Plasma fucosyltransferase as an indicator of imminent blastic crisis

Plasma fucosyltransferase activity was evaluated as an indicator of an impending blastic transformation in 25 patients with chronic granulocytic leukemia (CGL). Fifteen age-and sex-matched controls were also studied. The level of enzyme activity was significantly higher in the plasma of patients with blastic transformation (1,630 ± 570 units) compared with steady state chronic granulocytic leukemia (509 ± 110 units) and normal controls (354 ± 57 units). In three patients with CGL, a rise in fucosyltransferase activity preceded any other clinical or laboratory parameter of blastic transformation by 16–20 weeks.     

Model of birdsong learning based on gradient estimation by dynamic perturbation of neural conductances

We propose a model of songbird learning that focuses on avian brain areas HVC and RA, involved in song production, and area LMAN, important for generating song variability. Plasticity at HVC --> RA synapses is driven by hypothetical "rules" depending on three signals: activation of HVC --> RA synapses, activation of LMAN --> RA synapses, and reinforcement from an internal critic that compares the bird's own song with a memorized template of an adult tutor's song. Fluctuating glutamatergic input to RA from LMAN generates behavioral variability for trial-and-error learning. The plasticity rules perform gradient-based reinforcement learning in a spiking neural network model of song production. Although the reinforcement signal is delayed, temporally imprecise, and binarized, the model learns in a reasonable amount of time in numerical simulations. Varying the number of neurons in HVC and RA has little effect on learning time. The model makes specific predictions for the induction of bidirectional long-term plasticity at HVC --> RA synapses.     

Effect of garlic on lipid peroxidation and antioxidation enzymes in DMBA-induced skin carcinoma

ObjectiveNaturally occurring phytochemicals display an active cancer preventive strategy to inhibit, delay, or reverse human carcinogenesis. Studies have indicated that certain daily-consumed dietary phytochemicals have cancer protective effects mediated by carcinogens. Lipid peroxide plays a detrimental role in all cancers including skin carcinogenesis. Garlic, a phytochemical, has acquired a special position in the folklore of many cultures as a formidable prophylactic and therapeutic medicinal agent. In this report, we pursue the chemopreventive effect of aqueous garlic on skin carcinogenesis.Methods“Swiss albino mice” were divided into five groups depending on the combination of skin cancer–inducing 7,12-dimethylbenz[a]anthracene and garlic treatments. Histology of the affected skin and biochemical assays for lipid peroxide, catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase were performed to demonstrate the effect of garlic in mice. Immunoblotting was performed with cyclo-oxygenase-2, p53, and caspase-3 to demonstrate expressions of the respective proteins in skin lysates.ResultsGarlic extracts inhibited the oxidative modification of lipids, thus protecting cells from injury by the oxidized molecules. The best chemopreventive action of garlic was observed in mice in which garlic treatment was performed before and after the induction of skin carcinogenesis. Garlic ingestion delayed formation of skin papillomas in animals and simultaneously decreased the size and number of papillomas, which was also reflected in the skin histology of the mice treated.ConclusionThe protective effects against skin cancer elicited by garlic in mice are believed to be due at least in part to the induction cellular defense systems.     

Repeat Descemetopexy after Descemet's Membrane Detachment following Phacoemulsification

Descemet''s membrane detachment (DMD) is an uncommon condition with a wide range of possible etiologies. Probably the commonest cause is a localized detachment occurring after cataract extraction surgery. Descemetopexy gives good anatomic attachment rates and visual outcomes and has become the standard treatment for DMD. However, in cases with failed initial descemetopexy, the next step in the management of such cases remains unclear. Before initiating a complex surgical procedure like keratoplasty, which requires good postoperative care and regular follow-ups, repeat descemetopexy with a long-term tamponade using 14% C3F8 gas for recurrent DMD is definitely a worthwhile attempt.Key words: Repeat descemetopexy, Descemet''s membrane detachment, C3F8 gas     

Grid cells generate an analog error-correcting code for singularly precise neural computation

Entorhinal grid cells in mammals fire as a function of animal location, with spatially periodic response patterns. This nonlocal periodic representation of location, a local variable, is unlike other neural codes. There is no theoretical explanation for why such a code should exist. We examined how accurately the grid code with noisy neurons allows an ideal observer to estimate location and found this code to be a previously unknown type of population code with unprecedented robustness to noise. In particular, the representational accuracy attained by grid cells over the coding range was in a qualitatively different class from what is possible with observed sensory and motor population codes. We found that a simple neural network can effectively correct the grid code. To the best of our knowledge, these results are the first demonstration that the brain contains, and may exploit, powerful error-correcting codes for analog variables.     

