Helping hands for budding prospects: ENTH/ANTH/VHS accessory proteins in endocytosis, vacuolar transport, and secretion.
Coated vesicles provide a major mechanism for the transport of proteins through the endomembrane system of plants. Transport between the endoplasmic reticulum and the Golgi involves vesicles with COPI and COPII coats, whereas clathrin is the predominant coat in endocytosis and post-Golgi trafficking. Sorting of cargo, coat assembly, budding, and fission are all complex and tightly regulated processes that involve many proteins. The mechanisms and responsible factors are largely conserved in eukaryotes, and increasing organismal complexity tends to be associated with a greater numbers of individual family members. Among the key factors is the class of ENTH/ANTH/VHS domain-containing proteins, which link membrane subdomains, clathrin, and other adapter proteins involved in early steps of clathrin coated vesicle formation. More than 30 Arabidopsis thaliana proteins contain this domain, but their generally low sequence conservation has made functional classification difficult. Reports from the last two years have greatly expanded our knowledge of these proteins and suggest that ENTH/ANTH/VHS domain proteins are involved in various instances of clathrin-related endomembrane trafficking in plants. This review aims to summarize these new findings and discuss the broader context of clathrin-dependent plant vesicular transport.


Metabolism of [1-(14)C] and [2-(14)C] leucine in cultured skin fibroblasts from patients with isovaleric acidemia. Characterization of metabolic defects.
Leucine metabolism in cultured skin fibroblasts from patients with isovaleric acidemia was compared with that in normal fibroblasts and in cells from patients with maple syrup urine disease using [1-(14)C] and [2-(14)C] leucine as substrates. Inhibitory effects of methylenecyclopropylacetic acid on leucine metabolism in normal cells were also investigated. Production of 14CO2 from [2-(14)C] leucine was very reduced (96-99%) in both types of mutant cells. Radioactive isovaleric acid accumulated in assay media with isovaleric acidemia cells but not in those with maple syrup urine disease cells. Unexpectedly, 14CO2 production from [1-(14)C] leucine was partially depressed (80%) in isovaleric acidemia cells whereas in maple syrup urine disease cells it was strongly depressed (99%) as expected. These two mutant cells were clearly distinguished by detection of 14C-isovaleric acid accumulation after incubation with [2-(14)C] leucine. A pattern of inhibition of leucine oxidation similar to that seen in isovaleric acidemia cells was induced in normal cells by the addition of 0.7 mM methylenecyclopropylacetic acid to the assay medium. The partial inhibition of [1-(14)C] leucine oxidation seen in isovaleric acidemia cells and also in normal cells in the presence of the inhibitor appears to be, at least in part, due to an accumulation of isovalerate in the cells. Isovaleric acid (5-10) mM) inhibited [1-(14)C] leucine oxidation 32-68% when added to the assay medium with normal cells. Addition of flavin adenine dinucleoside to culture medium or assay medium or both did not restore oxidation of either leucine substrate in isovaleric acidemia cells.


Biomimetic Remineralization of Carious Lesions by Self-Assembling Peptide.
Caries is the most common disease in the world. Great efforts have been undertaken for prevention and to identify a regenerative treatment solution for dental caries. Self-assembling β-sheet forming peptides have previously shown to form 3-dimensional fiber networks supporting tissue regeneration. In particular, the self-assembling peptide P11-4 has shown potential in the treatment and prevention of dental caries. It has previously been shown that application of monomeric P11-4 solution to early carious lesions can increase net mineral gain by forming de novo hydroxyapatite crystals. The hypothesis for the mode of action was that monomeric self-assembling peptide P11-4 diffuses into the subsurface lesion body and assembles therein into higher order fibrils, facilitating mineralization of the subsurface volume by mimicking the natural biomineralization of the tooth enamel, and it remains within the lesion body as a scaffold built-in by the newly formed hydroxyapatite. The aim of the present study was to investigate the mechanism of action of the self-assembling peptide P11-4 supporting mineralization of carious enamel. By various analytical methods, it could be shown that the self-assembling peptide P11-4 diffuses into the subsurface lesion, assembles into higher formed aggregates throughout the whole volume of the lesion, and supports nucleation of de novo hydroxyapatite nanocrystals and consequently results in increased mineral density within the subsurface carious lesion. The results showed that the application of self-assembling peptide P11-4 can facilitate the subsurface regeneration of the enamel lesion by supporting de novo mineralization in a similar mode of action as has been shown for the natural formation of dental enamel.


Relationships between local circulatory changes in the tibia and kidney of male and female rats after castration and administration of estradiol or testosterone.
The effects of castration and of the four weeks' administration of estradiol or testosterone on the blood circulation in the tibia and the kidney (expressed as the 85Sr-microsphere uptake values, which are not influenced by simultaneous changes in cardiac output) were studied in four experiments on a total of 147 rats (68 females, 79 males), relative weights being noted at the same time. 85Sr-microsphere uptake in the tibia rose markedly after castration in both males and females, fell after estradiol benzoate in intact females and intact and orchidectomized males and also fell after testosterone in intact and oophorectomized females and orchidectomized males. 85Sr-microsphere uptake in the kidney rose after castration only in males in experiments B; it fell after estradiol in orchidectomized males and fell after testosterone in intact females and males and in orchidectomized males. Relative tibial weight fell in castrated females, but in castrated males only in experiment D; after estradiol it rose only in males (intact and orchidectomized) and rose after testosterone in intact and oophorectomized females and orchidectomized males. Relative kidney weight fell after castration in both males and females, rose after estradiol in intact females and intact and orchidectomized males and rose after testosterone in intact and castrated males and females. In all four experiments there was a demonstrable statistically significant correlation between the 85Sr-microsphere uptake values in the tibia and the kidney. The relative weights displayed a similar correlation.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of opioid receptors in modulating Alzheimer's Disease.
Alzheimer's disease (AD) is a complex neurological disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles. Long term investigation of AD pathogenesis suggests that β-site amyloid precursor protein [APP] cleaving enzyme 1 (BACE1) and γ-secretase enzymes promote the amyloidogenic pathway and produce toxic Aβ peptides that are predisposed to aggregate in the brain. Hence, the targeted inhibition of BACE1/γ-secretase expression and function is a promising approach for AD therapy. Several reports have suggested that the opioid family of G-protein coupled receptors modulate the etiology of AD progression. It has also been found that changes in the signaling pathways of opioid receptors increased the expression of BACE1 and γ-secretase, and is strongly correlated with abnormal production of Aβ and pathogenesis of AD. Thus, the opioid receptor family is a promising candidate for targeted drug development to treat AD. In this review, we outline the involvement and mechanisms of opioid receptor signaling modulation in Alzheimer's Disease progression.


Chemotherapy-resistant side-population of colon cancer cells has a higher sensitivity to TRAIL than the non-SP, a higher expression of c-Myc and TRAIL-receptor DR4.
Cancer stem cells are resistant to chemotherapy and provide an important target for drug development. We found that, surprisingly, the dye-effluxing side population (SP) within SW480 human colon tumor cells, a population defined to possess stem cell characteristics, expresses a 10-fold higher level of pro-apoptotic TRAIL receptor DR4 as compared to non-SP cells. The TRAIL receptors are activated by the anti-tumor host immune system through the TRAIL ligand. SW480 SP-cells express similar levels of another TRAIL receptor (DR5), as non-SP cells. SP-cells from multiple tumorigenic human cell lines, which are most often resistant to chemotherapeutic agents such as etoposide, cisplatin and 5-FU, are more sensitive to TRAIL than non-SP cells. SP-cells express higher levels of c-Myc than non-SP cells which may explain their sensitivity to TRAIL. We have found c-Myc activates DR4 transcription through E-box DNA-response elements located in the DR4 promoter, thereby increasing the expression of cell-surface pro-apoptotic death receptors in TRAIL-resistant cell lines. TRAIL sensitivity of SP-cells may represent a safeguard against malignancy, and therefore, offers a therapeutic window and opportunity.


