How distant? An experimental analysis of students' COVID-19 exposure and physical distancing in university buildings.

Closed university buildings proved to be one of the main hot spots for virus transmission during pandemics. As shown during the COVID-19 pandemic, physical distancing is one of the most effective measures to limit such transmission. As universities prepare to manage in-class activities, students' adherence to physical distancing requirements is a priority topic. Unfortunately, while physical distancing in classrooms can be easily managed, the movement of students inside common spaces can pose high risk of close proximity. This paper provides an experimental analysis of unidirectional student movement inside a case-study university building to investigate how physical distancing requirements impact student movement and grouping behaviour. Results show general adherence with the minimum required physical distancing guidance, but spaces such as corridors pose higher risk of exposure than doorways. Doorway width, in combination with group behaviour, affect the students' capacity to keep the recommended physical distance. Furthermore, questionnaire results show that students report higher perceived vulnerability while moving along corridors. Evidence-based results can support decision-makers in understanding individuals' exposure to COVID-19 in universities and researchers in developing behavioural models in preparation of future outbreaks and pandemics.

Inflammatory and oxidative stress biomarkers in alkaptonuria: data from the DevelopAKUre project.

OBJECTIVE: The aim of this work was to assess baseline serum levels of established biomarkers related to inflammation and oxidative stress in samples from alkaptonuric subjects enrolled in SONIA1 (n = 40) and SONIA2 (n = 138) clinical trials (DevelopAKUre project). METHODS: Baseline serum levels of Serum Amyloid A (SAA), IL-6, IL-1ß, TNFα, CRP, cathepsin D (CATD), IL-1ra, and MMP-3 were determined through commercial ELISA assays. Chitotriosidase activity was assessed through a fluorimetric method. Advanced Oxidation Protein Products (AOPP) were determined by spectrophotometry. Thiols, S-thiolated proteins and Protein Thiolation Index (PTI) were determined by spectrophotometry and HPLC. Patients' quality of life was assessed through validated questionnaires. RESULTS: We found that SAA serum levels were significantly increased compared to reference threshold in 57.5% and 86% of SONIA1 and SONIA2 samples, respectively. Similarly, chitotriosidase activity was above the reference threshold in half of SONIA2 samples, whereas CRP levels were increased only in a minority of samples. CATD, IL-1ß, IL-6, TNFα, MMP-3, AOPP, thiols, S-thiolated protein and PTI showed no statistically significant differences from control population. We provided evidence that alkaptonuric patients presenting with significantly higher SAA, chitotriosidase activity and PTI reported more often a decreased quality of life. This suggests that worsening of symptoms in alkaptonuria (AKU) is paralleled by increased inflammation and oxidative stress, which might play a role in disease progression. CONCLUSIONS: Monitoring of SAA may be suggested in AKU to evaluate inflammation. Though further evidence is needed, SAA, chitotriosidase activity and PTI might be proposed as disease activity markers in AKU.

Surface properties of nanocrystalline TiO2 coatings in relation to the in vitro plasma protein adsorption.

This study reports on the selective adsorption of whole plasma proteins on hydrothermally (HT) grown TiO2-anatase coatings and its dependence on the three main surface properties: surface charge, wettability and roughness. The influence of the photo-activation of TiO2 by UV irradiation was also evaluated. Even though the protein adhesion onto Ti-based substrates was only moderate, better adsorption of any protein (at pH = 7.4) occurred for the most negatively charged and hydrophobic substrate (Ti non-treated) and for the most nanorough and hydrophilic surface (HT Ti3), indicating that the mutual action of the surface characteristics is responsible for the attraction and adhesion of the proteins. The HT coatings showed a higher adsorption of certain proteins (albumin 'passivation' layer, apolipoproteins, vitamin D-binding protein, ceruloplasmin, α-2-HS-glycoprotein) and higher ratios of albumin to fibrinogen and albumin to immunoglobulin γ-chains. The UV pre-irradiation affected the surface properties and strongly reduced the adsorption of the proteins. These results provide in-depth knowledge about the characterization of nanocrystalline TiO2 coatings for body implants and provide a basis for future studies on the hemocompatibility and biocompatibility of such surfaces.

