Il gioco della logica tra uso del linguaggio e costruzione della scienza.

E tanto più intendo tanto più ignoro, motto di Tommaso Campanella, può servire a spiegare, bene, le virgolette messe attorno alla parola: gioco, ed il suo carattere, ambiguo e contraddittorio, essendo tutto ciò vero tanto nello uso del linguaggio, quanto nella costruzione della scienza. Quanto segue si dipana in alcuni meandri della filosofia analitica, a partire dal positivismo logico, dove molto forte è l’accanirsi contro la metafisica. A riguardo, avendo presente l’uso rinnovato del termine, fatto da giovani filosofi contemporanei, corre il dovere di precisare la sua validità, se significa andare oltre le cose fisiche, con le assunzioni necessarie per pensare e fare scienza. Al contrario, validissimo è il rigetto della metafisica, quando questa voglia dire, come nella tradizione della storia del pensiero, rifarsi a principi primi indiscutibili ed assoluti. Rudolf Carnap e Karl Raimund Popper sono i maggiori esponenti delle scuole filosofiche, prese in esame. La trattazione collega linguaggio e costruzione della scienza, perché una concezione moderna descrive la scienza come un linguaggio, capace di leggere la realtà fisica, dove la complessità della analisi cresce al crescere della complessità della modellazione adottata. Infatti oltre a muoversi liberamente nello spazio, parametrizzato con righe, colonne e pile, è spesso necessario muoversi congiuntamente nel tempo e/o nel cosiddetto spazio delle scale, entrambi parametrizzati con pioli e montanti, a seconda che si permanga ad un dato livello, oppure si passi da un livello ad un altro. Da altra parte, un esempio musicale dà il segno della complessità: le cinque note pentatoniche (la si do re mi fa sol) permettono 720 permutazioni, mentre le dodici note (mettendo insieme i tasti bianchi e neri del pianoforte) permettono 479.001.600 permutazioni e, anche limitandosi alle ventiquattro scale armoniche, maggiori e minori (sulle sette note del clavicembalo ben temperato), il numero di permutazioni è 120.960. In questo contesto, il superamento della empiria fa passare dalla capacità di verificazione alla sola possibilità di falsificazione, dove è possibile dire quello che è errato, ma non è possibile certificare quello che è esatto. Infatti la verità è sempre provvisoria e precaria, valida fino ad una possibile smentita, più o meno prossima, e le costruzioni tecniche, sociali, economiche e politiche sono, sempre e solo, governate dal dubbio ed altrettanto precarie e provvisorie. Infine con un salto notevole di contenuto, ma affatto estraneo alla vita ed alle concezioni dei pensatori (qui già citati e/o citati nel seguito), è davvero difficile, soprattutto in questi tempi così tanto travagliati, separare il parlare alto di ricerca scientifica e tecnologica, nonché di storia della scienza e della tecnica, e di epistemologia, dai casi della vita quotidiana, vari e diversi. Di fronte a tutti questi è davvero difficile scegliere la strada migliore, in ogni caso, ben sapendo come occorra, sempre ed ovunque, il coraggio e lo impegno e talvolta anche la ribellione

Brain connectivity changes after osteopathic manipulative treatment: A randomized manual placebo-controlled trial

The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT and Placebo treatment (P) in 30 healthy asymptomatic young participants randomized into OMT and placebo groups (OMTg; Pg). fMRI brain activity measures, performed before (T0), immediately after (T1) and three days after (T2) OMT or P were used for inferring treatment effects on brain circuit functional organization. Repeated measures ANOVA and post-hoc analysis demonstrated that Right Precentral Gyrus (F (2, 32) = 5.995, p < 0.005) was more influential over the information flow immediately after the OMT, while decreased betweenness centrality in Left Caudate (F (2, 32) = 6.496, p < 0.005) was observable three days after. Clustering coefficient showed a distinct time-point and group effect. At T1, reduced neighborhood connectivity was observed after OMT in the Left Amygdala (L-Amyg) (F(2, 32) = 7.269, p < 0.005) and Left Middle Temporal Gyrus (F(2, 32) = 6.452, p < 0.005), whereas at T2 the L-Amyg and Vermis-III (F(2, 32) = 6.772, p < 0.005) increased functional interactions. Data demonstrated functional connectivity re-arrangement after OMT

Cell starvation increases uptake of extracellular Thymosin β4 and its complexes with calcium

Cell metastasis is the main cause of cancer mortality. Inhibiting early events during cell metastasis and invasion could significantly improve cancer prognosis, but the initial mechanisms of cell transition and migration are barely known. Calcium regulates cell migration, whilst Thymosin β4 is a G-actin and iron binding peptide associated with tumor metastasis and ferroptosis. Under normal cell growth conditions, intracellular free calcium ions and Thymosin β4 concentrations are strictly regulated, and are not influenced by extracellular supplementation. However, cell starvation decreases intracellular Thymosin β4 and increases extracellular peptide uptake above the normal range. Unexpectedly, cell starvation significantly increases internalization of extracellular Ca2+/Thymosin β4 complexes. Elucidating the role of Ca2+/Thymosin β4 in the early events of metastasis will likely be important in the future to develop therapies targeting metastasis

