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Abstract The Charcot-Marie-Tooth-1E (CMT1E) disease is typically described as a peripheral neuropathy in humans, causing decreased nerve conduction, spastic paralysis, and tremor. The Trembler-J (TrJ) mice serve as a high fidelity model of this disease. Here, we use functional ultrasound (fUS) and functional connectivity (FC) to analyze TrJ mice’s brain activity during sensory stimulation and resting state experiments against wild type (WT) mice - the healthy counterpart. fUS is an imaging technique that measures cerebral blood volume (CBV) temporal changes. We study these changes in the primary somatosensory cortex barrel field (S1BF) of both mice populations during periodic vibrissae stimulation, measuring the number of pixels that correlate to the stimulation (i.e., the size of the activation area), the average correlation of these pixels (i.e., the response strength), and the CBV’s rate of change for each stimulation (i.e., the hemodynamic response). Then, we construct a FC matrix for each genotype and experiment by correlating the CBV signals from the eight cortical regions defined by the Paxinos and Franklin atlas. Our results show that TrJ mice have significantly diminished neurovascular responses and altered brain connectivity with respect to WT mice, pointing to central nervous system effects that could shift our understanding of the CMT1E disease.

Abstract Lagoviruses are viruses of the Caliciviridae family affecting lagomorphs. Both pathogenic and non-pathogenic lagoviruses affect the European rabbit (Oryctolagus cuniculus), and they are phylogenetically distinguished. Rabbit Hemorrhagic Disease Virus (RHDV/GI.1) and Rabbit Hemorrhagic Disease Virus-2 (RHDV-2/GI.2) belong to the first group, while in the second group, several genotypes of Rabbit Calicivirus (RCV/GI.3-GI.4) are present. The first RCV strain was described in Italy in 1996, and since then, several RCV strains have been characterised in Europe and Australia. RCVs, different from the pathogenic hepatotropic RHDVs, have an enteric tropism and could be identified from the duodenum/intestine and faeces. This study aimed firstly to indirectly show through a seroepidemiological survey from 1998 to 2008 the circulation of RCVs strains in rabbit farms and then to genetically characterise RCV strains diagnosed in Italy in faecal and intestinal samples of wild and farmed rabbits collected in various regions in the following years (2000–2022). Of 262 analysed samples, 69 resulted in RT-PCR positive for lagovirus but negative for RHDV. Eleven RCV strains were characterised by complete vp60 sequencing. Phylogenetic analysis showed that the Italian RCV strains are grouped in European (RCV_E1/GI.3) and Australian (RCV_E2/GI.4) RCV clusters, with an estimated country prevalence of 26%. Based on the proposed genotype classification, considering the nucleotide differences of vp60 higher than 15%, we can hypothesise that two other genotypes, GI.5 and GI.6, might exist within the cluster of non-pathogenic viruses.

Abstract Large Language Models (LLMs) are recruited in applications that span from clinical assistance and legal support to question answering and education. Their success in specialized tasks has led to the claim that they possess human-like linguistic capabilities related to compositional understanding and reasoning. Yet, reverse-engineering is bound by Moravec’s Paradox, according to which easy skills are hard. We systematically assess 7 state-of-the-art models on a novel benchmark. Models answered a series of comprehension questions, each prompted multiple times in two settings, permitting one-word or open-length replies. Each question targets a short text featuring high-frequency linguistic constructions. To establish a baseline for achieving human-like performance, we tested 400 humans on the same prompts. Based on a dataset of n = 26,680 datapoints, we discovered that LLMs perform at chance accuracy and waver considerably in their answers. Quantitatively, the tested models are outperformed by humans, and qualitatively their answers showcase distinctly non-human errors in language understanding. We interpret this evidence as suggesting that, despite their usefulness in various tasks, current AI models fall short of understanding language in a way that matches humans, and we argue that this may be due to their lack of a compositional operator for regulating grammatical and semantic information.