Distinctive gene expression profiles in Balb/3T3 cells exposed to low dose cobalt nanoparticles, microparticles and ions: potential nanotoxicological relevance.

Size-dependent characteristics of novel engineered nanomaterials might result in unforeseen biological responses and toxicity. To address this issue, we used cDNA microarray analysis (13443 genes) coupled with bioinformatics and functional gene annotation studies to investigate the transcriptional profiles of Balb/3T3 cells exposed to a low dose (1 μM) of cobalt nanoparticles (CoNP), microparticles (CoMP) and ions (Co2+). CoNP, CoMP and Co2+ affected 124, 91 and 80 genes, respectively. Hierarchical clustering revealed two main gene clusters, one up-regulated, mainly after Co2+, the other down-regulated, mainly after CoNP and CoMP. The significant Gene Ontology (GO) terms included oxygen binding and transport and hemoglobin binding for Co2+, while the GOs of CoMP and CoNP were related to nucleus and intracellular components. Pathway analysis highlighted: i) mitochondrial dysfunction for Co2+, ii) signaling, activation of innate immunity, and apoptosis for CoNP, and iii) cell metabolism, G1/S cell cycle checkpoint regulation and signaling for CoMP. Unlike ions, particles affected toxicologically-relevant pathways implicated in carcinogenesis and inflammation.

Fish welfare and genomics.

There is a considerable public and scientific debate concerning welfare of fish in aquaculture. In this review, we will consider fish welfare as an integration of physiological, behavioral, and cognitive/emotional responses, all of which are essentially adaptative responses to stressful situations. An overview of fish welfare in this context suggests that understanding will rely on knowledge of all components of allostatic responses to stress and environmental perturbations. The development of genomic technologies provides new approaches to this task, exemplified by how genome-wide analysis of genetic structures and corresponding expression patterns can lead to the discovery of new aspects of adaptative responses. We will illustrate how the genomic approach may give rise to new biomarkers for fish welfare and also increase our understanding of the interaction between physiological, behavioral, and emotional responses. In a first part, we present data on expression of candidate genes selected a priori. This is a common avenue to develop molecular biomarkers capable of diagnosing a stress condition at its earliest onset, in order to allow quick corrective intervention in an aquaculture setting. However, most of these studies address isolated physiological functions and stress responses that may not be truly indicative of animal welfare, and there is only rudimentary understanding of genes related to possible cognitive and emotional responses in fish. We also present an overview on transcriptomic analysis related to the effect of aquaculture stressors, environmental changes (temperature, salinity, hypoxia), or concerning specific behavioral patterns. These studies illustrate the potential of genomic approaches to characterize the complexity of the molecular mechanisms which underlies not only physiological but also behavioral responses in relation to fish welfare. Thirdly, we address proteomic studies on biological responses to stressors such as salinity change and hypoxia. We will also consider proteomic studies developed in mammals in relation to anxiety and depressive status which may lead to new potential candidates in fish. Finally, in the conclusion, we will suggest new developments to facilitate an integrated view of fish welfare. This includes use of laser microdissection in the transcriptomic/proteomic studies, development of meta-analysis methods for extracting information from genomic data sets, and implementation of technological advances for high-throughput proteomic studies. Development of these new approaches should be as productive for our understanding of the biological processes underlying fish welfare as it has been for the progress of pathophysiological research.

Immunotoxicity of nanoparticles.

