Intra-ocular melanoma metastatic to an axillary lymph node: A case report

<p>Abstract</p> <p>Background</p> <p>Unusual metastatic presentation of intra-ocular melanoma.</p> <p>Study Design</p> <p>Case report.</p> <p>Discussion</p> <p>Extra-regional lymphatic spread of intra-ocular melanoma has not been reported previously in the literature. The usual pattern of metastasis for intra-ocular melanoma is hematogenous. There are few reports of regional spread to the maxillofacial bones. We report an interesting case of a 51 year old female with prior history of right eye melanoma, now presenting with metastasis to the left axilla, which is an extra-regional nodal basin.</p> <p>Conclusion</p> <p>In female patients presenting with an isolated axillary mass, with a negative breast work up and known prior history of melanoma, the differential diagnosis should include possible metastatic melanoma. Core biopsy will confirm the diagnosis and tailor subsequent management.</p

Investigation of fiber/matrix adhesion: test speed and specimen shape effects in the cylinder test

The cylinder test, developed from the microdroplet test, was adapted to assess the interfacial adhesion strength between fiber and matrix. The sensitivity of cylinder test to pull-out speed and specimen geometry was measured. It was established that the effect of test speed can be described as a superposition of two opposite, simultaneous effects which have been modeled mathematically by fitting two parameter Weibull curves on the measured datas. Effects of the cylinder size and its geometrical relation on the measured strength values have been analyzed by finite element method. It was concluded that the geometry has a direct influence on the stress formation. Based on the results achieved, recommendations were given on how to perform the novel single fiber cylinder test

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs

Control and Characterization of Individual Grains and Grain Boundaries in Graphene Grown by Chemical Vapor Deposition

The strong interest in graphene has motivated the scalable production of high quality graphene and graphene devices. Since large-scale graphene films synthesized to date are typically polycrystalline, it is important to characterize and control grain boundaries, generally believed to degrade graphene quality. Here we study single-crystal graphene grains synthesized by ambient CVD on polycrystalline Cu, and show how individual boundaries between coalescing grains affect graphene's electronic properties. The graphene grains show no definite epitaxial relationship with the Cu substrate, and can cross Cu grain boundaries. The edges of these grains are found to be predominantly parallel to zigzag directions. We show that grain boundaries give a significant Raman "D" peak, impede electrical transport, and induce prominent weak localization indicative of intervalley scattering in graphene. Finally, we demonstrate an approach using pre-patterned growth seeds to control graphene nucleation, opening a route towards scalable fabrication of single-crystal graphene devices without grain boundaries.Comment: New version with additional data. Accepted by Nature Material

Human depression: a new approach in quantitative psychiatry

The biomolecular approach to major depression disorder is explained by the different steps that involve cell membrane viscosity, Gsα protein and tubulin. For the first time it is hypothesised that a biomolecular pathway exists, moving from cell membrane viscosity through Gsα protein and Tubulin, which can condition the conscious state and is measurable by electroencephalogram study of the brain's γ wave synchrony

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Assessment of the proportion of neonates and children in low and middle income countries with access to a healthcare facility: A systematic review

<p>Abstract</p> <p>Background</p> <p>Comprehensive antenatal, perinatal and early postnatal care has the potential to significantly reduce the 3.58 million neonatal deaths that occur annually worldwide. This paper systematically reviews data on the proportion of neonates and children < 5 years of age that have access to health facilities in low and middle income countries. Gaps in available data by WHO region are identified, and an agenda for future research and advocacy is proposed.</p> <p>Methods</p> <p>For this paper, "utilization" was used as a proxy for "access" to a healthcare facility, and the term "facility" was used for any clinic or hospital outside of a person's home staffed by a "medical professional". A systematic literature search was conducted for published studies of children up to 5 years of age that included the neonatal age group with an illness or illness symptoms in which health facility utilization was quantified. In addition, information from available Demographic and Health Surveys (DHS) was extracted.</p> <p>Results</p> <p>The initial broad search yielded 2,239 articles, of which 14 presented relevant data. From the community-based neonatal studies conducted in the Southeast Asia region with the goal of enhancing care-seeking for neonates with sepsis, the 10-48% of sick neonates in the studies' control arms utilized a healthcare facility. Data from cross-sectional surveys involving young children indicate that 12 to 86% utilizing healthcare facilities when sick. From the DHS surveys, a global median of 58.1% of infants < 6 months were taken to a facility for symptoms of ARI.</p> <p>Conclusions</p> <p>There is a scarcity of data regarding the access to facility-based care for sick neonates/young children in many areas of the world; it was not possible to generalize an overall number of neonates or young children that utilize a healthcare facility when showing signs and symptoms of illness. The estimate ranges were broad, and there was a paucity of data from some regions. It is imperative that researchers, advocates, and policy makers join together to better understand the factors affecting health care utilization/access for newborns in different settings and what the barriers are that prevent children from being taken to a facility in a timely manner.</p

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure