Newborn screening for Pompe disease: impact on families.

Pompe disease (PD) is an autosomal recessive lysosomal storage disorder causing progressive glycogen accumulation in muscles, with variability in age of onset and severity. For infantile-onset PD (IOPD), initiation of early treatment can be life-saving; however, current newborn screening (NBS) technology cannot distinguish IOPD from late-onset PD (LOPD) without clinical workup. Therefore, families of LOPD infants diagnosed by NBS may now spend years or even decades aware of their illness before symptoms appear, creating a pre-symptomatic awareness phase with which the medical community has little experience. The present study examines the effects of receiving a positive NBS result for PD on families. In-depth qualitative interviews were conducted with mothers of nine children (three IOPD and six LOPD) diagnosed via NBS, exploring their experiences, understanding of PD, how they are coping, and what impact diagnosis is having on family life. Interviews were coded using MaxQDA v.12 and analyzed for thematic trends. While overall opinion of NBS was favorable, it is clear many of the concerns anticipated by HCPs, patients, and families regarding NBS for late-onset LSDs are being realized to varying degrees; LOPD families are becoming patients-in-waiting. Increased fear/anxiety and living with uncertainty (regarding diagnosis, their children's future, and when to start treatment) were predominant themes, with all families voicing considerable emotional reactions and varied social and healthcare support concerns. Coping strategies and psychosocial challenges are interpreted using Rolland & Williams' Family Systems Genetic Illness model. Recommendations for improvement in delivery of service, as well as families' advice for future parents and HCPs, are discussed.

Embryonic morphogenetic field induces phenotypic reversion in cancer cells. Review article.

Cancer cells introduced into developing embryos can be committed to a complete reversion of their malignant phenotype. It is unlikely that such effects could be ascribed to only few molecular components interacting according to a simple linear-dynamics model, and they claim against the somatic mutation theory of cancer. Some 50 years ago, Needham and Waddington speculated that cancer represents an escape from morphogenetic field like those which guide embryonic development. Indeed, disruption of the morphogenetic field of a tissue can promote the onset as well as the progression of cancer. On the other hand, placing tumor cells into a "normal" morphogenetic field - like that of an embryonic tissue - one can reverse malignant phenotype, "reprogramming" tumor into normal cells. According to the theoretical framework provided by the thermodynamics of dissipative systems, morphogenetic fields could be considered as distinct attractors, to which cell behaviors are converging. Cancer-attractors are likely positioned somewhat close to embryonic-attractors. Indeed, tumors share several morphological and ultra-structural features with embryonic cells. The recovering of an "embryonic-like" cell shape might enable the gene regulatory network to reactivate embryonic programs, and consequently to express antigenic and biochemical embryonic characters. This condition confers to cancer an unusual sensitivity to embryonic regulatory cues. Thus, it is not surprising that cancer cells exposed to specific embryonic morphogenetic fields undergoes significant modifications, eventually leading to a complete phenotypic reversion.

Hints of theta13>0 from global neutrino data analysis.

Nailing down the unknown neutrino mixing angle theta{13} is one of the most important goals in current lepton physics. In this context, we perform a global analysis of neutrino oscillation data, focusing on theta{13}, and including recent results [ (unpublished)]. We discuss two converging hints of theta{13}>0, each at the level of approximately 1sigma: an older one coming from atmospheric neutrino data, and a newer one coming from the combination of solar and long-baseline reactor neutrino data. Their combination provides the global estimate sin{2}theta{13}=0.016+/-0.010(1sigma), implying a preference for theta{13}>0 with non-negligible statistical significance ( approximately 90% C.L.). We discuss possible refinements of the experimental data analyses, which might sharpen such intriguing indications.

Probing possible decoherence effects in atmospheric neutrino oscillations.

It is shown that the results of the Super-Kamiokande atmospheric neutrino experiment, interpreted in terms of nu(mu)<-->nu(tau) flavor transitions, can probe possible decoherence effects induced by new physics (e.g., by quantum gravity) with high sensitivity, supplementing current laboratory tests based on kaon oscillations and on neutron interferometry. By varying the (unknown) energy dependence of such effects, one can either obtain strong limits on their amplitude or use them to find an unconventional solution to the atmospheric nu anomaly based solely on decoherence.

