Comparing the outcomes of rheumatic heart disease in pregnancy complicated with and without atrial fibrillation: A propensity score matched analysis.

BACKGROUND: Atrial fibrillation (AF) may increase the risk of adverse maternal and fetal outcomes among pregnant with rheumatic valvular lesions (RHD). We aimed to assess the rate of occurrence of AF in pregnant with RHD and its impact on cardiac and maternal-fetal outcomes compared to those without it. METHODS: The study group consisted of pregnant women with RHD and AF (cases) and a matched comparison group of pregnant women with RHD but without AF (controls) was derived from the database of pregnant women with RHD receiving care at our center between 2011 and 2021. Incidence of composite adverse outcomes(maternal death, heart failure, or thrombo-embolic events) and pregnancy outcomes were compared between them. RESULTS: Seventy-one (5.1%; 95%CI 4.1%-6.4%) pregnant women with RHD had AF during pregnancy and childbirth, most occurring in the late second or early third trimester. New-onset AF was diagnosed in 34 (47.9%) of them. After matching, the incidence of composite outcome was higher in women with AF (77.5% (95%CI 66.3%-85.7%) compared to women without AF (17.3%(95%CI 13.3%-22.1%), P < .001), with seven (9.9%) maternal deaths among cases and two (0.7%) in controls. Heart failure was the most common adverse cardiac event (26.7% vs. 4.2%, P < .001, cases vs controls). Those with AF had higher odds (adjusted OR 56.6 (14.1-226.8)) of adverse cardiac outcomes after adjusting for other risk factors. The frequency of most non-cardiac pregnancy complications was similar in both groups. However, there was a trend towards a higher rate of miscarriage (16.9% vs. 9.9%), small-for-gestational-age babies(16.3 vs. 9.0%), and cesarean rates(31.9% vs. 18.3%) women with AF compared to those who did not experience AF. CONCLUSIONS: Atrial fibrillation in pregnancy among women with RHD was associated with an increased risk of maternal morbidity and mortality, with a trend towards an increase in some non-cardiac pregnancy complications compared to those pregnant women without AF. Our study results provide background data for developing and implementing a pregnancy-specific management strategy tailored to middle-income settings.

Percutaneous balloon mitral valvotomy during pregnancy: A systematic review and meta-analysis.

INTRODUCTION: The objective of this study was to systematically review the maternal and fetal outcomes in pregnant women who underwent percutaneous balloon mitral valvuloplasty (PBMV) during pregnancy. MATERIAL AND METHODS: A search was conducted on MEDLINE and Embase databases to identify studies published between 2000 and 2018 that reported on maternal and fetal outcomes following PBMV performed in pregnancy. Randomized controlled trials, cohort studies, case-control studies, cross-sectional studies and case series with four or more pregnancies in which PBMV was performed during pregnancy were included. Reference lists from relevant articles were also hand-searched for relevant citations. A successful procedure was defined as one where there was a reported improvement in the valve area or reduction in the mitral valve gradient. A random effects model was used to derive pooled estimates of various outcomes and the final estimates were reported as percentages with a 95% confidence interval (95% CI). RESULTS: Twenty-one observational studies reporting 745 pregnancies were included in the review, all of them having reported outcomes without a comparison group. Most of the studies fell into the low-risk category as determined using the Joanna Briggs Institute (JBI) critical appraisal checklist for case series. Most of the studies (86%) were reported from low- to middle-income countries and PBMV was mostly performed during the second trimester of pregnancy. Forty-three procedures (5.7%) were unsuccessful, nearly half (n = 19) of them reported among women with the severe subvalve disease (Wilkins subvalve score 3 or more). There were 11 maternal deaths among those with suboptimal valve anatomy (severe subvalve disease or Wilkin score >8). Mitral regurgitation was the most common cardiac complication (12.7%; 95% CI 7.3%-19.1%), followed by restenosis (2.4%; 95% CI 0.02%-7.2%). Pooled incidence of cesarean section was 12.1% (95% CI 3.6%-23.8%), preterm delivery 3.9% (95% CI 0.6%-9.0%), stillbirth 0.9% (95%CI 0.2%-2.2%) and low birthweight 5.4% (95% CI 0.2%-14.7%). CONCLUSIONS: PBMV may be an effective and safe procedure for optimizing outcomes in pregnant women with mitral stenosis in the absence of severe subvalve disease.

