Prognostic Value of Left Ventricular Global Longitudinal Strain in Transcatheter Edge-to-Edge Repair for Chronic Primary Mitral Regurgitation.

AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-center, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9-(-16)%, -15.9-(-12)%, > -12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability - all along the first year after intervention. Subjects with worse (i.e., less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9 vs 6.3%, Log-Rank p = 0.005, HR 1.75, 95% CI 1.08-4.74, p = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1 vs 11.5%, Log-Rank p = 0.037, HR 1.68, 95% CI 1.02-5.46, p = 0.047). No association was demonstrated with other endpoints. Upon exploratory analysis, 1-month postprocedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value - but not the presence/extent of deterioration - conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favorable postprocedural course, presumably reflecting a higher-risk patient profile.

Case report: a transcatheter aortic valve replacement failure secondary to COVID-19 infection.

Background: Valve thrombosis is a well-documented cause of bioprosthetic valve failure. Case reports have been published of prosthetic valve thrombosis secondary to COVID-19 infection. This is the first case report of COVID-19 associated valve thrombosis in a patient with transcatheter aortic valve replacement (TAVR). Case summary: A 90-year-old female with atrial fibrillation on therapeutic apixaban and status-post TAVR presented with COVID-19 infection and was found to have severe bioprosthetic valvular regurgitation with features suggestive of valve thrombosis. She underwent valve-in-valve TAVR with resolution of valvular dysfunction. Discussion: This case report contributes to a growing body of evidence describing the occurrence of thrombotic complications in patients with valve replacement and COVID-19 infection. Increased vigilance and continued investigation are warranted to better characterize thrombotic risk and to inform optimal antithrombotic strategies during COVID-19 infection.

Palaeolithic cave art in Borneo.

Figurative cave paintings from the Indonesian island of Sulawesi date to at least 35,000 years ago (ka) and hand-stencil art from the same region has a minimum date of 40 ka1. Here we show that similar rock art was created during essentially the same time period on the adjacent island of Borneo. Uranium-series analysis of calcium carbonate deposits that overlie a large reddish-orange figurative painting of an animal at Lubang Jeriji Saléh-a limestone cave in East Kalimantan, Indonesian Borneo-yielded a minimum date of 40 ka, which to our knowledge is currently the oldest date for figurative artwork from anywhere in the world. In addition, two reddish-orange-coloured hand stencils from the same site each yielded a minimum uranium-series date of 37.2 ka, and a third hand stencil of the same hue has a maximum date of 51.8 ka. We also obtained uranium-series determinations for cave art motifs from Lubang Jeriji Saléh and three other East Kalimantan karst caves, which enable us to constrain the chronology of a distinct younger phase of Pleistocene rock art production in this region. Dark-purple hand stencils, some of which are decorated with intricate motifs, date to about 21-20 ka and a rare Pleistocene depiction of a human figure-also coloured dark purple-has a minimum date of 13.6 ka. Our findings show that cave painting appeared in eastern Borneo between 52 and 40 ka and that a new style of parietal art arose during the Last Glacial Maximum. It is now evident that a major Palaeolithic cave art province existed in the eastern extremity of continental Eurasia and in adjacent Wallacea from at least 40 ka until the Last Glacial Maximum, which has implications for understanding how early rock art traditions emerged, developed and spread in Pleistocene Southeast Asia and further afield.

Proteasome regulates transcription-favoring histone methylation, acetylation and ubiquitination in long-term synaptic plasticity.

Histone modifications, such as lysine methylation, acetylation and ubiquitination, are epigenetic tags that shape the chromatin landscape and regulate transcription required for synaptic plasticity and memory. Here, we show that transcription-promoting histone H3 trimethylated at lysine 4 (H3K4me3), histone H3 acetylated at lysine 9 and 14 (H3K9/14ac), and histone H2B monoubiquitinated at lysine 120 (H2BK120ub) are enhanced after the induction of long-lasting chemically-induced long-term potentiation (cLTP) in the murine hippocampus. While H3K4me3 and H3K9/14ac were transiently upregulated, H2BK120ub levels oscillated after cLTP induction. In addition, we present results showing that blocking the proteasome, a molecular complex specialized for targeted protein degradation, inhibited the upregulation of these epigenetic tags after cLTP. Thus, our study provides the initial steps toward understanding the role of the proteasome in regulating histone modifications critical for synaptic plasticity.

Estradiol-17beta stimulates gonadotropin II expression and release in the protandrous male black porgy Acanthopagrus schlegeli Bleeker: a possible role in sex change.

The objective of the present study was to investigate the in vivo effects of sex steroids (estradiol-17beta, E(2); testosterone, T) and the nonaromatizable androgen 5alpha-dihydrotestosterone (DHT) on the levels of gonadotropin II (GTH II) in plasma and pituitary and on aromatase activity in 2-year-old male black porgy, Acanthopagrus schlegeli, during the prereproductive season. Black porgy GTH II and GTH II beta subunits were purified and anti-GTH II beta serum was induced. A specific radioimmunoassay for black porgy GTH II was developed. cDNA GTH II beta was also cloned from a black porgy pituitary cDNA library for use as a probe for Northern analysis. Male fish were divided into eight groups (n = 64): control; E(2) (3 doses, 2.4 ng, 72 ng, and 2.2 microg/g body weight); T (2 doses, 72 ng and 2.2 microg/g body weight); and DHT (2 doses, 72 ng and 2.2 microg/g body weight). Fish were injected with the respective vehicle or different doses of material on days 0, 8, and 16. Plasma was collected at 4-day intervals from days 4 to 20. Plasma GTH II concentrations were significantly increased (up to 45-fold) in the E(2) group from days 4 to 20 in a dose-dependent manner. In a further experiment during the late reproductive season, plasma GTH II levels increased at 4 h and on days 1 and 2 following a single injection of 1.0 microg E(2)/g body weight (on day 0). Androgens (T or DHT) had little or no effect on plasma GTH II. Pituitary GTH II contents on day 20 were significantly lower in the 72-ng E(2) and 2.2-microg E(2) groups but not in the 2.4-ng E(2) group compared with the control group. Pituitary GTH II beta mRNA levels were significantly stimulated in the 72-ng and 2.2-microg E(2) groups on day 20. Gonadal aromatase activity was not significantly changed in any of the treated or control groups. It is concluded that GTH II secretion in black porgy is regulated by an estrogen-specific effect. Increased plasma GTH II levels or other factors in addition to E(2) might be involved in the regulation of gonadal aromatase activity and sex change in protandrous black porgy.

Environmental events and induction of metamotivational reversals.

Three administrations of the Telic State Measure were used to test the notion from reversal theory that environmental events may induce reversals in metamotivational state. Significant changes in scores on Telic State Measure items from three different groups of students experiencing three different environmental events and one student control group (total N=96) confirmed that unexpected environmental events could induce reversals from the telic to the paratelic metamotivational state.

Profiles of gonadal development, sex steroids, aromatase activity, and gonadotropin II in the controlled sex change of protandrous black porgy, Acanthopagrus schlegeli Bleeker.

The objectives of the present study were to investigate the effects of oral administration of estradiol-17 beta (E(2)) on the sex steroids and gonadotropin II (GTH II) in plasma, aromatase activity in gonad and brain, and sex change in protandrous black porgy, Acanthopagus schlegeli Bleeker. Two-year-old black porgy were divided into two groups, one fed a control diet and the other a diet mixed with E(2) (4.0 mg/kg feed) for 7 months. Significantly higher GSI was observed in the E(2) group. Fish treated with E(2) showed complete suppression of spermatogenesis and spermiation and induced sex change with vitellogenic oocytes and large primary oocytes. Lower levels of plasma 11-ketotestosterone and higher levels of plasma vitellogenin were shown in the E(2) group. Higher gonadal aromatase activity in concordance with elevated plasma levels of GTH II was observed in the E(2) group. The highest aromatase activity in the forebrain in the control group was observed in January. Higher aromatase activity in forebrain, midbrain, and hindbrain was also detected in the E(2) group than the control group. The change of aromatase activity in brain was more susceptible than that in gonad. The data showed that the increase of plasma GTH II levels and gonadal aromatase activity may be important to the controlled sex change by administration in black porgy.

