To describe the dermoscopic features of congenital melanocytic nevi (CMN) and assess whether predominant dermoscopic patterns present in CMN are related to an individual's age ( Ͻ12 years vs Ն12 years), sex, or lesional site (head, neck, and trunk vs extremities).

Therapeutic angiogenesis utilizing genetic and cellular modalities in the treatment of arterial obstructive diseases continues to evolve. This is, in part, because the mechanism of vasculogenesis, angiogenesis, and arteriogenesis (the three processes by which the body responds to obstruction of large conduit arteries) is a complex process that is still under investigation. To date, the majority of human trials utilizing molecular, genetic, and cellular modalities for therapeutic angiogenesis in the treatment of peripheral artery disease (PAD) have not shown efficacy. Consequently, the current available knowledge is yet to be translated into novel therapeutic approaches for the treatment of PAD. The aim of this review is to discuss relevant scientific and clinical advances in therapeutic angiogenesis and their potential application in the treatment of ischemic diseases of the peripheral arteries. Additionally, this review article discusses past and recent developments, such as some unconventional approaches that have the potential to be applied as therapeutic targets. The article also includes advances in the delivery of genetic, cellular, and bioactive endothelial growth factors.

Species living in extremely cold environments resist the freezing conditions through antifreeze proteins (Afps). Apart from being essential proteins for various organisms living in sub-zero temperatures, Afpshave numerous applications in different industries. They possess very small resemblance to each other and cannot be easily identified using simple search algorithms such as BLAST and PSI-BLAST. Diverse AFPs found in fishes (Type I, II, III, IV and antifreeze glycoproteins (AFGPs)), are sub-types and show low sequence and structural similarity, making their accurate prediction challenging. Although several machine-learning methods have been proposed for the classification of AFPs, prediction methods that have greater reliability are required. In this paper, we propose a novel machine-learning-based approach for the prediction of AFP sequences using latent space learning through a deep auto-encoder method. For latent space pruning, we use the output of the auto-encoder with a deep neural network classifier to learn the non-linear mapping of the protein sequence descriptor and class label. The proposed method outperformed the existing methods, yielding excellent results in comparison. A comprehensive ablation study is performed, and the proposed method is evaluated in terms of widely used performance measures. In particular, the proposed method demonstrated a high Matthews correlation coefficient of 0.52, F-score of 0.49, and Youden's index of 0.81 on an independent test dataset, thereby outperforming the existing methods for Afp prediction.In Antarctic fish, a survival mechanism that prevented them from freezing in seawater at sub-zero temperatures was observed, which led to the discovery of antifreeze proteins (AFP) 1 . AFPs have been identified as a crucial substance for resisting a freezing environment in various species including plants, bacteria, fungi, insects, and animals 2 . Ice exists in different geometric shapes due to the varying arrangements of oxygen atoms; therefore, the structural and sequential arrangements of AFPs largely vary to accommodate this heterogeneity of ice molecules 3 . Ice also exhibits the property of recrystallization, by which small ice crystals bind to the water molecules, thus becoming a large ice lattice, causing severe damage to the cell membrane, which, in some cases, may be lethal 4 . AFPs are commonly categorized into glycoproteins (AFGPs) and non-glycoproteins (AFPs) 5 . They protect the organisms using two mechanisms: (i) thermal hysteresis (TH), by which the freezing point of water is depressed to a few degrees by the adsorption-inhibition effect without altering the melting point 6 ; (ii) ice crystal inhibition, by which the AFP sites bind to the surfaces of ice and inhibit their growth to become a larger ice lattice, developing either small harmless ice crystals or forming a needle-shaped lattice, thus diminishing the recrystallization property of ice 2 .AFPs are indispensable in organisms such as fish 7 , fungi 8 , bacteria 9 , plants 10 , and insects 11 . Furthermo...

