Explore the vast range of titles available.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 μm (PM 10 ) and nitrogen dioxide (NO 2 ), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM 10 and NO 2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO 2 , but not PM 10 . Age and previous NO 2 exposure were independent predictors for mortality. NO 2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO 2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

Background: Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration. Methods: Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor- β or basic fibroblast growth factor. Results: A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors. Conclusion: These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.

Optical neural networks process information at the speed of light and are energetically efficient. Photonic artificial intelligence allows speech recognition, image classification, and Ising machines. Modern machine learning paradigms, as extreme learning machines, reveal that disordered and biological materials may realize optical neural networks with thousands of nodes trained only at the input and at the readout. May we use living matter for machine learning? Here, we employ living three-dimensional tumor brain models to demonstrate a random optical learning machine (ROM) for the investigation of glioblastoma. The tumor spheroid act as a computational reservoir. The ROM detects cancer morphodynamics by laser-induced hyperthermia, quantifies chemotherapy, and cell metabolism. The ROM is a sensitive noninvasive smart probe for cytotoxicity assay and enables real-time investigation of tumor dynamics. We hence design and demonstrate a novel bio-hardware for optical computing and the study of light/complex matter interaction. Can living systems function as artificial neural networks for biophysical applications? Here, the authors show that living tumor spheroids can be employed as random optical learning machines and used to investigate cancer morphodynamics and quantify the effect of chemotherapy.

Objective To collect medical data on women's boxing. Design Cross-sectional and longitudinal study. Setting Medical examinations requested by Italian laws. Participants A retrospective study was conducted on all female boxing competitions in Italy from April 2001 to December 2007. Sixty-one amateur female boxers were evaluated longitudinally. Interventions (1) Retrospective study: All pre-/postmatch medical reports were analysed. (2) Prospective study: Breast, gynaecologic, brain, eyes, ear, nose and throat examinations were carried out. Main outcome measurements (1) Retrospective study: Any injury assessed before/after the match. (2) Prospective study: Health problems which could be related to boxing activity. Results (1) Retrospective study: Data from 5600 examinations were collected. Precompetition, a medical problem was recorded in three athletes (one conjunctiva hyperemia, one zygomatic bruise, one eyelid haematoma). Post competition, 51/2800 medical checks showed mild common injuries, such as soft tissue facial lesions, epistaxis and hand-wrist problems. Only one concussion was recorded with hospitalisation (for a thorough evaluation). Another athlete was hospitalised for a nasal fracture. (2) Prospective study: Two fibroadenomas, three ovarian cysts and one intramural uterine myoma were diagnosed. In four boxers, non-specific electroencephalographic abnormalities were detected, however, with a normal brain MRI in three (the fourth is still waiting for the radiologic procedure). Nasal septum deviation was common (42.6%) and a transmissive hypoacusia was observed in two athletes. No major eye injuries were reported. Conclusions Female boxing seems to be a safe sport with a very low incidence of events requiring hospitalisation. No specific diseases in female boxers could be observed, in particular regarding the breast and reproductive system.

The first cryomodule of the new HIE-ISOLDE rare isotope accelerator has recently been commissioned with beam at CERN, with the second cryomodule ready for installation. Each cryomodule contains five superconducting low-beta quarter wave cavities, produced with the technology of sputtering a thin niobium film onto the copper substrate (Nb/Cu ). This technology has several benefits compared to the bulk niobium solution, but also drawbacks among which the most relevant is the increase of surface resistance with accelerating field. Recent work has established the possible connection of this phenomenon to local defects in the Nb/Cu interface, which may lead to increased thermal impedance and thus local thermal runaway. We have analyzed the performance of the HIE-ISOLDE cavities series production, as well as of a few prototypes’, in terms of this model, and found a strong correlation between the rf properties and one of the model characteristic quantities, namely the total surface having increased interface thermal impedance.

