Effect of different preparation methods on physicochemical properties of salidroside liposomes.
Salidroside liposomes were prepared by using five different methods: thin film evaporation, sonication, reverse phase evaporation, melting, and freezing-thawing. The effect of different preparation methods and salidroside loading capacity on the formation of liposomes and their physicochemical properties were evaluated by means of encapsulating efficiency, particle size, morphology, and zeta potential. Results showed that the encapsulating efficiency of liposomes was highest when prepared by freezing-thawing, followed by thin film evaporation, then reverse phase evaporation and the lowest with melting and sonication. Loading capacity of salidroside had a significant effect on encapsulating efficiency, average diameter, and zeta potential of liposomes. Liposomal systems prepared by sonication, melting, and reverse phase evaporation displayed better dispersivity. Determination of leakage of salidroside from different liposomal systems revealed that the melting method had the lowest leakage of 10% and 15%, at 4 and 30 degrees C after 1 month of storage, respectively. In all cases, a straight-line leakage behavior of salidroside was found. This revealed that the leakage of salidroside was a diffusion process from the membrane of liposomes. Furthermore, the storage stability of different liposomal systems showed that salidroside liposomes prepared by melting had a better physicochemical stability. Instability in the systems was exacerbated when temperature increased. Salidroside liposomes showed the slower increase in particle size than liposomes without salidroside. This could indicate that salidroside played an important role in preventing the aggregation and fusion of liposomes.


Deep neural network heatmaps capture Alzheimer's disease patterns reported in a large meta-analysis of neuroimaging studies.
Deep neural networks currently provide the most advanced and accurate machine learning models to distinguish between structural MRI scans of subjects with Alzheimer's disease and healthy controls. Unfortunately, the subtle brain alterations captured by these models are difficult to interpret because of the complexity of these multi-layer and non-linear models. Several heatmap methods have been proposed to address this issue and analyze the imaging patterns extracted from the deep neural networks, but no quantitative comparison between these methods has been carried out so far. In this work, we explore these questions by deriving heatmaps from Convolutional Neural Networks (CNN) trained using T1 MRI scans of the ADNI data set and by comparing these heatmaps with brain maps corresponding to Support Vector Machine (SVM) activation patterns. Three prominent heatmap methods are studied: Layer-wise Relevance Propagation (LRP), Integrated Gradients (IG), and Guided Grad-CAM (GGC). Contrary to prior studies where the quality of heatmaps was visually or qualitatively assessed, we obtained precise quantitative measures by computing overlap with a ground-truth map from a large meta-analysis that combined 77 voxel-based morphometry (VBM) studies independently from ADNI. Our results indicate that all three heatmap methods were able to capture brain regions covering the meta-analysis map and achieved better results than SVM activation patterns. Among them, IG produced the heatmaps with the best overlap with the independent meta-analysis.


Bankruptcy is the tip of a medical-debt iceberg.
Medical bankruptcy, whatever its actual frequency, is an extreme example of a much broader phenomenon. Medical debt is surprisingly common, affecting about twenty-nine million nonelderly adult Americans, with and without health insurance. The presence of medical debt, even for the insured, appears to create health care access barriers akin to those faced by the uninsured. Policymakers, researchers, and medical providers should consider medical debt a risk factor for reduced health access and poorer health status. Simply reducing the number of uninsured Americans would be a hollow policy victory if the problems arising from medical debt persist.


Quantitation of ceramides in nude mouse skin by normal-phase liquid chromatography and atmospheric pressure chemical ionization mass spectrometry.
A sensitive and accurate normal-phase liquid chromatography and atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) method for determining the standard ceramide [NS] (Cer[NS]) was developed and validated so as to improve the traditional thin-layer chromatography (TLC) technique and LC-electrospray ionization (ESI)-MS method to profile and quantify ceramides in nude mouse skin. Normal-phase LC-APCI-MS was optimized to separate the nine classes of ceramides presented in the stratum corneum (SC) of nude mouse skin. A normal-phase silica column eluted with the gradient system from heptane:acetone/butanol (90:10, v/v) of 75:25 to 100% acetone/butanol (90:10, v/v) (with each solvent containing 0.1% [v/v] triethylamine and 0.1% [v/v] formic acid) at a flow rate of 0.8 ml/min was found to be optimal for analyzing standard Cer[NS]. The analysis of Cer[NS] was validated and employed as the standard for constructing a calibration curve to quantitate all classes of ceramides. This method was applied to profile the classes and contents of ceramides in the SC of nude mouse skin and proved to be workable. It was concluded that this improved method can be used to directly detect and quantify all classes of ceramides in the SC of nude mouse skin and that it is more convenient and labor-saving than the traditional TLC method.


Rapid-injection NMR study of iodo- and cyano-Gilman reagents with 2-cyclohexenone: observation of pi-complexes and their rates of formation.
Rapid-injection is a very useful technique for the preparation of temperature-sensitive and air-sensitive compounds in the cold, nitrogen-filled probe of an NMR spectrometer. We have used this method to prepare solutions of pi-complexes from 2-cyclohexenone and prototypical cuprates Me2CuLi.LiI and Me2CuLi.LiCN, and we have assigned structures on the basis of 1H and 13C NMR. In each case two pi-complexes were observed, and in the former, their rates of formation were measured by rapid-injection 1H NMR and EXSY spectroscopy. These results provide insights into the normal and anomalous conjugate addition reactions of organocuprates.


Combining fixed- and moving-grid methods to study direct dissociation processes involving nonadiabatic transitions.
We present a novel quantum-dynamics approach suitable for computing direct dissociation processes, including electronic transitions. This approach combines quantum trajectories in the Lagrangian reference frame with standard fixed-grid wave packets in order to overcome the limitations and difficulties of both techniques. As a model application, we consider the ultrafast photodissociation of H2 excited by a femtosecond extreme UV laser pulse.


Effect of postoperative hypoalbuminemia and supplement of human serum albumin on the development of surgical site infection following spinal fusion surgery: a retrospective study.
To determine the association between postoperative hypoalbuminemia and the development of surgical site infection (SSI) and evaluate whether the supplement of exogenous human serum albumin (HSA) in patients following spinal surgery would decrease the rate of postoperative SSI. We performed a retrospective review of all patients who underwent lumbar spinal fusion surgery in our institution between January 2014 and December 2018. Patients with postoperative SSI were identified. We reviewed the demographic and clinical records of the patients and performed multiple logistic regression models to clarify the relevance between postoperative hypoalbuminemia, the supplement of HSA and SSI. Statistical adjustment for the potential confounders was also performed to exclude possible variation. Twenty-four of 602 patients developed SSI after lumbar spinal fusion surgery. No statistical significance was found between postoperative hypoalbuminemia and SSI rate (OR 0.74; 95% CI 0.22-2.48; P = 0.6199). However, the supplement of exogenous HSA was significantly associated with increased postoperative SSI rate (OR 1.21; 95% CI 1.05-1.41; P = 0.0094). Interestingly, stratified analyses showed supplement of HSA in patients without postoperative hypoalbuminemia increased the risk of SSI (OR 2.55; 95% CI 1.01-6.45; P = 0.0475), compared with patients with postoperative hypoalbuminemia (OR 1.17; 95% CI 1.00-1.36; P = 0.0434). The present study suggests that postoperative hypoalbuminemia is not associated with the development of SSI after spinal surgery. However, the supplement of HSA following spinal surgery will increase the rate of SSI. These slides can be retrieved under Electronic Supplementary Material.


Surface Characteristics of Nanotube Formed Ti–25Nb–xZr Alloys.
The purpose of this study was to investigate surface characteristics of nanotube formed Ti–25Nb–xZr alloys. Ti–25Nb–xZr ternary alloys with 0–15 wt% Zr were manufactured in a vacuum arcmelting furnace. Ingots of the alloys were homogenized in an Ar atmosphere at 1000 °C for 12 h, followed by quenching in ice water. Nanotube layers were formed by an electrochemical method in 1 M H₃PO₄ and 0.8 wt% NaF at 30 V for 1 h. As the Zr content of the Ti–25Nb–xZr Alloys increased, the crystals transformed from a needle-like to equiaxed structure. Two nanotube sizes were obtained on the Ti–25Nb–xZr alloys. As the Zr content was increased, the diameters of the larger tubes decreased, whereas those of the smaller tubes increased. However, increased Zr content in the Ti–25Nb–xZr alloys had little effect on wettability.


Free fatty-acid uptake by isolated rat hepatocytes.
In isolated rat hepatocytes, the rate of palmitic acid binding and uptake is directly related to the concentration of free fatty acid (FFA) in the medium. After their entry into the cell, FFA are immediately incorporated into cellular phospholipids and triglycerides and no accumulation of free fatty acids can be demonstrated inside the cell. The rate of free fatty-acid uptake remains unchanged after incubation in a 2 mM KCN containing medium, indicating that in the range of fatty-acid concentrations used in this study, this phenomenon does not require energy.


Ferroelasticity in Two-Dimensional Tetragonal Materials.
Ferroelasticity is a prominent material property analogous to ferroelectricity and ferromagnetism, but its characteristic spontaneous structural polarization has remained less studied and poorly understood. Here, we use a high-throughput computation approach in conjunction with first-principles calculations to identify 65 (M=transition metal, X=nonmetal) monolayers exhibiting in-plane ferroelasticity out of 166 stable tetragonal monolayers. Molecular orbital theory analysis reveals that ferroelastic distortion arises when M-d/X-p and M-d/M-d couplings are both sufficiently weak. We have developed a physically interpretable one-dimensional descriptor that correctly predicts 89% of ferroelastics or nonferroelastics among the examined MX monolayers. Moreover, we find eleven MX compounds that exhibit strongly coupled ferroelasticity and magnetism driven by strain-controlled magnetocrystalline anisotropy, raising the prospects of developing 2D ferroelasticity-based multiferroics.


Structural insights into the backbone-circularized granulocyte colony-stimulating factor containing a short connector.
Backbone circularization is a powerful approach for enhancing the structural stability of polypeptides. Herein, we present the crystal structure of the circularized variant of the granulocyte colony-stimulating factor (G-CSF) in which the terminal helical region was circularized using a short, two-amino acid connector. The structure revealed that the N- and C-termini were indeed connected by a peptide bond. The local structure of the C-terminal region transited from an α helix to 310 helix with a bend close to the N-terminal region, indicating that the structural change offset the insufficient length of the connector. This is the first-ever report of a crystal structure of the backbone of a circularized protein. It will facilitate the development of backbone circularization methodology.