Abstract An established hallmark of cancer cells is metabolic reprogramming, largely consisting in the exacerbated glucose uptake. Adipocytes in the tumor microenvironment contribute toward breast cancer (BC) progression and are highly responsive to metabolic fluctuations. Metabolic conditions characterizing obesity and/or diabetes associate with increased BC incidence and mortality. To explore BC-adipocytes interaction and define the impact of glucose in such dialogue, Mammary Adipose-derived Mesenchymal Stem Cells (MAd-MSCs) were differentiated into adipocytes and co-cultured with ER+ BC cells while exposed to glucose concentration resembling hyperglycemia or normoglycemia in humans (25mM or 5.5mM). The transcriptome of both cell types in co-culture as in mono-culture was profiled by RNA-Seq to define the impact of adipocytes on BC cells and viceversa (i), the action of glucose on BC cells, adipocytes (ii) and their crosstalk (iii). Noteworthy, we provided evidence that co-culture with adipocytes in a glucose-rich environment determined a re-program of BC cell transcriptome driving lipid accumulation, a hallmark of BC aggressiveness, promoting stem-like properties and reducing Tamoxifen responsiveness. Moreover, our data point out to a transcriptional effect through which BC cells induce adipocytes de-lipidation, paralleled by pluripotency gain, as source of lipids when glucose lowering occurs. Thus, modulating plasticity of peri-tumoral adipocytes may represent a key point for halting BC progression in metabolically unbalanced patients.

Abstract Marine and coastal ecosystems respond to climate change in various ways, such as the type of ecosystem, the species composition, interactions, and distribution, and the effect of local stressors. Metazoan organisms, particularly zooplankton, are important indicators for monitoring the effects climate-driven warming in marine coastal ecosystems over the long term. In this study, the diversity and distribution of zooplankton communities in the Mediterranean Sea (Canyon Dohrn and LTER-MareChiara, Gulf of Naples), a known biodiversity and climate changes hotspot, have been assessed using the integration of morphological-based identification and organismal eDNA. Our findings showed that the multi-locus strategy including the mitochondrial cytochrome c oxidase I (COI) gene and the hypervariable region V9 of the 18S rDNA (18S V9) as targets, improved the taxonomic overview, with the COI gene being more effective than the 18S V9 region for metazoans at the species level. However, appendicularians were detected only with the 18S V9 region. Overall, organismal eDNA is a powerful approach for revealing hidden biodiversity, especially for gelatinous and meroplankton components, and provided new insights into biodiversity patterns. The ecological importance of calanoid copepods in coastal ecosystems has been confirmed. In contrast, the discovery of 13 new metazoan records in the Mediterranean Sea, including two non-indigenous copepod species, suggested that local stressors affect zooplankton community structure and resilience, highlighting the importance of biomonitoring and protecting marine coastal ecosystems.

Abstract Adhesive Capsulitis of the shoulder is a painful pathology limiting shoulder movements, commonly known as “Frozen Shoulder”. Since this pathology limits movement, it is important to make an early diagnosis. Diagnosing capsulitis relies on clinical assessment, although diagnostic imaging, such as Magnetic Resonance Imaging, can provide predictive or supportive information for specific characteristic signs. However, its diagnosis is not so simple nor so immediate, indeed it remains a difficult topic for many general radiologists and expert musculoskeletal radiologists. This study aims to investigate whether it is possible to use disease signs within a medical image to automatically diagnose Adhesive Capsulitis. To this purpose, we propose an automatic Model Checking-based approach to quickly diagnose the Adhesive Capsulitis taking as input the radiomic feature values from the medical images. Furthermore, we compare the performance achieved by our method with diagnostic results obtained by professional radiologists with different levels of experience. To the best of our knowledge, this is the first method for the automatic diagnosis of Adhesive Capsulitis of the Shoulder.

Abstract The aim of this study was to evaluate the antimicrobial efficacy of an air gas soft jet CAP for its potential use in removing oral biofilms, given that plasma-based technologies have emerged as promising methods in periodontology. Two types of biofilms were developed, one by Streptococcus mutans UA 159 bacterial strain and the other by a complex mixture of saliva microorganisms isolated from a patient with periodontitis. This latter biofilm was characterized via Next Generation Sequencing to determine the main bacterial phyla. The CAP source was applied at a distance of 6 mm for different time points. A statistically significant reduction of both CFU count and XTT was already detected after 60 s of CAP treatment. CLSM analysis supported CAP effectiveness in killing the microorganisms inside the biofilm and in reducing the thickness of the biofilm matrix. Cytotoxicity tests demonstrated the possible use of CAP without important side effects towards human gingival fibroblasts cell line. The current study showed that CAP treatment was able to significantly reduce preformed biofilms developed by both S. mutans and microorganisms isolated by a saliva sample. Further studies should be conducted on biofilms developed by additional saliva donors to support the potential of this innovative strategy to counteract oral pathogens responsible for periodontal diseases.

