Endothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated ...receptors-γ (PPARγ) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), among others. We investigated the possible modulatory effect of PPARγ activation on the vascular effects of ET-1 in hypertension. In spontaneously hypertensive rats (SHR), but not in normotensive rats, ET-1 enhanced phenylephrine-induced contraction through ET
by a mechanism dependent on activation of TP receptors by COX-2-derived prostacyclin and reduction in NO bioavailability due to enhanced ROS production. In SHR, the PPARγ agonist pioglitazone (2.5 mg/Kg·day, 28 days) reduced the increased ET
levels and increased those of ET
. After pioglitazone treatment of SHR, ET-1 through ET
decreased ROS levels that resulted in increased NO bioavailability and diminished phenylephrine contraction. In vascular smooth muscle cells from SHR, ET-1 increased ROS production through AP-1 and NFκB activation, leading to enhanced COX-2 expression. These effects were blocked by pioglitazone. In summary, in hypertension, pioglitazone shifts the vascular ET
/ET
ratio, reduces ROS/COX-2 activation and increases NO availability; these changes explain the effect of ET-1 decreasing phenylephrine-induced contraction.
Abstract A pellet-induced enhanced confinement (PiEC) phase, with general characteristics similar to those reported for the stellarator W7-X, is observed after single pellet injection (>10 19 H ...atoms) into the neutral beam injection heated phase of plasmas in the mid-sized heliac-type stellarator TJ-II. In addition to a step-like increase in density, plasma diamagnetic energy content rises significantly with respect to that of reference discharges, energy confinement time is similarly enhanced when compared to International Stellarator Scaling law predictions (Yamada et al 2005 Nucl. Fusion 45 1684) renormalized for TJ-II, and the triple product, n e · T i · τ E , exhibits a clear bifurcation towards an improved confinement branch when compared to the branch product predicted by the same law. In this work, multiple pellets are injected in series into NBI-heated plasmas in the TJ-II and post-injection plasma performance is reported and discussed. For instance, a charge-exchange recombination spectroscopy diagnostic reveals significantly increased core ion temperatures after pellet injection compared to temperatures achieved in comparable reference plasmas, this pointing to increased ion energy content and improved ion energy confinement during a PiEC phase. It is also found that enhanced performance is independent of whether co- or counter-NBI heating beam is employed. Finally, record stored diamagnetic energy content and plasma beta values are achieved when the largest available pellets are employed. The results indicate that pellet injections extend the operational regime well beyond limits previously achieved in TJ-II without pellets.
The knowledge of risk perceptions in primary care could help health authorities to manage epidemics.
A European multi-center cross-sectional study was conducted in France, Belgium and Spain to ...describe the perceptions, the level of anxiety and the feeling of preparedness of primary healthcare physicians towards the COVID-19 infection at the beginning of the pandemic. The factors associated with the feeling of preparedness were studied using multivariate logistic regressions.
A total of 511 physicians participated to the study (response rate: 35.2%). Among them, only 16.3% (n=82) were highly anxious about the pandemic, 50.6% (n=254) had the feeling to have a high level of information, 80.5% (n=409) found the measures taken by the health authorities suitable to limit the spread of COVID-19, and 45.2% (n=229) felt prepared to face the epidemic. Factors associated with feeling prepared were: being a Spanish practitioner (adjusted OR=4.34; 95%CI 2.47; 7.80), being a man (aOR=2.57, 95%CI 1.69; 3.96), finding the measures taken by authorities appropriate (aOR=1.72, 95%CI 1.01; 3.00) and being highly informed (aOR=4.82, 95%CI 2.62; 9.19).
Regarding the dramatic evolution of the pandemic in Europe in the weeks following the study, it appears that information available at this time and transmitted to the physicians could have given a wrong assessment of the spread and the severity of the disease. It seems essential to better integrate the primary care physicians into the information, training and protection channels. A comparison between countries could help to select the most effective measures in terms of information and communication.
•All dogs showed anti-Wolbachia antibodies, confirming the important role of the bacteria.•Different doses of doxycycline were administered to heartworm-infected dogs.•In all cases, antibodies ...decreased significantly at the end of the adulticide treatment.•The administration of a lower dose of doxycycline may be effective.
The endosymbiont bacteria Wolbachia plays an important role in the pathogenesis and inflammatory immune response to heartworm (Dirofilaria immitis) infection in dogs. Doxycycline is used to reduce Wolbachia from all life stages of heartworm to avoid large releases of the bacteria during the death of the worms. However, the dose and duration currently recommended have been extrapolated from the treatment of other rickettsial infections. Therefore, the aim was to study the dynamics of Wolbachia IgG antibodies in heartworm-infected dogs under adulticide treatment using different dosages of doxycycline. Forty-nine heartworm-infected dogs were recruited. On day 0 (diagnosis), monthly ivermectin (6 μg/kg) was prescribed, as well as daily doxycycline for 30 days, at 10 mg/kg/12 h (n = 13), 5 mg/kg/12 h (n = 19), and 10 mg/kg/24 h (n = 17). Dogs underwent adulticide treatment and blood samples were collected on days 0, 30, 90, and 120. All dogs had antibodies against recombinant Wolbachia surface protein (rWSP), confirming the important role of the bacteria in heartworm. No significant differences were found in anti-rWSP response by presence/absence of microfilariae, or by parasite burden on day 0. In all treated groups, the anti-rWSP antibody response was not significantly different between days 0 and 30 but was significantly lower between days 0 and 120 (p < 0.05). The results of the present study suggest that the administration of a lower dose than currently recommended is sufficient to achieve a significant reduction of Wolbachia in dogs infected by D. immitis.
