Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation.

Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent.

An observational, prospective study on surgical treatment of secondary mitral regurgitation: The SMR study. Rationale, purposes, and protocol.

The natural history of secondary mitral regurgitation (MR) is unfavorable. Nevertheless, there are no evidence that its correction can improve the outcome. If from one side the original cause of secondary MR can be such to limit the possibilities of improvement, from the other side it is possible that the surgical technique widely applied to repair, restrictive mitral annuloplasty, is not adequate to correct the regurgitation. The addition of valvular and/or subvalvular techniques has been considered a possible technical solution. However, we do not know the prevalence of each technique, how many times mitral replacement is used to correct secondary MR. This aspect is of particular importance, as we know that a successful mitral repair causes a better left ventricular systolic remodeling than a unsuccessful repair or replacement. This study is a prospective, observational registry, conceived to understand what is done in the real world. Any surgeon will use the technique he thinks the most suitable for the patient. Every year, for 5 years, patients will have a clinical and echocardiographic follow-up, to evaluate the risk factors for a worse result (death, rehospitalization for heart failure, reoperation for MR return, moderate, or more MR return). This knowledge will give us the possibility to understand which is the technique, or the strategy, more efficient to treat this disease and the real efficacy of the surgical treatment.

Core valve implant failure in the presence of mechanical mitral prosthesis: importance of assessing left ventricular outflow tract.

Transcatheter aortic valve replacement in the presence of a mitral prosthetic valve is a technically challenging endeavor. The presence of a mitral prosthesis can alter the geometry of the landing zone for the device. A multi slice computerized tomography with comprehensive review of left ventricular outflow tract and aortic root in its entirety is critical for preventing implant failure. Technical expedients to treat implant failure involve understanding of the device as well its relationship with the mitral prosthesis.

Evaluation of iron-modified biochar on arsenic accumulation by rice: a pathway to assess human health risk from cooked rice.

Arsenic (As) contamination of rice grain poses a serious threat to human health. Therefore, it is crucial to reduce the bioavailability of As in the soil and its accumulation in rice grains to ensure the safety of food and human health. In this study, mango (Mangifera indica) leaf-derived biochars (MBC) were synthesized and modified with iron (Fe) to produce FeMBC. In this study, 0.5 and 1% (w/w) doses of MBC and FeMBC were used. The results showed that 1% FeMBC enhanced the percentage of filled grains/panicle and biomass yield by 17 and 27%, respectively, compared to the control. The application of 0.5 and 1% FeMBC significantly (p < 0.05) reduced bioavailable soil As concentration by 33 and 48%, respectively, in comparison to the control. The even higher As flux in the control group as compared to the biochar-treated groups indicates the lower As availability to biochar-treated rice plant. The concentration of As in rice grains was reduced by 6 and 31% in 1% MBC and 1% FeMBC, respectively, compared to the control. The reduction in As concentration in rice grain under 1% FeMBC was more pronounced due to reduced bioavailability of As and enhanced formation of Fe-plaque. This may restrict the entry of As through the rice plant. The concentrations of micronutrients (such as Fe, Zn, Se, and Mn) in brown rice were also improved after the application of both MBC and FeMBC in comparison to the control. This study indicates that the consumption of parboiled rice reduces the health risk associated with As compared to cooked sunned rice. It emphasizes that 1% MBC and 1% FeMBC have great potential to decrease the uptake of As in rice grains.

Transcatheter aortic valve implantation for severe regurgitation in native and degenerated bioprosthetic aortic valves.

OBJECTIVES: We evaluated transcatheter aortic valve Implantation (TAVI) in high-risk patients with severe aortic regurgitation (AR) in native or degenerated bioprosthetic valves. BACKGROUND: TAVI has emerged as a viable treatment modality for severe aortic stenosis in inoperable or high-risk patients. The use of TAVI for treatment of severe AR has remained largely unexplored. METHODS: Eight patients (age 79.6 years ± 5.75 years) with severe AR underwent TAVI at six tertiary hospitals between April 2010 and May 2011. All patients were considered to be at prohibitive risk for surgical aortic valve replacement (SAVR).TAVI with the nitinol based Core Valve bioprosthesis (CRS) (Medtronic) was performed in all patients. RESULTS: Transfemoral access was used in all cases. Procedural success was obtained in all cases without any intraprocedural complications. There was no in hospital or 30-day mortality. There were no cases of atrioventricular blocks requiring permanent pacemaker implantation. At a mean follow up of 15.5 ± 15 months; all patients had improvement in New York Heart Association functional class. Follow up echocardiography revealed improved or stable left ventricular ejection fraction and optimal device function in all cases. CONCLUSIONS: TAVI with the CRS bioprosthesis is feasible and effective in appropriately selected cases of severe aortic regurgitation in native and bioprosthetic aortic valves.

