Preliminary observations on tear film interferometry performed in horses.

This retrospective study evaluated tear film (TF) interferometry on horses examined in Northern Italy in 2019-2021. The objectives were to evaluate horses affected by keratitis, and to describe TF values in horses with no evidence of ocular disease. All horses received a complete ophthalmic examination and were examined with the Ocular Surface Analyser, Veterinary-setting, prior to eye manipulation, staining and sample collection. Eighteen horses with no evidence of ocular disease were included in the comparison group. Additionally, 46 horses displaying signs of keratitis (neovascularization, corneal opacities, ulceration, epithelial and subepithelial infiltrates) were evaluated. These horses were divided into presumed non-infectious and infectious or presumed infectious keratitis groups (one with proven bacterial origin, and the others with diagnosed or presumptive keratomycosis) with the former including immune-mediated keratitis. From the observations of TF interferometry in the comparison population the authors concluded that for non-invasive break-up time (NIBUT), the estimated preliminary reference interval was 10.4-31.2s, and for tear meniscus height (TMH), it was 0.215-0.457mm. Moreover, within the keratitis population, from an interferometric point of view punctate lesions of the ocular surface were present in all cases of active diagnosed or presumptive subepithelial keratomycosis but not in any of the non-infectious cases, either non-ulcerative or ulcerative. Limitations of the study include a relatively low number of horses examined and the fact that the diagnosis of infectious keratitis was presumptive and based on clinical improvement after treatment in some cases. To the authors' knowledge, this is the first report of TF interferometry performed in horses.

Serum concentration-guided intravenous magnesium sulfate administration for neuroprotection in patients with aneurysmal subarachnoid hemorrhage: a retrospective evaluation of a 12-year single-center experience.

Delayed cerebral infarction (DCI) is a major cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). The benefits of magnesium sulfate as an alternative treatment are controversial, and most previous studies examined its benefits only as adjunctive treatment to traditional nimodipine. We retrospectively analyzed aSAH patients records with magnesium sulfate between 2010 and 2021. We aimed for a serum magnesium concentration of 2-2.5 mmol/l between post-hemorrhage days 3 and 12. The patients were separated in three groups based on average serum magnesium concentration (magnesium >2 mmol/l, reduced magnesium 1.1-1.9 mmol/l, and no magnesium). Additionally, we assessed delayed cerebral infarction (DCI) and clinical outcome at follow-up, using the modified Rankin Scale (mRS), categorized in favorable (0-3) and unfavorable outcome (4-5). In this analysis, 548 patients were included. Hereof, radiological evidence of DCI could be found in 23.0% (n = 126) of patients. DCI rates were lower if patients' average serum magnesium was higher than 2 mmol/l (magnesium 18.8%, n = 85; reduced magnesium 38.3%, n = 23; no magnesium 51.4%, n = 18; p < 0.001). Also, at the last follow-up, patients in the group with a higher serum magnesium concentration had better outcome (favorable outcome: magnesium 64.7%, n = 293; reduced magnesium 50.0%, n = 30; no magnesium 34.3%, n = 12; p < 0.001). This 12-year study reveals the value of serum concentration-guided magnesium administration in aSAH patients. Our findings demonstrate the safety and efficacy when titrated to a serum concentration of 2-2.5 mmol/l. We observed higher rates of delayed cerebral infarction and unfavorable outcomes in patients with serum concentrations below 2 mmol/l.

BV equivalence with boundary.

An extension of the notion of classical equivalence of equivalence in the Batalin-Vilkovisky (BV) and Batalin-Fradkin-Vilkovisky (BFV) frameworks for local Lagrangian field theory on manifolds possibly with boundary is discussed. Equivalence is phrased in both a strict and a lax sense, distinguished by the compatibility between the BV data for a field theory and its boundary BFV data, necessary for quantisation. In this context, the first- and second-order formulations of nonabelian Yang-Mills and of classical mechanics on curved backgrounds, all of which admit a strict BV-BFV description, are shown to be pairwise equivalent as strict BV-BFV theories. This in particular implies that their BV complexes are quasi-isomorphic. Furthermore, Jacobi theory and one-dimensional gravity coupled with scalar matter are compared as classically equivalent reparametrisation-invariant versions of classical mechanics, but such that only the latter admits a strict BV-BFV formulation. They are shown to be equivalent as lax BV-BFV theories and to have isomorphic BV cohomologies. This shows that strict BV-BFV equivalence is a strictly finer notion of equivalence of theories.