Vision screening and the private practitioner--a status report.
Private optometric practitioners have traditionally been involved with schools and other organizations in conducting vision screening programs, although the extent of the involvement varies considerably from one location to another. A national survey of 500 optometrists (49% response rate) was conducted to examine the extent of optometric involvement in screening programs. Seventy percent of the optometrists surveyed have participated in screening during their professional careers although only 30% are currently active. Most screenings were done in the schools with the Modified Clinical Technique (MCT) battery although only 7% knew of perceptual screening activities. The study indicates that in areas where vision screening is conducted, most practitioners are involved and where programs are infrequent, knowledge about screenings is limited.


Serial transrectal ultrasonography for monitoring the reproductive activity of the Asiatic black bear (Ursus thibetanus ussuricus).
This study evaluated the structural changes in the reproductive tract of Asiatic black bears using serial transrectal ultrasonography. In addition, the ultrasonographic observations were compared with the results of vaginal cytology and hormonal analyses. The collection of blood for hormonal analysis, vaginal cytology and transrectal ultrasonography was performed in two bears (Bears 1 and 2) from June 2011 to August 2013 without mating and in a third bear (Bear 3) from April to December 2012, allowing natural mating. Serial ultrasonographic observations showed cyclic changes in ovarian structures (e.g. emergence of small follicles, growth and ovulation of dominant follicles and corpus luteum (CL) formation) during the reproductive cycles of the three bears. The diameter of the uterine horns remained similar throughout the reproductive cycle in Bears 1 and 2, and it remained similar from April until October, but an enlargement containing foetuses was observed in Bear 3 in December. The ultrasonographic observations were consistent with the data obtained through vaginal cytology and progesterone analysis during the reproductive cycle. An average of 4.0 (±0.4) dominant follicles was observed during the oestrous stage (May-August), during which the superficial cells accounted for >90% of the total vaginal cells. In addition, the detection of an average of 2.6 (±0.2) CL was associated with increased plasma progesterone concentrations (3.0 ± 0.4 ng/ml) between June and December (near hibernation). In conclusion, serial transrectal ultrasonography demonstrated yearly oestrous (ovulation) cycles via follicular dynamics and CL formation on ovaries, accordingly with vaginal cytology and hormonal level in the Asiatic black bear.


Atypical neuroleptic malignant syndrome associated with risperidone treatment in two adolescents.
Neuroleptic Malignant Syndrome (NMS) is a known, life threatening, side effect of classical antipsychotic drugs. We report two cases of 16 and 17 year old males, who suffered life-threatening "NMS-Like" syndromes in association with Risperidone treatment. Further controlled studies are needed.


The Importance of Liver-Fatty Acid Binding Protein in Diagnosis of Liver Damage in Patients with Acute Hepatitis.
Acute hepatitis is acute inflammation of liver elicited by a large number of causes. It sometimes spontaneously recovers, sometimes may progress to chronic hepatitis. Liver- Fatty Acid Binding Protein (L-FABP) is a small protein that is abundant in hepatocytes, and which binds most of the long-chain fatty acids present in the cytosol. The present study was aimed to investigate the levels of serum and urine L-FABP in acute hepatitis and diagnostic value of serum and urine L-FABP levels in patients with acute hepatitis. The present study included a total of 85 patients. Total number of patients with acute hepatitis were 17 (five of acute hepatitis B, one of acute hepatitis A, two of acute hepatitis C, five of autoimmune hepatitis and four of toxic hepatitis), 19 of hepatic encephalopathy, 29 of liver cirrhosis, and 20 controls were included. Serum and urinary L-FABP levels were analyzed by the Enzyme-Linked Immunosorbent Assay (ELISA). Serum L-FABP levels were 9110±3352.5, 9410±1355, 9715±2462 and 3672±982.5 ng/l in patients with acute hepatitis, hepatic encephalopathy and cirrhosis and control subjects, respectively. There were statistically significant positive correlations between serum levels of L-FABP and Aspartate Aminotransferases (AST), Alanine Aminotransferases (ALT), Creatinine (Cre) and Gamma Glutamyl Transferases (GGT) (p<0.001, p<0.001, p<0.001 and p<0.001, respectively). While the cut-off value of serum L-FABP for all of the patients was 5183 ng/l {p<0.001 and Area Under Curve (AUC) 0.985}, the sensitivity and specificity were 95.4% and 100%, respectively. Positive and negative predictive values for serum L-FABP were 100% and 87%, respectively. Serum and urine L-FABP may be a new diagnostic marker for liver damage in patients with acute hepatitis. However, our study showed that except of aminotransferases, L-FABP should be used for diagnosis of liver damage in patients with acute hepatitis, chronic hepatitis and also cirrhosis.


Triple-q Order in Na_{2}Co_{2}TeO_{6} from Proximity to Hidden-SU(2)-Symmetric Point.
In extended Heisenberg-Kitaev-Gamma-type spin models, hidden-SU(2)-symmetric points are isolated points in parameter space that can be mapped to pure Heisenberg models via nontrivial duality transformations. Such points generically feature quantum degeneracy between conventional single-q and exotic multi-q states. We argue that recent single-crystal inelastic neutron scattering data place the honeycomb magnet Na_{2}Co_{2}TeO_{6} in proximity to such a hidden-SU(2)-symmetric point. The low-temperature order is identified as a triple-q state arising from the Néel antiferromagnet with staggered magnetization in the out-of-plane direction via a 4-sublattice duality transformation. This state naturally explains various distinctive features of the magnetic excitation spectrum, including its surprisingly high symmetry and the dispersive low-energy and flat high-energy bands. Our result demonstrates the importance of bond-dependent exchange interactions in cobaltates, and illustrates the intriguing magnetic behavior resulting from them.


Atherosclerosis in chronic renal failure.
Atherosclerotic cardiovascular disease is a significant cause of morbidity and mortality in patients with chronic renal failure. It is unclear, however, if atherosclerosis in fact occurs at a higher incidence compared with the nonuremic population matched for age, hypertension, and diabetes mellitus or if it occurs at an accelerated rate following the onset of end-stage renal disease. The extent of true atherosclerotic lesions, versus clinically diagnosed "atherosclerosis," in patients with chronic renal failure is equally unclear. Potentially, the uremic state per se, the dialysis treatment, and factors unrelated to renal failure may participate in atherogenesis. The relative contribution of each of these factors is unknown. In this review, we discuss the pathology of "atherosclerotic" lesions in patients with chronic renal failure and the putative factors involved in atherogenesis in this population and describe the results of available studies examining the issue of accelerated atherosclerosis in uremia.


Insight into the Selectivity of Kir3.2 toward Phosphatidylinositides.
Activation of G-protein-gated inwardly rectifying potassium channels (Kir3.x) requires the direct binding of phosphorylated phosphatidylinositides (PIPs). Previous studies have established that PIP isoforms activate Kir channels to varying degrees and the binding affinity between PIPs and Kir3.2 appears to be correlated with the level of activation. However, how individual residues contribute to the selectivity of Kir channels toward PIP isoforms is poorly understood. Here, we employ native mass spectrometry (MS) and fluorescent lipid binding assays to gain insight into the contribution of specific Kir3.2 residues binding to phospholipids. For the wild-type channel, we demonstrate the importance of membrane protein samples devoid of co-purified contaminants for protein-lipid binding studies and show that PIP(4,5)P2 cooperatively binds Kir3.2 with a Hill coefficient of 2.7. We also find lipid binding profiles determined from native MS and solution binding assays are in direct agreement. Point mutations of Kir3.2 residues that interact with PIPs distinctly alter selective lipid binding. The K64Q mutation results in altered binding profiles with the highest binding affinity for PIP(4,5)P2 with specific acyl chains. Mutation of R92 to Pro, a residue found in Kir6.2, results in promiscuous binding of PIP isoforms. Kir3.2 with the K194A mutation results in a distinct binding preference for PIP(3,4,5)P3 over other PIP isoforms. Taken together, our results underscore the utmost importance of protein quality for protein-lipid binding studies and show that a single mutation in Kir3.2 can alter the selectivity toward PIPs.


