Histological changes in the heart and the proximal aorta in experimental diabetic rats fed with Piper sarmentsoum

Cardiovascular complications are one of the major causes of death in diabetes mellitus. Piper sarmentosum (P.s) is an herb that possesses antihyperglycaemic effects. The main aim of the study was to observe the histological changes in the heart and the proximal aorta of streptozotocin-induced diabetic rats following P.s administration. Twenty-four male Sprague-Dawley rats (n=24) were equally randomized into four groups: control group supplemented with normal saline (C); control group supplemented with P.s (CTx) ; diabetic group supplemented with normal saline (D) and, diabetic group supplemented with P.s (DTx). Diabetes was induced by STZ (50mg/kg body weight) intramuscularly. P.s extract (0.125g/kg) was administered orally for 28 days, following four weeks of STZ induction. The cardiac and aortic tissues were collected and processed under different stains: Haematoxylin and Eosin (H & E), Verhoeff-Van Gieson (VVG), Masson’s Trichome (MT) and Periodic Acid- Schiff (PAS). There were abnormal cardiomyocytes nuclei, disarray of myofibres and increase in connective tissue deposits in cardiac tissues of the diabetic untreated group. The thickness of tunica media and ratio of tunica intima to media were found to be significantly increased in the aorta of diabetic untreated group (P < 0.05) compared to the control group. There weredegenerative changes in the proximal aorta in diabetic untreated groups. All the histological damages of cardiac and aortic tissues were found to be lesser in the diabetic treated groups. Supplementation with P.s extract prevented the oxidative damage arising from diabetes mellitus, and reduced its complications

Mir-434-5p mediates skin whitening and lightening

Utilization of gene silencing effectors, such as microRNA (miRNA) and small hairpin RNA (shRNA), provides a powerful new strategy for human skin care in vivo, particularly for hyperpigmentation treatment and aging prevention. In this study, tyrosinase (Tyr), the rate-limiting enzyme of melanin (black pigment) biosynthesis, was served as a target for treatment of hyperpigmentation in mouse and human skins. There are over 54 native microRNA capable of silencing human tyrosinase for skin whitening and lightening. To this, we have designed a mir-434-5p homologue and used it to successfully demonstrate the feasibility of miRNA-mediated skin whitening and lightening in vitro and in vivo. Under the same experimental condition in the trials, Pol-II-directed intronic mir-434-5p expression did not cause any detectable sign of cytotoxicity, whereas siRNAs targeting the same sequence often induced certain nonspecific mRNA degradation as previously reported. Because the intronic miRNA-mediated gene silencing pathway is tightly regulated by multiple intracellular surveillance systems, including Pol-II transcription, RNA splicing, exosomal digestion and nonsense-mediated RNA decay (NMD), the current findings underscore the fact that intronic miRNA agents, such as manually re-designed mir-434-5p homologues, are effective, target-specific and safe to be used for skin whitening without any detectable cytotoxic effect. Given that the human skins also express a variety of other native miRNAs, we may re-design these miRNAs based on their individual functions for skin care, which may provide significant insights into areas of opportunity for new cosmetic and/or therapeutical applications

Diagnostic Value of Methylated Human Telomerase Reverse Transcriptase in Human Cancers: A Meta-Analysis

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Energy loss in perturbative QCD

We review the properties of energetic parton propagation in hot or cold QCD matter, as obtained in recent works. Advances in understanding the energy loss - collisional and radiative - are summarized, with emphasis on the latter: it features very interesting properties which may help to detect the quark-gluon plasma produced in heavy ion collisions. We describe two different theoretical approaches, which lead to the same radiated gluon energy spectrum. The case of a longitudinally expanding QCD plasma is investigated. The energy lost by a jet with given opening angle is calculated in view of making predictions for the suppression (quenching) of hard jet production. Phenomenological implications for the difference between hot and cold matter are discussed. Numerical estimates of the loss suggest that it may be significantly enhanced in hot compared to cold matter.Comment: 49 pages latex file with 11 embedded PS figures. Uses ar.sty (included), one equation revised. submitted to Annual Review of Nuclear and Particle Scienc

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS

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Studies in RF power communication, SAR, and temperature elevation in wireless implantable neural interfaces

