The withdrawal from oncogenetic counselling and testing for hereditary and familial breast and ovarian cancer. A descriptive study of an Italian sample

<p>Abstract</p> <p>Background</p> <p>Oncogenetic counselling is seldom followed through, even when individuals are eligible according to the test criteria. The basic variables which influence the decision to undergo the genetic counselling process are: risk perception, expected benefit or limitations of genetic testing, general psychological distress or cancer-specific distress, lack of trust in one's emotional reactions when faced with negative events, expected level of family support and communications within the family. The aim of this study was to describe the psychosocial variables of an Italian sample that forgoes genetic counselling.</p> <p>Methods</p> <p>From May 2002 to December 2006 a psychological questionnaire was sent out to one hundred and six subjects, who freely requested a first genetic informative consultation, and never asked to have a second visit and the family tree drawn up in order to inquire about their eligibility for genetic testing. Statistical analysis was performed by Pearson chi-square test, t-test and Spearman RHO coefficient.</p> <p>Results</p> <p>The survey presents a lack of emotional cohesion and structured roles and rules within the family system and a positive correlation between the number of children, anxiety and risk perception. The main reasons for giving up on counselling were a sense that testing was a waste of time and the inability to emotionally handle the negative consequences of the test outcome. The subjects who maintained that test and an early diagnosis were a "waste of time" experienced more anxiety.</p> <p>Conclusion</p> <p>The study revealed the importance to ac knowledging the whole persona and their family system as well as provide information highlighting usefulness of early diagnosis.</p

Autonomy Supportive Contexts, Autonomous Motivation, and Self-Efficacy Predict Academic Adjustment of First-Year University Students

Aim: The purpose of this study was to investigate the process that lead to academic adjustment of undergraduate students in the first year of higher education, by testing a predictive model based on self-determination theory with the inclusion of self-efficacy. The model posits that perceived autonomous forms of support from parents and teachers foster autonomous motivation and self-efficacy, which in turn predict academic adjustment.Method: A two-wave prospective design was adopted. Freshman students at an Italian university (N = 388; 73.5% females, Mage = 21.38 years ± 4.84) completed measures of autonomous motivation, perceived autonomy support from parents and teachers, self-efficacy, and intention to drop out from university at the start of their academic year. Students' past performance and socioeconomic background were also measured. At the end of the first semester, information about number of course modules passed and credits attained for each student were obtained from the department office and matched with the data collected in the first wave by an identification number.Results: Findings of structural equation modeling analysis supported the proposed model for first-year university students, after controlling for the influence of past performance and socioeconomic background. Specifically, autonomous motivation and self-efficacy predicted dropout intention and academic adjustment a few months later. Autonomous motivation and self-efficacy were encouraged by autonomy supportive behaviors provided by teachers and parents.Conclusion: According to our findings, in order to promote higher degree of academic adjustment in freshman students, interventions should aim to encourage autonomous motivation and self-efficacy through autonomous supportive behavior from the university and the family contexts

Cryogenic Characterization of FBK HD Near-UV Sensitive SiPMs

We report on the characterization of near-ultraviolet high density silicon photomultiplier (\SiPM) developed at Fondazione Bruno Kessler (\FBK) at cryogenic temperature. A dedicated setup was built to measure the primary dark noise and correlated noise of the \SiPMs\ between 40 and 300~K. Moreover, an analysis program and data acquisition system were developed to allow the precise characterization of these parameters, some of which can vary up to 7 orders of magnitude between room temperature and 40~K. We demonstrate that it is possible to operate the \FBK\ near-ultraviolet high density \SiPMs\ at temperatures lower than 100~K with a dark rate below 0.01 cps/mm$^2$ and total correlated noise probability below 35\% at an over-voltage of 6~V. These results are relevant for the development of future cryogenic particle detectors using \SiPMs\ as photosensors

The role of echocardiography in SARS-CoV-2 pandemic: a compromise among appropriateness, safety and clinical impact

SARS-CoV-2 infection, responsible for COVID-19, can determine cardiac events, which require a quick diagnosis and management, and should not be overlooked due to the presence of COVID-19 infection. In some cases, cardiovascular symptoms can also be the first and only manifestation of SARS-CoV-2 infection. In patients with COVID-19, the full cardiovascular disease diagnostic algorithm can be hindered by logistic restrain mainly derived from the difficulty of transporting patients in critical conditions to Radiology or Hemodynamics wards. The echocardiography in SARS-CoV-2 pandemic can help for differential diagnosis of cardiac events, which can be related or unrelated by the infection and can likely impact on short-term prognosis. Indeed, transthoracic echocardiography plays a key role in the screen for CV complications of COVID-19 infection: it must be focused cardiac ultrasound study (FoCUS) performed at bedside. All transthoracic, transesophageal and stress echocardiograms in patients in which test results are unlikely to change the management strategy should be postponed

