Contrast venography vs. microwire assisted axillary venipuncture for cardiovascular implantable electronic device implantation.

Aims: This study was conducted to compare the safety and efficacy of microwire assisted technique with contrast venography guided axillary venipuncture in patients undergoing cardiovascular implantable electronic device (CIED) implantation. Methods and results: This prospective randomized study included 212 consecutive adult patients undergoing CIED implantation at our institute between 2013 and 2015. Patients were randomized to either venography guided technique (Group I; n = 105) or microwire assisted technique (Group II; n = 107) for axillary venipuncture. In Group I axillary venogram was used as a roadmap for guiding the puncture. In Group II, a 0.014 inch hydrophilic coronary guidewire ('microwire') was introduced through the ipsilateral antecubital vein and puncture needle was aimed to hit the microwire over the first or second rib. Outcome measures including technical success rates; number of attempts to successful puncture; puncture duration; fluoroscopy times and adverse events were compared in the two groups. Overall success rates were similar in both groups (97.4% in Group I and 100% in Group II, P = 0.061). We demonstrated significantly higher first attempt success rates; shorter puncture durations and fluoroscopy times; and lower number of attempts to successful puncture with microwire assisted technique (89.3% vs. 65.6%; 36.7 ± 23.1 s vs. 67.8 ± 44.9 s; 62.4 ± 35.3 s vs. 118.9 ± 63.2 s; and 1.21 ± 0.82 vs. 2.16 ± 1.54 respectively, P < 0.001). Adverse event rates were significantly lower with microwire assisted technique (0.9% vs. 8.6%, P = 0.009). Conclusion: Microwire assisted technique is a simple, quicker, safer and more efficacious alternative to contrast venography guided axillary venipuncture.

Transradial versus transfemoral approach for coronary angiography and angioplasty - A prospective, randomized comparison.

BACKGROUND: PCI has been done traditionally through transfemoral route. But now transradial and transbrachial routes are also coming up in practice. We compared transradial versus transfemoral routes for ease of operability, time for procedure, complications, and failure rates through a prospective study. METHODS: Four hundred Patients admitted in department of cardiology for percutaneous interventions were enrolled in the study. 200 patients were assigned to each group randomly. A single team did all the procedures. Pre procedure, intra procedure and post procedure data of all the patients was collected, tabulated and analysed properly. RESULTS: Access time (6.0 ± 1vs 4.2 ± 0.7; P =0.001); Fluoroscopy time and overall procedure time (29 ± 11.3 Vs. 27.3 ± 12.4 min) were more with trans radial than transfemoral route, respectively. The most common post procedure complication, ecchymosis was seen in 20.5% in transfemoral group compared to 12.5% in transradial group (P 0.031). Thrombophelibites (17.5 VS 8%, P0.004); Hematoma (14.5 Vs 0%, P 0.005); post procedure access bleed (7 VS 3%, P 0.039) were seen in transfemoral than transradial group, respectively. Failure rates were almost similar. None of our patients had post procedure myocardial infarction, stroke, acute renal failure and infections. CONCLUSION: Transradial approach of PCI is better than transfemoral route with respect to complications like bleeding, haematoma formation, thrombophelebites and ecchymosis is concerned. However access and fluoroscopic time is more with the former. We recommend the transradial route for PCI. TRIAL REGISTRATION: Trial is retrospectively registered in ClinicalTrials.gov with the Identifier: NCT02983721 , Date of registration is December 2, 2016.

An Innovation in Pacemaker Lead Implantation via Persistent Left Superior Vena Cava: The "3D Alpha Curve" Stylet.

Persistent left superior vena cava (PLSVC) draining into coronary sinus is typically detected incidentally during transcatheter interventions using left subclavian venous approach. In our experience, we have encountered this anomaly on a few occasions and in all these cases we successfully implanted leads in the right ventricle (RV) by shaping the stylet into a "U-shaped" or "pigtail-shaped" curve. Herein, we report a case of an adult male who underwent successful dual-chamber pacemaker implantation via PLSVC through left axillary venous approach. In this case, we were unable to deliver the lead into RV using aforementioned stylets. As an innovation, we used a "three-dimensional alpha curve"-shaped stylet that facilitated an easy entry of pacing lead into the RV.

Clinical, Demographic, and Angiographic Profiles of Amarnath Pilgrims Presenting With Acute Coronary Syndrome.

INTRODUCTION: The challenges posed by high altitude are particularly significant in terms of cardiovascular health. There are currently no data available on acute coronary syndrome (ACS) among Amarnath pilgrims. The objective of this study was to investigate the clinical and angiographic profiles of ACS among Amarnath pilgrims, focusing on demographic characteristics, risk factors, types of ACS, clinical presentation, angiographic findings, and in-hospital outcomes. By examining these aspects, we aimed to provide insights into the unique challenges faced by pilgrims during their spiritual journey and to identify potential strategies for improving the prevention and management of ACS in this population.  Methods: This was a hospital-based, prospective, observational study that included patients who had participated in the pilgrimage and presented with ACS between 2022 and 2023.  Results: Sixty patients were recruited for the study, with a mean age of 51.19 ± 11.17 years. Of these, 43 (71.7%) were male. Risk factors identified in the study included hypertension in 35 (58.3%), smoking in 23 (38.3%), diabetes mellitus in 18 (30%), and dyslipidemia in 25 (41.6%) patients. ST-elevation myocardial infarction (STEMI) was present in 46 (76.66%) patients, Anterior wall myocardial infarction (AWMI) occurred in 29 (48.3%), inferior wall myocardial infarction (IWMI) in 15 (25%), and high lateral wall myocardial infarction (HLWMI) in two (3.3%) patients. Of the 60 patients, 19 (31.6%) were in Killip class I, 16 (26.6%) were in class II, and 25 (41.6%) were in classes III or IV. The average time from the onset of symptoms to hospitalization was 7.6 ± 3.1 hours, significantly higher in those with Killip class III or IV (9.3 ± 3.6 vs. 5.4 ± 2.7 hours, p = 0.01). There were nine (15%) in-hospital deaths, and in the multivariate analysis, advanced Killip class (p = 0.04) and delays in hospitalization of more than six hours (p = 0.03) were found to be significant predictors of mortality. CONCLUSION: In conclusion, 40% of patients presented in the advanced Killip class, and 15% experienced in-hospital mortality. The average time from the onset of symptoms to hospitalization was significantly higher for those categorized in the advanced Killip classes. Our study highlights a significant association between advanced Killip class, delay in hospitalization, and in-hospital mortality among Amarnath pilgrims with ACS, underscoring the importance of timely intervention. It is recommended that appropriate measures be taken to improve patient outcomes in these cases.

Clinical profile, treatment patterns and one-year outcome of heart failure patients admitted in tertiary care hospital of North India.

Introduction: Because of wide heterogeneity in the epidemiology of heart failure among different populations, it is imperative to establish population-specific databases. Aims and Objectives: To describe the clinical profile, treatment patterns, and outcomes of heart failure patients admitted to our tertiary care hospital. Material and Methods: The study was a prospective observational study conducted over two years at our tertiary care hospital. It included patients admitted with acute and acute-on-chronic heart failure. Results: We recruited 264 patients. Mean age of the study population was 57.8 ± 15.14 years. Males were 157 (59.5%). Dilated cardiomyopathy was the most common cause followed by ischemic heart disease. Most common risk factors were hypertension, tobacco use, anemia, and diabetes. Heart failure with reduced ejection fraction was present in 154 (62%) patients. Acute de novo heart failure was present in 91 (34.5%) patients. The most common precipitant for heart failure exacerbation was infection, followed by ischemic causes and non-adherence to drugs. The mean duration of hospital stay was 7.5 ± 3.1 days. The in-hospital mortality was 8.7%, and cumulative six-month and one-year mortality was 23% and 28%, respectively. In multivariate analysis, renal failure, readmission, and not being on guideline-directed medical treatment were significant predictors of mortality. Conclusion: Our patients were younger, predominantly males, with dilated and ischemic cardiomyopathy as commonest etiology. Hypertension and tobacco smoking were most common risk factors, with infections as most common precipitants. Only one-third of patients were on guideline-directed medical therapy. The one-year mortality was 28% and was higher in those without guideline-directed medical therapy.

Role of cardiac magnetic resonance imaging in identifying infarct related artery and non-ischemic pathogenesis in patients presenting with non ST elevation myocardial infarction.

