Concurrent warming and browning eliminate cold-water fish habitat in many temperate lakes.

Cold-water species in temperate lakes face two simultaneous climate-driven ecosystem changes: warming and browning of their waters. Browning refers to reduced transparency arising from increased dissolved organic carbon (DOC), which absorbs solar energy near the surface. It is unclear whether the net effect is mitigation or amplification of climate warming impacts on suitable oxythermal habitat (<20 °C, >5 mgO/L) for cold-loving species because browning expands the vertical distribution of both cool water and oxygen depletion. We analyzed long-term trends and high-frequency sensor data from browning lakes in New York's Adirondack region to assess the contemporary status of summertime habitat for lacustrine brook trout. Across two decades, surface temperatures increased twice as fast and bottom dissolved oxygen declined >180% faster than average trends for temperate lakes. We identify four lake categories based on oxythermal habitat metrics: constrained, squeezed, overheated, and buffered. In most of our study lakes, trout face either seasonal loss (7 of 15) or dramatic restriction (12 to 21% of the water column; 5 of 15) of suitable habitat. These sobering statistics reflect rapid upward expansion of oxygen depletion in lakes with moderate or high DOC relative to compression of heat penetration. Only in very clear lakes has browning potentially mitigated climate warming. Applying our findings to extensive survey data suggests that decades of browning have reduced oxythermal refugia in most Adirondack lakes. We conclude that joint warming and browning may preclude self-sustaining cold-water fisheries in many temperate lakes; hence, oxythermal categorization is essential to guide triage strategies and management interventions.

The Erice 58 Charter on 'The health of migrants. An equity challenge for the public health system'.

Abstract: The Erice 58 Charter titled "The Health of Migrants: a Challenge of Equity for the Public Health System", was unanimously approved at the conclusion of the 58th Residential Course of the School of Epidemiology and Preventive Medicine 'Giuseppe D'Alessandro' entitled "The Health of Migrants: a Challenge of Equity for the Public Health System. Epidemiological, clinical-relational, regulatory, organisational, training and public communication aspects at international, national and local level', which took place from 28 March to 2 April 2022 in Erice (Sicily, Italy), at the 'Ettore Majorana' Foundation and Centre for Scientific Culture. The Course was promoted by the Italian Society of Migration Medicine (S.I.M.M.) and the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI), with the collaboration and patronage of the Istituto Superiore di Sanità (ISS). 72 learners participated (mainly resident doctors in 'Hygiene and Preventive Medicine' but also other health service professionals), whose average age was 37 years; on the basis of territorial origin, 13 of the 20 Italian regions were represented. During the intense learning experience, which consisted of 18 frontal lessons (with 20 lecturers from the bio-medical, socio-anthropological and journalistic fields) and 7 working group sessions (supported by 4 classroom tutors in addition to the lecturers) in 'blended learning' mode, the various dimensions and critical issues related to the possibility of guaranteeing truly inclusive health policies for foreigners/migrants, throughout the country, were identified and discussed from an 'Health Equity' perspective. This enabled a small editorial group to draw up the basic document that, in the last session of the Course, was discussed and modified by all participants into the version of the 'Erice 58 Charter' presented here.

Formoterol and fluticasone propionate combination improves histone deacetylation and anti-inflammatory activities in bronchial epithelial cells exposed to cigarette smoke.

