Parent-child communication about sex and romantic feelings: does having older siblings make a difference?

Parental involvement in sex education and the quality of parent-child communication about romantic feelings appear to have a protective effect on adolescent sexual behaviours. However, little research has been conducted on the role played by birth order in the level of parental involvement in sex education. This is the first study seeking to address if the quality of parent-child communication about sex and romantic sentiments differs according to whether respondents have—or do not have—older siblings in Italy. Hypotheses concerning the role of sib-ship gender composition have been tested in order to explain potential intervening mechanisms. Data were drawn from the Sexual and Emotional Life of Youths survey(SELFY), a cross-sectional survey conducted in 2000 and in 2017 on Italian university students (N= 12,265). Our findings identify later-born children as the least likely to confide in parents. Although boys are generally less likely to talk to parents than girls, respondent gender does not moderate the effect of birth order. Instead, sib-ship gender composition plays a role: having grown up with at least one same-gender sibling is associated with a lower communication with parents about intimate matters. This study suggests that growing up with siblings, namely with same-gender siblings, make a difference in parent-child communication, and this should be considered while evaluating the role of parental involvement in adolescent sexual education

Vulnerabilities in Mental Health due to Covid-19 Pandemic: The Response of the Italian Physicians

COVID-19 pandemic has exacerbated the pre-existing vulnerabilities and inequalities in societies. In this paper we analyse the categories that have suffered more than others from the pandemic and the restrictions on social life in terms of mental health. We rely on the Serendipity project based on a survey administered between November 2021 and February 2022 to a sample of Italian physicians (n = 1281). The survey aimed to assess the perception of general practitioners, paediatricians, geriatricians, and mental health specialists (psychiatrists, neurologists, child neuropsychiatrists), about changes in the mental health of the population as an effect of the COVID-19 pandemic and the lockdown. The strategies implemented by the doctors interviewed in terms of the intensity of the prevention, emergence, and treatment of mental health interventions, and their association with physicians' characteristics and their opinions on patient vulnerability have been illustrated by means of a multiple correspondence analysis. An overall result of the survey is the consensus of doctors on the worsening of mental health in general population, especially among their patients, due to the pandemic and on the onset of new discomforts. The most exposed individuals to the risk of onset or worsening of mental disorders include women, young people, and patients with psychiatric comorbidity. The paper also illustrates the interventions put in place by the physicians and deemed necessary from a public heath response perspective, that include providing psychoeducation to the general population, improving telehealth services, and increasing financial and human resources for community-based care

Dissecting molecular mechanisms of resistance to NOTCH1-targeted therapy in T-cell acute lymphoblastic leukemia xenografts

Despite substantial progress in treatment of T-cell acute lymphoblastic leukemia (T-ALL), mortality remains relatively high, mainly due to primary or acquired resistance to chemotherapy. Further improvements in survival demand better understanding of T-ALL biology and development of new therapeutic strategies. The Notch pathway has been involved in the pathogenesis of this disease and various therapeutic strategies are currently under development, including selective targeting of NOTCH receptors by inhibitory antibodies. We previously demonstrated that the NOTCH1-specific neutralizing antibody OMP52M51 prolongs survival in TALL patient-derived xenografts bearing NOTCH1/FBW7 mutations. However, acquired resistance to OMP52M51 eventually developed and we used patient-derived xenografts models to investigate this phenomenon. Multi-level molecular characterization of T-ALL cells resistant to NOTCH1 blockade and serial transplantation experiments uncovered heterogeneous types of resistance, not previously reported with other Notch inhibitors. In one model, resistance appeared after 156 days of treatment, it was stable and associated with loss of Notch inhibition, reduced mutational load and acquired NOTCH1 mutations potentially affecting the stability of the heterodimerization domain. Conversely, in another model resistance developed after only 43 days of treatment despite persistent down-regulation of Notch signaling and it was accompanied by modulation of lipid metabolism and reduced surface expression of NOTCH1. Our findings shed light on heterogeneous mechanisms adopted by the tumor to evade NOTCH1 blockade and support clinical implementation of antibody-based target therapy for Notch-addicted tumors

A real-world retrospective, observational study of first-line pembrolizumab plus chemotherapy for metastatic non-squamous non-small cell lung cancer with PD-L1 tumor proportion score < 50% (PEMBROREAL)