INTRODUCTION: Identifying an Infarct-related artery (IRA)in Non-STEMI is sometimes tricky. Besides, myocardial infarction with non-obstructive coronary arteries (MINOCA) mimickers are often labeled as myocardial infarction. Late Gadolinium enhancement (LGE) on cardiac MRI can help in identifying IRA besides MINOCA mimickers. AIMS: To study the role of LGE on cardiac MRI(CMR) in NSTEMI. MATERIAL METHODS: It was a prospective observational, double-blinded study. 70 NSTEMI patients were prospectively enrolled over two years. CMR was done before coronary angiography (CAG) during the index hospitalization. Matching was done between IRA selected by CAG and IRA as determined by LGE on MRI. RESULTS: Mean age was 58 ± 15 years. CAG could not identify IRA in 38.6% (n = 27) patients. In this patient group, LGE-CMR identified IRA in 48.1% (n = 13) & a new non-CAD diagnosis was identified in 18.5% (n = 5) patients. IRA was identified in 61.4% (n = 43) by CAG & in this patient group, LGE-CMR identified a different IRA in 6.9% (n = 3) patients. LGE-CMR also identified a new non-CAD diagnosis in 11.6% (n = 5) of patients from this group. Overall, LGE-CMR led to a new IRA diagnosis in 23% (n = 16) patients & a diagnosis of non-ischemic pathogenesis in 14% (n = 10) patients. Non-Ischemic diagnosis on CMR included stress cardiomyopathy in 3, myocarditis in 6, and infiltrative disorder in 1 patient. CONCLUSION: CMR leads to new IRA diagnoses or non-ischemic pathogenesis in one-third of the cohort.

Left ventricular diastolic function and cardiotoxic chemotherapy.

BACKGROUND: Left ventricular ejection fraction falls when the myocardium has already lost a significant portion of its functional capacity. There are conflicting data on whether diastolic dysfunction precedes systolic dysfunction after cardiotoxic chemotherapy. We aimed to study systolic and diastolic dysfunction after cardiotoxic chemotherapy and whether diastolic dysfunction can predict subsequent risk of systolic dysfunction. It was an observational prospective cohort study, and patients receiving cardiotoxic chemotherapy were included. Baseline, demographic, and clinical details were recorded. Echocardiographic measurements of left ventricular systolic function, global longitudinal strain, and diastolic function were noted at baseline, three months, and 6 months. RESULTS: We included eighty patients. The mean age of the patients was 54.92 ± 7.6 years, predominantly females (80%). The mean left ventricular ejection fraction fell from 64.92 ± 1.96 to 60.97 ± 4.94 at 6 months. Low ejection fraction was seen in 8 (10%) patients at 6 months. The mean global longitudinal strain (GLS) at baseline was - 18.81 ± 0.797 and fell to - 17.65 ± 2.057 at 6 months, with 12 (15%) patients having low GLS (< - 18). Grade 1 diastolic dysfunction was seen in 22 (27.5%) patients, and grade 2 diastolic dysfunction was seen in 3 (3.8%) patients at 6 months. There was a significant decrease in E/A ratio (inflow early diastolic velocity/Inflow late diastolic velocity), mitral tissue Doppler velocity, and an increase in isovolumic relaxation time, mitral valve deceleration time, and E/e' (inflow early diastolic velocity/tissue Doppler mitral annular velocity), at three months and 6 months. Ejection fraction at 6 months was significantly and negatively correlated with diastolic dysfunction at three months (r = - 0.595, p = 0.02). CONCLUSIONS: Cardiotoxic chemotherapy is associated with early diastolic dysfunction. Early diastolic dysfunction predicts subsequent left ventricular systolic dysfunction.

Therapeutic efficacy and promise of stem cell-derived extracellular vesicles in Alzheimer's disease and other aging-related disorders.