Selenium-centered, undecanuclear silver cages surrounded by iodo and dialkyldiselenophosphato ligands. Syntheses, structures, and photophysical properties.
Three clusters [Ag11(mu9-Se)(mu3-I)3{Se2P(OR)2}6] (R = Et, 1; iPr, 2; 2Bu, 3) were isolated from the reaction of [Ag(CH3CN)4](PF6), NH4[Se2P(OR)2], and Bu4NI in a molar ratio of 4:3:1 in CH2Cl2 in 47-55% yield. Compounds 1 and 2 can also be synthesized with high yield from the reaction of Ag10(Se)[Se2P(OR)2]8 with 8 equiv of Bu4NI. In the positive fast atom bombardment mass spectra of 1-3, two major peaks that correspond to the intact molecule with the loss of an iodide ion, [Ag11(mu9-Se)(mu3-I)(2){Se2P(OR)2}6]+, and a diselenophosphate ligand, [Ag11(mu9-Se)(mu3-I)3{Se2P(OR)2}5]+, were identified. Single-crystal X-ray analyses of 2 and 3 reveal an Ag11Se core stabilized by three iodide anions and six diselenophosphato ligands in a tetrametallic tetraconnective (mu2,mu2) coordination mode. The central core adopts the geometry of a 3,3,4,4,4-pentacapped trigonal prism with a selenium atom in the center. In addition, weak intermolecular Se...I interactions exist in 2 and form a one-dimensional polymeric chain structure. Furthermore, all compounds exhibit orange-red luminescence in both the solid state and solution.


Low temperature catalytic hydrodeoxygenation of lignin-derived phenols to cyclohexanols over the Ru/SBA-15 catalyst.
Cyclohexanol and its derivatives are widely used as chemical intermediates and fuel additives. Herein, Ru/SBA-15 catalysts were prepared via impregnation, and used for the production of cyclohexanols from lignin-derived phenols. The catalyst samples were characterized by XRD, XPS, TEM, etc., where the Ru0 species was speculated as the active phase. 5 wt% Ru/SBA-15 with small Ru particle size (4.99 nm) and high Ru dispersion (27.05%) exhibited an excellent hydrogenation activity. A high cyclohexanol yield of >99.9% was achieved at 20 °C for 5 h in an aqueous phase, and the catalyst indicated stable activity and selectivity after five runs. Crucially, Ru/SBA-15 exhibited a zero-order reaction rate with an apparent activation energy (Ea) as low as 10.88 kJ mol-1 and a TON of 172.84 at 80 °C. Simultaneously, demethoxylation activity was also observed in the hydrodeoxygenation (HDO) of G- and S-type monophenols, and a high yield of 37.4% of cyclohexanol was obtained at 80 °C and 4 h when using eugenol as substrate.


Acute epididymitis in boys: evidence of a post-infectious etiology.
We studied the etiology and management of pediatric epididymitis. We performed 1-year prospective study in children with epididymitis. All patients underwent an immediate sonographic study of the scrotum. Microbiological studies included throat and urine cultures as well as viral cultures of nasopharyngeal and stool specimens. Serological tests for group A streptococcus and Mycoplasma pneumoniae as well as for enteroviruses, adenoviruses, influenza and parainfluenza viruses in the appropriate seasons were performed in patients and controls. A total of 44 patients 2 to 14 years old (mean age 9.8 +/- 3.2) were studied. Hospital admissions peaked during the summer and winter. The incidence of epididymitis was around 1.2/1,000 boys yearly. One patient had familial Mediterranean fever and another had Henoch-Schonlein purpura. Microbiological studies of the urine, throat, nasopharynx and stool yielded bacterial/viral growth in 9 patients (20.4%). Serological studies revealed significantly elevated titers to certain pathogens in patients with epididymitis compared with controls, including M. pneumoniae (53% vs 20%), enteroviruses (62.5% vs 10%) and adenoviruses (20% vs 0%). Most patients were treated with analgesics and 3 patients received antibiotics intravenously. Systemic and local signs and symptoms resolved gradually in 1 to 7 days. Our results suggest that epididymitis in boys is not rare and it is mostly an inflammatory phenomenon (presumably post-infectious) with a benign course. The treatment of these patients is basically with analgesics with a little role for antibiotics.


Influence of Organic Solvent Species on Dehydration Behaviors of NaA-Type Zeolite Membrane.
In this study, an NaA-type zeolite membrane was prepared, and the dehydration performances of the membrane were determined by the pervaporation for several organic solvents to understand the lower dehydration performances of zeolite membranes for NMP solutions than those for alcohols. For a 90 wt% ethanol solution at 348 K, the permeation flux and separation factor of the membrane were 3.82 kg m-2 h-1 and 73,800, respectively. The high dehydration performances were also obtained for alcohols and low boiling solvents (acetonitrile, acetone, methyl ethyl ketone (MEK) and tetrahydrofuran (THF)). However, the permeation flux and separation factors decreased significantly for high boiling solvents, such as N,N-dimethylacetamide (DMA), N,N-dimethyl formamide (DMF), dimethyl sulfoxide (DMSO) and N-methyl-2-pyrrolidone (NMP). The influences of the water content and temperature on the dehydration performances for the NMP solutions were determined to understand the lower dehydration performances for those solvents. Those results suggest that the lower dehydration performances for the high boiling solvents were attributed to the lower vapor pressures of water and the higher permeances of those solvents. Furthermore, this study proposes that the permeation behaviors through zeolite membranes could be understood by the determination of the effect of temperature on the permeance of individual components.


Sensitivity of perceptuomotor measures for very low birthweight (VLBW < or = 1500 g) pre-schoolers.
This longitudinal study investigated whether very low birthweight (VLBW < or = 1500 g) pre-schoolers with no major handicap differed in cognitive and perceptuomotor development from a control group of normal birthweight children, matched for gender, ethnic origin, birth order, social class and maternal age. There were statistically significant differences between the groups at 24, 30 and 36 months. At all test ages, the VLBW group showed less optimal fine motor skills, and at 36 months, obtained lower IQ scores. The implications of the developmental differences and the sensitivity of the measures are discussed.


Novel compound heterozygous mutations in OCA2 gene associated with non-syndromic oculocutaneous albinism in a Chinese Han patient: a case report.
Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders. The present study aimed to identify the genetic cause of a Chinese Han family with non-syndromic oculocutaneous albinism (OCA). Here, we report an 11-month-old male proband from a Chinese Han non-consanguineous family, who presented with milky skin, yellow white hair, nystagmus, astigmatism, and hypermetropia. We performed the targeted next-generation sequencing (NGS) on the proband and identified two novel compound heterozygous variants (c.1865 T > C (p.Leu622Pro) and exons 17-21 deletion) in OCA2 gene associated with OCA type 2 (OCA2, OMIM 203200). Meanwhile, a previously reported heterozygous mutation (c.4805G > A) in MYO7 gene related with Usher syndrome type 1B was found. The online tools SIFT, PolyPhen-2, and Mutation Taster predicted variant c.1865 T > C was probably damaging. The residue p.Leu622 was in a highly conserved region among species by CLUSTALW. Three-dimensional homology model with I-TASSER indicated that p.Leu622Pro variant disturbed the formation of the α-helix, resulting in a random coil structure. The gross deletion (exons 17-21) in OCA2 gene has was not been reported previously. These two novel variants in OCA2 gene were inherited from each parent respectively, after verification by Sanger sequencing and quantitative PCR (qPCR) in the family. This study indicates the two novel compound heterozygous mutations in OCA2 gene may be responsible for clinical manifestations of OCA2. It expands the mutation spectrum of OCA2 gene and is helpful to screen for large deletions with targeted NGS protocol in monogenic disease. It also assists the genetic counselling, carrier screening and personalized healthcare of the disease.


Modulation of gut microbiota and intestinal immune response in gilthead seabream (Sparus aurata) by dietary bile salt supplementation.
Given their role in lipid digestion, feed supplementation with bile salts could be an economic and sustainable solution to alterations in adiposity and intestinal inflammation generated by some strategies currently used in aquaculture. An important part of the metabolism of bile salts takes place in the intestine, where the microbiota transforms them into more toxic forms. Consequently, we aimed to evaluate the gut immune response and microbial populations in gilthead seabream (Sparus aurata) fed a diet supplemented with a blend of bile salts with proven background as a regulator of lipid metabolism and fat content. After the 90-day feeding trial, a differential modulation of the microbiota between the anterior and posterior intestine was observed. While in the anterior intestine the relative abundance of Desulfobacterota doubled, in the posterior intestine, the levels of Firmicutes increased and Proteobacteria, Actinobacteriota, and Campylobacterota were reduced when supplementing the diet with bile salts. Even so, only in the anterior intestine, there was a decrease in estimated richness (Chao1 and ACE indices) in presence of dietary bile salts. No significant differences were displayed in alpha (Shannon and Simpson indices) nor beta-diversity, showing that bile sales did not have a great impact on the intestinal microbiota. Regarding the gene expression profile in 2 h postprandial-fish, several changes were observed in the analyzed biomarkers of epithelial integrity, nutrient transport, mucus production, interleukins, cell markers, immunoglobulin production and pathogen recognition receptors. These results may indicate the development of an intestinal immune-protective status to tackle future threats. This work also suggests that this immune response is not only regulated by the presence of the dietary bile salts in the intestine, but also by the microbial populations that are in turn modulated by bile salts. After a fasting period of 2 days, the overall gene expression profile was stabilized with respect to fish fed the unsupplemented diet, indicating that the effect of bile salts was transient after short periods of fasting. On the balance, bile salts can be used as a dietary supplement to enhance S. aurata farming and production without compromising their intestinal health.


Nuanced Reporting of Fistulas in Laryngectomy Studies.
Pharyngocutaneous fistula is an important complication of laryngectomy and can vary significantly in severity. Many authors have advocated for the use of vascularized flaps (eg, pectoralis major) to reduce the risk of fistula. Prevention of small, self-limited fistulas may not be worth the morbidity of a vascularized flap in some cases. More nuanced analysis of fistula outcomes, stratified by severity, may enable better surgeon-patient decision making regarding the use of vascularized flaps in laryngectomy.


Role of iduronate-2-sulfatase in glucose-stimulated insulin secretion by activation of exocytosis.
Iduronate-2-sulfatase (IDS) is a lysosomal enzyme expressed in pancreatic islets responsible for the degradation of proteoglycans such as perlecan and dermatan sulfate. Previous findings of our group demonstrated the involvement of IDS in the normal pathway of lysosomal degradation of secretory peptides, suggesting a role of this enzyme in beta-cell secretory functionality. The present study was undertaken to characterize the effect of IDS overexpression on insulin release. INS1E cells were transiently transfected with a construct encoding human IDS (hIDS). hIDS overexpression was associated with a gain of function detected by a reduction in heparan sulfate content. hIDS potentiated the glucose-stimulated insulin secretory response compared with controls (61%) with no changes in insulin mRNA levels or insulin peptide content. Results on quantification of the exocytotic process showed a significant increase in hIDS-transfected cells compared with controls. Furthermore, ultramorphological analysis demonstrated an increase in the number of granules in the immediate vicinity of the plasma membrane in hIDS-transfected cells and a decrease in total vesicles per square micrometer. hIDS overexpression induced phosphorylation of protein kinase C (PKC) alpha and its newly myristoylated alanine-rich C kinase substrate, MARCKS. We conclude that IDS has a role in glucose-stimulated insulin secretion via a mechanism that involves the activation of exocytosis through phosphorylation of PKCalpha and MARCKS.