A modified Warthin-Starry procedure at low pH for melanin.
The Warthin-Starry argyrophilic silver stain peformed at pH 3.2 is a highly effective method for the demonstration of melanin in tissue sections. Eighty-five melanocytic tumors were studied using the Warthin-Starry and the Fontana-Masson procedures. The Warthin-Starry technic stained a greater number of cells in 68% of the tumors, with no loss of cellular detail. Twenty-three per cent of the tumors that appeared amelanotic on hematoxylin-and-eosin-stained sections were positive for melanin with the Warthin-Starry stain, but negative with the Fontana-Masson technic. The Warthin-Starry stain is more sensitive and specific for melanin than is the Fontana-Masson procedure.


The bioenergetics of alkalophilic bacilli.
A summary, cum speculation, of the major bioenergetic characteristics of alkalophilic bacilli is presented in Figure 5. Further progress will depend heavily on the purification and characterization of the relevant proteins that catalyze the ion fluxes and on the development of much more potent genetic approaches to the outstanding issues of this interesting group of bacteria.


Neutrophil Gelatinase-Associated Lipocalin Attenuates Ischemia/Reperfusion Injury in an In Vitro Model via Autophagy Activation.
BACKGROUND The aim of this study was to investigate the protective effects of neutrophil gelatinase-associated lipocalin (NGAL) on hypoxia/reoxygenation (H/R) induced acute kidney injury (AKI) in vitro. MATERIAL AND METHODS We used NRK-52E cells and H/R treatments to mimic ischemia/reperfusion injury (IRI) in vitro. Experimental groups were: the control group, the H/R group, the 3-methyladenine (3-MA)+H/R group, the NGAL (0.25, 0.5, and 1 ug/mL)+H/R group, and the NGAL (0.25, 0.5, 1 ug/mL)+3-MA+H/R group. After 24 hours of culture, cell proliferation was analyzed by CCK-8 assay. Expression of LC3-II was detected by immunoblot assay. Autophagy was detected by electron microscopy. RESULTS The expression of LC3-II was increased in the H/R group compared with normoxic condition (p<0.05) and proliferation also improved. Autophagy was significantly inhibited by 3-MA, with downregulated of LC3-II, followed by decreased cell viability (p<0.05). We further detected the effect of different doses of NGAL in H/R induced injury, and found that low doses of NGAL alone slightly increased LC3-II protein accumulation, and autophagy was further induced with higher dose of NGAL treatment. Meanwhile, cell viability assays showed induced cell survival. We found that in the NGAL+3-MA group, cell viability assays revealed reduced cell damage, followed concomitantly with depressed autophagy. The formulation of autophagosomes were correlated with LC3-II protein expression in each group. CONCLUSIONS Autophagy plays a renoprotective role in H/R injury, as well in AKI. NGAL might be related to attenuated tubular epithelial cell damage via adjusting autophagy.


[Definition of crime and judiciary procedures].
The word crime takes various definitions depending on the criminal, sociological, political, or even penal viewpoint. On the one hand, it relies upon various references which can be sizeable or superficial values, individual or collective values, moral or material values, national or universal values. On the other hand, the notion of crime gathers behaviours that are considered by the entire population and the legislator as the strongest violations of the fundamental interests of the human being, of the social group and of the state-controlled institutions. Despite the multiplicity of those meanings, repression of crime comes within the framework of a precise judiciary procedure, dooming to failure any attempt at arbitrary decisions. The unfolding proceedings in the assizes courts are the most obvious demonstrations of that.


Photoinduced Controlled/Living Polymerizations.
The application of photochemistry in polymer synthesis is of interest due to the unique possibilities offered compared to thermochemistry, including topological and temporal control, rapid polymerization, sustainable low-energy processes, and environmentally benign features leading to established and emerging applications in adhesives, coatings, adaptive manufacturing, etc. In particular, the utilization of photochemistry in controlled/living polymerizations often offers the capability for precise control over the macromolecular structure and chain length in addition to the associated advantages of photochemistry. Herein, the latest developments in photocontrolled living radical and cationic polymerizations and their combinations for application in polymer syntheses are discussed. This Review summarizes and highlights recent studies in the emerging area of photoinduced controlled/living polymerizations. A discussion of mechanistic details highlights differences as well as parallels between different systems for different polymerization methods and monomer applicability.


Inhibitory effects of lemon grass (Cymbopogon citratus Stapf) on formation of azoxymethane-induced DNA adducts and aberrant crypt foci in the rat colon.
The 80%-ethanol extract of lemon grass (Cymbopogon citratus Stapf), a medicinal plant in Thailand, has been reported to be antimutagenic against various known mutagens in the Salmonella mutation assay. To investigate chemoprevention in an animal carcinogenesis model, we examined inhibitory effects of the lemon grass extract on the formation of azoxymethane (AOM)-induced DNA adducts and aberrant crypt foci (ACF) in the rat colon. One week after the start of the treatment with lemon grass extract at doses of 0.5 or 5 g/kg body wt by gavage, F344 rats received two s.c. injections of 15 mg of AOM per kg body weight at 1 week apart. For DNA adduct analysis of the colon and liver, the rats were killed 12 h after the second AOM injection. The DNA from the liver and colon were used for O6-methylguanine and N7-methylguanine analysis. For ACF analysis in the initiation stage, AOM-injected rats were continuously treated with lemon grass extract and were killed 3 weeks after the second AOM injection. For analysis in the promotion stage the treatment with the lemon grass extract (0.5 g/kg) started 2 weeks after the second AOM injection and continued for 12 weeks until the animals were killed. Lemon grass treatment significantly inhibited DNA adduct formation in both the colonic mucosa and the muscular layer but not in the liver. In addition, lemon grass extract treatment significantly inhibited ACF formation in both the initiation stage and the promotion stage. Especially in the promotion stage, lemon grass treatment inhibited the formation of larger ACF (with four or more crypts per focus), which was predictive of tumor incidence. Furthermore, lemon grass extract inhibited fecal beta-glucuronidase competitively and had antioxidant activity. These results suggest that the lemon grass extract inhibits the release of activated aglycon, methylazoxymethanol, from a glucuronide conjugate in the colon, and decreases the DNA adducts and ACF formation in the rat colon.


The imaging appearances of non-calcified ductal carcinoma in situ: A pictorial essay.
Non-calcified ductal carcinoma in situ (NCDCIS) presents as a heterogeneous entity on various imaging modalities, most frequently presenting symptomatically as a palpable lump. The combination of multiple modalities and knowledge of its potential radiological appearances are important in minimising misdiagnosis. Compared to conventional 2D mammography, both sonography and digital breast tomosynthesis show higher diagnostic accuracy in the detection of NCDCIS. Newer modalities of contrast-enhanced digital mammography and MRI have limited data at present, but early results indicate greater sensitivity for the detection of lesions that may be occult on ultrasound or mammography. Here, we present an illustrative study highlighting the varied appearances of NCDCIS on several imaging modalities including a brief review of the literature.


Meta-Analysis of Soybean-based Biodiesel.
Biofuel policy changes in the United States have renewed interest in soybean [ (L.) Merr.] biodiesel. Past studies with varying methodologies and functional units can provide valuable information for future work. A meta-analysis of nine peer-reviewed soybean life cycle analysis (LCA) biodiesel studies was conducted on the northern Great Plains in the United States. Results of LCA studies were assimilated into a standardized system boundary and functional units for global warming (GWP), eutrophication (EP), and acidification (AP) potentials using biodiesel conversions from peer-reviewed and government documents. Factors not fully standardized included variations in NO accounting, mid- or end-point impacts, land use change, allocation, and statistical sampling pools. A state-by-state comparison of GWP lower and higher heating values (LHV, HHV) showed differences attributable to variations in spatial sampling and agricultural practices (e.g., tillage, irrigation). The mean GWP of LHV was 21.1 g·CO-eq MJ including outliers, and median EP LHV and AP LHV was 0.019 g·PO-eq MJ and 0.17 g·SO-eq MJ, respectively, using the limited data available. An LCA case study of South Dakota soybean-based biodiesel production resulted in GWP estimates (29 or 31 g·CO-eq MJ; 100% mono alkyl esters [first generation] biodiesel or 100% fatty acid methyl ester [second generation] biodiesel) similar to meta-analysis results (30.1 g·CO-eq MJ). Meta-analysis mean results, including outliers, resemble the California Low Carbon Fuel Standard for soybean biodiesel default value without land use change of 21.25 g·CO-eq MJ. Results were influenced by resource investment differences in water, fertilizer (e.g., type, application), and tillage. Future biofuel LCA studies should include these important factors to better define reasonable energy variations in regional agricultural management practices.


Leptin Levels in Patients with Type 1 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant.
Our objective was to determine leptin levels in patients with type 1 diabetes mellitus after fetal pancreatic stem cell transplant. Seven patients, aged 20 to 42 years, with type 1 diabetes mellitus received a fetal pancreatic stem cell transplant by intravenous infusion. The quantity of fetal stem cells infused was ≥ 5 × 10⁶, and the cells were of 12 to 14 weeks of gestation. We analyzed the levels of leptin, C-peptide, and antibodies to the islets of Langerhans before and 3 months after the transplant procedure. Fetal pancreatic stem cell transplant led to significant increases in leptin and C-peptide levels, from 4.63 ± 1.17 ng/mL and 0.09 ± 0.02 ng/mL to 7.71 ± 1.45 ng/mL (P < .05) and 0.22 ± 0.05 ng/mL (P < .005), respectively, without an increase in antibodies to the islets of Langerhans, which measured 0.64 ± 0.13 U/mL before transplant and 0.57 ± 0.18 U/mL 3 months later (P > .05). Leptin levels increase significantly within 3 months of fetal pancreatic stem cell transplant in patients with type 1 diabetes mellitus.


The road ahead to continuous 24-hour intraocular pressure monitoring in glaucoma.
Intraocular pressure (IOP) is the only treatable risk factor for glaucoma. Yet, current glaucoma management usually relies on single IOP measurements during clinic hours despite the fact that IOP is a dynamic parameter with individual rhythms. Single IOP measurements underpin all major clinical guidelines on treatment of glaucoma. Other potentially informative parameters, such as IOP fluctuations and peak IOP, have been neglected, and effects of IOP-lowering interventions on such measures are largely unknown. The search for continuous 24-hour IOP monitoring started over 50 years ago, but only recent technological advances have provided clinician-researchers with devices for continuous IOP monitoring. Herein, we discuss innovative approaches with permanent and temporary devices for 24-hour IOP monitoring, such as a contact lens sensor. Despite being in their infancy, these devices may soon enable clinicians to use 24-hour IOP data to improve glaucoma management and reduce the glaucoma-related burden of disease.


Proton magnetic resonance spectroscopy reveals medial temporal metabolic abnormalities in adolescents with history of preterm birth.
Prematurity is associated with volumetric reductions in specific brain areas such as the hippocampus and with metabolic changes that can be detected by spectroscopy. Short echo time (35 ms) Proton magnetic resonance spectroscopy (1H MRS) was performed to assess possible medial temporal lobe metabolic abnormalities in 21 adolescents with preterm birth (mean age: 14.8, SD: 1.3) compared with an age-matched control sample (mean age: 14.8, SD: 1.6). 1H MRS spectra were analyzed with linear combination model fitting, obtaining the absolute metabolite concentrations for Creatine (Cr), and myo-inositol (Ins). In addition, the following metabolite sums were measured: total Cho (glycerophospho-choline + phosphocholine), total N-acetyl-aspartate + N-acetyl-aspartylglutamate (NA), and total Glx (glutamate + glutamine). A stereological analysis was performed to calculate hippocampal volume. Absolute Cr, and total NA values were decreased in the preterm group (p = 0.016; p = 0.002, respectively). The preterm also showed a hippocampal reduction (p < 0.0001). Significant relationships were found between gestational age and different metabolites and the hippocampal volume. Moreover, hippocampal volume correlated with brain metabolites in the whole sample. Results demonstrate that prematurity affects medial temporal lobe metabolites, and that the alteration is related to structural changes, suggesting that the cerebral changes persist until adolescence.


Villin severing activity enhances actin-based motility in vivo.
Villin, an actin-binding protein associated with the actin bundles that support microvilli, bundles, caps, nucleates, and severs actin in a calcium-dependant manner in vitro. We hypothesized that the severing activity of villin is responsible for its reported role in enhancing cell plasticity and motility. To test this hypothesis, we chose a loss of function strategy and introduced mutations in villin based on sequence comparison with CapG. By pyrene-actin assays, we demonstrate that this mutant has a strongly reduced severing activity, whereas nucleation and capping remain unaffected. The bundling activity and the morphogenic effects of villin in cells are also preserved in this mutant. We thus succeeded in dissociating the severing from the three other activities of villin. The contribution of villin severing to actin dynamics is analyzed in vivo through the actin-based movement of the intracellular bacteria Shigella flexneri in cells expressing villin and its severing variant. The severing mutations abolish the gain of velocity induced by villin. To further analyze this effect, we reconstituted an in vitro actin-based bead movement in which the usual capping protein is replaced by either the wild type or the severing mutant of villin. Confirming the in vivo results, villin-severing activity enhances the velocity of beads by more than two-fold and reduces the density of actin in the comets. We propose a model in which, by severing actin filaments and capping their barbed ends, villin increases the concentration of actin monomers available for polymerization, a mechanism that might be paralleled in vivo when an enterocyte undergoes an epithelio-mesenchymal transition.


[Serial strain gauge measurement of bone healing in Hoffmann external fixation].
Since 1978, the author has applied Hoffmann external fixation to the treatment of open fractures and infected pseudoarthrosis of long bones in the lower limbs, but has some difficulties in determining when weight bearing should be started after operation, how much weight bearing should be and when the pin should be removed. As new method to mechanically analyze the callus strength, I tried to estimate the amount of strain at intervals of 2 to 3 weeks, beginning from the second week after operation, by bending or compressing the fracture site through the strain gauge glued to the middle of the external fixator's connecting rod. From a strength test by means of a model of fracture using a vinyl chloride pipe and also from a study of computer calculation using the model of plane beam structure for architectural design, it was found that the amount of the strain on the connecting rod decreased hyperbolically when the mechanical properties of the callus increased, and that it became constant when the mechanical properties of the callus reached 50% of the intact bone. The strength test using an cadaveric skin bone demonstrated that the callus volume was one of the most important and affecting factor. Twenty-three cases were treated by Hoffmann external fixation, and the bone healing was achieved in 20 of them. On the basis of the bone healing curve obtained by the serial strain gauge measurement in those cases, the bone healing process could be classified into 5 types: normal healing, slow healing, non-union, arrest in evolution and breakage of callus; and were employed as indexes in the post-operative rehabilitation program.


Oxidative stress and glutathione S-transferase genetic polymorphisms in medical staff professionally exposed to ionizing radiation.
Ionizing radiation (IR) is considered as a diagnostic and therapeutic tool in medicine. However, chronic occupational exposure of medical staff to IR may affect the antioxidant status and, as a result, DNA damage and cancers as well. The objective of our study was to evaluate the oxidative stress profile caused by IR in 29 Tunisian medical staff from radiology and radiotherapy departments, and to find an association between the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val polymorphisms and oxidative stress biomarkers. The oxidant biomarkers malondialdehyde (MDA) and advanced oxidation protein product (AOPP) and the activities of the antioxidant superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) enzymes were spectrophotometrically determined in erythrocytes hemolysates. The analysis of GSTT1 null, GSTM1 null, and GSTP1 Ile105Val polymorphisms was determined for each participant using PCR methods. A significant increase of white blood cell (WBC) numbers (p < .05) and a significant decrease by 11% of hemoglobin (Hb) (p < .01) were noted in the exposed subjects in our study. Moreover, we report a significant increase of MDA level and the activities of SOD and CAT enzymes of the IR-exposed group compared to controls (p < .001). Interestingly, a close association was noted between the genotypes GSTP1 low active, GSTT1 null, GSTM1 null, and both GSTT1/GSTM1 null and oxidative stress biomarkers, especially with MDA level, SOD, and CAT activities. Our findings indicate that the medical staff exposed to low IR levels were under risk of significant oxidative stress that was enhanced by their glutathione S-transferase (GST) polymorphisms.


