Dual effect of Thymosin α 1 on human monocyte-derived dendritic cellin vitrostimulated with viral and bacterial toll-like receptor agonists

OBJECTIVES: Thymosin α 1 (Tα1) recently gained interest as immune adjuvant for vaccines because of its ability to modulate the T-cell/dendritic cell (DC) axis and to improve antibody production. The objective of this study was to determine whether Tα1 would address in vitro the response of human primary monocyte-derived DC, crucial regulators of vaccine-induced immunity, upon exposure to different toll-like receptor (TLR) agonists or infection with viruses or bacteria. METHODS: DC maturation and production of pro-inflammatory cytokines were analyzed. RESULTS: Our data revealed a dual effect of Tα1 on DC biology upon viral or bacterial stimulation. Interestingly, Tα1 enhanced human leukocyte antigen (HLA)-I and II surface expression and secretion of IL-6, TNF-α and IL-8 when DCs were treated with viral TLR3 and TLR7/8 agonists. Similarly, in pandemic H1N1 influenza A-infected DCs, Tα1 raised the expression of maturation markers and type I and III Interferon (IFN). In contrast, following bacterial TLR2 and 4 stimulation, as well as upon Bacillus Calmette-Guerin infection, the presence of Tα1 in DC cultures drastically lowered the analyzed cellular parameters. CONCLUSION: The knowledge that Tα1 pleiotropic effect might ameliorate anti-viral immune responses and, at the same time, dampen inflammation caused by bacterial infections could lay the groundwork for a more appropriate therapeutic application of this molecule

Demand side management analysis of a supermarket integrated HVAC, refrigeration and water loop heat pump system

Supermarkets are intensive energy consumers because of a high electricity demand, mainly due to refrigeration utilities. Thus, in this work a supermarket integrated HVAC, refrigeration and water loop heat pump (WLHP) system was analyzed according to a demand side management approach, adopting a demand response strategy coupled with real-time pricing predictive rule based controls. The system was modeled with TRNSYS and several DR strategies were applied to both the space heating/cooling and the WLHP to determine the plant configuration with the most effective electricity cost saving. It was found that two setups guarantee the highest economic savings. The first consists of a predictive rule based control applied to the space heating/cooling only, which is basically inexpensive and allows an annual cost saving of 4.06% respect to the baseline configuration. The second, instead, combines predictive rule based controls applied to both the space heating/cooling and the WLHP auxiliary heater, and shows the best performance with the adoption of a 200\u202fm3 water-based thermal energy storage. Respect to the baseline, this configuration provides an annual cost saving of 4.67%

Can partial splenectomy preserve humoral immunity in pediatric patients? Risks and benefts of partial splenectomy

Te spleen plays an important role in removing normal and abnormal cells from the blood and in providing an immunologic response to encapsulated bacteria. Surgical splenectomy provides efective treatment for several pediatric disorders, such as congenital and acquired hemolytic anemias, abdominal traumas and immunological and metabolic disorders, but it is associated with an immediate and lifelong risk of overwhelming infection. An alternative to conventional splenectomy is partial splenectomy, recommended especially in children younger than 5 years of age. Recommendations for the prevention of overwhelming post-total splenectomy infection include: Pneumococcal, Haemophilus infuenzae type B and Meningococcal immunizations, antimicrobial prophylaxis and prompt antibiotic treatment of acute febrile illness; conversely, there is no clear evidence indicating which prevention measures are to be performed in patients undergoing partial splenectomy

Shwachman Diamond Syndrome: an emergency challenge

Shwachman Diamond Syndrome is a rare congenital disorder characterized by pancreatic insufficiency, bone marrow dysfunction and skeletal abnormalities. No specific test is available for a definitive diagnosis for SDS. In the presence of clinical features of SDS, pancreatic insufficiency should be tested for or lipomatosis radiologically demonstrated. New directions might be found in genetic analysis. Sometimes, a life-threatening event may be the first clinical manifestation of the syndrome

Shwachman Diamond Syndrome: an emergency challenge

Shwachman Diamond Syndrome is a rare congenital disorder characterized by pancreatic insufficiency, bone marrow dysfunction and skeletal abnormalities. No specific test is available for a definitive diagnosis for SDS. In the presence of clinical features of SDS, pancreatic insufficiency should be tested for or lipomatosis radiologically demonstrated. New directions might be found in genetic analysis. Sometimes, a life-threatening event may be the first clinical manifestation of the syndrome

Treatment and Long-Term Sequelae in Childhood Brain Tumors

In children treated for brain tumors, important deficits in cognitive development have been described. The reduction of Intelligence Quotient (IQ) is correlated with multiple conditions such as tumor location, obstructive hydrocephalus, surgical intervention, and above all, the use of radiotherapy, especially in young children. Demyelinization represents the most striking microscopic alteration following radiation: cerebral white matter's loss and failure to white matter development could partly account for changes in IQ score.Recently, combined chemo-radiotherapeutic approaches and the improvement of radiotherapy techniques have enabled the reduction of neurocognitive symptoms and improved the standard of life of childhood brain tumor survivors