Effect of egg deprivation on sex steroids, gonadotropin, prolactin, and growth hormone profiles during the reproductive cycle of the mouthbrooding cichlid fish Oreochromis niloticus.

Various hormones were analyzed during the course of a reproductive cycle in the cichlid fish Oreochromis niloticus: plasma levels of the gonadal steroids 17beta-estradiol (E2), testosterone (T), 17, 20beta-OH progesterone (17,20beta-P), gonadotropin (taGtH), and plasma and pituitary concentrations of prolactin (tiPRL(I) and tiPRL(II)) and growth hormone (tiGH). Two categories of fish were sampled and sacrificed on days 1 and 3 postspawning and at 3-day intervals thereafter: typical incubating females (INC), and nonincubating females (NI), deprived of their eggs just after spawning. Such deprivation is known to suppress maternal behavior and to accelerate ovarian development and especially vitellogenesis, thus shortening the mean interspawning interval. In both groups, variations of the plasma concentrations of E2 and T appeared to depend on ovarian stages, and differences between groups appeared to reflect underlying differences in the kinetics of ovarian development. The observation of noticeable levels of 17,20beta-P in plasma before spawning, when high values of taGtH could also be detected in NI females, suggests the implication of this progestin in the control of final maturation events, as in some other teleosts. Moreover, 17,20beta-P, which was still detected a few days after spawning, but at low concentrations and only in the plasma of INC females, might play a role at the beginning of the reproductive cycle in incubating females (maternal behavior and/or slowing down of ovarian growth). The pituitary and plasma profiles of both tiPRLs isoforms appeared to depend mainly on the kinetics of ovarian development in each group of fish, suggesting a role during the beginning of vitellogenesis. However, the variance of plasma tiPRL(II), which was significantly enhanced during maternal behavior in INC females, also suggests an implication of this hormone in the control of that behavior. Concerning tiGH, comparison of the plasma profiles in INC and NI fish also suggest an influence on the control of maternal behavior, but a main effect of starvation of INC during mouthbrooding cannot be excluded.

The endocrine mechanism of sex reversal in the protandrous black porgy, Acanthopagrus schlegeli: a review.

Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite, is a functional male for the first 2 years of life but begin to sexually reverse to female after the third year. This sex pattern provides a very good model to study the mechanism of sex reversal in fish. The gonad at 5 month of age consisted of testicular tissue with few primary oocytes at 5 month of age. The ovarian tissue became dominant at 18 months of age during the non-spawning season. Testicular and ovarian tissues were separated by connective tissue. Plasma estradiol-17 beta(E2), vitellogenin and 11-ketotestosterone (11-KT) profiles in males were significantly different from those in the 3-year-old reversing females. Peak levels of plasma E2 in the reversing females occurred during the early prespawning season (in October). Lower levels of plasma E2 were, however, observed in the males. Plasma 11-KT levels significant decreased but no changes of plasma testosterone were detected in the reversing females. Exogenous E2 suppressed the testicular development but induced the gonadal aromatase activity, ovarian development and sex reversal in 2-year-old black porgy. Exogenous T and LHRH analog did not have effects on the sex reversal. Higher concentrations of pituitary GtH II and mRNA of GtH II-beta subunit were detected in the reversed females. These data suggested that E2 and gonadal aromatase closely associated to the occurrence of sex reversal. A working model of the sex reversal in black porgy is proposed.