Isolating stem cells from skin: designing a novel highly efficient non-enzymatic approach

Stem cells are undifferentiated elements capable to acquire a specific cellular phenotype under the influence of specific stimuli, thus being involved in tissue integrity and maintenance. In the skin tissue self-renewal and wound healing after injury is a complex process, especially in adulthood, due to the aging process and the continuous exposure to damaging agents. The importance of stem cells in regenerative medicine is well known and defining or improving their isolation methods is therefore a primary and crucial step. In the present paper we present a novel method to isolate stem cells from human skin, including the involvement of a novel medium for the maintenance and expansion of in vitro cultures. The biopsies were mechanically digested and put in culture. The migrating cells were positive selected with magnetic cell sorting, characterized by flow-cytometry analysis, and viability detected by MTT assay. Cells exhibited a mesenchymal phenotype, as demonstrated by the positive acquirement of an osteogenic or adipogenic phenotype when cultured in specific conditioned media. Taken together our results disclose a novel method for culturing and expanding stem cells from skin and pave the way for future clinical applications in tissue regeneration

Hypertensive Cardiomyopathy: Diagnostic Approach and Clinical Differentiation from Hypertrophic Cardiomyopathy

Hypertensive Cardiomyopathy (HTN-CM) is a structural cardiac disorder generally accompanied by concentric or eccentric Left Ventricular Hypertrophy (LVH) associated with diastolic or/and systolic dysfunction in patients with persistent systemic hypertension. It occurs in the absence of other cardiac diseases capable of causing myocardial hypertrophy or cardiac dysfunction. Long standing arterial hypertension (HTN) leads to structural and functional myocardial abnormalities resulting in myocardial ischemia, fibrosis, and hypertrophy. HTN-CM is predominantly a disease of impaired relaxation rather than impaired contractility, although subtle myocardial systolic abnormalities could be detected recently by Global Longitudinal Systolic Strain (GLS) Speckle Tracking Echocardiography (STE). Importantly, the accompanying LVH is itself a risk factor for mortality and morbidity and is considered an independent predictor for Sudden Cardiac Death (SCD). Therefore, early detection of LVH development in patients with Hypertensive Hypertrophic Cardiomyopathy (HTN-CM) is crucial for optimal treatment. In addition to pathological findings, echocardiography and cardiac magnetic resonance imaging are ideal tools for the diagnosis of HTN-CM and can differentiate it from Hypertrophic Cardiomyopathy (HCM). Timely diagnosis of this condition and utilization of appropriate treatment are required to improve morbidity and mortality in hypertensive patients. This review presents an overview of utilization of multidisciplinary imaging modalities approach for proper diagnosis of HTN-CM and its differentiation from HCM. Relevant article highlighted key points in differentiation of HTN-CM from HCM and the effects of hypertension on cardiac hypertrophy and heart failure development are discussed in clinical case study

Myocardial Deformation Imaging Meta-Analysis in Two Cohorts of Patients from UAE and Heart Hospital Hamadmedical Corporation: A Potential Role in Assessment of Coronary Artery Disease Severity and Myocardial Viability

