The Use of CRISPR-Cas9 Genetic Technology in Cardiovascular Disease: A Comprehensive Review of Current Progress and Future Prospective.

Over the last century, there have been major landmark developments in the field of medicine, enabling us to control and cure various diseases on a larger scale. A few of these include the discovery of antibiotics, the development of vaccines, and the origin of organ and tissue transplants. The continued quest for innovation in microbiology and medicine has helped humankind save millions of lives and decrease morbidity at the global level. Genetic medicine has grown significantly in the last two decades and appears to be the next frontier of curative therapies for chronic diseases. One important landmark in genetic medicine is the development of CRISPR (clustered, regularly interspaced short palindromic repeats) technology. In this article, we describe the basic structure and function of the CRISPR-Cas9 system, which, simply put, consists of an RNA part and a protein. It works as a molecular scissor that can perform targeted cuts followed by repairs in and around the genes of interest to attain favorable translational outcomes. We focused on summarizing recent studies using CRISPR-Cas9 technology in diagnosing and treating cardiovascular disease. These studies are primarily experimental and limited to animal models. However, their results are promising enough to anticipate that this technology will undoubtedly be available in clinical medicine in the coming years. CRISPR-Cas9-mediated gene editing has been used to study and potentially treat congenital heart disease, hyperlipidemias, arrhythmogenic cardiomyopathies, and the prevention of ischemia-reperfusion injury. Despite the current progress, we recognize the several challenges this technology faces, including funding for research, improving precision and reproducible results for human subjects, and establishing protocols for ethical compliance so that it is acceptable to the scientific community and the general public.

Comorbidities and their association with COVID-19 mortality in Mexico between January 2020 and August 2021.

By August 17, 2021, 4.3 million people had died globally as a result of SARS-CoV-2 infection. While data collection is ongoing, it is abundantly obvious that this is one of the most significant public health crises in modern history. Consequently, global efforts are being made to attain a greater understanding of this disease and to identify risk factors associated with more severe outcomes. The goal of this study is to identify clinical characteristics and risk factors associated with COVID-19 mortality in Mexico. The dataset used in this study was released by Sistema Nacional de Vigilancia Epidemiologica de Enfermedades Respiratorias (SISVER) de la Secretaría de Salud and contains 2.9 million COVID-19 cases. The effects of risk factors on COVID-19 mortality were estimated using multivariable logistic regression models with generalized estimation equation and Kaplan-Meier curves. Case fatality rates, case hospitalization rates are also reported using the Centers for Disease Control and Prevention (CDC) USA death-to-case ratio method. In general, older males with pre-existing conditions had higher odds of death. Age greater than 40, male sex, hypertension, diabetes, and obesity are associated with higher COVID-19 mortality. End-stage renal disease, chronic obstructive pulmonary disease, and immunosuppression are all linked with COVID-19 patient fatalities. Smoking and Asthma are associated with lower COVID-19 mortality which is consistent with findings from the article published in Nature based on National Health Service (NHS) of UK dataset (17 million cases). Intensive care unit (ICU), patient intubation, and pneumonia diagnosis are shown to substantially increase mortality risk for COVID-19 patients.

Management of carotid atherosclerosis in stroke.

Internal carotid artery atherosclerosis is a major risk factor for stroke, accounting for 15-20% of ischaemic strokes. Revascularisation procedures-either carotid endarterectomy or carotid artery stenting-can reduce the risk of stroke for those with significant (>50%) luminal stenosis but particularly for those with more severe (70-99%) stenosis. However, advances in medical pharmacotherapy have implications for the relative benefit from surgery for symptomatic carotid atherosclerosis, as well as our approach to asymptomatic disease. This review considers the evidence underpinning the current medical and surgical management of symptomatic carotid atherosclerosis, the importance of factors beyond the degree of luminal stenosis, and developments in therapeutic strategies. We also discuss the importance of non-stenotic but high-risk carotid atherosclerotic plaques on the cause of stroke, and their implications for clinical practice.

Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis.

