Osteosarcoma Pathogenesis Leads the Way to New Target Treatments

Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.     

Extracellular Vesicles in CNS Developmental Disorders

The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.     

Epidemiological study of hypertension and its determinants in an urban population of North India

OBJECTIVES: To determine age-specific prevalence of hypertension and blood pressure (BP) levels in relation to diet and lifestyle factors in North Indians. DESIGN AND SETTING: Cross-sectional survey in 20 randomly selected streets in Moradabad, North India. SUBJECTS AND METHODS: A total of 1806 subjects from North India (904 males and 902 females) age range 25-64 years. The survey methods were as follows: dietary diaries for 7 days food intake record; BP measurements; physician administered questionnaire and anthropometric measurements. Diagnosis of hypertension was based on new World Health Organization/International Society of Hypertension (WHO/ISH) criteria. Risk factors were assessed based on WHO guidelines. RESULTS: The prevalence of hypertension according to WHO/ISH criteria was 23.7% and by old WHO criteria 13.3%. In the WHO/ISH hypertensive group, isolated diastolic hypertension was present in 47.3% males and 40.6% females. Males have a slightly higher prevalence than females in the young age group, however, the prevalence rates are comparable in the older age groups. In both sexes, the prevalence rates and BP level increased with older age. Multivariate analysis revealed that age, higher body mass index, central obesity and higher socioeconomic status were independently and strongly associated with hypertension in both sexes. Higher dietary fat and salt intake and lower physical activity were weakly but significantly associated with hypertension. CONCLUSION: Association of higher socioeconmic status, higher body mass index and central obesity in North Indian adults with higher fat intake, lower physical activity and higher prevalence and level of hypertension indicate that these populations may benefit by decreasing the dietary fat intake and increasing physical activity, with an aim to decrease central obesity for decreasing hypertension in North Indians.     

Protein analysis of human von Ebner saliva and a method for its collection from the foliate papillae

The lingual serous glands of von Ebner are located close to the foliate and circumvallate papillae. Saliva secreted by these glands provides the immediate environment of the taste buds, and it has been hypothesized that it modulates taste perception. The purpose of this study was to develop a technique for collection of unstimulated and stimulated saliva from human von Ebner glands. Saliva was collected under resting conditions and after application of various gustatory stimuli (sweet, sour, salt, and bitter) by insertion of periostrips into the folds of the foliate papillae of healthy human volunteers. Stimulated saliva was also collected in glass microcapillaries or micropipettes. The flow-rates of unstimulated von Ebner saliva were 2.3 +/- 0.6 (S.E.) microL/min and 4.5 +/- 1.2 (S.E.) microL/min with 1% citric acid stimulation. The protein content was 2.5 +/- 0.5 (S.E.) mg/mL. The SDS gel electrophoretic profile of von Ebner saliva revealed two protein bands of Mr 18,000 that were identified on Western blots as von Ebner gland (VEG) proteins. Although lingual lipase activity was detected at very low levels by enzyme assay, this protein was not detected on Western blots. This collection technique should prove useful for analysis of specific functions associated with secretion from von Ebner glands.     

Preparation and characterization of chitosan‐based dispersions

Complexation of chitosan in aqueous solutions by low molecular weight electrolytes is one of the simplest methods for the preparation of aqueous chitosan dispersions. In this work, the influence of storage time, sulfate concentration, method of preparation and surfactant content on some properties of the resultant chitosan dispersions (turbidity, viscosity and zeta potential) was analyzed. Turbidimetry was adequate to monitor the formation of particles, while viscometry was suitable to monitor changes in the dispersing phase. An analysis of the properties of these systems, mainly in terms of particle–particle and macromolecule–macromolecule interactions was carried out. Copyright © 2004 Society of Chemical Industry     

