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The advent of neuromorphic electronics is increasingly revolutionizing the concept of computation. In the last decade, several studies have shown how materials, architectures, and neuromorphic devices can be leveraged to achieve brain-like computation with limited power consumption and high energy efficiency. Neuromorphic systems have been mainly conceived to support spiking neural networks that embed bioinspired plasticity rules such as spike time-dependent plasticity to potentially support both unsupervised and supervised learning. Despite substantial progress in the field, the information transfer capabilities of biological circuits have not yet been achieved. More importantly, demonstrations of the actual performance of neuromorphic systems in this context have never been presented. In this paper, we report similarities between biological, simulated, and artificially reconstructed microcircuits in terms of information transfer from a computational perspective. Specifically, we extensively analyzed the mutual information transfer at the synapse between mossy fibers and granule cells by measuring the relationship between pre- and post-synaptic variability. We extended this analysis to memristor synapses that embed rate-based learning rules, thus providing quantitative validation for neuromorphic hardware and demonstrating the reliability of brain-inspired applications.

Kokumi taste-active compounds enhance salty taste perception. In animal models, sodium (salt) detection is mediated by the amiloride-sensitive epithelial sodium channel, ENaC. This ion channel works as a sodium receptor in the so-called sodium-taste cells. It is not known whether kokumi taste substances are able to affect the activity of functional ENaCs in these cells. Here, we use the patch-clamp technique to study the effect of kokumi-active tripeptides, glutathione (GSH) and γ-glutamyl-valyl-glycine (EVG), on the ENaC-mediated membrane current in rat fungiform sodium-taste cells. GSH and EVG reduced slightly this current and the effect disappeared in the presence of amiloride, a specific ENaC blocker. No effect on membrane current was detected in other taste cells (Type II and Type III cells) that do not express functional ENaC. Our findings suggest that the enhancing effect of kokumi taste-active γ-glutamyl peptides on salt reception is not explained by an increase in the activity of ENaC.

Abstract The brain functions can be reversibly modulated by the action of general anesthetics. Despite a wide number of pharmacological studies, an extensive analysis of the cellular determinants of anesthesia at the microcircuits level is still missing. Here, by combining patch-clamp recordings and mathematical modeling, we examined the impact of sevoflurane, a general anesthetic widely employed in the clinical practice, on neuronal communication. The cerebellar microcircuit was used as a benchmark to analyze the action mechanisms of sevoflurane while a biologically realistic mathematical model was employed to explore at fine grain the molecular targets of anesthetic analyzing its impact on neuronal activity. The sevoflurane altered neurotransmission by strongly increasing GABAergic inhibition while decreasing glutamatergic NMDA activity. These changes caused a notable reduction of spike discharge in cerebellar granule cells (GrCs) following repetitive activation by excitatory mossy fibers (mfs). Unexpectedly, sevoflurane altered GrCs intrinsic excitability promoting action potential generation. Computational modelling revealed that this effect was triggered by an acceleration of persistent sodium current kinetics and by an increase in voltage dependent potassium current conductance. The overall effect was a reduced variability of GrCs responses elicited by mfs supporting the idea that sevoflurane shapes neuronal communication without silencing neural circuits.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current pandemic of coronavirus disease 2019 (COVID-19). This pandemic is characterized by a high variability in death rate (defined as the ratio between the number of deaths and the total number of infected people) across world countries. Several possible explanations have been proposed, but it is not clear whether this variability is due to a single predominant factor or instead to multiple causes. Here we addressed this issue using multivariable regression analysis to test the impact of the following factors: the hospital stress (defined as the ratio between the number of infected cases and the total number of hospital beds), the population median age, and the quality of the National Health System (NHS). For this analysis, we chose countries of the world with over 3000 infected cases as of April 1, 2020. Hospital stress was found to be the crucial factor in explaining the variability of death rate, while the others had negligible relevance. Different procedures for quantifying cases of infection and death for COVID-19 could affect the variability in death rate across countries. We therefore applied the same statistical approach to Italy, which is divided into 20 Regions that share the same protocol for counting the outcomes of this pandemic. Correlation between hospital stress and death rate was even stronger than that observed for countries of the world. Based on our findings and the historical trend for the availability of hospital beds, we propose guidelines for policy-makers to properly manage future pandemics.

A central hypothesis on brain functioning is that long-term potentiation (LTP) and depression (LTD) regulate the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granule cells have been shown to control the gain of signals transmitted through the mossy fiber pathway by exploiting synaptic inhibition in the glomeruli. However, the way LTP and LTD control signal transformation at the single-cell level in the space, time and frequency domains remains unclear. Here, the impact of LTP and LTD on incoming activity patterns was analyzed by combining patch-clamp recordings in acute cerebellar slices and mathematical modeling. LTP reduced the delay, increased the gain and broadened the frequency bandwidth of mossy fiber burst transmission, while LTD caused opposite changes. These properties, by exploiting NMDA subthreshold integration, emerged from microscopic changes in spike generation in individual granule cells such that LTP anticipated the emission of spikes and increased their number and precision, while LTD sorted the opposite effects. Thus, akin with the expansion recoding process theoretically attributed to the cerebellum granular layer, LTP and LTD could implement selective filtering lines channeling information toward the molecular and Purkinje cell layers for further processing.

Multiphoton microscopy is the most widespread method for preclinical brain imaging when sub-micrometer resolution is required. Nonetheless, even in the case of optimal experimental conditions, only a few hundred micrometers under the brain surface can be imaged by multiphoton microscopy. The main limitation preventing the acquisition of images from deep brain structures is the random light scattering which, until recently, was considered an unsurmountable obstacle. When in 2007 a breakthrough work by Vellekoop and Mosk [1] proved it is indeed possible to compensate for random scattering by using high resolution phase modulators, the neuro-photonics community started chasing the dream of a multiphoton microscopy capable of reaching arbitrary depths within the brain. Unfortunately, more than 10 years later, despite a massive improvement of technologies for scattering compensation in terms of speed, performances and reliability, clear images from deep layers of biological tissues are still lacking. In this work, we review recent technological and methodological advances in the field of multiphoton microscopy analyzing the big issue of scattering compensation. We will highlight the limits hampering image acquisition, and we will try to analyze the road scientists must tackle to target one of the most challenging issue in the field of biomedical imaging.

Human dental pulp is considered an interesting source of adult stem cells, due to the low-invasive isolation procedures, high content of stem cells and its peculiar embryological origin from neural crest. Based on our previous findings, a dental pulp stem cells sub-population, enriched for the expression of STRO-1, c-Kit, and CD34, showed a higher neural commitment. However, their biological properties were compromised when cells were cultured in adherent standard conditions. The aim of this study was to evaluate the ability of three dimensional floating spheres to preserve embryological and biological properties of this sub-population. In addition, the expression of the inwardly rectifying potassium channel Kir4.1, Fas and FasL was investigated in 3D-sphere derived hDPSCs. Our data showed that 3D sphere-derived hDPSCs maintained their fibroblast-like morphology, preserved stemness markers expression and proliferative capability. The expression of neural crest markers and Kir4.1 was observed in undifferentiated hDPSCs, furthermore this culture system also preserved hDPSCs differentiation potential. The expression of Fas and FasL was observed in undifferentiated hDPSCs derived from sphere culture and, noteworthy, FasL was maintained even after the neurogenic commitment was reached, with a significantly higher expression compared to osteogenic and myogenic commitments. These data demonstrate that 3D sphere culture provides a favorable micro-environment for neural crest-derived hDPSCs to preserve their biological properties.