BACKGROUND: The addition of long-acting beta2-agonists (LABAs) to corticosteroids improves asthma control. Cigarette smoke exposure, increasing oxidative stress, may negatively affect corticosteroid responses. The anti-inflammatory effects of formoterol (FO) and fluticasone propionate (FP) in human bronchial epithelial cells exposed to cigarette smoke extracts (CSE) are unknown. AIMS: This study explored whether FP, alone and in combination with FO, in human bronchial epithelial cellline (16-HBE) and primary bronchial epithelial cells (NHBE), counteracted some CSE-mediated effects and in particular some of the molecular mechanisms of corticosteroid resistance. METHODS: 16-HBE and NHBE were stimulated with CSE, FP and FO alone or combined. HDAC3 and HDAC2 activity, nuclear translocation of GR and NF-κB, pERK1/2/tERK1/2 ratio, IL-8, TNF-α, IL-1ß mRNA expression, and mitochondrial ROS were evaluated. Actin reorganization in neutrophils was assessed by fluorescence microscopy using the phalloidin method. RESULTS: In 16-HBE, CSE decreased expression/activity of HDAC3, activity of HDAC2, nuclear translocation of GR and increased nuclear NF-κB expression, pERK 1/2/tERK1/2 ratio, and mRNA expression of inflammatory cytokines. In NHBE, CSE increased mRNA expression of inflammatory cytokines and supernatants from CSE exposed NHBE increased actin reorganization in neutrophils. FP combined with FO reverted all these phenomena in CSE stimulated 16-HBE cells as well as in NHBE cells. CONCLUSIONS: The present study provides compelling evidences that FP combined with FO may contribute to revert some processes related to steroid resistance induced by oxidative stress due to cigarette smoke exposure increasing the anti-inflammatory effects of FP.

Increased expression of IL-19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. AIMS: Among proteins expressed by nasal epithelial cells in CRS, IL-19 may have key functions. We here aimed to determine the expression and regulation of IL-19. METHODS: Nasal biopsies from normal subjects (n = 12), subjects with CRS but without nasal polyps (NP) (CRSsNP, n = 12) and with CRS with NP (CRSwNP, n = 15) were collected. Human Asthma Gene Array and real-time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for IL-19 were confirmed by real-time PCR. The constitutive and stimulated (LPS, TGF ß) expression of IL-19 and cell proliferation were evaluated in a nasal epithelial cell line (RPMI 2650). RESULTS: Human Asthma Gene Array showed an increased IL-19 gene expression in NP from patients with CRS in comparison with normal subjects. Real-time PCR confirmed the IL-19 mRNA up-regulation in patients with CRSwNP and showed an up-regulation of IL-19, at lower extent, in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) in comparison with normal subjects. Western blot analysis confirmed that IL-19 is increased also at protein level in patients with CRSwNP in comparison with normal subjects. In NP, IL-19 is highly expressed in the metaplastic nasal epithelium when compared to normal or hyperplastic epithelium. LPS stimulation increased IL-19 expression, and recombinant IL-19 increased cell proliferation in nasal epithelial cells. CONCLUSIONS: IL-19 is overexpressed in the epithelium in CRSwNP and increases epithelial cell proliferation.

Risk factors for third-generation cephalosporin-resistant and extended-spectrum ß-lactamase-producing Escherichia coli carriage in domestic animals of semirural parishes east of Quito, Ecuador.

Extended-spectrum ß-lactamase (ESBL)-producing and other antimicrobial resistant (AR) Escherichia coli threaten human and animal health worldwide. This study examined risk factors for domestic animal colonization with ceftriaxone-resistant (CR) and ESBL-producing E. coli in semirural parishes east of Quito, Ecuador, where small-scale food animal production is common. Survey data regarding household characteristics, animal care, and antimicrobial use were collected from 304 households over three sampling cycles, and 1195 environmental animal fecal samples were assessed for E. coli presence and antimicrobial susceptibility. Multivariable regression analyses were used to assess potential risk factors for CR and ESBL-producing E. coli carriage. Overall, CR and ESBL-producing E. coli were detected in 56% and 10% of all fecal samples, respectively. The odds of CR E. coli carriage were greater among dogs at households that lived within a 5 km radius of more than 5 commercial food animal facilities (OR 1.72, 95% CI 1.15-2.58) and lower among dogs living at households that used antimicrobials for their animal(s) based on veterinary/pharmacy recommendation (OR 0.18, 95% CI 0.04-0.96). Increased odds of canine ESBL-producing E. coli carriage were associated with recent antimicrobial use in any household animal (OR 2.69, 95% CI 1.02-7.10) and purchase of antimicrobials from pet food stores (OR 6.83, 95% CI 1.32-35.35). Food animals at households that owned more than 3 species (OR 0.64, 95% CI 0.42-0.97), that used antimicrobials for growth promotion (OR 0.41, 95% CI 0.19-0.89), and that obtained antimicrobials from pet food stores (OR 0.47, 95% CI 0.25-0.89) had decreased odds of CR E. coli carriage, while food animals at households with more than 5 people (OR 2.22, 95% CI 1.23-3.99) and located within 1 km of a commercial food animal facility (OR 2.57, 95% CI 1.08-6.12) had increased odds of ESBL-producing E. coli carriage. Together, these results highlight the complexity of antimicrobial resistance among domestic animals in this setting.

