Novel role for polycystin-1 in modulating cell proliferation through calcium oscillations in kidney cells

Objectives: Polycystin-1 (PC1), a signalling receptor regulating Ca2+-permeable cation channels, is mutated in autosomal dominant polycystic kidney disease, which is typically characterized by increased cell proliferation. However, the precise mechanisms by which PC1 functions on Ca2+ homeostasis, signalling and cell proliferation remain unclear. Here, we investigated the possible role of PC1 as a modulator of non-capacitative Ca2+ entry (NCCE) and Ca2+ oscillations, with downstream effects on cell proliferation. Results and discussion: By employing RNA interference, we show that depletion of endogenous PC1 in HEK293 cells leads to an increase in serum-induced Ca2+ oscillations, triggering nuclear factor of activated T cell activation and leading to cell cycle progression. Consistently, Ca2+ oscillations and cell proliferation are increased in PC1-mutated kidney cystic cell lines, but both abnormal features are reduced in cells that exogenously express PC1. Notably, blockers of the NCCE pathway, but not of the CCE, blunt abnormal oscillation and cell proliferation. Our study therefore provides the first demonstration that PC1 modulates Ca2+ oscillations and a molecular mechanism to explain the association between abnormal Ca2+ homeostasis and cell proliferation in autosomal dominant polycystic kidney disease

A consensus panel review of central nervous system effects of the exposure to low-intensity extremely low-frequency magnetic fields

BACKGROUND: A large number of studies explored the biological effects of extremely low-frequency (0-300 Hz) magnetic fields (ELF-MFs) on nervous system both at cellular and at system level in the intact human brain reporting several functional changes. However, the results of different studies are quite variable and the mechanisms of action of ELF-MFs are still poorly defined. The aim of this paper is to provide a comprehensive review of the effects of ELF-MFs on nervous system. METHODS: We convened a workgroup of researchers in the field to review and discuss the available data about the nervous system effects produced by the exposure to ELF-MFs. MAIN FINDINGS/DISCUSSION: We reviewed several methodological, experimental and clinical studies and discussed the findings in five sections. The first section analyses the devices used for ELF-MF exposure. The second section reviews the contribution of the computational methods and models for investigating the interaction between ELF-MFs and neuronal systems. The third section analyses the experimental data at cellular and tissue level showing the effects on cell membrane receptors and intracellular signaling and their correlation with neural stem cell proliferation and differentiation. The fourth section reviews the studies performed in the intact human brain evaluating the changes produced by ELF-MFs using neurophysiological and neuropsychological methods. The last section shows the limits and shortcomings of the available data, evidences the key challenges in the field and tracks directions for future research

The pandemic within the pandemic: the surge of neuropsychological disorders in Italian children during the COVID-19 era

Background: Quarantine and isolation measures during COVID-19 pandemic may have caused additional stress and challenged the mental health of the youth. Aim of the study is to investigate the COVID-19 pandemic impact on neuropsychological disorders (NPD) of Italian children and adolescents to provide general pediatric recommendations. Material and methods: A retrospective multicenter observational study was planned by the Italian Pediatric Society (SIP) to explore the impact of COVID-19 on the access of children to pediatric Emergency Departments (pED) for the evaluation of neuropsychological symptoms, collecting the classification codes of diagnoses between March 1, 2019 and March 2, 2021. The period study was split into two sub-periods: a pre COVID-19 period (from March 1 2019 to March 1, 2020) and a COVID-19 period (from March 2, 2020 to March 2, 2021). As additional information, data on NPD hospitalizations in any pediatric department of the involved centers were recorded. Results: During the study period, a total of 533,318 children were admitted to the pED involved in the study. Despite a 48.2% decline of pED admissions, there was a significant increase (83.1%) in patient admissions for NPD. The most frequent NPD conditions which increased during the COVID-19 pandemic were suicidal ideation (+ 147%), depression (+ 115%), eating disorder (+ 78.4%), and psychosis (+ 17.2%). During the pandemic period, a 39.5% increase in NPD hospitalizations was observed as well. The NPD disorders that mostly required hospitalizations were suicidal ideation (+ 134%), depression (+ 41.4%), eating disorder (+ 31.4%), and drug abuse (+ 26.7%). COVID-19 pandemic had a major impact on children's health, mainly on their NPD development. Neuropsychological assessment should be required at the primary level, in the pediatrician's office, to facilitate early capture of the sign of impairment and provide an adequate treatment. Conclusion: SIP underlines the psychological consequences of COVID 19 pandemic on the youngest and recommends an early identification of NPD in the pediatric population to avoid other serious consequences for children's physical and mental health

Study on psychoeducation enhancing results of adherence in patients with schizophrenia (SPERA-S): study protocol for a randomized controlled trial.