The treatment of decorative tattoos with the carbon dioxide laser.
The carbon dioxide laser was used in the treatment of 51 patients with decorative tattoos. Sixty-eight treatments were performed under local anaesthesia. Morbidity from treatment was low. Results 6 months after treatment in 44 patients revealed excellent or good results in 24 patients and hypertrophic scarring in three patients. These results confirm the value of this laser in the treatment of tattoos and demonstrate the advantages of this therapy over other treatments currently employed.


Mass Spectrometry-Guided Discovery of Multi-N-Methylated Cyclodecapeptides Auyuittuqamides E-H from Sesquicillium sp. QL0466.
Mass spectrometry-based dereplication and prioritization led to the discovery of four multi-N-methylated cyclodecapeptides, auyuittuqamides E-H (1-4), from a soil-derived Sesquicillium sp. The planar structures of these compounds were elucidated based on analysis of HRESIMS and NMR data. Absolute configurations of the chiral amino acid residues were assigned by a combination of the advanced Marfey's method, chiral-phase LC-MS analysis, and J-based configuration analysis, revealing that 1-4 contain both d- and l-isomers of N-methylleucine (MeLeu). Differentiation of d- and l-MeLeu in the sequence was achieved by advanced Marfey's analysis of the diagnostic peptide fragments generated from partial hydrolysis of 1. Bioinformatic analysis identified a putative biosynthetic gene cluster (auy) for auyuittuqamides E-H, and a plausible biosynthetic pathway was proposed. These newly identified fungal cyclodecapeptides (1-4) displayed in vitro growth inhibitory activity against vancomycin-resistant Enterococcus faecium with MIC values of 8 μg/mL.


Age-related site-specific muscle loss in the thigh and zigzag walking performance in older men and women.
To investigate the relationships between site-specific muscle loss in the thigh, muscle quality and zigzag walking performance, 40 men and 41 women aged 65-79 years had muscle thickness (MTH) measured by ultrasound at nine sites on the anterior and posterior aspects of the body. Skeletal muscle mass (SM) was estimated from an ultrasound-derived prediction equation. Site-specific thigh sarcopenia was calculated using ultrasound-measured MTH at the anterior/posterior aspects of the thigh (AP-MTH ratio). Zigzag walking time (ZWT) and maximum isometric knee extension (KE) and flexion (KF) torques were measured. Muscle quality (torque/thigh SM) and knee joint strength index (torque/body mass) were calculated. There were no significant correlations between SM index and ZWT. However, AP-MTH ratio was inversely correlated (P < 0.05) to ZWT in men (r = -0.335) and women (r = -0.309). ZWT was also inversely correlated (P < 0.05) to KE-strength index in both sexes (men, r = -0.328; women, r = -0.372). Similarly, ZWT was correlated to KF-strength index (r = -0.497) and muscle quality (r = -0.322) in women, but not in men. After adjusting for age, height and body mass, AP-MTH ratio was inversely correlated to ZWT in men (r = -0.325) and tended to be correlated to ZWT in women (r = -0.263). Zigzag walking performance may be associated with site-specific thigh sarcopenia in older men and women.


Transethosomes: A Promising Challenge for Topical Delivery Short Title: Transethosomes for Topical Delivery.
Skin provides an excellent barrier to molecular transport, as the stratum corneum is the most formidable barrier to the passage of most pharmaceuticals. Various attempts have been made to improve drug administration into the body through intact skin. Though very few routes are as attractive as the topical route, drug transport through the skin is challenging. To overcome the challenges, researchers have found a system in which the drug is encapsulated into the vesicle, penetrating deeper into the skin to hit the target site. Vesicular systems like transethosome, an ultra- deformable vesicle (UDV), tend to accumulate in the skin layers. Since transethosomes have small particle size and can easily alter the shape of vesicles compared to other vesicular systems, they can penetrate through the layers of skin. Hence, the drug encapsulated into transethosomes can easily reach the target site. Transethosomes consist of ethanol and phospholipids along with an edge activator. Ethanol and edge activator help to enhance the skin permeation of transethosomes. Various methods of preparation of transethosomes, comparison of transethosomes with other lipid vesicles, characterization of transethosomes, and application of transethosomes have been covered in this review. Transethosomes can deliver a different variety of drugs, such as anticancer, corticosteroids, proteins and peptides, analgesics.


Pregnant women's knowledge, attitude, and practice towards COVID-19 infection prevention in Ethiopia: A systematic review and meta-analysis.
Coronavirus disease (COVID-19) infection during pregnancy causes adverse maternal and perinatal outcomes such as preterm birth, low birth weight, severe illness, intensive care unit admission, mechanical ventilation, and death. Pregnant women's knowledge, attitude, and practice (KAP) towards COVID-19 infection prevention are crucial to ensure the health of the mother and foetus. Therefore, this systematic review and meta-analysis aimed to estimate the pooled prevalence of pregnant women's KAP towards COVID-19 infection prevention in Ethiopia. We searched PubMed, Scopus, Google Scholar, African Online Journal, and Web of Sciences database to retrieve related articles. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline was used. Funnel plot and Eggers test were done to assess publication bias. Cochrane Q-test and I2 statistic were done to chick evidence of heterogeneity. Subgroup analysis was computed based on the study region and year of publication. Data were extracted using a Microsoft Excel spreadsheet and analyzed using STATA version 14 statistical software. Weighted inverse variance random effect model was run to estimate the pooled prevalence of pregnant women's KAP towards COVID-19 infection prevention. A total of 9 studies with 4,103 pregnant women were included. The pooled prevalence of knowledge, attitude, and practice towards COVID-19 infection prevention among pregnant women's in Ethiopia were 60.24% (95% CI; 53.69 to 66.79, I2 = 95%), 62.46% (95% CI; 45.68, 79.23, I2 = 98.8%), and 52.29% (95% CI; 43.91%-60.66% I2 = 96.5%) respectively. Maternal age (AOR = 1.87, 1.40-2.49), residence (AOR = 2.23, 1.50-3.31), secondary and above educational status (AOR = 3.36, 2.46-4.58), good knowledge (AOR = 2.73, 2.18-3.41), and fear of COVID-19 infection (AOR = 2.60, 1.78, 3.80) were factors associated with COVID-19 infection prevention practice among pregnant women's in Ethiopia. The knowledge, attitude, and practice of COVID-19 infection prevention among pregnant women were low. Therefore, policymakers, maternal and child health program planners, and stakeholders should target to improve pregnant women's awareness regarding COVID-19 infection preventive measures.


High-activity radio-iodine labeling of conventional and stealth liposomes.
A new method to label preformed liposomes with high activities of radiohalogenated compounds has been developed. It uses activated esters of simple synthetic molecules that may be readily halogenated, such as Bolton-Hunter reagent (BH), and arginine-containing liposomes. BH, in the form of an activated ester, crosses the liposome membrane to react with arginine inside the liposomes, as demonstrated by thin-layer chromatography and by the fact that saline-containing liposomes, or hydrolyzed BH or the water soluble sulfo-BH afforded only marginal encapsulation yields. Under optimized conditions, between 37 and 55 degrees C, 62 +/- 4% (mean +/- SD) of radiolabeled BH were consistently encapsulated in the liposomes within 30 min. In molar amounts, this corresponds to a mean of 56 nmol of BH per micromol of lipids. Based on achievable specific activity, up to 2.8 GBq of iodine-131 could be entrapped per micromol of lipids. Leakage of radioactivity was very low, with less than 5% of the encapsulated activity released within 6 days at 4 degrees C in phosphate-buffered saline and less than 50% within 24 h in human serum at 37 degrees C. The labeling stability, and the fact that both conventional and PEGylated liposomes can be readily labeled with high doses of radioactivity, will make this technique useful for in vivo targeting applications, such as tumor detection (using iodine-123 or iodine-124) or therapy (with iodine-131 or astatine-211).


Speculations on the early course of evolution.
The proposal that RNA preceded DNA in evolution is more than 15 years old. In light of recent studies on RNA processing (including protein-free reactions), present knowledge about eukaryotic gene structure, and studies comparing ribosomal RNA sequences, we propose a train of events for precellular and early cellular evolution.


Prevalence and clinical implications of bronchiectasis in patients with overlapping asthma and chronic rhinosinusitis: a single-center prospective study.
As a typical "united airway" disease, asthma-chronic rhinosinusitis (CRS) overlap has recently drawn more attention. Bronchiectasis is a heterogeneous disease related to a variety of diseases. Whether bronchiectasis exists and correlates with asthma-CRS patients has not been fully elucidated. The purpose of the study was to explore the presence and characteristics of bronchiectasis in patients with overlapping asthma and CRS. This report describes a prospective study with consecutive asthma-CRS patients. The diagnosis and severity of bronchiectasis were obtained by thorax high-resolution computed tomography (HRCT), the Smith radiology scale and the Bhalla scoring system. CRS severity was evaluated by paranasal sinus CT and the Lund-Mackay (LM) scoring system. The correlations between bronchiectasis and clinical data, fraction of exhaled nitric oxide, peripheral blood eosinophil counts and lung function were analyzed. Seventy-two (40.91%) of 176 asthma-CRS patients were diagnosed with bronchiectasis. Asthma-CRS patients with overlapping bronchiectasis had a higher incidence rate of nasal polyps (NPs) (P = 0.004), higher LM scores (P = 0.044), higher proportion of ≥ 1 severe exacerbation of asthma in the last 12 months (P = 0.003), lower postbronchodilator forced expiratory volume in one second (FEV1) % predicted (P = 0.006), and elevated peripheral blood eosinophil counts (P = 0.022). Smith and Bhalla scores were shown to correlate positively with NPs and negatively with FEV1% predicted and body mass index. Cutoff values of FEV1% predicted ≤ 71.40%, peripheral blood eosinophil counts > 0.60 × 109/L, presence of NPs, and ≥ 1 severe exacerbation of asthma in the last 12 months were shown to differentiate bronchiectasis in asthma-CRS patients. Bronchiectasis commonly overlaps in asthma-CRS patients. The coexistence of bronchiectasis predicts a more severe disease subset in terms of asthma and CRS. We suggest that asthma-CRS patients with NPs, severe airflow obstruction, eosinophilic inflammation, and poor asthma control should receive HRCT for the early diagnosis of bronchiectasis.


