An elliptic problem involving critical Choquard and singular discontinuous nonlinearity

The present article investigates the existence, multiplicity and regularity of weak solutions of problems involving a combination of critical Hartree type nonlinearity along with singular and discontinuous nonlinearity. By applying variational methods and using the notion of generalized gradients for Lipschitz continuous functional, we obtain the existence and the multiplicity of weak solutions for some suitable range of $\lambda$ and $\gamma$. Finally by studying the $L^\infty$-estimates and boundary behavior of weak solutions, we prove their H\"{o}lder and Sobolev regularity

Choquard equation involving mixed local and nonlocal operators

In this article, we study an elliptic problem involving an operator of mixed order with both local and nonlocal aspects and in the presence of critical nonlinearity of Hartree type. To this end, we first investigate the corresponding Hardy-Littlewood-Sobolev inequality and detect the optimal constant. Using variational methods and a Poho\v{z}aev identity we then show the existence and nonexistence results for the corresponding subcritical perturbation problem

Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1

The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. We observed that, compared to wildtype, pkr2-null mice were more resistant to nociceptive sensitization to temperatures ranging from 46 to 48 \ub0C, to capsaicin and to protons, highlighting a positive interaction between PKR2 and the non-selective cation channels TRPV1. Moreover, PKR2 knock-out mice showed reduced nociceptive response to cold temperature (4 \ub0C) and to mustard oil-induced inflammatory hyperalgesia, suggesting a functional interaction between PKR2 and transient receptor potential ankyrin 1 ion (TRPA1) channels. This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and\u2013pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1 12/ 12 than in PKR2 12/ 12 mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics

Fractional Hamiltonian type system on R\mathbb{R} with critical growth nonlinearity

This article investigates the existence and properties of ground state solutions to the following nonlocal Hamiltonian elliptic system: \begin{align*} \begin{cases} (-\Delta)^\frac12 u +V_0 u =g(v),~x\in \mathbb{R} (-\Delta)^\frac12 v +V_0 v =f(u),~x\in \mathbb{R}, \end{cases} \end{align*} where $(-\Delta)^\frac12$ is the square root Laplacian operator, $V_0 >0$ and $f,~g$ have critical exponential growth in $\mathbb{R}$. Using minimization technique over some generalized Nehari manifold, we show that the set $\mathcal{S}$ of ground state solutions is non empty. Moreover for $(u,v) \in \mathcal{S}$, $u,~v$ are uniformly bounded in $L^\infty(\mathbb{R})$ and uniformly decaying at infinity. We also show that the set $\mathcal{S}$ is compact in $H^\frac12(\mathbb{R}) \times H^\frac12(\mathbb{R})$ up to translations. Furthermore under locally lipschitz continuity of $f$ and $g$ we obtain a suitable Poho\v{z}aev type identity for any $(u,v) \in \mathcal{S}$. We deduce the existence of semi-classical ground state solutions to the singularly perturbed system \begin{align*} \begin{cases} \epsilon(-\Delta)^\frac12 \varphi +V(x) \varphi =g(\psi),~x\in \mathbb{R} \epsilon (-\Delta)^\frac12 \psi +V(x) \psi =f(\varphi),~x\in \mathbb{R}, \end{cases} \end{align*} where $\epsilon>0$ and $V \in C(\mathbb{R})$ satisfy the assumption $(V)$ given below (see Section 1). Finally as $\epsilon \rightarrow 0$, we prove the existence of minimal energy solutions which concentrate around the closest minima of the potential $V$

Teachers' emotional well-being during the SARS-CoV-2 pandemic with long school closures: a large-scale cross-sectional survey in Northern Italy

Objectives: This study aimed to evaluate the magnitude of emotional burden on teaching staff during the SARS-CoV-2 pandemic in a significantly impacted region. In addition, the correlates of emotional burden were analysed to enable the design of targeted interventions. Study design: This study was a cross-sectional survey. Methods: An electronic survey was administered to the teaching staff at public schools and kindergartens in a specific geographical area. Cross-sectional assessments of pandemic-specific variables were performed using the Pandemic Fatigue Scale, the Depression Anxiety Stress Scale (DASS)-21, the Satisfaction with Life Scale, and the Resilient Coping Scale. DASS-21 results were compared with results from a parallel survey that was representative of the local general population. Results: In total, 3251 teaching staff members participated in the survey. Teachers showed a higher emotional burden for depression, anxiety and stress than the general population during the pandemic. According to a linear regression model, this burden is correlated with the language in which the questionnaires were answered, mistrust towards institutions, specific SARS-CoV-2 anxiety, past infection with SARS-CoV-2, avoidance of information about the pandemic and pandemic fatigue; emotional burden was negatively correlated with measures for life satisfaction, resilience and team atmosphere. Some independent variables were shown to contribute differentially to the variance of depression, anxiety or stress. Conclusions: Emotional distress during the pandemic among teachers is higher than in the general population and correlates with variables that could, at least in principle, be targeted for specific interventions

Effects of NSAIDs and paracetamol (acetaminophen) on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons.