Fluid migrations and volcanic earthquakes from depolarized ambient noise.

Ambient noise polarizes inside fault zones, yet the spatial and temporal resolution of polarized noise on gas-bearing fluids migrating through stressed volcanic systems is unknown. Here we show that high polarization marks a transfer structure connecting the deforming centre of the caldera to open hydrothermal vents and extensional caldera-bounding faults during periods of low seismic release at Campi Flegrei caldera (Southern Italy). Fluids pressurize the Campi Flegrei hydrothermal system, migrate, and increase stress before earthquakes. The loss of polarization (depolarization) of the transfer and extensional structures maps pressurized fluids, detecting fluid migrations after seismic sequences. After recent intense seismicity (December 2019-April 2020), the transfer structure appears sealed while fluids stored in the east caldera have moved further east. Our findings show that depolarized noise has the potential to monitor fluid migrations and earthquakes at stressed volcanoes quasi-instantaneously and with minimum processing.

A Case of Reversible Cerebral Vasoconstriction Syndrome: Postpartum Cerebral Angiopathy in a 32-Year-Old Primigravid Treated with Intravenous Immunoglobulin.

This is a case of a 32-year-old primigravid who developed sudden severe headache on the 7th day postpartum associated with focal neurologic deficits and altered sensorium. She had a GCS score of 6, anisocoric pupils and an NIHSS score of 31. Cranial MRI with MRA showed multifocal hyperacute to acute infarcts on the left occipital lobe, left thalamus, and midbrain which was more prominent on the right. Due to clinical deterioration, a repeat Cranial MRI with MRA was done and showed progression of infarcts involving both thalami and right pons with interval appearance of contour irregularities in the proximal anterior cerebral, posterior cerebral, basilar and internal carotid arteries. Serial transcranial Doppler showed significant distal right middle cerebral artery vasospasm. She was managed as a case of reversible cerebral vasoconstriction syndrome, associated with postpartum cerebral angiopathy. Intravenous pulse methylprednisolone was started subsequently IVIG was initiated. Intravenous immunoglobulin was given for 5 days. The patient gradually improved, underwent rehabilitation therapy, and was discharged stable after 6 weeks.

A record of seafloor methane seepage across the last 150 million years.

Seafloor methane seepage is a significant source of carbon in the marine environment. The processes and temporal patterns of seafloor methane seepage over multi-million-year time scales are still poorly understood. The microbial oxidation of methane can store carbon in sediments through precipitation of carbonate minerals, thus providing a record of past methane emission. In this study, we compiled data on methane-derived carbonates to build a proxy time series of methane emission over the last 150 My and statistically compared it with the main hypothesised geological controllers of methane emission. We quantitatively demonstrate that variations in sea level and organic carbon burial are the dominant controls on methane leakage since the Early Cretaceous. Sea level controls methane seepage variations by imposing smooth trends on timescales in the order of tens of My. Organic carbon burial is affected by the same cyclicities, and instantaneously controls methane release because of the geologically rapid generation of biogenic methane. Both the identified fundamental (26-27 My) and higher (12 My) cyclicities relate to global phenomena. Temporal correlation analysis supports the evidence that modern expansion of hypoxic areas and its effect on organic carbon burial may lead to higher seawater methane concentrations over the coming centuries.

Ceftaroline modulates the innate immune and host defense responses of immunocompetent cells exposed to cigarette smoke.