Feedback regulation of murine Ly-1 B cell development.
Studies presented here, conducted with allotype homozygotes, demonstrate the existence of a feedback mechanism that regulates development of Ly-1 B cells from immature progenitors. In the preceding study (P. A. Lalor et al., Eur. J. Immunol. 1989. 19:501), conducted with allotype heterozygotes, we showed that treating neonates with monoclonal antibody to the paternal allotype IgM depletes roughly half of the neonatal B cell population (i.e. those expressing the paternal IgM allotype) and that paternal allotype Ly-1 B cells specificically remain depleted for the life of the animal. Here we show that treating allotype homozygotes with the same antibody depletes all (rather than half) of the B cells and that, under these conditions, relatively normal numbers of Ly-1 B cells reappear shortly after the treatment antibody disappears. The recovery, we also show, is prevented by restoring allotype-congenic Ly-1 B cells to the treated homozygotes, i.e. by reconstituting treated neonates with allotype-congenic peritoneal cells, sorted Ly-1 B cells or a monoclonal population of Ly-1 B "tumor" cells. These findings in essence reveal a feedback mechanism through which mature Ly-1 B cells prevent further Ly-1 B cell development from Ig- precursors. This feedback regulation is independent of Ig secretion by the mature Ly-1 B cells, since the monoclonal Ly-1 B "tumor" population that prevents endogenous Ly-1 B development does not secrete Ig. Furthermore, it appears to be independent of Ly-1 B surface Ig specificity, since a monoclonal population is sufficient to block all Ly-1 B cell development. This mechanism appears to operate normally to fix the composition of the Ly-1 B population, which survives through self-replenishment in adults, in accord with conditions that influence Ly-1 B development during neonatal life.


[Solubilization of O/W microemulsion for volatile oil from Houttuynia Cordra].
To study the solubilization of O/W microemulsion system for volatile oil from Houttuynia Cordra and determine the formulation of its microemulsion. The solubilization curve was drawn from pseudo-ternary phase diagram plotted by using the method of titration. The microemulsion's effect on solubilization for volatile oil from Houttuynia Cordra was systematically studied and the difference solubilization effects between colloid fluid and microemulsion were compared. Excipient varieties and amount of microemulsion had effects on solubilization for volatile oil from Houttuynia Cordra. The formulation of its microemulsion was determined and we chose medium-chain triglycerides as oil phase, polyoxyethylene castor oil EL-35 as surfactant, propylene glycol as cosurfactant and the surfactant to cosurfactant ratio was 2. Suitable microemulsion formulation can solubilize volatile oil from Houttuynia Cordra and it can provide research foundation for further development of microemulsion preparation for volatile oil from Houttuynia Cordra.


[Principle and application of Chinese medicine syndrome differentiation and disease classification].
Taxonomy of diseases is usable in Western medicine and also in Chinese medicine, but with different measures of sorting, i.e. disease classification in Western medicine and the syndrome differentiation in Chinese medicine. Actually, an integrative mode of the above two measures is already the chief mode of sorting applied in clinical practice of Chinese medicine and integrative medicine. The two measures are introduced in this paper, and the integrative mode is deeply analyzed as well. Its biomedical interpretation and protocol are operational explained, and its important values, involving clinical practice for assessments of therapeutic efficacy, drug action and safety; new drug research and development; medical innovation; and research on internal relation among diseases, are discussed with illustration. The authors indicated that the integrative taxonomic mode of disease classification and syndrome differentiation is an important theoretical representation for mutual-supplementing of Chinese medicine and Western medicine in integrative medicine, also the important measure and approach for developing Chinese medicine and innovating biomedicine, and it is meaningful in both theoretical guidance and actual clinical practice.


Comparison of Pediatric and General Orthopedic Surgeons' Approaches in Management of Developmental Dysplasia of the Hip and Flexible Flatfoot: the Road to Clinical Consensus.
Developmental dysplasia of the hip (DDH) and flatfoot are common pediatric orthopedic disorders, being referred to and managed by both general and pediatric orthopedic surgeons, through various modalities. Our study aimed to evaluate their consensus and perspective disagreements in terms of diagnostic and therapeutic approaches of the mentioned deformities. Forty participants in two groups of general orthopedic surgeons (GOS) (n=20) and pediatric orthopedic surgeons (POS) (n=20), were asked to answer an 8-item questionnaire on DDH and flexible flatfoot. The questions were provided with two- or multiple choices and a single choice was accepted for each one. Chi-square and Fisher's exact tests was performed to compare the responses. For a neonate with limited hip abduction, hip ultrasonography was the agreed-upon approach in both groups (100% POS vs 71% GOS), and for its interpretation 79% of POS relied on their own whereas 73% of GOS relied on radiologist's report (P=0.002). In failure of a 3-week application of the Pavlik harness, ending it and closed reduction (57% POS vs. 41% GOS) followed by surgery quality assessment with CT scan (64% POS vs. 47% GOS) and without the necessity for avascular necrosis evaluation (79% POS vs. 73% GOS) were the choice measures. In case of closed reduction failure, open reduction via medial approach was the favorite next step in both groups (62% POS and 80% GOS). For the patient with flexible flat foot, reassurance was the choice plan of 79% of pediatric orthopedists. Our findings demonstrated significant disagreements among the orthopedic surgeons. This proposes insufficiency of high-level evidence.


Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. Multiple actions.
Purified recombinant human B cell growth factor-1/IL-4 was evaluated, alone and in combination, with purified preparations of recombinant human (rhu) CSF or erythropoietin (Epo) for effects on colony formation by human bone marrow CFU-GM progenitor cells (GM) and burst forming unit-E progenitor cells. rhu IL-4 synergized with rhu G-CSF to enhance granulocyte colony formation, but had no effect on CFU-GM colony formation stimulated by rhu GM-CSF, rhu IL-3, or rhu CSF-1. Rhu IL-4 synergized with Epo to enhance BFU-E colony formation equal to that of Epo plus either rhu IL-3, rhu GM-CSF, or rhu G-CSF. Removal of adherent cells and T lymphocytes did not influence the synergistic activities of rhu IL-4. Rmu IL-4, synergized with rhu G-CSF, but not with rmu GM-CSF, rmu IL-3, or natural mu CSF-1, to enhance CFU-GM (mainly granulocyte) colony numbers by a greater than 90% pure preparation of murine CFU-GM. Also, rhu IL-4 at low concentrations enhanced release of CSF and at higher concentrations the release also of suppressor molecules from human monocytes and PHA-stimulated human T lymphocytes. Use of specific CSF antibodies suggested that rhu IL-4 was enhancing the release of G-CSF and CSF-1 from monocytes and the release of GM-CSF and possibly G-CSF from PHA-stimulated T lymphocytes. Use of antibodies for TNF-alpha, IFN-gamma, or TNF-beta as well as measurement of TNF and IFN titers suggested that the suppressor molecule(s) released from monocytes were acting with TNF-alpha and those released from PHA-stimulated T lymphocytes were acting with IFN-gamma. These results implicate B cell growth factor-1/IL-4 as a synergistic activity for hematopoietic progenitors and suggest that the actions can be on both progenitor and accessory cells.