Self-adjusting the intensity of assortative mating in genetic algorithms

Mate selection plays a crucial role in both natural and artificial systems. While traditional Evolutionary Algorithms (EA) usually engage in random mating strategies, that is, mating chance is independent of genotypic or phenotypic distance between individuals, in natural systems non-random mating is common, which means that somehow this mechanism has been favored during the evolutionary process. In non-random mating, the individuals mate according to their parenthood or likeness. Previous studies indicate that negative assortative mating (AM)—also known as dissortative mating—, which is a specific type of non-random mating, may improve EAs performance by maintaining the genetic diversity of the population at a higher level during the search process. In this paper we present the Variable Dissortative Mating Genetic Algorithm (VDMGA). The algorithm holds a mechanism that varies the GA’s mating restrictions during the run by means of simple rule based on the number of chromosomes created in each generation and indirectly influenced by the genetic diversity of the population. We compare VDMGA not only with traditional Genetic Algorithms (GA) but also with two preceding non-random mating EAs: the CHC algorithm and the negative Assortative Mating Genetic Algorithm (nAMGA). We intend to study the effects of the different methods in the performance of GAs and verify the reliability of the proposed algorithm when facing an heterogeneous set of landscapes. In addition, we include the positive Assortative Mating Genetic Algorithm (pAMGA) in the experiments in order test both negative and positive AM mechanisms, and try to understand if and when negative AM (or DM) speeds up the search process or enables the GAs to escape local optima traps. For these purposes, an extensive set of optimization test problems was chosen to cover a variety of search landscapes with different characteristics. Our results confirm that negative AM is effective in leading EAs out of local optima traps, and show that the proposed VDMGA is at least as efficient as nAMGA when applied to the range of our problems, being more efficient in very hard functions were traditional GAs usually fail to escape local optima. Also, scalability tests have been made that show VDMGA ability to decrease optimal population size, thus reducing the amount of evaluations needed to attain global optima. We like to stress that only two parameters need to be hand-tuned in VDMGA, thus reducing the tuning effort present in traditional GAs and nAMGA.     

The Simulation of Impact Loads on Beam-type Structures using a Pseudo-dynamic Procedure

Abstract:  This study proposes an alternate method for the analysis of beams with solid cross-section or built as a framed structure and subjected to transverse impact loads from an external striker. The procedure used in the analysis is a combination of two essential tools using pseudo-dynamic techniques. The method reported here involves only one degree of freedom for the structure modelling and assumes an elastic contact between an external striker and the beam structure, which in reality does not happen. As only one degree of freedom is considered in the analysis, some important limitations are inherent to the method proposed here. Essentially, there is the difficulty of modelling the displacement field associated with the transient structure behaviour accurately, as a consequence of fast-rate impact loads. Another difficulty faced by the method refers to a local structure behaviour associated with contact loads. The present method can deal with large displacements in transversely loaded beams associated to a collapse mechanism having a simple geometry and defined with precision from a single parameter. This ensures reasonable accuracy in the evaluation of the strain energy absorbing capacity of transversely impacted beam structures using a single degree of freedom model in a pseudo-dynamic procedure.     

P300 latency: abnormal in sleep apnea with somnolence and idiopathic hypersomnia, but normal in narcolepsy

To evaluate cognitive abnormalities in excessive daytime sleepiness (EDS) using cognitive evoked potentials (P300), and to evaluate if P300 measures differentiate among disorders of EDS, a series of EDS subjects were administered a polysomnogram, auditory and visual P300 testing using 31 scalp electrodes, and a multiple sleep latency test. P300 variables were compared with those of normal subjects. Forty normal subjects ages 16 to 65 years, and 69 EDS patients ages 16 to 65 years were used. Of these, 39 had profound obstructive sleep apnea (OSA, Respiratory Disturbance Index or RDI > 80/h sleep) with severe somnolence (Mean Sleep Latency < 5 min). Twenty-two had idiopathic hypersomnia (IH). Eight had narcolepsy. The normals and the three EDS groups did not differ in age. IH and profound OSA patients had longer visual P300 latency than normals or narcolepsy patients (p < 0.05). (p < 0.05). IH and profound OSA patients had longer auditory P300 latency than normals. They had smaller auditory P300 amplitude than narcolepsy patients. There were visual P300 latency topographic differences between normals and profound OSA patients. In conclusion, IH and profound OSA patients show cognitive evoked potential evidence of cognitive dysfunction. Narcolepsy patients do not show such evidence. Visual P300 latency differentiates among disorders of EDS.     