Discontinuation of ECMO-a review with a note on Indian scenario.

Extracorporeal membrane oxygenation (ECMO) has strikingly progressed over the last 20 years in the management of adult and pediatric severe respiratory and cardiac dysfunctions refractory to conventional management. In this review, we will discuss the weaning strategies of veno-venous and veno-arterial ECMO including the bridge to recovery and bridge to transplant along with post-ECMO care. We will also discuss the futility and the management of bridge to nowhere from Indian perspectives.

Nanotherapeutic potential of antibacterial folic acid-functionalized nanoceria for wound-healing applications.

Aim: The functionalization and characterization of antibacterial nanoceria with folic acid (FA) and elucidation of their in vivo wound-healing application. Materials & methods: Functionalization of nanoceria were done with FA using a chemical method and their antibacterial activity, cellular biocompatibility and in vivo wound-healing application were evaluated. Results: The functionalization of nanoceria with FA was done with 10-20 nm size and -20.1 mV zeta potential. The nanoformulation showed a bacteriostatic effect along with biocompatibility to different cell lines; 0.1% w/v spray of FA-nanoceria demonstrated excellent wound-healing capacity within 14 days in a Wister rat model. Conclusion: The antioxidant and reactive oxygen species scavenging activity of the FA-nanoceria make it a promising therapeutic agent as a unique spray formulation in wound-healing applications.

The emergence of chronic wounds is a main reason for mortality in patients with diabetes and other severe pathological complications. Advances in the use of nanotechnology have resulted in beneficial technology for tailoring of pharmacokinetic properties of different drug-delivery vehicles for different biomedical applications. In this study, folic acid (FA) functionalized nanoceria (FA-nanoceria) were formulated and their potential efficacy in the wound-healing process was explored. The nanoformulation showed a remarkable bacteriostatic effect on both Gram-negative and Gram-positive bacteria. In vitro cell line studies showed satisfactory biocompatibility in three different types of cell lines. In addition, a 0.1% w/v spray of FA-nanoceria was applied to full-thickness wounds in an in vivo mice model where it demonstrated excellent wound-healing capacity within 14 days. The combined antioxidant and reactive oxygen species scavenging activity of both the FA and nanoceria makes FA-nanoceria a promising therapeutic agent as a unique spray formulation in wound-healing applications.

Bifenthrin disrupts cytochrome c oxidase activity and reduces mitochondrial DNA copy number through oxidative damage in pool barb (Puntius sophore).

Bifenthrin (BF), a synthetic pyrethroid is used worldwide for both agricultural and non-agricultural purposes due to its high insecticidal activity and low toxicity in mammals. However, its improper usage implies a possible risk to aquatic life. The study was aimed to correlate the association of BF toxicity with mitochondrial DNA copy number variation in edible fish Punitus sophore. The 96-h LC50 of BF in P. sophore was 3.4 µg/L, fish was treated with sub-lethal doses ((⅒ and ⅕ of LC50;0.34 µg/L, 0.68 µg/L) of BF for 15 days. The activity and expression level of cytochrome c oxidase (Mt-COI) were measured to assess mitochondrial dysfunction caused by BF. Results showed BF reduced the level of Mt-COI mRNA in treated groups, hindered complex IV activity and increased ROS generation leading to oxidative damage. mtDNAcn was decreased in the muscle, brain and liver after BF treatment. Furthermore, BF induced neurotoxicity in brain and muscle cells through the inhibition of AchE activity. The treated groups showed elevated level of malondialdehyde (MDA) and an imbalance of antioxidant enzymes activity. Molecular docking and simulation analysis also predicted that BF binds to the active sites of the enzyme and restricts the fluctuation of its residues. Hence, outcome of the study suggests reduction of mtDNAcn could be a potential biomarker to assess Bifenthrin induced toxicity in aquatic ecosystem.

Asymmetric fabrication and in vivo evaluation of the wound healing potency of electrospun biomimetic nanofibrous scaffolds based on collagen crosslinked modified-chitosan and graphene oxide quantum dot nanocomposites.