Abstract Enterobacter asburiae, member of the Enterobacter cloacae complex (ECC) group, shows an increasing clinical relevance being responsible for infections like pneumonia, urinary tract infections and septicemia. The aim of the present study was the investigation of the genomic features of two XDR E. asburiae ST229 clinical strains co-carrying blaNDM-1 and blaVIM-1 determinants, collected in October 2021 and in June 2022, respectively. Two E. asburiae strains were collected from rectal swabs of as many patients admitted to the cardiopulmonary intensive care unit of Fondazione I.R.C.C.S. “Policlinico San Matteo” in Pavia, Italy. Based on the antibiotic susceptibility profile results, both isolates showed an XDR phenotype, retaining susceptibility only to fluoroquinolones. Both isolates shared identical resistome, virulome, plasmid content, and belonged to ST229, a rarely reported sequence type. They co-harbored blaNDM-1 and blaVIM-1 genes, that resulted located on transferable plasmids by conjugation and transformation. Moreover, both strains differed in 24 SNPs and showed genetic relatedness with E. asburiae ST709 and ST27. We described the first case of ST229 E. asburiae co-harboring blaNDM-1 and blaVIM-1 in Italy. This study points out the emergence of carbapenemases in low-risk pathogens, representing a novel challenge for public health, that should include such types of strains in dedicated surveillance programs. Antimicrobial susceptibility testing was carried out using Thermo Scientific™ Sensititre™ Gram Negative MIC Plates DKMGN. Both strains underwent whole-genome sequencing (WGS) using Illumina Miseq platform. Resistome, plasmidome, virulome, MLST, plasmid MLST and a SNPs-based phylogenetic tree were in silico determined.

Abstract Data on the SARS-CoV-2 infection among primary health care workers (PHCWs) are scarce but essential to reflect on policy regarding prevention and control measures. We assessed the prevalence of PHCWs who have been infected by SARS-CoV-2 in comparison with modeling from the general population in metropolitan France, and associated factors. A cross-sectional study was conducted among general practitioners (GPs), pediatricians, dental and pharmacy workers in primary care between May and August 2021. Participants volunteered to provide a dried-blood spot for SARS-CoV-2 antibody assessment and completed a questionnaire. The primary outcome was defined as the detection of infection-induced antibodies (anti-nucleocapsid IgG, and for non-vaccinees: anti-Spike IgG and neutralizing antibodies) or previous self-reported infection (positive RT-qPCR or antigenic test, or positive ELISA test before vaccination). Estimates were adjusted using weights for representativeness and compared with prediction from the general population. Poisson regressions were used to quantify associated factors. The analysis included 1612 PHCWs. Weighted prevalences were: 31.7% (95% CI 27.5–36.0) for GPs, 28.7% (95% CI 24.4–33.0) for pediatricians, 25.2% (95% CI 20.6–31.0) for dentists, and 25.5% (95% CI 18.2–34.0) for pharmacists. Estimates were compatible with model predictions for the general population. PHCWs more likely to be infected were: GPs compared to pharmacist assistants (adjusted prevalence ratio [aPR] = 2.26; CI 95% 1.01–5.07), those living in Île-de-France (aPR = 1.53; CI 95% 1.14–2.05), South-East (aPR = 1.57; CI 95% 1.19–2.08), North-East (aPR = 1.81; CI 95% 1.38–2.37), and those having an unprotected contact with a COVID-19 case within the household (aPR = 1.48; CI 95% 1.22–1.80). Occupational factors were not associated with infection. In conclusion, the risk of SARS-CoV-2 exposure for PHCWs was more likely to have occurred in the community rather than at their workplace.

Abstract Bilingualism is linked to both enhanced and hampered performance in various cognitive measures, yet the extent to which these bilingual advantages and disadvantages co-occur is unclear. To address this gap, we perform a systematic review and two quantitative analyses. First, we analyze results from 39 studies, obtained through the PRISMA method. Less than 50% of the studies that show up as results for the term “bilingual disadvantage” report exclusively a disadvantage, that shows bilinguals performing worse than monolinguals in a task. A Bayesian analysis reveals robust evidence for bilingual effects, but no evidence for differences in the proportion of advantages and disadvantages, suggesting that when results from different cognitive domains such as executive functions and verbal fluency are analyzed together, bilingual effects amount to a zero-sum game. This finding was replicated by repeating the analysis, using the datasets of two recent meta-analyses. We propose that the equilibrium we observe between positive and negative outcomes may not be accidental. Contrary to widespread belief, advantageous and disadvantageous effects are not stand-alone outcomes in free variation. We reframe them as the connatural components of a dynamic trade-off, whereby enhanced performance in one cognitive measure is offset by an incurred cost in another domain.