Exposure to chronic stress impairs the ability to cope with an acute challenge: Modulation by lurasidone treatment.

Chronic stress represents a major contributor for the development of mental illness. This study aimed to investigate how animals exposed to chronic mild stress (CMS) responded to an acute stress (AS), as a vulnerability's challenge, and to establish the potential effects of the antipsychotic drug lurasidone on such mechanisms. Adult male Wistar rats were exposed or not (controls) to a CMS paradigm for 7 weeks. Starting from the end of week 2, animals were randomized to receive vehicle or lurasidone for 5 weeks. Sucrose intake was used to measure anhedonia. At the end, half of the animals were exposed to an acute stress before sacrifice. Exposure to CMS produced a significant reduction in sucrose consumption, whereas lurasidone progressively normalized such alteration. We found that exposure to AS produced an upregulation of Brain derived neurotrophic factor (Bdnf) in the prefrontal cortex of controls animals. This response was impaired in CMS rats and restored by lurasidone treatment. While in control animals, AS-induced increase of Bdnf mRNA levels was specific for Parvalbumin cells, CMS rats treated with lurasidone show a significant upregulation of Bdnf in pyramidal cells. Furthermore, when investigating the activation of different brain regions, CMS rats showed an impairment in the global response to the acute stressor, that was largely restored by lurasidone treatment. Our results suggest that lurasidone treatment in CMS rats may regulate specific circuits and mechanisms, which will ultimately contribute to boost resilience under stressful challenges.

Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson's disease before brain pathology.

Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson's disease (PD). This study examined, in a descriptive manner, the correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1ß, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1ß release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central pathology.

General Relativity and the AKSZ Construction.

In this note the AKSZ construction is applied to the BFV description of the reduced phase space of the Einstein-Hilbert and of the Palatini-Cartan theories in every space-time dimension greater than two. In the former case one obtains a BV theory for the first-order formulation of Einstein-Hilbert theory, in the latter a BV theory for Palatini-Cartan theory with a partial implementation of the torsion-free condition already on the space of fields. All theories described here are BV versions of the same classical system on cylinders. The AKSZ implementations we present have the advantage of yielding a compatible BV-BFV description, which is the required starting point for a quantization in presence of a boundary.

Gravitational Constraints on a Lightlike Boundary.

We analyse the boundary structure of general relativity in the coframe formalism in the case of a lightlike boundary, i.e. when the restriction of the induced Lorentzian metric to the boundary is degenerate. We describe the associated reduced phase space in terms of constraints on the symplectic space of boundary fields. We explicitly compute the Poisson brackets of the constraints and identify the first- and second-class ones. In particular, in the 3+1-dimensional case, we show that the reduced phase space has two local degrees of freedom, instead of the usual four in the non-degenerate case.

Gene Expression of Disease-related Genes in Alzheimer's Disease is Impaired by Tau Aggregation.

Neuronal hyperexcitability linked to an increase in glutamate signalling is a peculiar trait of the early stages of Alzheimer's disease (AD) and tauopathies, however, a progressive reduction in glutamate release follows in advanced stages. We recently reported that in the early phases of the neurodegenerative process, soluble, non-aggregated Tau accumulates in the nucleus and modulates the expression of disease-relevant genes directly involved in glutamatergic transmission, thus establishing a link between Tau instability and altered neurotransmission. Here we report that while the nuclear translocation of Tau in cultured cells is not impaired by its own aggregation, the nuclear amyloid inclusions of aggregated Tau abolish Tau-dependent increased expression of the glutamate transporter. Remarkably, we observed that in the prefrontal cortex (PFC) of AD patient brain, the glutamate transporter is upregulated at early stages and is downregulated at late stages. The Gene Set Enrichment Analysis indicates that the modulation of Tau-dependent gene expression along the disease progression can be extended to all protein pathways of the glutamatergic synapse. Together, this evidence links the altered glutamatergic function in the PFC during AD progression to the newly discovered function of nuclear Tau.

