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Introduction: Since Glycated Albumin (GA) reflects short term variations and glycated protein shows degrees of hyperglycaemia, the objective of this study was to find GA and microalbuminuria as a early risk markers along with the duration of Uncontrolled Diabetes Mellitus in type 2 diabetic nephropathy. Material and Methods: The present cross-sectional study included randomly selected Uncontrolled Type 2DM (n = 75), controlled Type 2DM (n = 75) and healthy controls (n = 75). Their fasting venous blood samples were obtained for GA and serum creatinine, while their morning urine samples were obtained for detection of microalbuminuria. Statistical analysis was done by using SPSS, version 16.0. One-Way ANOVA was performed. All p-values which were ≤ 0.05 were considered as statistically significant. Results: The mean GA, microalbuminuria and serum creatinine were the highest in Uncontrolled DM as compared to those in Controlled DM respectively. Microalbuminuria and GA had a significant correlation with the duration of diabetes (p

Abstract Therapy resistance and recurrence are irrefutably ascribed to the unique attributes of the cancer stem cell (CSC) population. Therefore, discerning the underlying mechanism is imperative in arbitrating a strategic therapeutic approach. In this study, we have observed the coexistence of neuron‐like cell (NLC) subpopulations in different cancer cell lines. The NLC subset was further validated by transfection studies and was found to be positive for PSD‐95. As a proof of concept, we have also demonstrated the transpiration of neurological phenomena such as long‐term potentiation (LTP) and long‐term depression (LTD) in cancer. We have utilized PMA drug and IL‐13 cytokine to study LTD and LTP, respectively, and observed a correlation between the memory marker (GLUN2B) and stemness markers (CD95 and CD58). Moreover, the transcriptional protein pCREB, which plays a crucial role in memory formation, was found to influence CD44 protein levels. These findings suggest that the instigation of LTD can impair cellular memory and sensitize CSC to the metabolic inhibitor, 3Bromopyruvate. Furthermore, this study interfaces the neurobiology of cancer and nanomedicine, wherein we have used biomimetic nanocarriers for the active targeting of drugs and demonstrate their ability to augment therapeutic efficiency.

Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution. Nanoparticles are currently being utilized in the pharmaceutical sector; however, there is a persistent worry regarding their potential danger to human health due to the usage of toxic chemicals, which makes the utilization of nanoparticles highly hazardous to eukaryotic cells. Multiple nanoparticle-based techniques are now being developed, offering essential understanding regarding the synthesis of components that play a crucial role in producing anti-microbial nanotherapeutic pharmaceuticals. In this regard, green nanoparticles are considered less hazardous than other forms, providing potential options for avoiding the extensive harm to the human microbiome that is prevalent with existing procedures. This review article aims to comprehensively assess the current state of knowledge on green nanoparticles related to antibiotic activity as well as their potential to assist antibiotics in treating opportunistic clinical phytopathogenic illnesses.

Abstract In this research work, carbon dots (CDs) were synthesized from the renewable leaves of an indigenous medicinal plant by the one-pot sand bath method, Azadirachta indica. The synthesized CDs were characterized for its optical properties using UV–Vis, Fluorescence and Fourier transform infrared (FT-IR) spectrophotometry and for structural properties using dynamic light scattering (DLS), X-ray Diffraction (XRD) and high resolution Transmission electron microscopy (HR-TEM). The synthesized CDs exhibited concentration dependent biocompatibility when tested in mouse fibroblast L929 cell line. The EC50 values of biomedical studies, free radical scavenging activity (13.87 μgmL−1), and total antioxidant capacity (38 μgmL−1) proved CDs were exceptionally good. These CDs showed an appreciable zone of inhibition when examined on four bacterial (two gram-positive and gram-negative) and two fungal strains at minimum concentrations. Cellular internalisation studies performed on human breast cancer cells (MCF 7- bioimaging) revealed the applicability of CDs in bioimaging, wherein the inherent fluorescence of CDs were utilised. Thus, the CDs developed are potential as bioimaging, antioxidants and antimicrobial agents.

