970 research outputs found

    Access to the Work Product of an Attorney Disqualified for Opposing a Former Client: First Wisconsin Mortgage Trust

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    The purposes of this Recent Development are to analyze the effect of the Seventh Circuit\u27s work product decision on disqualification standards and to develop a consistent framework for determining whether access to the work product of an attorney disqualified for opposing a former client should be allowed. This Recent Development urges that in order to provide the effective guidance necessary for both voluntary compliance and judicial enforcement, the Code must incorporate those judicial standards that most closely reflect its standards in this area. Thus the Recent Development proposes an Ethical Consideration regarding access to work product that reflects the ethical concerns underlying Canon

    The weight-inclusive vs. weight-normative approach to health: Evaluating the evidence for prioritizing well-being over weight

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    Using an ethical lens, this review evaluates two methods of working within patient care and public health: the weight-normative approach (emphasis on weight and weight loss when defining health and well-being) and the weight-inclusive approach (emphasis on viewing health and well-being as multifaceted while directing efforts toward improving health access and reducing weight stigma). Data reveal that the weight-normative approach is not effective for most people because of high rates of weight regain and cycling from weight loss interventions, which are linked to adverse health and well-being. Its predominant focus on weight may also foster stigma in health care and society, and data show that weight stigma is also linked to adverse health and well-being. In contrast, data support a weight-inclusive approach, which is included in models such as Health at Every Size for improving physical (e.g., blood pressure), behavioral (e.g., binge eating), and psychological (e.g., depression) indices, as well as acceptability of public health messages. Therefore, the weight-inclusive approach upholds nonmaleficience and beneficience, whereas the weight-normative approach does not. We offer a theoretical framework that organizes the research included in this review and discuss how it can guide research efforts and help health professionals intervene with their patients and community

    Multiplicative noise: A mechanism leading to nonextensive statistical mechanics

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    A large variety of microscopic or mesoscopic models lead to generic results that accommodate naturally within Boltzmann-Gibbs statistical mechanics (based on S1kdup(u)lnp(u)S_1\equiv -k \int du p(u) \ln p(u)). Similarly, other classes of models point toward nonextensive statistical mechanics (based on Sqk[1du[p(u)]q]/[q1]S_q \equiv k [1-\int du [p(u)]^q]/[q-1], where the value of the entropic index qq\in\Re depends on the specific model). We show here a family of models, with multiplicative noise, which belongs to the nonextensive class. More specifically, we consider Langevin equations of the type u˙=f(u)+g(u)ξ(t)+η(t)\dot{u}=f(u)+g(u)\xi(t)+\eta(t), where ξ(t)\xi(t) and η(t)\eta(t) are independent zero-mean Gaussian white noises with respective amplitudes MM and AA. This leads to the Fokker-Planck equation tP(u,t)=u[f(u)P(u,t)]+Mu{g(u)u[g(u)P(u,t)]}+AuuP(u,t)\partial_t P(u,t) = -\partial_u[f(u) P(u,t)] + M\partial_u\{g(u)\partial_u[g(u)P(u,t)]\} + A\partial_{uu}P(u,t). Whenever the deterministic drift is proportional to the noise induced one, i.e., f(u)=τg(u)g(u)f(u) =-\tau g(u) g'(u), the stationary solution is shown to be P(u,){1(1q)β[g(u)]2}11qP(u, \infty) \propto \bigl\{1-(1-q) \beta [g(u)]^2 \bigr\}^{\frac{1}{1-q}} (with qτ+3Mτ+Mq \equiv \frac{\tau + 3M}{\tau+M} and β=τ+M2A\beta=\frac{\tau+M}{2A}). This distribution is precisely the one optimizing SqS_q with the constraint q{du[g(u)]2[P(u)]q}/{du[P(u)]q}=_q \equiv \{\int du [g(u)]^2[P(u)]^q \}/ \{\int du [P(u)]^q \}= constant. We also introduce and discuss various characterizations of the width of the distributions.Comment: 3 PS figure

    Involvement of phosphodiesterase-cGMP-PKG pathway in intracellular Ca2+ oscillations in pituitary GH3 cells