BACKGROUND: Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system's response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke. AIMS AND METHODS: The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release were evaluated by ELISA. RESULTS: The constitutive expression of TLR2 and TLR4 and LPS binding were higher in differentiated compared to undifferentiated THP-1 cells. In undifferentiated THP-1 cells, CSE increased TLR2 and TLR4 protein levels, LPS binding and TNF-α release and reduced HBD2 release and ceftaroline counteracted all these effects. In differentiated THP-1, CSE did not significantly affect TLR2 and TLR4 expression and LPS binding but reduced HBD2 release and increased TNF-α release. Ceftaroline counteracted the effects of CSE on HBD2 release in differentiated THP-1. CONCLUSION: Ceftaroline counteracts the effect of CSE in immune cells by increasing the effectiveness of the innate immune system. This effect may also assist in reducing pathogen activity and recurrent exacerbations in COPD patients.

Temporal and spatial expression of genes involved in DNA methylation during reproductive development of sexual and apomictic Eragrostis curvula.

Recent reports in model plant species have highlighted a role for DNA methylation pathways in the regulation of the somatic-to-reproductive transition in the ovule, suggesting that apomixis (asexual reproduction through seeds) likely relies on RdDM downregulation. Our aim was therefore to explore this hypothesis by characterizing genes involved in DNA methylation in the apomictic grass Eragrostis curvula. We explored floral transcriptomes to identify homologs of three candidate genes, for which mutations in Arabidopsis and maize mimic apomixis (AtAGO9/ZmAGO104, AtCMT3/ZmDMT102/ZmDMT105, and AtDDM1/ZmCHR106), and compared both their spatial and temporal expression patterns during reproduction in sexual and apomictic genotypes. Quantitative expression analyses revealed contrasting expression patterns for the three genes in apomictic vs sexual plants. In situ hybridization corroborated these results for two candidates, EcAGO104 and EcDMT102, and revealed an unexpected ectopic pattern for the AGO gene during germ line differentiation in apomicts. Although our data partially support previous results obtained in sexual plant models, they suggest that rather than an RdDM breakdown in the ovule, altered localization of AtAGO9/ZmAGO104 expression is required for achieving diplospory in E. curvula. The differences in the RdDM machinery acquired during plant evolution might have promoted the emergence of the numerous apomictic paths observed in plants.

Clues on the origin of post-2000 earthquakes at Campi Flegrei caldera (Italy).

The inter-arrival times of the post 2000 seismicity at Campi Flegrei caldera are statistically distributed into different populations. The low inter-arrival times population represents swarm events, while the high inter-arrival times population marks background seismicity. Here, we show that the background seismicity is increasing at the same rate of (1) the ground uplift and (2) the concentration of the fumarolic gas specie more sensitive to temperature. The seismic temporal increase is strongly correlated with the results of recent simulations, modelling injection of magmatic fluids in the Campi Flegrei hydrothermal system. These concurrent variations point to a unique process of temperature-pressure increase of the hydrothermal system controlling geophysical and geochemical signals at the caldera. Our results thus show that the occurrence of background seismicity is an excellent parameter to monitor the current unrest of the caldera.

Effects of ceftaroline on the innate immune and on the inflammatory responses of bronchial epithelial cells exposed to cigarette smoke.

The tobacco smoking habit interferes with the innate host defence system against infections. Recurrent infections accelerated the functional respiratory decline. The present study assessed the effects of ceftaroline on TLR2 and TLR4 and on pro-inflammatory responses in airway epithelial cells (16HBE cell line and primary bronchial epithelial cells) with or without cigarette smoke extracts (CSE 10%). TLR2, TLR4, LPS binding and human beta defensin 2 (HBD2) were assessed by flow cytometry, NFkB nuclear translocation by western blot analysis, IL-8 and HBD2 mRNA by Real Time PCR; the localization of NFkB on the HBD2 and IL-8 promoters by ChiP Assay. CSE increased TLR4, TLR2 expression, LPS binding and IL-8 mRNA; CSE decreased HBD2 (protein and mRNA), activated NFkB and promoted the localization of NFkB on IL-8 promoter and not on HBD2 promoter. Ceftaroline counteracted the CSE effect on TLR2 expression, on LPS binding, on IL-8 mRNA, HBD2 and NFkB in 16HBE. The effects of ceftaroline on HBD2 protein and on IL-8 mRNA were confirmed in primary bronchial epithelial cells. In conclusion, ceftaroline is able to counteract the effects of CSE on the innate immunity and pro-inflammatory responses modulating TLR2, LPS binding, NFkB activation and activity, HBD2 and IL-8 expression in bronchial epithelial cells.