Urine is a highly advantageous biological specimen for biomarker research and is a non-invasive source. Most of the urinary biomarkers are non-specific, volatile and need extensive validation before clinical adoption. Extracellular vesicles are secreted by almost all cells and are involved in homoeostasis, intercellular communication, and cellular processes in healthy and pathophysiological states. Urinary extracellular vesicles (UEVs) are released from the urogenital system and mirror the molecular processes of physiological and pathological states of their source cells. Therefore, UEVs serve as a valuable source of biomarkers for the non-invasive diagnosis of various pathologies. They hold a promising source of multiplex biomarkers suitable for prognosis, diagnosis, and therapy monitoring. UEVs are easily accessible, non-invasive, and suited for longitudinal sampling. Although various techniques are available for isolating UEVs, there is yet to be a consensus on a standard and ideal protocol. We have optimized an efficient, reliable, and easily adoptable polyethylene glycol (PEG) based UEV isolation technique following MISEV guidelines. The method is suitable for various downstream applications of UEVs. This could be a cost-effective, consistent, and accessible procedure for many clinical labs and is most suited for longitudinal analysis. Adopting the protocol will pave the way for establishing UEVs as the ideal biomarker source. • Urine can be collected non-invasively and repeatedly, hence a very useful specimen for biomarker discovery. Urinary EVs (UEVs), derived from urine, offer a stable diagnostic tool, but standardised isolation and analysis approaches are warranted. • To have enough UEVs for any study, large volumes of urine sample are necessary, which limits different isolation methods by cost, yield, and time. • The protocol developed could help researchers by offering a cost-effective and dependable UEV isolation method and may lay the foundation for UEVs adoption in clinical space.

Abstract The growing need for innovative drug delivery systems has led to extensive research to address the limitations associated with conventional dosage forms. Lipid nanoparticles have become prominent as frontline nanocarriers for the delivery of drugs and vaccine formulations. However, the pursuit of new materials and modifications to improve lipid nanocarrier properties remains ongoing. In this context, transethosomes have gained attention as a promising solution, offering distinct advantages over traditional formulations. Transethosomes minimize plasma fluctuations, first‐pass metabolism, organ toxicity, and poor bioavailability. This comprehensive review provides an in‐depth exploration of transethosomes, starting with an overview of the impact of formulation components on their properties and effective targeting. This article delves into the production techniques and evaluation properties employed to ensure efficient drug delivery. A significant contribution of this review lies in the analysis of various routes of administration for transethosomes, including transdermal, transvaginal, pulmonary, and ocular delivery, showcasing the versatility of transethosome‐loaded with drugs and their potential to target specific tissues to achieve controlled release. Furthermore, the potential of functionalization and photodynamic therapy approaches to enhance drug delivery efficacy are explored. Overall, this review emphasizes the significant potentiality of transethosomes as a promising drug delivery system addressing the challenges associated with conventional drug delivery approaches.

Abstract Cancer is one of the most prevailing causes of mortality worldwide. Standard therapies for cancer patients include surgical intervention, chemotherapy, and radiotherapy. Nevertheless, chemoresistance and toxicity are clinical implications of advanced disease. New treatments are obliged to overcome these challenges. According to clinical investigations, melatonin (MLT) has the potential to prevent and cure cancer. It is nontoxic and has a plethora of anticancer properties including apoptosis, antiangiogenic, antiproliferative, and metastasis‐inhibitory mechanisms. It enhances the therapeutic sensitivity of malignancies when coupled with conventional medications. The investigations that demonstrate how MLT possesses antitumor characteristics are reviewed in this manuscript. We provided an overview of recent research on the etiology, factors associated, therapeutic property of MLT on various cancer types. We discussed the clinical implications of MLT alone or in conjunction with chemotherapeutic drugs or radiation therapy. Furthermore, we have addressed the mechanisms of its anticancer activities against several types of cancers along with research findings of various investigations done by researchers and advancements in the field of nanotechnology for efficient delivery of MLT. The recent clinical investigations of MLT in various cancer types are reported in this review.

