Membrane immunoglobulin (Ig)mu (mIg mu) associated with Ig alpha-Ig beta but was unable to activate the pre-B cell transition in RAG-1-/-lambda 5-/- mice. Either lambda 5 or kappa light chains were sufficient to complement this deficiency. Therefore light chains are absolutely required for a functional Ig signaling module in early B cell development. Our data provide direct evidence for the existence of two pathways for induction of early B cell development: one which is activated through surrogate light chains and mIg mu, and an alternative pathway which uses conventional light chains and mIg mu.

The cytoplasmic domains of immunoglobulin (Ig) alpha and Ig beta can independently induce the precursor B cell transition and allelic exclusion.

In mature B cells, signals transduced through membrane immunoglobulin (Ig) produce cellular activation, yet the same receptor can also mediate deletion and silencing of autoreactive B cells. In addition, Ig expression during the antigen-independent phase of B cell development regulates the precursor B (pre-B) cell transition and allelic exclusion. To account for the diverse regulatory functions induced by membrane Ig, it has been proposed that individual receptor components have independent physiologic activities. Here we establish a role for Ig alpha in the pre-B cell transition and allelic exclusion. We find that the cytoplasmic domain of Ig alpha contains sufficient information to trigger both of these antigen-independent events. Direct comparisons of the cytoplasmic domains of Ig alpha and Ig beta show that the two are indistinguishable in the induction of the pre-B cell transition and allelic exclusion. Our experiments suggest that, despite the reported differences in certain biochemical assays, Ig alpha and Ig beta have redundant functions in the developing B cell.

The cysteine-rich domain of the macrophage mannose receptor is a multispecific lectin that recognizes chondroitin sulfates A and B and sulfated oligosaccharides of blood group Lewis(a) and Lewis(x) types in addition to the sulfated N-glycans of lutropin.

The mannose receptor (MR) is an endocytic protein on macrophages and dendritic cells, as well as on hepatic endothelial, kidney mesangial, tracheal smooth muscle, and retinal pigment epithelial cells. The extracellular portion contains two types of carbohydrate-recognition domain (CRD): eight membrane-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR). The former bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, and may be important in innate immunity towards microbial pathogens, and in antigen trapping for processing and presentation in adaptive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitary hormones and may have a role in hormonal clearance. A second feature of Cys-MR is binding to macrophages in marginal zones of the spleen, and to B cell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel classes of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of the type found on proteoglycans produced by cells of the immune system, and sulfated blood group chains. We further demonstrate that Cys-MR interacts with cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may variously regulate the trafficking and function of MR-bearing cells.

Precision-based exercise as a new therapeutic option for children and adolescents with haematological malignancies.

Children and adolescents with haematological malignancies (PedHM) are characterized by a severe loss of exercise ability during cancer treatment, lasting throughout their lives once healed and impacting their social inclusion prospects. The investigation of the effect of a precision-based exercise program on the connections between systems of the body in PedHM patients is the new frontier in clinical exercise physiology. This study is aimed at evaluating the effects of 11 weeks (3 times weekly) of combined training (cardiorespiratory, resistance, balance and flexibility) on the exercise intolerance in PedHM patients. Two-hundred twenty-six PedHM patients were recruited (47% F). High or medium frequency participation (HAd and MAd) was considered when a participant joined; > 65% or between 30% and < 64% of training sessions, respectively. The "up and down stairs'' test (TUDS), "6 min walking" test (6MWT), the "5 Repetition Maximum strength" leg extension and arm lateral raise test (5RM-LE and 5RM-ALR), flexibility (stand and reach), and balance (stabilometry), were performed and evaluated before and after training. The TUDS, the 5RM-LE and 5RM-ALR, and the flexibility exercises showed an increase in HAd and MAd groups (P < 0.05), while the 6MWT and balance tests showed improvement only in HAd group (P < 0.0001). These results support the ever-growing theory that, in the case of the treatment of PedHM, 'exercise is medicine' and it has the potential to increase the patient's chances of social inclusion.

Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2.

