Hyaluronan and cardiac regeneration

Hyaluronan (HA) is abundantly expressed in several human tissues and a variety of roles for HA has been highlighted. Particularly relevant for tissue repair, HA is actively produced during tissue injury, as widely evidenced in wound healing investigations. In the heart HA is involved in physiological functions, such as cardiac development during embryogenesis, and in pathological conditions including atherosclerosis and myocardial infarction. Moreover, owing to its relevant biological properties, HA has been widely used as a biomaterial for heart regeneration after a myocardial infarction. Indeed, HA and its derivatives are biodegradable and biocompatible, promote faster healing of injured tissues, and support cells in relevant processes including survival, proliferation, and differentiation. Injectable HA-based therapies for cardiovascular disease are gaining growing attention because of the benefits obtained in preclinical models of myocardial infarction. HA-based hydrogels, especially as a vehicle for stem cells, have been demonstrated to improve the process of cardiac repair by stimulating angiogenesis, reducing inflammation, and supporting local and grafted cells in their reparative functions. Solid-state HA-based scaffolds have been also investigated to produce constructs hosting mesenchymal stem cells or endothelial progenitor cells to be transplanted onto the infarcted surface of the heart. Finally, applying an ex-vivo mechanical stretching, stem cells grown in HA-based 3D scaffolds can further increase extracellular matrix production and proneness to differentiate into muscle phenotypes, thus suggesting a potential strategy to create a suitable engineered myocardial tissue for cardiac regeneration

Sex attribution, gender identity and quality of life in disorders of sex development due to 45,X/46,XY mosaicism: methods for clinical and psychosocial assessment.

The choice of sex in newborns with genital ambiguity is challenging. Information concerning the satisfaction of subjects with disorders of sex development from childhood to adulthood is required in order to address sex attribution policies. This study focuses on the methods that enable clinicians to investigate the alignment of phenotypes with gender identity and quality of life in people with disorders of this kind. These methods are presented as tools for studying a cohort of ten subjects with 45,X/46,XY mosaicism examined between 1985 and 2014 in the Department of Pediatric Endocrinology, Regina Margherita Children's Hospital, Turin: five children and five young adults, four reared as females and six as males. Clinical outcome was assessed by means of a clinical scoring system considering height, genital appearance, gonads and pubertal development. The Gender Identity Questionnaire for Children and the World Health Organization Quality of Life assessment were adopted. The four male children strongly identified with their assigned sex: male attribution was satisfactory until pubertal age. In young adults the clinical scores ranged between 55-65% for both genders. In the young male, the reduced sexual activity and the poor body image perception strongly affected his quality of life. The clinical scores of the two young female adults (60% for both) were not balanced with their quality of life scores (87.5% and 68.75% respectively): individual traits and social-familial context should be investigated in order to explain these differences. Clinical and psychosocial assessment in people with disorders of sex development is mandatory in order to plan care procedures; a detailed analysis requires adequate tools. Clinical scoring system, Gender Identity Questionnaire for Children and World Health Organization Quality of Life assessment can be used to investigate the alignment of physical phenotype with gender identity and quality of life

Parental Relationship with Twins from Pregnancy to 3 Months: The Relation Among Parenting Stress, Infant Temperament, and Well-Being