Flow cytometric measurement of DNA content in human solid tumors: a comparison with cytogenetics.

The aims of this study were: (1) to test the accuracy of flow cytometery (FC) in the measurement of DNA content in human solid tumors, (2) to correlate the FC DNA-index (DI) with the chromosome modal number (CMN) provided by cytogenetic analysis (CG), and (3) to investigate the most frequent pitfalls in FC histograms classification. FC and CG analyses were performed in parallel on 113 samples of human solid tumors of different origin. FC provided an evaluable histogram in 110 out of 113 cases (97%), whereas a successful CG culture was obtained in 79 out of 113 samples (72%). In the 79 cases evaluable by both FC and CG, a concordant ploidy status was found in 66 cases (84%) (47 diploid and 19 aneuploid) (P < 0.001, chi-square test). In the 19 concordant aneuploid tumors a close correlation between the CMN and the DI was found (y = 0.019 x + 0.151; r = 0.860). Concerning the 13 discordant cases, 11 (85%) were classified as aneuploid by FC and as diploid by CG, while 2 cases (15%) were CG aneuploid (1 near-diploid and 1 tetraploid) and FC diploid. The current study suggests that FC is a reliable method for the measurement of tumor DNA content of the studied solid tumors. Special attention should be paid to the improvement of DNA histograms quality, in order to reduce the difficulties in the detection of near-diploid and near-tetraploid cell populations. Multiple sampling should be warranted whenever possible.

A rare case of cytogenetic discrepancy between extraembryonic and fetal tissue.

We present a case of false-negative discrepancy between extraembryonic and fetal tissue sampled at 14 weeks of amenorrhoea when ultrasound examination showed morphological anomalies of the fetus. The same cytogenetic characteristic was confirmed on tissue samples after abortion.

Identification of hematopoietic progenitor cells in human amniotic fluid before the 12th week of gestation.

Due to technical difficulties in performing amniocentesis before the 12th week of pregnancy, very little is known about the components of human amniotic fluid before that time. Amniocentesis was performed between the 7th-11th week of gestation in 25 informed and consenting patients, who had to undergo therapeutic interruption of pregnancy. The cells from the amniotic fluid were stained, counted on a hemocytometer, and checked for vitality. The origin of these cells was determined from cellular cultures the intracellular content of the hemoglobin and the chloroacetate esterase content of the hemoglobin and the chloroacetate esterase contents were also studied. Taking advantage of the "in vitro" adhesive properties of these cells to the bone marrow stromal feeder layer, we obtained clonal growth of an erythroid nature from 18 out of 33 samples. At the 17th week of gestation, an increased number of cells and a decrease in their vitality was found. Between the 7th and 12th week, the cellular composition of the fluid was totally different from that found later in the pregnancy. Small nucleated, round cells were identified as hematopoietic progenitor cells. At the beginning of the 11th week, a cellular population, typically used to perform prenatal diagnosis of chromosomal abnormalities from the 14th week of pregnancy appeared. Since hematopoietic progenitor cells were found in the amniotic fluid before the 12th week of gestation, these cells most probably come from the hematopoietic cells of the yolk sac through the thin membrane of the yolk sac at this time.

Prevalence of hepatitides in our hemodialyzed population.

We evaluated the prevalence of hepatitis in our hemodialysed population (65 patients, 37 M and 28 F). Screening for A and B hepatitis was tested with the RIA method and research of the anti-HCV with the immunoenzymatic method (Ortho HCV ELISA test of 2nd generation). 15 patients (23.07%) were anti-HCV positive (anti-HCV+); 23 (35.38%) showed positivity for 1 or more markers of B hepatitis (HBV+). A meaningful greater prevalence of B virus infections in anti-HCV+ patients (86.66%), compared to negatives, (20.00%) resulted. All non-A, non-B hepatitides are anti-HCV+. The dialytic treatment of the anti-HCV+ patients was meaningfully longer than in the negatives (p less than 0.05). The prevalence of the seropositive patients to B and C virus is not correlated to the number of transfusions, while it is to the number of surgical operations carried out in the predialytic period. This information suggests common pathogenetic mechanisms between the 2 forms of hepatitis and increased probability to find anti-HCV+ with a longer dialytic treatment.