The induction of long-term potentiation and depression (LTP and LTD) is thought to trigger gene expression and protein synthesis, leading to consolidation of synaptic and neuronal changes. However, while LTP and LTD have been proposed to play important roles for sensori-motor learning in the cerebellum granular layer, their association with these mechanisms remained unclear. Here, we have investigated phosphorylation of the cAMP-responsive element binding protein (CREB) and activation of the immediate early gene c-Fos pathway following the induction of synaptic plasticity by theta-burst stimulation (TBS) in acute cerebellar slices. LTP and LTD were localized using voltage-sensitive dye imaging (VSDi). At two time points following TBS (15 min and 120 min), corresponding to the early and late phases of plasticity, slices were fixed and processed to evaluate CREB phosphorylation (P-CREB) and c-FOS protein levels, as well as Creb and c-Fos mRNA expression. High levels of P-CREB and Creb/c-Fos were detected before those of c-FOS, as expected if CREB phosphorylation triggered gene expression followed by protein synthesis. No differences between control slices and slices stimulated with TBS were observed in the presence of an N-methyl-D-aspartate receptor (NMDAR) antagonist. Interestingly, activation of the CREB/c-Fos system showed a relevant degree of colocalization with long-term synaptic plasticity. These results show that NMDAR-dependent plasticity at the cerebellum input stage bears about transcriptional and post-transcriptional processes potentially contributing to cerebellar learning and memory consolidation.

Although general anesthetics are thought to modify critical neuronal functions, their impact on neuronal communication has been poorly examined. We have investigated the effect induced by desflurane, a clinically used general anesthetic, on information transfer at the synapse between mossy fibers and granule cells of cerebellum, where this analysis can be carried out extensively. Mutual information values were assessed by measuring the variability of postsynaptic output in relationship to the variability of a given set of presynaptic inputs. Desflurane synchronized granule cell firing and reduced mutual information in response to physiologically relevant mossy fibers patterns. The decrease in spike variability was due to an increased postsynaptic membrane excitability, which made granule cells more prone to elicit action potentials, and to a strengthened synaptic inhibition, which markedly hampered membrane depolarization. These concomitant actions on granule cells firing indicate that desflurane re-shapes the transfer of information between neurons by providing a less informative neurotransmission rather than completely silencing neuronal activity.

The authors report a case of perineal leiomyosarcoma treated using a combined surgical and radiotherapy protocol. Exeresis was performed through an incision in the left anterior perineum, beside the vagina. The patient then underwent TCT with excellent results.

The paper reports a case of ureteral [correction of urethral] stenosis with ureterorectal [correction of urethro-rectal] fistula due to diverticulitis of the sigmoid [correction of sigma] which resolved following reconstruction of the urinary tract by ureterocystostomy [correction of urethrocystotomy] using a modified version of Boari's technique, with satisfactory renal functional recovery. On the basis of an analysis of the literature, the authors comment on ureteral [correction of urethral] stenosis and its etiological diagnosis.

A case of pseudocyst of the suprarenal gland in a 32-years-old woman is reported. Stress is laid on the description of the clinical case and the diagnostic and therapeutic problems involved are reviewed.

The Authors report a case of Castleman's disease in a 45-year-old woman. She was admitted to hospital because of a thrombophlebitis of the left lower limb. An abdominal echotomography showed evidence of a mass with a diameter of about 6 cm at the pancreatic isthmus, and a cyst (diameter 25 mm) in the right ovary. An explorative laparotomy was performed and the masses were removed. Histological examination identified them respectively as a Castleman's disease of hyaline-vascular type and an endometrioid carcinoma of the ovary.

A case of biliary cystadenoma is reported. The neoplasm was located at the left lobe of the liver and its diameter was 18 cm. It presented with abdominal swelling and palpable mass in epigastric region. A left hepatectomy was performed, to achieve a complete resection of the tumor.