Cigarette smoke alters cell cycle and induces inflammation in lung fibroblasts.

BACKGROUND: Lung fibroblasts are crucial for the integrity of alveolar structure. Cigarette smoking, the major risk factor for chronic obstructive pulmonary disease, impairs the repair functions of lung fibroblasts. AIMS: The study simultaneously assessed for the first time cell cycle, p53, p21, p38, ERK 1/2 and IL-8. MAIN METHODS: Primary foetal lung fibroblasts (HFL-1) and primary lung fibroblasts from former (n = 5) and current (n = 5) smokers with/without cigarette smoke extracts (CSEs) and inhibitors of p38 and ERK1/2 were studied for cell cycle events and for marker expression by flow-cytometry, western-blot analysis and ELISA. KEY FINDINGS: CSE exposure did not induce caspase 3 cleavage or DNA laddering but reduced S phase, and increased G1 and G2/M in HFL-1. Furthermore CSE increased: p53 and p21 expression; p38 and ERK 1/2 pathway activation; and IL-8 release. Inhibitors of p38 and ERK 1/2 reversed the effects of CSE on cell cycle and on IL-8 release. ERK 1/2 inhibitor was able to reverse the effects of CSE on p21 expression. Primary lung fibroblasts from current smokers had higher ERK 1/2 activation in comparison to normal primary fibroblasts and higher percentage of cells in G1 phase and lower percentage of cells in S phase in comparison to former smoker fibroblasts. SIGNIFICANCE: Cigarette smoke may affect the reparative potential of lung fibroblasts altering the expression of p53 and p21 and the progression of the cell cycle to S phase. All these events are promoted by the activation of pro-inflammatory pathways.

Effects of gemcitabine on cell proliferation and apoptosis in non-small-cell lung cancer (NSCLC) cell lines.

We evaluated the antiproliferative and the proapoptotic ability of gemcitabine in three non-small-cell lung cancer (NSCLC) cell lines. NCI-H292 (mucoepidermoid carcinoma), NCI-CorL23 (large-cell carcinoma) and NCI-Colo699 (adenocarcinoma) cells were cultured with and without 0.5, 0.05 and 0.005 microM gemcitabine for 24, 48 and 72 h, respectively. Gemcitabine exerted a stronger and earlier antiproliferative and proapoptotic effect on H292 cells than on CorL23 or Colo699 cells. Fas receptor expression was increased in all three cell lines and was higher in Colo699 than in CorL23 cells. The incubation of NSCLC with anti-Fas agonistic monoclonal antibody (CH11) induced cell apoptosis in H292 cells, demonstrating that the Fas receptor was functionally active. Finally, gemcitabine and CH-11 exerted a synergistic effect on cell apoptosis in H292 cells. This study demonstrates that gemcitabine induces apoptosis in NSCLC and that this effect might be exerted by modulating functionally active Fas expression, and these effects of gemcitabine were stronger in H292 cells than in either CorL23 or Colo699 cells.

Cochlear blood flow modifications induced by anaesthetic drugs in middle ear surgery: comparison between sevoflurane and propofol.