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    AbstractThe present study investigates the potential role of the Ca2+-calmodulin-dependent type I phosphodiesterase (PDE)-cGMP-protein kinase G (PKG) pathway in spontaneous [Ca2+]i oscillations in GH3 cells using fura-2 single cell videoimaging. Vinpocetine (2.5–50 μM), a selective inhibitor of type I PDE, induced a concentration-dependent inhibition of spontaneous [Ca2+]i oscillations in these pituitary cells, and at the same time produced an increase of the intracellular cGMP content. The cell permeable cGMP analog N2,2′-O-dibutyryl-cGMP (dB-cGMP) (1 mM) caused a progressive reduction of the frequency and the amplitude of spontaneous [Ca2+]i oscillations when added to the medium. KT5823 (400 nM), a selective inhibitor of cGMP-dependent protein kinase (PKG), produced an increase of baseline [Ca2+]i and the disappearance of spontaneous [Ca2+]i oscillations. When KT5823 was added before vinpocetine, the PKG inhibitor counteracted the [Ca2+]i lowering effect of the cGMP catabolism inhibitor. Finally, the removal of extracellular Ca2+ or the blockade of L-type voltage-sensitive calcium channels (VSCC) by nimodipine produced a decrease of cytosolic cGMP levels. Collectively, the results of the present study suggest that spontaneous [Ca2+]i oscillations in GH3 cells may be regulated by the activity of type I PDE-cGMP-PKG pathway

    Diffusion entropy and waiting time statistics of hard x-ray solar flares

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    We analyze the waiting time distribution of time distances τ\tau between two nearest-neighbor flares. This analysis is based on the joint use of two distinct techniques. The first is the direct evaluation of the distribution function ψ(τ)\psi(\tau), or of the probability, Ψ(tau)\Psi(tau), that no time distance smaller than a given τ\tau is found. We adopt the paradigm of the inverse power law behavior, and we focus on the determination of the inverse power index μ\mu, without ruling out different asymptotic properties that might be revealed, at larger scales, with the help of richer statistics. The second technique, called Diffusion Entropy (DE) method, rests on the evaluation of the entropy of the diffusion process generated by the time series. The details of the diffusion process depend on three different walking rules, which determine the form and the time duration of the transition to the scaling regime, as well as the scaling parameter δ\delta. With the first two rules the information contained in the time series is transmitted, to a great extent, to the transition, as well as to the scaling regime. The same information is essentially conveyed, by using the third rules, into the scaling regime, which, in fact, emerges very quickly after a fast transition process. We show that the significant information hidden within the time series concerns memory induced by the solar cycle, as well as the power index μ\mu. The scaling parameter δ\delta becomes a simple function of μ\mu, when memory is annihilated. Thus, the three walking rules yield a unique and precise value of μ\mu if the memory is wisely taken under control, or cancelled by shuffling the data. All this makes compelling the conclusion that μ=2.138±0.01\mu = 2.138 \pm 0.01.Comment: 23 pages, 13 figure

    miR-16-5p, miR-103-3p, and miR-27b-3p as Early Peripheral Biomarkers of Fetal Growth Restriction

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    Current tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus (FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidates for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p. All four selected miRNAs, measured by RT-PCR, resulted upregulated in FGR blood samples before the 32nd week of gestation. By contrast, miRNA103-3p and miRNA107-3p, analyzed between the 32nd and 37th week of gestation, showed lower expression in the FGR group compared to aged matched controls. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic interventions to alleviate the burden of this disease

    Ncx3-induced mitochondrial dysfunction in midbrain leads to neuroinflammation in striatum of A53t-α-synuclein transgenic old mice

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    The exact mechanism underlying selective dopaminergic neurodegeneration is not completely understood. The complex interplay among toxic alpha-synuclein aggregates, oxidative stress, altered intracellular Ca2+-homeostasis, mitochondrial dysfunction and disruption of mitochondrial integrity is considered among the pathogenic mechanisms leading to dopaminergic neuronal loss. We herein investigated the molecular mechanisms leading to mitochondrial dysfunction and its relationship with activation of the neuroinflammatory process occurring in Parkinson’s disease. To address these issues, experiments were performed in vitro and in vivo in mice carrying the human mutation of α-synuclein A53T under the prion murine promoter. In these models, the expression and activity of NCX isoforms, a family of important transporters regulating ionic homeostasis in mammalian cells working in a bidirectional way, were evaluated in neurons and glial cells. Mitochondrial function was monitored with confocal microscopy and fluorescent dyes to measure mitochondrial calcium content and mitochondrial membrane potential. Parallel experiments were performed in 4 and 16-month-old A53T-α-synuclein Tg mice to correlate the functional data obtained in vitro with mitochondrial dysfunction and neuroinflammation through biochemical analysis. The results obtained demonstrated: 1. in A53T mice mitochondrial dysfunction occurs early in midbrain and later in striatum; 2. mitochondrial dysfunction occurring in the midbrain is mediated by the impairment of NCX3 protein expression in neurons and astrocytes; 3. mitochondrial dysfunction occurring early in midbrain triggers neuroinflammation later into the striatum, thus contributing to PD progression during mice aging

    miR-16-5p, miR-103-3p, and miR-27b-3p as Early Peripheral Biomarkers of Fetal Growth Restriction