Asymmetric scaffolds were developed through electrospinning by utilizing biocompatible materials for effective wound healing applications. First of all, the chitosan surface was modified with decanoyl chloride and crosslinked with collagen to synthesize collagen crosslinked modified-chitosan (CG-cross-CS-g-Dc). Then, the asymmetric scaffolds were fabricated through electrospinning, where the top layer was a monoaxial nanofiber of the PCL/graphene oxide quantum dot (GOQD) nanocomposite and the bottom layer was a coaxial nanofiber having PCL in the core and the CG-cross-CS-g-Dc/GOQD nanocomposite in the shell layer. The formation of monoaxial (∼130 ± 50 nm) and coaxial (∼320 ± 40 nm) nanofibers was confirmed by transmission electron microscopy (TEM). The presence of GOQDs contributed to antioxidant and antimicrobial efficacy. These scaffolds showed substantial antibacterial activity against the common wound pathogens Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The scaffolds exhibited excellent cytocompatibility (MTT assay) and anti-inflammatory behaviour as analysed via the cytokine assay and biochemical analysis. The in vivo wound healing potential of the nanofibrous scaffolds was assessed with full-thickness excisional wounds in a rat model. The scaffolds accelerated the re-epithelialization as well as the collagen deposition, thereby facilitating the wound healing process in a very short span of time (10 days). Both in vitro and in vivo analyses thus provide a compelling argument for the use of these scaffolds as therapeutic biomaterials and their suitability for application in rapid wound regeneration and repair.

Five-year outcomes of off and on-pump CABG: Insights from PROMOTE Patency Trial.

BACKGROUND: There are limited studies reporting follow-up outcome data comparing of off-pump coronary artery bypass (OPCAB) with on-pump (ONCAB) technique. The aim of the study was to report the 5-year clinical outcomes of OPCAB and ONCAB in a post hoc analysis of the PROMOTE patency trial. METHODS: From March 2016 through March 2017, a total of 321 patients undergoing coronary artery bypass grafting (CABG) were randomised to either the off-pump or the on-pump technique. Data on all-cause mortality, myocardial infarction (MI), cerebrovascular accident (CVA), repeat revascularisation and need for renal replacement therapy (RRT) were recorded. The composite and each of these individual outcomes are reported at 5-year interval. RESULTS: The mean follow-up period was 65.9 months (±3.39). A total of 275 (85.93%) patients followed up at the 5-year interval who underwent CABG by the off-pump (n = 158) and the on-pump (n = 162) technique. The all-cause mortality was 8.9% and 5.7% in ONCAB and OPCAB, respectively (hazard ratio [HR] = 0.62; 95% confidence interval [CI] 0.25-1.57, p = 0.31). The composite of all-cause mortality, non-fatal MI, non-fatal CVA, RRT and need for repeat revascularisation was comparable in both groups (7.1% vs. 11.9%, HR = 0.57; 95% CI 0.25-1.31, p = 0.18 in OPCAB and ONCAB, respectively). The rates of 5-year non-fatal MI (p = 0.2), non-fatal CVA (p = 0.36) and need for repeat revascularisation (p = 1) were similar in both groups. A sub-group analysis did not show any significant interaction or effect modification with either of the techniques. CONCLUSIONS: The 5-year clinical outcomes of OPCAB are comparable to ONCAB in low-risk patients undergoing CABG. Off-pump coronary artery bypass had no additional benefit in any subgroup.

Accuracy of intracardiac echocardiography for aortic root assessment in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Multislice computed tomography (MSCT) has generally been accepted as the most accurate modality fulfilling this purpose with good reproducibility. A major drawback of MSCT consists in the use of contrast dye, which may be unsafe in transcatheter aortic valve implantation (TAVI) patients who frequently are affected by renal failure. We sought to appraise the accuracy of intracardiac echocardiography (ICE) in measurements of structures in the aortic root in patients undergoing TAVI. METHODS: Aortic annulus and sinus of Valsalva diameters were measured using ICE, performed during standard invasive preprocedural assessment in 30 consecutive patients with severe aortic stenosis referred for TAVI. Multislice computed tomography was performed in all patients afterward, and aortic root measurements were made by an independent radiologist. RESULTS: Effective ICE measurements were obtained in all patients, easily and without any complication. Mean aortic annulus diameters were 21.9 ± 1.8 mm using ICE, 22.0 ± 1.9 mm using MSCT (3-chamber [3-C] view) and 22.8 ± 1.8 mm using the mean of long-axis and short-axis (L-ax/S-ax) view MSCT (P = .192, ICE vs 3-C MSCT; P < .001, ICE vs L-ax/S-ax MSCT, respectively). Correlation between ICE and both MSCT measurements was good (r(2) = 0.83, P < .001; r(2) = 0.80, P < .001, respectively). Mean sinus of Valsalva diameters were 32.3 ± 3.3 mm using ICE and 32.5 ± 3.1 mm using 3-C MSCT view (P = .141). Even in this case, correlation between ICE and both MSCT measurements was excellent (r(2) = 0.96, P < .001). CONCLUSIONS: In patients referred for TAVI, measurements of the aortic annulus and the sinus of Valsalva using ICE compare favorably with those made at MSCT. This approach might be a useful and reproducible strategy in patients with severe renal impairment to avoid the administration of contrast dye during MSCT.

