Experiences of patients with Poland syndrome of diagnosis and care in Italy: A pilot survey

Background: Poland Syndrome (PS) is a rare congenital malformation involving functional and aesthetic impairments. Early diagnosis and timely therapeutic approaches play an important role in improving the quality of life of patients and kindred. This study aims to explore healthcare experiences of the diagnosis of patients affected by PS and to investigate the factors associated with diagnostic delay in Italy. Results: Seventy-two patients affected by PS were asked to fill in a self-administered questionnaire on: a) diagnostic path; b) perceived quality of care received after diagnosis; c) knowledge of the rights and the socio-economic hardships related to their disease; d) evaluation of the integration of various professional skills involved in the diagnostic and therapeutic approach; e) perception of the social support provided by the Italian Association of Poland Syndrome (AISP). The average age at diagnosis was around 14 years; diagnosis was made at birth in only 31.58% of cases. Although typical symptomatology had appeared on average at an early age (4 months), only 23 patients (40.35%) received an early diagnosis (within the first year of life). Just over half of the patients (n = 30) were diagnosed in their region of origin, while 27 were diagnosed elsewhere. Furthermore, 12.28% were self-diagnoses. Among the patients who were diagnosed outside their region, 15 (88.24%) stated they had foregone some visits or treatments owing to costs and/or organizational issues. Conclusions: An analysis of the patients' experiences highlights several gaps and a lack of homogeneity in the diagnostic and therapeutic follow-up of PS patients in Italy. A specific national diagnostic and therapeutic path is essential to guarantee patients complete and appropriate health services, compliant with the ethical principles of non-discrimination, justice and empathy. Implementation of an effective information and research network and empowerment of patients' associations are necessary conditions to encourage clinical collaboration and improve the quality of life of people living with rare diseases

Giving meaning to alternative methods to animal testing

The 3 rd edition of the advanced theoretical-training course \u201c Giving meaning to alternative methods to animal testing \u201d was held in Genoa on July 6-7, 2017. The theoretical modules included talks by specialists from companies engaged in the field of advanced in vitro technologies, who offered participants the possibility to try out their technologies in the training modules

Relationship between Breast Cancer Surgical Treatment and Psychiatric Symptomatology: Which Sociodemographic and Clinical Factors Could Influence It? A Preliminary Study

This study aimed to investigate psychiatric symptomatology in a sample of patients affected by breast cancer undergoing surgery, evaluating the potential mediators on perceived stress levels, depression and hopelessness. The study was conducted on eighty-five patients with breast cancer, admitted consecutively to the Breast Unit of the IRCCS Ospedale Policlinico San Martino, between May 2018 and December 2019. Sociodemographic (age of diagnosis, gender, marital and occupational status, educational level, having children) and clinical (type and side of surgery, previous breast surgery, neoadjuvant chemotherapy and axillary dissection) characteristics were investigated through a semi-structured interview. The following rating scales were administered: Beck Depression Inventory, Beck Hopelessness Scale, and Perceived Stress Scale. Our findings indicate that the presence of children and of a partner was associated with a lower total score on the clinical dimensions evaluated. Furthermore, we found demolitive surgery to be a mediator between perceived stress and hopelessness, while history of previous breast surgery was found to be a mediator between demolitive surgery and perceived stress. In conclusion, patients affected by breast cancer undergoing more complex and demolitive surgery or with history of previous breast surgery should be mostly monitored from a psychological and psychiatric point of view from the beginning of treatments to evaluate the first manifestations of psychiatric symptomatology

The PRRT2 knockout mouse recapitulates the neurological diseases associated with PRRT2 mutations.

Heterozygous and rare homozygous mutations in PRoline-Rich Transmembrane protein 2 (PRRT2) underlie a group of paroxysmal disorders including epilepsy, kinesigenic dyskinesia episodic ataxia and migraine. Most of the mutations lead to impaired PRRT2 expression and/or function. Recently, an important role for PRTT2 in the neurotransmitter release machinery, brain development and synapse formation has been uncovered. In this work, we have characterized the phenotype of a mouse in which the PRRT2 gene has been constitutively inactivated (PRRT2 KO)beta-galactosidase staining allowed to map the regional expression of PRRT2 that was more intense in the cerebellum, hindbrain and spinal cord, while it was localized to restricted areas in the fore-brain. PRRT2 KO mice are normal at birth, but display paroxysmal movements at the onset of locomotion that persist in the adulthood. In addition, adult PRRT2 KO mice present abnormal motor behaviors characterized by wild running and jumping in response to audiogenic stimuli that are ineffective in wild type mice and an increased sensitivity to the convulsive effects of pentylentetrazol. Patch-clamp electrophysiology in hippocampal and cerebellar slices revealed specific effects in the cerebellum, where PRRT2 is highly expressed, consisting in a higher excitatory strength at parallel fiber-Purkinje cell synapses during high frequency stimulation. The results show that the PRRT2 KO mouse reproduces the motor paroxysms present in the human PRRT2-linked pathology and can be proposed as an experimental model for the study of the pathogenesis of the disease as well as for testing personalized therapeutic approaches