Noble-Metal-Free C-H Allylation of Tetrahydroisoquinolines Using a Cobalt-Organophotoredox Dual Catalyst System.
Metallaphotoredox-catalyzed allylation represents an emerging synthetic methodology that enables allylic substitution using nucleophilic radical species. The C-H allylation of N-aryl tetrahydroisoquinolines is an innovative example in this area and allows access to synthetically useful precursors for the further derivatization of tetrahydroisoquinolines. However, previous methods have required the use of noble metals, which has hampered their application due to concerns over their sustainability. Here we report the C-H allylation of N-aryl tetrahydroisoquinolines using a cobalt/organophotoredox dual catalyst system. Based on precedent, control experiments and controlled irradiation experiments, a mechanism for the cobalt/photoredox-catalyzed allylation that involves a π-allyl cobalt complex is proposed.


Atopic dermatitis: from new pathogenic insights toward a barrier-restoring and anti-inflammatory therapy.
Recent published work on atopic dermatitis focusing on the pathogenesis and epidemiology, which have a direct effect on treatment, is presented. Worldwide, the incidence of atopic dermatitis is still increasing, although a plateau seems to be reached in certain industrialized countries. In addition to the filaggrin missense mutations, other mechanisms responsible for impaired skin-barrier function have been identified. These findings have a direct impact on therapy as well as behavior strategies. The barrier defect and the resulting inflammation in the skin, in particular interleukin (IL)-17-mediated responses, play an important role in promoting allergic airway responses and food allergy. These recent findings on epithelial barrier defects, as well as cells and cytokines important for atopic dermatitis development, provide new insights into its pathogenesis, help to characterize patient subgroups, and identify new therapeutic strategies.


Raptorial jaws in the throat help moray eels swallow large prey.
Most bony fishes rely on suction mechanisms to capture and transport prey. Once captured, prey are carried by water movement inside the oral cavity to a second set of jaws in the throat, the pharyngeal jaws, which manipulate the prey and assist in swallowing. Moray eels display much less effective suction-feeding abilities. Given this reduction in a feeding mechanism that is widespread and highly conserved in aquatic vertebrates, it is not known how moray eels swallow large fish and cephalopods. Here we show that the moray eel (Muraena retifera) overcomes reduced suction capacity by launching raptorial pharyngeal jaws out of its throat and into its oral cavity, where the jaws grasp the struggling prey animal and transport it back to the throat and into the oesophagus. This is the first described case of a vertebrate using a second set of jaws to both restrain and transport prey, and is the only alternative to the hydraulic prey transport reported in teleost fishes. The extreme mobility of the moray pharyngeal jaws is made possible by elongation of the muscles that control the jaws, coupled with reduction of adjacent gill-arch structures. The discovery that pharyngeal jaws can reach up from behind the skull to grasp prey in the oral jaws reveals a major innovation that may have contributed to the success of moray eels as apex predators hunting within the complex matrix of coral reefs. This alternative prey transport mode is mechanically similar to the ratcheting mechanisms used in snakes--a group of terrestrial vertebrates that share striking morphological, behavioural and ecological convergence with moray eels.


1,10-Phenanthroline-5,6-Dione-Based Compounds Are Effective in Disturbing Crucial Physiological Events of Phialophora verrucosa.
Phialophora verrucosa is a dematiaceous fungus able to cause chromoblastomycosis, phaeohyphomycosis and mycetoma. All these fungal diseases are extremely difficult to treat and often refractory to the current therapeutic approaches. Therefore, there is an urgent necessity to develop new antifungal agents to combat these mycoses. In this context, the aim of the present work was to investigate the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based derivatives [Ag(phendione)2]ClO4 = ([Ag(phendione)2]+) and [Cu(phendione)3](ClO4)2.4H2O = ([Cu(phendione)3]2+) on crucial physiological events of P. verrucosa conidial cells. Using the CLSI protocol, we have shown that phendione, [Ag(phendione)2]+ and [Cu(phendione)3]2+ were able to inhibit fungal proliferation, presenting MIC/IC50 values of 12.0/7.0, 4.0/2.4, and 5.0/1.8 μM, respectively. [Cu(phendione)3]2+ had fungicidal action and when combined with amphotericin B, both at sub-MIC (½ × MIC) concentrations, significantly reduced (~40%) the fungal growth. Cell morphology changes inflicted by phendione and its metal-based derivatives was corroborated by scanning electron microscopy, which revealed irreversible ultrastructural changes like surface invaginations, cell disruption and shrinkages. Furthermore, [Cu(phendione)3]2+ and [Ag(phendione)2]+ were able to inhibit metallopeptidase activity secreted by P. verrucosa conidia by approximately 85 and 40%, respectively. Ergosterol content was reduced (~50%) after the treatment of P. verrucosa conidial cells with both phendione and [Ag(phendione)2]+. To different degrees, all of the test compounds were able to disturb the P. verrucosa conidia-into-mycelia transformation. Phendione and its Ag+ and Cu2+ complexes may represent a promising new group of antimicrobial agents effective at inhibiting P. verrucosa growth and morphogenesis.


[Pictorial essay: Evaluation of intracranial lipomatous masses with MRI].
The lipid containing tumors of the intracranial region are rare and usually benign masses. The major lipomatous masses may be listed as lipomas, dermoid cysts, and the tumors with lipoid metaplasia, most common of which is lipomatous meningioma. MRI characteristics of these rare entities have been presented, and the underlying reasons for those appearances on MRI have been discussed in this pictorial review.


Free and pedicled flaps for reconstruction of the weightbearing sole of the foot: a comparative analysis of functional results.
Reconstruction of the weightbearing sole of the foot is complex and requires soft tissue that is resistant to weight, pressure, and shear stress. Despite a variety of flap types and techniques, it is still challenging to meet these demands. The present retrospective study included 21 patients after reconstruction of plantar tissue defects from 2001 to 2011. The outcome was evaluated using the lower extremity functional scale, Weber score, pedobarography, assessment of shifting, and sensory recovery. The patients' quality of life was documented using the SF-36 questionnaire. Plantar reconstruction was performed using 12 free and 9 pedicled flaps. No differences in functional results were observed between the flap types, despite a better sense of temperature in the adipocutaneous flaps. The extent of flap shifting was independent of the flap type and did not correlate with the functional results. Pedobarography showed a tendency for increased peak pressure and prolonged contact time in the reconstructed weightbearing plantar areas compared with the sound feet and a control group. The present study found no relevant differences in the functional results between different flap types and free or pedicled techniques. Flap selection should be based on the individual requirements and availability of donor sites.


Unexplained protracted infant deaths.
Seven unexplained, protracted infant deaths with similar clinical, biochemical and laboratory characteristics are described, being similar to other groups reported previously. Although autopsy examination frequently revealed extensive tissue damage, a primary cause of death could not be elucidated. It is argued that this condition represents a protracted form of conventional cot death and should be considered in any severely shocked infant where the cause is not readily identifiable. Many of the clinical and pathological manifestations are similar to those described in endotoxic shock and a small intestinal mucosal abnormality on histology of unknown pathogenesis was common.


Multifocal alterations of white matter accompany the transition from normal cognition to dementia in Parkinson's disease patients.
The purpose of the present study was to investigate the pattern of white matter (WM) changes associated with Parkinson's disease (PD)-related cognitive impairment by using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) measures. Diffusion Tensor Imaging (DTI) was performed in 21 PD-patients with dementia (PDD) and in an age-matched control group including 40 PD-patients without dementia (PD-CTRL). The Parkinson's disease-Cognitive Rating Scale (PD-CRS) was used for patients' neuropsychological assessment. Local microstructural WM differences associated with the presence of cognitive impairment were tested using tract-based spatial statistics analysis. Multiple regression models investigated the association of DTI indices with total PD-CRS score, PD-CRS raw items and other clinical measures across the whole study sample. Significant FA decreases were found in PDD compared to PD-CTRL patients mainly in the body of corpus callosum, corona radiata and cingulum. Lower PD-CRS score was significantly associated with decreased FA, MD and AD values in multiple WM tracts primarily located in prefrontal and limbic areas as well as across the corpus callosum. Lower performance in specific PD-CRS raw items was also associated with FA decreases in major WM tracts. The results suggest that multifocal microstructural changes of WM accompany the transition from normal to demented cognitive state in PD-patients. The corpus callosum, the corona radiata and the cingulum are among the regions mostly affected during this course. A progressive axonal degeneration is proposed as a key underlying mechanism.


Should the Woodward-Hoffmann Rules be Applied to Mechanochemical Reactions?
Since decades, pericyclic reactions have been well-understood by means of the Woodward-Hoffmann rules and their classification as thermally or photochemically "allowed" or "forbidden". Recently, stunning results on such reactions subject to mechanochemical activation by external forces instead of heat or light have revealed reaction pathways at sufficiently large forces, which are not expected from the Woodward-Hoffmann rules. This led to the much reiterated idea that the "Woodward-Hoffmann rules are broken in mechanochemistry". Here, by studying ring-opening of cyclopropane, we show that the electronic structure underlying the dis- and conrotatory pathways, which are greatly distorted upon applying forces to an extent that eventually the "thermally forbidden" process becomes "mechanochemically allowed", does not change along both pathways. It is rather the mechanical work that lowers the activation barrier of the thermally forbidden conrotatory process relative to the disrotatory one at large forces.


Focal Myositis of the Deltoid Muscle: The Role of Magnetic Resonance Imaging for Diagnosis.
Focal myositis is a rare condition first described by Heffner et al., in 1977, as a self-limiting condition of unknown aetiology. It presents as an inflammatory pseudo tumour in skeletal muscle and can present diagnostic difficulty, being commonly mistaken for tissue of vascular, inflammatory, or neoplastic origin. Diagnosis is traditionally confirmed by muscle biopsy. We present a case where magnetic resonance imaging (MRI) was used to confirm the diagnosis without need for biopsy. A 19-year year-old female presented with a two2-year history of intermittent swelling of the deltoid associated with pain and tenderness to palpation. . There was no history of trauma or systemic illness. . She was symptomatic with pain, swelling, and tenderness over the left deltoid with no restriction in range of movement of the shoulder or neck. Plain radiographs were normal and MRI magnetic resonance imaging showed diffuse odeamatousedematous signal changes on the proton density weighted sequence within the deltoid muscle and no plexiform neurofibroma. Nerve conduction and electromyography studies were within normal limits excluding an axillary nerve lesion. The patient underwent extensive screening for connective tissue disorders and creatine kinase and lactate dehydrogenase levels were within limits. The patient underwent neuromuscular specialist review confirming that this appeared to be a rare case of focal myositis in the deltoid. . The serial MRI scans confirmed resolution of the condition. Focal myositis of the deltoid is a rare cause of shoulder pain. . We have shown that sequential MRI scanning can obviate the need for muscle biopsy, which has historically been required for diagnostic confirmation. The MRI appearance on the proton density weighted sequence showed diffuse odeamatousedematous signal changes and no plexiform neurofibroma within the deltoid and is a description that has not been previously used for this rare diagnosis.