A worldwide issue affecting the world is waste disposal; hence, the need to construct a waste detection system that is based on deep learning. Ten wastes are evaluated in this article with a view of providing an integrated framework for measurement and evaluation. It also offers a comprehensive account of the wastes studied further by looking at its detail finding and the challenges they pose as well as views associated with waste detection. Recycling both has economical and ecological benefits which help to eliminate pollution. Technology can now be used to turn waste into resource materials thus recycling more than before especially through the use of deep learning among other technologies.

Abstract Aims We hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ventricular ejection fraction (LVEF). Methods and results One hundred seventy‐one patients with CHF were analysed [age 65 ± 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid‐range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF)]. All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut‐off of peak VO2 (pVO2; 14 mL/kg/min). Seventy‐seven (45%) patients reached pVO2

Cancer is characterized by the uncontrolled growth of cells that also metastasis, owing to the mutation in p53 (tumor suppressor gene), making cancer a deadly disease. Though Chemotherapy, Photothermal therapy (PTT), and Photodynamic therapy (PDT) have promising results, acute side effects such as light sensitivity, immune system suppression, and weakness associated with these treatments demand a new strategy that can ameliorate the drawbacks associated with the same. In this regard, Nanobubble therapy (NBT) plays a vital role in plasmonic nanoparticles killing cancer cells by disrupting the cancer cell membrane. As NBT targets only the cancer cells, the side effects associated are almost nil or significantly less compared with Chemotherapy, PTT, and PDT. This article reviews the rationale and significance of NBT over other therapies while providing insight into the metal-based nanobubble systems and their biological applications.

The viral infection spreads with the assistance of a host. Traditional antiviral therapies cannot provide long-term immunity against emerging and drug-resistant viral infections. Immunotherapy has evolved as an efficient approach for disease prevention and treatment, which include cancer, infections, inflammatory, and immune disorders. Immunomodulatory nanosystems can dramatically enhance therapeutic outcomes by combating many therapeutic challenges, such as poor immune stimulation and off-target adverse effects. Recently, immunomodulatory nanosystems have emerged as a potent antiviral strategy to intercept viral infections effectively. This review introduces major viral infections with their primary symptoms, route of transmission & targeted organ, and different stages of the viral life cycle with respective traditional blockers. The IMNs have an exceptional capacity for precisely modulating the immune system for therapeutic applications. The nano sized immunomodulatory systems permit the immune cells to interact with infectious agents enhancing lymphatic drainage and endocytosis by the over-reactive immune cells in the infected areas. Immune cells that can be modulated upon viral infection via various immunomodulatory nanosystems have been discussed. Advancement in theranostics can yield an accurate diagnosis, adequate treatment, and real-time screening of viral infections. Nanosystem-based drug delivery can continue to thrive in diagnosing, treating, and preventing viral infections. The curative medicine for remerging and drug-resistant viruses remains challenging, though certain systems have expanded our perception and initiated a new research domain in antiviral treatments.

Abstract Aims Exercise intolerance is the leading manifestation of heart failure with preserved or mid‐range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF. Methods and results Sixty‐five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT‐proBNP). LA function was evaluated through speckle‐tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO2 cut‐off of prognostic value (14 mL/kg/min). NT‐pro‐BNP was measured. Twenty‐nine patients (45%) reached a peak VO2

This paper reports the colorimetric analysis of cervical-cancer-affected clinical samples by the in situ formation of gold nanoparticles (AuNPs) formed with cervico-vaginal fluids collected from healthy and cancer-affected patients in a clinical setup, termed “C-ColAur”. We evaluated the efficacy of the colorimetric technique against the clinical analysis (biopsy/Pap smear) and reported the sensitivity and specificity. We investigated if the aggregation coefficient and size of the nanoparticles responsible for the change in color of the AuNPs (formed with clinical samples) could also be used as a measure of detecting malignancy. We estimated the protein and lipid concentrations in the clinical samples and attempted to investigate if either of these components was solely responsible for the color change, enabling their colorimetric detection. We also propose a self-sampling device, CerviSelf, that could enable the rapid frequency of screening. We discuss two of the designs in detail and demonstrate the 3D-printed prototypes. These devices, in conjugation with the colorimetric technique C-ColAur, have the potential to be self-screening techniques, enabling women to undergo rapid and frequent screening in the comfort and privacy of their homes, allowing a chance at an early diagnosis and improved survival rates.