Aims: Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results: Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography-tandem mass spectrometry (LC-MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques' R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd-enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC-MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III-V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC-MSMS. Conclusion: We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.

Exploring the antioxidant and antimicrobial potential of three common seaweeds of Saint Martin's Island of Bangladesh.

Antioxidants, which have long been deemed an indispensable guardian of human health, play a pivotal role in bolstering the body's defense against a plethora of diseases. Three well-recognized seaweeds in Bangladesh, including Caulerpa racemosa, Padina tetrastromatica, and Hypnea musciformis, were subjected to meticulous analysis to reveal their phytochemical composition, antioxidant activity, and antimicrobial efficacy using advanced spectroscopic and disc diffusion methods. Intriguingly, we observed that C. racemosa emerges as frontrunners, possessing a substantial arsenal of phenol (143.08 ± 18.51 mg gallic acid equivalent g─1) and flavonoid (63.79 ± 2.16 mg rutin equivalent g─1). More fundamentally, C. racemosa exhibits a notable enrichment in the content of tannin (73.58 mg RE g─1) and chlorophyll (13.50 mg g─1), as well as, antioxidant capacity (4457.67 µg g─1). P. tetrastromatica, on the other hand, displayed commendable effectiveness in scavenging the DPPH radical, with percentages ranging from 53.98 to 62.17%. In terms of hydroxyl radical (OH•) scavenging activity, C. racemosa exhibited the highest efficacy at 400 g mL─1. Fascinatingly, C. racemosa exhibited an impressive antioxidant potential, as evidenced by its exceptionally low IC50 value of 5.58 µg mL-1 for OH• scavenging, whereas P. tetrastromatica showed impressively low value of 0.96 µg mL-1 for DPPH scavenging. Although the three seaweeds demonstrated limited efficacy against a spectrum of five human pathogenic bacteria, their potential as abundant sources of antioxidants remains unscathed. Notably, heatmap and PCA analysis revealed that C. racemosa and P. tetrastromatica emerge as the leading contender for studied antioxidant compounds, demonstrating their proclivity for antioxidant extraction, a trait that could be exploited for large-scale production of these valuable compounds.

Environmental quality and its impact on total fertility rate: an econometric analysis from a new perspective.

BACKGROUND: Environmental quality significantly affects various aspects of human existence. This study employs ecological footprint as a proxy to assess the impact of environmental quality on the TFR, measured as births per woman. This study investigates the extent to which ecological footprint indicators impact on the TFR in across 31 countries between from 1990 to 2017. METHODS: We gathered data on ecological footprints, specifically carbon, agricultural land, grazing land, forest products, and fisheries, from the Global Footprint Network. Information on the TFR, Human Development Index (HDI), and per capita Gross National Income (GNI) were sourced from the World Bank and the United Nations. We applied static panel and quantile regression models to scrutinize the connection between the ecological footprint and TFR, showing how the former influences the latter. RESULTS: The outcomes reveal that, in both fixed and random effects models, factors including HDI, carbon, and fishing grounds exert a negative influence on TFR, all at a significance level of p < 0.01. Conversely, cropland and forest product footprints exhibited a favorable impact on the TFR (p < 0.01). Furthermore, GNI per capita positively affected the TFR in both models, with a p-value of 0.01. Quantiles regression analysis demonstrated that HDI and carbon footprint had a negative impact on TFR across all quantiles. This statistical significance is maintained for all quantiles, although it is only significant for the carbon footprint up to the 60th quantile, at p < 0.01. CONCLUSIONS: This study establishes a negative correlation between specific ecological footprint indicators, such as carbon and fishing grounds, and TFR. Conversely, there was a positive correlation between the footprint of forest products and the TFR. The primary conclusion drawn is that there is heterogeneity in the results regarding the relationship between ecological footprint and TFR. Moreover, the ecological footprint indicators considered in this study did not uniformly influence TFR. Each ecological footprint indicator exhibited distinct effects on the TFR, displaying either positive or negative correlation coefficients. Future research endeavors may delve into how ecological footprints impact other population dynamics, such as mortality and migration.

