Evaluation of early stage human bone marrow stromal proliferation, cell migration and osteogenic differentiation on μ-MIM structured stainless steel surfaces

It is well established that surface topography greatly affect cell—surface interactions. In a recent study we showed that microstructured stainless steel surfaces characterized by the presence of defined hexagonally arranged hemisphere-like structures significantly affected cell architecture (shape and focal adhesion size) of primary human bone mesenchymal stromal cells. This study aimed at further investigating the influence these microstructures (microcline protruding hemispheres) on critical aspects of cell behaviour namely; proliferation, migration and osteogenic differentiation. As with previously reported data, we used primary human bone mesenchymal stromal cells to investigate such effects at an early stage in vitro. Cells of different patients were utilised for cell migration studies. Our data showed that an increase in cell proliferation was exhibited as a function of surface topography (hemispheres). Cell migration velocity also varied as a function of surface topography on patient specific basis and seems to relate to the differentiated state of the seeded cell population (as demonstrated by bALP positivity). Osteogenic differentiation, however, did not exhibit significant variations (both up and down-regulation) as a function of both surface topography and time in cultur

Age at Menarche (MA) in chronic diseases: celiac disease (CD), insulin-dependent diabetes (T1DM) and growth hormone deficiency (GHD).

Background: MA is an important indicator of physiological development in women and MA delayed was been associated with chronic illness. Objective: to investigate predictors and factors at diagnosis that influence MA in chronic diseases. Methods: A cohort of 391 Italian girls aged 11-24 years with chronic illness was assessed. 245 girls (107 with T1DM, 75 with CD, 12 with both T1DM and CD, 51 with GDH) were included. We investigate their anthropometric data, metabolic status, diagnosis parameters, presence of irregular menses and we compared their MA with healthy italian girls MA. Results: mean MA for all girls included is 12.7 \ub1 1.2 years. MA in different groups was: 12.52 years for girls with T1DM, 12.27 years for girls with CD, 13.52 years in girls with both T1DM and CD, 13.38 years in girls with GHD. In T1DM group a strong positive correlation is also found between menarcheal glycated hemoglobin (HbA1c) and mean HbA1c (p<0.0001, R 0.54). 36.2% of patients with T1DM or CD or both present menses abnormalities. Girls with irregular menses showed MA significantly delayed than girls with regular cycles. Conclusions: No differences in MA were observed in Italian girls with CD and T1DM compared to Italian healthy population. Instead patients with GHD and girls with both CD and T1DM showed delayed MA compared to healthy population and to girls with only CD or T1DM. Our data on menarcheal HbA1c and mean HbA1c showed that achieve a good metabolic status can let girls with T1DM reach pubertal stages as healthy peers. Data about menses abnormalities probably show that chronic diseases can predispose young adult age menses abnormalities as delayed puberty although it remains to understand the pathophysiological mechanism

A Mindfulness-Based App Intervention for Pregnant Women: Protocol for a Pilot Feasibility Study

Background: Pregnancy is a complex time characterised by major transformations in the woman, which impact her physical, mental, and social well-being. How a woman adapts to these changes can affect her quality of life and psychological well-being. Indeed, the literature reports how pregnant women experience various psychological symptoms, the most frequent and common of which are symptoms of anxiety, stress, and/or depression. Indeed, promoting a healthy lifestyle focused on a woman's psychological well-being is crucial. Recently developed digital solutions have assumed a crucial role in supporting psychological well-being in physiologically pregnant women. Therefore, the development and implementation of digital solutions, such as a virtual coach implemented in a smartphone, as a support for the psychological well-being of pregnant women who do not present psychological/psychiatric disorders becomes evident. Objective: Our objective was to assess a mindfulness-based mobile app's feasibility, acceptability, and utility. The primary objective of the present research is to explore the feasibility of using a virtual coach, Maia, developed within the Trec Mamma app to promote women's psychological well-being during pregnancy through a psychoeducational module based on mindfulness. Finally, through the delivery of this module, the level of psychological well-being will be explored as a secondary objective. Methods: The present research is a proof-of-concept study in which a small sample is sufficient to achieve the intended purposes (N=50). Recruitment will occur within the group of pregnant women belonging to the Pregnancy Care Services of the Trento APSS, and the sampling will be convenience sampling. Maia will interact with women for eight weeks, starting from weeks 24/26 of pregnancy. Specifically, there are two sessions per week, which the woman can choose to allow more flexibility towards her needs. Expected results: The psychoeducational pathway is hoped to lead to significant results in terms of usability and engagement in interaction with Maia by women. In addition, there is expected to be an increase in psychological well-being and quality of life. The analysis of the data collected in the present study will be mainly descriptive, oriented toward assessing the achievement of the study objectives. Conclusions: Literature has shown that women during the perinatal period preferred online support, suggesting that implementing digital interventions can overcome barriers to social stigma and asking for help. Maia can be a valuable resource for regular psycho-educational support for women during pregnancy

Clinical performance indicators for monitoring the management of cutaneous melanoma: a population-based perspective

