Novel vaccination strategies based on optimal stimulation of CD4+ T helper cells for the treatment of oral squamous cell carcinoma

Oral Squamous Cell Carcinoma (OSCC) is the most common malignant tumor of the oral cavity. Despite recent advances in the field of oral cancer therapy, including the introduction of immunotherapeutic approaches, the 5-year survival rate remains steadily assessed around 50%. Thus, there is an urgent need for new therapeutic strategies. After the characterization of the immune phenotype of three human OSCC cell lines (CAL-27, SCC-25, and SCC-4) and one mouse OSCC cell line (MOC2) showing their similarities to resected patient tumors, we explored for the first time an experimental preclinical model of therapeutic vaccination with mouse OSCC MOC2 cell line stably expressing MHC class II antigens after CIITA gene transfection (MOC2-CIITA). Mice injected with MOC2-CIITA reject or strongly retard tumor growth; more importantly, vaccinated animals that fully reject MOC2-CIITA tumors display anti-tumor immunological memory protective against challenge with parental MOC2 tumor cells. Further experiments of adoptive cell transfer or in vivo cell depletion show that both CD4+ and CD8+ T lymphocytes prove fundamental in tumor rejection. This unprecedented approach for oral cancer opens the way for possible future translation of novel immunotherapeutic strategies to the human setting for the treatment of this tumor

European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria

Correction: Volume16 Issue1 Article Number225 DOI10.1186/s13019-021-01606-8Background: Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient's conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods: Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient's comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion: The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD.Peer reviewe

Genome-wide expression profiling and functional characterization of SCA28 lymphoblastoid cell lines reveal impairment in cell growth and activation of apoptotic pathways

BACKGROUND: SCA28 is an autosomal dominant ataxia associated with AFG3L2 gene mutations. We performed a whole genome expression profiling using lymphoblastoid cell lines (LCLs) from four SCA28 patients and six unrelated healthy controls matched for sex and age. METHODS: Gene expression was evaluated with the Affymetrix GeneChip Human Genome U133A 2.0 Arrays and data were validated by real-time PCR. RESULTS: We found 66 genes whose expression was statistically different in SCA28 LCLs, 35 of which were up-regulated and 31 down-regulated. The differentially expressed genes were clustered in five functional categories: (1) regulation of cell proliferation; (2) regulation of programmed cell death; (3) response to oxidative stress; (4) cell adhesion, and (5) chemical homeostasis. To validate these data, we performed functional experiments that proved an impaired SCA28 LCLs growth compared to controls (p\u2009<\u20090.005), an increased number of cells in the G0/G1 phase (p\u2009<\u20090.001), and an increased mortality because of apoptosis (p\u2009<\u20090.05). We also showed that respiratory chain activity and reactive oxygen species levels was not altered, although lipid peroxidation in SCA28 LCLs was increased in basal conditions (p\u2009<\u20090.05). We did not detect mitochondrial DNA large deletions. An increase of TFAM, a crucial protein for mtDNA maintenance, and of DRP1, a key regulator of mitochondrial dynamic mechanism, suggested an alteration of fission/fusion pathways. CONCLUSIONS: Whole genome expression profiling, performed on SCA28 LCLs, allowed us to identify five altered functional categories that characterize the SCA28 LCLs phenotype, the first reported in human cells to our knowledge. \ua9 2013 Mancini et al.; licensee BioMed Central Ltd

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

SIMBIO-SYS: Scientific Cameras and Spectrometer for the BepiColombo Mission

The SIMBIO-SYS (Spectrometer and Imaging for MPO BepiColombo Integrated Observatory SYStem) is a complex instrument suite part of the scientific payload of the Mercury Planetary Orbiter for the BepiColombo mission, the last of the cornerstone missions of the European Space Agency (ESA) Horizon + science program

Container core home solution. Progetto di un modello abitativo a basso consumo energetico per il contesto statunitense