Adherence to vascular care guidelines for emergency revascularization of chronic limb-threatening ischemia.

Objective: In 2022, the National Health Service Commissioning for Quality and Innovation (CQUIN) indicator for vascular surgery, with its pay-for-performance incentive for timely (5-day) revascularization of chronic limb-threatening ischemia (CLTI), was introduced. We sought to assess its effects in terms of (1) changes in the care pathway process measures relating to timing and patient outcomes; and (2) adherence to the Peripheral Arterial Disease Quality Improvement Framework (PAD-QIF) guidelines for patients admitted with CLTI. Methods: A retrospective before-and-after cohort study was performed from January to June 2022 of nonelective admissions for CLTI who underwent revascularization (open, endovascular, or hybrid) at Cambridge University Hospitals National Health Service Foundation Trust, a regional vascular "hub." The diagnostic and treatment pathway timing-related process measures recommended in the PAD-QIF were compared between two 3-month cohorts-before vs after introduction of the CQUIN. Results: For the two cohorts (before vs after CQUIN), 17 of 223 and 17 of 219 total admissions met the inclusion criteria, respectively. After introduction of financial incentives, the percentage of patients meeting the 5-day targets for revascularization increased from 41.2% to 58.8% (P = .049). Improvements were also realized in the attainment of PAD-QIF targets for a referral-to-admission time of ≤2 days (from 82.4% to 88.8%; P = .525) and admission-to-specialist-review time of ≤14 hours (from 58.8% to 76.5%; P = .139). An increase also occurred in the percentage of patients receiving imaging studies within 2 days of referral (from 58.8% to 70.6%; P = .324). The reasons for delay included operating list pressures and unsuitability for intervention (eg, active COVID-19 [coronavirus disease 2019] infection). No statistically significant changes to patient outcomes were observed between the two cohorts in terms of complications (pre-CQUIN, 23.5%; post-CQUIN, 41.2%; P = .086), length of stay (pre-QUIN, 12.0 ± 12.0 days; post-QUIN, 15.0 ± 21.0 days; P = .178), and in-hospital mortality (pre-QUIN, 0%; post-QUIN, 5.9%). Other PAD-QIF targets relating to delivery of care were poorly documented for both cohorts. These included documented staging of limb threat severity with the WIfI (wound, ischemia, foot infection) score (2.9% of patients; target >80%), documented shared decision-making (47.1%; target >80%), documented issuance of written information to patient (5.9%; target 100%), and geriatric assessment (6.3%; target >80%). Conclusions: The pay-for-performance incentive CQUIN indicators appear to have raised the profile for the need for early revascularization to treat CLTI, engaging senior hospital management, and reducing the time to revascularization in our cohort. Further data collection is required to detect any resultant changes in patient outcomes. Documentation of guideline targets for delivery of care was often poor and should be improved.

Arrhythmogenic Left Ventricular Cardiomyopathy Associated With a Phospholamban Gene Mutation in a Young Female: A Case Report and Literature Review.

Arrhythmogenic cardiomyopathy (ACM) is a myocardium disease characterized by phenotypic features of myocardial scarring due to fibrofatty myocardial replacement often associated with global or regional ventricular dysfunction. For years after arrhythmogenic right ventricular cardiomyopathy (ARVC) was first described, the left ventricle (LV) was generally considered normal or minimally involved. In recent years, however, LV involvement has been recognized. It usually presents with early-on arrhythmias more than heart failure symptoms compared to dilated cardiomyopathy. It can be right ventricular, biventricular, or left ventricular. The underlying pathophysiology involves either desmosomal or non-desmosomal mutations. Phospholamban (PLN) mutation is one of those and is associated with more severe arrhythmias and SCD. Primary prevention with ICD implantation should be considered in these patients, even the ones with an ejection fraction greater than 35%. In addition, if such patients progress to Stage D heart failure, they need to be evaluated for advanced heart failure therapies.