Core Valve embolization: technical challenges and management.

Transcatheter Aortic Valve Implantation with the Core Valve self expanding prosthesis can be complicated by hemodynamic instability in cases of low deployment (implant failure). The management of a low implant may necessitate repositioning the prostheses with the help of a snare catheter. Snaring can however be complicated by embolization of the prosthesis which presents a series of technical challenges that need to be addressed. We have discussed the technical issues and the approach to address them successfully in a systematic manner to ensure optimal procedural and patient outcomes.

Early- and mid-term outcomes of transcatheter aortic valve implantation in patients with logistic EuroSCORE less than 20%: a comparative analysis between different risk strata.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an emerging alternative to medical therapy reserved to a limited population with severe aortic stenosis. The European consensus document recommended TAVI for prohibitive-risk patients not eligible for conventional surgery (prohibitive risk defined as expected mortality ≥ 20% calculated with the Logistic EuroScore (LES) in association with clinical judgment). To date, there is lack of clarity on data about outcomes of TAVI in lower risk patients. We sought to evaluate the outcomes of patients undergoing TAVI with LES ≥ 20% in comparison with patients with LES < 20%. METHOD: Of 165 patients who underwent TAVI using the 18-French Medtronic CoreValve (N = 153) and the Sapien Edwards™ (N = 12) at our Institution between June 2007 and September 2010, we identified those with LES < 20%, with prosthesis implantation (n = 84), and reported on their clinical outcome compared with patients with LES ≥ 20% (n = 78). The primary endpoint was the incidence of overall death and major adverse cerebrovascular and cardiac events (MACCE) at 30-day and midterm follow-up stratifying patients by clinical characteristics. RESULTS: At 30-day, a significant higher incidence of MACCE (20.8% vs. 6.0%, odds ratio [OR] 4.08 95% confidence interval [CI] 1.42-11.74, P = 0.009) and death (15.6% vs. 2.4%, OR 7.45 95% CI 1.61-34.48, P = 0.010) was reported in the LES ≥ 20% group as compared with the LES < 20% group, respectively. The 12-month MACCE rates was (27.1% vs. 11.4%, hazard ratio [HR] 2.47 95% CI 0.93-6.63, P = 0. 071) for LES ≥ 20% and LES < 20% patients, respectively (mortality rates was 25.7% vs. 6.8% HR 4.21 95% CI 1.24-14.30, P = 0.021). CONCLUSION: This study tends to suggest that current mortality reported after TAVI could be significantly affected by the very-high risk profile of the population which currently undergoes this procedure, making comparison with surgical series rather unreliable.

IACTS position statement on "2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization": section 7.1-a consensus document.

American College of Cardiology (ACC), American Heart Association (AHA) and Society for Cardiovascular Angiography and Interventions (SCAI) recently released the Clinical Practice Guidelines for myocardial revascularization [1]. The guidelines were the felt need of the fraternity and this single all-encompassing document, relegating the previous six guidelines on the subject to archives, is indeed welcome. However, the downgrading of coronary artery bypass surgery for stable multivessel coronary artery disease and its bracketing with percutaneous coronary interventions has caused a lot of anguish in the surgical fraternity. This document presents the official viewpoint of the Indian Association of Cardiovascular and Thoracic Surgeons on the matter.

Homozygous GRHPR C.494G>A mutation is deleterious that causes early onset of nephrolithiasis in West Bengal, India.

Pediatric nephrolithiasis (NL) or Kidney stone disease (KSD) is an untethered topic in Asian population. In Western countries, the annual incidence of paediatric NL is around 6-10%. Here, we present data from West Bengal, India, on lower age (LA, 0-20 years) NL and its prevalence for the first time. To discover the mutations associated with KSD, twenty-four (18 + 6) rare LA-NL patients were selected for Whole Exome Sequencing (WES) and Sanger sequencing, respectively. It was found that GRHPR c. 494G>A mutation (MZ826703) is predominant in our study cohort. This specific homozygous mutation is functionally studied for the first time directly from human peripheral mononuclear cell (PBMC) samples. Using expression study with biochemical activity and computational analysis we assumed that the mutation is pathogenic with loss of function. Moreover, three genes, AGXT, HOGA1 and GRHPR with Novel variants known to cause hyperoxaluria were found frequently in the study cohort. Our study analyses the genes and variations that cause LA-NL, as well as the molecular function of the GRHPR mutation, which may serve as a clinical marker in the population of West Bengal, Eastern India.

Aortic valve perforation during aortic valvuloplasty: Identification and strategies for prevention.

Balloon aortic valvuloplasty has seen a revival in interest because of its role in predilation and preparation of the annulus before trans catheter aortic valve implantation. Aortic valve cusp perforation is a serious complication that needs early recognition and prompt corrective measures to prevent a poor procedural outcome or conversion to emergent surgery. A number of useful angiographic and technical findings can alert the operator about the possibility of this complication. Failure to recognize cusp perforation can lead to serious procedural complications like severe aortic regurgitation, suboptimal prosthesis deployment, and function that can necessitate emergent open cardiac surgery.

Transcatheter aortic valve implantation for severe aortic regurgitation in a stentless bioprosthetic valve with the Core Valve revalving system-technical tips and role of the Accutrak system.

Transcatheter aortic valve implantation may offer a less invasive alternate to surgical reoperation in patients with failed aortic bioprosthetic valves. Prior reports have focussed on successful transcatheter treatment of stented bioprosthesis. Newer stentless valves offer unique technical challenges. In the absence of radiopaque markers, the deployment is carried out under angiographic control. Device stability is also an important issue in cases of severe regurgitation. We report on the first case of percutaneous replacement of a severely regurgitant degenerated stentless bioprosthesis treated with the new iteration of the core valve system incorporating the Accutrak stability layer. Salient technical expedients have been mentioned and discussed in detail.

Trans catheter aortic valve implantation with core valve revalving system in uncoiled (horizontal) aorta. Overcoming anatomical and technical challenges for successful deployment.

Uncoiling of the aortic root (horizontal aorta) offers a considerable technical challenge in successful deployment of core valve prosthesis. The problem is compounded in the presence of significant calcification of the ascending aorta that limits the capability to control the tension on delivery catheter during device release and may lead to implant failure. Recognition of adverse anatomical features and use of proximal access sites such as subclavian artery are likely to attenuate the degree of technical difficulty in these cases. Familiarity and facility with retrieval techniques using a snare catheter is desirable in cases of implant failure.

Assessment of the surface water quality improvement during pandemic lockdown in ecologically stressed Hooghly River(Ganges) Estuary, West Bengal, India.

The countrywide COVID-19 pandemic lockdown accomplished what aggressive plans could not do throughout the long-term cleaning of the Ganga River. Here, we illustrated Hooghly River surface water quality [physico-chemical parameters, biological parameters, dissolved heavy metals] improvement by analyzing eight sampling station before and during the lockdown. Because of shutdown of industrial units and individuals staying at home, a complete decrease in industrial wastes, contaminants, and self-purging of the stream improved significantly water quality by about 40% to 50%. Among dissolved heavy metals, the concentrations of Cd (50%), Pb (53%), demonstrated noteworthy variations during the lockdown. Diminishing trends were also observed for TDS (62%), and BOD (52%), with significant reduction in the total coliform (63%), faecal coliform (61%), notably. Principal component analysis and paired t-test signify the alteration of water quality. The study concludes that the aquatic ecosystem can be revived if wastewater, and anthropogenic activities are properly managed by environmental surveillance.

Ischemic mitral regurgitation: the way ahead is a step back.

Ischemic mitral regurgitation (IMR) has a profound negative effect on survival of patients following myocardial infarction. It occurs when the closing forces are overpowered by the tethering forces as a consequence of ventricular remodeling. Surgeons sought to correct moderate and severe IMR by mitral annuloplasty. Though short-term results were encouraging, survival after 2 years were not so. Higher recurrence rates were also noted with severe mitral regurgitation (MR). Parameters defining severity of IMR were initially formulated in 2003. These were revised enabling intervention in moderate MR in 2014. With the lack of positive medium and long-term evidence, 2017 guidelines have raised the bar, discouraging intervention in moderate IMR. Current guidelines have taken a conservative stance in advocating repair only for severe MR and very symptomatic patients. Till emergence of fresh evidence surgical enthusiasm for repair of IMR has to be restrained.