BACKGROUND: Poor adherence to pharmacotherapy negatively affects the course and the outcome of schizophreniaspectrum psychoses, enhancing the risk of relapse. Falloon and coworkers developed a Psychoeducation Program aimed at improving communication and problem-solving abilities in patients and their families. This study set out to evaluate changes in adherence to pharmacotherapy in patients diagnosed with schizophrenia-spectrum psychoses, by comparing one group exposed to the Falloon Psychoeducation Program (FPP) with another group exposed to family supportive therapy with generic information on the disorders. METHODS: 340 patients diagnosed with schizophrenia and related disorders according to standardized criteria from 10 participating units distributed throughout the Italian National Health System (NHS), will be enrolled with 1:1 allocation by the method of blocks of randomized permutations. Patients will be reassessed at 6, 12 and 18 months after start of treatment (duration: 6 months).The primary objective is to evaluate changes in adherence to pharmacotherapy after psychoeducation. Adherence will be assessed at three-month intervals by measuring blood levels of the primary prescribed drug using high pressure liquid chromatography, and via the Medication Adherence Questionnaire and a modified version of the Adherence Interview. Secondary objectives are changes in the frequency of relapse and readmission, as the main indicator of the course of the disorder.Enrolled patients will be allocated to the FPP (yes/no) randomly, 1:1, in a procedure controlled by the coordinating unit; codes will be masked until the conclusion of the protocol (or the occurrence of a severe negative event). The raters will be blind to treatment allocation and will be tested for blinding after treatment completion. Intention-to-treat will be applied in considering the primary and secondary outcomes. Multiple imputations will be applied to integrate the missing data. The study started recruitment in February 2013; the total duration of the study is 27 months. DISCUSSION: If the psychoeducation program proves effective in improving adherence to pharmacotherapy and in reducing relapse and readmissions, its application could be proposed as a standard adjunctive psychosocial treatment within the Italian NHS

Adenosine and lymphocyte regulation

Adenosine is a potent extracellular messenger that is produced in high concentrations under metabolically unfavourable conditions. Tissue hypoxia, consequent to a compromised cellular energy status, is followed by the enhanced breakdown of ATP leading to the release of adenosine. Through the interaction with A2 and A3 membrane receptors, adenosine is devoted to the restoration of tissue homeostasis, acting as a retaliatory metabolite. Several aspects of the immune response have to be taken into consideration and even though in general it is very important to dampen inflammation, in some circumstances, such as the case of cancer, it is also necessary to increase the activity of immune cells against pathogens. Therefore, adenosine receptors that are defined as ‘sensors–of metabolic changes in the local tissue environment may be very important targets for modulation of immune responses and drugs devoted to regulating the adenosinergic system are promising in different clinical situations

Modulation of the Akt/Ras/Raf/MEK/ERK pathway by A3 adenosine receptor

Downstream A3 receptor signalling plays an important role in the regulation of cell death and proliferation. Therefore, it is important to determine the molecular pathways involved through A3 receptor stimulation. The phosphatidylinositide-3-OH kinase (PI3K)/Akt and the Raf/mitogen-activated protein kinase (MAPK/ERK) kinase (MEK)/mitogen-activated protein kinase (MAPK) pathways have central roles in the regulation of cell survival and proliferation. The crosstalk between these two pathways has also been investigated. The focus of this review centres on downstream mediators of A3 adenosine receptor signalling

Alexithymia in juvenile primary headache sufferers: a pilot study

Starting in the 1990s, there has been accumulating evidence of alexithymic characteristics in adult patients with primary headache. Little research has been conducted, however, on the relationship between alexithymia and primary headache in developmental age. In their research on alexithymia in the formative years, the authors identified one of the most promising prospects for research, as discussed here. The aim of this study was to verify whether there is: (a) a link between tension-type headache and alexithymia in childhood and early adolescence; and (b) a correlation between alexithymia in children/preadolescents and their mothers. This study was based on an experimental group of 32 patients (26 females and 6 males, aged from 8 to 15 years, mean 11.2 ± 2.0) suffering from tension-type headache and 32 control subjects (26 females and 6 males, aged from 8 to 15 years, mean 11.8 ± 1.6). Tension-type headache was diagnosed by applying the International Headache Classification (ICHD-II, 2004). The alexithymic construct was measured using an Italian version of the Alexithymia Questionnaire for Children in the case of the juvenile patients and the Toronto Alexithymia Scale (TAS-20) for their mothers. Higher rates of alexithymia were observed in the children/preadolescents in the experimental group (EG) than in the control group; in the EG there was no significant correlation between the alexithymia rates in the children/preadolescents and in their mothers