Evidence for a role of autoinflammation in early-phase psoriasis.

Psoriasis is a common, inflammatory immune-mediated skin disease mainly presenting with plaques whose pathogenesis is based on the central role of the interleukin (IL)-23/IL-17 axis. However, the mechanisms acting in papular lesions of early-phase psoriasis are not fully understood. The aim of this study was to assess the involvement of autoinflammation, a state of sterile inflammation mainly driven by IL-1 over-production that has been recently hypothesized to act in the early phase of disease. Lesional skin of 10 patients with recent onset, untreated psoriasis has been investigated for expression of IL-1ß, IL-17, IL-23 and other cytokines involved in the disease in comparison with normal skin of 10 healthy controls using a protein array method. Immunohistochemical phenotyping of inflammatory infiltrate and co-localization experiments with immunofluorescence confocal microscopy were conducted. IL-1ß was significantly more expressed in psoriasis than in normal skin (P < 0·0001). The chemokine IL-8 was also over-expressed in psoriasis (P = 0·03) while IL-12, IL-17, IL-23, tumour necrosis factor-α and interferon-γ were only slightly more expressed in psoriasis than in normal skin, without reaching statistical significance. The inflammatory infiltrate consisted mainly of neutrophils with a relevant number of macrophages and dendritic cells and only scattered, predominantly T helper 1 lymphocytes. IL-1ß co-localized mainly with CD66b, a neutrophil marker, suggesting that neutrophils were the major source of this cytokine. IL-1ß over-expression in combination with low expression of cytokines that are predominant in late-phase plaque psoriasis may support the role of autoinflammation in early-phase disease, possibly paving the way to randomized trials with IL-1 antagonists.

Current and emerging avenues for Alzheimer's disease drug targets.

Alzheimer's disease (AD), the most frequent cause of dementia, is escalating as a global epidemic, and so far, there is neither cure nor treatment to alter its progression. The most important feature of the disease is neuronal death and loss of cognitive functions, caused probably from several pathological processes in the brain. The main neuropathological features of AD are widely described as amyloid beta (Aß) plaques and neurofibrillary tangles of the aggregated protein tau, which contribute to the disease. Nevertheless, AD brains suffer from a variety of alterations in function, such as energy metabolism, inflammation and synaptic activity. The latest decades have seen an explosion of genes and molecules that can be employed as targets aiming to improve brain physiology, which can result in preventive strategies for AD. Moreover, therapeutics using these targets can help AD brains to sustain function during the development of AD pathology. Here, we review broadly recent information for potential targets that can modify AD through diverse pharmacological and nonpharmacological approaches including gene therapy. We propose that AD could be tackled not only using combination therapies including Aß and tau, but also considering insulin and cholesterol metabolism, vascular function, synaptic plasticity, epigenetics, neurovascular junction and blood-brain barrier targets that have been studied recently. We also make a case for the role of gut microbiota in AD. Our hope is to promote the continuing research of diverse targets affecting AD and promote diverse targeting as a near-future strategy.

The scaffold protein Ajuba suppresses CdGAP activity in epithelia to maintain stable cell-cell contacts.

Levels of active Rac1 at epithelial junctions are partially modulated via interaction with Ajuba, an actin binding and scaffolding protein. Here we demonstrate that Ajuba interacts with the Cdc42 GTPase activating protein CdGAP, a GAP for Rac1 and Cdc42, at cell-cell contacts. CdGAP recruitment to junctions does not require Ajuba; rather Ajuba seems to control CdGAP residence at sites of cell-cell adhesion. CdGAP expression potently perturbs junctions and Ajuba binding inhibits CdGAP activity. Ajuba interacts with Rac1 and CdGAP via distinct domains and can potentially bring them in close proximity at junctions to facilitate activity regulation. Functionally, CdGAP-Ajuba interaction maintains junctional integrity in homeostasis and diseases: (i) gain-of-function CdGAP mutants found in Adams-Oliver Syndrome patients strongly destabilize cell-cell contacts and (ii) CdGAP mRNA levels are inversely correlated with E-cadherin protein expression in different cancers. We present conceptual insights on how Ajuba can integrate CdGAP binding and inactivation with the spatio-temporal regulation of Rac1 activity at junctions. Ajuba provides a novel mechanism due to its ability to bind to CdGAP and Rac1 via distinct domains and influence the activation status of both proteins. This functional interplay may contribute towards conserving the epithelial tissue architecture at steady-state and in different pathologies.

