Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

<p>Abstract</p> <p>Background</p> <p>The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored.</p> <p>Methods</p> <p>Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting).</p> <p>Results</p> <p>Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics <it>vs. </it>nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 ± 37, 431.3 ± 36, 316.2 ± 5, 363.8 ± 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 ± 25.21, 73.40 ± 53.30, 148.4 ± 93 in RD-SHR, STZ-SHR- and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 ± 0.9, 2.12 ± 0.9, 7.38 ± 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups <it>vs</it>. SHR.</p> <p>Conclusions</p> <p>Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.</p

The first observed stellar occultations by the irregular satellite Phoebe (Saturn IX) and improved rotational period

peer reviewedWe report six stellar occultations by Phoebe (Saturn IX), an irregular satellite of Saturn, obtained between mid-2017 and mid-2019. The 2017 July 6 event was the first stellar occultation by an irregular satellite ever observed. The occultation chords were compared to a 3D shape model of the satellite obtained from Cassini observations. The rotation period available in the literature led to a sub-observer point at the moment of the observed occultations where the chords could not fit the 3D model. A procedure was developed to identify the correct sub-observer longitude. It allowed us to obtain the rotation period with improved precision compared to the currently known value from literature. We show that the difference between the observed and the predicted sub-observer longitude suggests two possible solutions for the rotation period. By comparing these values with recently observed rotational light curves and single- chord stellar occultations, we can identify the best solution for Phoebe's rotational period as 9.27365 ± 0.00002 h. From the stellar occultations, we also obtained six geocentric astrometric positions in the ICRS as realized by the Gaia DR2 with uncertainties at the 1-mas level

Plantar pressure and foot temperature responses to acute barefoot and shod running

Purpose. Increased contact pressure and skin friction may lead to higher skin temperature. Here, we hypothesized a relationship between plantar pressure and foot temperature. To elicit different conditions of stress to the foot, participants performed running trials of barefoot and shod running. Methods. Eighteen male recreational runners ran shod and barefoot at a self-selected speed for 15 min over different days. Before and immediately after running, plantar pressure during standing (via a pressure mapping system) and skin temperature (using thermography) were recorded. Results. No significant changes were found in plantar pressure after barefoot or shod conditions (p > 0.9). Shod running elicited higher temperatures in the forefoot (by 0.5-2.2 ºC or 0.1-1.2% compared with the whole foot, p -0.5, p > 0.05). Conclusions. The increase in temperature after the shod condition was most likely the result of footwear insulation. However, variation of the temperature in the rearfoot was higher after barefoot running, possible due to a higher contact load. Changes in temperature could not predict changes in plantar pressure and vice-versa

Enhanced spin current transmissivity in Pt/ CoFe2 O4 bilayers with thermally induced interfacial magnetic modification

We report on processes of generation of spin current and conversion into charge current in CoFe2O4/Pt bilayers by means of spin Hall magnetoresistance (SMR) and spin Seebeck effect (SSE) experiments. Specifically, we explore (001) full-textured CoFe2O4 (CFO) thin films grown onto (001)-oriented SrTiO3 substrates, covered with Pt layers deposited under two different conditions: one at room temperature and another at high temperature (400°C). The x-ray absorption spectroscopy measurements indicate that the Pt layer deposited at high temperature induces an interfacial magneticlike phase (Fe,Co)-Pt alloy, which influences the magnetic behavior of the structure and is responsible for the enhancement of the spin transmission at the interface. By analyzing the SMR data, we conclude that collinear and noncollinear magnetic domains coexist at the CFO-(Fe,Co)-Pt interface. By combining the data from the SMR and SSE measurements, we obtain the ratios between the values of the spin Hall angle (θSH) and between the ones of the spin-mixing conductance (geff↑↓) in the two samples. We demonstrate that while the value of θSH decreases by one-half with the heat treatment, the value of geff↑↓ increases by more than one order of magnitude. We interpret the increase of geff↑↓ in terms of unexpected magnetic reconstructions, which produce an enhancement of the magnetic moment arisen at the interface. Since the spin-mixing conductance determines the efficiency of the spin current transmission through the interface, the spinel ferrite cobalt in contact with a normal metal with a suitable heat treatment becomes a promising material for spintronics device applications.This research was supported in Brazil by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Financiadora de Estudos e Projetos (FINEP), Fundação de Amparo à Promoção da Ciência, Tecnologia e Inovação do Estado do Rio Grande do Norte (FAPERN), Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE), and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Grant No. 2022/04496-0; and in Chile by Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) Grant No. 1210641 and FONDEQUIP EQM180103. Ministerio de Ciencia, Universidades e Investigación (SPAIN) (Grants No. PID2020-118479RB-I00/AEI/10.13039/501100011033 and No. TED2021-129857B-I00. The authors acknowledge support of the INCT of Spintronics and Advanced Magnetic Nanostructures (INCT-SpinNanoMag), CNPq 406836/ 2022–1.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

