Cortisol-induced SRSF3 expression promotes GR splicing, RACK1 expression and breast cancer cells migration

Recent data have demonstrated that triple negative breast cancer (TNBC) with high glucocorticoid receptor (GR) expression are associated to therapy resistance and increased mortality. Given that GR alternative splicing generates mainly GRα, responsible of glucocorticoids action, we investigated its role in the regulation of RACK1 (Receptor for Activated C Kinase 1), a scaffolding protein with a GRE (Glucocorticoid Response Element) site on its promoter and involved in breast cancer cells migration and invasion. We provide the first evidence that GRα transcriptionally regulates RACK1 by a mechanism connected to SRSF3 splicing factor, which promotes GRα, essential for RACK1 transcriptional regulation and consequently for cells migration. We also establish that this mechanism can be positively regulated by cortisol. Hence, our data elucidate RACK1 transcriptional regulation and demonstrate that SRSF3 involvement in cells migration implies its role in controlling different pathways thus highlighting that new players have to be considered in GR-positive TNBC

Social distancing measures for COVID-19 are changing winter season

Health authorities worldwide have adopted measures of social distancing and movement restrictions, in addition to other public health measures to reduce exposure and to suppress interhuman SARS-CoV- 2 transmission. In Italy, a national lockdown with school closure was introduced from March to May 2020. From November 2020, Italy has been divided into zones according to regional epidemiological data, with primary schools reopened, associated with the mandatory use of face masks and different levels of social distance measures. For children with symptoms suggestive of COVID-19, the surveillance mechanism for the control of SARS-CoV- 2 infection is based on the performance of a real-time PCR on a nasopharyngeal swab. A diagnostic test has been introduced at the tertiary-level university hospital, Institute for Maternal and Child Health, IRCCS \u201cBurlo Garofolo\u201d of Trieste, consisting of a multiple nucleic acid amplification assay for 13 common viral respiratory pathogens on nasopharyngeal swab (Respiratory Flow Chip assay (Vitro, Sevilla, Spain), including SARS-CoV- 2, influenza A and B, adenovirus, other coronaviruses, parainfluenza virus 1\u20134, enteroviruses, bocavirus, metapneumovirus, respiratory syncytial virus (RSV), rhinoviruses, Bordetella pertussis, Bordetella parapertussis and Mycoplasma pneumoniae. Before routine utilisation, international standard quality control samples for each pathogen were used for test validation, and no cross-detection was found between the different pathogens. Criteria for testing referral did not change during the study period. Weekly variability of the number of total tests performed was due to the normal variations of acute illness. During the last winter season, from September 2020 (week 39) to February 2021 (week 7), 1138 nasopharyngeal swabs were tested for patients younger than 17 years old (figure 1). No influenza A or B nor RSV was detected during this period. The most common pathogen was rhinovirus (n=505), followed by adenoviruses (n=131), other coronaviruses (n=101) and SARS-CoV- 2 (n=57). Our data show that common winter pathogens circulation changed, and influenza virus and RSV did not produce a seasonal epidemic in the 2020\u20132021 winter season. These data suggest that social distancing measures and mask wearing profoundly changed the seasonality of winter paediatric respiratory infections that are mainly spread by respiratory droplets. The reasons why rhinovirus remains the main pathogen despite social distancing and face mask use are still a matter of debate. Similar data showing a decrease of common viral respiratory infections during the winter season have recently been reported in the southern hemisphere.1\u20134 Our data refer to a single institute, covering paediatric population of the Trieste Province (about 230 000 inhabitants), limiting the generalisation of our findings. However, our results highlight the need for continuing surveillance for the delayed spread of such viruses during spring and summer

Role of hormones in the regulation of RACK1 expression as a signaling checkpoint in immunosenescence

Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide (LPS) stimulation and cytokine release. The lack of PKC activation seems to be dependent on the reduced expression of the receptor for activated C kinase 1 (RACK1), a scaffolding protein involved in multiple signal transduction cascades. The defective expression of RACK1 may be dependent on age-related alteration of the balance between the adrenal hormones cortisol and dehydroepiandrosterone (DHEA). DHEA levels reduce with aging, while cortisol levels remain substantially unchanged, resulting in an overall increase in the cortisol:DHEA ratio. These hormonal changes are significant in the context of RACK1 expression and signaling function because DHEA administration in vivo and in vitro can restore the levels of RACK1 and the function of the PKC signaling cascade in aged animals and in human cells. In contrast, there is evidence that cortisol can act as a negative transcriptional regulator of RACK1 expression. The rack1 gene promoter contains a glucocorticoid responsive element that is also involved in androgen signaling. Furthermore DHEA may have an indirect influence on the post-transcriptional regulation of the functions of the glucocorticoid receptor. In this review, we will examine the role of the hormonal regulation of rack1 gene transcriptional regulation and the consequences on signaling and function in immune cells and immunosenescence

Impact of the first COVID-19 lockdown on the relationship with parents and peers in a cohort of adolescents with somatic symptom disorder