Management of diabetic patients by general practitioners in France 1997: an epidemiological study.
To describe the characteristics of diabetic patients, the associated risk factors, the complications of the disease and its management by general practitioners (GPs) in France, a randomised sample of French GPs was asked to record data on all consecutive diabetic patients attending a regular visit within 3 months. Data were obtained by interview, clinical examination and usual follow-up complementary examinations of the patients. Patients were classified into 3 groups:, patients treated with insulin and considered to have type 1 diabetes, [2i], insulin-treated patients expected to have type 2 diabetes, [2d], patients with type 2 diabetes and not treated with insulin. Data from 7540 diabetic out-patients were recorded by 3084 GPs: 657 patients (8.7%) belonged to group 1, 1383 patients (18.3%) to group 2i and 5351 (71.0%) to group 2d. Patients, including 53.7%, [2i] 54.1%, and [2d] 56.5% of men, were (mean +/- SE) 58.8 +/- 0.7, [2i] 63.4 +/- 0.3, and [2d] 63.9 +/- 0.2 years old, respectively. Duration of diabetes was 15.9 +/- 0.4, [2i] 11.4 +/- 0.2, and [2d] 10.1 +/- 0.1 yr. The last fasting blood glucose level (laboratory assay) was 1.61 +/- 0.02, [2i] 1.68 +/- 0.01, and [2d] 1.61 +/- 0.01 g/L, and the last HbA1c 8.5 +/- 0.1, [2i] 8.1 +/- 0.1, and [2d] 7.8 +/- 0.1%, respectively. Tobacco smoking was observed in 19.2%, [2i] 13.1%, and [2d] 12.6% of the patients, hypertension in 39.6%, [2i] 55.9%, and [2d] 58.6%, micro- or macro-albuminuria in 18.6%, [2i] 11. 2%, and [2d] 9.5%, retinopathy in 31.1%, [2i] 12.9%, and [2d] 8.6%, and history of coronary artery disease in 16.3%, [2i] 15.0%, and [2d] 12.8%. Self-monitoring of blood glucose was performed by 93.2%, [2i] 37.9%, and [2d] 16.9% of the patients. During the previous 12 months, a visit had been performed with a diabetologist in 54.0%, [2i] 20.7%, and [2d] 12.9% of the patients, with an ophthalmologist in 62.9%, [2i] 51.5%, and [2d] 49.4%. These results underline the specific characteristics of French diabetic patients. A high prevalence of uncontrolled risk factors, mainly hypertension, contrasts with a relatively low frequency of micro- and macro-angiopathy, maybe underestimated by non-systematic routine follow-up. Closer collaboration between GPs and specialists should be developed to improve the management and care of diabetic patients in France.


Observations on the structure and histochemistry of the skin of Mystus gulio (Ham.) (Osteichthyes: Siluriformes, Bagridae).
The skin of Mystus gulio (Ham.) is typical of siluroids in not having any scales. Large number of mucous cells and sacciform granular cells, interspersed with taste buds, were found in the epidermis. Histochemical tests showed the presence of weakly sulphated mucopolysaccharides in the mucous cells, while the sacciform granular club cells were found to be proteinaceous, with a small amount of lipids and phospholipids. The dermis is composed of a stratum laxum and a stratum compactum. The subcutis was found to consist of loosely arranged collagen fibres and fat cells.


Cutaneous macroglobulinosis: a report of 2 cases.
Specific cutaneous lesions of Waldenström macroglobulinemia are rare and include neoplastic cell infiltrates, IgM bullous disease, and so-called IgM-storage papules, which characterize cutaneous macroglobulinosis (CM). We report 2 patients with CM. In patient 1, CM started as small papules, as reported in most of the previously published case studies of CM. In patient 2, lesion evolution was remarkable by its severity, with large ulcerated nodules, and the disease progressed rapidly. As mentioned for half the previously described patients, peripheral neuropathy was suspected in patient 2 and demonstrated in patient 1, with production of antibodies to myelin-associated glycoprotein. To the best of our knowledge, rituximab treatment of Waldenström macroglobulinemia associated with CM has not been described previously. Rituximab caused complete remission of the lesions in patient 1, whereas disease rapidly progressed in patient 2, and the patient died. These observations suggest that evolution of the cutaneous IgM-storage lesions reflects that of the underlying Waldenström macroglobulinemia, and CM is not a prognostic marker.


Preoperative measurement of the intrathrombotic pressure of a thrombosed popliteal artery aneurysm for decision of surgical indication.
To evaluate the risk of rupture of a 77 mm thrombosed popliteal artery aneurysm (PAA) in an 82-year-old woman, the aneurysm was percutaneously punctured and the intrathrombotic pressure (ITP) was measured preoperatively. The percentage of the mean ITP to the mean brachial artery pressure was 80%. The aneurysm was judged to have the risk of rupture, and replacement with a prosthetic graft was performed. The percentages of the mean ITP to the mean radial artery pressure and to the mean femoral artery pressure measured intraoperatively were 83% and 71%, respectively, which approximated to the percentage measured preoperatively. PAA may have the risk of rupture even though thrombosed, and preoperative measurement of the ITP might be useful to decide surgical indication.


[Mediocarpal instability].
The author reports his personal experience of eleven cases of midcarpal instability. Diagnosis was essentially based on dynamic radiological investigations of the wrist with distraction and posterior "drawer" movements. Damage to the anterior capsuloligamentous complex is the underlying cause. According to the predominance on the ulnar or radial side, one may speak of anteromedial or anterolateral midcarpal instability. Management differs in the case of recent injuries which should be treated on a nonoperative basis as compared to the case of longstanding lesions whose treatment is difficult. It seems as though only intercarpal arthrodesis is the solution to adequate stabilization of the lesions. To avoid loss of motion, the author suggests the possibility of palliative treatment by arthroplastic resection of the proximal row of the carpus, which, in this type of indication, seems to be a last resort.


Optimized Monte Carlo simulations for voxel-based internal dosimetry.
Objective.The scientific community has considered internal dosimetry by the Monte Carlo method the gold standard. However, there is a trade-off between simulation processing time and the statistical quality of the results that makes it a challenge to obtain accurate absorbed dose values in some situations, such as dose estimation in organs affected by cross-irradiation or limited computing power. Variance reduction techniques are used to reduce computational processing time without impairing the statistical quality of the results, such as tracking energy cutoff, secondary particle production threshold, and parallelism of different types of emissions from radionuclides.Approach.In this work, GATE Monte Carlo code and its variance reduction techniques were evaluated to calculateSvalues of organs from the international commission on radiological protection (ICRP) report 110 male phantom for the lutetium-177, iodine-131, yttrium-90, and radium-223 radionuclides. The results are compared with the data from the OpenDose collaboration.Main results.A cutoff of 5 MeV for local electron deposition and 2.0 mm of secondary particle production range resulted in a computational efficiency increase of 7.9 and 1.05 times, respectively. Simulation of ICRP 107 spectra-based source proved to be about 5 times more efficient when compared to a decay simulation usingG4RadioactiveDecay(Geant4-based radioactive decay processes). Track length estimator (TLE) and split exponential track length estimator (seTLE) techniques were used to calculate the absorbed dose of photon emissions, resulting in computational efficiency up to 29.4 and 62.5 times higher when compared to traditional simulations, respectively. In particular, the seTLE technique accelerates the simulation time by up to 1426 times, achieving a statistical uncertainty of 10% in volumes affected by cross-irradiation.Significance.The variance reduction techniques used in this work drastically reduced the simulation time and maintained the statistical quality of the calculated absorbed dose values, proving the feasibility of the use of the Monte Carlo method in internal dosimetry under challenging situations and making it viable for clinical routine or web applications.


Early Gesture and Vocabulary Development in Infant Siblings of Children with Autism Spectrum Disorder.
This study examined longitudinal growth in gestures and words in infants at heightened (HR) versus low risk (LR) for ASD. The MacArthur-Bates Communicative Development Inventory was administered monthly from 8 to 14 months and at 18 and 24 months to caregivers of 14 HR infants diagnosed with ASD (HR-ASD), 27 HR infants with language delay (HR-LD), 51 HR infants with no diagnosis (HR-ND), and 28 LR infants. Few differences were obtained between LR and HR-ND infants, but HR-LD and HR-ASD groups differed in initial skill levels and growth patterns. While HR-LD infants grew at rates comparable to LR and HR-ND infants, growth was attenuated in the HR-ASD group, with trajectories progressively diverging from all other groups.


Alglucosidase alfa: Long term use in the treatment of patients with Pompe disease.
Pompe disease is a lysosomal storage disorder characterized by muscle weakness and cardiomyopathy. It shows a broad variability regarding the clinical severity as well as the age of onset. In the past, two different recombinant enzyme preparations have been developed for the treatment of Pompe patients: alpha-glucosidase, produced in rabbit milk, and alpha-glucosidase, produced in Chinese hamster ovary (CHO) cell lines. The CHO enzyme received marketing approval in 2006 after it was proven to be effective in ameliorating muscle strength and improving heart function. The other has not been approved. The clinical efficacy of this enzyme preparation could be confirmed by several clinical trials in patients with different age of onset and disease severity. Enzyme replacement therapy, however, has its limitations due to unsatisfactory access of recombinant alpha-glucosidase to the muscle cells and due to the formation of antibodies. To overcome these therapeutic restraints, the development of a more effective enzyme preparation may become necessary.


Effect of Γ-aminobutyric acid on kidney injury induced by renal ischemia-reperfusion in male and female rats: Gender-related difference.
The most important cause of kidney injury is renal ischemia/reperfusion injury (IRI), which is gender-related. This study was designed to investigate the protective role of Γ-aminobutyric acid (GABA (against IRI in male and female rats. Thirty-six female and male wistar rats were assigned to six experimental groups. The IRI was induced by clamping renal vessels for 45 min then was performed reperfusion for 24 h. The group sex posed to IRI were pretreated with GABA and were compared with the control groups. Serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score increased in the IRI alone groups, (P < 0.05), while GABA decreased these parameters in female significantly (P < 0.05), but not in male rats. Uterus weight decreased significantly in female rats treated with GABA. Testis weight did not alter in male rats. Serum level of nitrite and kidney level of malondialdehyde (MDA) had no significant change in both female and male rats. Kidney level of nitrite increased significantly in female rats experienced IRI and serum level of MDA increased significantly in males that were exposed to IRI (P < 0.05). GABA could ameliorate kidney injury induced by renal IRI in a gender dependent manner.