Quantitative evaluation of pancreatic enhancement during dual-phase helical CT

PURPOSE: To determine the improvement in pancreatic enhancement at helical computed tomography (CT) performed with an early delay after administration of contrast material compared with that performed with a standard delay. MATERIALS AND METHODS: Dual-phase helical CT of the abdomen was performed in 120 patients with a 150-mL bolus of contrast material infused at 5 mL/sec. Early and standard delayed scanning was performed beginning at 20 seconds and 49-71 seconds, respectively. Regions of interest were measured in the head, body, and tail of the pancreas in 92 patients. The difference in enhancement between early and standard delayed scanning was calculated. RESULTS: Mean pancreatic enhancement was 82 HU +/- 3 (standard error) with an early delay, whereas enhancement on standard delay scans was 62 HU +/- 2 (P < .001). An improvement in enhancement greater than 10 HU was attained in 66 of 92 cases (72%). CONCLUSION: Pancreatic enhancement at helical CT with an early delay after contrast material administration is often significantly greater than the enhancement seen with a standard delay when a monophasic, rapidly infused bolus of contrast material is used.     

Vesicoureteral reflux and ureteropelvic junction obstruction: association, treatment options and outcome

PURPOSE: We investigated the association, treatment options and outcomes of patients with ureteropelvic junction obstruction and concomitant vesicoureteral reflux. MATERIALS AND METHODS: We analyzed 6,790 consecutive pediatric urology records at our university. Treatment options included observation, and primary pyeloplasty, ureteroneocystostomy and nephroureterectomy. Hydronephrosis, reflux and obstruction were judged as resolved, improved, unchanged or worse. RESULTS: A total of 1,140 patients had vesicoureteral reflux, 224 had ureteropelvic junction obstruction and 41 had both conditions (39 ipsilateral and 6 contralateral kidneys). There was no increased risk of obstruction in patients with reflux when all grades of reflux were grouped (odds ratio 1.26, confidence interval 0.91 to 1.71). In contrast, subgroup analysis of patients with high grade reflux demonstrated a 5-fold increased risk of obstruction (odds ratio 5.0, confidence interval 2.4 to 10.8). One patient was lost to followup. Observation of 6 kidneys led to resolution of reflux in 3 (50%), resolution of obstruction in 3 (50%) and resolution or improvement of hydronephrosis in 4 (67%). Primary pyeloplasty was done on 29 kidneys with 10 (35%) requiring subsequent ureteroneocystostomy. At latest followup hydronephrosis resolved or improved in 24 patients (83%), vesicoureteral reflux resolved or improved in 19 (66%) and ureteropelvic junction obstruction resolved in all. Primary ureteroneocystostomy was performed on 5 kidneys, all of which required subsequent pyeloplasty. Hydronephrosis resolved in 3 patients (60%), and reflux and obstruction resolved in all. Two patients treated with primary nephroureterectomy, and 1 who underwent concomitant pyeloplasty and ureteroneocystostomy have had no subsequent urological problems. One patient awaits primary pyeloplasty. CONCLUSIONS: High grade vesicoureteral reflux is associated with ureteropelvic junction obstruction. No association with low or intermediate grade reflux was demonstrated. While some patients may be monitored expectantly, in our series pyeloplasty or nephrectomy was required in 81% and ureteroneocystostomy was required in 36%. In no case did primary ureteroneocystostomy protect against the subsequent need for pyeloplasty.