Abstract Chemical space modelling has great importance in unveiling and visualising latent information, which is critical in predictive toxicology related to drug discovery process. While the use of traditional molecular descriptors and fingerprints may suffer from the so-called curse of dimensionality, complex networks are devoid of the typical drawbacks of coordinate-based representations. Herein, we use chemical space networks (CSNs) to analyse the case of the developmental toxicity (Dev Tox), which remains a challenging endpoint for the difficulty of gathering enough reliable data despite very important for the protection of the maternal and child health. Our study proved that the Dev Tox CSN has a complex non-random organisation and can thus provide a wealth of meaningful information also for predictive purposes. At a phase transition, chemical similarities highlight well-established toxicophores, such as aryl derivatives, mostly neurotoxic hydantoins, barbiturates and amino alcohols, steroids, and volatile organic compounds ether-like chemicals, which are strongly suspected of the Dev Tox onset and can thus be employed as effective alerts for prioritising chemicals before testing.

Abstract Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like “where” and “when” still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increase. However, the public health costs associated with these delays tend to grow with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality, and stress on the healthcare system.

Abstract Medulloblastoma (MB) is the most common malignant brain tumour in children. High-risk MB patients harbouring MYC amplification or overexpression exhibit a very poor prognosis. Aberrant activation of MYC markedly reprograms cell metabolism to sustain tumorigenesis, yet how metabolism is dysregulated in MYC-driven MB is not well understood. Growing evidence unveiled the potential of BET-bromodomain inhibitors (BETis) as next generation agents for treating MYC-driven MB, but whether and how BETis may affect tumour cell metabolism to exert their anticancer activities remains unknown. In this study, we explore the metabolic features characterising MYC-driven MB and examine how these are altered by BET-bromodomain inhibition. To this end, we employed an NMR-based metabolomics approach applied to the MYC-driven MB D283 and D458 cell lines before and after the treatment with the BETi OTX-015. We found that OTX-015 triggers a metabolic shift in both cell lines resulting in increased levels of myo-inositol, glycerophosphocholine, UDP-N-acetylglucosamine, glycine, serine, pantothenate and phosphocholine. Moreover, we show that OTX-015 alters ascorbate and aldarate metabolism, inositol phosphate metabolism, phosphatidylinositol signalling system, glycerophospholipid metabolism, ether lipid metabolism, aminoacyl-tRNA biosynthesis, and glycine, serine and threonine metabolism pathways in both cell lines. These insights provide a metabolic characterisation of MYC-driven childhood MB cell lines, which could pave the way for the discovery of novel druggable pathways. Importantly, these findings will also contribute to understand the downstream effects of BETis on MYC-driven MB, potentially aiding the development of new therapeutic strategies to combat medulloblastoma.

Abstract The gut microbiota exerts a variety of positive effects on the intestinal homeostasis, including the production of beneficial molecules, control of the epithelial barrier integrity and the regulation of the balance between host’s cell death and proliferation. The interactions between commensal bacteria and intestinal cells are still under-investigated and is then of paramount importance to address such interactions at the molecular and cellular levels. We report an in vitro analysis of the effects of molecules secreted by Lactobacillus gasseri SF1183 on HCT116 cells, selected as a model of intestinal epithelial cells. SF1183 is a L. gasseri strain isolated from an ileal biopsy of a human healthy volunteer, able to prevent colitis symptoms in vivo. Expanding previous findings, we show that bioactive molecules secreted by SF1183 reduce the proliferation of HCT116 cells in a reversible manner determining a variation in cell cycle markers (p21WAF, p53, cyclin D1) and resulting in the protection of HCT116 cells from TNF-alfa induced apoptosis, an effect potentially relevant for the protection of the epithelial barrier integrity and reconstitution of tissue homeostasis. Consistently, SF1183 secreted molecules increase the recruitment of occludin, a major component of TJ, at the cell–cell contacts, suggesting a reinforcement of the barrier function.