Influence of Cu induced crystallographic disorder on the optical and lattice vibrational properties of ZnO nanoparticles.

In this study, the vibrational and optical responses of 0-10% excess Cu incorporated ZnO nanoparticles (NPs) prepared by the low temperature (∼400 °C) wet chemical route were investigated experimentally and were found to be predominantly linked to the formation of both intrinsic and Cu induced crystallographic defects instead of substitutional Cu itself for the first time. For low temperature chemical synthesis, the effective band gap (Eg) of pristine ZnO NPs was found to be as low as 2.84 eV, which was followed by a further reduction by as high as ∼24.4% with gradual Cu inclusion. Excess Cu incorporation was found to drastically restrict the particle growth phenomenon by ∼61% and alter the shape morphology from anisotropic to irregular isotropic. Although all NPs showed a single phase structure with hexagonal P63mc symmetry, the X-ray peak profile analysis along with the characteristic E2(High) Raman peak and electron-phonon coupling strength obtained from the 2nd order Raman mode suggested the presence of appreciable crystallographic disorders pertaining to point defects like Cu induced Zn and O interstitials and vacancies. Optical analysis revealed a gradual increase in Urbach tailing (Eu) from 0.35 to 0.96 eV directly associated with both intrinsic and Cu induced disorders arising from successive Cu incorporation at low processing temperature. A correlation between Eg and Eu predicted a direct-type band-to-band transition energy of ∼3.2 eV for the pristine ZnO crystal, suggesting both intrinsic and excess Cu induced extrinsic disorders to be the primary source of optical modulation of the NPs for the low temperature processing condition.

Outcomes of atherectomy in patients undergoing lower extremity revascularisation.

BACKGROUND: There is a paucity of real-world data on the in-hospital (IH) and post-discharge outcomes in patients undergoing lower extremity peripheral vascular intervention (PVI) with adjunctive atherectomy. AIMS: In this retrospective, registry-based study, we evaluated IH and post-discharge outcomes among patients undergoing PVI, treated with or without atherectomy, in the National Cardiovascular Data Registry PVI Registry. METHODS: The IH composite endpoint included procedural complications, bleeding or thrombosis. The primary out-of-hospital endpoint was major amputation at 1 year. Secondary endpoints included repeat endovascular or surgical revascularisation and death. Multivariable regression was used to identify predictors of atherectomy use and its association with clinical endpoints. RESULTS: A total of 30,847 patients underwent PVI from 2014 to 2019, including 10,971 (35.6%) treated with atherectomy. The unadjusted rate of the IH endpoint occurred in 524 (4.8%) of the procedures involving atherectomy and 1,041 (5.3%) of non-atherectomy procedures (p=0.07). After adjustment, the use of atherectomy was not associated with an increased risk of the combined IH endpoint (p=0.68). In the 6,889 (22.4%) patients with out-of-hospital data, atherectomy was associated with a reduced risk of amputation (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI]: 0.51-0.85; p<0.01) and surgical revascularisation (aHR 0.63, 95% CI: 0.44-0.89; p=0.017), no difference in death rates (p=0.10), but an increased risk of endovascular revascularisation (aHR 1.21, 95% CI: 1.06-1.39; p<0.01) at 1 year. CONCLUSIONS: The use of atherectomy during PVI is common and is not associated with an increase in IH adverse events. Longitudinally, patients treated with atherectomy undergo repeat endovascular reintervention more frequently but experience a reduced risk of amputation and surgical revascularisation.

Management and Follow-Up of Biventricular Thrombi.

A thrombus is the most common intracardiac lesion. Isolated thrombi usually occur in the setting of ventricular dysfunction, such as a dyskinetic or hypokinetic myocardial wall, following an acute myocardial infarction (MI) or in cardiomyopathies (CM). Concurrent biventricular thrombus formation is rare. There are no clear guidelines for the treatment of biventricular thrombus. In this report, we describe our experience of the successful treatment of a case of biventricular thrombus with warfarin and rivaroxaban.