Treatment of retinoblastoma is limited due to its delayed detection and inaccesbility of drugs to reach the retina crossing the blood-retinal barrier. With the advancements in nanotechnology, photothermal therapy (PTT) employing plasmonic nanomaterials and/or NIR dyes have emerged as an affordable alternative owing to the spatial control that is offered by the modality leading to localized and enhanced therapeutic efficacy with minimal invasiveness. However, the modality is limited in its clinical application owing to the increased heat shock resistance of the tumor cells in response to the heat that is generated via PTT. Hence, in this study, we explore the role of novel biomolecular fraction of Moringa oleifera (DFM) encapsulated within a polymeric nanosystem, for its anti-heat shock protein (HSP) activity. The MO extract was co-encapsulated with NIR sensitizing dye, IR820 into a biodegradable polycaprolactone (PCL) nano-delivery system (PMIR NPs). The photothermal transduction efficacy of PMIR NPs was validated in vitro against retinoblastoma cell lines. The inherent fluorescence of DFM was utilized to evaluate the cellular internalization of the PMIR NPs using fluorescence microscopy and flow cytometry. The overall oxidative protein damage and downregulation of HSP70 expression upon treatment with PMIR NPs and NIR laser irradiation was evaluated using densiometric protein analysis and Western blotting. Overall, the PMIR NPs exhibited excellent anti-cancer activity when combined with PTT with downregulated HSP70 expression against retinoblastoma cells.

Understanding various responses of cells towards change in their external environment, presence of other species and is important in identifying and correlating the mechanisms leading to malignant transformations and cancer development. Although uncovering and comprehending the association between bacteria and cancer is highly challenging, it promises excellent perspectives and approaches for successful cancer therapy. This review introduces various bacterial species, their virulence factors, and their role in cell transformations leading to cancer (particularly gastric, oral, colon, and breast cancer). Bacterial dysbiosis permutates host cells, causes inflammation, and results in tumorigenesis. This review explored bacterial-mediated host cell transformation causing chronic inflammation, immune receptor hyperactivation/absconding immune recognition, and genomic instability. Bacterial infections downregulate E-cadherin, leading to loosening of epithelial tight junction polarity and triggers metastasis. In addition to understanding the role of bacterial infections in cancer development, we have also reviewed the application of bacteria for cancer therapy. The emergence of bacteriotherapy combined with conventional therapies led to new and effective ways of overcoming challenges associated with available treatments. This review discusses the application of bacterial minicells, microswimmers, and outer cell membrane vesicles (OMV) for drug delivery applications.

One of the most effective cancer therapies, cancer immunotherapy has produced outstanding outcomes in the field of cancer treatment. However, the cost is excessive, which limits its applicability. A smart way to address this issue would be to apply the knowledge gained through immunotherapy to develop strategies for the immunoprevention of cancer. The use of cancer vaccines is one of the most popular methods of immunoprevention. This paper reviews the technologies and processes that support the advantages of cancer immunoprevention over traditional cancer immunotherapies. Nanoparticle drug delivery systems and nanoparticle-based nano-vaccines have been employed in the past for cancer immunotherapy. This paper outlines numerous immunoprevention strategies and how nanotechnology can be applied in immunoprevention. To comprehend the non-clinical and clinical evaluation of these cancer vaccines through clinical studies is essential for acceptance of the vaccines.

Cancer metastasis remains the major cause of global cancer deaths. Radiation therapy remains one of the golden standards for cancer treatment. Nanomedicine based strategies have been designed and developed in order to improve the clinical outcomes of cancer therapy and diagnosis at molecular levels. Over the years, several researchers have shown their interest in using radiosensitizers made of high Z elements. Metal-based nanosystems also play a dual role by enhancing the synergistic effect of cell killing via various biological immune responses. This review summarizes the role of Nano-sensitizers in boosting radiation (ionizing/non-ionizing radiations) induced biological responses in treatment of metastatic cancer models.