Ptychography enables coherent diffractive imaging (CDI) of extended samples by raster scanning across the illuminating XUV/X-ray beam, thereby generalizing the unique advantages of CDI techniques. Table-top realizations of this method are urgently needed for many applications in sciences and industry. Previously, it was only possible to image features much larger than the illuminating wavelength with table-top ptychography although knife-edge tests suggested sub-wavelength resolution. However, most real-world imaging applications require resolving of the smallest and closely-spaced features of a sample in an extended field of view. In this work, resolving features as small as 2.5 λ (45 nm) using a table-top ptychography setup is demonstrated by employing a high-order harmonic XUV source with record-high photon flux. For the first time, a Rayleigh-type criterion is used as a direct and unambiguous resolution metric for high-resolution table-top setup. This reliably qualifies this imaging system for real-world applications e.g. in biological sciences, material sciences, imaging integrated circuits and semiconductor mask inspection.

Abstract A small-scale plant was built for measuring the ability of solid sorbents towards the capture of carbon dioxide (CO2) in exhaust flue gas from an internal combustion engine. The investigated sorbents were calcium and lithium hydroxides. Both sorbents are low cost and used in the breathing gas purification systems. The carbonation capacity of each sorbent was measured for different sorbent granulometry (pellets and powder), different temperature (from ambient up to 300 °C), gas space velocity, moisture content and chemical composition of the gaseous stream. The aim was, in fact, to expose the sorbents to a gas stream with chemical and physical parameters close to those at the exhaust of an internal combustion engine. Carbonation capacity was measured with a double technique: on-line by continuously CO2 measurement with a non-dispersive infrared analyzer and off-line by using scanning electron microscopy on carbonated sorbents. Experimental results showed good CO2 uptake capacity of calcium hydroxide at low temperature (between 20 and 150 °C). Performance improvements came from the fine granulometry due to the increased exposed surface area; moreover, the presence of the moisture in gas stream also enhanced CO2 capture. The presence of sulphur dioxide and nitric oxide, instead, greatly decreased the carbonation capacity of sorbents.

Abstract COVID-19 is strongly influenced by age and comorbidities. Acute kidney injury (AKI) is a frequent finding in COVID-19 patients and seems to be associated to mortality and severity. On the other hand, the role of kidney dysfunction in COVID-19 is still debated. We performed a retrospective study in a cohort of 174 hospitalized COVID-19 patients in Italy from March 3rd to May 21st 2020, to investigate the role of kidney dysfunction on COVID-19 severity and mortality. Moreover, we examined in depth the relationship between kidney function, age, and progression of COVID-19, also using different equations to estimate the glomerular filtration rate (GFR). We performed logistic regressions, while a predictive analysis was made through a machine learning approach. AKI and death occurred respectively in 10.2% and 19.5%, in our population. The major risk factors for mortality in our cohort were age [adjusted HR, 6.2; 95% confidence interval (CI) 1.8–21.4] and AKI [3.36 (1.44–7.87)], while, in these relationships, GFR at baseline mitigated the role of age. The occurrence of AKI was influenced by baseline kidney function, D-dimer, procalcitonin and hypertension. Our predictive analysis for AKI and mortality reached an accuracy of ≥ 94% and ≥ 91%, respectively. Our study scales down the role of kidney function impairment on hospital admission , especially in elderly patients. BIS-1 formula demonstrated a worse performance to predict the outcomes in COVID-19 patients when compared with MDRD and CKD-EPI.

Abstract Endometriosis is a chronic gynecological disorder involved in the pathogenesis of chronic pelvic pain, based on a probable up regulation of the inflammatory system. The objective of the study is to investigate the peritoneal and serum levels of ENA-78 with the severity of endometriosis symptoms (dysmenorrhea, chronic pelvic pain and dyspareunia) using the visual analogue scale (VAS). This is a prospective case–control study that included 53 symptomatic women with evidence of endometriosis and 53 age-matched controls who underwent elective laparoscopic surgery for benign diseases. The concentration of ENA-78 was assessed in blood and peritoneal fluid samples in the follicular phase. In peritoneal fluid and plasma, the concentration of ENA-78 was significantly higher in cases than in controls (p

