Ki-67, p53, and p16 expression, and G691S RET polymorphism in desmoplastic melanoma (DM): A clinicopathologic analysis of predictors of outcome.

Background: The prognostic role Ki-67, p53, and p16 immunostains and RET (rearranged during transfection) polymorphism in desmoplastic melanoma has not been evaluated.

Objective: We sought to identify potential prognostic markers.

Methods: We performed Ki-67, p53, and p16 immunostains on 66 desmoplastic melanomas, and sequenced RET G691 polymorphism and recurrent mutations of 17 cancer genes in 55 and 20 cases, respectively.

The effects of gamelike features and test location on cognitive test performance and participant enjoyment.

Computerised cognitive assessments are a vital tool in the behavioural sciences, but participants often view them as effortful and unengaging. One potential solution is to add gamelike elements to these tasks in order to make them more intrinsically enjoyable, and some researchers have posited that a more engaging task might produce higher quality data. This assumption, however, remains largely untested.

Gamification of Cognitive Assessment and Cognitive Training: A Systematic Review of Applications and Efficacy.

Background: Cognitive tasks are typically viewed as effortful, frustrating, and repetitive, which often leads to participant disengagement. This, in turn, may negatively impact data quality and/or reduce intervention effects. However, gamification may provide a possible solution.

Interaction of Tarantula Venom Peptide ProTx-II with Lipid Membranes Is a Prerequisite for Its Inhibition of Human Voltage-gated Sodium Channel NaV1.7.

ProTx-II is a disulfide-rich peptide toxin from tarantula venom able to inhibit the human voltage-gated sodium channel 1.7 (hNaV1.7), a channel reported to be involved in nociception, and thus it might have potential as a pain therapeutic.

Development of cell-penetrating peptide-based drug leads to inhibit MDMX:p53 and MDM2:p53 interactions.

The transcription factor p53 has a tumor suppressor role in leading damaged cells to apoptosis. Its activity is regulated/inhibited in healthy cells by the proteins MDM2 and MDMX. Overexpression of MDM2 and/or MDMX in cancer cells inactivates p53, facilitating tumor development.

Molecular Insights into Division of Single Human Cancer Cells in On-Chip Transparent Microtubes.

In vivo, mammalian cells proliferate within 3D environments consisting of numerous microcavities and channels, which contain a variety of chemical and physical cues. External environments often differ between normal and pathological states, such as the unique spatial constraints that metastasizing cancer cells experience as they circulate the vasculature through arterioles and narrow capillaries, where they can divide and acquire elongated cylindrical shapes. While metastatic tumors cause most cancer deaths, factors impacting early cancer cell proliferation inside the vasculature and those that can promote the formation of secondary tumors remain largely unknown.

Neurofeedback of visual food cue reactivity: a potential avenue to alter incentive sensitization and craving.

FMRI-based neurofeedback transforms functional brain activation in real-time into sensory stimuli that participants can use to self-regulate brain responses, which can aid the modification of mental states and behavior. Emerging evidence supports the clinical utility of neurofeedback-guided up-regulation of hypoactive networks. In contrast, down-regulation of hyperactive neural circuits appears more difficult to achieve.

Leg Rejuvenation: A Combination Approach: A Review and Our Experience.

Background: Patients increasingly seek to enhance the appearance of their legs. Elimination of unwanted leg veins, reduction of epidermal photo-aging changes such as solar lentigines and keratoses, tightening of skin laxity and reduction of adipose tissue are among the most commonly requested goals. Many patients require a combination approach to address their concerns.

Subgenual Cingulum Microstructure Supports Control of Emotional Conflict.

Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure.

Analysis of millimetre-wave polarization diverse multiple-input multiple-output capacity.

Millimetre-waves offer the possibility of wide bandwidth and consequently high data rate for wireless communications. For both uni- and dual-polarized systems, signals sent over a link may suffer severe degradation due to antenna misalignment. Orientation robustness may be enhanced by the use of mutual orthogonality in three dimensions.

Rapid Analysis of Copper Ore in Pre-Smelter Head Flow Slurry by Portable X-ray Fluorescence.

Copper laden ore is often concentrated using flotation. Before the head flow slurry can be smelted, it is important to know the concentration of copper and contaminants. The concentration of copper and other elements fluctuate significantly in the head flow, often requiring modification of the concentrations in the slurry prior to smelting.