Personality traits and mental prognosis in patients with congenital hypothyroidism not treated from early life.

Congenital hypothyroidism, if not treated in very early life, severely impairs the neuropsychological development of affected subjects. We have carried out a detailed analysis of cognitive functioning and personality traits in 18 congenital hypothyroid patients treated late and/or unproperly. Significant cognitive defects were observed, the most important being a defective learning ability and an impaired capacity to judge socially significant events and to project complex actions in a temporal perspective. A mental retardation (IQ less than 70) was observed in 8/18 (44.4%) of these patients, a moderate intellective deficit in 5/18 (27.8%) and an IQ greater than 85 in the remaining 5 patients (27.8%). These data indicate that the mental defect of congenital hypothyroid patients may be overestimated. The patients personality was characterized by dependence on the mother, worrying about their body, maladjustment and socialization problems. Since the intellective prognosis of these patients may significantly improve when the environmental conditions are optimized, social and psychological help must always be suggested.

[Y chromosome abnormalities and azoospermia. Description of 2 cases]. / Anomalies du chromosome Y et azoospermie. Description de deux cas.

We describe clinical features and laboratory findings in two azoospermic males with a large Yq deletion involving both the fluorescent and part of the non-fluorescent segment. This report give strong support to the localization of fertility factors in the euchromatic Yq portion.

Endemic cretinism in Sicily.

This work reports the presence of endemic cretinism in a small district located inside an endemic goiter area in north-eastern Sicily, personally described. The study covers 19 mental defectives (11 females and 8 males, mean age 35.8 +/- 15.5 yr) selected on the basis of severe mental retardation recognized by the local doctors. No systematic survey for cretinism was carried out in the total population. Marked mental retardation was evident in all subjects. Nine of them exhibited clinical and biochemical signs of hypothyroidism (myxedematous cretins). The 10 others were clinically euthyroid and had deaf-mutism and/or pyramidal tract dysfunction (neurological cretinism). Familial aggregation of cretinism was also observed. In both myxedematous and neurological cretins and urinary iodine excretion was very low, but not significantly different from that recorded in the euthyroid controls of the same area. The data available do not clarify the pathogenesis of endemic cretinism in Sicily. However, the marked height retardation, the observation of delayed bone maturation and the severity of mental deficiency suggest that thyroid failure was present in early life. The presence of endemic cretinism today in Sicily constitutes a strong argument in favour of the immediate introduction of adequate iodine prophylaxis.

Measurement of reverse triiodothyronine in dried blood spot: methodology and clinical application as a screening procedure for detection of congenital hypothyroidism.

A new sensitive radioimmunoassay method for measuring reverse triiodothyronine (rT3) concentrations in dried blood samples, designed to screen newborn infants for congenital hypothyroidism, has been developed. Paper strips are impregnated with cord blood and dried. Duplicate 5-mm diameter discs are punched from the paper strips and added directly to the radioimmunoassay reaction mixture. After incubation, bound and free hormone are separated by dextran-coated charcoal. The disc remains in the solution throughout the procedure and the assay can be completed within 24 hr. Recovery of rT3 is greater than 95% and coefficients of variation are 9.4% (intraassay) and 12.2% (interassay) at an rT3 concentration of 220 ng/dl. At very low rT3 concentrations (25 ng/dl), coefficients of variation are 14.2% (intraassay) and 18.7% (interassay). The method readily detects 12.5 ng/dl of rT3. With this paper disc method, rT3 was measured in 38 newborns and compared with serum rT3 measured in the same subjects by a standard radioimmunoassay method. The correlation between rT3 values measured in dried blood disc and in serum was very high (r = 0.918). The rT3 in dried blood discs from the cord blood of 745 normal newborns was 228.9 +/- 76.0 ng/dl (mean +/- SD). In contrast, two infants with proven congenital hypothyroidism had rT3 values of 35 and 75 ng/dl, respectively. This study indicates that rT3 can be easily measured in dried blood discs and suggests that the described method may be a useful screening procedure in a program for the detection of neonatal hypothyroidism.