Abstract SARS-CoV-2 enters the intestine by the spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors in enterocyte apical membranes, leading to diarrhea in some patients. Early treatment of COVID-19-associated diarrhea could relieve symptoms and limit viral spread within the gastrointestinal (GI) tract. Diosmectite, an aluminomagnesium silicate adsorbent clay with antidiarrheal effects, is recommended in some COVID-19 management protocols. In rotavirus models, diosmectite prevents pathogenic effects by binding the virus and its enterotoxin. We tested the trapping and anti-inflammatory properties of diosmectite in a SARS-CoV-2 model. Trapping effects were tested in Caco-2 cells using spike protein receptor-binding domain (RBD) and heat-inactivated SARS-CoV-2 preparations. Trapping was assessed by immunofluorescence, alone or in the presence of cells. The effect of diosmectite on nuclear factor kappa B (NF-kappaB) activation and CXCL10 secretion induced by the spike protein RBD and heat-inactivated SARS-CoV-2 were analyzed by Western blot and ELISA, respectively. Diosmectite bound the spike protein RBD and SARS-CoV-2 preparation, and inhibited interaction of the spike protein RBD with ACE2 receptors on the Caco-2 cell surface. Diosmectite exposure also inhibited NF-kappaB activation and CXCL10 secretion. These data provide direct evidence that diosmectite can bind SARS-CoV-2 components and inhibit downstream inflammation, supporting a mechanistic rationale for consideration of diosmectite as a management option for COVID-19-associated diarrhea.

Abstract In Europe, multiple waves of infections with SARS-CoV-2 (COVID-19) have been observed. Here, we have investigated whether common patterns of cytokines could be detected in individuals with mild and severe forms of COVID-19 in two pandemic waves, and whether machine learning approach could be useful to identify the best predictors. An increasing trend of multiple cytokines was observed in patients with mild or severe/critical symptoms of COVID-19, compared with healthy volunteers. Linear Discriminant Analysis (LDA) clearly recognized the three groups based on cytokine patterns. Classification and Regression Tree (CART) further indicated that IL-6 discriminated controls and COVID-19 patients, whilst IL-8 defined disease severity. During the second wave of pandemics, a less intense cytokine storm was observed, as compared with the first. IL-6 was the most robust predictor of infection and discriminated moderate COVID-19 patients from healthy controls, regardless of epidemic peak curve. Thus, serum cytokine patterns provide biomarkers useful for COVID-19 diagnosis and prognosis. Further definition of individual cytokines may allow to envision novel therapeutic options and pave the way to set up innovative diagnostic tools.

Abstract The control of Covid 19 epidemics by public health policy in Italy during the first and the second epidemic waves has been driven by using reproductive number Rt(t) to identify the supercritical (percolative), the subcritical (arrested), separated by the critical regime. Here we show that to quantify the Covid-19 spreading rate with containment measures there is a need of a 3D expanded parameter space phase diagram built by the combination of Rt(t) and doubling time Td(t). In this space we identify the Covid-19 dynamics in Italy and its administrative Regions. The supercritical regime is mathematically characterized by (i) the power law of Td vs. [Rt(t) − 1] and (ii) the exponential behaviour of Td vs. time, either in the first and in the second wave. The novel 3D phase diagram shows clearly metastable states appearing before and after the second wave critical regime. for loosening quarantine and tracing of actives cases. The metastable states are precursors of the abrupt onset of a next nascent wave supercritical regime. This dynamic description allows epidemics predictions needed by policymakers interested to point to the target "zero infections" with the elimination of SARS-CoV-2, using the Finding mobile Tracing policy joint with vaccination-campaign, in order to avoid the emergence of recurrent new variants of SARS-CoV-2 virus, accompined by recurrent long lockdowns, with large economical losses, and large number of fatalities.

Abstract Efficient prevention and control of healthcare associated infections (HAIs) is still an open problem. Using contact data from wearable sensors at a short-stay geriatric ward, we propose a proof-of-concept modeling study that reorganizes nurse schedules for efficient infection control. This strategy switches and reassigns nurses’ tasks through the optimization of shift timelines, while respecting feasibility constraints and satisfying patient-care requirements. Through a Susceptible-Colonized-Susceptible transmission model, we found that schedules reorganization reduced HAI risk by 27% (95% confidence interval [24, 29]%) while preserving timeliness, number, and duration of contacts. More than 30% nurse-nurse contacts should be avoided to achieve an equivalent reduction through simple contact removal. Nurse scheduling can be reorganized to break potential chains of transmission and substantially limit HAI risk, while ensuring the timeliness and quality of healthcare services. This calls for including optimization of nurse scheduling practices in programs for infection control in hospitals.