Inflammatory Impact on Tissues Surrounding the Dental Implant of Singular Abutments Bonded onto Titanium Base - A Randomized Controlled Trial.

Introduction: In dental implants, the biochemical connection between titanium (ti) and bony tissue has been well established. The properties of dental implants such as osseointegration and stability depend upon composition, design of the implant, connection, and design of the abutment, and additional removal of abutments. Recently, laser-generated micro-grooved surface (LSS) and TI abutments are the main focus of preventing peri-implant inflammation. Objectives: To assess the inflammatory impact of singular abutments bonded onto titanium bases on tissues surrounding the dental implant. Methods: Twenty subjects were enrolled. Only those subjects were enrolled who were scheduled to undergo prosthetic rehabilitation of missing teeth. Random division of subjects was done. Group A: Test abutment group and Group B: Control abutment group. The test abutments comprised Computer-Aided Design/Computer-Aided Manufacturing (CAD/CAM) titanium abutments bonded onto titanium abutments. However, control abutments were customized and only one-piece CAD/CAM titanium abutments were enrolled.On 6 months and 12 months of follow-up, the clinical and radiographic examination was done. Assessment of the bone level changes, clinical variables, and IL-1b levels was assessed. Results: Mean IL-1b levels in Group A subjects at baseline, 6 months, and 12 months were 1.52 pg/mL, 1.69 pg/mL, and 1.55 pg/mL, respectively. Mean IL-1b levels among the patients of group B at baseline, 6 months, and 12 months were 1.56 pg/mL, 1.71 pg/mL, and 1.54 pg/mL, respectively. Conclusion: Within the limitation of the study, it can be concluded that the impact on the inflammatory condition of surrounding tissues of dental implant does not vary significantly between single abutments bonded onto Titanium bases and singular abutments.

Comparison of Root Dentinal Crack Formation after Coronal Pre-Flaring using Different Rotary Instruments: An In vitro Study.

Background and Objectives: The aim of this study was to see the incidence of cracks in root dentin after coronal flaring using various rotary instruments such as Gates Glidden (GG) drills, ProTaper Universal SX, OneFlare, and HyFlex EDM. Materials and Methods: Seventy freshly extracted premolar teeth with single canal were collected. All the teeth were randomly divided into five groups of fourteen each (n = 14), of which one group served as the control and the rest of the four groups were instrumented with GG drills, ProTaper Universal SX, OneFlare, and HyFlex EDM, respectively. Results: The GG drills resulted in a higher rate of crack formation in root dentin (P < 0.05) than the ProTaper Universal SX, OneFlare, and HyFlex EDM instruments (P > 0.05). Conclusion: The use of GG drills resulted in more crack formation. However, the results for the ProTaper Universal SX, OneFlare, and HyFlex EDM flaring instruments were less in terms of crack formation.

Concurrent valve replacement and caesarean section for rheumatic mitral valve disease with refractory heart failure in late pregnancy.

Objective: To assess clinical characteristics and outcomes of women who underwent concurrent valve replacement with caesarean section for severe rheumatic mitral valve disease with refractory heart failure. Methods: All women admitted to a single centre from 2011 to 2020 with severe rheumatic mitral valve disease, having recurrent episodes of pulmonary edema on optimal medical therapy and contraindication to percutaneous balloon mitral valvotomy, who underwent concurrent valve replacement (for native valve disease) along with caesarean section, were included. Results: Among 1300 pregnancies with rheumatic heart disease, six underwent the concurrent procedure. All had replacement of mitral valve except one who had both aortic and mitral valve replacements, between 33 and 39 weeks of gestation. There were no maternal deaths, and there was one neonatal loss from late-onset sepsis. Conclusion: Pregnant women with severe rheumatic mitral valve disease with refractory heart failure, unsuitable for minimal access interventions, can be considered for a concurrent valve replacement with caesarean section.

Impact of nurse-led cardiac rehabilitation on patient's behavioral and physiological parameters after a coronary intervention: A pilot randomized controlled trial.