Intermittent MEK inhibition for the treatment of metastatic uveal melanoma.
Uveal melanoma (UM) is associated with poor outcomes in the metastatic setting and harbors activating mutations resulting in upregulation of MAPK signaling in almost all cases. The efficacy of selumetinib, an oral allosteric inhibitor of MEK1/2, was limited when administered at a continual dosing schedule of 75 mg BID. Preclinical studies demonstrate that intermittent MEK inhibition reduces compensatory pathway activation and promotes T cell activation. We hypothesized that intermittent dosing of selumetinib would reduce toxicity, allow for the administration of increased doses, and achieve more complete pathway inhibition, thus resulting in improved antitumor activity. We conducted a phase Ib trial of selumetinib using an intermittent dosing schedule in patients with metastatic UM. The primary objective was to estimate the maximum tolerated dose (MTD) and assess safety and tolerability. Secondary objectives included assessment of the overall response rate (RR), progression-free survival (PFS) and overall survival (OS). Tumor biopsies were collected at baseline, on day 3 (on treatment), and between days 11-14 (off treatment) from 9 patients for pharmacodynamic (PD) assessments. 29 patients were enrolled and received at least one dose of selumetinib across 4 dose levels (DL; DL1: 100 mg BID; DL2: 125 mg BID; DL3: 150 mg BID; DL4: 175 mg BID). All patients experienced a treatment-related adverse event (TRAE), with 5/29 (17%) developing a grade 3 or higher TRAE. Five dose limiting toxicities (DLT) were observed: 2/20 in DL2, 2/5 in DL3, 1/1 in DL4. The estimated MTD was 150 mg BID (DL3), with an estimated probability of toxicity of 29% (90% probability interval 16%-44%). No responses were observed; 11/29 patients achieved a best response of stable disease (SD). The median PFS and OS were 1.8 months (95% CI 1.7, 4.5) and 7.1 months (95% CI 5.3, 11.5). PD analysis demonstrated at least partial pathway inhibition in all samples at day 3, with reactivation between days 11-14 in 7 of those cases. We identified 150 mg BID as the MTD of intermittent selumetinib, representing a 100% increase over the continuous dose MTD (75 mg BID). However, no significant clinical efficacy was observed using this dosing schedule.


A new photoproduct of 5-methylcytosine and adenine characterized by high-performance liquid chromatography and mass spectrometry.
The UV portion of sunlight is mutagenic and can modify DNA by producing various photoproducts. UV photodamage often occurs at dipyrimidine sites, to give cyclobutane, pyrimidine-(6-4)-pyrimidone (6-4), and pyrimidine-(6-4)-Dewar pyrimidone (Dewar) photoproducts, and at TA and AA sites. There is no reported evidence, however, of UV photoproduct formation between C or 5-methylC ((m)C) and A. Irradiation of d(GTAT(m)CATGAGGTGC) with UVB light at physiological pH gives an unexpected photoproduct that undergoes fast thermal deamination but does not revert to its original structure under UVC irradiation. Evidence from nuclease P1 digestion coupled with electrospray ionization (ESI)-MS/MS is in accord with product formation between (m)C and A. HPLC analysis indicates that deamination gives a T<>A photoproduct that coelutes on reverse-phase chromatography with the well-known TA* photoproduct, formed from an initial [2 + 2] reaction between C5-C6 and C6-C5 of the adjacent thymine and adenine [as shown by Zhao , X. , et al. ( 1996 ) Nucleic Acids Res. 24 , 1554 - 1560 and Davies , R. J. , et al. ( 2007 ) Nucleic Acids Res. 35 , 1048 - 1053 ]. Furthermore, the deamination product of the unknown (m)C<>A photoproduct and the TA* photoproduct undergo nearly identical fragmentation in tandem MS. The evidence, taken together, indicates that the deamination product of the unknown (m)CA photoproduct has the same chemical structure as the TA* photoproduct. Therefore, the unknown photoproduct is referred to as the (m)CA* photoproduct, which, upon deamination, gives the TA* photoproduct.


Research Advances in the Analysis of Estrogenic Endocrine Disrupting Compounds in Milk and Dairy Products.
Milk and dairy products are sources of exposure to estrogenic endocrine disrupting compounds (e-EDCs). Estrogenic disruptors can accumulate in organisms through the food chain and may negatively affect ecosystems and organisms even at low concentrations. Therefore, the analysis of e-EDCs in dairy products is of practical significance. Continuous efforts have been made to establish effective methods to detect e-EDCs, using convenient sample pretreatments and simple steps. This review aims to summarize the recently reported pretreatment methods for estrogenic disruptors, such as solid-phase extraction (SPE) and liquid phase microextraction (LPME), determination methods including gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), Raman spectroscopy, and biosensors, to provide a reliable theoretical basis and operational method for e-EDC analysis in the future.


[Isolation and enrichment of hematopoietic stem/progenitor cells from human placenta tissue].
The aim of this study was to establish the standard protocols for isolating and enriching hematopoietic stem/progenitor cells (HSPC) from human placenta tissue (PT). Single-cell suspension from of human PT was prepared by mechanical method combined with collagenase digestion. Mononucleated cells (MNC) derived from PT were separated by hydroxyethyl starch (6% HES), then the three cell subsets of different immunophenotypes (CD34(-), CD34(+)CD38(-), CD34(+)CD38(+)) contained in MNC were isolated by Magnetic Activated Cell Sorting (MACS). The cell immunophenotype of each sorting steps was analyzed by flow cytometer (FCM). The cell enrichment and recovery rate of each sorting step were calculated. The results showed that MNC could be harvested up to (12.30 +/- 3.51) x 10(8) from a single-cell suspension of human PT by mechanical method and collagenase digestion, no significant difference existed as compared with umbilical cord blood (UCB) initial sample [(8.86 +/- 5.38) x 10(8)], but the percentage of CD34(+) cells in MNC of human PT was (3.93 +/- 2.31)%, much higher than that in UCB [(0.44 +/- 0.29)%] (P < 0.001). recovery rate of MNC and CD34(+) cells from PT after separation with 6% HES were (45.3 +/- 11.7)% and (51.1 +/- 9.8)%, respectively. After MNC being sorted by MACS, the enrichment and recovery rate of CD34(+) cells in CD34(+) group were (73.4 +/- 14.1)% and (52.7 +/- 11.7)% respectively. It is concluded that the protocols established here for isolating and enriching hematopoietic stem/progenitor cells from human placenta can acquire HSPC with high abundance, enrichment and viability and may be a useful reference of isolating methods for future related study.


Chlorhexidine Mucoadhesive Buccal Tablets: The Impact of Formulation Design on Drug Delivery and Release Kinetics Using Conventional and Novel Dissolution Methods.
Oropharyngeal candidiasis (OPC) is a mucosal infection caused by Candida spp., and it is common among the immunocompromised. This condition is mainly treated using oral antifungals. Chlorhexidine (CHD) is a fungicidal and is available as a mouth wash and oral gel. It is used as an adjuvant in the treatment of OPC due to the low residence time of the current formulations. In this study, its activity was tested against C. albicans biofilm and biocompatibility with the HEK293 human cell line. Then, it was formulated as mucoadhesive hydrogel buccal tablets to extend its activity. Different ratios of hydroxypropyl methylcellulose (HPMC), poloxamer 407 (P407), and three different types of polyols were used to prepare the tablets, which were then investigated for their physicochemical properties, ex vivo mucoadhesion, drug release profiles, and the kinetics of drug release. The release was performed using Apparatus I and a controlled flow rate (CFR) method. The results show that CHD is biocompatible and effective against Candida biofilm at a concentration of 20 µg/mL. No drug excipient interaction was observed through differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The increase in P407 and polyol ratios showed a decrease in the swelling index and an increase in CHD in vitro release. The release of CHD from the selected formulations was 86-92%. The results suggest that chlorhexidine tablets are a possible candidate for the treatment of oropharyngeal candidiasis.


Use of an ocular wound chamber for the prevention of exposure keratopathy in a guinea pig model.
Current therapies available to treat and heal ocular surface injuries and periocular burns are frequently inadequate, costly, and labor intensive. To address these limitations, we have employed a flexible, semitransparent ocular wound chamber (OWC) to provide protection as well as a watertight seal to allow for the constant delivery of therapeutics to the ocular surface and surrounding periocular tissue. This study demonstrates the safety and utilization of the OWC on uninjured eyes and in our exposure keratopathy model. For initial safety studies (N = 3 per group), the eyelids remained intact and the eye uninjured. A blepharotomy (N = 6 per group) was performed to remove the upper and lower eyelids surrounding the left (OS) eye to create our exposure keratopathy model. Right (OD) eyes served as uninjured controls in all studies. Following OWC placement, 0.5 mL HPMC gel or balanced saline solution (BSS) was injected into the chamber. Animals were monitored daily and fully assessed via white light, fluorescein, and OCT imaging at least through 72 hours post OWC placement. In studies that included a blepharotomy, skin samples were analyzed by multiplex cytokine analysis. Results of safety experiments revealed no significant differences between treatment groups in corneal thickness, fluorescein staining, OCT imaging, or histological eye or skin sections when compared to control eyes. In our exposure keratopathy model, OWC treated eyes showed significantly less fluorescein uptake and also were found to have significantly lower levels of cytokines IL-13 and IL-5 in skin samples. These results demonstrate for the first time that treatment using the OWC device is not only safe, but significantly protects against blepharotomy-induced exposure keratopathy. As a whole, this study advances our overall efforts to develop a feasible solution to treat ocular surface injuries, infections, and periocular burns.


Strong epigenetic similarity between maize centromeric and pericentromeric regions at the level of small RNAs, DNA methylation and H3 chromatin modifications.
Both kinetochore function and sister chromatid cohesion can depend upon pericentromere chromatin structure, and factors associated with heterochromatin have been proposed to have general, conserved roles in distinguishing centromeres and pericentromeres and in conferring pericentromere-intrinsic functions. We applied genome-wide sequencing approaches to quantify RNA expression, DNA methylation and histone modification distributions in maize (Zea mays), focusing on two maize chromosomes with nearly fully sequenced centromeres and pericentromeres. Aside from the presence of the Histone H3 variant common to all centromeres, Centromeric Histone H3 (CENH3), we found no RNA expression or chromatin modifications that clearly differentiate pericentromeres from either centromeres or from chromosome arms, nor did we identify an epigenetic signature that accurately predicts CENH3 location. RNA expression and chromatin modification frequencies were broadly associated with distance from centromeres, gradually peaking or dipping toward arms. When interpreted in the context of experimental data from other systems, our results suggest that centromeres may confer essential functions (such as cohesion retention) to flanking sequence regardless of the local heterochromatin profile.


[Post-traumatic retrograde amnesia].
A case of post traumatic retrograde amnesia is described. The patient presented after an initial coma a global amnesia, but the fixation deficit rapidly disappeared, and a severe retrograde amnesia dating back to childhood experience and learning remained the main symptom. Amnesia for remote events was associated with didactic memory deficit and, at a lesser degree, with a verbal memory deficit. Recovery of fixation allowed a progressive relearning. This pattern of impairment was recently related to mesencephalic lesions, but we think that the role of temporal lobe involvement cannot be neglected.


