Science is perception: what can our sense of smell tell us about ourselves and the world around us?

Human sensory processes are well understood: hearing, seeing, perhaps even tasting and touch—but we do not understand smell—the elusive sense. That is, for the others we know what stimuli causes what response, and why and how. These fundamental questions are not answered within the sphere of smell science; we do not know what it is about a molecule that … smells. I report, here, the status quo theories for olfaction, highlighting what we do not know, and explaining why dismissing the perception of the input as ‘too subjective’ acts as a roadblock not conducive to scientific inquiry. I outline the current and new theory that conjectures a mechanism for signal transduction based on quantum mechanical phenomena, dubbed the ‘swipe card’, which is perhaps controversial but feasible. I show that such lines of thinking may answer some questions, or at least pose the right questions. Most importantly, I draw links and comparisons as to how better understanding of how small (10’s of atoms) molecules can interact so specially with large (10 000’s of atoms) proteins in a way that is so integral to healthy living. Repercussions of this work are not just important in understanding a basic scientific tool used by us all, but often taken for granted, it is also a step closer to understanding generic mechanisms between drug and receptor, for example

Evaluation of the hydro-meteorological chain in Piemonte Region, north western Italy - analysis of two HYDROPTIMET test cases

International audienceThe HYDROPTIMET Project, Interreg IIIB EU program, is developed in the framework of the prediction and prevention of natural hazards related to severe hydro-meteorological events and aims to the optimisation of Hydro-Meteorological warning systems by the experimentation of new tools (such as numerical models) to be used operationally for risk assessment. The object of the research are the Mesoscale weather phenomena and the response of watersheds with size ranging from 102 to 103 km2. Non-hydrostatic meteorological models are used to catch such phenomena at a regional level focusing on the Quantitative Precipitation Forecast (QPF). Furthermore hydrological Quantitative Discharge Forecast (QDF) are performed by the simulation of run-off generation and flood propagation in the main rivers of the interested territory. In this way observed data and QPF are used, in a real-time configuration, for one-way forcing of the hydrological model that works operationally connected to the Piemonte Region Alert System. The main hydro-meteorological events that interested Piemonte Region in the last years are studied, these are the HYDROPTIMET selected test cases of 14-18 November 2002 and 23-26 November 2002. The results obtained in terms of QPF and QDF offer a sound basis to evaluate the sensitivity of the whole hydro-meteorological chain to the uncertainties in the numerical simulations. Different configurations of non-hydrostatic meteorological models are also analysed

BIM and Mixed Reality for the New Management of Storage Area

The fourth industrial revolution that has touched the last decades, has involved several sectors including the construction world. The digitization and automation of industrial processes has implemented the development of connection platforms that can communicate many information for different users such as Smart Glasses or immersive headset. Most of the time, innovation does not only concern the technological field, but involves the entire organizational and managerial sphere. Digitization allows new tools such as Building Information Modelling to expand its application scale, making it an excellent tool for integrating and sharing data with their own information management systems (MES). The aims of this contribution are reproducing a virtual warehouse through parametric digital modelling, to which all the management data have been associated; for example, the average stock, the rotation index, etc. Thanks to the export of the database extrapolated from its management system of the analyzed industry, it was possible to define the correct visualization of the virtual model, interrogating the real data coming from the real warehouse. Through Smart Glasses, the user of the area could allocate the products in the correct position and update in the cloud the information properties associated with the individual product and the entire department. The use of virtual platforms for the visualization and the sharing of the data, facilitate the optimization of the industrial processes

Selecting b-thalassemia patients for gene therapy: a decision-making algorithm

The Societ\ue0 Italiana Talassemie ed Emoglobinopatie (Italian Society of Thalassemias and Hemoglobinopathies, SITE) has developed this document based on multidisciplinary discussions of a panel of experts to provide guidance on the identification and selection of patients with transfusion-dependent beta-thalassemia (\u3b2-TDT) who could benefit from gene therapy. Currently, allogeneic transplantation of hematopoietic stem cells is the only curative and most widely used therapy treatment for \u3b2-TDT. However, recent trials of gene therapy have reported very promising results in terms of overall survival and thalassemia-free survival and are opening a new landscape of treatment. This algorithm for the selection of patients suitable for gene therapy and the supporting notes were formulated by consensus review after an evaluation of currently available scientific evidence using validated criteria. The evidence was interpreted with caution because clinical trial experience of gene therapy is currently limited, a conventional treatment is available for patients with \u3b2-TDT and the availability of gene therapy will, at least initially, be quite limited. Clinical experience of allogeneic transplantation in \u3b2-TDT, which began in 1981, immediately showed the importance of patient risk stratification in order to achieve the best results (see the Pesaro experience and their classification of patients according to risk). Published data in the literature and the recent analysis of clinical evidence by the European Registry of Hemoglobinopathies of a large number of patients (2011 and 2018 analyses) confirm that young patient age (<14 years) and the availability of a human leukocyte antigen (HLA)-identical family donor are factors that offer the best outcome from allogeneic transplantation. Current knowledge of, and experience with, non-conventional treatments, such as allogeneic transplantation and gene therapy, are discussed in order to identify the best available treatment and indication for these patients according to their characteristics. At this point in time, when we can see the emergence of \u2018the age of gene therapy\u2019, it is essential to establish the optimal patient setting in which gene therapy can be applied, or better, to define the setting that represents the most suitable indication for gene therapy, identify the patients who should have clinical priority for access to the procedure, and set out requirements and recommendations for the identification of qualified treatment centers for gene therapy. When considering changes to the treatment of patients with \u3b2-TDT, including gene therapy, it is essential that a detailed consultation is held with the patient and their caregiver/family to discuss all possible risks and potential benefits from the treatment. Discussion of this aspect of care is outside of the scope of this document but remains an important element of patient care