Acute and chronic viral hepatitis are common public health problems in Pakistan, and associated with serious complications. The carrier rate of HBsAg is quoted to be around 10% in general population while the prevalence of HCV in blood donors is 4.8 %. Data regarding the prevalence of hepatitis B and C virus infections among healthy blood donors is well established in Karachi, Rawalpindi, Islamabad, Faisalabad, Lahore and Abbotabad areas, but similar data is not available for Multan population. Data regarding the epidemiology of HIV infection among blood donors is not available at most of the blood transfusion centers. In this study six thousands (6000) consecutive young healthy voluntary blood donors (age 16-50 years) comprising of 5476 males and 524 females, belonging to Multan region were included from "Blood Transfusion Center Nishtar Hospital Multan" & "Fatmid Blood Transfusion Center Multan" and were tested for HbsAg, Anti-HCV and HIV. Prevalence of Hepatitis B, C and HIV Infection was 3.37%, 0.27% and 0% respectively. The reported prevalence figures for HBsAg & Anti-HCV in other studies are quite variable, depending upon screening protocol, study groups selected and methodology of testing. If data from all the blood transfusion centers of Pakistan is collected and published, we can get representative prevalence values of HBV, HCV and HIV infection of the general population.

Background Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death. Purpose This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor β (TGFβ) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFβ silencing and CXCR4 Inhibition, respectively, to treat CCl 4 -induced liver fibrosis in a mouse model. Methods Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFβ silencing of PEI-Cyclam polyplex was authenticated by Western blotting. Results The 1 H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFβ polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFβ polyplex significantly downregulated α-smooth muscle actin, TGFβ, and collagen type III. Conclusion Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFβ siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl 4 -induced liver fibrosis.

An algorithm for real time humanoid sound localization and tracking using only two microphones in a highly reverberant environment is proposed. Several recently developed 3D humanoid sound localization algorithms require the environment to be anechoic. Also, the resolution of front-back ambiguity problem during sound localization requires the knowledge about the reference signals. Using HRTF based sound localization together with extended kalman filtering, we are able to accurately track moving sound sources in real time in a highly reverberant environment. This algorithm uses only two microphones and requires no prior knowledge of the reference signals.

Background Postprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides (TG) by restricting free fatty acid (FFA). Immediate-release niacin reduced postprandial TGs, but extended-release niacin failed to do so when dosed the night before a fat challenge. Aims 1) Determine whether extended-release niacin dosed before a fat challenge suppresses postprandial TG. 2) Determine whether postprandial TG is related to FFA restriction. Methods Double-blinded, placebo-controlled, random-order crossover experiment, where healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours, and report TG and FFA as means±SD for incremental area under the curve (iAUC) and nadir. Results Combining 43 fat challenges from 22 subjects, postprandial TG iAUC was +312±200 on placebo vs +199±200 mg/dL*h on extended-release niacin (33% drop, p= 0.02). The incremental nadir for FFA was −0.07±0.15 on placebo vs −0.27±0.13 mmol/L on extended-release niacin (p<0.0001), and FFA iAUC fell from +2.9±1.5 to +1.5±1.5 mmol/L*h on extended-release niacin (20% drop, p=0.0015). The TG iAUC was strongly related to the post-dose drop in FFA (r=+0.58, p=0.0007). Conclusions Given right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial TG suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked FFA restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy.

Personalized medicine refers to the application of an individual’s biological fingerprint – the comprehensive dataset of unique biological information – to optimize medical care. While the principle itself is straightforward, its implementation remains challenging. Advances in pharmacogenomics as well as functional assays of vascular biology now permit improved characterization of an individual’s response to medical therapy for vascular disease. This review describes novel strategies designed to permit tailoring of four major pharmacotherapeutic drug classes within vascular medicine: antiplatelet therapy, antihypertensive therapy, lipid-lowering therapy, and antithrombotic therapy. Translation to routine clinical practice awaits the results of ongoing randomized clinical trials comparing personalized approaches with standard of care management.