In vivo distribution of vesicles loaded with radiopharmaceuticals: a study of different routes of administration.
The in vivo distribution of vesicles containing radiopharmaceuticals in their cavities has been studied using three routes of administration: intravenous, subcutaneous, and intraperitoneal. The in vivo distribution in mice was determined by dissection of the animals and calculation of radioactivity in the organs. In rats the in vivo distribution was assessed by scintigraphy using a scintillation camera-digital computer unit. After intravenous injection of vesicles, radioactivity is concentrated to some extent in the liver and spleen but the pattern of distribution is different from that of the corresponding free radiopharmaceutical or radiocolloid made of the corresponding radionuclide. The permeability of the vesicular membrane to contained radiopharmaceutical has been shown to vary according to the chemical composition of the vesicles. Vesicles can be used to introduce materials in vivo and the potential exists for their specific targeting by coupling other molecules to their surfaces.


Preparation of Nano-Porous Activated Carbon Aerogel Using a Single-Step Activation Method for Use as High-Power EDLC Electrode in Organic Electrolyte.
Carbon aerogel was chemically activated with KOH using two different activation methods (conventional activation method and single-step activation method) to yield the nano-porous activated carbon aerogel. Both nano-porous activated carbon aerogels exhibited a better capacitive behavior than carbon aerogel in organic electrolyte. However, a drastic decrease in the specific capacitance with increasing current density was observed in the ACA_C (activated carbon aerogel prepared by a conventional activation method), which is a general tendency of carbon electrode for EDLC in organic electrolyte. Interestingly, the specific capacitance of ACA_S electrode (activated carbon aerogel prepared by a single-step activation method) decreased slowly with increasing current density and its CV curve maintained a rectangular shape well even at a high scan rate of 500 mV/s. The enhanced electrochemical performance of ACA_S at a high current density was attributed to its low ionic resistance caused by the well-developed pore structure with appropriate pore size for easy moving of organic electrolyte ion. Therefore, it can be concluded that single-step activation method could be one of the efficient methods for preparation of nano-porous activated carbon aerogel electrode for high-power EDLC in organic electrolyte.


Strategies contributing to effectiveness of health science faculty training.
Strategies contributing to effectiveness of design, development, and operation of national training programs for health science faculty are presented. Focus is on programs similar to those conducted by the National Medical Audiovisual Center (NMAC)-programs that involve improvement of teaching skills and cooperative efforts (non-funded) between a development agency and geographically dispersed, independent training organizations. Although strategies presented here emanated from experience at NMAC, they may be generalized to encompass training conducted by other networks of cooperating organizations operating in similar contexts. Further, the strategies are consonant with literature on instructional design, adult learning, and innovation.


Cooking with Active Oxygen and Solid Alkali: A Promising Alternative Approach for Lignocellulosic Biorefineries.
Lignocellulosic biomass, a matrix of biopolymers including cellulose, hemicellulose, and lignin, has gathered increasing attention in recent years for the production of chemicals, fuels, and materials through biorefinery processes owing to its renewability and availability. The fractionation of lignocellulose is considered to be the fundamental step to establish an economical and sustainable lignocellulosic biorefinery. In this Minireview, we summarize a newly developed oxygen delignification for lignocellulose fractionation called cooking with active oxygen and solid alkali (CAOSA), which can fractionate lignocellulose into its constituents and maintain its processable form. In the CAOSA approach, environmentally friendly chemicals are applied instead of undesirable chemicals such as strong alkalis and sulfides. Notably, the alkali recovery for this process promises to be relatively simple and does not require causticizing or sintering. These features make the CAOSA process an alternative for both lignocellulose fractionation and biomass pretreatment. The advantages and challenges of CAOSA are also discussed to provide a comprehensive perspective with respect to existing strategies.


Social network analyses of patient-healthcare worker interactions: implications for disease transmission.
Patients and healthcare workers (HCW) in healthcare settings represent a unique social network in which the risk of transmission of an infection is considered to be higher for both HCW and patients. Using data from existing clinical informatics resources, we constructed social networks of patient-HCW interactions in the emergency department of a tertiary care pediatric hospital. The structural properties of these networks were analyzed and compared to other well known networks. Patient-HCW networks do not demonstrate the classical power-law distribution of scale-free networks, thus indicating that they are different from social networks of individuals in a community. The clustering coefficient is larger as compared to a random network, indicating small world properties. The eigenvector centrality, used to identify the most important nodes, reveals HCW to be more connected than patients. These properties imply differences that must be taken into account when analyzing patient-HCW networks and planning interventions and mitigation strategies to prevent the spread of infectious diseases in healthcare settings.


Tunable Magnetism and Extraordinary Sunlight Absorbance in Indium Triphosphide Monolayer.
Atomically thin two-dimensional (2D) materials have received considerable research interest due to their extraordinary properties and promising applications. Here we predict the monolayered indium triphosphide (InP3) as a new semiconducting 2D material with a range of favorable functional properties by means of ab initio calculations. The 2D InP3 crystal shows high stability and promise of experimental synthesis. It possesses an indirect band gap of 1.14 eV and a high electron mobility of 1919 cm2 V-1 s-1, which can be strongly manipulated with applied strain. Remarkably, the InP3 monolayer suggests tunable magnetism and half-metallicity under hole doping or defect engineering, which is attributed to the novel Mexican-hat-like bands and van Hove singularities in its electronic structure. A semiconductor-metal transition is also revealed by doping 2D InP3 with electrons. Furthermore, monolayered InP3 exhibits extraordinary optical absorption with significant excitonic effects in the entire range of the visible light spectrum. All these desired properties render 2D InP3 a promising candidate for future applications in a wide variety of technologies, in particular for electronic, spintronic, and photovoltaic devices.


Antiphospholipid antibodies in patients with coronary artery disease: new cardiac risk factors?
Antiphospholipid antibodies (aPL) have been implicated in the pathogenesis of coronary artery disease (CAD). We evaluated the presence of aPL in patients with chest pain/acute coronary syndromes (ACS) to determine if aPL were associated with the presence and severity of CAD, adverse outcomes, and other coronary risk factors. Patients with chest pain/ACS were evaluated for aPL prior to diagnostic and therapeutic investigations. Coronary angiograms were graded according to the severity of disease. Risk factors, including family histories, were assessed and patients were followed for adverse outcomes. To date, 232 patients (116 M, 116 F, mean age 63 years) with a mean follow-up of 9 months were studied. Thirty-seven percent (86/232) were positive for one or more aPL. More women, 49/86 (57%), were aPL positive versus men, 37/86 (43%). The presence of aPL appeared associated with both presence and severity of CAD (P = 0.176 women; P = 0.163 men). In patients undergoing procedures (angioplasty, stent, bypass), aPL was significantly associated with both an increase in adverse cardiac outcomes (P = 0.045) and extracardiac thrombotic events (P = 0.033). Anti-beta2 glycoprotein-1 (abeta2GP1) was the most frequent aPL, occurring in 68.5% of aPL-positive patients with CAD. Anticardiolipin antibody (aCL) occurred in only 7.4%. IgM isotypes were the most frequent for all categories of aPL (range 55-90%). Family history of antiphospholipid syndrome (APS)-related events was more significant in aPL-positive than aPL-negative individuals (P = 0.027).


Behavioral sensitization to methamphetamine induces specific interneuronal mRNA pathology across the prelimbic and orbitofrontal cortices.
Schizophrenia is associated with significant pathophysiological changes to interneurons within the prefrontal cortex (PFC), with mRNA and protein changes associated with the GABA network localized to specific interneuron subtypes. Methamphetamine is a commonly abused psychostimulant that can induce chronic psychosis and symptoms that are similar to schizophrenia, suggesting that chronic METH induced psychosis may be associated with similar brain pathology to schizophrenia in the PFC. The aim of this study, therefore, was to examine mRNA expression of interneuron markers across two regions of the PFC (prelimbic (PRL) and orbitofrontal cortices (OFC)) following METH sensitization, an animal model of METH psychosis. We also studied the association between GABA mRNA expression and interneuronal mRNA expression to identify whether particular changes to the GABA network could be localized to a specific inhibitory cellular phenotype. METH sensitization increased the transcriptional expression of calbindin, calretinin, somatostatin, cholecyctokinin and vasoactive intestinal peptide in the PRL while parvalbumin, calbindin, cholectokinin and vasoactive intestinal peptide were upregulated in the OFC. Based on our previous findings, we also found significant correlations between GAD67, GAT1 and parvalbumin while GAD67, GAD65 and GAT1 were positively correlated with cholecystokinin in the PRL of METH sensitized rats. Within the OFC, the expression of GABAAα1 was positively correlated with somatostatin while GABAAα5 was negatively associated with somatostatin and calbindin. These findings suggest that METH sensitization differentially changes the expression of mRNAs encoding for multiple peptides and calcium binding proteins across the PRL and the OFC. Furthermore, these findings support that changes to the GABA network may also occur within specific cell types. These results, therefore, provide the first evidence that METH sensitization mediates differential interneuronal pathology across the PRL and OFC and such changes could have profound consequences on behavior and cognitive output.