Effects of mild ozonisation on gene expression and nuclear domains organization in vitro.

In the last two decades, the use of ozone (O3) as a complementary medical approach has progressively been increasing; however, its application is still limited due to the numerous doubts about its possible toxicity, despite the low concentrations used in therapy. For an appropriate and safe clinical application of a potentially toxic agent such as O3, it is crucial to elucidate the cellular response to its administration. Molecular analyses and transmission electron microscopy were here combined to investigate in vitro the effects of O3 administration on transcriptional activity and nuclear domains organization of cultured SH-SY5Y neuronal cells; low O3 concentrations were used as those currently administered in clinical practice. Mild ozonisation did not affect cell proliferation or death, while molecular analyses showed an O3-induced modulation of some genes involved in the cell response to stress (HMOX1, ERCC4, CDKN1A) and in the transcription machinery (CTDSP1). Ultrastructural cytochemistry after experiments of bromouridine incorporation consistently demonstrated an increased transcriptional rate at both the nucleoplasmic (mRNA) and the nucleolar (rRNA) level. No ultrastructural alteration of nuclear domains was observed. Our molecular, ultrastructural and cytochemical data demonstrate that a mild toxic stimulus such as mild ozonisation stimulate cell protective pathways and nuclear transcription, without altering cell viability. This could possibly account for the positive effects observed in ozone-treated patients.

Nerve growth factor derivative NGF61/100 promotes outgrowth of primary sensory neurons with reduced signs of nociceptive sensitization.

Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators. NGF61/100 displays a neurotrophic activity on DRG neurons comparable to that of control NGF61, despite a reduced activation of PLCγ, Akt and Erk1/2. NGF61/100 does not differ from NGF61 in its ability to up-regulate Substance P (SP) and Calcitonin Gene Related Peptide (CGRP) expression. However, upon Bradykinin (BK) stimulation, NGF61/100-treated DRG neurons release a much lower amount of SP and CGRP, compared to control NGF61 pre-treated neurons. This effect of painless NGF is explained by the reduced up-regulation of BK receptor 2 (B2R), respect to control NGF61. As a consequence, BK treatment reduced phosphorylation of the transient receptor channel subfamily V member 1 (TRPV1) in NGF61/100-treated cultures and induced a significantly lower intracellular Ca2+ mobilization, responsible for the lower release of noxious mediators. Transcriptomic analysis of DRG neurons treated with NGF61/100 or control NGF allowed identifying a small number of nociceptive-related genes that constitute an "NGF pain fingerprint", whose differential regulation by NGF61/100 provides a strong mechanistic basis for its selective reduced pain sensitizing actions.

Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events.

Stressful life events occurring in adulthood have been found able to affect mood and behavior, thus increasing the vulnerability for several stress-related psychiatric disorders. However, although there is plenty of clinical data supporting an association between stressful life events in adulthood and an enhanced vulnerability for psychopathology, the underlying molecular mechanisms are still poorly investigated. Thus, in this study we performed peripheral/whole-genome transcriptomic analyses in blood samples obtained from 53 adult subjects characterized for recent stressful life events occurred within the previous 6 months. Transcriptomic data were analyzed using Partek Genomics Suite; pathway and network analyses were performed using Ingenuity Pathway Analysis and GeneMANIA Software. We found 207 genes significantly differentially expressed in adult subjects who reported recent stressful life experiences (n=21) compared with those without such experiences (n=32). Moreover, the same subjects exposed to such stressful experiences showed a reduction in leukocyte telomere length. A correlation analyses between telomere length and transcriptomic data indicated an association between the exposures to recent stressful life events and the modulation of several pathways, mainly involved in immune-inflammatory-related processes and oxidative stress, such as natural killer cell signaling, interleukin-1 (IL-1) signaling, MIF regulation of innate immunity and IL-6 signaling. Our data suggest an association between exposures to recent stressful life events in adulthood and alterations in the immune, inflammatory and oxidative stress pathways, which could be also involved in the negative effect of stressful life events on leukocyte telomere length. The modulation of these mechanisms may underlie the clinical association between the exposure to recent Stressful life events in adulthood and an enhanced vulnerability to develop psychiatric diseases in adulthood.