IntroductionThe phase III Keynote-189 trial established a first-line treatment combining pembrolizumab with pemetrexed and platinum as a standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) without known EGFR and ALK driver mutations and independent of programmed cell death ligand 1 (PD-L1) expression. However, in Italy, eligibility for the National Health Service payment program is limited to patients with PD-L1 &lt;50%. The PEMBROREAL study assesses the real-world effectiveness and safety of pembrolizumab in patients eligible for the National Health Service payment program.MethodsPEMBROREAL is a retrospective, observational study on patients with NSCLC who started pembrolizumab combined with pemetrexed and platinum within the reimbursability time window, considered as December 2019 to December 2020. The primary endpoints were to assess progression-free survival (PFS) and overall survival (OS; using the Kaplan–Meier method), response to therapy, and tolerability.ResultsUntil February 2022, 279 patients (median follow-up: 19.7 months) have been observed. The median PFS was 8.0 months (95% confidence interval: 6.5–9.2). OS was not reached, but we can estimate a 12- to 24-month survival rate for the combined treatment: 66.1% and 52.5%, respectively. PD-L1 expression and Eastern Cooperative Group (ECOG) Performance Status were both associated with PFS and OS. Overall, only 44.4% of patients reported an adverse event, whereas toxicity led to a 5.4% discontinuation rate.ConclusionThe results of the PEMBROREAL study have shown that the combined treatment of pembrolizumab with pemetrexed and platinum is effective for metastatic non-squamous NSCLC, even for patients with PD-L1 levels below 50%, despite the differences in patient demographics and pathological features compared to the Keynote-189 study. The adverse events reported during the study were more typical of chemotherapy treatment rather than immunotherapy, and physicians were able to manage them easily

Acute stress enhances the expression of neuroprotection- and neurogenesis-associated genes in the hippocampus of a mouse restraint model

Stress arises from an external demand placed on an organism that triggers physiological, cognitive and behavioural responses in order to cope with that request. It is thus an adaptive response useful for the survival of an organism. The objective of this study was to identify and characterize global changes in gene expression in the hippocampus in response to acute stress stimuli, by employing a mouse model of short-term restraint stress. In our experimental design mice were subjected to a one time exposure of restraint stress and the regulation of gene expression in the hippocampus was examined 3, 12 and 24 hours thereafter. Microarray analysis revealed that mice which had undergone acute restraint stress differed from non-stressed controls in global hippocampal transcriptional responses. An up-regulation of transcripts contributing directly or indirectly to neurogenesis and neuronal protection including, Ttr, Rab6, Gh, Prl, Ndufb9 and Ndufa6, was observed. Systems level analyses revealed a significant enrichment for neurogenesis, neuron morphogenesis- and cognitive functions-related biological process terms and pathways. This work further supports the hypothesis that acute stress mediates a positive action on the hippocampus favouring the formation and the preservation of neurons, which will be discussed in the context of current data from the literature

Different KNIME workflows for read-across and successive use for weight-of-evidence strategy

The evaluation of the toxic effects of substances is a complex task, due to the huge amount of factors involved in the biological processes at the basis of the effect. This requires taking advantage of all elements that can be used in the assessment of the property values. The read-across approach and the in silico methods, collectively called non-testing methods, can be integrated within a weight-ofevidence strategy. This integration is typically performed manually. Furthermore, also the read-across process in most of the cases relies on expert decisions, which may be subjective, and based on some initial choices. In this approach, there is a risk of making poorly reproducible results besides losing important pieces of information. In addition, a main shortcoming in read-across is that the process may not identify some of the relevant source compounds. In order to cope with these problems, we explored software tools able to assist the expert. The factors related to similarity which we used to select source compounds were: structural, physico-chemical, toxicological and pharmacokinetic features. These tools analyse the similarities of the compounds in “full or partial” way, i.e. merging all the features or selecting only those more relevant. Furthermore, the steps of the process can be done in a parallel or sequential way. Finally, we combined the results of the read-across procedure with those from in silico models. We will describe the added value of these programs, implemented in KNIME. We acknowledge the project EU-ToxRisk (a project funded by the European Union’s Horizon 2020 research and innovation program under grant agreement No 681002)

Similar foliar lesions but opposite hormonal patterns in a tomato mutant impaired in ethylene perception and its near isogenic wild type challenged with ozone

The accumulation of ethylene (Er), hydrogen peroxide (H(2)O(2)), nitric oxide (NO), salicylic (SA) and jasmonic (JA) acids, as well as the transcriptional activation of JA-biosynthetic and hypersensitive response (HR) marker genes were examined in ET-insensitive Never ripe (Nr) mutant of tomato (Lycopersicon esculentum L) and in its near isogenic wild type (WT, cv. New Yorker) during and after an acute ozone (03) fumigation. The scoring of O(3)-induced foliar symptoms indicated similar sensitivity between WT and Nr. In both genotypes the O(3)-induced ET emission peaked after 3 h of fumigation, although with different intensities between them; H(2)O(2) and NO bursts occurred, both showing a biphasic time course. However, SA and JA revealed opposite accumulation patterns: in Nr a high level of SA but a low JA accumulation were observed, whereas in WT a marked evolution of JA but a weak SA accumulation were detected. The transcription of certain JA-biosynthetic and HR-inducible genes was similarly activated by O(3) in the two tomato lines. According to the current models on the molecular events leading to the development of O(3)-induced foliar symptoms, here we suggest that the partial ET-insensitivity of Nr would have promoted a SA build-up, leading to cell death and to a reduced JA accumulation. In WT the O(3)-induced leaf injury without SA build-up but with JA accumulation would have arisen from the perception of high ET and H(2)O(2) level