Five-year Clinical Outcomes of CAD Patients Complicated with Diabetes after StentBoost-optimized Percutaneous Coronary Intervention.
Objective To evaluate the instant effects and five-year clinical outcomes of coronary artery disease patients complicated with diabetes mellitus after StentBoost-optimized percutaneous coronary intervention (PCI). Methods From March 2009 to July 2010, 184 patients undergoing PCI at our hospital were found stent underexpansion or malapposition by StentBoost after stents implantation and were divided into the diabetic (n=73, 39.67%) and the non-diabetic group (n=111, 60.33%). All patients received StentBoost-guided post-dilatation after stent implantation. The instant procedural results were measured and clinical outcome after five-year follow-up was analyzed in each group. Between-group comparisons were performed using Chi-square test or Student's t test. Multivariate logistic regression analysis was carried out to reveal the independent predictors for long-term clinical outcomes of StentBoost-optimized PCI . Results After StentBoost-guided post-dilatation, the minimum diameter (MinLD), maximum diameter (MaxLD) and average diameter in both groups increased significantly than before (P<0.001), the (MaxLD-MinLD)/MaxLD ratio and the in-stent residual stenosis decreased accordingly (P<0.001). The five-year follow-up showed similar mortality rate (4.92% vs. 2.86%, P=0.67) and major adverse cardiac event rate (11.48% vs. 11.43%, P = 1.0) between the diabetic and the non-diabetic group, whereas the recurrence of angina pectoris was higher in the diabetic group compared to the non-diabetic group (47.54% vs. 29.52%; P=0.02). A multivariate logistic regression analysis revealed that age and left ventricular ejection fraction rather than diabetes mellitus were independent predictors for long-term clinical outcomes. Conclusions StentBoost could effectively improve instant PCI results; the long-term clinical outcomes of StentBoost-optimized PCI were similar between diabetic and non-diabetic patients. Age and left ventricular ejection fraction were the independent predictors for long-term clinical outcomes.


Diastereodifferentiation of novel naphthalene dyads by fluorescence quenching and excimer formation.
Four new bichromophoric naphthalene dyads in form of diastereomeric pairs are synthesized and photophysically characterized. For a closely related group of compounds (NAP-NAP, MNAP-NAP, MNAP-MNAP), systematic variation of the urea linker led to the observation of intramolecular fluorescence quenching for tertiary urea, but not for secondary urea. Chiral information contained in the dyads has an impact on the efficiency of this process. Furthermore, for the case of (R,R)-MNAP-MNAP, excimer formation in the pre-organized dyad was noted, while being absent in the corresponding (R,S) diastereomer. These differences in photophysical behavior are ascribed to the geometry of the linker and to the chiral information contained in the diastereomeric compounds. Other dyads, such as NPX-NPX, included naproxen as the chromophore. For these compounds strong excimer emission is obtained, however, only very small diastereodifferentiation is observed for the two investigated stereoisomers.


Immunohistochemical detection of olfactory-specific sensory transduction proteins in olfactory neuroblastoma.
Olfactory neuroblastoma (ONB) is a malignant tumor found in the superior nasal cavity. Although there is not adequate molecular evidence, ONB is considered to develop from olfactory sensory neurons (OSNs). Here, we immunohistochemically detected intense signals for the olfactory-specific sensory transduction proteins, G(αolf), adenylyl cyclase III, and cyclic-nucleotide-gated channel A2 in ONB, together with the conventional ONB marker, neuron-specific enolase, while the established OSN markers, olfactory marker protein and growth-associated protein 43, were not detected. These results indicate that ONB and OSNs share the same lineage and that the detected transduction proteins could serve as specific tumor markers for ONB.


Res-FLNet: human-robot interaction and collaboration for multi-modal sensing robot autonomous driving tasks based on learning control algorithm.
Res-FLNet presents a cutting-edge solution for addressing autonomous driving tasks in the context of multimodal sensing robots while ensuring privacy protection through Federated Learning (FL). The rapid advancement of autonomous vehicles and robotics has escalated the need for efficient and safe navigation algorithms that also support Human-Robot Interaction and Collaboration. However, the integration of data from diverse sensors like cameras, LiDARs, and radars raises concerns about privacy and data security. In this paper, we introduce Res-FLNet, which harnesses the power of ResNet-50 and LSTM models to achieve robust and privacy-preserving autonomous driving. The ResNet-50 model effectively extracts features from visual input, while LSTM captures sequential dependencies in the multimodal data, enabling more sophisticated learning control algorithms. To tackle privacy issues, we employ Federated Learning, enabling model training to be conducted locally on individual robots without sharing raw data. By aggregating model updates from different robots, the central server learns from collective knowledge while preserving data privacy. Res-FLNet can also facilitate Human-Robot Interaction and Collaboration as it allows robots to share knowledge while preserving privacy. Our experiments demonstrate the efficacy and privacy preservation of Res-FLNet across four widely-used autonomous driving datasets: KITTI, Waymo Open Dataset, ApolloScape, and BDD100K. Res-FLNet outperforms state-of-the-art methods in terms of accuracy, robustness, and privacy preservation. Moreover, it exhibits promising adaptability and generalization across various autonomous driving scenarios, showcasing its potential for multi-modal sensing robots in complex and dynamic environments.


A genetic lesion that arrests plasma cell homing to the bone marrow.
The coordinated regulation of chemokine responsiveness plays a critical role in the development of humoral immunity. After antigen challenge and B cell activation, the emerging plasma cells (PCs) undergo CXCL12-induced chemotaxis to the bone marrow, where they produce Ab and persist. Here we show that PCs, but not B cells or T cells from lupus-prone NZM mice, are deficient in CXCL12-induced migration. PC unresponsiveness to CXCL12 results in a marked accumulation of PCs in the spleen of mice, and a concordant decrease in bone marrow PCs. Unlike normal mice, in NZM mice, a majority of the splenic PCs are long-lived. This deficiency is a consequence of the genetic interactions of multiple systemic lupus erythematosus susceptibility loci.


Relationship between premortem and postmortem diagnosis in critically ill bone marrow transplantation patients.
To determine the relationship between the premortem and postmortem diagnosis in critically ill bone marrow transplantation patients Also, to evaluate the appropriateness of the reliance on clinical diagnosis for withdrawal of active treatment decision-making. Retrospective cohort study. Two university-affiliated tertiary care medical surgical intensive care units. Critically ill bone marrow transplantation patients who died in the intensive care unit between November 1,1994, and June 30,1999, and underwent postmortem examination. Review of medical records by two independent data extractors. Clinical diagnosis and cause of death in the intensive care unit were compared with the final autopsy report. Premortem clinical diagnoses were classified according to the Goldman criteria and compared with postmortem findings. Twenty-eight autopsies were done. Ten of 28 (36%) patients had discrepancies uncovered on autopsy; only two discrepancies would have influenced patient management and none would have altered patient outcome. Twenty patients had their active treatment withdrawn and underwent postmortem examination. None of the discrepancies noted would have altered outcome in these patients. In the bone marrow transplantation population, there is significant concordance between clinical diagnosis and postmortem findings. Reliance on clinical diagnosis may be valid for withdrawal of active treatment decision-making in these patients.