Thymosin Beta 4 may translocate from the cytoplasm in to the nucleus in HepG2 cells following serum starvation. An ultrastructural study

Due to its actin-sequestering properties, thymosin beta-4 (Tβ4) is considered to play a significant role in the cellular metabolism. Several physiological properties of Tβ4 have been reported;, however, many questions concerning its cellular function remain to be ascertained. To better understand the role of this small peptide we have analyzed by means of transmission immunoelectron microscopy techniques the ultrastructural localization of Tβ4 in HepG2 cells. Samples of HepG2 cells were fixed in a mixture of 3% formaldehyde and 0.1% glutaraldehyde in 0.1 M cacodylate buffer and processed for standard electron microscopic techniques. The samples were dehydrated in a cold graded methanol series and embedded in LR gold resin. Ultrathin sections were labeled with rabbit antibodies to Tβ4, followed by gold-labeled goat anti-rabbit, stained with uranyl acetate and bismuth subnitrate, observed and photographed in a JEOL 100S transmission electron microscope. High-resolution electron microscopy showed that Tβ4 was mainly restricted to the cytoplasm of HepG2 growing in complete medium. A strong Tβ4 reactivity was detected in the perinuclear region of the cytoplasmic compartment where gold particles appeared strictly associated to the nuclear membrane. In the nucleus specific Tβ4 labeling was observed in the nucleolus. The above electron microscopic results confirm and extend previous observations at light microscopic level, highlighting the subcellular distribution of Tβ4 in both cytoplasmic and nuclear compartments of HepG2 cells. The meaning of Tβ4 presence in the nucleolus is not on the best of our knowledge clarified yet. It could account for the interaction of Tβ4 with nucleolar actin and according with this hypothesis, Tβ4 could contribute together with the other nucleolar acting binding proteins to modulate the transcription activity of the RNA polymeras

New driver alterations in non-small cell lung cancer. A narrative review

Objective: This review aims to provide an up-to-date snapshot on the state of development of novel biomarker-driven treatments in non-small cell lung cancer (NSCLC). Background: The introduction of immune checkpoint inhibitors and target therapies has revolutionized the natural history of many NSCLCs, allowing for lasting and profound responses. In particular, mutations in the epidermal growth factor receptor (EGFR), rearrangements of the anaplastic lymphoma kinase (ALK), or oncogene c-Ros 1 (ROS1) have marked a paradigm shift in the treatment of NSCLC. Furthermore, new inhibitors for B-Raf proto-oncogene (BRAF), rearranged during transfection (RET), mesenchymal-to-epithelial transition factor (MET), or neurotrophic tyrosine kinase (NTRK) 1–3 have revealed fascinating data, obtaining accelerated approvals from the Food and Drug Administration (FDA) and European Medicines Agency (EMA). Today, the extensive use of next-generation sequencing (NGS) techniques has shown a broad molecular heterogeneity of NSCLC. Many of the mutations identified are considered potential therapeutic targets, and numerous studies are currently evaluating the efficacy of selective inhibitors. Methods: We carried out an extensive review of the literature on PubMed, Web of Science, and Scopus databases and the congress abstracts presented at the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and World Conference on Lung Cancer (WCLC) in the last 5 years. Our analysis considered works regarding new inhibitors for alterations of Kirsten rat sarcoma viral oncogene homolog (KRAS), PIK3CA, neuregulin-1 (NRG-1), human epidermal growth factor receptor 2 (HER2), fibroblast growth factor receptor (FGFR), genes that have recently become no longer undruggable. Conclusions: Precision oncology is revolutionizing the natural history of NSCLC. Several alterations have been identified as possible treatment targets, and numerous inhibitors show promising results in ongoing clinical trials

Multimodal-based Diversified Summarization in Social Image Retrieval

In this paper, we describe our approach and its results for the MediaEval 2015 Retrieving Diverse Social Images task. The main strength of the proposed approach is its flexibility that permits to filter out irrelevant images, and to obtain a reli- able set of diverse and relevant images. This is done by first clustering similar images according to their textual descrip- tions and their visual content, and then extracting images from different clusters according to a measure of user’s cred- ibility. Experimental results shown that it is stable and has little fluctuation in both single-concept and multi-concept queries

Washingtonia filifera seed extracts inhibit the islet amyloid polypeptide fibrils formations and α-amylase and α-glucosidase activity