Restaurant owners and indeed all the personnel need to create a pleasant servicescape and provide service quality excellence in all their encounters with their customers. Servicescape is the physical environment of a service business where service is delivered to paying or non-paying customers. Servicescape has a very strong effect on all consumption experiences where service is delivered. In India the service sector contributes nearly half of the GDP. Restaurant owners, managers and all the personnel need to be servicescape oriented in order to increase a restaurant’s performance and improve its sustainability prospects. Servicescape is thus the physical facility and services which are considered to enhance customer satisfaction and sustain business. The purpose of the present study was to establish the relationship between Servicescape and customer’s loyalty towards fine dine restaurants in Jaipur. A total of 436 subjects who visited fine dining restaurant of Jaipur, age from 21 to 60 years of age, were selected for the study. To measure the servicescape parameters, a scale established by Mehrabian and Russell (1974) was adopted. To find out the relation between servicescape and customers’ loyalty, the Pearson product minute correlation was used. To develop a model for customers’ loyalty, linear regression was employed. Results revealed that there was a strong relationship between servicescape and customer’s loyalty and this allowed a significant model for customer’s loyalty to be developed. Hence, it is concluded that the loyalty of the customers can be predicted by using the proposed model.

Aims: Exercise training (ET) has been consistently shown to increase peak oxygen consumption (V̇O 2 ) in patients with heart failure with preserved ejection fraction (HFpEF); however, inter-individual responses vary significantly. Because it is unlikely that ET-induced improvements in peak V̇O 2 are significantly mediated by an increase in peak heart rate (HR), we aimed to investigate whether baseline peak O 2 -pulse (V̇O 2  × HR -1 , reflecting the product of stroke volume and arteriovenous oxygen difference), not baseline peak V̇O 2 , is inversely associated with the change in peak V̇O 2 (adjusted by body weight) following ET versus guideline control (CON) in patients with HFpEF., Methods and Results: This was a secondary analysis of the OptimEx-Clin (Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure, NCT02078947) trial, including all 158 patients with complete baseline and 3 month cardiopulmonary exercise testing measurements (106 ET, 52 CON). Change in peak V̇O 2 (%) was analysed as a function of baseline peak V̇O 2 and its determinants (absolute peak V̇O 2 , peak O 2 -pulse, peak HR, weight, haemoglobin) using robust linear regression analyses. Mediating effects on change in peak V̇O 2 through changes in peak O 2 -pulse, peak HR and weight were analysed by a causal mediation analysis with multiple correlated mediators. Change in submaximal exercise tolerance (V̇O 2 at the ventilatory threshold, VT1) was analysed as a secondary endpoint. Among 158 patients with HFpEF (66% female; mean age, 70 ± 8 years), changes in peak O 2 -pulse explained approximately 72% of the difference in changes in peak V̇O 2 between ET and CON [10.0% (95% CI, 4.1 to 15.9), P = 0.001]. There was a significant interaction between the groups for the influence of baseline peak O 2 -pulse on change in peak V̇O 2 (interaction P = 0.04). In the ET group, every 1 mL/beat higher baseline peak O 2 -pulse was associated with a decreased mean change in peak V̇O 2 of -1.45% (95% CI, -2.30 to -0.60, P = 0.001) compared with a mean change of -0.08% (95% CI, -1.11 to 0.96, P = 0.88) following CON. None of the other factors showed significant interactions with study groups for the change in peak V̇O 2 (P > 0.05). Change in V̇O 2 at VT1 was not associated with any of the investigated factors (P > 0.05)., Conclusions: In patients with HFpEF, the easily measurable peak O 2 -pulse seems to be a good