Circulating kisspeptin and anti-müllerian hormone levels, and insulin resistance in women with polycystic ovary syndrome: a systematic review, meta-analysis, and meta-regression

Objective: This systematic review and meta-analysis aimed to summarize the available evidence regarding circulating kisspeptin and anti-müllerian hormone (AMH) and the homeostasis model assessment of insulin resistance (HOMA-IR) index in adolescents and women with and without polycystic ovary syndrome (PCOS). Method: We performed a comprehensive literature search in Medline, Embase, Cochrane, Scopus, and Web of Science for studies evaluating circulating kisspeptin levels in women with and without PCOS published until September 24th, 2020. Co-primary outcomes were the HOMA-IR index and AMH. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Random-effects models were used to estimate outcomes, and effects reported as mean difference (MD) or standardized MD (SMD) and their 95 % confidence interval (CI). The systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42020205030. Results: We evaluated 18 studies including, 1282 PCOS cases and 977 controls. Participants with PCOS were younger (MD = −2.38 years, 95 %CI -4.32 to -0.44), with higher BMI (MD = 1.16, 95 % CI 0.54–1.78), waist-to-hip ratio (MD = 0.04, 95 %CI 0.02 to 0.05), circulating kisspeptin (SMD = 1.15, 95 %CI 0.68–1.62), luteinizing hormone (SMD = 1.29, 95 %CI 0.76–1.83), AMH (SMD = 0.97, 95 %CI 0.60–1,34), total testosterone (SMD = 2.48, 95 %CI 1.73–3.23), free testosterone (SMD = 1.37, 95 %CI 0.56–2.17), and dehydroepiandrosterone sulphate (SMD = 0.72, 95 %CI 0.32–1.13) levels, and Ferriman-Gallwey score (SMD = 5.08, 95 %CI 2.76–7.39), and lower sex hormone-binding globulin level (SMD = −1.34, 95 %CI −2.15 to −0.52). Besides, participants with PCOS had higher HOMA-IR index (SMD = 0.76, 95 %CI 0.35–1.17), and circulating insulin (SMD = 0.75, 95 %CI 0.30–1.19), leptin (SMD = 2.82, 95 %CI 1.35–4.29), and triglycerides (SMD = 2.15, 95 %CI 1.08–3.23) levels than participants without the syndrome. The meta-regression did not identify significant factors influencing circulating kisspeptin. Conclusion: Patients with PCOS showed higher kisspeptin, LH, insulin, AMH, and androgen levels and HOMA-IR index, and lower sex hormone-binding globulin levels than those without the syndrome

The effect of endometriosis on sexual function as assessed with the Female Sexual Function Index: systematic review and meta-analysis

Aim: To systematically compare sexual function between non-treated women with and without endometriosis. Methods: A systematic review was performed on PubMed/Medline, Scopus, EMBASE, Web of Science and Cochrane Library databases searching studies that analyzed sexual function (assessed with the 19-item Female Sexual Function Index [FSFI]), and dyspareunia, chronic pelvic pain and dysmenorrhea (assessed with a visual analogue scale [VAS]) in women with and with endometriosis. Results: In 4 studies, non-treated women with endometriosis presented a higher risk of female sexual dysfunction (mean total FSFI score = 26.55; OR = 2.38; 95% confidence interval [CI] = 1.12, 5.04). Although mean total FSFI scores were not significantly different between women with and without endometriosis (mean difference [MD] = -2.15; 95% CI -4.96, 0.67); all FSFI domain scores were significantly lower in women with endometriosis (n = 4 studies): desire (MD = -0.43; 95% CI -0.57, -0.19); arousal (MD = -0.66; 95% CI -1.15, -0.17); lubrication (MD = -0.41; 95% CI -0.79, -0.02); orgasm (MD = -0.40; 95% CI -0.73, -0.06); satisfaction (MD = -0.45; 95% CI -0.72, -0.18); and pain (MD = -1.03; 95% CI -1.34, -0.72). Women with endometriosis displayed differences (more severity) in terms of VAS scores (2 studies) for dyspareunia (MD = 1.88; 95% CI 0.38, 3.37) and chronic pelvic pain (MD = 2.92; 95% CI 1.26, 4.58); but not for dysmenorrhea. Conclusion: Non-treated women with endometriosis displayed altered sexual function as evidenced by lower scores in all FSFI domains, and severity of dyspareunia and chronic pelvic pain