Short telomeres in ESCs lead to unstable differentiation

SummaryFunctional telomeres are critical for stem cell proliferation; however, whether they are equally important for the stability of stem cell differentiation is not known. We found that mouse embryonic stem cells (ESCs) with critically short telomeres (Tert−/− ESCs) initiated normal differentiation after leukemia inhibitory factor (LIF) withdrawal but, unlike control ESCs, failed to maintain stable differentiation when LIF was reintroduced to the growth medium. Tert−/− ESCs expressed higher levels of Nanog and, overall, had decreased genomic CpG methylation levels, which included the promoters of Oct4 and Nanog. This unstable differentiation phenotype could be rescued by telomere elongation via reintroduction of Tert, via suppression of Nanog by small hairpin RNA (shRNA) knockdown, or via enforced expression of the de novo DNA methyltransferase 3b. These results demonstrate an unexpected role of functional telomeres in the genome-wide epigenetic regulation of cell differentiation and suggest a potentially important role of telomere instability in cell fate during development or disease

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

Clinical characteristics of a large cohort of patients with narcolepsy candidate for pitolisant: a cross-sectional study from the Italian PASS Wakix® Cohort

Introduction Narcolepsy is a chronic and rare hypersomnia of central origin characterized by excessive daytime sleepiness and a complex array of symptoms as well as by several medical comorbidities. With growing pharmacological options, polytherapy may increase the possibility of a patient-centered management of narcolepsy symptoms. The aims of our study are to describe a large cohort of Italian patients with narcolepsy who were candidates for pitolisant treatment and to compare patients' subgroups based on current drug prescription (drug-naive patients in whom pitolisant was the first-choice treatment, switching to pitolisant from other monotherapy treatments, and adding on in polytherapy). Methods We conducted a cross-sectional survey based on Italian data from the inclusion visits of the Post Authorization Safety Study of pitolisant, a 5-year observational, multicenter, international study. Results One hundred ninety-one patients were enrolled (76.4% with narcolepsy type 1 and 23.6% with narcolepsy type 2). Most patients (63.4%) presented at least one comorbidity, mainly cardiovascular and psychiatric. Pitolisant was prescribed as an add-on treatment in 120/191 patients (62.8%), as switch from other therapies in 42/191 (22.0%), and as a first-line treatment in 29/191 (15.2%). Drug-naive patients presented more severe sleepiness, lower functional status, and a higher incidence of depressive symptoms. Conclusion Our study presents the picture of a large cohort of Italian patients with narcolepsy who were prescribed with pitolisant, suggesting that polytherapy is highly frequent to tailor a patient-centered approach

A Chromosomal Memory Triggered by Xist Regulates Histone Methylation in X Inactivation

We have elucidated the kinetics of histone methylation during X inactivation using an inducible Xist expression system in mouse embryonic stem (ES) cells. Previous reports showed that the ability of Xist to trigger silencing is restricted to an early window in ES cell differentiation. Here we show that this window is also important for establishing methylation patterns on the potential inactive X chromosome. By immunofluorescence and chromatin immunoprecipitation experiments we show that histone H3 lysine 27 trimethylation (H3K27m3) and H4 lysine 20 monomethylation (H4K20m1) are associated with Xist expression in undifferentiated ES cells and mark the initiation of X inactivation. Both marks depend on Xist RNA localisation but are independent of silencing. Induction of Xist expression after the initiation window leads to a markedly reduced ability to induce H3K27m3, whereas expression before the restrictive time point allows efficient H3K27m3 establishment. Our data show that Xist expression early in ES cell differentiation establishes a chromosomal memory, which is maintained in the absence of silencing. One consequence of this memory is the ability to introduce H3K27m3 efficiently after the restrictive time point on the chromosome that has expressed Xist early. Our results suggest that this silencing-independent chromosomal memory has important implications for the maintenance of X inactivation, where previously self-perpetuating heterochromatin structures were viewed as the principal form of memory

The withdrawal from oncogenetic counselling and testing for hereditary and familial breast and ovarian cancer. A descriptive study of an Italian sample

<p>Abstract</p> <p>Background</p> <p>Oncogenetic counselling is seldom followed through, even when individuals are eligible according to the test criteria. The basic variables which influence the decision to undergo the genetic counselling process are: risk perception, expected benefit or limitations of genetic testing, general psychological distress or cancer-specific distress, lack of trust in one's emotional reactions when faced with negative events, expected level of family support and communications within the family. The aim of this study was to describe the psychosocial variables of an Italian sample that forgoes genetic counselling.</p> <p>Methods</p> <p>From May 2002 to December 2006 a psychological questionnaire was sent out to one hundred and six subjects, who freely requested a first genetic informative consultation, and never asked to have a second visit and the family tree drawn up in order to inquire about their eligibility for genetic testing. Statistical analysis was performed by Pearson chi-square test, t-test and Spearman RHO coefficient.</p> <p>Results</p> <p>The survey presents a lack of emotional cohesion and structured roles and rules within the family system and a positive correlation between the number of children, anxiety and risk perception. The main reasons for giving up on counselling were a sense that testing was a waste of time and the inability to emotionally handle the negative consequences of the test outcome. The subjects who maintained that test and an early diagnosis were a "waste of time" experienced more anxiety.</p> <p>Conclusion</p> <p>The study revealed the importance to ac knowledging the whole persona and their family system as well as provide information highlighting usefulness of early diagnosis.</p