BACKGROUND: Coronary artery disease, one of the leading causes of mortality and morbidity globally, is a major burden on healthcare resources. Cardiovascular rehabilitation is highly recommended for the early recovery of patients with Ischemic heart disease by improving the functional capacity and decreasing disease progression. A randomized controlled trial was conducted to assess the effect of nurse-led cardiac rehabilitation (CR) on behavioural parameters. MATERIALS AND METHODS: Sixty-two adult patients who underwent percutaneous coronary intervention (PCI) were randomised to two groups to assess the effect of nurse-led cardiac rehabilitation (CR) on behavioural parameters, including adherence to drugs, cardiac diet, lifestyle changes, and selected physiological parameters. The intervention group had nurse-led individualized discharge counseling and clinical follow-up by telephone, whereas the control group received usual care. The comparisons between the control and intervention groups were made using independent Student's t-test or Mann-Whitney U test as appropriate. Pre-test and post-test scores were compared using paired t-test; all tests performed at 5% significance level. RESULTS: Participants in the intervention group presented with moderate to good smoking cessation, improved adherence to drugs (P < 0.0001), physically active lifestyle in 90.3 versus 45.2% (P < 0.0001), adherence to dietary changes, and improved healthcare satisfaction (P < 0.0001). There was also a significant reduction in triglycerides level in the intervention group at 62.51 versus 20.12 mg/dl in the control arm with (P < 0.05), and better controlled physiological indices, including a reduction in systolic blood pressure of 1.54 vs-7.12 mmHg (P = 0.003), bodyweight reduction of 2.48 kg versus-0.09 kg (P < 0.0001) and body mass index of 0.9 versus-0.05 (P < 0.0001). CONCLUSION: Personalised, nurse-led CR significantly improved the participants adherence to healthy lifestyle behaviors and decreased the cardiac risk factors in patients with coronary artery disease.

A validated and optimized method for separation and quantification of total fatty acids by gas chromatography-ion trap mass spectrometry in human plasma.

Fatty acids (FAs) are associated with many physiological functions of tissues, and their alteration has been linked with tissue-specific or systemic diseases. The current situation warrants us to have a sensitive and specific method for analysis of total FAs simultaneously from the biological fluid so that the risk prediction, diagnosis or prognosis of the disease can be made effectively. Because of greater sensitivity and resolution, a method of gas chromatography-ion trap mass spectrometry (GC-IT/MS) has been optimized and validated to quantify simultaneously 19 total FAs levels in plasma and compared with GC-triple quadrupole mass spectrometry. FAs have been transesterified by methanolic acetyl chloride to fatty acid methyl esters (FAMEs). A 65 min GC method separated all 19 FAMEs. The calibration curve had good linearity up to 313-922 µM with a correlation coefficient between 0.9882 and 0.9998. The LODs and LOQs of FAMEs were in the range of 0.63 to 9.55 and 2.12 to 31.8 µM, respectively. The method has recovery up to 144 %, stability at 4 °C for 48 h and one freeze-thaw cycle, and good intra-day and inter-day precision. The optimized method has been used to quantify plasma total FAs in type 2 diabetes mellitus patients with and without acute coronary syndrome. Though a significant difference has been found between IT/MS and triple quadrupole mass spectrometry, the GC-IT/MS can help to quantify total FAs in the clinical setting.

Influence of maternal and perinatal characteristics on risk of postpartum chronic hypertension after pre-eclampsia.

OBJECTIVE: To assess the prevalence of new-onset postpartum chronic hypertension (PPCH) after pre-eclampsia and to determine the factors are associated with it. METHODS: This study was conducted in a tertiary center in south India, between June 2018 and February 2019, consisting of pre-eclamptic women who were recruited as part of an ongoing cohort and had completed at least 3 months of postpartum follow-up. Demographic, medical, and laboratory details were collected. Primary outcome was a diagnosis of new-onset PPCH at 3 months. RESULTS: PPCH at 3 months was noted in 32 (18.1%) women. During postnatal follow-up, 2 (1.1%) women experienced hemiplegia from stroke and 19 (10.7%) had elevated serum creatinine levels (>1.1 mg/dL). On multivariate analysis, advancing maternal age (adjusted odds ratio [aOR] 1.10, 95% confidence interval [CI] 1.01-1.21), multiparity (aOR 2.79, 95% CI 1.07-7.24), and eclampsia (aOR 3.07, 95% CI 1.03-9.13) increased the risk of PPCH at 3 months postpartum. CONCLUSION: One in five women present with a diagnosis of new-onset PPCH within 3 months postpartum in a cohort of predominantly preterm and/or severe pre-eclampsia. A significant but weak association of PPCH with peripartum clinical characteristics was noted. The role of biochemical, hemodynamic, and echocardiographic biomarkers should be evaluated for prediction of PPCH after pre-eclampsia in future studies.