Distinctive dielectric properties of nematic liquid crystal dimers

We provide an overview of the effect of the molecular structure on the dielectric properties of dimers exhibiting nematic and twist-bend nematic phases with special focus on how the conformational distribution changes are reflected by the dielectric behaviour. Nematic dimers show distinctive dielectric properties which differ from those of archetypical nematic liquid crystals, as for example, unusual temperature dependence of the static permittivity or dielectric spectra characterised by two low-frequency relaxation processes with correlated strengths. The interpretation of such characteristic behaviour requires that account is taken of the effect of molecular flexibility on the energetically favoured molecular shapes. The anisotropic nematic interactions greatly influence the conformational distribution. Dielectric behaviour can be used to track those conformational changes due to dependence of the averaged molecular dipole moment on the averaged molecular shape. Results for a number of dimers are compared and analysed on the basis of the influence of details of the molecular structure, using a recently developed theory for the dielectric properties of dimers.Postprint (author's final draft

Miscibility studies of two twist-bend nematic liquid crystal dimers with different average molecular curvatures. A comparison between experimental data and predictions of a Landau mean-field theory for the NTB-N phase transition

We report a calorimetric study of a series of mixtures of two twist-bend liquid crystal dimers, the 1'',7''-bis(4-cyanobiphenyl)-4'-yl heptane (CB7CB) and 1''-(2',4-difluorobiphenyl-4'-yloxy)-9''-(4-cyanobiphenyl-4'-yloxy) nonane (FFO9OCB), the molecules of which have different effective molecular curvatures. High-resolution heat capacity measurements in the vicinity of the NTB-N phase transition for a selected number of binary mixtures clearly indicate a first order NTB-N phase transition for all the investigated mixtures, the strength of which decreases when the nematic range increases. Published theories predict a second order NTB-N phase transition, but we have developed a self-consistent mean field Landau model using two key order parameters: A symmetric and traceless tensor for the orientational order and a short-range vector field which is orthogonal to the helix axis and rotates around of the heliconical structure with an extremely short periodicity. The theory, in its simplified form, depends on two effective elastic constants and explains satisfactorily our heat capacity measurements and also predicts a first-order NTB-N phase transition. In addition, as a complementary source of experimental measurements, the splay (K1) and bend (K3) elastic constants in the conventional nematic phase for the pure compounds and some selected mixtures have been determined.Postprint (author's final draft

Molecular dynamics of a binary mixture of twist-bend nematic liquid crystal dimers studied by dielectric spectroscopy

We report a comprehensive dielectric characterization of a liquid crystalline binary mixture composed of the symmetric mesogenic dimer CB7CB and the nonsymmetric mesogenic dimer FFO9OCB. In addition to the high-temperature nematic phase, such a binary mixture shows a twist-bend nematic phase at room temperature which readily vitrifies on slow cooling. Changes in the conformational distribution of the dimers are reflected in the dielectric permittivity and successfully analyzed by means of an appropriate theoretical model. It is shown that the dielectric spectra of the mixture reflect the different molecular dipole properties of the components, resembling in the present case the characteristic dielectric spectra of nonsymmetric dimers. Comparison of the nematic and twist-bend nematic phases reveals that molecular dynamics are similar despite the difference in the molecular environment.Postprint (author's final draft

Lack of evidence for participation of TMEM150C in sensory mechanotransduction

The membrane protein TMEM150C has been proposed to form a mechanosensitive ion channel that is required for normal proprioceptor function. Here, we examined whether expression of TMEM150C in neuroblastoma cells lacking Piezo1 is associated with the appearance of mechanosensitive currents. Using three different modes of mechanical stimuli, indentation, membrane stretch, and substrate deflection, we could not evoke mechanosensitive currents in cells expressing TMEM150C. We next asked if TMEM150C is necessary for the normal mechanosensitivity of cutaneous sensory neurons. We used an available mouse model in which the Tmem150c locus was disrupted through the insertion of a LacZ cassette with a splice acceptor that should lead to transcript truncation. Analysis of these mice indicated that ablation of the Tmem150c gene was not complete in sensory neurons of the dorsal root ganglia (DRG). Using a CRISPR/Cas9 strategy, we made a second mouse model in which a large part of the Tmem150c gene was deleted and established that these Tmem150c(-/-) mice completely lack TMEM150C protein in the DRGs. We used an ex vivo skin nerve preparation to characterize the mechanosenstivity of mechanoreceptors and nociceptors in the glabrous skin of the Tmem150c(-/-) mice. We found no quantitative alterations in the physiological properties of any type of cutaneous sensory fiber in Tmem150c(-/-) mice. Since it has been claimed that TMEM150C is required for normal proprioceptor function, we made a quantitative analysis of locomotion in Tmem150c(-/-) mice. Here again, we found no indication that there was altered gait in Tmem150c(-/-) mice compared to wild-type controls. In summary, we conclude that existing mouse models that have been used to investigate TMEM150C function in vivo are problematic. Furthermore, we could find no evidence that TMEM150C forms a mechanosensitive channel or that it is necessary for the normal mechanosensitivity of cutaneous sensory neurons