RAG1 and RAG2 are essential for V(D)J recombination and lymphocyte development. These genes are thought to encode a transposase derived from a mobile genetic element that was inserted into the vertebrate genome 450 million years ago. The regulation of RAG1 and RAG2 was investigated in vivo with bacterial artificial chromosome (BAC) transgenes containing a fluorescent indicator. Coordinate expression of RAG1 and RAG2 in B and T cells was found to be regulated by distinct genetic elements found on the 5' side of the RAG2 gene. This observation suggests a mechanism by which asymmetrically disposed cis DNA elements could influence the expression of the primordial transposon and thereby capture RAGs for vertebrate evolution.

Evaluation of galectin-8 expression in thyroid tumors.

The expression of galectin-8 (gal-8) has been shown to be altered during neoplastic transformation of certain cell types. This is the first study aimed to analyze the expression of this protein in normal and pathological human thyroid tissue. A total of 41 archival thyroid tissue samples (5 follicular adenomas, 31 papillary carcinomas, 5 follicular carcinomas) together with 36 adjacent hyperplastic or normal thyroid tissues were analyzed by immunohistochemistry. Galectin-8 was expressed in the majority of papillary carcinomas (27/31; 87%). Positive but weaker staining was also found in some of the follicular thyroid carcinomas (2/5; 40%) and adenomas (2/5; 40%). This protein was not detectable in five normal thyroid tissue samples, whereas hyperplastic areas adjacent to tumor were weakly positive in 9 out of 31 cases (29%). High gal-8 immunostaining in papillary thyroid carcinoma indicates that gal-8 may potentially serve as a marker of papillary thyroid carcinoma. However, it does not seem to be helpful in the differential diagnostics of follicular carcinoma and adenoma. Further studies are required to determine biological functions and molecular mechanisms underlying the increased expression of gal-8 protein in thyroid lesions, particularly, in papillary thyroid carcinoma.

Massive recurrent post-tonsillectomy bleedings revealing a transient factor XIII deficiency in a 10-year-old boy. A case report.

A previously healthy 10-year-old boy was hospitalized for a left cervical abscess associated with massive tonsillar hypertrophy. He underwent abscess drainage and bilateral tonsillectomy. At H36 post-surgery, he presented with tonsillar hemorrhage requiring surgical revision. Hemorrhage relapsed 2 days later, with a total of 7 episodes, 5 of which required surgical revisions. Laboratory investigations were normal except for a markedly low factor XIII (FXIII) activity at 7%. After administration of a single dose of 40 IU/kg plasma-derived FXIII (Fibrogammin®) I.V., the bleeding stopped with no further recurrence. FXIII activity gradually normalized (75%) at 6 weeks, confirming the transient character of factor XIII deficiency. Severe congenital FXIII deficiency (FXIIID) (<1%) is very rare (1:2,000,000 births), whereas partial congenital deficiency and/or acquired deficiency may be more frequent but likely underreported. Acquired FXIIID may result from impaired synthesis (liver failure) or increased consumption (surgery, sepsis, leukemia, Henoch-Schönlein, inflammatory bowel disease, stroke, disseminated intravascular coagulation). FXIII replacement in form of fresh frozen plasma (FFP) or plasma-derived FXIII may be necessary for the presence of bleeding.

[Therapeutic relationship with the child and the adolescent affected with leukemia]. / La relazione terapeutica con il bambino e l'adolescente affetti da leucemia.

The main psychosocial purpose in treating childhood cancer is to help children and their families to face the diagnosis of cancer and subsequent consequences. Children and their families, most of whose are in front of this new diagnosis without showing any sign of failure, need our help. We should try from one side to help the child and his/her family who need a very quick support from us, from the other side a controlled and scientifically valid research, finalized to differentiate effective from non-effective interventions, should be carried on. The optimal clinical assistance is related to the application of the best discoveries nowadays available, based on evidence and applied in the local cultural context. The health care team can carefully listen to the children and their families to detect in which way they work and answer to the request of assistance that was offered to them. To modify own approach based on the level of satisfaction of families looking at the type of offered assistance could help in making better service.

Identification of mutations in the PARK2 gene in Serbian patients with Parkinson's disease.