Enhancement of inosine-mediated A2AR signaling through positive allosteric modulation.

Inosine is an endogenous nucleoside that is produced by metabolic deamination of adenosine. Inosine is metabolically more stable (half-life 15h) than adenosine (half-life <10s). Inosine exerts anti-inflammatory and immunomodulatory effects similar to those observed with adenosine. These effects are mediated in part through the adenosine A2A receptor (A2AR). Relative to adenosine inosine exhibits a lower affinity towards the A2AR. Therefore, it is generally believed that inosine is incapable of activating the A2AR through direct engagement, but indirectly activates the A2AR upon metabolic conversion to higher affinity adenosine. A handful of studies, however, have provided evidence for direct inosine engagement at the A2AR leading to activation of downstream signaling events and inhibition of cytokine production. Here, we demonstrate that under conditions devoid of adenosine, inosine as well as an analog of inosine 6-S-[(4-Nitrophenyl)methyl]-6-thioinosine selectively and dose-dependently activated A2AR-mediated cAMP production and ERK1/2 phosphorylation in CHO cells stably expressing the human A2AR. Inosine also inhibited LPS-stimulated TNF-α, CCL3 and CCL4 production by splenic monocytes in an A2AR-dependent manner. In addition, we demonstrate that a positive allosteric modulator (PAM) of the A2AR enhanced inosine-mediated cAMP production, ERK1/2 phosphorylation and inhibition of pro-inflammatory cytokine and chemokine production. The cumulative effects of allosteric enhancement of adenosine-mediated and inosine-mediated A2AR activation may be the basis for the sustained anti-inflammatory and immunomodulatory effects observed in vivo and thereby provide insights into potential therapeutic interventions for inflammation- and immune-mediated diseases.

The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias.

Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h. Resembling adenosine, inosine acting through adenosine receptors (ARs) exerts a wide range of anti-inflammatory and immunomodulatory effects in vivo. The immunomodulatory effects of inosine in vivo, at least in part, are mediated via the adenosine A2A receptor (A2AR), an observation that cannot be explained fully by in vitro pharmacological characterization of inosine at the A2AR. It is unclear whether the in vivo effects of inosine are due to inosine or a metabolite of inosine engaging the A2AR. Here, utilizing a combination of label-free, cell-based, and membrane-based functional assays in conjunction with an equilibrium agonist-binding assay we provide evidence for inosine engagement at the A2AR and subsequent activation of downstream signaling events. Inosine-mediated A2AR activation leads to cAMP production with an EC50 of 300.7µM and to extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation with an EC50 of 89.38µM. Our data demonstrate that inosine produces ERK1/2-biased signaling whereas adenosine produces cAMP-biased signaling at the A2AR, highlighting pharmacological differences between these two agonists. Given the in vivo stability of inosine, our data suggest an additional, previously unrecognized, mechanism that utilizes inosine to functionally amplify and prolong A2AR activation in vivo.

Resection of the large bowel suppresses hunger and food intake and modulates gastrointestinal fermentation.