Chern-Simons production during preheating in hybrid inflation models

We study the onset of symmetry breaking after hybrid inflation in a model having the field content of the SU(2) gauge-scalar sector of the standard model, coupled to a singlet inflaton. This process is studied in (3+1)-dimensions in a fully non-perturbative way with the help of lattice techniques within the classical approximation. We focus on the role played by gauge fields and, in particular, on the generation of Chern-Simons number. Our results are shown to be insensitive to the various cut-offs introduced in our numerical approach. The spectra preserves a large hierarchy between long and short-wavelength modes during the whole period of symmetry breaking and Chern-Simons generation, confirming that the dynamics is driven by the low momentum sector of the theory. We establish that the Chern-Simons production mechanism is associated with local sphaleron-like structures. The corresponding sphaleron rates are of order 10^{-5} m^4, which, within certain scenarios of electroweak baryogenesis and a (not unnaturally large) additional source of CP violation, could explain the present baryon asymmetry of the universe.Comment: 28 pages, 15 figures, ReVTeX. With minor corrections, version to appear in Phys. Rev.

Dynamics of a large extra dimension inspired hybrid inflation model

In low scale quantum gravity scenarios the fundamental scale of nature can be as low as TeV, in order to address the naturalness of the electroweak scale. A number of difficulties arise in constructing specific models; stabilisation of the radius of the extra dimensions, avoidance of overproduction of Kaluza Klein modes, achieving successful baryogenesis and production of a close to scale-invariant spectrum of density perturbations with the correct amplitude. We examine in detail the dynamics, including radion stabilisation, of a hybrid inflation model that has been proposed in order to address these difficulties, where the inflaton is a gauge singlet residing in the bulk. We find that for a low fundamental scale the phase transition, which in standard four dimensional hybrid models usually ends inflation, is slow and there is second phase of inflation lasting for a large number of e-foldings. The density perturbations on cosmologically interesting scales exit the Hubble radius during this second phase of inflation, and we find that their amplitude is far smaller than is required. We find that the duration of the second phase of inflation can be short, so that cosmologically interesting scales exit the Hubble radius prior to the phase transition, and the density perturbations have the correct amplitude, only if the fundamental scale takes an intermediate value. Finally we comment briefly on the implications of an intermediate fundamental scale for the production of primordial black holes and baryogenesis.Comment: 9 pages, 2 figures version to appear in Phys. Rev. D, additional references and minor changes to discussio

Plant-Frugivore Interactions Across the Caribbean Islands: Modularity, Invader Complexes and the Importance of Generalist Species

Aim: Mutualistic interactions between plants and animals are fundamental for the maintenance of natural communities and the ecosystem services they provide. However, particularly in human‐dominated island ecosystems, introduced species may alter mutualistic interactions. Based on an extensive dataset of plant–frugivore interactions, we mapped and analysed a meta‐network across the Caribbean archipelago. Specifically, we searched for subcommunity structure (modularity) and identified the types of species facilitating the integration of introduced species in the Caribbean meta‐network. Location: Caribbean archipelago (Lucayan archipelago, Greater Antilles, Lesser Antilles). Methods: We reviewed published scientific literature, unpublished theses and other nonpeer‐reviewed sources to compile an extensive dataset of plant–frugivore interactions. We visualized spatial patterns and conducted a modularity analysis of the cross‐island meta‐network. We also examined which species were most likely to interact with introduced species: (1) endemic, nonendemic native or introduced species, and (2) generalized or specialized species.We reported 3060 records of interactions between 486 plant and 178 frugivore species. Results: The Caribbean meta‐network was organized in 13 modules, driven by a combination of functional or taxonomic (modules dominated by certain groups of frugivores) and biogeographical (island‐specific modules) mechanisms. Few introduced species or interaction pairs were shared across islands, suggesting little homogenization of the plant–frugivore meta‐network at the regional scale. However, we found evidence of “invader complexes,” as introduced frugivores were more likely to interact with introduced plants than expected at random. Moreover, we found generalist species more likely to interact with introduced species than were specialized species. Main Conclusions: These results demonstrate that generalist species and “invader complexes” may facilitate the incorporation of introduced species into plant–frugivore communities. Despite the influx of introduced species, the meta‐network was structured into modules related to biogeographical and functional or taxonomic affinities. These findings reveal how introduced species become an integral part of mutualistic systems on tropical islands

Distribution, occurrence and biotoxin composition of the main

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