Washingtonia filifera seeds have revealed to possess antioxidant properties, butyrylcholinesterase and xanthine oxidase inhibition activities. The literature has indicated a relationship between Alzheimer’s disease (AD) and type-2 diabetes (T2D). Keeping this in mind, we have now evaluated the inhibitory properties of W. filifera seed extracts on α-amylase, α-glucosidase enzyme activity and the Islet Amyloid Polypeptide (IAPP) fibrils formation. Three extracts from seeds of W. filifera were evaluated for their enzyme inhibitory effect and IC50 values were calculated for all the extracts. The inhibition mode was investigated by Lineweaver-Burk plot analysis and the inhibition of IAPP aggregate formation was monitored. W. filifera methanol seed extract appears as the most potent inhibitor of α-amylase, α-glucosidase, and for the IAPP fibril formation. Current findings indicate new potential of this extract that could be used for the identification or development of novel potential agents for T2D and AD

Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation

Background Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59 adjuvant which, in 3 Phase II trials, demonstrated 43–50% efficacy in preventing HCMV acquisition in seronegative healthy women or adolescents and reduction in virological parameters after SOT. However, the mechanism of vaccine protection in seronegative recipients remains undefined. Methods We evaluated samples from the cohort of seronegative SOT patients enroled in the Phase II glycoprotein-B/MF59 vaccine trial who received organs from seropositive donors. Samples after SOT (0–90 days) were tested by real-time quantitative PCR for HCMV DNA. Anti-gB antibody levels were measured by ELISA. Neutralization was measured as a decrease in infectivity for fibroblast cell cultures revealed by expression of immediate-early antigens. Findings Serological analyses revealed a more rapid increase in the humoral response against gB post transplant in vaccine recipients than in those randomised to receive placebo. Importantly, a number of patient sera displayed HCMV neutralising responses – neutralisation which was abrogated by pre-absorbing the sera with recombinant gB. Interpretation We hypothesise that the vaccine primed the immune system of seronegative recipients which, when further challenged with virus at time of transplant, allowed the host to mount rapid immunological humoral responses even under conditions of T cell immune suppression during transplantation

Toward the renal vesicle: Ultrastructural investigation of the cap mesenchyme splitting process in the developing kidney

Background: A complex sequence of morphogenetic events leads to the development of the adult mouse kidney. In the present study, we investigated the morphological events that characterize the early stages of the mesenchymal-to-epithelial transition of cap mesenchymal cells, analyzing in depth the relationship between cap mesenchymal induction and ureteric bud (UB) branching. Design and methods: Normal kidneys of newborn non-obese diabetic (NOD) mice were excised and prepared for light and electron microscopic examination. Results: Nephrogenesis was evident in the outer portion of the renal cortex of all examined samples. This process was mainly due to the interaction of two primordial derivatives, the ureteric bud and the metanephric mesenchyme. Early renal developmental stages were initially characterized by the formation of a continuous layer of condensed mesenchymal cells around the tips of the ureteric buds. These caps of mesenchymal cells affected the epithelial cells of the underlying ureteric bud, possibly inducing their growth and branching. Conclusions: The present study provides morphological evidence of the reciprocal induction between the ureteric bud and the metanephric mesenchyme showing that the ureteric buds convert mesenchyme to epithelium that in turn stimulates the growth and the branching of the ureteric bud

Neo-adjuvant chemo/immunotherapy in the treatment of stage III (N2) non-small cell lung cancer: a phase I/II pilot study.

In a previous randomized study, we showed that adjuvant immunotherapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 (rIL-2) significantly improved survival in resected N2-Non Small Cell Lung Cancer (NSCLC) patients. The present study assesses feasibility, safety and potential efficacy of combined neo-adjuvant chemotherapy and immunotherapy with peripheral blood mononuclear cells (PBMC) and rIL-2 in resectable N2-NSCLC patients. Eighty-two consecutive N2-NSCLC patients underwent neo-adjuvant chemotherapy with cisplatin and gemcitabine. Out of the 82 patients, 23 were also subjected to leukapheresis prior to neo-adjuvant chemotherapy while the remaining 59 did not. Collected PBMC were analyzed for viability and phenotype and then stored frozen in liquid nitrogen. Thawed PBMC were infused intravenously, 5 days before surgery. After the infusion, rIL-2 was administered subcutaneously until surgery. Only patients with a partial or complete response to neoadjuvant chemotherapy underwent surgery: 13 patients in the experimental immunotherapy group (A) and 32 in the reference group (B). The two groups were homogeneous for all major prognostic factors. Median leukapheresis yield was 10 billion PBMC, (range 3–24 billions). Two to six billion PBMC were infused. The phenotypic analysis showed that similar proportions of CD4 and CD8 cells were present in leukapheresis products, and thawed PBMC, as well as in T lymphocytes isolated from the removed tumours. No severe adverse effects were observed following immunotherapy. No significant differences in overall survival (OS) and event-free survival (EFS) were seen between the two groups. However, the 5-year OS in group A was almost twice as much compared to group B (59% vs 32%). After adjustment for major prognostic factors, a statistically significant 66% reduction in the hazard of death was seen in patients receiving immunotherapy. The OS benefit was more evident in patients with adenocarcinoma than in those with squamous cell carcinoma. This study supports the favorable toxicity profile and potential efficacy of combining neo-adjuvant chemotherapy and immunotherapy with PBMC and rIL-2 in the treatment of N2-NSCLC patients