The term extracellular vesicles (EVs) refers to a variety of heterogeneous nanovesicles secreted by almost all cell types, primarily for intercellular communication and maintaining cellular homeostasis. The role of EVs has been widely reported in the genesis and progression of multiple pathological conditions, and these vesicles are suggested to serve as 'liquid biopsies'. In addition to their use as biomarkers, EVs secreted by specific cell types, especially with stem cell properties, have shown promise as cell-free nanotherapeutics. Stem cell-derived EVs (SC-EVs) have been increasingly used as an attractive alternative to stem cell therapies and have been reported to promote regeneration of aging-associated tissue loss and function. SC-EVs treatment ameliorates brain and peripheral aging, reproductive dysfunctions and inhibits cellular senescence, thereby reversing several aging-related disorders and dysfunctions. The anti-aging therapeutic potential of SC-EVs depends on multiple factors, including the type of stem cells, the age of the source stem cells, and their physiological state. In this review, we briefly describe studies related to the promising effects of SC-EVs against various aging-related pathologies, and then we focus in-depth on the therapeutic benefits of SC-EVs against Alzheimer's disease, one of the most devastating neurodegenerative diseases in elderly individuals. Numerous studies in transgenic mouse models have reported the usefulness of SC-EVs in targeting the pathological hallmarks of Alzheimer's disease, including amyloid plaques, neurofibrillary tangles, and neuroinflammation, leading to improved neuronal protection, synaptic plasticity, and cognitive measures. Cell culture studies have further identified the underlying molecular mechanisms through which SC-EVs reduce amyloid beta (Aß) levels or shift microglia phenotype from pro-inflammatory to anti-inflammatory state. Interestingly, multiple routes of administration, including nasal delivery, have confirmed that SC-EVs could cross the blood-brain barrier. Due to this, SC-EVs have also been tested to deliver specific therapeutic cargo molecule/s (e.g., neprilysin) to the brain. Despite these promises, several challenges related to quality control, scalability, and biodistribution remain, hindering the realization of the vast clinical promise of SC-EVs.

Management of PDA device closure complicated by severe hemolysis by transcatheter retrieval and deployment of new device.

BACKGROUND: Hemolysis after Patent ductus arteriosus (PDA) device closure is rare. Although in most cases, hemolysis settles on its own; however, in some cases it may not settle spontaneously and may require additional procedures like putting additional coils, gel foam or thrombin instillation, balloon occlusion, or removing it surgically. We report a case of adult PDA device closure who persisted with hemolysis and was managed by transcatheter retrieval. CASE PRESENTATION: A 52-year-old gentleman presented to us with a diagnosis of large PDA with operable hemodynamics. Descending thoracic aortic Angio showed a large 11 mm PDA. Transcatheter device closure was done in the same sitting with a 16 × 14 Amplatzer Ductal Occluder I(ADO) device,;however, after device release, the aortic end of the device was not fully formed and there was residual flow. The next morning patient started with gross hematuria with persistent residual flow. We tried to manage with conservative means including hydration, and blood transfusion; however, residual flow persisted for 10 days and his hemoglobin dropped from 13 gm/dl preprocedural to 7 gm/dl, creatinine increased from 0.5 mg/dl to 1.9 mg/dl, bilirubin increased to 3.5 mg/dl & urine showed hemoglobinuria. As the patient continued to deteriorate it was planned to retrieve the device by transcatheter approach. 10 French amplatzer sheath was parked in the pulmonary artery near the ductus. We tried with a combination of multiple catheters and Gooseneck snare (10 mm) and finally, we successfully retrieved with a combination of Multipurpose (MP) catheter and 10 mm Gooseneck snare. After that, we closed the defect successfully with a double disk device (muscular Ventricular septal defect 14 mm Amplatzer). The patient's hematuria settled and was discharged after 2 days with normal hemoglobin and creatinine. CONCLUSIONS: Patent ductus arteriosus ADO 1 device should not be released if the aortic end of the disk is not fully formed Patient should be carefully monitored for hemolysis if evidence of residual shunt and given supportive treatment. If conservative treatment fails, residual flow needs to be eliminated. Transcatheter retrieval although technically challenging is a feasible treatment. A muscular VSD device is a good alternative to the usual PDA device to close PDA, especially in adults.

Prognostic value of hematological parameters in older adult patients with acute coronary syndrome undergoing coronary intervention: a single centre prospective study.