High proteolytic degradation and poor absorption through epithelial barriers are major challenges to successful oral delivery of therapeutics. Nanoparticle platforms can enhance drug stability and extend the residence time in gastrointestinal (GI) tract. However, drug delivery systems are often inactivated in acidic environment of stomach or suffer poor absorption from intestinal cells due to the mucus layer. To overcome these issues we developed a drug delivery system constituted by a protein construct made by a Rotavirus capsid protein (VP6) and the small ubiquitin-like modifier SUMO. This chimeric construct allows specificity towards intestinal cells, the Rotavirus natural target, combined by an enhanced stability given by the eukaryotic protein transporter SUMO. Furthermore SUMO can act as a molecular switch that facilitates import/export of its ligand to the nucleus, the hypersensitive subcellular site target of many cell killing therapies. In this paper we show that SUMO-VP6 constructs self-assembly into stable nanocarriers. SUMO-VP6 nanocarriers display ideal features for drug delivery: a small size and high monodispersity, a high stability in different pH conditions and a high uptake in the nuclear and cytoplasmic compartment of intestinal cells. These features make SUMO-VP6 nanocarriers a promising novel system for oral delivery of poorly soluble drugs.

Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (\"epidrugs\") is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials is evaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF. Keywords: heart failure, personalized therapy, epidrugs

The pancreas is vulnerable to ethanol toxicity, but the pathogenesis of alcoholic pancreatitis is not fully defined. The intracellular oxidative balance and the characteristics of the secretion of isolated rat pancreatic acinar cells stimulated with the cholecystokinin analogue cerulein were assayed after acute oral ethanol (4 g/kg) load. Pancreatic acinar cells from ethanol-treated rats showed a significant (p < 0.02) lower content of total glutathione and protein sulfhydryls, and higher levels of oxidized glutathione (p < 0.03), malondialdehyde, and protein carbonyls (p < 0.05). Ethanol-intoxicated acinar cells showed a lower baseline amylase output compared to controls, with the difference being significantly exacerbated by cerulein stimulation. After cerulein, the release of protein carbonyls by ethanol-treated cells was significantly increased, whereas that of protein sulfhydryls was significantly decreased. In conclusion, ethanol oxidatively damages pancreatic acinar cells; cerulein stimulation is followed by a lower output of amylase and by a higher release of oxidized proteins by pancreatic acinar cells from ethanol-treated rats. These findings may account for the decreased exocrine function, intraductular plug formation, and protein precipitation in alcoholic pancreatitis.

Future experiments on neutrinoless double beta-decay with the aim of exploring the inverted hierarchy region have to employ detectors with excellent energy resolution and zero background in the energy region of interest. Cryogenic scintillating bolometers turn out to be a suitable candidate since they offer particle discrimination: the dual channel detection of the heat and the scintillation light signal allows for particle identification. In particular such detectors permit for a suppression of α-induced backgrounds, a key-issue for next-generation tonne-scale bolometric experiments. We report on the progress and current status of the LUCIFER/CUPID-0 demonstrator, the first array of scintillating bolometers based on enriched Zn82Se crystals which is expected to start data taking in 2016 and the potential of this detection technique for a future tonne-scale bolometric experiment after CUORE.

Objective: To assess the effects of a diet rich in protein of animal origin in comparison to one with a protein intake of about 15% of the total daily calories on body composition and arterial function. Design: Randomized prospective study with parallel groups. Body weight (BW), blood pressure (BP), main parameters of carbohydrate and lipid metabolism, body mass composition by bioelectrical impedance analysis, forearm blood flow at rest and in the postischaemic phase by strain gauge plethysmography and flow-mediated dilation of the brachial artery by echography were measured at baseline and after 6 months of the dietary intervention. Subjects: In total, 15 clinically healthy male volunteers, regularly performing a mixed training three times weekly for 90 min. Intervention: The participants were randomly prescribed a diet with high (1.9 g/kg BW) or normal (1.3 g/kg BW) protein content. Statistical analysis: Differences between means were evaluated by the t-tests for paired or unpaired data and by one way analysis of variance. The strength of correlation between variables was investigated by bivariate Pearson correlation. Results: Serum cholesterol significantly decreased with both diets in comparison to baseline values, whereas BW was slightly but significantly reduced only by the high-protein (HP) diet. No change was detected in BP and the other metabolic parameters. Body mass composition was not significantly modified by either diet. On the other hand, postischaemic flow-mediated dilation of the brachial artery was enhanced by the sole normal protein (NP) diet, whereas no change in the forearm blood flow, both at rest and in the postischaemic phase, was detected. Conclusions: These preliminary results indicate that HP diet was found to be not useful in increasing the muscle mass in comparison to a NP intake. In contrast to this, the latter diet seems to enhance the endothelial function of the arterial vessels with a more pronounced dilatation of the lumen in response to the increase in blood flow.