The prognosis of cutaneous malignant melanoma (CMM) is based on disease progression. The highly heterogeneous clinical-pathological characteristics of CMM necessitate standardized diagnostic and therapeutic interventions tailored to cancer's stage. This study utilizes clinical performance indicators to assess the quality of CMM care in Veneto (Northeast Italy). This population-based study focuses on all incidences of CMMs registered by the Veneto Cancer Registry in 2015 (1279 patients) and 2017 (1368 patients). An interdisciplinary panel of experts formulated a set of quality-monitoring indicators for diagnostic, therapeutic, and end-of-life clinical interventions for CMM. The quality of clinical care for patients was assessed by comparing the reference thresholds established by experts to the actual values obtained in clinical practice. The prevalence of stage I-CMM decreased significantly from 2015 to 2017 (from 71.8 to 62.4%; P &lt; 0.001), and almost all the pathology reports mentioned the number of nodes dissected during a lymphadenectomy. More than 90% of advanced CMMs were promptly tested for molecular BRAF status, but the proportion of patients given targeted therapies fell short of the desired threshold (61.1%). The proportion of stage I-IIA CMM patients who inappropriately underwent computerized tomography/MRI/PET dropped from 17.4 to 3.3% ( P &lt; 0.001). Less than 2% of patients received medical or surgical anticancer therapies in the month preceding their death. In the investigated regional context, CMM care exhibited both strengths and weaknesses. The evaluated clinical indicators shed essential insight on the clinical procedures requiring corrective action. It is crucial to monitor clinical care indicators to improve care for cancer patients and promote the sustainability of the healthcare system

Inconclusive chromosomal assessment after blastocyst biopsy: prevalence, causative factors and outcomes after re-biopsy and re-vitrification. A multicenter experience

Study question: Can a second round of biopsy, vitrification and chromosomal testing provide a valid diagnosis where the first attempt fails? Summary answer: The risk of inconclusive chromosomal-assessment after trophectoderm biopsy was 2.5% but a further biopsy and vitrification-warming appeared not to impair the competence of euploid blastocysts. What is known already: The increasing implementation of multicell trophectoderm biopsy has significantly reduced the risk of inconclusive diagnosis after preimplantation-genetic-testing (PGT). Yet, few reports have defined the variables that influence the risk of failure or described the technical and clinical outcomes after re-biopsy. Study design, size, duration: Retrospective multicenter study involving 8990 blastocyst biopsies conducted between April 2013 and September 2017 at six IVF centers but analyzed at a single genetic laboratory. A total of 206 blastocysts were successfully re-biopsied after warming and re-expansion, then re-vitrified. And 49 of these blastocysts were diagnosed euploid and used in single-embryo-transfers (SETs). Logistic regression analyses were conducted. Participants/materials, setting, methods: A total of 3244 PGT-for-aneuploidies (PGT-A) cycles with a freeze-all approach, vitrification and qPCR-based analysis were performed by 2687 consenting couples. DNA amplification failure (AF) or non-concurrent data resulted in inconclusive diagnoses. In case of DNA amplification, the cellularity of the biopsy was estimated according to a previously validated method. Euploid SETs were performed. Clinical pregnancy, miscarriage, live birth rates (LBR) and perinatal outcomes were monitored. Main results and the role of chance: Overall, 2.5% of trophectoderm biopsies resulted in an inconclusive diagnosis (N = 228/8990). Specifically, 2% (N = 176/8990) resulted in AF and 0.5% (N = 52/8990) in non-concurrent results. The only parameters significantly associated with inconclusive diagnoses were the IVF center and the embryo age (days) at biopsy. Among samples with successful amplification, the number of cells in the biopsy and the day of biopsy were critical to limit non-concurrent results. In total, 213 blastocysts with an inconclusive diagnosis were warmed for re-analysis and the survival rate was 96.7% (N = 206/213). The euploidy rate in blastocysts biopsied twice was 51.9% (N = 107/206) and the euploid embryos were re-vitrified. Overall, 49 euploid embryos were warmed for replacement and all survived. The LBR after SET was 38.8% (N = 19/49). No minor/major obstetrical/perinatal complication was reported. Limitations, reasons for caution: A single aneuploidy-testing method was adopted in this retrospective analysis. A more powered report of the clinical and obstetrical/perinatal outcomes after re-biopsied and re-vitrified blastocysts euploid SET requires a larger sample size. Wider implications of the findings: It is important to re-biopsy and re-vitrify undiagnosed blastocysts since healthy live births can result from them. Study funding/competing interest(s): None. Trial registration number: None

Molecular Characterization of Pancreatic Ductal Adenocarcinoma Using a Next-Generation Sequencing Custom-Designed Multigene Panel

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence compared with KRAS wild-type tumors. Intriguingly, KRAS wild-type cases had a better short-term prognosis despite the lymph node status. In conclusion, our work highlights that the combination of KRAS mutation with the age of the patient and the lymph node status may help in predicting the outcome in PDAC patients

Indicators of clinical performance in monitoring soft tissue sarcoma management: a population-based perspective

Background: Soft tissue sarcomas (STS) are rare malignancies which prognosis varies significantly by primary site, histological subtype, and tumor stage. Their low incidence, and the complexity of their clinico-pathological characteristics demand standardized, cancer-tailored diagnostics and therapies managed at high-volume, multidisciplinary care centers. This study evaluates the quality of STS management in north-east Italy (Veneto Region) through a list of ad hoc defined clinical indicators. Methods: This population-based study concerns all incident cases of STS in 2018 (214 cases) recorded in the adult population censored by the Veneto's regional Cancer Registry. Based on the international literature, a multidisciplinary working group of experts identified a set of indicators for monitoring the quality of diagnostic, therapeutic, and end-of-life clinical interventions. The quality of care was assessed by comparing the reference thresholds with the indicators' values achieved in clinical practice. Results: Diagnostic procedures showed poor adherence to the thresholds, with a low percentage of histological diagnoses validated by a second opinion. The indicators relating to the surgical treatment of superficial, small, low-grade STS, or of medium, high-grade STS of the head-neck, trunk, or limbs were consistent with the thresholds, while for intermediate, high-grade (large-sized, deep) and retroperitoneal STS they fell significantly below the thresholds. Conclusion: A critical evaluation of the clinical indicators allowed to uncover the procedures needing corrective action. Monitoring clinical care indicators improves cancer care, confirms the importance of managing rare cancers at highly specialized, high-volume centers, and promotes the ethical sustainability of the healthcare system