A State-of-the-Art Review of Intra-Operative Imaging Modalities Used to Quality Assure Endovascular Aneurysm Repair.

Endovascular aortic aneurysm repair (EVAR) is the preferred method for elective abdominal aortic aneurysm (AAA) repair. However, the success of this technique depends greatly on the technologies available. Intra-operative imaging is essential but can come with limitations. More complex interventions lead to longer operating times, fluoroscopy times, and greater contrast doses. A number of intra-operative imaging modalities to quality assure the success of EVAR have been developed. A systematic literature search was performed with separate searches conducted for each imaging modality in the study: computed tomography (CT), digital subtraction angiography (DSA), fusion, ultrasound, intra-operative positioning system (IOPS), and non-contrast imaging. CT was effective at detecting complications but commonly resulted in increased radiation and contrast dose. The effectiveness of DSA can be increased, and radiation exposure reduced, through the use of adjunctive technologies. We found that 2D-3D fusion was non-inferior to 3D-3D and led to reduced radiation and contrast dose. Non-contrast imaging occasionally led to higher doses of radiation. Ultrasound was particularly effective in the detection of type II endoleaks with reduced radiation and contrast use but was often operator dependent. Unfortunately, no papers made it past full text screening for IOPS. All of the imaging techniques discussed have advantages and disadvantages, and clinical context is relevant to guide imaging choice. Fusion and ultrasound in particular show promise for the future.

Diagnostic and Therapeutic Challenges Associated With Left Ventricular Tumors.

Cardiac tumors are uncommon. Sometimes it is challenging to differentiate non-invasively between different kinds of cardiac tumors and thrombi, which is critical to dictate the subsequent treatment. In addition, not all high-risk cardiac tumors are amenable to surgical resection posing a therapeutic challenge. We report a case of cardiac papillary fibroelastoma in the left ventricular cavity with a 10-year follow-up, with no embolic complications.

Allium vegetables: Traditional uses, phytoconstituents, and beneficial effects in inflammation and cancer.

The genus Allium comprises of at least 918 species; the majority grown for dietary and medicinal purposes. This review describes the traditional uses, phytoconstituents, anti-inflammatory and anticancer activity, and safety profile of six main species, namely Allium sativum L. (garlic), Allium cepa L. (onions), Allium ampeloprasum L. (leek), Allium fistulosum L. (scallion), Allium schoenoprasum L. (chives) and Allium tuberosum Rottler (garlic chives). These species contain at least 260 phytoconstituents; mainly volatile compounds-including 63 organosulfur molecules-, saponins, flavonoids, anthocyanins, phenolic compounds, amino acids, organic acids, fatty acids, steroids, vitamins and nucleosides. They have prominent in vitro anti-inflammatory activity, and in vivo replications of such results have been achieved for all except for A. schoenoprasum. They also exert cytotoxicity against different cancer cell lines. Several anticancer phytoconstituents have been characterized from all except for A. fistulosum. Organosulfur constituents, saponins and flavonoid glycosides have demonstrated anti-inflammatory and anticancer activity. Extensive work has been conducted mainly on the anti-inflammatory and anticancer activity of A. sativum and A. cepa. The presence of anti-inflammatory and anticancer constituents in these two species suggests that similar bioactive constituents could be found in other species. This provides future avenues for identifying new Allium-derived anti-inflammatory and anticancer agents.

The risk of harm whilst waiting for varicose veins procedure.