LAUREA MAGISTRALECONTAINER_CORE-HOME SOLUTION Il dibattito globale sull’impatto delle attività dell’uomo non è mai stato così rilevante come ora; tra le attività più invasive sicuramente va annoverata anche l’edilizia. Tra i paesi industrializzati l’America è il primo per emissioni globali di CO2 da imputare al solo settore residenziale; infatti il 50% del totale delle emissioni americane viene dalle abitazioni (in Italia questo valore si attesta al 31%). Da ciò emerge chiara la necessità di una maggiore considerazione delle logiche costruttive, dell’industrializzazione e delle riduzioni dei consumi energetici nell’architettura americana. L’idea di progetto parte dalla risposta al bando “Best” promosso da Invitalia, in cooperazione con la Commissione Fulbright e con l’Ambasciata USA in Italia, che incoraggia lo sviluppo di un’idea imprenditoriale, da svilupparsi in California; in questo modello il campo di competenza della tesi e l’obiettivo che questa si pone è quello di cercare di definire un modello abitativo alternativo a quello attuale a Balloon Frame. Per fare ciò è stata condotta un’approfondita analisi sociologica e di mercato con il fine di definire dei requisisiti progettuali diventati punti fermi di un modello che deve rispecchiare i bisogni della società americana, per essere considerato valido ed appetibile sul mercato statunitense. Tra le possibili soluzioni quella sperimentata è stata quella del riutilizzo dei containers in fase di dismissione. L’obiettivo della tesi, è quello di una verifica della validità della proposta nella sua complessità. Per fare ciò gli strumenti utilizzati sono stati due: - quello imprenditoriale di valutazione di fattibilità e di riuscita dell’ idea di business - quello tecnico di progettazione architettonica di un edificio IL riutilizzo del container, racchiude in se la vera sfida, il fulcro dal quale sono nate e state approfondite tutte le sfaccettature del progetto. In quest’ottica il prossimo US Solar Decathlon che si terrà proprio in California nell’ottobre 2015, è stato preso come secondo bando di riferimento dove testare l’idea imprenditoriale, progettando un padiglione solare in accordo alle regole della manifestazione.CONTAINER_CORE – HOME SOLUTION The global debate on the impacts of human activities has never been so relevant as it is today; among the most invasive activities the buildings are one of the main actors. Between the industrializated countries U.S.A. is the first one for global CO2 emissions from the residential sectors. In fact 50% of the total amount of American emissions come from the houses. (in Italy a threshold as high as 31% is recorded). In compliance with such a statement my thesis is aimed at dropping the USA’s overall CO2 emission in the construction branch. The main idea originates from the application to the “Best programme”, issued by “Invitalia”, in cooperation with the Fulbright commission and the American Embassy in Italy, which fosters the development of an entrepreneurial idea to be developed within the Californian borders. In this model the field of expertise of the thesis and the final goal is trying to identify a new model home alternative to the current Balloon Frame solution. In order to accomplish the task, a deep sociological and market analysis has been accomplished with the objective of understanding the designing constraints be matching the American habits and which have obviously been milestones for the project. By following this planning strategy the item to be released to the market would be the most appreciable and viable. Among the different technical solutions, that chosen was the recycling of shipping containers. The definitive thesis’ goal is the validation of such a technical solution, with its feasibility analysis at 360°: technical, strategical, and business real application. The tools being used, therefore have been both technical and managerial. The real challange of the thesis regards the reuse of the shipping containers, the hub from which the thesis was born. In this perspective the next US Solar Decathlon which will be held in California in October 2015, could be the opportunity where to test the entrepreneurial idea, by designing a solar pavillion in compliance with the competition rules

Molecular phylogeny and morphology of the marine diatom Talaroneis posidoniae gen. et sp. nov. (Bacillariophyta) advocate the return of the Plagiogrammaceae to the pennate diatoms

A new genus, Talaroneis Kooistra & De Stefano, gen. nov. and a new species T. posidoniae Kooistra & De Stefano, sp. nov. are described. The elongate cells, which were found on a leaf of Posidonia oceanica, formed star-, zigzag- or ribbon-shaped colonies in culture. The distinctive character of T. posidoniae was the presence of two silica wings flanking a furrow near each apical pore field. Uniseriate, transverse striae were arranged perpendicular to the apical axis; those on one side of the valve offset with respect to those on the other side. Valve poroids were occluded by perforated rotae. These morphological characteristics placed the taxon unambiguously within the supposedly centric family Plagiogrammaceae. The taxon would be excluded from the morphologically similar araphid family Rhaphoneidaceae because it lacked apical labiate processes and a clearly defined sternum. Nonetheless, a phylogeny inferred from nuclear-encoded SSU ribosomal DNA sequences of a range of diatoms unambiguously recovered T. posidoniae within the araphid pennates, close to Rhaphoneis cf. belgica (Rhaphoneidaceae). Apparently, labiate processes were lost secondarily in T. posidoniae and possibly in the common ancestor of all Plagiogrammaceae. Valve ultrastructural features of T. posidoniae would allow placement of the new species in Dimeregrammopsis but this genus was invalidly described. We transferred the single species of this genus to T. furcigerum (Grunow) Sterrenburg, comb. nov. and designated it as the type species of Talaroneis

Both Light Stimuli and Predation Risk Affect the Adult Behavior of a Stygobiont Crustacean

Stygobiont species show common, typical traits derived from their adaptation to subterranean life. Due to the general absence of light in cave environments, the majority of them are eyeless. Although the absence of eyes generally does not allow them to perceive luminous stimuli, some stygobionts still present phototaxis. Previous studies determined that different species of the eyeless amphipod crustaceans of the genus Niphargus are able to react to light; this has been interpreted as an adaptation to avoid dangerous surface habitats, even if recent studies suggest that this could also be an adaptation to exploit them when a situation is less dangerous (i.e., during the night). Niphargus thuringius is a stygobiont amphipod that can also be observed in spring environments despite possessing all the main morphological features of subterranean organisms, such as depigmentation and a lack of eyes. In the present study, we test how the species respond to light stimuli according to the light cycle and predation risk experienced during a conditioning period. We assessed the reactions to light stimuli of adult individuals of N. thuringius after 30 days of rearing in microcosms with different conditions of light occurrence (total darkness or a light/darkness daily cycle) and predation risk (without predators, with one predator, and with two predators). Both light stimuli during the test and rearing conditions affected the behavior of Niphargus thuringius. With light stimuli, individuals presented a strong photophobic response. Moreover, individuals reared in conditions of high predation risk preferred a more sheltered environment during behavioral tests than individuals reared in safe conditions. Our results add a new species to those of stygobiont amphipods known to display negative phototaxis, confirming that this pattern is widespread and conserved in the field. N. thuringius could be a good candidate model to perform further studies aiming to assess if differences occur between spring populations and populations present in deeper groundwater.</jats:p