Celecoxib, diclofenac, ibuprofen, and nimesulide are nonsteroidal anti-inflammatory drugs (NSAIDs) very commonly used for the treatment of moderate to mild pain, together with paracetamol (acetaminophen), a very widely used analgesic with a lesser anti-inflammatory effect. In the study reported here, we tested the efficacy of celecoxib, diclofenac, and ibuprofen on preprotachykinin mRNA synthesis, substance P (SP) release, prostaglandin E(2) (PGE(2)) release, and protein kinase C epsilon (PKC\u25b) translocation in rat cultured sensory neurons from dorsal root ganglia (DRGs). The efficacy of these NSAIDs was compared with the efficacy of paracetamol and nimesulide in in vitro models of hyperalgesia (investigated previously). While nimesulide and paracetamol, as in previous experiments, decreased the percentage of cultured DRG neurons showing translocation of PKC\u25b caused by 100 nM thrombin or 1 \u3bcM bradykinin in a dose-dependent manner, the other NSAIDs tested did not have a significant effect. The amount of SP released by peptidergic neurons and the expression level of preprotachykinin mRNA were assessed in basal conditions and after 70 minutes or 36 hours of stimulation with an inflammatory soup (IS) containing potassium chloride, thrombin, bradykinin, and endothelin-1. The release of SP at 70 minutes was inhibited only by nimesulide, while celecoxib and diclofenac were effective at 36 hours. The mRNA basal level of the SP precursor preprotachykinin expressed in DRG neurons was reduced only by nimesulide, while the increased levels expressed during treatment with the IS were significantly reduced by all drugs tested, with the exception of ibuprofen. All drugs were able to decrease basal and IS-stimulated PGE(2) release. Our study demonstrates novel mechanisms of action of commonly used NSAIDS

Mobilidade e a rastreabilidade da ferrugem asiática da soja no Brasil.

A ferrugem asiática da soja, causada pelo fungo Phakopsora pachyrhizi possui fácil disseminação e pode causar perdas de 30% à 75% na produção. O monitoramento da ferrugem e sua identificação nos estádios iniciais são essenciais para um controle eficiente (YORINORI, 2005). Afim de permitir uma rápida visualização sobre a dispersão desta doença no Brasil, foi desenvolvida uma versão móvel para a plataforma iOS do sistema Web do Consórcio Antiferrugem. O usuário, com o uso do aplicativo em um iPhone, iPod Touch ou iPad, pode ter acesso às informações sobre a dispersão da doença diretamente no seu dispositivo, a qualquer hora e lugar, podendo perceber a aproximação dos focos da doença na sua região e adiantar-se na procura por sinais de infecção na sua lavoura, evitando grandes perdas na produção. O aplicativo traz como diferencial, além da sua mobilidade, a possibilidade de apresentação de informações completas sobre as ocorrências da doença, registradas por laboratórios conveniados ao consórcio. Permite, também, a rastreabilidade sobre a evolução da doença no decorrer das safras, apresentando pontos geolocalizados para os focos da doença. O aplicativo foi desenvolvido sob uma arquitetura de serviços disponíveis na plataforma Web do Consórcio Antiferrugem. Desde que foi disponibilizado, o aplicativo já foi baixado centenas de vezes por usuários do mundo todo, deixando claro o interesse pelas informações não só por produtores e técnicos brasileiros, mas também pelo mercado comprador de soja. Objetivando proporcionar maior agilidade na disseminação das informações, suporte a tecnologia push, para notificações automáticas, está sendo implementado e disponibilizado na loja de aplicativos da Apple (APPLE, 2011).SBIAGRO

Protease activated receptors 1 and 4 sensitize TRPV1 in nociceptive neurones.

Protease-activated receptors (PAR1-4) are activated by proteases released by cell damage or blood clotting, and are known to be involved in promoting pain and hyperalgesia. Previous studies have shown that PAR2 receptors enhance activation of TRPV1 but the role of other PARs is less clear. In this paper we investigate the expression and function of the PAR1, 3 and 4 thrombin-activated receptors in sensory neurones. Immunocytochemistry and in situ hybridization show that PAR1 and PAR4 are expressed in 10 - 15% of neurons, distributed across all size classes. Thrombin or a specific PAR1 or PAR4 activating peptide (PAR1/4-AP) caused functional effects characteristic of activation of the PLCβ/PKC pathway: intracellular calcium release, sensitisation of TRPV1, and translocation of the epsilon isoform of PKC (PKCε) to the neuronal cell membrane. Sensitisation of TRPV1 was significantly reduced by PKC inhibitors. Neurons responding to thrombin or PAR1-AP were either small nociceptive neurones of the peptidergic subclass, or larger neurones which expressed markers for myelinated fibres. Sequential application of PAR1-AP and PAR4-AP showed that PAR4 is expressed in a subset of the PAR1-expressing neurons. Calcium responses to PAR2-AP were by contrast seen in a distinct population of small IB4+ nociceptive neurones. PAR3 appears to be non-functional in sensory neurones. In a skin-nerve preparation the release of the neuropeptide CGRP by heat was potentiated by PAR1-AP. Culture with nerve growth factor (NGF) increased the proportion of thrombin-responsive neurons in the IB4- population, while glial-derived neurotropic factor (GDNF) and neurturin upregulated the proportion of thrombin-responsive neurons in the IB4+ population. We conclude that PAR1 and PAR4 are functionally expressed in large myelinated fibre neurons, and are also expressed in small nociceptors of the peptidergic subclass, where they are able to potentiate TRPV1 activity.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Prevalence of and risk factors for fatty liver in the general population of Northern Italy: The Bagnacavallo Study

Background: The estimation of the burden of disease attributable to fatty liver requires studies performed in the general population. Methods: The Bagnacavallo Study was performed between October 2005 and March 2009. All the citizens of Bagnacavallo (Ravenna, Italy) aged 30 to 60 years as of January 2005 were eligible. Altered liver enzymes were defined as alanine transaminase > 40 U/l and/or aspartate transaminase > 37 U/l. Results: Four thousand and thirty-three (58%) out of 6920 eligible citizens agreed to participate and 3933 (98%) had complete data. 393 (10%) of the latter had altered liver enzymes and 3540 had not. After exclusion of subjects with HBV or HCV infection, liver ultrasonography was available for 93% of subjects with altered liber enzymes and 52% of those with normal liver enzymes. The prevalence of fatty liver, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) was 0.74 (95%CI 0.70 to 0.79) vs. 0.35 (0.33 to 0.37), 0.46 (0.41 to 0.51) vs. 0.22 (0.21 to 0.24) and 0.28 (0.24 to 0.33) vs. 0.13 (0.11 to 0.14) in citizens with than in those without altered liver enzymes. Ethanol intake was not associated and all the components of the metabolic syndrome (MS) were associated with fatty liver. All potential risk factors were associated with a lower odds of normal liver vs. NAFLD while they were unable to discriminate AFLD from NAFLD. Conclusions: Fatty liver as a whole was highly prevalent in Bagnacavallo in 2005/9 and was more common among citizens with altered liver enzymes

The Variscan subduction inheritance in the Southern Alps Sub-Continental Lithospheric Mantle: clues from the Middle Triassic shoshonitic magmatism of the Dolomites (NE Italy)

Although often speculated, the link between the Middle Triassic shoshonitic magmatism at the NE margin of the Adria plate and the subduction-related metasomatism of the Southern Alps Sub-Continental Lithospheric Mantle (SCLM) has never been constrained. In this paper, a detailed geochemical and petrological characterization of the lavas, dykes and ultramafic cumulates belonging to the shoshonitic magmatic event that shaped the Dolomites (Southern Alps) was used to model the composition and evolution of the underlying SCLM in the time comprised between the Variscan subduction and the opening of the Alpine Tethys. Geochemical models and numerical simulations enabled us to define that 5–7% partial melting of an amphibole + phlogopite-bearing spinel lherzolite, similar to the Finero phlogopite peridotite, can account for the composition of the primitive Mid-Triassic SiO2-saturated to -undersaturated melts with shoshonitic affinity (87Sr/86Sri = 0.7032–0.7058; 143Nd/144Ndi = 0.51219–0.51235; Mg # ~ 70; ~1.1 wt% H2O). By taking into account the H2O content documented in mineral phases from the Finero phlogopite peridotite, it is suggested that the Mid-Triassic SCLM source was able to preserve a significant enrichment and volatile content (600–800 ppm H2O) for more than 50 Ma, i.e. since the slab-related metasomatism connected to the Variscan subduction. The partial melting of a Finero-like SCLM represents the exhaustion of the subduction-related signature in the Southern Alps lithosphere that predated the Late Triassic-Early Jurassic asthenospheric upwelling related to the opening of the Alpine Tethys