Metformin and Everolimus: A Promising Combination for Neuroendocrine Tumors Treatment

Introduction: Treatment options for neuroendocrine tumors (NETs) are rarely curative, as NETs frequently show resistance to medical therapy. The use of everolimus, an mTOR inhibitor, is limited by the development of resistance, probably due to the activation of Akt signaling. In this context, the antidiabetic drug metformin is able to inhibit mTOR, providing a rationale for the use of metformin and everolimus in combination. Methods: We investigated the effects of the metformin and everolimus combination on NET cell proliferation, apoptosis, colony formation, cell viability, NET spheroids growth and the involvement of the Akt and mTOR pathways, and also developed everolimus-resistant NET cells to further study this combination. Results: Metformin and everolimus in combination are more effective than monotherapy in inhibiting pancreatic NET (PAN-NET) cell proliferation (-71% \ub1 13%, p < 0.0001 vs. basal), whereas no additive effects were observed on pulmonary neuroendocrine tumor (PNT) cell proliferation. The combinatorial treatment is more effective than monotherapy in inhibiting colony formation, cell viability, NET spheroids growth rate and mTOR phosphorylation in both NET cell lines. In a PAN-NET cell line, metformin did not affect Akt phosphorylation; conversely, it significantly decreased Akt phosphorylation in a PNT cell line. Using everolimus-resistant NET cells, we confirmed that metformin maintained its effects, acting by two different pathways: Akt-dependent or independent, depending on the cell type, with both leading to mTOR suppression. Conclusions: Considering the promising effects of the everolimus and metformin combination in NET cells, our results provide a rationale for its use in NET patients

The impact of COVID-19 pandemic on breast surgery in Italy: a multi-centric retrospective observational study

COVID-19 pandemic had an impact on surgical activities. The aim of this multi-centric, retrospective study was to evaluate the impact of the COVID-19 pandemic on breast surgery. The patients who operated during the pre-pandemic year 2019 were compared to those operated in 2020. Fourteen Breast Care Units provided data on breast surgical procedures performed in 2020 and 2019: total number of breast-conserving surgery (BCS), number of 1st level oncoplastic breast surgery (OBS), number of 2nd level OBS; total number of mastectomies, mastectomies without reconstruction, mastectomies with a tissue expander, mastectomies with direct to implant (DTI) reconstruction, mastectomies with immediate flap reconstruction; total number of delayed reconstructions, number of expanders to implant reconstructions, number of delayed flap reconstructions. Overall 20.684 patients were included: 10.850 (52.5%) operated during 2019, and 9.834 (47.5%) during 2020. The overall number of breast oncologic surgical procedures in all centers in 2020 was 8.509, compared to 9.383 in 2019 (- 9%). BCS decreased by 744 cases (- 13%), the overall number of mastectomies decreased by 130 cases (- 3.5%); mastectomy-BCS ratio was 39-61% in 2019, and 42-58% in 2020. Regarding immediate reconstructive procedures mastectomies with DTI reconstruction increased by 166 cases (+ 15%) and mastectomies with immediate expander reconstruction decreased by 297 cases (- 20%). Breast-delayed reconstructive procedures in all centers in 2020 were 142 less than in 2019 (- 10%). The outburst of the COVID-19 pandemic in 2020 determined an implemented number of mastectomies compared to BCS, an implemented number of immediate breast reconstructions, mainly DTI, and a reduction of expander reconstruction

Pharmacokinetics and pharmacogenetics of SSRIs during pregnancy : An observational study

Background: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. Methods: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses. Results: Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway. Conclusions: Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn

Multicore liquid perfluorocarbon-loaded multimodal nanoparticles for stable ultrasound and ¹⁹ F MRI applied to in vivo cell tracking

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative 19 F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core–shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with 19 F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging. </p

Emergent Functional Properties of Neuronal Networks with Controlled Topology

The interplay between anatomical connectivity and dynamics in neural networks plays a key role in the functional properties of the brain and in the associated connectivity changes induced by neural diseases. However, a detailed experimental investigation of this interplay at both cellular and population scales in the living brain is limited by accessibility. Alternatively, to investigate the basic operational principles with morphological, electrophysiological and computational methods, the activity emerging from large in vitro networks of primary neurons organized with imposed topologies can be studied. Here, we validated the use of a new bio-printing approach, which effectively maintains the topology of hippocampal cultures in vitro and investigated, by patch-clamp and MEA electrophysiology, the emerging functional properties of these grid-confined networks. In spite of differences in the organization of physical connectivity, our bio-patterned grid networks retained the key properties of synaptic transmission, short-term plasticity and overall network activity with respect to random networks. Interestingly, the imposed grid topology resulted in a reinforcement of functional connections along orthogonal directions, shorter connectivity links and a greatly increased spiking probability in response to focal stimulation. These results clearly demonstrate that reliable functional studies can nowadays be performed on large neuronal networks in the presence of sustained changes in the physical network connectivity