Mutations in the PARK2 (PRKN) gene are the most common cause of autosomal-recessive (AR) juvenile parkinsonism and young-onset Parkinson's disease (YOPD). >100 different variants have been reported, including point mutations, small indels and single or multiple exon copy number variations. Mutation screening of PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with disease onset before 50 years and/or positive family history with apparent AR inheritance. All coding regions and their flanking intronic sequences were amplified and directly sequenced. Whole exon multiplications or deletions were detected using Multiple Ligation Probe Amplification (MLPA) method. We identified 12 PD patients with PARK2 mutations (5.3%). Five patients (2.2%) had biallelic mutations and seven (3.1%) were single mutation carriers. Patients with compound heterozygous mutations had earlier onset of the disease compared to non-carriers (p = 0.005) or heterozygotes (p = 0.001). Other clinical features in mutation carriers were not different compared to non-carriers. In our cohort, sequence and dosage variants were equally represented in patients, inducing their first symptoms mainly before the age of 30. For efficient genetic testing strategy, patients with early, especially juvenile onset of PD were strong candidates for both dosage and sequence variants screening of PARK2 gene.

Control of immunoglobulin gene rearrangements in developing B cells.

The antigen receptor on B lymphocytes is the product of a series of gene rearrangements which ends when a functional receptor gene is assembled. Recent work has shown that the receptor-associated molecules Ig alpha and Ig beta provide the signals that lead to inhibition of further recombination. Furthermore, Ig beta has been implicated in initiating the last step of the recombination reaction.

Glycobiochemical characterization of salivary carcinoembryonic antigen.

PURPOSE: Carcinoembryonic antigen (CEA) is a highly glycosylated molecule, expressed in both normal and pathological conditions. This study was aimed at isolation and glycobiochemical characterization of human salivary CEA, and comparison of its structural properties with those of cancer-derived CEA. MATERIALS AND METHODS: CEA was isolated by immunoaffinity chromatography on an anti-CEA IgG-Sepharose 4B column. The isolated antigen was characterized by SDSPAGE, gel filtration on Sepharose 4B and lectin-affinity chromatography using a panel of 6 plant lectins. RESULTS: The isolated salivary CEA had a molecular mass of 180 kD and retained its structural and antigenic properties. Lectin-affinity chromatography indicated pronounced microheterogeneity of both salivary and cancer-derived CEA. Comparison of the lectin-binding patterns demonstrated lower relative amounts of distinct Phaseolus vulgaris agglutinin-reactive and Pisum sativum agglutinin-reactive glycoforms in salivary CEA than in cancer-derived CEA. CONCLUSION: The observed microheterogeneity of salivary CEA could have both functional and clinical relevance in relation to normal as well as to pathological oral physiology.

The Fourier analysis applied to the relationship between (7)Be activity in the Serbian atmosphere and meteorological parameters.

Air sample monitoring in Serbia, Belgrade started in the 1960s, while (7)Be activity in air and total (dry and wet) deposition has been monitored for the last 22 years by the Environment and Radiation Protection Department of the Institute for Nuclear Sciences, Vinca. Using this data collection, the changes of the (7)Be activity in the air and the total (wet and dry) deposition samples, as well as their correlation with meteorological parameters (temperature, pressure, cloudiness, sunshine duration, precipitation and humidity) that affect (7)Be concentration in the atmosphere, were mathematically described using the Fourier analysis. Fourier analysis confirmed the expected; the frequency with the largest intensity in the harmonic spectra of the (7)Be activity corresponds to a period of 1 year, the same as the largest intensity frequency in Fourier series of meteorological parameters. To analyze the quality of the results produced by the Fourier analysis, we compared the measured values of the parameters with the values calculated according to the Fourier series. Absolute deviations between measured and predicted mean monthly values are in range from 0.02 mBq/m(3) to 0.7 mBq/m(3) for (7)Be activity in air, and 0.01 Bq/m(2) and 0.6 Bq/m(2) for (7)Be activity in deposition samples. Relatively good agreement of measured and predicted results offers the possibility of prediction of the (7)Be activity.