Diagnosis of Dopamine in Brain Neuro Cell Using a Nafion-immobilized Carbon Electrode.
Nafion immobilized onto a graphite pencil carbon electrode (NPE) was used to a voltammetric assay of dopamine. The optimum analytical conditions of 150 Hz frequency, 150 mV amplitude, -2.0 V accumulation potential and 15 mV increment potential were obtained. The SW working range was attained to 0.0-80.0 ugL-1 and the CV range of 0.0-90 mgL-1. The statistic relative standard deviation of the 10.0mgL-1 dopamine was 0.041 (n = 20) at the optimum conditions. The analytical detection limit (S/N) was attained to 0.49 ugL-1 (2.62×10-9 M). The developed method was applied to diagnostic assay at the fish brain core and diluted nerve tissue within a pre-concentration time of 60 sec.


Update on the 2009 pandemic influenza A H1N1 in children.
To provide an updated review of the epidemiology, clinical presentations, and outcomes of the 2009 pandemic influenza A H1N1 in children. The majority of cases of 2009 pandemic influenza A H1N1 in children have been mild. However, neurological complications, hospitalization, and even deaths have been reported in children. Death and severe illnesses have mostly occurred in children below 5 years of age and children with high-risk conditions. Coinfections with bacteria have also been reported. Most strains are sensitive to oseltamivir and all to zanamivir. Even though the majority of cases of 2009 pandemic influenza A H1N1 are mild, severe disease does occur in children. In addition, neurological complications and coinfection with bacteria exist. Treatment with antiviral medications should be initiated within 48 h to be most effective. When pandemic H1N1 vaccines become available, the safety and efficacy of these vaccines in this vulnerable population will be important to document.


Prospective ultrasonographic study of blood flow and testicular volume in patients submitted to surgical repair of inguinal hernia without using prosthesis.
To evaluate the behavior of arterial circulation and testicular volume in patients submitted to conventional inguinal hernia repair without the use of a synthetic prosthesis to reinforce the posterior wall. A prospective observational clinical trial was performed on 26 male patients with unilateral inguinal hernia types I and II by the Nyhus classification, who underwent surgical correction using the modified Bassini technique. Bilateral Doppler ultrasonography was performed preoperatively, at the third and at the sixth postoperative month. The studied variables were: systolic peak velocity (SPV), diastolic peak velocity (DPV), resistance index (RI), pulsatility index (PI) and testicular volume. There were no statistically significant changes over time in the variables studied on the operated side: SPV (p = 0.916), DPV (p = 0.304), RI (p = 0.879), PI (p = 0.475), and testicular volume (p = 0.100). The variables on the control side also did not change statistically until the sixth postoperative month: SPV (p = 0.784), DPV (p = 0.446), RI (p = 0.672), PI (p = 0.607), and testicular volume (p = 0.413). Surgical correction of the inguinal hernia without the use of a prosthesis does not cause alterations in vascularization and testicular volume in the first six months postoperatively.


Effect of a single oral dose of aspirin on the platelet aggregation response to arachidonic acid.
1 The platelet aggregation response to arachidonic acid ex vivo was measured in six volunteers daily before and for 10 days after a single oral dose of 600 mg aspirin. 2 Arachidonic acid induced aggregation of platelets from all subjects before aspirin and aggregation occurred after an interval which varied inversely with the concentration of arachidonic acid. No aggregation occurred for 4 days after aspirin; a reduced response, compared with pre-aspirin values, was obtained on the 5th, 6th and 8th day. The values on days 7, 9 and 10 were not consistently different from the pre-aspirin values. In 6 subjects 24 h after aspirin ingestion the addition of 10--25% v/v normal platelets restored the aggregation response. 3 It is concluded that aspirin has an effect on the platelet precursors in the marrow in addition to its effect on circulating platelets.


Perspectives on the manufacture of combination vaccines.
Evolving regulatory requirements in the United States and Europe create major challenges for manufacturers tasked with production of vaccines that contain > or =9 separate antigens capable of protecting against infectious diseases, such as diphtheria, tetanus, pertussis, polio, hepatitis B, and Haemophilus influenza b, in a single shot. This article describes 10 steps that can facilitate the process of licensing these complex vaccines. It also points out problems associated with the use of animal tests for the crucial step of potency testing for batch release caused by the inherent variability of such tests and the difficulties of interpreting their results.


Fibrosarcoma arising in the paranasal sinus: a clinicopathological and radiological analysis.
To analyze the clinicopathological features and the CT and MRI features of patients with paranasal sinus fibrosarcoma. Seven patients with surgically and pathologically confirmed paranasal sinus fibrosarcoma were enrolled. Their CT and MRI data and imaging features were retrospectively analyzed in detail. The study participants were two males and five females (median age, 43 years; range, 22-73 years). CT or MRI showed a well-defined (n = 5) or ill-defined (n = 2), irregular (n = 6) or oval (n = 1) mass, with heterogeneous (n = 7) density. The lesions were isointense (n = 4) or hypointense (n = 2) on T1 weighted images, and showed heterogeneous (n = 6) mild hypointensity on T2 weighted images. Expansive (n = 6) and osteolytic (n = 1) bone destruction were observed. The tumors showed marked heterogeneous delayed enhancement (n = 6) on contrast-enhanced MRI images. Paranasal sinus fibrosarcomas should be included in the differential diagnosis when a sinonasal neoplasm appears as a well- or ill-defined unilateral large irregular mass with characteristic mild hypointensity on T2 weighted MR images and shows expansive or osteolytic bone destruction and a marked heterogeneous delayed contrast-enhancement pattern.


RNAi-mediated silencing of TEL/AML1 reveals a heat-shock protein- and survivin-dependent mechanism for survival.
The TEL/AML1 fusion gene results from the most frequent t(12;21)(p13;q22) translocation in childhood acute lymphoblastic leukemia (ALL). Its contribution to transformation is largely unknown, in particular with respect to survival and apoptosis. We therefore silenced TEL/AML1 expression in leukemic REH cells by RNA inhibition, which eventually led to programmed cell death. Microarray and 2D gel electrophoresis data demonstrated a differential regulation of heat-shock proteins (HSPs), among them HSP90, as well as of its client, survivin. Consistent with these findings, ectopic expression of TEL/AML1 in Ba/F3 cells increased protein levels of HSP90 and survivin and conferred resistance to apoptotic stimuli. Our data suggest that TEL/AML1 not only contributes to leukemogenesis by affecting an antiapoptotic network but also seems to be indispensable for maintaining the malignant phenotype. The functional relationship between TEL/AML1, HSP90, and survivin provides the rational for targeted therapy, be it the fusion gene or the latter 2 proteins.


[Specific morphological and functional features of the mucous membrane in the upper respiratory tract and the middle ear and the methods for their study].
The currently available data on the peculiarities of the morphological structure of the mucous membrane in the middle ear cavities are presented in conjunction with information on the functional features of the upper respiratory tract and the middle ear. A comprehensive review of the modern methods for the study od the mucociliary activity of the mucous membrane of the upper respiratory tract is provided.


The fractal characteristic of facial anthropometric data for developing PCA fit test panels for youth born in central China.
New principal component analysis (PCA) respirator fit test panels had been developed for current American and Chinese civilian workers based on anthropometric surveys. The PCA panels used the first two principal components (PCs) obtained from a set of 10 facial dimensions. Although the PCA panels for American and Chinese subjects adopted the bivairate framework with two PCs, the number of the PCs retained in the PCA analysis was different between Chinese subjects and Americans. For the Chinese youth group, the third PC should be retained in the PCA analysis for developing new fit test panels. In this article, an additional number label (ANL) is used to explain the third PC in PCA analysis when the first two PCs are used to construct the PCA half-facepiece respirator fit test panel for Chinese group. The three-dimensional box-counting method is proposed to estimate the ANLs by calculating fractal dimensions of the facial anthropometric data of the Chinese youth. The linear regression coefficients of scale-free range R2 are all over 0.960, which demonstrates that the facial anthropometric data of the Chinese youth has fractal characteristic. The youth subjects born in Henan province has an ANL of 2.002, which is lower than the composite facial anthropometric data of Chinese subjects born in many provinces. Hence, Henan youth subjects have the self-similar facial anthropometric characteristic and should use the particular ANL (2.002) as the important tool along with using the PCA panel. The ANL method proposed in this article not only provides a new methodology in quantifying the characteristics of facial anthropometric dimensions for any ethnic/racial group, but also extends the scope of PCA panel studies to higher dimensions.


[Effect of intranasal glucocorticoid on the pathological change of nasal mucosa in rats with allergic rhinitis.].
To investigate the influence of inhaled glucocorticoid on the pathological change of the nasal mucosa in allergic rhinitis. One hundred and eighty Sprague-Dawley (SD) rats were selected. According to the random number table, these animals were randomly divided into two groups: the control Group A and the experimental group. There were 60 rats in Group A and 120 rats in experimental group. First of all, the rats in experimental group were sensitized by intra-peritoneal injection with ovalbumin (OVA), enhanced and local stimulated. Next, the rats in the experimental group were randomly divided into B and C groups. The number of rats in each group was 60. Group B still had the intranasal dropping on each side with OVA in the same volume and concentration twice a week. The rats in Group C also had the intranasal dropping on each side with OVA in the same volume and concentration twice a week. But, at the same time, these animals had fluticasone propionate (FP) nasal spray each side 50 microl/per day. While doing intra-peritoneal injection with physiological saline in the same volume and intranasal dropping on the rats in normal Group A. Ten rats from each group were randomly selected to be killed at the end of first, second, fourth, eighth, twelfth and sixteenth weeks after treatment. One from the ten rats in each group was used for micro-vascular casting of nasal mucosa, and the remaining nine were used for pathological examination. The model of the rats in experimental group was established successfully. After allergen stimulation, the nasal mucosa showed metaplasia of the goblet cells, epithelial denudation, inflammatory cells infiltration especially eosinophils, hyperplasia of the number of gland and density of micro-blood vessels. The capillary became netted. Cilia of epithelial shed to different extent and were uneven, and the layers of reticular formation of basal membrane became thick, and collagen deposition and fabric hyperplasia were seen under the electron microscope. In Group B, due to continuously contact with allergen, the mucosa remodeling enhanced. In Group C, glucocorticoid controlled the symptoms of allergic rhinitis better, but the cilia of epithelial shed, metaplasia of the goblet cells, inflammatory cells infiltration, hyperplasia of gland and micro-blood vessels, collagen deposition and fabric hyperplasia also could be seen in rat nasal mucosa. The pathological change of the nasal mucosa was found in allergic rhinitis. If the allergen was continuously contacted, the pathological change aggravated. Glucocorticoid could control the symptoms of allergic rhinitis better and reverse the mucosa pathological change to some extent, but it could not retro-converse or repair the nasal mucosa while the irreversibile change had occurred.