OBJECTIVE: To assess appetite and gut hormone levels in patients following partial (PR) or total resection (TR) of the large bowel. METHODS: A comparative cross sectional study was carried out with healthy controls (n = 99) and patients who had undergone PR (n = 64) or TR (n = 12) of the large bowel. Participants consumed a standard (720 kcal) breakfast meal at 0830 (t = 0) h followed by lactulose (15 g) and a buffet lunch (t = 210 min). Participants rated the subjective feelings of hunger at t = -30, 0, 30, 60, 120, and 180 min. Breath hydrogen (BH) concentrations were also evaluated. In a matched subset (11 controls, 11 PR and 9 TR patients) PYY and GLP-1 concentrations were measured following breakfast. The primary outcome measure was appetite, as measured using visual analogue scales and the buffet lunch. The secondary outcome was BH concentrations following a test meal. RESULTS: PR and TR participants had lower hunger and energy intake at the buffet lunch meal compared to controls. PR subjects had higher BH concentrations compared to controls and TR subjects. BH levels correlated with circulating GLP-1 levels at specific time points. CONCLUSIONS: PR or TR of the large bowel reduced feelings of hunger and energy intake, and PR increased gastrointestinal fermentation.

Positive allosteric modulation of the adenosine A2a receptor attenuates inflammation.

BACKGROUND: Adenosine is produced at high levels at inflamed sites as a by-product of cellular activation and breakdown. Adenosine mediates its anti-inflammatory activity primarily through the adenosine A2a receptor (A2aR), a member of the G-protein coupled receptors. A2aR agonists have demonstrated anti-inflammatory efficacy, however, their therapeutic utility is hindered by a lack of adenosine receptor subtype selectivity upon systemic exposure. We sought to harness the anti-inflammatory effects of adenosine by enhancing the responsiveness of A2aR to endogenously produced adenosine through allosteric modulation. We have identified a family of positive allosteric modulators (PAMs) of the A2aR. Using one member of this PAM family, AEA061, we demonstrate that A2aRs are amenable to allosteric enhancement and such enhancement produces increased A2aR signaling and diminished inflammation in vivo. METHODS: A2aR activity was evaluated using a cell-based cAMP assay. Binding affinity of A2aR was determined using [(3)H]CGS 21680. A2aR-mediated G-protein activation was quantified using [(35)S]GTP-γS. The effect of AEA061 on cytokine production was evaluated using primary monocytes and splenocytes. The anti-inflammatory effect of AEA061 was evaluated in the LPS-induced mouse model of inflammation. RESULTS: AEA061 had no detectable intrinsic agonist activity towards either rat or human A2aRs. AEA061 enhanced the efficacy of adenosine to rat and human A2aRs by 11.5 and 2.8 fold respectively. AEA061 also enhanced the maximal response by 4.2 and 2.1 fold for the rat and the human A2aR respectively. AEA061 potentiated agonist-mediated Gα activation by 3.7 fold. Additionally, AEA061 enhanced both the affinity as well as the Bmax at the human A2aR by 1.8 and 3 fold respectively. Consistent with the anti-inflammatory role of the A2aR, allosteric enhancement with AEA061 inhibited the production of TNF-α, MIP-1α, MIP-1ß, MIP-2, IL-1α, KC and RANTES by LPS-stimulated macrophages and/or splenocytes. Moreover, AEA061 reduced circulating plasma TNF-α and MCP-1 levels and increased plasma IL-10 in endotoxemic A2aR intact, but not in A2aR deficient, mice. CONCLUSIONS: AEA061 increases affinity and Bmax of A2aR to adenosine, thereby increasing adenosine potency and efficacy, which translates to enhanced A2aR responsiveness. Since the A2aR negatively regulates inflammation, PAMs of the receptor offer a novel means of modulating inflammatory processes.

In Vitro Propagation of Salt-Tolerant Wild Rice Relative, Porteresia coarctata Tateoka.

Micropropagation of Porteresia coarctata Tateoka, a wild relative of rice with useful genetic traits of salinity and submergence tolerance, was achieved through nodal segment culture. Woody Plant (WP) medium supplemented with benzyladenine (5.5 µm) and kinetin (2.3 µm) gave the greatest response to initiation and multiplication. The multiplication rate of 11 shoots/explant with an average shoot length of 3.5 cm was observed after 8 weeks of culture period. The rooting response was observed simultaneously in the multiplication media, but subsequent establishment was poor. When the in vitro raised shoots were transferred to optimal 1/2 WP and 1/2 MS media with 10.7 µm alpha-naphthaleneacetic acid, the rooting response was enhanced. Such rooted plants were hardened successfully under field conditions. Key Words. Conservation-Mangrove associates-Micropropagation-Nodal explants-Porteresia coarctata-Salt tolerance