Objective: The transition to parenthood, from pregnancy to postpartum period, is a critical process, particularly for couples expecting twins. There is very little literature regarding the links between anxiety, depression, dyadic adjustment, parental stress, and infant temperament spanning from pregnancy to postpartum. This study has two aims: first, to examine whether mothers' and fathers' anxiety, depression, and dyadic adjustment, assessed at the sixth month of pregnancy and 3 months postpartum, are associated with infants' negative affectivity (NA) and parenting stress; second, to examine whether there is any difference between fathers' and mothers' levels of parenting stress and perception of the twins' temperament, as well as to evaluate, separately for mothers and fathers, whether the levels of parenting stress and perception of child temperament differ for each twin. Method: The study participants were 58 parents (29 couples) and their healthy 58 twin babies (51.7% boys, 48.3% girls). Mothers' ages ranged from 30 to 44 years, (M Age = 36.3 years, SD = 3.2 years), and fathers' ages ranged from 32 to 52 years, (M Age = 38.2 years, SD = 4.4 years). The parents, during the pregnancy period and 3 months after delivery, filled out the Edinburgh Postnatal Depression Scale, the State-Trait Anxiety Inventory, and the Dyadic Adjustment Scale. Three months after delivery they also filled out the Parenting Stress Index-Short Form and the Infant Behavior Questionnaire Revised. Results: The analyses showed a significant correlation between parental anxiety/depression symptoms and infants' NA and parenting stress (in both mothers and fathers). Moreover, compared to fathers, mothers reported higher scores on specific dimensions of the infants' NA, [t(28)= -2.62 and p < 0.05; t(28) = 2.09 and p < 0.05], and parenting stress, [t(28) = 2.19 and p < 0.05; t(28) = 2.23 and p < 0.05], but only for Twin 2. Finally, the results showed that mothers' perceptions of child temperament vary between two twins, [e.g., distress to limitations: t(28) = 2.08 and p < 0.05]. Discussion: This study highlights the peculiarity of twin parenthood during the fourth trimester. In particular, the differences between twins' mothers' and fathers' perceptions are relevant from a clinical perspective and for perinatal professionals. It would be interesting to study the long-term impact of mothers' and fathers' differing perceptions of their twins

Caspase activation in etoposide‐treated fibroblasts is correlated to ERK phosphorylation and both events are blocked by polyamine depletion

Activation of the extracellular signal‐regulated kinases (ERKs) 1 and 2 is correlated to cell survival, but in some cases ERKs can act in signal transduction pathways leading to apoptosis. Treatment of mouse fibroblasts with 20 μM etoposide elicited a sustained phosphorylation of ERK 1/2, that increased until 24 h from the treatment in parallel with caspase activity. The inhibitor of ERK activation PD98059 abolished caspase activation, but caspase inhibition did not reduce ERK 1/2 phosphorylation, suggesting that ERK activation is placed upstream of caspases. Both ERK and caspase activation were blocked in cells depleted of polyamines by the ornithine decarboxylase inhibitor α‐difluoromethylornithine (DFMO). In etoposide‐treated cells, DFMO also abolished phosphorylation of c‐Jun NH2‐terminal kinases triggered by the drug. Polyamine replenishment with exogenous putrescine restored the ability of the cells to undergo caspase activation and ERK 1/2 phosphorylation in response to etoposide. Ornithine decarboxylase activity decreased after etoposide, indicating that DFMO exerts its effect by depleting cellular polyamines before induction of apoptosis. These results reveal a role for polyamines in the transduction of the death signal triggered by etoposide

Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats

One of the main cause of ineffective cell therapy in repairing the damaged heart is the poor yield of grafted cells. To overcome this drawback, rats with 4-week-old myocardial infarction (MI) were injected in the border zone with human adipose-derived stem cells (ADSCs) conveyed by poly(lactic-co-glycolic acid) microcarriers (PAMs) releasing hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) (GFsPAMs). According to treatments, animals were subdivided into different groups: MI_ADSC, MI_ADSC/PAM, MI_GFsPAM, MI_ADSC/GFsPAM, and untreated MI_V. Two weeks after injection, a 31% increase in ADSC engraftment was observed in MI_ADSC/PAM compared with MI_ADSC (p < 0.05). A further ADSC retention was obtained in MI_ADSC/GFsPAM with respect to MI_ADSC (106%, p < 0.05) and MI_ADSC/PAM (57%, p < 0.05). A 130% higher density of blood vessels of medium size was present in MI_ADSC/GFsPAM compared with MI_ADSC (p < 0.01). MI_ADSC/GFsPAM also improved, albeit slightly, left ventricular remodeling and hemodynamics with respect to the other groups. Notably, ADSCs and/or PAMs, with or without HGF/IGF-1, trended to induce arrhythmias in electrically driven, Langendorff-perfused, hearts of all groups. Thus, PAMs releasing HGF/IGF-1 markedly increase ADSC engraftment 2 weeks after injection and stimulate healing in chronically infarcted myocardium, but attention should be paid to potentially negative electrophysiological consequences

The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country