On the Viability of Minimal Neutrinophilic Two-Higgs-Doublet Models

We study the constraints that electroweak precision data can impose, after the discovery of the Higgs boson by the LHC, on neutrinophilic two-Higgs-doublet models which comprise one extra $SU(2)\times U(1)$ doublet and a new symmetry, namely a spontaneously broken $\mathbb{Z}_2$ or a softly broken global $U(1)$. In these models the extra Higgs doublet, via its very small vacuum expectation value, is the sole responsible for neutrino masses. We find that the model with a $\mathbb{Z}_2$ symmetry is basically ruled out by electroweak precision data, even if the model is slightly extended to include extra right-handed neutrinos, due to the presence of a very light scalar. While the other model is still perfectly viable, the parameter space is considerably constrained by current data, specially by the $T$ parameter. In particular, the new charged and neutral scalars must have very similar masses.Comment: 22 pages, 3 figures, references and comments added, conclusions unchanged, matches version to appear in JHE

The effects of curcumin on weight loss among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials

Background and objective: The current systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to assess the influence of curcumin intake on weight among patients with metabolic syndrome and related disorders. Methods: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95 confidence intervals (95 CI). Results: Eighteen articles (21 studies) that comprised a total of 1,604 individuals were finally included in the meta-analysis. Curcumin intake significantly reduced body mass index (BMI) (SMD �0.37; 95 CI, �0.61, �0.13; P < 0.01), weight (SMD �0.23; 95 CI, �0.39, �0.06; P < 0.01), waist-circumference (WC) (SMD �0.25; 95 CI, �0.44, �0.05; P = 0.01), leptin levels (SMD �0.97; 95 CI, �1.18, �0.75; P < 0.001) and increased adiponectin levels (SMD 1.05; 95 CI, 0.23, 1.87; P = 0.01). We found no significant effect of curcumin intake on hip ratio (HR) (SMD �0.17; 95 CI, �0.42, 0.08; P = 0.18). Conclusions: Overall, we have found that curcumin intake among patients with metabolic syndrome and related disorders was correlated with a significant reduction in BMI, weight, WC, and leptin, and a significant increase in adiponectin levels, but did not affect HR. Copyright © 2019 Akbari, Lankarani, Tabrizi, Ghayour-Mobarhan, Peymani, Ferns, Ghaderi and Asemi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

The impact of third party reproduction on family and kinship

The development of in vitro fertilization (IVF) in the UK, in 1978, proved a major breakthrough in the process of human reproduction, which had remained constant in human history. The impact of IVF and the ensuing assisted reproductive technologies (ARTs) has not been limited in revolutionizing the "natural" practice of biological reproduction, but has reached out to and affected almost every institution in society. Family and kinship, as the social expression of reproduction and the institutions which are the most transparently structured realm of human life are those most profoundly affected by ARTs. Although literature on the implications of ARTs is in general abundant, this article presents new insights on their impact on family and kinship in Iran, which remains a unique case in the Muslim world. It explores the particular way ARTs, especially third-party donation, have been endorsed and practiced in Iran, and their consequences for the family, the infertile individuals, and their position vis-à -vis their kin and social group. The conclusion points to the lack of clarity concerning the initial rulings by the Islamic jurists, who allowed the practice of ARTs, and which has led to a number of unintended consequences regarding the legal, religious, cultural, and ethical issues, affecting the family, its structure and the relationship between the kin group. These consequences range, inter alia, from the question of the anonymity of third-party donor, to the permissibility of gamete donation between blood relatives, and to the absence of enforceable legislation. © 2021 Avicenna Research Institute. All rights reserved

The expression pattern of VISTA in the PBMCs of relapsing-remitting multiple sclerosis patients: A single-cell RNA sequencing-based study

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). Dysregulated immune responses have been implicated in MS development. Growing evidence has indicated that inhibitory immune checkpoint molecules can substantially regulate immune responses and maintain immune tolerance. V-domain Ig suppressor of T cell activation (VISTA) is a novel inhibitory immune checkpoint molecule that can suppress immune responses; however, its expression pattern in the peripheral blood mononuclear cells (PBMCs) of relapsing-remitting multiple sclerosis (RRMS) has not thoroughly been studied. Herein, we evaluated Vsir expression in PBMCs of RRMS patients and characterized the expression pattern of the Vsir in the PBMCs of MS patients. Besides, we investigated the effect of fingolimod, IFNβ-1α, glatiramer acetate (GA), and dimethyl fumarate (DMF) on Vsir expression in PBMCs of RRMS patients. Our results have shown that Vsir expression is significantly downregulated in the PBMCs of patients with RRMS. Besides, the single-cell RNA sequencing results have demonstrated that Vsir expression is downregulated in classical monocyte, intermediate monocytes, non-classical monocytes, myeloid DCs (mDC), Plasmacytoid dendritic cells (pDCs), and naive B-cells of PBMCs of MS patients compared to the control. In addition, DMF, IFNβ-1α, and GA have significantly upregulated Vsir expression in the PBMCs of RRMS patients. Collectively, the current study has shed light on Vsir expression in the PBMCs of MS patients; however, further studies are needed to elucidate the significance of VISTA in the mentioned immune cells