Neuroimaging in specific phobia disorder: a systematic review of the literature

ObjectiveSpecific phobia (SP) is characterized by irrational fear associated with avoidance of specific stimuli. In recent years, neuroimaging techniques have been used in an attempt to better understand the neurobiology of anxiety disorders. The objective of this study was to perform a systematic review of articles that used neuroimaging techniques to study SP.MethodA literature search was conducted through electronic databases, using the keywords: imaging, neuroimaging, PET, spectroscopy, functional magnetic resonance, structural magnetic resonance, SPECT, MRI, DTI, and tractography, combined with simple phobia and specific phobia. One-hundred fifteen articles were found, of which 38 were selected for the present review. From these, 24 used fMRI, 11 used PET, 1 used SPECT, 2 used structural MRI, and none used spectroscopy.ResultThe search showed that studies in this area were published recently and that the neuroanatomic substrate of SP has not yet been consolidated.ConclusionIn spite of methodological differences among studies, results converge to a greater activation in the insula, anterior cingulate cortex, amygdala, and prefrontal and orbitofrontal cortex of patients exposed to phobia-related situations compared to controls. These findings support the hypotheses of the hyperactivation of a neuroanatomic structural network involved in SP.     

A novel precision-engineered microfiltration device for capture and characterisation of bladder cancer cells in urine

BackgroundSensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells.ObjectiveEvaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection.MethodsA total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies.ResultsFive samples were paucicellular by standard cytology; no samples processed by microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p < 0.001). Microfilter cytology was more concordant (κ = 50.4%) than standard cytology (κ = 33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by microfilter cytology compared to 5.5 min by standard cytology. Median microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively.ConclusionsThe microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.     

Pediatric pulmonary arterial hypertension: current and emerging therapeutic options

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease in neonates, infants and children that is associated with significant morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking and although mortality has decreased as therapeutic options have increased over the past several decades, outcomes remain unacceptable. AREAS COVERED: This review summarizes the currently available therapies for neonates, infants and children with PAH and describes emerging therapies in the context of what is known about the underlying pathophysiology of the disease. EXPERT OPINION: All of the currently approved PAH therapies impact one of three endothelial-based pathways: nitric oxide-guanosine-3'-5'cyclic monophosphate, prostacyclin or endothelin-1. The beneficial effects of these agents may relate to their impact on pulmonary vascular tone, and/or their antiproliferative and antithrombotic properties. Fundamental advances in PAH therapy are likely to relate to: i) a better understanding of PAH subpopulations, allowing for therapies to be better tailored to individual patients and pathophysiologic processes; and ii) therapies that promote the regression of advanced structural remodeling.     

A novel synthetic route for the preparation of hydrolytically degradable synthetic hydrogels

A variety of approaches have been described for the modification of synthetic, water soluble polymers with hydrolytically degradable bonds and terminal vinyl groups that can be crosslinked in situ by photo- or redox-initiated free radical polymerization. However, changes in macromer concentration, functionality, and molecular weight commonly used to achieve variable degradation rates simultaneously alter hydrogel mechanical properties. Herein, we describe a novel, two-step synthetic route for the preparation of hydrolytically degradable, crosslinkable PEG-based macromers based on chemical intermediaries that form ester linkages with variable alkyl chain length. Changes in the concentration of a single macromer were shown to provide effective variation of degradation, but with corresponding significant changes in tensile properties. Through variation in the alkyl chain length of the chemical intermediary, variable degradation times ranging from weeks to months are achieved, without significantly affecting initial gelation efficiency, swelling, or tensile properties. When modified with adhesive ligands, hydrogels supported viability of encapsulated and adherent cells. Controlled release of a model protein (Immunoglobulin G) was attained as a function of hydrogel degradation rate. Independent control of hydrogel degradation and mechanical properties will offer improved flexibility for studying the effect of these material characteristics on cellular function and may be useful in the design of matrices for tissue engineering and controlled release of bioactive molecules.