BACKGROUND: Cardiovascular disease is a significant contributor to the disease burden in geriatric patients. Underlying systemic inflammation is thought to be the cause of age-related changes in the bone marrow and a major risk factor for atherosclerosis. The purpose of the study was to assess the accuracy of these hematological biomarkers in predicting 30-day mortality in older patients with acute coronary syndrome (ACS). METHODS: This was a prospective observational study of 601 older adult patients (age > 60 years) with ACS who underwent percutaneous coronary intervention over two years (2017-2019). The relationship between baseline hematological parameters and mortality was assessed during the 30-day follow-up. Logistic regression analysis and receiver operating characteristic curve analysis were done to evaluate for diagnostic accuracy of various hematological parameters. RESULTS: The mean age of presentation was 77 ± 17 years. The mean neutrophil-lymphocyte ratio (NLR) value was 5.07 ± 4.90 and the mean platelet-lymphocyte ratio (PLR) value was 108.65 ± 85.82. On univariate analysis, total leucocyte count [odds ratio (OR) = 0.85, P = 0.021], hematocrit (OR = 0.91, P = 0.018), NLR (OR = 1.10, P = 0.001) and PLR (OR = 1.05, P = 0.001) were associated with mortality. On receiver operating characteristic curve analysis, NLR predicted mortality with 68.1% and PLR with 65.7% accuracy. On multivariate analysis, NLR (OR = 1.096, 95% CI: 1.006-1.15, P = 0.035) was an independent predictor of 30-day mortality. CONCLUSIONS: For the risk classification of all elderly ACS patients, we highly advise using NLR rather than the total white blood cell count.

Echocardiographic Measurements in Normal Healthy Adult Population of North India.

BACKGROUND AND AIM:  Interpretation of imaging modalities depends on robust normal reference limits. Ethnicity is an essential determinant of cardiac chamber sizes. Though few studies from India have focused on this research, it has yet to include the Kashmiri population. We aimed to study normal echocardiographic values of healthy Kashmiri adults and compare them with Western and Indian studies. METHODS:  It was a prospective observational study on healthy adults of Kashmir Valley. A comprehensive echocardiographic analysis following standardized protocols was performed. RESULTS:  A total of 2245 study participants were analyzed. The mean age was 32.52±11.55 years. There were 1100 (49%) males. Males had higher absolute left ventricular volumes and mass, left atrial volumes, right ventricular diameter, and aortic size, while females had higher absolute left ventricular ejection fraction and early and late diastolic mitral inflow velocities. Males had higher indexed left ventricular end-systolic volume, while females had higher indexed left ventricular end diastole diameter, aorta diameter, right ventricle, and left and right atrial sizes. Left ventricular mass and diastolic parameters were significantly associated with age. Compared with the American Society of Echocardiography/European Association of Cardiovascular Imaging, absolute values of left ventricle size, volumes, mass, right ventricle size, aortic size, and left and right atrial size were higher than those in our study. Our study population had a higher left ventricle ejection fraction. Among indexed parameters, left ventricle volumes, left ventricle systolic diameter, aortic annulus, and left and right atrial volumes were still significantly higher in Western data. While comparing with Indian data, we noted significant regional differences. CONCLUSION:  We provide normal reference values for our local population. We noted significant differences with Western as well as other Indian populations. Our study highlights the need for developing ethnic-specific reference values of various echocardiographic measurements.

Prevalence and Predictors of Venous Stenosis Following First Transvenous Cardiac Implantable Electronic Device Implantation.

Objectives: Very few studies have been done on Venous stenosis following the first transvenous cardiac device implantation. We aimed to assess the prevalence and predictors of Venous stenosis/Occlusion following the first transvenous cardiac device implantation with venous angiography at one year of follow-up. Methods: This study was a single-center prospective, observational study. Demographic, clinical, procedural, and device data was collected. All patients underwent a preimplant contrast and repeated venography at twelve months to look for upper limb venous anatomy, obstruction, or collaterals. Results: A total of 146 patients were included in the final analysis. 60 (41 %) patients developed some degree of venous stenosis. Most patients had mild to moderate stenosis, and almost all were asymptomatic. Among patient-related factors increasing age (64.66 ± 10.07 vs 60.91 ± 11.94 years p = 0.04), presence of hypertension (50.5 % vs 19.6 % p = 0.0004), diabetes (73 % vs 29.6 % p = 0.000) and dyslipidemia (66.7 % vs 36.3 p = 0.009) were significantly associated with Venous stenosis/occlusion. Among procedure-related factors, larger total lead diameter (3.88 ± 1.09 vs. 3.50 ± 1.03 mm p = 0.03) and implantation of biventricular devices (p = 0.0037) seem to be significantly associated with venous obstruction. In logistic regression analysis, hypertension (p = 0.018), total lead diameter (p = 0.024), and use of CRT-P/CRTD/ICD (p = 0.03) remained significant predictors of severe venous stenosis. Conclusions: Our study demonstrates venous obstruction in 40 % of cardiac implantable electronic device patients at one-year follow-up. Most patients have mild to moderate stenosis, and almost all are asymptomatic. Increasing age, hypertension, diabetes, dyslipidemia, larger total lead diameter, and implantation of biventricular devices are significantly associated with venous obstruction.