OBJECTIVE: Because it is necessary to maintain controlled hypotension during middle ear surgery in order to avoid bleeding and as it is known that cochlear blood flow (CBF) is related to blood pressure (BP), it is useful to evaluate CBF modifications induced by anaesthetics in order to prevent cochlear damage. The aim of this paper is to evaluate, using laser Doppler flowmetry, which anaesthetic drug, out of sevoflurane and propofol, has the smallest effect on CBF. MATERIAL AND METHODS: Twenty consenting adult patients scheduled for myringoplasty under general anaesthesia for simple tympanic membrane perforation were studied. Patients were divided into two groups: the first group was treated with sevoflurane and the second with propofol. For the first group, CBF measurement was carried out on three different occasions: (i) at a basal low drug dosage; (ii) having increased the drug dosage to a higher level; and (iii) having reduced the drug dosage to the basal low level again. For the second group, CBF measurement was carried out on three different occasions: (i) 10 min after injecting a bolus of propofol; (ii) immediately after a second propofol injection; and (iii) 10 min after a third injection of propofol. A probe was placed over the promontory in order to measure CBF levels. RESULTS: In the subjects treated with sevoflurane, after having increased the drug dosage, BP decreased significantly while CBF did not change significantly. In the subjects treated with propofol we recorded a significant reduction in BP, as well as a decrease in CBF. CONCLUSION: The results obtained show that sevoflurane has a hypotensive effect without modifying CBF, while propofol, although having a similar effect on BP to sevoflurane, has less of a protective effect on inner ear microcirculation.

Markers of acute airway inflammation.

In asthma, acute inflammation induced by allergen challenge in allergic patients leads to an early and a late phase reaction. Immunoglobulin E (IgE)-mediated cell activation plays a crucial role in acute inflammation and leads to the release of proinflammatory mediators, such as histamine, eicosanoids, platelet-activating factor, oxygen-free radicals, neuropeptides and cytokines. These mediators are capable of inducing constriction of airways smooth muscle, increased secretion of mucus, and vasodilatation, as well as several important biological events, including modulation of the expression of adhesion molecules in endothelial and epithelial cells, and of inflammatory cell recruitment. Clinically, acute airway inflammation is characterized by a bronchoconstrictive response with acute symptoms, including wheezing and dyspnoea which can be reversed by short-acting bronchodilators, among which beta 2-agonists play a major role.

[Crohn's disease of the appendix: a rare nosological entity]. / Il morbo di Crohn dell'appendice: una rara entità nosologica.

In this study, the authors describe a case of Crohn's disease confined to the vermiform appendix out of a total of 1,263 appendectomies performed over the past 10 years in a Clinical Surgery Department (Clinica Chirurgica III) of the Policlinico S. Orsola in Bologna. In agreement with other reports in the scientific literature, the essentially non-specific clinical picture prevents pre-operative identification of the condition, whereas a diagnosis of Crohn's disease can be reached only on the basis of histological characteristics. The extreme rarity of Crohn's disease confined to the appendix is, however, confirmed. Follow-up at 3 years revealed no involvement of other areas of the digestive tract.

[The measurement of cochlear flow by laser Doppler in man: the preliminary results]. / Misurazione del flusso cocleare mediante laser Doppler nell'uomo: risultati preliminari.

Laser-Doppler flowmetry is presently one of the methods of choice in measuring cochlear blood flow. The techniques is non-invasive and is based on the frequency shift of the laser beam induced by the red blood cell movement. Previous studies of cochlear blood flow carried out on animals and humans demonstrated the reliability of laser-Doppler flowmetry and its usefulness in understanding inner ear microcirculation physiology. In this paper we present preliminary data obtained from three patients examined under general anesthesia while undergoing tympanoplasty. Results showed that tracings, whose baseline is proportional with the blood flow, are characterized by waves correlated to pulse beat and automatic ventilation. Moreover, intrinsic contractions of inner ear vessels (waves of vasomotion) as exist in cerebral microcirculation, were observed. Pharmacological hypotension hypocapnia and the application of epinephryne determine a significant reduction of cochlear blood flow. These results suggest that while cochlear blood flow is related to systemic pressure, it has an intrinsic control system. As well since we did not obtain any modification in bone conduction threshold after surgery, we conclude that laser-Doppler flowmetry is a safe technique.

[2 cases of chylothorax during total parenteral nutrition: the etiopathogenetic considerations]. / Su due casi di chilotorace in corso di Nutrizione Parenterale Totale: considerazioni etio-patogenetiche.

The authors report the onset of bilateral chylothorax during postoperative total parenteral nutrition. They underline the peculiar origin of the complication. Therefore, attention is payed to the possible pathogenic causes. The overload of fluids, in the elderly with minimal functional reserves, may increase central blood pressure, so to adversely affect lymphatic drainage causing chylothorax.