In the eye of the beholder: Assessing the water quality of shoreline parks around the Island of Montreal through citizen science.

As a part of the FreshWater Watch project aiming to promote volunteers' water monitoring in 25 cities around the world, St. Lawrence River water quality was characterized at 28 public shoreline parks around Montreal Island, Quebec, Canada. This involved training of 69 citizen scientists by researchers of the Université de Montréal in five one-day sessions. Shoreline sampling yielded 174 data points over three summers (May 2013 to November 2015). Water turbidity, nitrate and phosphate concentrations were measured in situ, together with the thickness and type of beach-cast vegetation, and the relative abundance of different types of beach litter. Data generated by citizen scientists provided 1) an overview of the water quality of the St. Lawrence and Des Prairies rivers around the Island of Montreal, 2) an estimation of the quantity and types of beach-cast aquatic plants and filamentous algae, and 3) novel insights into the distribution of the nuisance cyanobacterium Lyngbya wollei. Overall, half of the sites were classified as "good" being characterized by low turbidity, nitrate and phosphate concentrations, and little deposition of beach-cast vegetation. Lyngbya wollei was found at 57% of the sites, revealing a more frequent occurrence than initially anticipated. The amount of litter recorded along the shoreline was generally small, comprising items related to picnicking (cans/bottles), smoking, and fishing activities in most parks. Wind exposure and rain events explained a significant fraction of the variability in nutrient concentration and turbidity among sites and dates. Shoreline condition assessed from water quality and vegetation data from this study was not correlated, however, with the most serious problem of faecal coliform counts gathered by the City of Montreal. This assessment of the quality and utilization of shoreline parks provides additional information to support planning and management activities of municipalities.

The human BDNF gene: peripheral gene expression and protein levels as biomarkers for psychiatric disorders.

Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders. We will discuss several mechanisms as possibly underlying BDNF modulation, including epigenetic mechanisms. We will also discuss the potential use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the factors that can influence BDNF gene expression and protein levels. Within this context, we have also characterized, for we believe the first time, the expression of BDNF transcripts in the blood, with the aim to provide novel insights into the molecular mechanisms and signaling that may regulate peripheral BDNF gene expression levels.

Stress-induced mechanisms in mental illness: A role for glucocorticoid signalling.

Stress represents the main environmental risk factor for mental illness. Exposure to stressful events, particularly early in life, has been associated with increased incidence and susceptibility of major depressive disorders as well as of other psychiatric illnesses. Among the key players in these events are glucocorticoid receptors. Dysfunctional glucocorticoid signalling may indeed contribute to psychopathology through a number of mechanisms that regulate the response to acute or chronic stress and that affect the function of genes and systems known to be relevant for mood disorders. Indeed, exposure to chronic stress early in life as well as in adulthood has been shown to reduce the expression of glucocorticoid receptors (GR), also through epigenetic mechanisms, and to up-regulate the expression of the co-chaperone gene FKBP5, which restrains GR activity by limiting the translocation of the receptor complex to the nucleus. Another mechanism that contributes to changes in GR responsiveness is the state of receptor phosphorylation that controls activation, subcellular localization as well as its transcriptional activity. Moreover, GR phosphorylation may represent an important mechanism for the cross talk between neurotrophic signalling and GR-dependent transcription, bridging two important players for mood disorders. One gene that lies downstream from GR and may contribute to stress-related changes is serum glucocorticoid kinase-1 (SGK1). We have demonstrated that the expression of SGK1 is significantly increased after exposure to chronic stress in rodents as well as in the blood of drug-free depressed patients. We have also shown that SGK1 up-regulation may ultimately reduce hippocampal neurogenesis and contribute to the structural abnormalities that have been reported to occur in depressed patients. In summary, GR signalling may represent a point of convergence as well as of divergence for defects associated with pathologic conditions characterized by heightened vulnerability to stress. The characterization of these abnormalities is crucial to identify novel targets for therapeutic intervention that may counteract more effectively stress-induced neurobiological abnormalities.