The interaction between NPs and immune system has been demonstrated, however, the data available are limited. Among all traits, i.s. hydrophilicity, lipophilicity, catalytic activity, composition, electronic structure, capacity to bind or coat surface species and solubility, the dimension, and consequently the surface area, seems to be the main factor that contribute to the interactions of NPs with biological tissues and immune system in particular. Certain NPs accumulate to regional lymph nodes, where they can be taken up and processed by dendritic cells, interact with self-proteins and, hence, modify their antigenicity and elicit altered immune responses and even autoimmunity. Other NPs may induce allergic sensitization, i.e. allergic contact dermatitis to Pd. In vitro studies demonstrated that NPs can modulate cytokine production toward Th1 (Pl, Pd, Ni, Co) or Th2 (Ti, mw and sw Carbon) production patterns. Some NPs have been linked to allergic sensitization, however, It is unlikely that NPs can act as a hapten inducing a specific IgE production, likely they can act as adjuvant and induce a specific pattern of cytokines, antibody and cells that favor allergic sensitization to environmental allergens. Furthermore, NPs demonstrated pro-inflammatory effects in the lung in experimental animal with increased expression on IL-1beta, MIP-1alpha, MCP-1, MIP-2, keratinocyte chemoattractant, TARC, GM-CSF, MIP-1alpha and activation of the stress-activated MAPKs p38 and JNKs. All considered, the available data suggest that through the elicitation of an oxidative stress mechanism, engineered NPs may contribute to pro-inflammatory disease processes in the lung, particularly allergy.

Conformations and biological activities of amyloid beta peptide 25-35.

Amyloid-beta (Abeta) peptide is commonly found in human Alzheimer's disease (AD) brain and is the main component of Alzheimer amyloid plaques. The predominant forms of Abeta in the human brain are Abeta(1-40) and Abeta(1-42), but Abeta(25-35) fragment, physiologically present in elderly people, is the more toxic region and has been recently found to play a relevant role in AD, due to its peculiar aggregation properties. In this work, we review the current understanding on the conformations and biological activity of Abeta(25-35) exploring aggregation, cytotoxic and neurodegenerative properties of this fundamental Abeta fragment, in order to provide an effective starting point to better approach a pathology spread and problematic as AD.

Antibacterial activity of grape extracts on cagA-positive and -negative Helicobacter pylori clinical isolates.

There is considerable interest in alternative/adjuvant approaches for the eradication of Helicobacter pylori using biologically active compounds, especially antioxidants from plants. In the present work, we tested the antioxidant and antimicrobial activities of hydro-alcoholic extracts from Colorino, Sangiovese and Cabernet Sauvignon grape cultivars against H. pylori G21 (cagA-negative, cagA-) and 10K, (cagApositive, cagA+) clinical isolates. We determined the minimum bactericidal concentration (MBC) by incubating strain suspensions in Brucella broth with fetal bovine serum and samples at different concentrations in a final volume of 100 microl in a microaerobic atmosphere. After incubation, subcultures were carried out on Brucella agar plates which were incubated for 3-5 days in a microaerobic environment. The lowest concentration in broth, where the subculture on agar showed complete absence of growth, was considered the MBC.The Colorino extract showed the highest antibacterial activity against G21 strain (MBC=1.35 mg/ml), while Sangiovese and Carbernet MBCs were 4.0 mg/ml ca. H. pylori 10K was only susceptible to Colorino after 48 hours (MBC = 3.57 mg/ml). Resveratrol exhibited the highest antibacterial activity. interestingly, the most pathogenic strain (10K) was less susceptible to both the grape extracts and the isolated compounds. These results suggest that the administration of grape extracts and wine constituents, in addition to antibiotics, might be useful in the treatment of H. pylori infection. Should the reduced susceptibility of 10K strain be extended to all the cagA+ H. pylori isolates, which are endowed with cancer promoter activity, this observation may help explain why the organisms expressing CagA are more closely associated with atrophic gastritis and gastric carcinoma development.

Natural killer cells and gamma/delta T cells in synovial fluid and in peripheral blood of patients with psoriatic arthritis.