Introduction: The increasing prevalence of heart failure (HF) in coronary artery disease (CAD) urgently requires the establishment of new imaging techniques for early diagnosis and also to guide treatment of patients presented with acute coronary syndromes (ACS). Conventional echocardiography (CE) and electrocardiogram (ECG) are the gold standard methods in assessing myocardial ischemia (MI) and the function of the heart in patients with coronary artery disease (CAD). The lack of ST elevation by ECG and regional wall motion abnormalities by CE in non-ST segment elevation myocardial infarction (NSTEACS) in ACS patients reflect limited sensitivity of ECG and CE in identifying patients with acute coronary occlusion (ACO) and proper assessment of myocardial viability. Aim of this study: This study now evaluates the ability of strain parameters in grading the severity of CAD to detect myocardial viability in ACS through a comparative meta-analysis in two cohorts of patients living in the UAE and Qatar. The study investigates the diagnostic accuracy of left ventricular longitudinal systolic strain function (GLS) by 2D-speckle tracking echocardiography (2D-STE), Territorial Longitudinal Strain (TLS) analysis and post systolic strain (PSS) in ACS patients admitted at the emergency departments. All the patients had acute chest pain which is highly suggestive of NSTEACS along with coronary angiography (CA). Methods: The study recruited two groups, comprising of 347 patients, who were presented with acute coronary syndrome (NSTEACS) at the emergency department. The first group had 214 consecutive patients who had acute chest pain and high-risk profile and they were admitted to the emergency department at Eastern Emirates Hospitals, El-Fujairah-Dibba (EEEH), UAE. The second group consisted of 133 from emergency department at Heart Hospital- Hamad Medical Corporation (HHHMC), Qatar. In both groups, 85% of the patients were men with ages from 32 to 65 years (mean ± SD: 49.4 ± 9.5 years). Significant CAD was defined as having at least one epicardial vessel with ≥ 70% or left main>50% stenosis. All patients enrolled in this study underwent basic echocardiography, speckle tracking analysis, and coronary angiography. In 70 patients, PSS was calculated and myocardial perfusion imaging (MPI) was utilized as gold standards for the assessment of myocardial viability in patients with documented NSTEACS. The sensitivity, specificity, positive and negative predictive values of peak longitudinal systolic strain (2D-STE) and PSS were calculated. Left ventricular systolic strain was displayed as bull’s eye plot and territorial longitudinal strain (TLS) in the territory of the infarct-related artery. They were obtained within 24 hours from admission. Coronary angiography (CA) was performed within 24 hours from admission and used as a reference tests to assess the severity of CAD. Results: Echocardiogram obtained from the patients showed any no wall motion abnormalities at rest, although speckle tracking analysis was abnormal in 167 patients. In the first group of patients from the UAE, GLS showed a high sensitivity of 80% and a very high specificity of 93% for detection of significant CAD. In addition, PSS demonstrated a high sensitivity of 80% with an average specificity of 57%. The combination of GLS and PSS showed a further increase in sensitivity, specificity with positive and negative predictive values of 98%, 91%, 99% and 97%, respectively. Therefore, a very high correlation of GLS and PSS with coronary angiography was demonstrated: =0.90, p<0.0001 and R=0.88, p<0.0001, respectively. Furthermore, PSS showed a very high concordance with MPI scan (stress-rest-re injection studies) in detection of ischemic viable myocardium with very high sensitivity of 85%, r=0.79. In the Qatari (HHHMC) patients, a multi-vessel disease or left main disease (MV) was documented in 53.6%, and those with single vessel disease (SV) in 46.4%. LAD, circumflex and RCA lesions were found in 65, 50 and 39 patients, respectively. A control group of 129 cases was selected from outpatients referred to the echocardiography unit. The results showed that in comparison to CA, GLS sensitivity and specificity were 84% and 70%, respectively in all the patients. The sensitivity of GLS was 87% in MV and 80% in SV. Territorial strain sensitivity was 50%, 74% and 84.6% for the left anterior descending artery (LAD), circumflex and right coronary artery (RCA), respectively compared to specificity values of 64%, 65% and 61.7%, respectively. Conclusion: It is concluded that GLS by speckle tracking analysis is definitely an accurate method in early diagnosis of the severity of CAD in patients presenting with NSTE ACS. The combined use of GLS and PSS showed very high diagnostic accuracy for the identification of significant CAD in these patients. Strain imaging by STE may be applied to diagnose the severity of myocardial ischemia by showing reduction in peak systolic strain. Moreover, it is equally important to demonstrate post-systolic shortening which is a characteristic feature of ischemic viable myocardium after ACS requiring revascularization

Micro Vascular and Macro Vascular Disease in Systemic Hypertension: The Role of Cardiac Imaging and Nitric Oxide Synthase Gene Polymorphism

Systemic Hypertension (HTN) accounts for the largest amount of attributable Cardiovascular (CV) mortality worldwide. There are several factors responsible for the development of HTN and its CV complications. Multicenter trials revealed that risk factors responsible for Micro Vascular Disease (MVD) are similar for those attributable to Coronary Artery Disease (CAD) which include tobacco use, unhealthy cholesterol levels, HTN, obesity and overweight, physical inactivity, unhealthy diet, diabetes, insulin resistance, increasing age and genetic predisposition. In addition, the defective release of Nitric Oxide (NO) could be a putative candidate for HTN and MVD. This study reviewed the risk stratification of hypertensive population employing cardiac imaging modalities which are of crucial importance in diagnosis. It further emphasized the proper used of cardiac imaging to determine patients at increased CV risk and identify the management strategy. It is now known that NO has an important eff ect on blood pressure, and the basal release of endothelial Nitric Oxide (eNOS) in HTN may be reduced. Although there are diff erent forms of eNOS gene allele, there is no solid data revealing the potential role of the polymorphism of the eNOS in patients with HTN and coronary vascular diseases. In the present article, the prevalence of eNOS G298 allele in hypertensive patients with micro vascular angina will be demonstrated. This review provides an update on appropriate and justified use of non-invasive imaging tests in hypertensive patients and its important role in proper diagnosis of MVD and CAD. Second, eNOS gene allele and its relation to essential hypertension and angina pectoris are also highlighted

Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions.