Ozone-initiated terpene reaction products in five European offices: replacement of a floor cleaning agent.

Cleaning agents often emit terpenes that react rapidly with ozone. These ozone-initiated reactions, which occur in the gas-phase and on surfaces, produce a host of gaseous and particulate oxygenated compounds with possible adverse health effects in the eyes and airways. Within the European Union (EU) project OFFICAIR, common ozone-initiated reaction products were measured before and after the replacement of the regular floor cleaning agent with a preselected low emitting floor cleaning agent in four offices located in four EU countries. One reference office in a fifth country did not use any floor cleaning agent. Limonene, α-pinene, 3-carene, dihydromyrcenol, geraniol, linalool, and α-terpineol were targeted for measurement together with the common terpene oxidation products formaldehyde, 4-acetyl-1-methylcyclohexene (4-AMCH), 3-isopropenyl-6-oxo-heptanal (IPOH), 6-methyl-5-heptene-2-one, (6-MHO), 4-oxopentanal (4-OPA), and dihydrocarvone (DHC). Two-hour air samples on Tenax TA and DNPH cartridges were taken in the morning, noon, and in the afternoon and analyzed by thermal desorption combined with gas chromatography/mass spectrometry and HPLC/UV analysis, respectively. Ozone was measured in all sites. All the regular cleaning agents emitted terpenes, mainly limonene and linalool. After the replacement of the cleaning agent, substantially lower concentrations of limonene and formaldehyde were observed. Some of the oxidation product concentrations, in particular that of 4-OPA, were also reduced in line with limonene. Maximum 2 h averaged concentrations of formaldehyde, 4-AMCH, 6-MHO, and IPOH would not give rise to acute eye irritation-related symptoms in office workers; similarly, 6-AMCH, DHC and 4-OPA would not result in airflow limitation to the airways.

Temporal variation of size-fractionated particulate matter and carbon monoxide in selected microenvironments of the Milan urban area.

This article focuses on air pollution in specific urban microenvironments and conditions characterized by high relative concentration levels and by possible risk to human health. For this reason, monitoring of particle number concentration (PNC) with a wide, size-resolved particle-size range, and CO (an indicator of combustion sources, e.g., traffic), was performed in a variety of microenvironments. Concentrations of ultrafine particles (UFPs), size-fractionated particulate matter (PM), and carbon monoxide (CO) were measured in the central area of Milan over three-week-long periods, one each during summer, autumn, and winter, with three monitoring sessions per day. Experimental data were collected continuously during each monitoring period along an established urban pathway. To assess the relevance of time and spatial factors affecting atmospheric concentrations of UFPs, PM, and CO data were collected while walking or moving by different private and public means of transport. Measurements were divided on the basis of different microenvironments (MEs), seasons, days of the week, and periods of the day. Data analysis shows statistically significant differences across MEs and monitoring periods. The highest measured median concentrations and data variability were observed for busy streets, walking or moving by motorized vehicle (CO, UFP) and in metro trains (PM); the lowest concentrations were observed in park areas and in indoor environments. The highest concentrations were measured during working day morning monitoring sessions. Regarding seasonal variation, UFP, PM, and CO showed different patterns: the highest median concentrations were observed in summer for CO, and in autumn and winter for the UFP and PM. Appreciable differences among all MEs and monitoring periods were observed: concentration patterns and variations appear related to typical sources of urban pollutants (traffic), proximity to sources, and time of day. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a file containing Table VI: Tau b (Kendall) index for non-parametric correlation tau test.].