OBJECTIVE: NK surface markers and gamma/delta TCR antigen are involved in non-MHC-restricted cytotoxicity, which represents a major effector mechanism of the cell-mediated immune response. We evaluated in PsA patients SF and PB lymphocytes expressing these cellular subsets in order to obtain information on the possible role played by them in the disease. METHODS: We studied 29 PsA and 27 RA patients, as well as 27 healthy controls. In 17 PsA and 16 RA patients with knee joint effusion, analysis of SF was performed. SF and PB lymphocyte analysis was performed by direct dual immunofluorescence flow cytomettry using anti-CD3, anti-CD4, anti-CD8, anti-CD19, anti-TCR-gamma/delta-1 and anti-CD16 and anti-CD56 monoclonal antibodies. RESULTS: PsA and RA patients had, with respect to controls, lower values (both as percentages and in absolute numbers) of PB T cells expressing gamma/delta TCR. SF Iymphocytes of PsA and RA patients were characterised, as compared to PB lymphocytes, by lower numbers (both in absolute numbers and in relative terms) of NK and NK-T cells. Considering the absolute numbers of the various lymphocyte subsets, a strong correlation was found in PsA SF between gamma/delta T cells and NK (p < 0.0007) or NK-T cells (p < 0.0003), as well as between NK and NK-T cells (p < 0.0019). There was instead no statistically significant correlation among the different SF or PB lymphocytes and the most relevant clinical or serological parameters. CONCLUSION: This study, analyzing the impairment of different subsets involved in non-MHC-restricted cytotoxicity, suggests that this component of the cell-mediated immune response seems to play a pivotal role in the development of PsA.

Quantification of lethargy in the neuro-ICU: the 60-Second Test.

The authors evaluated the 60-Second Test (SST), a brief test of mental concentration, as a supplement to the Glasgow Coma Scale (GCS) for monitoring verbally responsive patients in the neuro-intensive care unit. The SST demonstrated excellent reliability and was abnormal in 79% of patients assigned a top GCS score of 15. However, both tests had poor responsiveness to clinically identified changes in level of consciousness (LOC). The SST is sensitive to subtle alterations in LOC but, like the GCS, may have limitations as a monitoring tool in the neurocritical care setting.

Global and domain-specific cognitive impairment and outcome after subarachnoid hemorrhage.

BACKGROUND: Cognitive dysfunction is the most common form of neurologic impairment after subarachnoid hemorrhage (SAH). OBJECTIVE: To evaluate the impact of global and domain-specific cognitive impairment on functional recovery and quality of life (QOL) after SAH. METHODS: One hundred thirteen patients (mean age 49 years; 68% women) were evaluated 3 months after SAH. Three simple tests of global mental status and neuropsychological tests to assess seven specific cognitive domains were administered. Four aspects of outcome (global handicap, disability, emotional status, and QOL) were compared between cognitively impaired and unimpaired patients with analysis-of-covariance models controlling for age, race/ethnicity, and education. Multiple linear regression was used to evaluate the relative contribution of global and domain-specific cognitive status for predicting concurrent modified Rankin Scale (mRS) and Sickness Impact Profile (SIP) scores. RESULTS: Impairment of global mental status on the Telephone Interview of Cognitive Status (TICS) was associated with poor performance in all seven cognitive domains (all p < 0.0005) and was the only cognitive measure associated with poor recovery in all four aspects of outcome (all p < or = 0.005). Cognitive impairment in four specific domains was also associated with functional disability or reduced QOL. After accounting for global cognitive impairment with the TICS, however, neuropsychological testing did not contribute additional predictive value for concurrent mRS or SIP total scores. CONCLUSIONS: Cognitive impairment impacts broadly on functional status, emotional health, and QOL after SAH. The TICS may be a useful alternative to more detailed neuropsychological testing for detecting clinically relevant global cognitive impairment after SAH.

Biological effect of the Planktothrix sp. FP1 cyanobacterial extract.

Cyanobacteria are common and potentially harmful inhabitants of freshwater and marine environments worldwide. Some waterbloom-forming cyanobacteria are toxic and they may cause animal death and adversely affect human health. A filamentous freshwater cyanobacterium, Planktothrix sp. FP1, was found to be responsible for a toxic algal bloom in Lake Varese (Italy) during August of 1997. In the present study, the biological effects of the Planktothrix sp. FP1 cell extract on Xenopus embryos and on human Peripheral Blood Mononuclear Cells (PBMC) were investigated. FETAX (Frog Embryo Teratogenesis Assay-Xenopus) showed that the cyanobacterial extract had no teratogenic potential, though embryotoxicity was detected (LC(50) 2.944g/l wet weight). The same extract inhibited the proliferation of PBMC stimulated in vitro by phytohemagglutinin (PHA), and strongly interfered with the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma).

Association of surgical specialty and processes of care with patient outcomes for carotid endarterectomy.

BACKGROUND AND PURPOSE: Because there is considerable variation in practice patterns and outcomes for carotid endarterectomy (CE), there is a need to study the processes of care that are associated with adverse outcomes. The purpose of this study was to examine the impact of processes of care and surgical specialty on adverse outcomes for CE. METHODS: A retrospective cohort study based on a voluntary CE registry containing 3644 patients undergoing CE between April 1, 1997, and March 31, 1999, in New York hospitals was used in the study. A multivariable statistical model was used to identify significant independent patient risk factors and to examine the association of processes of care and surgical specialty with outcomes after adjustment for differences in patient risk factors. RESULTS: The overall adverse outcome (in-hospital death or stroke) rate was 1.84%. After adjustment for differences in 7 patient risk factors that were significantly related to adverse outcomes, the use of >/=1 specific processes of care (eversion endarterectomy, protamine, or shunts) was found to be associated with lower odds of an adverse outcome relative to patients undergoing CE without the processes (OR=0.42, P=0.006). Similarly, patients undergoing surgery performed by vascular surgeons had lower odds of experiencing an adverse outcome (OR=0.36, P=0.009). Processes of care and surgical specialty were highly correlated with one another. CONCLUSIONS: Processes of care and surgical specialty are significant interrelated determinants of adverse outcome for CE.

The chemokine CXCL13 (BCA-1) inhibits FGF-2 effects on endothelial cells.

Several chemokines, belonging to both the CXC and CC classes, act as positive or negative regulators of angiogenesis. We sought to investigate the role of CXCL13, B cell-attracting chemokine 1 (BCA-1), also known as B-lymphocyte chemoattractant (BLC), on endothelial cell functions. We tested the effect of CXCL13 on HUVEC chemotaxis and proliferation in the presence of fibroblast growth factor (FGF)-2 and found that such chemokine inhibits FGF-2-induced functions, while is not active by itself. To test whether other FGF-2-mediated biological activities may be affected, we evaluated the ability of CXCL13 to rescue HUVEC from starvation-induced apoptosis, as FGF-2 is a survival factor for endothelial cells, and found that CXCL13 partially inhibits such rescue. Multiple mechanisms may be responsible for these biological activities as CXCL13 displaces FGF-2 binding to endothelial cells, inhibits FGF-2 homodimerization, and induces the formation of CXCL13-FGF-2 heterodimers. Our data suggest that CXCL13 may modulate angiogenesis by interfering with FGF-2 activity.

Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited.