Implantable neural interfaces are designed to provide a high spatial and temporal precision control signal implementing high degree of freedom real-time prosthetic systems. The development of a Radio Frequency (RF) wireless neural interface has the potential to expand the number of applications as well as extend the robustness and longevity compared to wired neural interfaces. However, it is well known that RF signal is absorbed by the body and can result in tissue heating. In this work, numerical studies with analytical validations are performed to provide an assessment of power, heating and specific absorption rate (SAR) associated with the wireless RF transmitting within the human head. The receiving antenna on the neural interface is designed with different geometries and modeled at a range of implanted depths within the brain in order to estimate the maximum receiving power without violating SAR and tissue temperature elevation safety regulations. Based on the size of the designed antenna, sets of frequencies between 1 GHz to 4 GHz have been investigated. As expected the simulations demonstrate that longer receiving antennas (dipole) and lower working frequencies result in greater power availability prior to violating SAR regulations. For a 15 mm dipole antenna operating at 1.24 GHz on the surface of the brain, 730 uW of power could be harvested at the Federal Communications Commission (FCC) SAR violation limit. At approximately 5 cm inside the head, this same antenna would receive 190 uW of power prior to violating SAR regulations. Finally, the 3-D bio-heat simulation results show that for all evaluated antennas and frequency combinations we reach FCC SAR limits well before 1 °C. It is clear that powering neural interfaces via RF is possible, but ultra-low power circuit designs combined with advanced simulation will be required to develop a functional antenna that meets all system requirements. © 2013 Zhao et al

Excision of sympathetic ganglia and the rami communicantes with histological confirmation offers better early and late outcomes in Video assisted thoracoscopic sympathectomy

<p>Abstract</p> <p>Background</p> <p>Video-Assisted Thoracoscopic Sympathectomy (VATS) is an established minimally invasive procedure for thoracic sympathetic blockade in patients with hyperhidrosis, facial flushing and intractable angina. Various techniques using clips, diathermy and excision are used to perform sympathectomy. We present our technique of excision of the sympathetic chain with histological proof and the analysis of the early and late outcomes.</p> <p>Methods</p> <p>We evaluated 200 procedures in 100 consecutive patients, who underwent Video Assisted Thoracoscopic Sympathectomy by a single surgeon in our centre between September 1996 to March 2007. All patients had maximum medical therapy prior to surgery and were divided into 3 groups based on indications, Group 1(hyperhidrosis: 48 patients), Group 2 (facial flushing: 26 patients) and Group 3(intractable angina: 26 patients). The demography and severity of symptoms for each group were analysed. The endpoints were success rate, 30 day mortality, complications and patient's satisfaction.</p> <p>Results</p> <p>99 patients had bilateral VATS sympathectomy and 1 had unilateral sympathectomy. The conversion rate to open was 1(1%). All patients had successful removal of ganglia proven histologically with no perioperative mortality in our series. The complications included pneumothorax (5%), acute coronary syndrome (2%), transient Horner's syndrome (1%), transient paraesthesia (1%), wound infection (4%), compensatory hyperhidrosis (18%), residual flushing (3%) and wound pain (5%). There were five late deaths in the intractable angina group at a mean follow up of 36.7 months. Overall success rates of abolishing the symptoms were 96.3%, 87.5% and 95.2% for Group 1, 2 and 3 respectively.</p> <p>Conclusion</p> <p>Excision of the sympathetic chain with histological confirmation during VATS sympathectomy is a safe and effective method in treating hyperhidrosis, facial flushing and intractable angina with good long term results and satisfaction.</p

Crude incidence in two-phase designs in the presence of competing risks.

BackgroundIn many studies, some information might not be available for the whole cohort, some covariates, or even the outcome, might be ascertained in selected subsamples. These studies are part of a broad category termed two-phase studies. Common examples include the nested case-control and the case-cohort designs. For two-phase studies, appropriate weighted survival estimates have been derived; however, no estimator of cumulative incidence accounting for competing events has been proposed. This is relevant in the presence of multiple types of events, where estimation of event type specific quantities are needed for evaluating outcome.MethodsWe develop a non parametric estimator of the cumulative incidence function of events accounting for possible competing events. It handles a general sampling design by weights derived from the sampling probabilities. The variance is derived from the influence function of the subdistribution hazard.ResultsThe proposed method shows good performance in simulations. It is applied to estimate the crude incidence of relapse in childhood acute lymphoblastic leukemia in groups defined by a genotype not available for everyone in a cohort of nearly 2000 patients, where death due to toxicity acted as a competing event. In a second example the aim was to estimate engagement in care of a cohort of HIV patients in resource limited setting, where for some patients the outcome itself was missing due to lost to follow-up. A sampling based approach was used to identify outcome in a subsample of lost patients and to obtain a valid estimate of connection to care.ConclusionsA valid estimator for cumulative incidence of events accounting for competing risks under a general sampling design from an infinite target population is derived