Abstract The COVID-19 pandemic forced authorities worldwide to implement moderate to severe restrictions in order to slow down or suppress the spread of the disease. It has been observed in several countries that a significant number of people fled a city or a region just before strict lockdown measures were implemented. This behavior carries the risk of seeding a large number of infections all at once in regions with otherwise small number of cases. In this work, we investigate the effect of fleeing on the size of an epidemic outbreak in the region under lockdown, and also in the region of destination. We propose a mathematical model that is suitable to describe the spread of an infectious disease over multiple geographic regions. Our approach is flexible to characterize the transmission of different viruses. As an example, we consider the COVID-19 outbreak in Italy. Projection of different scenarios shows that (i) timely and stricter intervention could have significantly lowered the number of cumulative cases in Italy, and (ii) fleeing at the time of lockdown possibly played a minor role in the spread of the disease in the country.

Abstract Natural killer (NK) cells mediate innate host defense against microbial infection and cancer. Hypoxia and low glucose are characteristic for these tissue lesions but do not affect early interferon (IFN) γ and CC chemokine release by interleukin 15 (IL-15) primed human NK cells in vitro. Hypoxia inducible factor 1α (HIF-1α) mediates cellular adaption to hypoxia. Its production is supported by mechanistic target of rapamycin complex 1 (mTORC1) and signal transducer and activator of transcription 3 (STAT3). We used chemical inhibition to probe the importance of mTORC1 and STAT3 for the hypoxia response and of STAT3 for the cytokine response in isolated and IL-15 primed human NK cells. Cellular responses were assayed by magnetic bead array, RT-PCR, western blotting, flow cytometry, and metabolic flux analysis. STAT3 but not mTORC1 activation was essential for HIF-1α accumulation, glycolysis, and oxygen consumption. In both primed normoxic and hypoxic NK cells, STAT3 inhibition reduced the secretion of CCL3, CCL4 and CCL5, and it interfered with IL-12/IL-18 stimulated IFNγ production, but it did not affect cytotoxic granule degranulation up on target cell contact. We conclude that IL-15 priming promotes the HIF-1α dependent hypoxia response and the early cytokine response in NK cells predominantly through STAT3 signaling.

Abstract The nervous system is one of the most complex expressions of biological evolution. Its high performance mostly relies on the basic principle of the action potential, a sequential activation of local ionic currents along the neural fiber. The implications of this essentially electrical phenomenon subsequently emerged in a more comprehensive electromagnetic perspective of neurotransmission. Several studies focused on the possible role of photons in neural communication and provided evidence of the transfer of photons through myelinated axons. A hypothesis is that myelin sheath would behave as an optical waveguide, although the source of photons is controversial. In a previous work, we proposed a model describing how photons would arise at the node of Ranvier. In this study we experimentally detected photons in the node of Ranvier by Ag+ photoreduction measurement technique, during electrically induced nerve activity. Our results suggest that in association to the action potential a photonic radiation takes place in the node.

Abstract The incidence of atrial fibrillation (AF) in cryptogenic stroke (CS) patients has been studied in carefully controlled clinical trials, but real-world data are limited. We investigated the incidence of AF in clinical practice among CS patients with an insertable cardiac monitor (ICM) placed for AF detection. Patients with CS admitted to our Stroke Unit were included in the study; they received an ICM and were monitored for up to 3 years for AF detection. All detected AF episodes of at least 120 sec were considered. From March 2016 to March 2019, 58 patients (mean age 68.1 ± 9.3 years, 67% male) received an ICM to detect AF after a CS. No patients were lost to follow-up. AF was detected in 24 patients (41%, AF group mean age 70.8 ± 9.4 years, 62% male) after a mean time of 6 months from ICM (ranging from 2 days to 2 years) and 8 months after CS (ranging from 1 month to 2 years). In these AF patients, anticoagulant treatment was prescribed and nobody had a further stroke. In conclusion, AF episodes were detected via continuous monitoring with ICMs in 41% of implanted CS patients. AF in CS patients is asymptomatic and difficult to diagnose by strategies based on intermittent short-term recordings. Therefore, we suggest that ICMs should be part of daily practice in the evaluation of CS patients.