Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome:phenotype comparison in two related syndromes

Background Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. Methods Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. Results Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. Conclusions Results show significant between and within syndrome variability. DifferentNFIXvariants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit

Pharmacological action and therapeutic effects of glutathione on hypokinetic spermatozoa for enzymatic dependent pathologies and correlated genetic aspects

In this study, the pharmacologic substance reduced glutathione (GSH) was used in men with hypofertility problems linked to varicocele, in bulls with spermatozoa hypomobility due to varicocele, and in rabbits with dispermy caused by cryptorchidism. An efficacious therapeutic effect of increased motility of the spermatozoa was seen in subjects who were submitted to appropriate doses of glutathione I.M. GSH also showed some neutralizing effect on the catabolytes produced during spontaneous or induced peroxidation processes of the unsaturated lipids contained in the membranes of male germinal cells. The genetic aspects of the involved enzymes were also evaluated and the research was extended in vitro by incubating samples of spermatozoa with arachidonic acid homogenates, L-tryptophan, hematein, and with an addition of glutathione. The results showed that polynsaturated fatty acid metabolic substances (PUFA) play an important role in the acrosomal reaction of spermatozoa and that GSH has a determining role in increasing the motility of spermatozoa with consequent improved fertilization. The spermatozoa of bulls provided us with a valid model to study for the morphostructural, biochemical and pharmacological analyses of human spermatozoa

Pharmacological effects of melatonin on reproductive activity : experimental bioimplants with sustained-release polymeric systems

A vast literature documents the role of melatonin in human reproductive function including: a) the relation between melatonin and the menstrual cycle in relation to the peak time of luteinizing hormone in the middle of the cycle [1]; b) the varying concentrations of melatonin in the control of puberty [2]; c) the fewer conceptions in some artic populations where melatonin is connected significantly to seasonal photoperiodicity during the months of the polar nights [3]. The aim of this paper is to report our findings on the pharmacological action of this molecule on reproduction in which gonadal activity is clearly connected to photoperiodicity. We used polymer bioimplants programmed for the sustained release of melatonin for experimental gynecologic protocols. These implants had beneficial results with respect to the use of progestinics because melatonin allowed ovarian activity to be induced for at least two to three consecutive cycles with one single bioimplant. We thought it indispensable to use pharmacological systems with a sustained release because different preliminary tests showed that the half-life of melatonin is limited at maximum to two to three hours and, consequently, any other tested modalities of administration would not provide any appreciable results for our study. As a model for our research we used goats to administer melatonin via targeted programs since these animals clearly respond (even against the rule of the light/dark relation) in contrast to humans in whom response is less evident. For controls, after inserting bioimplants in the animals, we tested their efficiency in vitro and subsequently in vivo, evaluating blood parameters and pharmacological effects of melatonin occurring during the treatment. The final results proved to be interesting in relation to reproductive activity in that regular and programmed births were achieved

Clinal patterns of human Y chromosomal diversity in continental Italy and Greece are dominated by drift and founder effects

We explored the spatial distribution of human Y chromosomal diversity on a microgeographic scale, by typing 30 population samples from closely spaced locations in Italy and Greece for 9 haplogroups and their internal microsatellite variation. We confirm a significant difference in the composition of the Y chromosomal gene pools of the two countries. However, within each country, heterogeneity is not organized along the lines of clinal variation deduced from studies on larger spatial scales. Microsatellite data indicate that local increases of haplogroup frequencies can be often explained by a limited number of founders. We conclude that local founder or drift effects are the main determinants in shaping the microgeographic Y chromosomal diversity. (C) 2003 Elsevier Science (USA). All rights reserved

Minimal Incidence of Neonatal/Infancy Onset Diabetes in Italy is 1:90,000 live births

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least two weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000-1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000-1:260,000 live births. Aim of the present work was to ascertain incidence of NDM (i.e. permanent + transient form) in Italy for years 2005-2010. Patients referred to the Italian reference laboratory for NDM between years 2005-2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8 and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005-2010 were referred to the reference laboratory. In this group a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000-1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year

Minimal Incidence of Neonatal/Infancy Onset Diabetes in Italy is 1:90,000 live births

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least two weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000-1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000-1:260,000 live births. Aim of the present work was to ascertain incidence of NDM (i.e. permanent + transient form) in Italy for years 2005-2010. Patients referred to the Italian reference laboratory for NDM between years 2005-2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8 and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005-2010 were referred to the reference laboratory. In this group a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000-1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year