INTRODUCTION: Varicose veins (VV) negatively impact quality of life (QoL) and have risks of major complications including bleeding, ulceration and phlebitis. During the COVID-19 pandemic, the VSGBI (Vascular Society of Great Britain and Ireland) and GIRFT (Get It Right First Time) classified VVs as lowest priority for intervention. OBJECTIVE: This study aims to determine harm caused and the impact on the QoL on patients waiting for their VVs procedures for more than 1 year. METHODS: This was a prospective study conducted at the Norfolk and Norwich University Hospital (NNUH). Patients with VVs awaiting intervention for >1 year were included in the study. Patients with CEAP C6 disease were considered to be too high risk to be invited for treatment during the Covid-19 pandemic. Patients were sent QoL questionnaires and underwent a telephone consultation to assess harm. Both generic (EQ-VAS and EQ-5D) and disease-specific (AVVQ and CIVIQ-14) instruments were utilised. There were no control groups available for comparison. RESULTS: 275 patients were identified (37.1% male) with median time on waiting list of 60 weeks (IQR 56-65). 19 patients (6.9%) came to major harm, including phlebitis (3.6%), bleeding (1.8%) and ulceration (1.8%). Fifty-two patients (18.9%) had minor harm, including worsening pain (12.7%) and swelling (6.2%). 6.9% reported psychological harm. Rising CEAP stage was also associated with worsening level of harm in patients with C5-6 disease (p < 0.0001). Only 8.7% stated they would decline surgery during the pandemic. 104 QoL questionnaires were returned. Median EQ-VAS and EQ-5D was 75 (IQR: 60-85) and 0.685 (0.566-0.761), respectively. Median AVVQ score was 23.2 (14.9-31.0) and CIVIQ-14 score was 33 (21-44).ConclusionsThis study highlights the impact of delaying VVs surgery during a pandemic. A significant rate of both major and minor as well as psychological harm was reported. In addition, VVs had a significant detriment to quality of life.

Comparing the Benefit of Duplex Ultrasound Surveillance Following Both Infrainguinal Bypass Surgery and Stenting for Femoro-Popliteal Disease.

OBJECTIVE: Duplex ultrasound surveillance (DUS) is commonly used following infrainguinal vein bypass. The role of DUS following endovascular revascularisation is as yet unclear. This study focuses on the role of DUS in a contemporary group of patients undergoing infrainguinal bypass or stent insertion. METHODS: All patients undergoing either an infrainguinal vein graft bypass or stent insertion into the femoro-popliteal segment (November 2014 - January 2017) were identified. Patients were followed up for 2 years. Data on entry into DUS, pre-operative characteristics, adjunctive pharmacotherapy and reintervention were collated. The primary outcomes were major lower limb amputation and mortality at 2 years post revascularisation. RESULTS: One hundred and thirty-five patients underwent infrainguinal vein bypass and 100 patients underwent stent insertion. 107 patients in the bypass cohort and 58 patients in the stent cohort entered DUS. For the bypass cohort, entering DUS was associated with a lower mortality rate (P = .003) but was not associated with an improvement in amputation rates. The odds ratio of major amputation or mortality was greater in the no surveillance group (4.58, 95% CI: 1.855 - 11.364). In the stent cohort, DUS was not associated with a significant improvement in either major amputation or death (odds ratio 2.13 (95% CI 0.903 - 5.051; P = .081). CONCLUSION: DUS was associated with improved survival rates in patients undergoing lower limb bypass but had no benefit in those patients undergoing stent insertion. The role of DUS following stent insertion in the femoropopliteal segment needs to be better defined.

Stem cell therapy for heart failure in the clinics: new perspectives in the era of precision medicine and artificial intelligence.

Stem/progenitor cells have been widely evaluated as a promising therapeutic option for heart failure (HF). Numerous clinical trials with stem/progenitor cell-based therapy (SCT) for HF have demonstrated encouraging results, but not without limitations or discrepancies. Recent technological advancements in multiomics, bioinformatics, precision medicine, artificial intelligence (AI), and machine learning (ML) provide new approaches and insights for stem cell research and therapeutic development. Integration of these new technologies into stem/progenitor cell therapy for HF may help address: 1) the technical challenges to obtain reliable and high-quality therapeutic precursor cells, 2) the discrepancies between preclinical and clinical studies, and 3) the personalized selection of optimal therapeutic cell types/populations for individual patients in the context of precision medicine. This review summarizes the current status of SCT for HF in clinics and provides new perspectives on the development of computation-aided SCT in the era of precision medicine and AI/ML.