The paper reports the authors' ten-year experience of the surgical treatment of cancer of the esophagus. A total of 625 patients with esophageal carcinoma were observed during the period 1980-89 of whom 490 were admitted to hospital and, of the latter, 172 (35.1%) were operated with a sectile rate of 86% (148 patients). Data from this period were analysed both retrospectively and prospectively using a computerised system. There were 105 radical operations (70.9%) and 43 palliative operations (29.1%). The 3-year actuarial survival rate was 21.7% and the difference between radical and palliative resections was at the limit of significance (p less than 0.1).

The paper reports the epidemiology and causal factors of esophageal carcinoma, and compares the authors' personal experience with already published data. The clinical importance of epidemiology is stressed as a means of identifying risk factors for esophageal carcinoma, thus aiding an early diagnosis. The authors underline the central role of surgery in the treatment of esophageal carcinoma.

A report is presented on an angiographic study of the gastric arterial system conducted on 20 human stomachs taken from cadavers during routine autopsies. The aim of the study was to define the anatomical bases for the supply of blood to the isoperistaltic gastric tubule in oesophagogastroplasty operations. The study reveals that on its own the right gastroepiploic artery cannot ensure adequate vascularisation of the gastric fundus. The importance of pressuring the right hand section of the vascular arch along the small curve was also noted and is due to the constant presence of major anastomoses at antral level with the right gastroepiploic artery. The study also revealed the constant presence of a direct intramural anastomotic circulation between the right and left gastroepiploic arteries.

At first, the authors mention indications and way of placement of the Angelchik prosthesis. Then after a wide review of the literature, they describe the complications and results. Finally a case of penetration into the stomach of an Angelchik prosthesis is reported. It was favourably resolved by an operation.

Patient with severe chronic obstructive pulmonary disease (COPD) can develop respiratory muscle weakness and fatigue. Arterial hypoxemia can predispose to this condition. To assess whether O2 administration improved respiratory muscle function and respiratory pattern in COPD 11 patients with chronic hypoxemia were examined. Each patient was first submitted to respiratory function studies, including lung volumes, in normal and recumbent position, respiratory frequency, Ti/Te, Ti/Tot, maximal inspiratory and expiratory pressures (Pimax, Pemax) and arterial gas analysis breathing room air. All these tests were repeated during oxygen Administration through a nasal cannula. The arterial PO2 improved from 50 +/- 7 mmHg to 81 +/- 28 mmHg but the breathing pattern, Pimax and Pemax as well as lung volumes remained unchanged. It is concluded that oxygen, in short term administration, doesn't influence respiratory pattern and muscle function.

The search for early tumour markers has brought to light CA 19-9 and CA 50, glycoproteins recognised by monoclonal antibodies. Since these markers are mainly used on the digestive tract it was thought useful to investigate their value in the diagnosis of lung cancer which is only rarely identified by markers in its early stages. The two markers were compared with the better known CEA on 43 healthy volunteers, 42 patients with chronic lung conditions, 26 people with localised non-neoplastic lung shadows and 255 patients with staged and histologically identified lung tumours. The results obtained reveal the two markers to be of little use in lung cancer since though satisfactorily specific they are not at all sensitive even in the advanced stages of the disease. They could however be used to advise against surgery if positive.

Neurone-specific enolase, a serum marker of neuroendocrine tumours has been determined in small-cell anaplastic bronchial carcinomas, in typical and atypical carcinoid. The marker presents good sensitivity in small-cell tumours and in atypical carcinoids, while blood levels are within normal limits in cases of typical carcinoid. The low serum levels of neurone-specific enolase found in typical carcinoid suggest a failure of the enzyme to express itself in the circulation owing to the poor or lack of cellular necrosis.

In the context of major surgery the predictive significance of respiratory function tests in relation to postoperative pleuro-pulmonary complications is assessed. A statistical analysis is performed on a series of 85 oesophagectomy after thoracotomy and laparotomy. The most significant respiratory function indices are found to be those relating to volume restriction and the Mottley index.