In Vitro and In Vivo Pharmacokinetics of Aminoalkylated Diarylpropanes NP085 and NP102.

Malaria remains a great burden on humanity. Although significant advances have been made in the prevention and treatment of malaria, malaria control is now hindered by an increasing tolerance of the parasite to one or more drugs within artemisinin combination therapies; therefore, an urgent need exists for development of novel and improved therapies. The University of the Free State Chemistry Department previously synthesized an antimalarial compound, NP046.

Species discovery and validation in a cryptic radiation of endangered primates: coalescent-based species delimitation in Madagascar's mouse lemurs.

Implementation of the coalescent model in a Bayesian framework is an emerging strength in genetically based species delimitation studies. By providing an objective measure of species diagnosis, these methods represent a quantitative enhancement to the analysis of multilocus data, and complement more traditional methods based on phenotypic and ecological characteristics. Recognized as two species 20 years ago, mouse lemurs (genus Microcebus) now comprise more than 20 species, largely diagnosed from mtDNA sequence data.

Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy.

Background: Neutrophil-to-lymphocyte ratio (NLR), if elevated, is associated with worse outcomes in several malignancies.

Objective: Investigation of NLR at baseline and during therapy for metastatic renal cell carcinoma.

Design, Setting, And Participants: Retrospective analysis of 1199 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC cohort) and 4350 patients from 12 prospective randomized trials (validation cohort).

Subcortical volumetric abnormalities in bipolar disorder.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles.

Versatility of the O-Z Flap in the Reconstruction of Facial Defects.

Background: The O-Z flap has traditionally been used for surgical defects adjacent to critical anatomic structures requiring a repair option that minimizes distortion and functional impairment. However, another advantage of the O-Z flap is that it is tissue conservative, particularly in comparison to primary closure. In fact, the design simply takes the Burow's triangles that would be discarded and rotates them inward.

Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A Novel Antimycobacterial Class Targeting Mycobacterial Respiration.

High-throughput screening of a library of small polar molecules against Mycobacterium tuberculosis led to the identification of a phthalimide-containing ester hit compound (1), which was optimized for metabolic stability by replacing the ester moiety with a methyl oxadiazole bioisostere. A route utilizing polymer-supported reagents was designed and executed to explore structure-activity relationships with respect to the N-benzyl substituent, leading to compounds with nanomolar activity. The frontrunner compound (5h) from these studies was well tolerated in mice.

Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization.

Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility.

Self-establishing communities enable cooperative metabolite exchange in a eukaryote.

Metabolite exchange among co-growing cells is frequent by nature, however, is not necessarily occurring at growth-relevant quantities indicative of non-cell-autonomous metabolic function. Complementary auxotrophs of Saccharomyces cerevisiae amino acid and nucleotide metabolism regularly fail to compensate for each other's deficiencies upon co-culturing, a situation which implied the absence of growth-relevant metabolite exchange interactions. Contrastingly, we find that yeast colonies maintain a rich exometabolome and that cells prefer the uptake of extracellular metabolites over self-synthesis, indicators of ongoing metabolite exchange.

Genome-wide modeling of transcription kinetics reveals patterns of RNA production delays.

Genes with similar transcriptional activation kinetics can display very different temporal mRNA profiles because of differences in transcription time, degradation rate, and RNA-processing kinetics. Recent studies have shown that a splicing-associated RNA production delay can be significant. To investigate this issue more generally, it is useful to develop methods applicable to genome-wide datasets.

Transfusion Patterns in All Patients Admitted to the Intensive Care Unit and in Those Who Die in Hospital: A Descriptive Analysis.

While it is known that the use of health care resources increases at the end of life in patients admitted to the Intensive Care Unit (ICU), the allocation of blood products at the end of life has not been described. The objective of this study was to describe overall transfusion patterns in the ICU, and specifically in patients who die in hospital. We conducted a retrospective cohort study of adult patients admitted to the ICU of a university-affiliated hospital, who were discharged or died between November 1, 2006 and June 30, 2012.

Fast Nonparametric Clustering of Structured Time-Series.

In this publication, we combine two Bayesian nonparametric models: the Gaussian Process (GP) and the Dirichlet Process (DP). Our innovation in the GP model is to introduce a variation on the GP prior which enables us to model structured time-series data, i.e.