Efficacy of transcranial direct-current stimulation (tDCS) in women with provoked vestibulodynia: study protocol for a randomized controlled trial

Abstract: Background: Provoked vestibulodynia is the most common form of vulvodynia. Despite its high prevalence and deleterious sexual, conjugal, and psychological repercussions, effective evidence-based interventions for provoked vestibulodynia remain limited. For a high proportion of women, significant pain persists despite the currently available treatments. Growing evidence suggests that the central nervous system (CNS) could play a key role in provoked vestibulodynia; thus, treatment targeting the CNS, rather than localized dysfunctions, may be beneficial for women suffering from provoked vestibulodynia. In this study, we aim to build on the promising results of a previous case report and evaluate whether transcranial direct-current stimulation, a non-invasive brain stimulation technique targeting the CNS, could be an effective treatment option for women with provoked vestibulodynia. Methods/design: This single-center, triple-blind, parallel group, randomized, controlled trial aims to compare the efficacy of transcranial direct-current stimulation with sham transcranial direct-current stimulation in women with provoked vestibulodynia. Forty women diagnosed with provoked vestibulodynia by a gynecologist, following a standardized treatment protocol, are randomized to either active transcranial direct-current stimulation treatment for ten sessions of 20 minutes at an intensity of 2 mA or sham transcranial direct-current stimulation over a 2-week period. Outcome measures are collected at baseline, 2 weeks after treatment and at 3-month follow-up. The primary outcome is pain during intercourse, assessed with a numerical rating scale. Secondary measurements focus on the sexual function, vestibular pain sensitivity, psychological distress, treatment satisfaction, and the patient’s global impression of change. Discussion: To our knowledge, this study is the first randomized controlled trial to examine the efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia. Findings from this trial are expected to provide significant information about a promising intervention targeting the centralization of pain in women with provoked vestibulodynia

Mapping long-term functional changes in cerebral blood flow by arterial spin labeling

Although arterial spin labeling (ASL) is appealing for mapping long-term changes in functional activity, inter-sessional variations in basal blood flow, arterial transit times (ATTs), and alignment errors, can result in significant false activation when comparing images from separate sessions. By taking steps to reduce these sources of noise, this study assessed the ability of ASL to detect functional CBF changes between sessions. ASL data were collected in three sessions to image ATT, resting CBF and CBF changes associated with motor activation (7 participants). Activation maps were generated using rest and task images acquired in the same session and from sessions separated by up to a month. Good agreement was found when comparing between-session activation maps to within-session activation maps with only a 16% decrease in precision (within-session: 90 ± 7%) and a 13% decrease in the Dice similarity (within-session: 0.75 ± 0.07) coefficient after a month. In addition, voxel-wise reproducibility (within-session: 4.7 ± 4.5%) and reliability (within-session: 0.89 ± 0.20) of resting grey-matter CBF decreased by less than 18% for the betweensession analysis relative to within-session values. ATT variability between sessions (5.0 ± 2.7%) was roughly half the between-subject variability, indicating that its effects on longitudinal CBF were minimal. These results demonstrate that conducting voxel-wise analysis on CBF images acquired on different days is feasible with only modest loss in precision, highlighting the potential of ASL for longitudinal studies

Scan-rescan and intra-observer variability of magnetic resonance imaging of carotid atherosclerosis at 1.5 T and 3.0 T

Carotid atherosclerosis measurements for eight subjects at baseline and 14 +/- 2 days later were examined using 1.5 T and 3.0 T magnetic resonance imaging (MRI). A single observer blinded to field strength, subject and timepoint manually segmented carotid artery wall and lumen boundaries in randomized images in five measurement trials. Mean increases in the signal-to-noise ratios (SNR) for T1-weighted images acquired at 3.0 T compared to 1.5 T were 90% (scan) and 80% (rescan). Despite significantly improved SNR and contrast-to-noise ratios (CNR) for images acquired at 3.0 T, vessel wall volume (VWV) intra-observer variability was not significantly different using coefficients of variation (COV), and intraclass correlation coefficients (ICC). VWV interscan variability and consistency at both field strengths were not statistically different (1.5 T/3.0 T COV = 5.7%/7.8%, R(2) = 0.96 for 1.5 T and R(2) = 0.87 for 3.0 T). A two-way analysis of variance showed a VWV dependence on field strength but not scan timepoint. In addition, a paired t-test showed significant differences in VWV measured at 3.0 T as compared to 1.5 T. These results suggest that although images acquired at 1.5 T have lower SNR and CNR VWV, measurement variability was not significantly different from 3.0 T VWV and that VWV is field-strength dependent which may be an important consideration for longitudinal studies

SARS-CoV-2 infection among employees working from home and on site: An occupational study in Switzerland.

During the COVID-19 pandemic, many companies implemented working from home to mitigate the spread of the disease among their employees. Using data from Corona Immunitas Nestlé, a seroepidemiological study conducted among employees from two Nestlé sites in Switzerland, we aimed to investigate whether there was a difference in SARS-CoV-2 infection rates between employees working most of the time from home and employees mobilized in a workplace equipped with a specialized occupational safety unit and strict sanitary measures. We also investigated whether this association was modified by household size, living with children, vulnerability, worries about an infection, and worries about adverse health consequences if infected. Data were collected between 8 December 2020, and 11 February 2021. Previous SARS-CoV-2 infections were ascertained by the presence of anti-SARS-CoV-2 IgG antibodies in the blood. Of the 425 employees included (53% women; mean age 42 years ranging between 21 and 64 years), 37% worked most of the time from home in 2020 and 16% had been infected with SARS-CoV-2. Participants who worked most of the time from home in 2020 had slightly higher odds of being infected with SARS-CoV-2 compared to participants who never or only sometimes worked from home (adjusted OR 1.29, 95% CI 0.73-2.27). The association was stronger in participants living alone or with one other person (adjusted OR 2.62, 95% CI 1.13-6.25). Among participants living with two or more other persons (adjusted OR 0.66, 95% CI 0.30-1.39) and among vulnerable participants (adjusted OR 0.53, 95% CI 0.13-1.93), working from home tended to be associated with lower odds of infection. In conclusion, in a context of strict sanitary measures implemented in the workplace, employees working from home did not seem to be at lower risk of infection compared to those working on site, especially if living alone or with one other person

The ATLAS3D project - XXIV. The intrinsic shape distribution of early-type galaxies

We use the ATLAS3D sample to perform a study of the intrinsic shapes of early-type galaxies, taking advantage of the available combined photometric and kinematic data. Based on our ellipticity measurements from the Sloan Digital Sky Survey Data Release 7, and additional imaging from the Isaac Newton Telescope, we first invert the shape distribution of fast and slow rotators under the assumption of axisymmetry. Theso-obtained intrinsic shape distribution for the fast rotators can be described with a Gaussian with a mean flattening of q=0.25 and standard deviation σq = 0.14, and an additional tail towards rounder shapes.The slow rotators are much rounder, and are well described with a Gaussian with mean q = 0.63 and σq =0.09. We then checked that our results were consistent when applying a different and independent method to obtain intrinsic shape distributions, by fitting the observed ellipticity distributions directly using Gaussian parametrizations for the intrinsic axis ratios. Although both fast and slow rotators are identified as early-type galaxies in morphological studies, and in many previous shape studies are therefore grouped together, their shape distributions are significantly different, hinting at different formation scenarios. The intrinsic shape distribution of the fast rotators shows similarities with the spiral galaxy population. Including the observed kinematic misalignment in our intrinsic shape study shows that the fast rotators are predominantly axisymmetric, with only very little room for triaxiality. For the slow rotators though there are very strong indications that they are (mildly) triaxial.PostprintPeer reviewe

The ATLAS3D project - XXVI : H I discs in real and simulated fast and slow rotators

One quarter of all nearby early-type galaxies (ETGs) outside Virgo host a disc/ring of H I with size from a few to tens of kpc and mass up to ∼109 M⊙. Here we investigate whether this H I is related to the presence of a stellar disc within the host making use of the classification of ETGs in fast and slow rotators (FR/SR). We find a large diversity of H I masses and morphologies within both families. Surprisingly, SRs are detected as often, host as much H I and have a similar rate of H I discs/rings as FRs. Accretion of H I is therefore not always linked to the growth of an inner stellar disc. The weak relation between H I and stellar disc is confirmed by their frequent kinematical misalignment in FRs, including cases of polar and counterrotating gas. In SRs the H I is usually polar. This complex picture highlights a diversity of ETG formation histories which may be lost in the relative simplicity of their inner structure and emerges when studying their outer regions. We find that Λ CDM hydrodynamical simulations have difficulties reproducing the H I properties of ETGs. The gas discs formed in simulations are either too massive or too small depending on the star formation feedback implementation. Kinematical misalignments match the observations only qualitatively. The main point of conflict is that nearly all simulated FRs and a large fraction of all simulated SRs host corotating H I. This establishes the H I properties of ETGs as a novel challenge to simulationsPeer reviewedFinal Accepted Versio

Differential and synergistic effects of low birth weight and western diet on skeletal muscle vasculature, mitochondrial lipid metabolism and insulin signaling in male guinea pigs

Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male “lean” offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload

Deep Earth carbon reactions through time and space

The authors acknowledge partial support from the Sloan Foundation grant G-2016-7157.Reactions involving carbon in the deep Earth have limited manifestation on Earth’s surface, yet they have played a critical role in the evolution of our planet. The metal-silicate partitioning reaction promoted carbon capture during Earth’s accretion and may have sequestered substantial carbon in Earth’s core. The freezing reaction involving iron-carbon liquid could have contributed to the growth of Earth’s inner core and the geodynamo. The redox melting/freezing reaction largely controls the movement of carbon in the modern mantle, and reactions between carbonates and silicates in the deep mantle also promote carbon mobility. The ten-year activity of the Deep Carbon Observatory has made important contributions to our knowledge of how these reactions are involved in the cycling of carbon throughout our planet, both past and present, and helped to identify gaps in our understanding that motivate and give direction to future studies.Publisher PDFPeer reviewe

A systematic variation of the stellar initial mass function in early-type galaxies

Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars. It depends on the stellar initial mass function (IMF) describing the distribution of stellar masses when the population formed. Consequently knowledge of the IMF is critical to virtually every aspect of galaxy evolution. More than half a century after the first IMF determination, no consensus has emerged on whether it is universal in different galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot be both universal, but they could not break the degeneracy between the two effects. Only recently indications were found that massive elliptical galaxies may not have the same IMF as our Milky Way. Here we report unambiguous evidence for a strong systematic variation of the IMF in early-type galaxies as a function of their stellar mass-to-light ratio, producing differences up to a factor of three in mass. This was inferred from detailed dynamical models of the two-dimensional stellar kinematics for the large Atlas3D representative sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass. Our finding indicates that the IMF depends intimately on a galaxy's formation history.Comment: 4 pages, 2 figures, LaTeX. Accepted for publication as a Nature Letter. More information about our Atlas3D project is available at http://purl.org/atlas3

Efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia

Abstract: Background: Provoked vestibulodynia (PVD) is a highly prevalent condition characterized by acute recurrent pain located at the vaginal entrance in response to pressure application or attempt of vaginal penetration. Despite a wide variety of treatments offered to women with PVD, a high proportion of women are refractory to conventional treatment. Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown effective for improving various chronic pain conditions. Growing evidence suggests that the central nervous system (CNS) could play a key role in PVD. Targeting the CNS could be a promising treatment avenue for women suffering from PVD. Objective: The purpose of this study was to evaluate and compare the efficacy of active and sham tDCS in reducing pain intensity during intercourse in women with PVD. Study design: We conducted a triple-blind, parallel group, randomized controlled trial (RCT). Women, aged between 17-45 years and diagnosed with PVD by a gynecologist using a validated protocol were randomized to 10 sessions of either active tDCS (intensity = 2mA) or 10 sessions of sham tDCS, over a 2-week period. Both active and sham tDCS were applied for 20 minutes, with the anode positioned over the primary motor cortex (M1), and the cathode, over the contralateral supraorbital area. Outcome measures were collected at baseline, 2 weeks after treatment and at 3-month follow-up by an evaluator blinded to group assignation. The primary objective was pain intensity during intercourse, as assessed with a numerical rating scale. Secondary outcomes focused on sexual function and distress, vestibular sensitivity, psychological distress, treatment ,satisfaction and patient impression of change. Statistical analyses were conducted on the intention-to-treat basis, and treatment effects were evaluated using a mixed linear model for repeated measures. Results: A total of 40 women were randomly assigned to received either active (n=20) or sham (n=20) tDCS treatments between November 2014 and February 2016. Baseline characteristics were similar between active and sham tDCS groups. Active tDCS did not significantly reduced pain during sexual intercourse compared to sham tDCS 2 weeks after treatment (p=0.84) and at follow-up (p=0.09). Mean [95% CI] baseline and 2-week assessment pain intensity were respectively 6.8 [5.9 - 7.7] and 5.6 [4.7 - 6.5] for active tDCS (p=0.03) versus 7.5 [6.6 - 8.4] and 5.7 [4.8 - 6.6] for sham tDCS (p=0.001). Non-significant differences between the two groups were also found in regards to sexual function and distress after treatment (p>0.20) and at follow-up (p>0.10). Overall, at 2-week assessment 68% women assigned to active tDCS reported being very much, much or slightly improved compared to 65% of women assigned to sham tDCS (p=0.82), and still comparable at follow-up 42% versus 65%, respectively (p=0.15). Conclusion: Findings suggest that active tDCS is not more effective than sham tDCS for reducing pain in women with PVD. Likewise, no significant effects were found on sexual function, vestibular sensitivity or psychological distress