BACKGROUND AND PURPOSE: Thick cisternal clot on CT is a well-recognized risk factor for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Whether intraventricular hemorrhage (IVH) or intracerebral hemorrhage (ICH) predisposes to DCI is unclear. The Fisher CT grading scale identifies thick SAH but does not separately account for IVH or ICH. METHODS: We studied 276 consecutively admitted patients with an available admission CT scan performed within 72 hours of onset. Demographic, clinical, laboratory, and neuroimaging data were recorded, and the amount and location of SAH, IVH, and ICH on admission CT scans were quantified. The relationship between these variables and DCI was analyzed separately and in combination with multiple logistic regression. RESULTS: DCI developed in 20% of patients (54 of 276). Among SAH variables, thick clot completely filling any cistern or fissure was the best predictor of DCI (P=0.008), and among IVH variables, blood in both lateral ventricles was most predictive (P=0.001). These variables had independent predictive value for DCI in a multivariate analysis of CT findings, and both were included in a final multivariate model when evaluated in conjunction with other clinical risk factors: IVH (OR 4.1, 95% CI 1.7 to 9.8), SAH (OR 2.3, 95% CI 1.5 to 9.5), mean arterial pressure >112 mm Hg (OR 4.9, 95% CI 2.1 to 11.4), and transcranial Doppler mean velocity >140 cm/s within 5 days of hemorrhage (OR 3.8, 95% CI 1.5 to 9.5). Similar results were obtained in a repeat analysis with infarction due to vasospasm as the dependent variable. CONCLUSIONS: SAH completely filling any cistern or fissure and IVH in the lateral ventricles are both risk factors for DCI, and their risk is additive. We propose a new SAH rating scale that accounts for the independent predictive value of subarachnoid and ventricular blood for DCI.

Delirium from nicotine withdrawal in neuro-ICU patients.

Five cases of presumed nicotine withdrawal delirium among brain-injured patients treated in a neurologic intensive care unit are presented. Each patient had a history of heavy tobacco use and experienced dramatic and sustained clinical improvement within hours of transdermal nicotine replacement. These preliminary observations suggest that nicotine withdrawal may be an under-recognized cause of delirium in patients with acute brain injury.

Molecular cloning of mouse allantoicase cDNA.

The uric acid degradation pathway is progressively lost during vertebrate evolution. In mammals, the end product of this catabolic pathway is allantoin and, therefore, no allantoicase should be present in mouse tissues. Surprisingly, we have found an expressed sequence tag (EST) from mouse testis with high similarity to allantoicase. To characterize this transcript, we have completely sequenced the corresponding EST clone insert and found a 1495 bp long cDNA coding for a 414 amino acid long protein. Identities of mouse versus microorganism allantoicases range from 25 to 30%. Identity reaches 54% when compared to Xenopus allantoicase. Among the tested tissues, only testis possesses the allantoicase transcript. Although no deleterious mutations were found in the coding region, no allantoicase activity could be detected in mouse testis.

Anticoagulation and induced hypertension after endovascular treatment for ruptured intracranial aneurysms.

OBJECTIVE: Guglielmi detachable coil (GDC) embolization may be used to prevent early rebleeding after aneurysmal subarachnoid hemorrhage, but anticoagulation and induced hypertension may increase this risk. We sought to determine retrospectively the relationship between levels of induced hypertension and anticoagulation and incidence of rebleeding in GDC-treated patients. METHODS: Twenty-five consecutive patients with acute (<14 days) subarachnoid hemorrhage who underwent GDC embolization were retrospectively analyzed with regard to percent obliteration of an aneurysm on postprocedure angiogram, the duration and intensity of anticoagulation, the duration and level of induced hypertension, and the frequency of thromboembolic and rebleeding complications. RESULTS: Complete angiographic obliteration of the aneurysm was achieved in five cases (20%). In some cases (n = 2), only the dome of the aneurysm was coiled to allow eventual surgical clipping. Heparin was given to 23 patients (92%) for an average of 6 days (range, 8 hrs to 22 days); the mean dose was 588 units/hr, and the mean partial thromboplastin time was 37 secs. Seven patients (28%) were treated with vasopressors for symptomatic vasospasm for a mean duration of 5 days (range, 8 hrs to 9 days); mean arterial blood pressure averaged 118 mm Hg, and peak systolic blood pressures ranged from 195 to 250 mm Hg. There were no episodes of aneurysm rebleeding. Three patients (12%) suffered intraoperative thromboembolic complications, which in one instance was fatal; two of these cases were associated with subtherapeutic partial thromboplastin time values. CONCLUSION: Induced hypertension (mean arterial blood pressure, 120 mm Hg) and heparinization do not appear to increase the risk of early rebleeding after GDC embolization. In a select group of patients, use of anticoagulation in the immediate perioperative period to prevent thromboembolic complications appears to be safe.