On December 17, 2018, the North American branch of the International Life Sciences Institute (ILSI North America) convened a workshop "Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?" with &gt;40 invited academic, government, and industry experts in Washington, DC. The workshop objectives were to 1) develop a collective expert assessment of the state of the evidence on the human gut microbiome and associated human health benefits, 2) see if there was sufficient evidence to establish measurable gut microbiome characteristics that could serve as indicators of "health," 3) identify short- and long-term research needs to fully characterize healthy gut microbiome-host relationships, and 4) publish the findings. Conclusions were as follows: 1) mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; 2) it is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease; 3) microbiome communities are highly individualized, show a high degree of interindividual variation to perturbation, and tend to be stable over years; 4) the complexity of microbiome-host interactions requires a comprehensive, multidisciplinary research agenda to elucidate relationships between gut microbiome and host health; 5) biomarkers and/or surrogate indicators of host function and pathogenic processes based on the microbiome need to be determined and validated, along with normal ranges, using approaches similar to those used to establish biomarkers and/or surrogate indicators based on host metabolic phenotypes; 6) future studies measuring responses to an exposure or intervention need to combine validated microbiome-related biomarkers and/or surrogate indicators with multiomics characterization of the microbiome; and 7) because static genetic sampling misses important short- and long-term microbiome-related dynamic changes to host health, future studies must be powered to account for inter- and intraindividual variation and should use repeated measures within individuals

New Insight in the Assessment of Left Ventricular Function in Paradoxical Low Flow Aortic Stenosis Patients with Normal Left Ventricular Ejection Fraction: A Mini-Review

Paradoxical valvular aortic stenosis (VAS) is a challenging area of clinical cardiology for the practitioners. It involves a small aortic valve area, low flow rate and mean pressure gradient although there is normal left ventricular ejection fraction. The aim of this study was to assess left ventricular (LV) dysfunction in a symptomatic severe aortic valve stenosis which is of crucial importance in identifying patients at risk of heart failure, postoperative complications and increased mortality. There are new insights which are involved in assessment of LV myocardial function including global longitudinal strain (GLS) by two-dimensional speckle tracking echocardiography (2D STE), myocardial performance index (MPI) and maximum rate of LV pressure rise (+dP/dt) during isovolumetric contraction time of the LV. This information can provide both diagnostic and prognostic information in addition to standard echocardiographic and clinical parameters. However, a profound understanding of the complex interaction between loading conditions, chamber geometry and contractility is necessary for the correct interpretation of myocardial deformation in order to draw appropriate conclusions in patients with aortic valve disease. This mini review is related to new and novel insights into the assessment of left ventricular function (LVF) in paradoxical low flow aortic stenosis patients with normal left ventricular ejection fraction (LVEF)

Comunidades de insectos fitófagos en árboles y lianas en el dosel y sotobosque del Parque Natural Metropolitano

The food and nutrient intake of Paleolithic hunter-gatherers (Homo erectus) and of Western populations (Homo economicus) show marked variations. With increase in wealth and affluence there is a decrease in the intake of omega-3 fatty acids, vitamins, antioxidants and amino acids and a significant increase in the intake of refined carbohydrates, fats (saturated & trans fats, omega-6 fatty acids) and salt in comparison with those of the Paleolithic period. The protein or amino acid intake was 2.5 fold greater (33 vs. 13%) in the Paleolithic diet of Homo erectus compared to that of the modern Western diet. Prior to the Agricultural Revolution, man's diet was based on an enormous variety of wild plants, eggs, fish and seeds. In comparison, today about 17% of plant species provide 90% of the world's food supply which is mainly contributed by grains produced from fertilizer-based rapidly grown crops potentially lower in nutrient density and higher in energy. Grains are high in omega-6 fatty acids and carbohydrates and low in omega-3 fatty acids and antioxidants compared to leafy green vegetables. The appropriate diet for Homo sapiens is characterized by high levels of protective essential nutrients; amino acids, minerals, vitamins, flavonoids, omega-6/3 fatty acids. Whereas the average diet of Homo erectus did comply with this evolutionary pattern, the modern Western dietary pattern of Homo economicus has excess of energy-rich refined carbohydrates, omega-6, trans and saturated fats. The consumption of such foods in wealthy countries in conjunction with sedentary behavior are associated with increased risk of deaths due to cardiovascular (CVDs) and other non-communicable diseases (NCDs). © Nova Science Publishers, Inc

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)