Effect of acute copper sulfate exposure on olfactory responses to amino acids and pheromones in goldfish (Carassius auratus)

Exposure of olfactory epithelium to environmentally relevant concentrations of copper disrupts olfaction in fish. To examine the dynamics of recovery at both functional and morphological levels after acute copper exposure, unilateral exposure of goldfish olfactory epithelia to 100 μM CuSO4 (10 min) was followed by electro-olfactogram (EOG) recording and scanning electron microscopy. Sensitivity to amino acids (L-arginine and L-serine), generally considered food-related odorants, recovered most rapidly (three days), followed by that to catecholamines(3-O-methoxytyramine),bileacids(taurolithocholic acid) and the steroid pheromone, 17,20 -dihydroxy-4-pregnen- 3-one 20-sulfate, which took 28 days to reach full recovery. Sensitivity to the postovulatory pheromone prostaglandin F2R had not fully recovered even at 28 days. These changes in sensitivity were correlated with changes in the recovery of ciliated and microvillous receptor cell types. Microvillous cells appeared largely unaffected by CuSO4 treatment. Cilia in ciliated receptor neurones, however, appeared damaged one day post-treatment and were virtually absent after three days but had begun to recover after 14 days. Together, these results support the hypothesis that microvillous receptor neurones detect amino acids whereas ciliated receptor neurones were not functional and are responsible for detection of social stimuli (bile acidsandpheromones).Furthermore, differences in sensitivity to copper may be due to different transduction pathways in the different cell types

Morbidity and mortality of sickle cell disease patients is unaffected by splenectomy: evidence from three decades of follow-up in a high-income setting

Sickle cell disease (SCD) is a globally widespread hereditary red cell disorder characterized by the production of pathological hemoglobin S (HbS).1 Patients with SCD include homozygous subjects for HbS (SS) and compound heterozygotes with HbS/HbC (SC) or HbS/β+/0-thalassemia (Sβ0/β+). In Italy, SCD is endemic with HbS/β+/0-thalassemia being prevalent in areas of southern Italy. In the last two decades, the number of SCD patients across Italy has increased due to migration from sub-Saharan Africa and th

Current challenges in the management of patients with sickle cell disease - A report of the Italian experience

Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a structural abnormality of hemoglobin called sickle hemoglobin (HbS). Clinical manifestations of SCD are mainly characterized by chronic hemolysis and acute vaso-occlusive crisis, which are responsible for severe acute and chronic organ damage. SCD is widespread in sub-Saharan Africa, in the Middle East, Indian subcontinent, and some Mediterranean regions. With voluntary population migrations, people harboring the HbS gene have spread globally. In 2006, the World Health Organization recognized hemoglobinopathies, including SCD, as a global public health problem and urged national health systems worldwide to design and establish programs for the prevention and management of SCD. Herein we describe the historical experience of the network of hemoglobinopathy centers and their approach to SCD in Italy, a country where hemoglobinopathies have a high prevalence and where SCD, associated with different genotypes including f-thalassemia, is present in the native population

Transfusional approach in multi-ethnic Sickle Cell patients: real-world practice data from a Multicenter survey in Italy

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications

Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa

Olfactory ensheathing cells (OECs) are a promising potential cell therapy to aid regeneration. However, there are significant challenges in isolating and characterizing them. In the current study, we have explored methods to enhance the recovery of cells expressing OEC marker p75NTR from rat mucosa. With the addition of a 24-hour differential adhesion step, the expression of p75NTR was significantly increased to 73 ± 5% and 46 ± 18% on PDL and laminin matrices respectively. Additionally, the introduction of neurotrophic factor NT-3 and the decrease in serum concentration to 2% FBS resulted in enrichment of OECs, with p75NTR at nearly 100% (100 ± 0% and 98 ± 2% on PDL and laminin respectively), and candidate fibroblast marker Thy1.1 decreased to zero. Culturing OECs at physiologically relevant oxygen tension (2–8%) had a negative impact on p75NTR expression and overall cell survival. Regarding cell potency, co-culture of OECs with NG108-15 neurons resulted in more neuronal growth and potential migration at atmospheric oxygen. Moreover, OECs behaved similarly to a Schwann cell line positive control. In conclusion, this work identified key bioprocessing fundamentals that will underpin future development of OEC-based cell therapies for potential use in spinal cord injury repair. However, there is still much work to do to create optimized isolation methods