indicator of the potential for improving peak V̇O 2 through exercise training. While changes in submaximal exercise tolerance were independent of baseline peak O 2 -pulse, patients with high O 2 -pulse may need to use additional therapies to significantly increase peak V̇O 2 ., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Purpose: To assess the role of P300 in patients with temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (HS) using magnetoencephalography (MEG) based auditory and visual oddball tasks, and to assess its correlation with neuropsychological tests., Methods: Thirty-patients (M:F-17:13, onset-11.77 ± 8.75 years, duration-16.10 ± 9.61 years) with TLE-HS (Left:15, Right:15) and fifteen-healthy age, gender and years of education matched controls (M:F-10:5, age-28.13 ± 4.76 years) underwent auditory and visual oddball tasks in MEG and cognition assessment using Indian Council of Medical Research (ICMR)-cognitive test battery. Independent component analysis (ICA) was applied to the magnetic evoked field responses for the detection of the P300 component. Source localization of P300 was performed with Classical LORETA Analysis Recursively Applied (CLARA). The latency and amplitude of P300 were estimated and subsequently correlated with cognitive scores., Results: The visual P300 amplitude in the TLE group was lower when compared to the control group. In subgroup comparison (controls vs. right HS vs. left HS), visual P300 amplitudes were lower in the right HS group compared to both left HS and control groups (p-value = 0.014). On the other hand, no significant difference for auditory P300 latency or amplitude was noted between patients and controls as well as between subgroups. A negative correlation found between the MEG visual P300 amplitude and Indian Trial Making Test (TMT)-B duration in the patient group., Conclusion: Patients with TLE-HS have decreased visual-P300 amplitude. A significant correlation found between visual P300 amplitude and cognitive tests of visuospatial attention and working memory. Overall, MEG based visual P300 amplitude can be further explored with large sample size studies to establish as a complementary objective test for cognitive assessment in TLE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: The aim of this study was to examine the potential usefulness and clinical relevance of a novel left atrial (LA) filling index using 2D speckle-tracking transthoracic echocardiography to estimate left ventricular (LV) filling pressures in patients with preserved LV ejection fraction (LVEF)., Methods and Results: The LA filling index was calculated as the ratio of the mitral early-diastolic inflow peak velocity (E) over LA reservoir strain (i.e. E/LA strain ratio). This index showed a good diagnostic performance to determine elevated LV filling pressures in a test-cohort (n = 31) using invasive measurements of LV end-diastolic pressure (area under the curve 0.82, cut-off > 3.27 = sensitivity 83.3%, specificity 78.9%), which was confirmed in a validation-cohort (patients with cardiovascular risk factors; n = 486) using the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging criteria (cut-off > 3.27 = sensitivity 88.1%, specificity 77.6%) and in a specificity-validation cohort (patients free of cardiovascular risk factors, n = 120; cut-off > 3.27 = specificity 98.3%). Regarding the clinical relevance of the LA filling index, an elevated E/LA strain ratio (>3.27) was significantly associated with the risk of heart failure hospitalization at 2 years (odds ratio 4.3, 95% confidence interval 1.8-10.5), even adjusting this analysis by age, sex, renal failure, LV hypertrophy, or abnormal LV global longitudinal systolic strain., Conclusion: The findings from this study suggest that a novel LA filling index using 2D speckle-tracking echocardiography could be of potential usefulness and clinical relevance in estimating LV filling pressures in patients with preserved LVEF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