To investigate the coping strategies of a group of adolescents with somatic symptom disorder compared to non-somatic symptom disorder peers during the COVID-19 related lockdown.This cross-sectional study is the second part of a previously published study showing an improved trend in depression and anxiety in a group of patients with somatic symptom disorder compared to non-somatic symptom disorder peers. An anonymous semi-structured survey was distributed to two groups of Italian adolescents to measure the impact of quarantine on their daily life and coping strategies.We recruited 115 adolescents, 58 (50.4%) mean age 15.3, with a recent diagnosis of somatic symptom disorder and 57 (49.6%) mean age 15.8, control peers.The aim of this study was to detect differences in coping strategies and relationships with parents and peers, during the lockdown period in a group of adolescents with somatic symptom disorder and low disease burden when compared with a non-somatic symptom disorder group.The relationship with parents significantly worsened in 4 (6.9%) of adolescents with somatic symptom disorder compared to 12 (21.1%) adolescents in the non-somatic symptom disorder group (p = 0.048). The relationship with peers significantly improved in 13 (22.4%) of adolescents with symptom disorder versus 3 (5.3%) of peers of the non- somatic symptom disorder group (p = 0.013).Adolescents with somatic symptom disorder with a low burden of physical symptoms experienced less deterioration in their relationships with parents and peers than the non-somatic symptom disorder group

The role of mercury, selenium and the Se-Hg antagonism on cognitive neurodevelopment: A 40-month follow-up of the Italian mother-child PHIME cohort

Despite a 15-year long effort to define the \u201csafety\u201d of fish intake during pregnancy, there remains still uncertainty on this important public health issue. The evaluation of the toxic effects of contaminants, particularly mercury (Hg) in fish-eating populations is complicated by the fact that sea-food is also rich in beneficial nutrients, such as selenium (Se). There is toxicological plausibility of an antagonistic effects between Se and Hg, and some theoretical support for the inclusion of the Se\u2013Hg interaction to better assess the risk linked with fish intake. To assess the effects of exposure to low-level Hg through fish consumption on the developing brain and the interaction between Hg and Se, we conducted an analysis at age 40 months in Italian children, enrolled in a prospective mother-child cohort, comparing additive and multiplicative models. Participant subjects were the 470 children born within the Northern Adriatic Cohort II (NAC-II) cohort who were tested by using the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) (BSID-III) at age 40. Family demographic and socioeconomic information, pregnancy and delivery history, parental and child medical history and food consumption were assessed through questionnaires. Maternal blood samples were collected during pregnancy, cord blood at birth and maternal milk 1 month after delivery. As other exposures of interest, we considered the level of Se in maternal and cord blood and in breast milk and the potential Se\u2013Hg antagonism. Se and inverse of THg (1:THg) concentrations were categorized according to the tertiles of their distributions, in low, medium and high levels of exposure. The lower end of the composite cognitive score distribution closest to 20% was defined as suboptimal development. Multiple logistic regression were applied to assess the association between the dichotomized composite cognitive score and the categorized exposure to Se and 1:THg, and the antagonism between Se and 1:THg. In the recruiting period, 900 pregnant women were enrolled in the cohort; 767 of these remained in the study at delivery and 470 children at 40 months. After excluding preterm births, 456 children were used in the final analyses. The larger difference in risk for suboptimal neurodevelopment was observed for the category with High THg and Low Se with OR = 2.55 (90% CI 1.02; 6.41) under the multiplicative and OR = 1.33 (90% CI 0.80; 1.87) under the additive model. The category High THg and High Se showed a very slightly better fit of the additive model (OR = 1.07, 90% CI 0.65; 1.50) versus the multiplicative (OR = 1.66, 90% CI 0.73; 1.77). A negative \u2013 antagonistic \u2013 interaction term for this category was estimated under the multiplicative model giving an OR = 1.17 (90% CI 0.42; 3.28). Although this evidence of the effects of the Se\u2013Hg antagonism on the children neuro-development needs to be confirmed, if Se can counterbalance Hg toxicity, the evaluation of the effect on human health of fish consumption, should also consider the diverse ratios between Se and Hg concentration in different fish species

Videogame playing as distraction technique in course of venipuncture.

Background: needle-related procedures (venipuncture, intravenous cannulation) are the most common source of pain and distress for children. reducing needle related pain and anxiety could be important in order to prevent further distress, especially for children needing multiple hospital admissions. the aim of the present open randomized controlled trial was to investigate the efficacy of adding an active distraction strategy (videogame) to eMlA premedication in needle-related pain in children. Methods: one-hundred and nine children (4 -10 years of age) were prospectively recruited to enter in the study. ninety-seven were randomized in two groups: CC group (conventional care: eMlA only) as control group and Ad group (active distraction: eMlA plus videogame) as intervention group. outcome measures were: selfreported pain by mean of FPS-r scale (main study outcome), observer-reported pain by FlACC scale, number of attempts for successful procedure. Results: in both groups FPS-r median rate was 0 (interquartile range: 0-2), with significant pain (FPS-r>4) reported by 9% of subjects. FlACC median rate was 1 in both groups (interquartile range 0-3 in CC group; 0-2 in Ad group). the percentage of children with major pain (FlACC>4) was 18% in CC group and 9% in Ad group (p=0.2). the median of necessary attempts to succeed in the procedures was 1 (interquartile range 1-2) in both groups.. Conclusion: Active distraction doesn't improve eMlA analgesia for iv cannulation and venipuncture. even though, it resulted in an easily applicable strategy appreciated by children. this technique could be usefully investigated in other painful procedures

Atypical onset as predictor of poor outcome in Pediatric Systemic Lupus Erythematosus (pSLE)

Poster Presentation

Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study

Periodic fever syndromes (PFS) are an emerging group of autoinflammatory disorders. Clinical overlap exists and multiple genetic analyses may be needed to assist diagnosis. We evaluated the diagnostic value of a 5-gene sequencing panel (5GP) in patients with undiagnosed PFS