The ß-Secretase 1 Enzyme as a Novel Therapeutic Target for Prostate Cancer.

Recent studies have demonstrated the association of APP and Aß with cancer, suggesting that BACE1 may play an important role in carcinogenesis. In the present study, we assessed BACE1's usefulness as a therapeutic target in prostate cancer (PCa). BACE1 expression was observed in human PCa tissue samples, patient-derived xenografts (PDX), human PCa xenograft tissue in nude mice, and transgenic adenocarcinoma of the mouse prostate (TRAMP) tissues by immunohistochemistry (IHC) analysis. Additionally, the downstream product of BACE1 activity, i.e., Aß1-42 expression, was also observed in these PCa tissues by IHC as well as by PET imaging in TRAMP mice. Furthermore, BACE1 gene expression and activity was confirmed in several established PCa cell lines (LNCaP, C4-2B-enzalutamide sensitive [S], C4-2B-enzalutamide resistant [R], 22Rv1-S, 22Rv1-R, PC3, DU145, and TRAMP-C1) by real-time PCR and fluorometric assay, respectively. Treatment with a pharmacological inhibitor of BACE1 (MK-8931) strongly reduced the proliferation of PCa cells in in vitro and in vivo models, analyzed by multiple assays (MTT, clonogenic, and trypan blue exclusion assays and IHC). Cell cycle analyses revealed an increase in the sub-G1 population and a significant modulation in other cell cycle stages (G1/S/G2/M) following MK-8931 treatment. Most importantly, in vivo administration of MK-8931 intraperitoneal (30 mg/kg) strongly inhibited TRAMP-C1 allograft growth in immunocompetent C57BL/6 mice (approximately 81% decrease, p = 0.019). Furthermore, analysis of tumor tissue using the prostate cancer-specific pathway array revealed the alteration of several genes involved in PCa growth and progression including Forkhead O1 (FOXO1). All together, these findings suggest BACE1 as a novel therapeutic target in advanced PCa.

A Liquid Biopsy-Based Approach to Isolate and Characterize Adipose Tissue-Derived Extracellular Vesicles from Blood.

Obesity is a major risk factor for multiple chronic diseases. Anthropometric and imaging approaches are primarily used to assess adiposity, and there is a dearth of techniques to determine the changes in adipose tissue (AT) at the molecular level. Extracellular vesicles (EVs) have emerged as a novel and less invasive source of biomarkers for various pathologies. Furthermore, the possibility of enriching cell or tissue-specific EVs from the biofluids based on their unique surface markers has led to classifying these vesicles as "liquid biopsies", offering valuable molecular information on hard-to-access tissues. Here, we isolated small EVs from AT (sEVAT) of lean and diet-induced obese (DIO) mice, identified unique surface proteins on sEVAT by surface shaving followed by mass spectrometry, and developed a signature of five unique proteins. Using this signature, we pulled out sEVAT from the blood of mice and validated the specificity of isolated sEVAT by measuring the expression of adiponectin, 38 adipokines on an array, and several adipose tissue-related miRNAs. Furthermore, we provided evidence of sEV applicability in disease prediction by characterizing sEVAT from the blood of lean and DIO mice. Interestingly, sEVAT-DIO cargo showed a stronger pro-inflammatory effect on THP1 monocytes compared to sEVAT-Lean and a significant increase in obesity-associated miRNA expression. Equally important, sEVAT cargo revealed an obesity-associated aberrant amino acid metabolism that was subsequently validated in the corresponding AT. Lastly, we show a significant increase in inflammation-related molecules in sEVAT isolated from the blood of nondiabetic obese (>30 kg/m2) individuals. Overall, the present study offers a less-invasive approach to characterize AT.

Polycaprolactone-collagen nanofibers loaded with dexamethasone and simvastatin as an osteoinductive and immunocompatible scaffold for bone regeneration applications.