Prolonged Survival of Allografts Induced by Mycobacterial Hsp70 Is Dependent on CD4+CD25+ Regulatory T Cells

Background: Heat shock proteins (Hsps) are stress induced proteins with immunomodulatory properties. The Hsp70 of Mycobacterium tuberculosis (TBHsp70) has been shown to have an anti-inflammatory role on rodent autoimmune arthritis models, and the protective effects were demonstrated to be dependent on interleukin-10 (IL-10). We have previously observed that TBHsp70 inhibited maturation of dendritic cells (DCs) and induced IL-10 production by these cells, as well as in synovial fluid cells. Methodology/Principal Findings: We investigated if TBHsp70 could inhibit allograft rejection in two murine allograft systems, a transplanted allogeneic melanoma and a regular skin allograft. In both systems, treatment with TBHsp70 significantly inhibited rejection of the graft, and correlated with regulatory T cells (Tregs) recruitment. This effect was not tumor mediated because injection of TBHsp70 in tumor-free mice induced an increase of Tregs in the draining lymph nodes as well as inhibition of proliferation of lymph node T cells and an increase in IL-10 production. Finally, TBHsp70 inhibited skin allograft acute rejection, and depletion of Tregs using a monoclonal antibody completely abolished this effect. Conclusions/Significance: We present the first evidence for an immunosuppressive role for this protein in a graft rejection system, using an innovative approach - immersion of the graft tissue in TBHsp70 solution instead of protein injection. Also, this is the first study that demonstrates dependence on Treg cells for the immunosuppressive role of TBHsp70. This finding is relevant for the elucidation of the immunomodulatory mechanism of TBHsp70. We propose that this protein can be used not only for chronic inflammatory diseases, but is also useful for organ transplantation management.Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Financiadora de Estudos e Projetos (FINEP

International comparisons of behavioral and emotional problems in preschool children: parents’ reports from 24 societies

International comparisons were conducted of preschool children’s behavioral and emotional problems as reported on the Child Behavior Checklist for Ages 1½–5 by parents in 24 societies (N¼19,850). Item ratings were aggregated into scores on syndromes; Diagnostic and Statistical Manual of Mental Disorders–oriented scales; a Stress Problems scale; and Internalizing, Externalizing, and Total Problems scales. Effect sizes for scale score differences among the 24 societies ranged from small to medium (3–12%). Although societies differed greatly in language, culture, and other characteristics, Total Problems scores for 18 of the 24 societies were within 7.1 points of the omnicultural mean of 33.3 (on a scale of 0–198). Gender and age differences, as well as gender and age interactions with society, were all very small (effect sizes<1%). Across all pairs of societies, correlations between mean item ratings averaged .78, and correlations between internal consistency alphas for the scales averaged .92, indicating that the rank orders of mean item ratings and internal consistencies of scales were very similar across diverse societies

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected