Miniaturized and High-Throughput Assays for Analysis of T-Cell Immunity Specific for Opportunistic Pathogens and HIV

Monitoring of antigen-specific T-cell responses is valuable in numerous conditions that include infectious diseases, vaccinations, and opportunistic infections associated with acquired or congenital immune defects. A variety of assays that make use of peripheral lymphocytes to test activation markers, T-cell receptor expression, or functional responses are currently available. The last group of assays calls for large numbers of functional lymphocytes. The number of cells increases with the number of antigens to be tested. Consequently, cells may be the limiting factor, particularly in lymphopenic subjects and in children, the groups that more often require immune monitoring. We have developed immunochemical assays that measure secreted cytokines in the same wells in which peripheral blood mononuclear cells (PBMC) are cultured. This procedure lent itself to miniaturization and automation. Lymphoproliferation and the enzyme-linked immunosorbent spot (ELISPOT) assay have been adapted to a miniaturized format. Here we provide examples of immune profiles and describe a comparison between miniaturized assays based on cytokine secretion or proliferation. We also demonstrate that these assays are convenient for use in testing antigen specificity in established T-cell lines, in addition to analysis of PBMC. In summary, the applicabilities of miniaturization to save cells and reagents and of automation to save time and increase accuracy were demonstrated in this study using different methodological approaches valuable in the clinical immunology laboratory

Effectiveness of Home_Positivity: A VR Program for Promoting Positive Mental Health. A Pilot Feasibility Study

Virtual reality (VR) has been recently used for the treatment of mental health conditions. While research shows symptom reduction, further investigation is required to ascertain the impact of VR on well-being indicators. This pilot study aims to assess the effectiveness of a new VR software, H.O.M.E (How to Observe and Modify Emotion)_Positivity, in promoting positive mental health, which implies addressing both psychological distress and well-being. A sample of 16 healthy college students participated in a six-session intervention involving individual interviews and VR experiences using H.O.M.E delivered at the university of Bologna. They were assessed before and after intervention and at 3-month follow-up with indicators of negative symptoms (i.e., Depression Anxiety Stress Scales (DASS) and the Negative affect scale of (PANAS) and of well-being (i.e., Mental Health Continuum (MHC) and the Positive Affect (PA) subscale of the PANAS. Moreover, they were asked to report their satisfaction and comments on the experience of the VR software. Following the intervention, participants reported significantly lower scores at DASS and higher scores at MHC and PA. In contrast, NA subscale score did not change significantly after the intervention or at three months follow-up. The results provide support to the use of H.O.M.E_Positivity for the promotion of positive mental health. Participants reported a reduction of psychological distress and improvement in well-being, and they were all highly satisfied and engaged while using the VR software. These findings indicate the potential value of this intervention, particularly in an increasingly digital society

Optical and structural properties of sol-gel derived materials embedded in porous anodic alumina

Structure composing a xerogel, doped with lanthanide ions (erbium, terbium and europium), embedded in porous anodic alumina (PAA) have been fabricated and their optical and electrical characterisitics have been studied. Erbium photoluminescence at 1.53 µm from titania xerogel/PAA was found to increase with the number of xerogel layers and erbium concnetration for the excitation wavelength 532 nm, matching the area of transparency of both titania xerogel and PAA. Visible green and red electroluminescence was observed for terbium- and europium-doped IN2O3 and SnO2 xerogels embedded in porous anodic alumina. The improvement of the electrical properties of the xerogel/PAA cell is discussed, taking into account the observed ability of conducting In2O3:Sn (ITO) nanoparticles to penetrate into the anodic alumina pores

Positive mental health, depression and burnout in healthcare workers during the second wave of COVID-19 pandemic

What is known on the subject?: In the past 2 years, the COVID-19 pandemic had a robust negative impact on the mental health of healthcare providers, with increasing rates of depression, anxiety, acute stress and burnout. Healthcare workers experiencing poor mental health are reluctant to seek help and treatment because they are afraid of being stigmatized and excluded by their colleagues and employers. During the pandemic positive emotions, resilience and psychological well-being buffered distress and burnout in healthcare workers. What this paper adds to existing knowledge?: This paper describes positive mental health, depression, anxiety and burnout in healthcare workers during the second wave of the pandemic. Forty-eight per cent of healthcare workers were flourishing (high levels of positive emotions and well-being), 10% languishing (absence of well-being and positivity). Flourishing individuals reported lower levels of depression, anxiety and burnout. These findings documented a relevant number of resilient healthcare workers, who restored/maintained their well-being also under stressful conditions. Vulnerable healthcare workers were less than 20%, and they reported severe anxiety, depression and burnout. No differences emerged between languishing and moderate mental health groups in their levels of anxiety, depression and burnout. What are the implications for practice?: The condition of flourishing is the only one that provides protection from depression and anxiety and burnout, while moderate mental health does not differ substantially from the languishing state. The study confirms the importance of maintaining and/or promoting the well-being of healthcare workers. Interventions for promoting positive mental health of vulnerable workers are needed. Mental health nurses can have the skills and expertise for evaluating early symptoms of psychological distress and for implementing interventions for promoting and restoring well-being. These interventions may include informational campaign (i.e. preparing and distributing pamphlets and guidelines) and emotional support programmes (psychoeducation and training, mental health support team, peer support and counselling) that can be delivered also via digital platforms. Abstract: Introduction: Few studies focused on healthcare workers' positive mental health (i.e. high levels of psychological well-being) and its association with anxiety, depression and burnout in the second wave of the pandemic. Aims: To evaluate the protective role of well-being in buffering burnout and psychological distress. Methods: We evaluated 173 Italian healthcare workers with indicators of psychological distress (Depression Anxiety Stress Scales [DASS]-21), burnout (Copenhagen Burnout Inventory [CBI]) and positive mental health (Mental Health Continuum) and we cross-classified them according to their levels of mental health (flourishing, languishing and moderate mental health) and their levels of anxiety, depression and burnout. Results: Forty-eight per cent of health workers were classified as flourishing, 10% as languishing and 42% as moderate mental health. Flourishing individuals presented lower scores on DASS and CBI scales, whereas no differences emerged between languishing and moderate mental health groups. More than 80% of health workers with clinically significant symptoms of anxiety, depression and risk of burnout were classified as not flourishing. Discussion: This investigation documented the presence of flourishing mental health in almost half of the sample of Italian healthcare workers. However, those with moderate or languishing mental health manifested higher levels of anxiety, depression and higher risks of burnout. Implication for Practice: The study confirms the importance of maintaining and/or promoting the well-being of this population, with a crucial role of mental health nurses who can easily approach other healthcare workers and provide them informational (training, guidelines) and emotional support programmes (psychoeducation, mental health support team, peer support and counselling) when facing adverse working conditions

Exploring the Neutrinoless Double Beta Decay in the Inverted Neutrino Hierarchy with Bolometric Detectors

Neutrinoless double beta decay (0nubb) is one of the most sensitive probes for physics beyond the Standard Model, providing unique information on the nature of neutrinos. In this paper we review the status and outlook for bolometric 0nubb decay searches. We summarize recent advances in background suppression demonstrated using bolometers with simultaneous readout of heat and light signals. We simulate several configurations of a future CUORE-like bolometer array which would utilize these improvements and present the sensitivity reach of a hypothetical next-generation bolometric 0nubb experiment. We demonstrate that a bolometric experiment with the isotope mass of about 1 ton is capable of reaching the sensitivity to the effective Majorana neutrino mass (|mee|) of order 10-20 meV, thus completely exploring the so-called inverted neutrino mass hierarchy region. We highlight the main challenges and identify priorities for an R&D program addressing them.Comment: 22 pages, 15 figures, submitted to EPJ

Stomach cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

BACKGROUND: A recent Monographs Working Group of the International Agency for Research on Cancer concluded that there is limited evidence for a causal association between exposure to asbestos and stomach cancer. METHODS: We performed a meta-analysis to quantitatively evaluate this association. Random effects models were used to summarise the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. RESULTS: We identified 40 mortality cohort studies from 37 separate papers, and cancer incidence data were extracted for 15 separate cohorts from 14 papers. The overall meta-SMR for stomach cancer for total cohort was 1.15 (95% confidence interval 1.03–1.27), with heterogeneous results across studies. Statistically significant excesses were observed in North America and Australia but not in Europe, and for generic asbestos workers and insulators. Meta-SMRs were larger for cohorts reporting a SMR for lung cancer above 2 and cohort sizes below 1000. CONCLUSIONS: Our results support the conclusion by IARC that exposure to asbestos is associated with a moderate increased risk of stomach cancer

CUORE-0 results and prospects for the CUORE experiment

With 741 kg of TeO2 crystals and an excellent energy resolution of 5 keV (0.2%) at the region of interest, the CUORE (Cryogenic Underground Observatory for Rare Events) experiment aims at searching for neutrinoless double beta decay of 130Te with unprecedented sensitivity. Expected to start data taking in 2015, CUORE is currently in an advanced construction phase at LNGS. CUORE projected neutrinoless double beta decay half-life sensitivity is 1.6E26 y at 1 sigma (9.5E25 y at the 90% confidence level), in five years of live time, corresponding to an upper limit on the effective Majorana mass in the range 40-100 meV (50-130 meV). Further background rejection with auxiliary bolometric detectors could improve CUORE sensitivity and competitiveness of bolometric detectors towards a full analysis of the inverted neutrino mass hierarchy. CUORE-0 was built to test and demonstrate the performance of the upcoming CUORE experiment. It consists of a single CUORE tower (52 TeO2 bolometers of 750 g each, arranged in a 13 floor structure) constructed strictly following CUORE recipes both for materials and assembly procedures. An experiment its own, CUORE-0 is expected to reach a sensitivity to the neutrinoless double beta decay half-life of 130Te around 3E24 y in one year of live time. We present an update of the data, corresponding to an exposure of 18.1 kg y. An analysis of the background indicates that the CUORE performance goal is satisfied while the sensitivity goal is within reach.Comment: 10 pages, 3 figures, to appear in the proceedings of NEUTRINO 2014, 26th International Conference on Neutrino Physics and Astrophysics, 2-7 June 2014, held at Boston, Massachusetts, US

T-cell depleted HLA-haploidentical HSCT in a child with neuromyelitis optica

Neuromyelitis optica is an immune-mediated disease characterized by a relapsing course, resulting in progressive disability. In children, given the long life expectancy, a disease-modifying treatment could be particularly desirable. Unfortunately, the currently available treatment strategies with this potential are scarce. Very limited data are available about the use of allogeneic hematopoietic stem cell transplantation (HSCT) for autoimmune neurological diseases. In this report, we present a pediatric case successfully treated with allogeneic HSCT from an HLA-haploidentical donor, after ex vivo TCR/CD19-depletion of the graft. To the best of our knowledge, this is the first case of a pediatric patient to benefit from such a treatment

Selective Depletion of αβ T Cells and B Cells for Human Leukocyte Antigen–Haploidentical Hematopoietic Stem Cell Transplantation. A Three-Year Follow-Up of Procedure Efficiency

HLA-haploidentical family donors represent a valuable option for children requiring allogeneic hematopoietic stem cell transplantation (HSCT). Because graft-versus-host diseases (GVHD) is a major complication of HLA-haploidentical HSCT because of alloreactive T cells in the graft, different methods have been used for ex vivo T cell depletion. Removal of donor αβ T cells, the subset responsible for GVHD, and of B cells, responsible for post-transplantation lymphoproliferative disorders, have been recently developed for HLA-haploidentical HSCT. This manipulation preserves, in addition to CD34+ progenitors, natural killer, γδ T, and monocytes/dendritic cells, contributing to anti-leukemia activity and protection against infections. We analyzed depletion efficiency and cell yield in 200 procedures performed in the last 3 years at our center. Donors underwent CD34+  hematopoietic stem cell (HSC) peripheral blood mobilization with granulocyte colony–stimulating factor (G-CSF). Poor CD34+ cell mobilizers (48 of 189, 25%) received plerixafor in addition to G-CSF. Aphereses containing a median of 52.5 × 109 nucleated cells and 494 × 106 CD34+ HSC were manipulated using the CliniMACS device. In comparison to the initial product, αβ T cell depletion produced a median 4.1-log reduction (range, 3.1 to 5.5) and B cell depletion led to a median 3.4-log reduction (range, 2.0 to 4.7). Graft products contained a median of 18.5 × 106 CD34+ HSC/kg recipient body weight, with median values of residual αβ T cells and B cells of 29 × 103/kg and 33 × 103/kg, respectively. Depletion efficiency monitored at 6-month intervals demonstrated steady performance, while improved recovery of CD34+ cells was observed after the first year (P = .0005). These data indicate that αβ T cell and B cell depletion of HSC grafts from HLA-haploidentical donors was efficient and reproducible