Physiological inflammation has been shown to promote bone regeneration; however, prolonged inflammation impedes the osteogenesis and bone repair process. To overcome the latter we aimed to develop a dual drug delivering nanofibrous scaffold to promote osteogenic differentiation of mesenchymal stromal cells (MSCs) and modulate the pro-inflammatory response of macrophages. The polycaprolactone (PCL)-collagen nanofibrous delivery system incorporating dexamethasone and simvastatin was fabricated by electrospinning process. The morphological analysis and mRNA, as well as protein expression of proinflammatory and anti-inflammatory cytokines in human monocytes (U937 cells), demonstrated the immunocompatibility effect of dual drug-releasing nanofibrous scaffolds. Nitric oxide estimation also demonstrated the anti-inflammatory effect of dual drug releasing scaffolds. The scaffolds demonstrated the osteogenic differentiation of adipose-derived MSCs by enhancing the alkaline phosphatase (ALP) activity and mineral deposition after 17 days of cell culture. The increased expression of Runt-related transcription factor-2 (RUNX-2) and osteocalcin at mRNA and protein levels supported the osteogenic potential of dual drug-loaded fibrous scaffolds. Hence, the results indicate that our fabricated nanofibrous scaffolds exhibit immunomodulatory properties and could be employed for bone regeneration applications after further in-vivo validation.

Role of ambulatory blood pressure monitoring in hypertensive patients having controlled office blood pressure.

BACKGROUND AND OBJECTIVES: Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In this study we tried to know the role of office and ambulatory BP in treated hypertensive patients. METHODS AND PATIENTS: Prospective cohort of 561 treated hypertensive patients were enrolled in the study. Hypertension definitions were according to JNC 8 classification. Office BP and ambulatory BP monitoring was done according to defined protocol. RESULTS: From a subgroup of 158 treated hypertensive patients, 91(16.2%) patients were having white coat hypertension (p value 0.00 by Pearson chi square test). In a subset of 403 patients who were having controlled BP on the day of enrolment as well as on the day of attaching ambulatory BP monitor; 98 (17.4%) patients were having masked uncontrolled hypertension (MUCH). In addition there was very significant percentage of non-dippers and reverse dippers. In our study we found that office BP has a moderate to low specificity and sensitivity and low negative predictive value for overall control in treated hypertensive patients. CONCLUSION: Ambulatory BP monitoring should be included in the management protocol of treated hypertensive patients, for the optimal BP control.

Mass Spectrometry-Based Proteome Profiling of Extracellular Vesicles Derived from the Cerebrospinal Fluid of Adult Rhesus Monkeys Exposed to Cocaine throughout Gestation.

Cocaine use disorder has been reported to cause transgenerational effects. However, due to the lack of standardized biomarkers, the effects of cocaine use during pregnancy on postnatal development and long-term neurobiological and behavioral outcomes have not been investigated thoroughly. Therefore, in this study, we examined extracellular vesicles (EVs) in adult (~12 years old) female and male rhesus monkeys prenatally exposed to cocaine (n = 11) and controls (n = 9). EVs were isolated from the cerebrospinal fluid (CSF) and characterized for the surface expression of specific tetraspanins, concentration (particles/mL), size distribution, and cargo proteins by mass spectrometry (MS). Transmission electron microscopy following immunogold labeling for tetraspanins (CD63, CD9, and CD81) confirmed the successful isolation of EVs. Nanoparticle tracking analyses showed that the majority of the particles were <200 nm in size, suggesting an enrichment for small EVs (sEV). Interestingly, the prenatally cocaine-exposed group showed ~54% less EV concentration in CSF compared to the control group. For each group, MS analyses identified a number of proteins loaded in CSF-EVs, many of which are commonly listed in the ExoCarta database. Ingenuity pathway analysis (IPA) demonstrated the association of cargo EV proteins with canonical pathways, diseases and disorders, upstream regulators, and top enriched network. Lastly, significantly altered proteins between groups were similarly characterized by IPA, suggesting that prenatal cocaine exposure could be potentially associated with long-term neuroinflammation and risk for neurodegenerative diseases. Overall, these results indicate that CSF-EVs could potentially serve as biomarkers to assess the transgenerational adverse effects due to prenatal cocaine exposure.

Extracellular matrix mimicking polycaprolactone-chitosan nanofibers promote stemness maintenance of mesenchymal stem cells via spheroid formation.