The palladium(ii)-catalyzed carbocyclization of benzenecarbaldehydes with internal alkynes to afford 2,3-disubstituted indenones was reported. The annulation reaction proceeded through the transmetalation of Pd(ii) with an aromatic aldehyde and the insertion of internal alkynes, followed by cyclization via the intramolecular nucleophilic addition of intermediate organopalladium(ii) species to the aldehyde group. This reaction proceeded in moderate to good yields with high regioselectivity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: The purpose of this study was to analyze the potential usefulness and clinical relevance of adding left atrial (LA) strain to left atrial volume index (LAVI) in the detection of left ventricular diastolic dysfunction (LVDD) in patients with preserved left ventricular ejection fraction (LVEF)., Background: Recent studies have suggested that LA strain could be of use in the evaluation of LVDD. However, the potential utility and clinical significance of adding LA strain to LAVI in the detection of LVDD remains uncertain., Methods: Using 2-dimensional speckle-tracking echocardiography, we analyzed a population of 517 patients in sinus rhythm at risk for LVDD such as those with arterial hypertension, diabetes mellitus, or history of coronary artery disease and preserved LVEF., Results: In patients with LV diastolic alterations and estimated elevated LV filling pressures, the rate of abnormal LA strain was significantly higher than an abnormal LAVI (62.4% vs. 33.6%, p < 0.01). In line with this, in patients with normal LAVI, high rates of LV diastolic alterations and abnormal LA strain were present (rates 80% and 29.4%, respectively). In agreement with these findings, adding LA strain to LAVI in the current evaluation of LVDD increased significantly the rate of detection of LVDD (relative and absolute increase 73.3% and 9.9%; rate of detection of LVDD: from 13.5% to 23.4%; p < 0.01). Regarding the clinical relevance of these findings, an abnormal LA strain (i.e., <23%) was significantly associated with worse New York Heart Association functional class, even when LAVI was normal. Moreover, in a retrospective post hoc analysis an abnormal LA strain had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio: 6.6 [95% confidence interval: 2.6 to 16.6]) even adjusting this analysis for age and sex and in patients with normal LAVI., Conclusions: The findings from this study provide important insights regarding the potential usefulness and clinical relevance of adding LA strain to LAVI in the detection of LVDD in patients with preserved LVEF., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of the present study was to determine the lower limit of normality and the clinical relevance of left ventricular (LV) early diastolic strain rate (LVSRe) for the detection of LV diastolic dysfunction (LVDD)., Methods and Results: Using 2D speckle-tracking echocardiography, we analysed 377 healthy subjects and 475 patients with risk for LVDD with preserved LV ejection fraction (LVEF). The normal range of LVSRe analysing the healthy subjects was 1.56 ± 0.28 s-1, with a lower limit of normality at 1.00 s-1. Using this cut-off, LVSRe was able to detect high rates of LV diastolic alterations (rate 71.1%), which was significantly better than using indirect diastolic parameters such as left atrial volume index (LAVI) and tricuspid regurgitation velocity (TR) (rates 22.9% and 9.1%) and similar to annular mitral parameters such as lateral and septal e' velocity (rates 70.9% and 72.4%). In line, adding LVSRe to the current evaluation of LVDD increased significantly the rate of detection of LVDD (absolute rate of increase 18.9%; rate of detection of LVDD: from 14.3% to 33.2%, P < 0.01). Regarding the clinical relevance of LVSRe, patients with abnormal LVSRe (i.e. <1.00 s-1) had significantly worse New York Heart Association functional class and symptomatic status than those with normal LVSRe. In addition, in a retrospective post hoc analysis, we found that an abnormal LVSRe had a significant association with the risk of heart failure hospitalization at 2 years (odds ratio 5.0, 95% confidence interval 1.3-18.4), which was better than using conventional diastolic parameters such as septal and lateral e' velocity, LAVI and TR velocity., Conclusion: The findings from this multicentre study provide important data regarding the normal range of LVSRe and highlight the potential clinical relevance of using this new diastolic parameter in the detection of LVDD in patients with preserved LVEF.

This study sought to examine whether early cardiac alterations could be detected by left atrial (LA) strain in patients with risk for cardiac abnormalities. In this cross-sectional and retrospective study, we included patients with (n = 234) and without (n = 48) risk for cardiac abnormalities (i.e. those with arterial hypertension, diabetes mellitus and/or a history of coronary artery disease) of similar age and with preserved left ventricular (LV) systolic and diastolic function according to standard criteria. LA strain was significantly altered in patients with risk for cardiac abnormalities in comparison to those without risk (29.2 ± 8.6 vs. 38.5 ± 12.6%; rate of impaired LA strain: 18.8% vs. 0%; all p < 0.01) and was the most sensitive parameter to detect early LA alterations in comparison with other LA functional parameters (rate of impaired LA strain rate, LA total emptying fraction, and LA expansion index 3.8%, 7.3%, and 3.8%, respectively). Moreover, in patients with risk for cardiac abnormalities LA strain was altered even in the absence of subtle LV systolic and diastolic alterations (rates 13.9% and 6.8%), albeit to a lesser extent than in patients with an abnormal LV longitudinal systolic strain or abnormal mitral annular e' velocities (rates 48.5% and 24.4%). Regarding the clinical relevance of these findings, an impaired LA strain (i.e. < 23%) was significantly linked to exertional dyspnea (OR 3.5 [1.7-7.0]) even adjusting the analyses by age, gender and subtle LV abnormalities. In conclusion, the findings from this study suggest that LA strain measurements could be useful to detect early cardiac alterations in patients with risk for cardiac abnormalities with preserved LV systolic and diastolic function and that these early LA strain alterations could be linked to exertional dyspnea.