Epstein-Barr virus persistence and infection of autoreactive plasma cells in synovial lymphoid structures in rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased Epstein-Barr virus (EBV) blood DNA load, a robust immune response to EBV and cross-reactive circulating antibodies to viral and self-antigens. However, the role of EBV in RA pathogenesis remains elusive. Here, we investigated the relationship between synovial EBV infection, ectopic lymphoid structures (ELS) and immunity to citrullinated self and EBV proteins. METHODS: Latent and lytic EBV infection was investigated in 43 RA synovial tissues characterised for presence/absence of ELS and in 11 control osteoarthritis synovia using RT-PCR, in situ hybridisation and immunohistochemistry. Synovial production of anti-citrullinated protein (ACPA) and anti-citrullinated EBV peptide (VCP1/VCP2) antibodies was investigated in situ and in vivo in the severe combined immunodeficiency (SCID)/RA chimeric model. RESULTS: EBV dysregulation was observed exclusively in ELS+ RA but not osteoarthritis (OA) synovia, as revealed by presence of EBV latent (LMP2A, EBV-encoded small RNA (EBER)) transcripts, EBER+ cells and immunoreactivity for EBV latent (LMP1, LMP2A) and lytic (BFRF1) antigens in ELS-associated B cells and plasma cells, respectively. Importantly, a large proportion of ACPA-producing plasma cells surrounding synovial germinal centres were infected with EBV. Furthermore, ELS-containing RA synovia transplanted into SCID mice supported production of ACPA and anti-VCP1/VCP2 antibodies. Analysis of CD4+ and CD8+ T-cell localisation and granzyme B expression suggests that EBV persistence in ELS-containing synovia may be favoured by exclusion of CD8+ T cells from B-cell follicles and impaired CD8-mediated cytotoxicity. CONCLUSIONS: We demonstrated active EBV infection within ELS in the RA synovium in association with local differentiation of ACPA-reactive B cells

Radiotherapy in the COVID-19 Pandemic Era

Background/Aim: In 2020, because of coronavirus pandemic, medical activities changed. The aim of this report is to compare the volumes of Pisa radiotherapy activities from March 9th to May 31st, 2020, with the same period in 2019. Patients and Methods: We analyzed the activity of our Unit to evaluate how logistics changes, related to the COVID-19 epidemic, impacted on volumes of radiotherapy (RT) activity and on the number of cases of COVID-19 infections observed in healthcare professionals and patients. Results: The total number of first-time visits between March-May 2020 was reduced by 18%, probably due to delays in diagnosis and histological tests as well as the temporary closure of the operating rooms. None of the healthcare professionals and only two patients contracted the infection. Conclusion: We were able to treat all patients referred to our hospital and we were able to reduce risk of infection for both our patients and healthcare staff, guaranteeing continuum of care for our oncological patien

Aplastic anaemia in childhood. Description of two cases and review of the literature

AbstractChildhood aplastic anaemia (AA) is an uncommon but potentially fatal haematological disorder. Patients with AA receive supportive care based on transfusions and timely treatment of opportunistic infections, along with specific therapies, which may be bone marrow transplantation and immunosuppressive therapy. Early diagnosis and supportive therapy are required to prevent fatal complications like overwhelming sepsis or life threatening haemorrhages. We report two cases of aplastic anaemia having a different aetiology. The diagnostic work-up and the therapeutic management for each case are described below

The impact of cognitive function deficits and their recovery on functional outcome in subjects affected by ischemic subacute stroke: results from the Italian multicenter longitudinal study CogniReMo

Background: The recovery of independence in activities of daily living is a fundamental goal of rehabilitation programs in subjects affected by subacute stroke. Rehabilitation is focused both on motor and cognitive aspects, and some evidence has reported cognitive deficits as prognostic factors of motor recovery. However, rehabilitation is a dynamic process during which executive functions and motor functions should be improved. Aim: The aim of the study is to evaluate the relationships between impairments in cognitive functions and recovery of functional independence in stroke patients during the subacute phase. Design: Multicenter observational study. Setting: Intensive rehabilitation units. Population: A sample of 319 stroke patients in subacute phase (70.6±11.6 years, 40.4% females), consecutively admitted from November 2019 to July 2021 at sixteen rehabilitation centers were enrolled in this observational, prospective and multicentric study with longitudinal assessments. Methods: Cognitive and functional assessments were performed at hospital admission and discharge, including Oxford Cognitive Screen, modified Barthel Index, Functional Independent Measure, Fugl-Meyer assessment scale and National Institutes of Health Stroke Scale. Results: A regression analysis identified five predictors (out of about 200 tested variables) of functional recovery related to four aspects assessed at admission: functional status (P<0.001), lower limb functioning (P=0.002), attention (P=0.011), and executive functions (P=0.017). Furthermore, patients who recovered deficits in executive functions had the same recovery of those without deficits, whereas those who maintained deficits had a smaller recovery (P=0.019). Conclusions: The relationship between cognitive and motor deficits is increasingly highlighted and the recovery of executive functions deficits seems to contribute to motor recovery. Clinical rehabilitation impact: Our results suggest that the recovery of executive functions may promote the recovery of the functional outcome of the patient with subacute stroke. Future treatment protocols may benefit from paying more attention to the recovery of executive functions