The effects of statin use on inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials

Current evidence suggests that statin use decreases the incidence of cardiovascular diseases (CVD) through reducing LDL cholesterol and decreasing inflammation. Metabolic syndrome (MetS) is usually associated with increased inflammatory markers and increased risk of CVD. We conducted a systematic review and meta-analysis to determine the effect of statin use on inflammatory markers including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 (IL-1) among patients with MetS and related disorders. PubMed, EMBASE, Web of Science databases, and Cochrane Library were searched for randomized controlled trials (RCTs) through April 2018. Three independent investigators evaluated study eligibilities, extracted data, and assessed study quality using the Cochrane Collaboration risk of bias tool and Jadad's quality scales. Heterogeneity was determined using Cochran's Q statistic and I-square (I 2 ) test. Based on the heterogeneity results, we pooled data using random-effect or fixed effect models presented as standardized mean differences (SMD) and corresponding 95 confidence intervals (CI). One hundred thirteen RCTs (19,644 patients) were included in our meta-analysis. The pooled results using random effects model showed that statin use statistically significantly decreased CRP level (SMD= -0.97; 95 CI, -1.10, -0.85; P &lt; 0.001; I 2 : 95.1), TNF-α (SMD= -1.88; 95 CI, -2.40, -1.38; P &lt; 0.001; I 2 : 97.2), IL-6 (SMD= -1.67; 95 CI, -1.98, -1.34; P &lt; 0.001; I 2 : 96.5), and IL-1 concentrations (SMD= -8.35; 95 CI, -10.49, -6.22; P &lt; 0.001; I 2 : 98.4) among patients with MetS and related disorders. Our meta-analysis showed beneficial effects of statin use on reducing inflammatory markers in patients with MetS and related disorders. © 2018 Elsevier Lt

EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias

Background and purpose:  These EFNS guidelines on the molecular diagnosis of neurogenetic disorders are designed to provide practical help for the general neurologist to make appropriate use of molecular genetics in diagnosing neurogenetic disorders.Methods:  Literature searches were performed before expert members of the task force wrote proposals, which were discussed in detail until final consensus had been reached among all task force members.Results and conclusion:  This paper provides updated guidelines for molecular diagnosis of two particularly complex groups of disorders, the ataxias and spastic paraplegias. Possibilities and limitations of molecular genetic diagnosis of these disorders are evaluated and recommendations are provided

Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r2 = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20–50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Placental kisspeptins differentially modulate vital parameters of estrogen receptor-positive and-negative breast cancer cells

Kisspeptins (KPs) are major regulators of trophoblast and cancer invasion. Thus far, limited and conflicting data are available on KP-mediated modulation of breast cancer (BC) metastasis; mostly based on synthetic KP-10, the most active fragment of KP. Here, we report for the first time comprehensive functional effects of term placental KPs on proliferation, adhesion, Matrigel invasion, motility, MMP activity and pro-inflammatory cytokine production in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive). KPs were expressed at high level by term placental syncytiotrophoblasts and released in soluble form. Placental explant conditioned medium containing KPs (CM) significantly reduced proliferation of both cell types compared to CM without (w/o) KP (CM-w/o KP) in a dose-and time-dependent manner. In MDA-MB-231 cells, placental KPs significantly reduced adhesive properties, while increased MMP9 and MMP2 activity and stimulated invasion. Increased invasiveness of MDA-MB-231 cells after CM treatment was inhibited by KP receptor antagonist, P-234. CM significantly reduced motility of MCF-7 cells at all time points (2-30 hr), while it stimulated motility of MDA-MB-231 cells. These effects were reversed by P-234. Co-treatment with selective ER modulators, Tamoxifen and Raloxifene, inhibited the effect of CM on motility of MCF-7 cells. The level of IL-6 in supernatant of MCF-7 cells treated with CM was higher compared to those treated with CM-w/o KP. Both cell types produced more IL-8 after treatment with CM compared to those treated with CM-w/o KP. Taken together, our observations suggest that placental KPs differentially modulate vital parameters of estrogen receptor-positive and-negative BC cells possibly through modulation of pro-inflammatory cytokine production. © 2016 Rasoulzadeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited