The Role of Sodium-Glucose Cotransporter-2 Inhibitors in the Treatment of Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women impacting their reproductive, mental, and metabolic health. Insulin resistance is a major driver of the pathophysiology of PCOS. There are several challenges with the management of this complex disorder including insufficient treatment options. Over the past 88 years, multiple hormonal and non-hormonal medications have been tried to treat the various components of this syndrome and there is no FDA (Food and Drug Administration)-approved medication specifically for PCOS yet. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have a unique mechanism of inhibiting the coupled reabsorption of sodium and glucose in renal proximal convoluted tubules. This review aims to examine the efficacy and side-effect profile of SGLT-2 inhibitors in patients with PCOS. In a limited number of studies, SGLT-2 inhibitors appear to be effective in improving menstrual frequency, reducing body weight and total fat mass, lowering total testosterone and DHEAS levels, and improving some glycemic indices in women with PCOS. SGLT2 inhibitors are generally well tolerated. With future research, it is possible that SGLT-2 inhibitors could become a key therapeutic option for PCOS.

Unveiling the combined effects of neutral dynamics and electrodynamic forcing on dayside ionosphere during the 3-4 February 2022 "SpaceX" geomagnetic storms.

Geomagnetic storms of G1-class were observed on 3 and 4 February 2022, which caused the loss of 38 out of 49 SpaceX satellites during their launch due to enhanced neutral density. The effects of storm-time neutral dynamics and electrodynamics over the American sector during this minor storm have been investigated using Global Positioning System-total electron content (TEC) and Global-scale Observations of the Limb and Disk (GOLD) mission measured thermospheric composition and temperature. Results revealed an unexpected feature in terms of increase in O/N2 and depletion in TEC over the American low-latitudes. This feature is in addition to the classic storm time ionospheric variations of enhancement in ionospheric electron density in presence of enhanced O/N2 and an intense equatorial electrojet (EEJ). Further, significant morning-noon electron density reductions were observed over the southern mid-high latitudes along the American longitudes. Results from Multiscale Atmosphere-Geospace Environment (MAGE) model simulations elucidated storm-induced equatorward thermospheric wind which caused the strong morning counter electrojet by generating the disturbance dynamo electric field. This further explains the morning TEC depletion at low-latitudes despite an increase in O/N2. Sub-storm related magnetospheric convection resulted in significant noon-time peak in EEJ on 4 February. Observation and modelling approaches together suggested that combined effects of storm-time neutral dynamic and electrodynamic forcing resulted in significant ionospheric variations over the American sector during minor geomagnetic storms.

The Role of Serum Anti-Mullerian Hormone Measurement in the Diagnosis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women with significant reproductive, metabolic, and psychological health implications. The lack of a specific diagnostic test poses challenges in making the diagnosis of PCOS, resulting in underdiagnosis and undertreatment. Anti-Mullerian hormone (AMH) synthesized by the pre-antral and small antral ovarian follicles appears to play an important role in the pathophysiology of PCOS, and serum AMH levels are often elevated in women with PCOS. The aim of this review is to inform the possibility of utilizing anti-Mullerian hormone either as a diagnostic test for PCOS or as an alternative diagnostic criterion in place of polycystic ovarian morphology, hyperandrogenism, and oligo-anovulation. Increased levels of serum AMH correlate highly with PCOS, polycystic ovarian morphology, hyperandrogenism, and oligo/amenorrhea. Additionally, serum AMH has high diagnostic accuracy as an isolated marker for PCOS or as a replacement for polycystic ovarian morphology.

The Ionospheric view of the 2011 Tohoku-Oki earthquake seismic source: the first 60 seconds of the rupture.

Using the specific satellite line of sight geometry and station location with respect to the source, Thomas et al. [Scientific Reports, https://doi.org/10.1038/s41598-018-30476-9] developed a method to infer the detection altitude of co-seismic ionospheric perturbations observed in Global Positioning System (GPS) - Total Electron Content (TEC) measurements during the Mw 7.4 March 9, 2011 Sanriku-Oki earthquake, a foreshock of the Mw 9.0, March 11, 2011 Tohoku-Oki earthquake. Therefore, in addition to the spatio-temporal evolution, the altitude information of the seismically induced ionospheric signatures can also be derived now using GPS-TEC technique. However, this method considered a point source, in terms of a small rupture area (~90 km) during the Tohoku foreshock, for the generation of seismo-acoustic waves in 3D space and time. In this article, we explore further efficacy of GPS-TEC technique during co-seismic ionospheric sounding for an extended seismic source varying simultaneously in space and time akin to the rupture of Mw 9.0 Tohoku-Oki mainshock and the limitations to be aware of in such context. With the successful execution of the method by Thomas et al. during the Tohoku-Oki mainshock, we not only estimate the detection altitude of GPS-TEC derived co-seismic ionospheric signatures but also delineate, for the first time, distinct ground seismic sources responsible for the generation of these perturbations, which evolved during the initial 60 seconds of the rupture. Simulated tsunami water excitation over the fault region, to envisage the evolution of crustal deformation in space and time along the rupture, formed the base for our model analysis. Further, the simulated water displacement assists our proposed novel approach to delineate the ground seismic sources entirely based on the ensuing ionospheric perturbations which were otherwise not well reproduced by the ground rupture process within this stipulated time. Despite providing the novel information on the segmentation of the Tohoku-Oki seismic source based on the co-seismic ionospheric response to the initial 60 seconds of the event, our model could not reproduce precise rupture kinematics over this period. This shortcoming is also credited to the specific GPS satellite-station viewing geometries.

Mapping the Impact of Non-Tectonic Forcing mechanisms on GNSS measured Coseismic Ionospheric Perturbations.

Global Navigation Satellite System (GNSS) measured Total Electron Content (TEC) is now widely used to study the near and far-field coseismic ionospheric perturbations (CIP). The generation of near field (~500-600 km surrounding an epicenter) CIP is mainly attributed to the coseismic crustal deformation. The azimuthal distribution of near field CIP may contain information on the seismic/tectonic source characteristics of rupture propagation direction and thrust orientations. However, numerous studies cautioned that before deriving the listed source characteristics based on coseismic TEC signatures, the contribution of non-tectonic forcing mechanisms needs to be examined. These mechanisms which are operative at ionospheric altitudes are classified as the i) orientation between the geomagnetic field and tectonically induced atmospheric wave perturbations ii) orientation between the GNSS satellite line of sight (LOS) geometry and coseismic atmospheric wave perturbations and iii) ambient electron density gradients. So far, the combined effects of these mechanisms have not been quantified. We propose a 3D geometrical model, based on acoustic ray tracing in space and time to estimate the combined effects of non-tectonic forcing mechanisms on the manifestations of GNSS measured near field CIP. Further, this model is tested on earthquakes occurring at different latitudes with a view to quickly quantify the collective effects of these mechanisms. We presume that this simple and direct 3D model would induce and enhance a proper perception among the researchers about the tectonic source characteristics derived based on the corresponding ionospheric manifestations.

Molecular docking and dynamic studies of crepiside E beta glucopyranoside as an inhibitor of snake venom PLA2.

Alternative treatments from plant-derived small molecules for neutralizing the venom lethality in snake envenomation are prevalent now. Elephantopus scaber, a tropical plant species has been recognized for its various pharmacological activities and especially anti-snake venom property; however, the molecular basis for this property is not understood. It is reported that snake venom PLA2 is a toxic factor with pharmacological effects independent of their catalytic activity. Here we report the inhibition of catalytic property of Cobra and Viper (group I and group II) snake venom PLA2 by the phytocompounds from E. scaber through molecular docking and dynamics studies. Initially, Lipinski's rule, ADMET, and molecular docking studies were carried out. Our results show that among 124 phytocompounds, crepiside E (deacylcynaropicrin-3' beta-glucopyranoside) has shown interactions with the conserved catalytic active site residues, His 48 and Asp 49, in both the PLA2s. Further, molecular dynamic simulations for 60 ns confirmed the stability of crepiside E in the active site of PLA2s and were found to be stable throughout the simulation. In order to understand the drug-likeness of crepiside E, pIC50 and MMGBSA scores were correlated by performing a linear regression analysis. Crepiside E was found to have similar chemical features to that of doxycycline, a known PLA2 inhibitor as indicated by a similarity score of 64.15%. Hence, it is concluded that crepiside E beta glucopyranoside present in Elephantopus scaber contributes to neutralizing the snake venom.

Author Correction: Revelation of early detection of co-seismic ionospheric perturbations in GPS-TEC from realistic modelling approach: Case study.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Revelation of early detection of co-seismic ionospheric perturbations in GPS-TEC from realistic modelling approach: Case study.