Background: The purpose of this meta-analysis was to confirm if the global longitudinal systolic function of the left ventricle (LV) is altered in patients with heart failure with preserved ejection fraction (HFpEF)., Methods: We searched in different databases (Medline, Embase and Cochrane) studies that analysed LV global longitudinal systolic strain (GLS) in patients with HFpEF and in controls (such as healthy subjects or asymptomatic patients with arterial hypertension, diabetes mellitus or coronary artery disease)., Results: Twenty-two studies (2284 patients with HFpEF and 2302 controls) were included in the final analysis. Patients with HFpEF had significantly lower GLS than healthy subjects (mean -15.7% (range -12% to -18.9%) vs mean -19.9% (range -17.1% to -21.5%), weighted mean difference -4.2% (95% CI -3.3% to -5.0%), p < 0.001, respectively). In addition, patients with HFpEF had also significantly lower GLS than asymptomatic patients (mean -15.5% (range -13.4% to -18.4%) vs mean -18.3% (range -15.1% to -20.4%), weighted mean difference -2.8%(95% CI -1.9% to -3.6%), p < 0.001, respectively). In line, 10 studies showed that the rate of abnormal GLS was significantly higher in patients with HFpEF (mean 65.4% (range 37%-95%)) than in asymptomatic subjects (mean 13% (range 0%-29.6%)). Regarding the prognostic relevance of abnormal GLS in HFpEF, two multicentre studies with large sample size (447 and 348) and high number of events (115 and 177) showed that patients with abnormal GLS had worse cardiovascular (CV) outcomes than those with normal GLS (HR for CV mortality and HF hospitalisation 2.14 (95% CI 1.26 to 3.66) and 1.94 (95% CI 1.22 to 3.07)), even adjusting these analyses for multiples clinical and echocardiographic variables., Conclusion: The present meta-analysis analysing 2284 patients with HFpEF and 2302 controls confirms that the longitudinal systolic function of the LV is significantly altered in high proportion of patients with HFpEF. Further large multicentre studies with the aim to confirm the prognostic role of abnormal GLS in HFpEF are warranted., Competing Interests: Competing interests: None declared.

One new homoisoflavonoid, (3E)-2,3-dihydro-6,7-dimethoxy-3[(3-hydroxy-4-methoxyphenyl)methylene]-4H-1-benzopyran-4-one and four naturally new analogues, (3E)-3-(1,3-benzodioxol-5-ylmethylene)-2,3-dihydro-7-hydroxy-4H-1-benzopyran-4-one, (3E)-3-(1,3-benzodioxol-5-ylmethylene)-2,3-dihydro-7-methoxy-4H-1-benzopyran-4-one, (3E)-2,3-dihydro-7-hydroxy-3-[(3-hydroxy-4-methoxyphenyl)methylene]-4H-1-benzopyran-4-one and (3E)-2,3-dihydro-3-[(3,4-dimethoxyphenyl)methylene]-7-methoxy-4H-1-benzopyran-4-one, along with four known homoisoflavonoids, bonducellin, sappanone A, 2'-methoxybonducellin and 7-O-methylbonducellin were isolated from aerial parts of Caesalpinia pulcherrima. The structures of the new compounds were elucidated by interpretation of their 1D and 2D NMR spectra. Syntheses of the naturally new compounds and the known compounds have also been accomplished. The antibacterial and antifungal activities of the isolated homoisoflavonoids were studied.