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    none9noCurrent tests available to diagnose fetal hypoxia in-utero lack sensitivity thus failing to identify many fetuses at risk. Emerging evidence suggests that microRNAs derived from the placenta circulate in the maternal blood during pregnancy and may be used as non-invasive biomarkers for pregnancy complications. With the intent to identify putative markers of fetal growth restriction (FGR) and new therapeutic druggable targets, we examined, in maternal blood samples, the expression of a group of microRNAs, known to be regulated by hypoxia. The expression of microRNAs was evaluated in maternal plasma samples collected from (1) women carrying a preterm FGR fetus (FGR group) or (2) women with an appropriately grown fetus matched at the same gestational age (Control group). To discriminate between early- and late-onset FGR, the study population was divided into two subgroups according to the gestational age at delivery. Four microRNAs were identified as possible candidates for the diagnosis of FGR: miR-16-5p, miR-103-3p, miR-107-3p, and miR-27b-3p. All four selected miRNAs, measured by RT-PCR, resulted upregulated in FGR blood samples before the 32nd week of gestation. By contrast, miRNA103-3p and miRNA107-3p, analyzed between the 32nd and 37th week of gestation, showed lower expression in the FGR group compared to aged matched controls. Our results showed that measurement of miRNAs in maternal blood may form the basis for a future diagnostic test to determine the degree of fetal hypoxia in FGR, thus allowing the start of appropriate therapeutic interventions to alleviate the burden of this disease.openTagliaferri S.; Cepparulo P.; Vinciguerra A.; Campanile M.; Esposito G.; Maruotti G.M.; Zullo F.; Annunziato L.; Pignataro G.Tagliaferri, S.; Cepparulo, P.; Vinciguerra, A.; Campanile, M.; Esposito, G.; Maruotti, G. M.; Zullo, F.; Annunziato, L.; Pignataro, G

    Hematological and Genetic Markers in the Rational Approach to Patients With HCV Sustained Virological Response With or Without Persisting Cryoglobulinemic Vasculitis

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    Background and Aims: Direct-acting antivirals (DAAs) usually lead to improvement/remission of cryoglobulinemic vasculitis (CV), although symptoms may persist/recur after a sustained virological response (SVR). We evaluated hematological and genetic markers in patients with HCV-SVR vasculitis with and without persisting/recurring symptoms to early predict the CV outcome. Approach and Results: Ninety-eight patients with HCV-CV were prospectively enrolled after a DAA-induced SVR: Group A: 52 with complete clinical response; Group B: 46 with symptom maintenance/recurrence. Monoclonal B-cell lymphocytosis, t(14;18) translocation, and abnormal free light chains κ/λ ratios were detected by flow cytometry or nested-PCR or nephelometry in 4% Group A versus 17% Group B (P = 0.04) patients, 17% Group A versus 40% Group B patients (P = 0.02), and 17% Group A versus 47% Group B (P = 0.003) patients, respectively. At least 1 out of 3 clonality markers was altered/positive in 29% of Group A versus 70% of Group B patients (P < 0.0001). When available, pretherapy samples were also tested for t(14;18) translocation (detected in 12/37 [32%] Group A and 21/38 [55%] Group B) and κ/λ ratios (abnormal in 5/35 [14%] Group A and 20/38 [53%] Group B) (P = 0.0006), whereas at least one clonality marker was detected/altered in 16/37 (43%) Group A and 30/38 (79%) Group B (P = 0.002). CV-associated single-nucleotide polymorphisms were tested by real-time PCR. Among them, notch4 rs2071286 T minor allele and TT genotype showed a higher frequency in Group B versus Group A (46% vs. 29%, P = 0.01, and 17% vs. 2%, P = 0.006, respectively). Conclusions: Hematological or genetic analyses could be used to foresee the CV clinical response after DAA therapy and could be valuable to assess a rational flowchart to manage CV during follow-up

    miR135a administration ameliorates brain ischemic damage by preventing TRPM7 activation during brain ischemia

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    Background: miRNA-based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity-independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT- PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia
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