GPS-derived Total Electron Content (TEC) is an integrated quantity; hence it is difficult to relate the detection of ionospheric perturbations in TEC to a precise altitude. As TEC is weighted by the maximum ionospheric density, the corresponding altitude (hmF2) is, generally, assumed as the perturbation detection altitude. To investigate the validity of this assumption in detail, we conduct an accurate analysis of the GPS-TEC measured early ionospheric signatures related to the vertical surface displacement of the Mw 7.4 Sanriku-Oki earthquake (Sanriku-Oki Tohoku foreshock). Using 3D acoustic ray tracing model to describe the evolution of the propagating seismo-acoustic wave in space and time, we demonstrate how to infer the detection altitude of these early signatures in TEC. We determine that the signatures can be detected at altitudes up to ~130 km below the hmF2. This peculiar behaviour is attributed to the satellite line of sight (LOS) geometry and station location with respect to the source, which allows one to sound the co-seismic ionospheric signatures directly above the rupture area. We show that the early onset times correspond to crossing of the LOS with the acoustic wavefront at lower ionospheric altitudes. To support the proposed approach, we further reconstruct the seismo-acoustic induced ionospheric signatures for a moving satellite in the presence of a geomagnetic field. Both the 3D acoustic ray tracing model and the synthetic waveforms from the 3D coupled model substantiate the observed onset time of the ionospheric signatures. Moreover, our simple 3D acoustic ray tracing approach allows one to extend this analysis to azimuths different than that of the station-source line.

Feature selection in classification of eye movements using electrooculography for activity recognition.

Activity recognition is needed in different requisition, for example, reconnaissance system, patient monitoring, and human-computer interfaces. Feature selection plays an important role in activity recognition, data mining, and machine learning. In selecting subset of features, an efficient evolutionary algorithm Differential Evolution (DE), a very efficient optimizer, is used for finding informative features from eye movements using electrooculography (EOG). Many researchers use EOG signals in human-computer interactions with various computational intelligence methods to analyze eye movements. The proposed system involves analysis of EOG signals using clearness based features, minimum redundancy maximum relevance features, and Differential Evolution based features. This work concentrates more on the feature selection algorithm based on DE in order to improve the classification for faultless activity recognition.

Association of systemic lupus erythematosus with angiographically defined coronary artery disease: a retrospective cohort study.

OBJECTIVE: To determine if systemic lupus erythematosus (SLE) is associated with a higher prevalence of coronary artery disease (CAD) in select patients undergoing coronary angiography. We compared the extent of angiographic abnormalities, CAD risk factors, and all-cause mortality in SLE patients with non-SLE controls. METHODS: We identified SLE patients (n = 86) and controls matched by sex and year of cardiac catheterization (n = 258) undergoing cardiac catheterization for the evaluation of CAD (median followup duration of 4.3 years). Multivariable logistic regression was used to determine if SLE was associated with obstructive CAD, defined as ≥70% stenosis in a major epicardial coronary artery. Risk-adjusted survival differences between the 2 groups were assessed using Cox proportional hazards modeling. RESULTS: The SLE patients (85% women) were younger than the non-SLE patients (median age 49 years versus 70 years; P < 0.001) and were less likely to have diabetes mellitus and hyperlipidemia, but had similar rates of hypertension (70% versus 71%; P = 0.892). In unadjusted analyses, SLE and non-SLE patients had similar rates of obstructive CAD by angiography (52% versus 62%; overall P = 0.11). After adjustment for known CAD risk factors, SLE was associated with a significantly increased likelihood of CAD (odds ratio 2.24 [95% confidence interval (95% CI) 1.08-4.67]). SLE was also associated with a nonsignificant increase in all-cause mortality (hazard ratio 1.683 [95% CI 0.98-2.89], P = 0.060). CONCLUSION: In this selected population, SLE was significantly associated with the presence of CAD as defined by coronary angiography, the gold standard for assessing flow-limiting lesions in this disease. The patients with SLE showed a similar severity of CAD as the controls despite having less than half the rate of diabetes mellitus and being 20 years younger.

Attitudes of final year dental students to the use of rubber dam.

AIM: To investigate the attitudes of final year dental students in Wales and Ireland to the use of rubber dam. METHODS: A pre-piloted questionnaire was distributed to final year dental students in Cardiff and Cork Dental Schools in January 2008. Information sought included attitudes to, and the current and anticipated use of, rubber dam for a variety of operative and endodontic treatments. RESULTS: Of 93 questionnaires distributed, 87 were completed and returned (response rate = 94%; Cardiff: 89%, n = 51; Cork: 100%, n = 36). Rubber dam was routinely used by 98% of respondents (n = 85) on adult patients, but only 32% of respondents (n = 28) had used rubber dam on child patients (P < 0.05). Rubber dam was never used by 75% of respondents (n = 65) when placing posterior amalgam restorations, and by 21% of respondents (n = 18) when placing anterior composite restorations. Rubber dam was used by 98% of the respondents (n = 85) when performing root canal treatments. Sixty-two per cent of respondents (n = 54) believed their use of rubber dam would decrease once leaving the dental school. CONCLUSION: Whilst dental students believe that rubber dam is relevant to clinical dentistry, there are negative perceptions associated with its use amongst dental students. More than half of those questioned predicted their use of rubber dam would decrease once in independent practice. Greater emphasis should be placed on the advantages of using rubber dam in clinical dentistry whilst at dental school.

Temporal changes in myeloid cells in the cervix during pregnancy and parturition.

Preterm birth occurs at a rate of 12.7% in the U.S. and is the primary cause of fetal morbidity in the first year of life as well as the cause of later health problems. Elucidation of mechanisms controlling cervical remodeling is critical for development of therapies to reduce the incidence of prematurity. The cervical extracellular matrix must be disorganized during labor to allow birth, followed by a rapid repair postpartum. Leukocytes infiltrate the cervix before and after birth and are proposed to regulate matrix remodeling during cervical ripening via release of proteolytic enzymes. In the current study, flow cytometry and cell sorting were used to determine the role of immune cells in cervical matrix remodeling before, during, and after parturition. Markers of myeloid cell differentiation and activation were assessed to define phenotype and function. Tissue monocytes and eosinophils increased in the cervix before birth in a progesterone-regulated fashion, whereas macrophage numbers were unchanged. Neutrophils increased in the postpartum period. Increased mRNA expression of Csfr1 and markers of alternatively activated M2 macrophages during labor or shortly postpartum suggest a function of M2 macrophages in postpartum tissue repair. Changes in cervical myeloid cell numbers are not reflected in the peripheral blood. These data along with our previous studies suggest that myeloid-derived cells do not orchestrate processes required for initiation of cervical ripening before birth. Additionally, macrophages with diverse phenotypes (M1 and M2) are present in the cervix and are most likely involved in the postpartum repair of tissue.

Influence of selenium on innate immune response in kids.

The effect is described of selenium supplemented in an inorganic and organic form on the innate immune response of goats. Though the phagocytic activity (as a marker of the immune function) was found to be lower in organic-Se-treated group than in control (54.5 +/- 4.32 vs. 60.2 +/- 9.15 %), it did not generally exhibit any significant differences; similarly, no differences were found in the phagocytic index. The production of reactive oxygen species (ROS) was determined using the luminol-enhanced chemiluminescence (CL) (estimated as peak CL, integral CL and a peak time after addition of calcium ionophore A23187, opsonised zymosan (OZP) and phorbol-12-myristate-13-acetate as effectors. A significant ROS increase reflected in integral CL and a peak time was found in the inorganic-Se-treated group when OZP was used as activator; other parameters did not exhibit significant changes. The supplementation of Se in inorganic form can thus be seen to influence positively the innate immune system of kids.

Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice.

Cervical remodeling during pregnancy and parturition is a single progressive process that can be loosely divided into four overlapping phases termed softening, ripening, dilation/labor, and post partum repair. Elucidating the molecular mechanisms that facilitate all phases of cervical remodeling is critical for an understanding of parturition and for identifying processes that are misregulated in preterm labor, a significant cause of perinatal morbidity. In the present study, biomechanical measurements indicate that softening was initiated between gestation days 10 and 12 of mouse pregnancy, and in contrast to cervical ripening on day 18, the softened cervix maintains tissue strength. Although preceded by increased collagen solubility, cervical softening is not characterized by significant increases in cell proliferation, tissue hydration or changes in the distribution of inflammatory cells. Gene expression studies reveal a potentially important role of cervical epithelia during softening and ripening in maintenance of an immunomucosal barrier that protects the stromal compartment during matrix remodeling. Expression of two genes involved in repair and protection of the epithelial permeability barrier in the gut (trefoil factor 1) and skin (serine protease inhibitor Kazal type 5) were increased during softening and/or ripening. Another gene whose function remains to be elucidated, purkinje cell protein 4, declines in expression as remodeling progressed. Collectively, these results indicate that cervical softening during pregnancy is a unique phase of the tissue remodeling process characterized by increased collagen solubility, maintenance of tissue strength, and upregulation of genes involved in mucosal protection.