Abstract
The crystal structure of the Sb
6
O
13
oxide, exhibiting a defect pyrochlore crystal structure with atomic vacancies, has been studied using a complete set of state-of-the-art techniques. ...The degree of antimony disproportionation in Sb
3+
and Sb
5+
valence states has been directly determined around 36% and 64%, respectively, using X-ray absorption near edge structure (XANES). These findings are in excellent agreement with our Rietveld analysis of synchrotron X-ray (SXRD) and neutron powder diffraction (NPD) results. Moreover, the highly distorted Sb
3+
coordination due to its lone electron pair has been critically revisited. The bonding distances and coordination of Sb
3+
and Sb
5+
species closely agree with an extensive dynamic and crystallographic determination using the Extended X-ray Absorption Fine Structure (EXAFS) technique. Most importantly, the specific local disorder of the two distinctive Sb ions has been crosschecked monitoring their unusual Debye–Waller factors.
Ovule formation is a complex developmental process in plants, with a strong impact on the production of seeds. Ovule primordia initiation is controlled by a gene network, including components of the ...signaling pathways of auxin, brassinosteroids and cytokinins. By contrast, gibberellins (GAs) and DELLA proteins, the negative regulators of GA signaling, have never been shown to be involved in ovule initiation. Here, we provide molecular and genetic evidence that points to DELLA proteins as novel players in the determination of ovule number in
and in species of agronomic interest, such as tomato and rapeseed, adding a new layer of complexity to this important developmental process. DELLA activity correlates positively with ovule number, acting as a positive factor for ovule initiation. In addition, ectopic expression of a dominant DELLA in the placenta is sufficient to increase ovule number. The role of DELLA proteins in ovule number does not appear to be related to auxin transport or signaling in the ovule primordia. Possible crosstalk between DELLA proteins and the molecular and hormonal network controlling ovule initiation is also discussed.
Abstract
The new modalities for treating patients with non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due ...to the development of new drugs. In this scenario, a new perspective is represented by OncoTherad nano-immunotherapy. We carried out a prospective, single-center (Municipal Hospital of Paulínia, São Paulo, Brazil), single-arm phase I/II study (Clinical Trial: RBR-6swqd2) in 29 (18 male, 11 female) patients with BCG-refractory, relapsed or intolerant NMIBC (≥ 1 previous course of BCG therapy). The median age of the 29 patients and follow-up were 65 years (range 34-96) and 24 months, respectively. OncoTherad treatment showed complete response of 79.3% and recurrence-free survival of 22.2 months at 24-month follow-up. Regarding toxicity, 62.1% of adverse events were Grade 1 or 2. The most commonly reported treatment-related adverse events were dysuria, cystitis, pruritus, rash, arthralgia and fatigue. Also, this study demonstrated an important effect of activation of the Toll-like Receptor 4 (TLR4) signaling pathway triggered by OncoTherad in the formation and organization of primary lymphoid follicles in most patients at 24-months follow-up, which may be related to antitumor and immunoprotective effects from this immunotherapy in bladder tissue. In conclusion, OncoTherad nano-immunotherapy seems a safe and effective treatment option for BCG-relapsed and/or intravesical chemotherapy-relapsed NMIBC patients and may provide benefit for preventing tumor recurrence.
Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. ...Results are inconsistent about pre-trauma predictors.
The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.
20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low odds-ratio (OR) 0.2-0.3 early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66-55% v. 43%) and later-recovery (75-68% v. 39%).
We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.
The olfactory bulb (OB) neurons establish a complex network that ensures the correct processing of the olfactory inputs. Moreover, the OB presents a lifelong addition of new neurons into its existing ...circuitry. This neurogenesis is considered essential for the OB function. However, its functional impact on physiology and behavior is still unclear. Here, we investigate the mechanisms of OB plasticity that underlie bulbar physiology in relation to severe damage of neurogenesis. The neurogenesis of young mice was altered by ionizing radiation. Afterwards, both multi-channel olfactometry and electrophysiological studies were performed. Furthermore, neurogenesis and differentiation of the newly formed cells were assessed using bromodeoxyuridine labeling combined with a wide battery of neuronal markers. Our results demonstrate a reduction in both neurogenesis and volume of the OB in irradiated animals. The number of neuroblasts reaching the OB was reduced and their differentiation rate into interneurons selectively changed; some populations were noticeably affected whereas others remained preserved. Surprisingly, both olfactory detection and discrimination as well as electrophysiology presented almost no alterations in irradiated mice. Our findings suggest that after damaging postnatal neurogenesis, the neurochemical fate of some interneurons changes within a new biological scenario, while maintaining homeostasis and olfaction.
We present deep near-infrared photometry and spectroscopy of the globular cluster 2MASS-GC 03 projected in the Galactic disc using MMT and Magellan Infrared Spectrograph on the Clay Telescope (Las ...Campanas Observatory) and VISTA Variables in the Via Lactea Survey data. Most probable cluster member candidates were identified from near-infrared photometry. Out of 10 candidates that were followed-up spectroscopically, 5 have properties of cluster members, from which we calculate 〈Fe/H〉= − 0.9 ± 0.2 and a radial velocity of 〈v
r〉 = − 78 ± 12 km s−1. A distance of 10.8 kpc is estimated from three likely RR Lyrae members. Given that the cluster is currently at a distance of 4.2 kpc from the Galactic Centre, the cluster's long survival time of an estimated 11.3 ± 1.2 Gyr strengthens the case for its globular-cluster nature. The cluster has a hint of elongation in the direction of the Galactic Centre.
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