Clinical implications of immunohistochemically demonstrated lymph node micrometastasis in resectable pancreatic cancer.
The purpose of this study was to determine the clinical significance of nodal micrometastasis detected by immunohistochemistry in patients that had undergone curative surgery for pancreatic cancer. Between 2005 and 2006, a total of 208 lymph nodes from 48 consecutive patients with pancreatic cancer that had undergone curative resection were immunostained with monoclonal antibody against pan-ck and CK-19. Micrometastasis was defined as metastasis missed by a routine H&E examination but detected during an immunohistochemical evaluation. Relations between immunohistochemical results and clinical and pathologic features and patient survival were examined. Nodal micrometastases were detected in 5 (29.4%) patients of 17 pN0 patients. Nodal micrometastasis was found to be related to tumor relapse (P = 0.043). Twelve patients without overt nodal metastasis and micrometastasis had better prognosis than 5 patients with only nodal micrometastasis (median survival; 35.9 vs 8.6 months, P < 0.001). The Cox proportional hazard model identified nodal micrometastasis as significant prognostic factors. Although the number of patients with micrometastasis was so small and further study would be needed, our study suggests that the lymph node micrometastasis could be the predictor of worse survival and might indicate aggressive tumor biology among patients undergoing curative resection for pancreas cancer.


Tooth loss and metabolic syndrome in middle-aged Japanese adults.
Metabolic syndrome is associated with periodontal disease and dental caries; however, little attention has been given to the association between metabolic syndrome and tooth loss, which is the endpoint of these two diseases. This study examined this association in middle-aged adults over a 5-year period. A retrospective study was performed in 2107 participants (1718 males and 389 females) aged 35-60 years who underwent annual dental check-ups, to evaluate tooth loss and metabolic components, including obesity, elevated triglycerides, blood pressure, fasting glucose, and reduced high-density lipoprotein. Logistic regression analysis was performed to evaluate the association between metabolic syndrome (≥3 components) at the baseline examination and tooth loss. Over a 5-year period, 10.8% of the participants lost at least one tooth. Compared to those with no metabolic components, participants with ≥3 components had an increased risk of tooth loss (odds ratio = 1.54; 95% confidence interval: 1.01-2.37), adjusting for age, gender, dental caries experience, attachment loss, oral hygiene status, number of teeth, tooth brushing frequency, smoking, and occupational status. Metabolic syndrome was associated with the incidence of tooth loss among middle-aged adults.


Improvement of growth and yield of soybean plants through the application of non-thermal plasmas to seeds with different health status.
Soybean (Glycine max (L.) Merrill) is a globally important crop, providing oil and protein. Diaporthe/Phomopsis complex includes seed-borne pathogens that affect this legume. Non-thermal plasma treatment is a fast, cost-effective and environmental-friendly technology. Soybean seeds were exposed to a quasi-stationary (50 Hz) dielectric barrier discharge plasma operating at atmospheric pressure air. Different carrying gases (O2 and N2) and barrier insulating materials were used. This work was performed to test if the effects of non-thermal plasma treatment applied to healthy and infected seeds persist throughout the entire cycle of plants. To this aim, lipid peroxidation, activity of catalase, superoxide dismutase and guaiacol peroxidase, vegetative growth and agronomic traits were analysed. The results here reported showed that plants grown from infected seeds did not trigger oxidative stress due to the reduction of pathogen incidence in seeds treated with cold plasma. Vegetative growth revealed a similar pattern for plants grown from treated seeds than that found for the healthy control. Infected control, by contrast, showed clear signs of damage. Moreover, plasma treatment itself increased plant growth, promoted a normal and healthy physiological performance and incremented the yield of plants. The implementation of this technology for seeds treatment before sowing could help reducing the use of agrochemicals during the crop cycle.


Alternaria alternata Mycotoxins Activate the Aryl Hydrocarbon Receptor and Nrf2-ARE Pathway to Alter the Structure and Immune Response of Colon Epithelial Cells.
After ingestion of food commodities, the gastrointestinal tract (GIT) poses the first barrier against xenobiotics and pathogens. Therefore, it is regularly confronted with external stressors potentially affecting the inflammatory response and the epithelial barrier. Alternaria mycotoxins such as alternariol (AOH) and altertoxin II (ATX-II) are frequently occurring food and feed contaminants that are described for their immunomodulatory capacities. Hence, this study aimed at exploring the effect of AOH and ATX-II as single compounds or binary mixtures on the immune response and epithelial homeostasis in noncancerous colon epithelial cells HCEC-1CT. Both toxins suppressed mRNA levels of proinflammatory mediators interleukin-8 (IL-8), tumor necrosis factor α (TNF-α), and secretion of IL-8, as well as mRNA levels of the matrix metallopeptidase 2 (MMP-2). Binary combinations of AOH and ATX-II reduced the response of the single toxins. Additionally, AOH and ATX-II modified immunolocalization of transmembrane proteins such as integrin β1, zona occludens 1 (ZO-1), claudin 4 (Cldn 4), and occludin (Ocln), which support colonic tissue homeostasis and intestinal barrier function. Moreover, the cellular distribution of ZO-1 was affected by ATX-II. Mechanistically, these effects could be traced back to the involvement of several transcription factors. AOH activated the nuclear translocation of the aryl hydrocarbon receptor (AhR) and the nuclear factor erythroid 2-related factor 2 (Nrf2), governing cell metabolic competence and structural integrity. This was accompanied by altered distribution of the NF-κB p65 protein, an important regulator of inflammatory response. ATX-II also induced AhR and Nrf2 translocation, albeit failing to substantiate the effect of AOH on the colonic epithelium. Hence, both toxins coherently repress the intestinal immune response on the cytokine transcriptional and protein levels. Furthermore, both mycotoxins affected the colonic epithelial integrity by altering the cell architecture.


Optimizing holographic data storage using a fractional Fourier transform.
We demonstrate a method to optimize the reconstruction of a hologram when the storage device has a limited dynamic range and a minimum grain size. The optimal solution at the recording plane occurs when the object wave has propagated an intermediate distance between the near and far fields. This distance corresponds to an optimal order and magnification of the fractional Fourier transform of the object.


[Comparison of different phenotypic methods detecting extended spectrum beta-lactamases in Pseudomonas aeruginosa and Acinetobacter baumannii strains].
Pseudomonas aeruginosa and Acinetobacter baumannii which are of great concern as the frequent causative agents of nosocomial infections, frequently exhibit resistance to beta-lactam antibiotics. One of the most common causes of this resistance is the presence of extended spectrum beta-lactamases (ESBL). There is still no standardized method for the detection of ESBLs in P. aeruginosa and A.baumannii strains. The aim of this study was to compare the results of Epsilomer test (E-test), combined disk (CD) and double disk synergy (DDS) methods for the detection of ESBL in a total of 38 P. aeruginosa and 45 A.baumannii strains with ceftazidim or cefotaxime MIC > or = 1 microg/ml, isolated from different clinical samples. Cefepime was included in the group of indicator antibiotics and the distance between clavulanic acid containing disk and indicator antibiotic disks was reduced to increase the sensitivity of DDS test. Of the P. aeruginosa strains, 78.9% was detected as ESBL producers by ceftazidime/ ceftazidime-clavulanic acid and 21.1% detected by cefotaxime/cefotaxime-clavulanic acid ratio. Among this group of strains, 31.5% was positive by DDS test and 84.2% was positive by CD method. Of the A.baumannii strains, 93.3% of them was positive by ceftazidime/ceftazidime-clavulanic acid and 6.6% was positive by cefotaxime/cefotaxime-clavulanic acid ratio. DDS test detected 20% and CD method detected 53.3% of the strains positive by E-test method. The use of cefotaxime together with ceftazidime as an indicator antibiotic increased the sensitivity of detection of ESBL enzymes. Although inclusion of cefepime and reduction of the distance between disks increased the detection of ESBL by DDS method, it was still less effective than E-test. Although, 28.9% of the P. aeruginosa and 13.3% of the A. baumannii strains were susceptible to ceftazidime by in vitro tests, they were ESBL producers. In conclusion, E-test method was found to be the most sensitive phenotypic method for the detection of ESBL in our study collection.


Pituitary tuberculosis presented with pituitary coma.
Pituitary tuberculosis is very rare. Its diagnosis is difficult unless a bacteriological or histological evidence of tuberculosis. We report the case of a 54 years old woman who presented with a pituitary coma that occurred two weeks after the initiation of antituberculous therapy for cervical lymph node tuberculosis. Resonance magnetic imaging showed a pseudotumoral aspect of the pituitary gland. She had hormonal replacement and anti-tuberculous therapy. Outcome was favourable with the normalization of both the pituitary function and the pituitary volume. However, an acute hypopituitarism happened eight months after the withdrawal of antituberculous, which were taken during 12 months. The re initiation of anti tuberculous therapy and its extension to two years leaded to a prolonged remission. the three-phase outcome confirms the tuberculous origin of the hypophysitis in our patient.


Ulnar dimelia without duplicated arterial anatomy.
In this case report a four-year-old girl with ulnar dimelia is described. She had six digits without mirror symmetry in her right hand. The first pre-axial digit was excised and true pollicisation performed for the second pre-axial digit. The arterial anatomy was abnormal but there was not symmetrical development of the arterial tree.


Optimisation of Strength Properties of FDM Printed Parts-A Critical Review.
Additive Manufacturing is currently growing fast, especially fused deposition modeling (FDM), also known as fused filament fabrication (FFF). When manufacturing parts use FDM, there are two key parameters-strength of the part and dimensional accuracy-that need to be considered. Although FDM is a popular technology for fabricating prototypes with complex geometry and other part product with reduced cycle time, it is also limited by several drawbacks including inadequate mechanical properties and reduced dimensional accuracy. It is evident that part qualities are greatly influenced by the various process parameters, therefore an extensive review of the effects of the following process parameters was carried out: infill density, infill patterns, extrusion temperature, layer thickness, nozzle diameter, raster angle and build orientation on the mechanical properties. It was found from the literature that layer thickness is the most important factor among the studied ones. Although manipulation of process parameters makes significant differences in the quality and mechanical properties of the printed part, the ideal combination of parameters is challenging to achieve. Hence, this study also includes the influence of pre-processing of the printed part to improve the part strength and new research trends such as, vacuum-assisted FDM that has shown to improve the quality of the printing due to improved bonding between the layers. Advances in materials and technologies that are currently under development are presented. For example, the pre-deposition heating method, using an IR lamp of other technologies, shows a positive impact on the mechanical properties of the printed parts.