Newer hormonal therapies: lower doses; oral, transdermal, and vaginal formulations.

Hormonal therapy remains the gold standard for treating menopausal symptoms. In addition, some formulations are indicated for preventing and treating bone loss. In this article, we review some of the hormonal regimens that have been approved in the past 5 years.

Update on hormonal contraception.

Several newer hormonal contraceptive agents have become available in recent years. Many of them are slight variations on previous agents. In this article, we review the advantages, side effects, and practical considerations of hormonal contraceptives approved in the last few years.

Dynamic changes in the cervical epithelial tight junction complex and differentiation occur during cervical ripening and parturition.

Cervical epithelia have numerous functions that include proliferation, differentiation, maintenance of fluid balance, protection from environmental hazards, and paracellular transport of solutes via tight junctions (TJs). Epithelial functions must be tightly regulated during pregnancy and parturition as the cervix undergoes extensive growth and remodeling. This study evaluated TJ proteins, as well as markers of epithelial cell differentiation in normal and cervical ripening defective mice to gain insights into how the permeability barrier is regulated during pregnancy and parturition. Although numerous TJ proteins are expressed in the nonpregnant cervix, claudins 1 and 2 are temporally regulated in pregnancy. Claudin 1 mRNA expression is increased, whereas claudin 2 expression declines. The cellular localization of claudin 1 shifts at the end of pregnancy (gestation d 18.75) to the plasma membrane in a lattice pattern, consistent with TJs in the apical cells. The timing of claudin 1-enriched TJs coincides with initiation of terminal differentiation of cervical squamous epithelia as evidenced by the increased expression of genes by differentiated epithelia late on gestation d 18. The cervical ripening defective steroid 5alpha-reductase type 1 deficient mouse, which has an elevated local progesterone concentration, also has aberrant claudin 1 and 2 expressions, fails to form claudin 1-enriched TJs, and lacks normal expression of genes involved in epithelial terminal differentiation. These data suggest that changes in permeability barrier properties during cervical ripening are, in part, negatively regulated by progesterone, and that dynamic changes in barrier properties of the cervix occur during pregnancy and parturition.

Oppositines A and B, sesquiterpene pyridine alkaloids from a Sri Lankan Pleurostylia opposita.

Two new sesquiterpene pyridine alkaloids, oppositines A (1) and B (2), have been isolated from the plant Pleurostylia opposita, collected in Sri Lanka. The compounds were isolated and purified by solvent/solvent partitioning, column chromatography, and HPLC. Their structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Oppositines A (1) and B (2) showed moderate cytotoxicity against HCT116 cell lines with EC50 values of 27 +/- 2 and 26 +/- 3 microM, respectively.

Utilization of different aquaporin water channels in the mouse cervix during pregnancy and parturition and in models of preterm and delayed cervical ripening.

Biochemical changes of cervical connective tissue, including progressive disorganization of the collagen network and increased water content, occur during gestation to allow for cervical dilatation during labor, but the mechanisms that regulate cervical fluid balance are not fully understood. We examined whether aquaporins (AQPs), a family of membrane channel proteins that facilitate water transport, help mediate fluid balance in the mouse cervix during parturition. Of the 13 known murine AQPs, AQP0-2, 6, 7, 9, 11, and 12 were absent or at the limits of detection. By Northern blot and real-time PCR, AQP3 expression was low in nongravid and mid-pregnancy cervices with peak expression on d 19 and postpartum d 1 (PP1). AQP4 expression was generally low throughout pregnancy but showed a small upward trend at the time of parturition. AQP5 and AQP8 expression were significantly increased on d 12-15 but fell to nongravid/baseline by d 19 and PP1. By in situ hybridization and immunohistochemistry, AQP3 was preferentially expressed in basal cell layers of the cervical epithelium, whereas AQP4, 5, and 8 were primarily expressed in apical cell layers. Females with LPS-induced preterm labor had similar trends in AQP4, 5, and 8 expression to mice with natural labor at term gestation. Mice with delayed cervical remodeling due to deletion of the steroid 5alpha-reductase type 1 gene showed significant reduction in the levels of AQP3, 4, and 8 on d 19 or PP1. Together, these studies suggest that AQPs 3, 4, 5, and 8 regulate distinct aspects of cervical water balance during pregnancy and parturition.