The development of clinical applications has led to a perpetual increase in the demand for mesenchymal stem cells (MSCs). However, the ex vivo expansion of MSCs while maintaining their stemness and differentiation potential remains an immense challenge. MSCs require high cell density for their intercellular communication and specific physico-chemical cues from the surrounding environment for spheroid formation in order to maintain their stemness. Inadequacy of the traditional in vitro cell culture method (tissue culture plastic surface) to fulfill any of these special requirements is responsible for inducing the loss of stem cell properties of the MSCs over time. In this study, we propose that glucosaminoglycan (GAG) mimicking ultrafine nanofibers could support the spheroid culture for in vitro human MSC expansion. The geometrical and biochemical properties of nanofibers provide biomimicking cues to MSCs, as well as enhance cell-cell interactions and stimulate spheroid formation in MSCs, which subsequently result in increased cell proliferation, enhanced expression of stem cell markers and maintenance of their multilineage differentiation potential. Furthermore, close monitoring of the behavior of MSCs on nanofibers serves as the key to understand their mode of action in niche formation. Interestingly, GAG mimicking substrate stimulated MSCs for long-distance intercellular communication via 'tunneling tubes', their subsequent migration and niche formation. These kinds of cellular interactions over long distances have rarely been observed in MSCs to provide better insight for future studies on MSC niche. Furthermore, PCL-CHT nanofibers were observed to be as conducive to use as tissue culture polystyrene for stem cell expansion. Overall, these polymeric nanofibers provide a more relevant, convenient and more suitable substrate than the conventional monolayer culture for in vitro MSC expansion.

Primary percutaneous coronary intervention with diagnostic catheter in an anomalous origin right coronary artery-a case report.

BACKGROUND: Although rare, the possibility of encountering an anomalous coronary artery is a reality. The outcome of such a procedure is greatly influenced by the awareness of the operator about the anatomical variations and the technique required. CASE PRESENTATION: A 50-year-old female patient presented with chest pain. On evaluation, she was found to have an inferior wall myocardial infarction. Left coronary angiography showed non-obstructive disease in the left anterior descending (LAD) and left circumflex artery (LCX). The right coronary artery could not be hooked despite multiple attempts and catheter changes. A non-specific aortic angiogram revealed anomalous origin of the right coronary artery (RCA) above the sinotubular junction on the left side. RCA was hooked with the AL-2 diagnostic catheter, and the percutaneous coronary intervention (PCI) procedure was completed via the same diagnostic catheter. CONCLUSION: In a life-threatening difficult situation like acute coronary syndrome with anomalous origin of coronary arteries, PCI can be done using a diagnostic catheter.

Dual drug-delivering polycaprolactone-collagen scaffold to induce early osteogenic differentiation and coupled angiogenesis.

Bone regeneration is a multi-step, overlapping process, in which angiogenesis and osteogenesis are the key players. Several attempts have been made to promote angiogenesis-coupled osteogenesis using scaffolding technology. However, the recreation of functional vasculature during bone regeneration is an unparalleled challenge. In this study, a dual drug-delivering polycaprolactone-collagen fibrous scaffold is reported to promote early osteogenesis and angiogenesis. Simvastatin as a pro-angiogenic and dexamethasone as an osteoinductive drug were encapsulated to functionalize the electrospun fibers. The optically transparent fibrous mat represented the sustained and sequential release of drugs for 28 days. The fibrous mesh increased cell proliferation and enhanced the osteogenic differentiation up to 21 days. The alkaline phosphatase activity and mineral deposition were comparatively higher on dual drug-releasing fibers when compared to control fibers. The dual drug-releasing osteoconductive fibers demonstrated osteogenesis as early as 7 days with a 3.7 and 1.5 fold increase in the expression of osteogenic differentiation markers (RUNX2 and osteocalcin), respectively. In vitro angiogenesis using primary human umbilical vein endothelial cells (pHUVECs) showed no significant difference in cell proliferation among control fibers and dual drug-releasing fibers. However, the angioinductive nature of simvastatin released from the fibers demonstrated tube formation and 2 fold higher angiogenic score. The mRNA and protein expression study of angiogenic markers (VEGFR2 and eNOS) by polymerase chain reaction and western blotting depicted the angioinducing potential of dual drug-releasing fibers. VEGFR2 and eNOS mRNA expressions increased by 1.1 and 1.6 fold, respectively, whereas their protein expression increased by 3.2 and 1.7 fold, respectively. The overall results demonstrate the synergistic effect of osteoconductive substrate and osteoinductive dual drugs to promote early osteogenesis, and release of the pro-angiogenic drug promotes angiogenesis.