Acute and Long-Term Consequences of Co-opted doublesex on the Development of Mimetic Butterfly Color Patterns.
Novel phenotypes are increasingly recognized to have evolved by co-option of conserved genes into new developmental contexts, yet the process by which co-opted genes modify existing developmental programs remains obscure. Here, we provide insight into this process by characterizing the role of co-opted doublesex in butterfly wing color pattern development. dsx is the master regulator of insect sex differentiation but has been co-opted to control the switch between discrete nonmimetic and mimetic patterns in Papilio alphenor and its relatives through the evolution of novel mimetic alleles. We found dynamic spatial and temporal expression pattern differences between mimetic and nonmimetic butterflies throughout wing development. A mimetic color pattern program is switched on by a pulse of dsx expression in early pupal development that causes acute and long-term differential gene expression, particularly in Wnt and Hedgehog signaling pathways. RNAi suggested opposing, novel roles for these pathways in mimetic pattern development. Importantly, Dsx co-option caused Engrailed, a primary target of Hedgehog signaling, to gain a novel expression domain early in pupal wing development that is propagated through mid-pupal development to specify novel mimetic patterns despite becoming decoupled from Dsx expression itself. Altogether, our findings provide multiple views into how co-opted genes can both cause and elicit changes to conserved networks and pathways to result in development of novel, adaptive phenotypes.


Effect of a change in lasmiditan dose on efficacy and safety in patients with migraine.
Background: Lasmiditan is a selective serotonin (1F) receptor agonist approved for acute treatment of migraine with 3 doses: 50, 100, and 200 mg.Objective: To help provide dosing insights, we assessed the efficacy and safety of lasmiditan in patients who treated two migraine attacks with the same or different lasmiditan doses.Methods: Integrated analyses used data from the migraine attack treated in either of two controlled, Phase 3, single attack studies (SAMURAI/SPARTAN), and after the first attack treated in the open-label GLADIATOR extension study. Eight patient groups were created based on the initial dose received in SAMURAI or SPARTAN and the subsequent dose in GLADIATOR: placebo-100, placebo-200, 50-100, 50-200, 100-100, 100-200, 200-100, 200-200. Migraine pain freedom, migraine-related functional disability freedom, most bothersome symptom (MBS) freedom, and pain relief were evaluated at 2-h post-dose. The occurrence of most common treatment-emergent adverse events (MC-TEAE) was evaluated. Shift analyses were performed for pain freedom and ≥1 MC-TEAE. The incidence of patients with a specific outcome from the first and subsequent doses were compared within each dose change group using McNemar's test.Results: Small, but consistent, increases in incidences of pain freedom, migraine-related functional disability freedom, MBS freedom, and pain relief occurred when the second lasmiditan dose was higher than the initial dose. For patients starting on 50 mg, increasing to 100 or 200 mg provided a positive efficacy-TEAE balance, despite an increase in incidence of ≥1 MC-TEAE. For patients starting on 100 mg, increasing to 200 mg provided a positive efficacy-TEAE balance. If the initial dose was 100 or 200 mg, the incidence of patients experiencing ≥1 MC-TEAE decreased or stayed the same with their subsequent dose, regardless of dose. Decreasing from 200 to 100 mg led to a decrease in patients with pain freedom and ≥1 MC-TEAE, resulting in a neutral efficacy-TEAE balance. Shift analyses supported these findings.Conclusion: A positive efficacy-TEAE balance exists for patients increasing their lasmiditan dose for treatment of a subsequent migraine attack. These results could be important for optimizing dosing for individual patients.Clinicaltrials.gov: SAMURAI (NCT02439320); SPARTAN (NCT02605174); GLADIATOR (NCT02565186).


Staff experiences of a new tool for comprehensive geriatric assessment in primary care (PASTEL): a focus group study.
Objective: Comprehensive geriatric assessment (CGA) is recommended for the management of frailty. Little is known about professionals' experiences of CGA; therefore we wanted to investigate the experiences of staff in primary care using a new CGA tool: the Primary care Assessment Tool for Elderly (PASTEL).Design: Focus group interviews. Manifest qualitative content analysis.Setting: Nine primary health care centres in Sweden that participated in a CGA intervention. These centres represent urban as well as rural areas.Subjects: Nine nurses, five GPs and one pharmacist were divided into three focus groups.Main outcome measures: Participants' experiences of conducting CGA with PASTEL.Results: The analysis resulted in four main categories. A valuable tool for selected patients: The participants considered the assessment tool to be feasible and valuable. They stated that having enough time for the assessment interview was essential but views about the ideal patient for assessment were divided. Creating conditions for dialogue: The process of adapting the assessment to the individual and create conditions for dialogue was recognised as important. Managing in-depth conversations: In-depth conversations turned out to be an important component of the assessment. Patients were eager to share their stories, but talking about the future or the end of life was demanding. The winding road of actions and teamwork: PASTEL was regarded as a good preparation tool for care planning and a means of support for identifying appropriate actions to manage frailty but there were challenges to implement these actions and to obtain good teamwork.Conclusion: The participants reported that PASTEL, a tool for CGA, gave a holistic picture of the older person and was helpful in care planning.Key pointsTo manage frailty using comprehensive geriatric assessment (CGA) in primary care, there is a need for tools that are efficient, user-friendly and which support patient involvement and teamwork•This study found that the Primary care Assessment tool for Elderly (PASTEL) is regarded as both valuable and feasible by primary care professionals•Use of carefully selected items in the tool and allowing enough time for dialogue may enhance patient-centeredness•The PASTEL tool supports the process of identifying actions to manage frailty in older adults. Teamwork related to the tool and CGA in primary care needs to be further investigated and developed.


Clinical and pharmacogenetic predictors of circulating atorvastatin and rosuvastatin concentrations in routine clinical care.
A barrier to statin therapy is myopathy associated with elevated systemic drug exposure. Our objective was to examine the association between clinical and pharmacogenetic variables and statin concentrations in patients. In total, 299 patients taking atorvastatin or rosuvastatin were prospectively recruited at an outpatient referral center. The contribution of clinical variables and transporter gene polymorphisms to statin concentration was assessed using multiple linear regression. We observed 45-fold variation in statin concentration among patients taking the same dose. After adjustment for sex, age, body mass index, ethnicity, dose, and time from last dose, SLCO1B1 c.521T>C (P<0.001) and ABCG2 c.421C>A (P<0.01) were important to rosuvastatin concentration (adjusted R(2)=0.56 for the final model). Atorvastatin concentration was associated with SLCO1B1 c.388A>G (P<0.01) and c.521T>C (P<0.05) and 4β-hydroxycholesterol, a CYP3A activity marker (adjusted R(2)=0.47). A second cohort of 579 patients from primary and specialty care databases were retrospectively genotyped. In this cohort, genotypes associated with statin concentration were not differently distributed among dosing groups, implying providers had not yet optimized each patient's risk-benefit ratio. Nearly 50% of patients in routine practice taking the highest doses were predicted to have statin concentrations greater than the 90th percentile. Interindividual variability in statin exposure in patients is associated with uptake and efflux transporter polymorphisms. An algorithm incorporating genomic and clinical variables to avoid high atorvastatin and rosuvastatin levels is described; further study will determine whether this approach reduces incidence of statin myopathy.


ESTIMATING REPRODUCIBLE FUNCTIONAL NETWORKS ASSOCIATED WITH TASK DYNAMICS USING UNSUPERVISED LSTMS.
We propose a method for estimating more reproducible functional networks that are more strongly associated with dynamic task activity by using recurrent neural networks with long short term memory (LSTMs). The LSTM model is trained in an unsupervised manner to learn to generate the functional magnetic resonance imaging (fMRI) time-series data in regions of interest. The learned functional networks can then be used for further analysis, e.g., correlation analysis to determine functional networks that are strongly associated with an fMRI task paradigm. We test our approach and compare to other methods for decomposing functional networks from fMRI activity on 2 related but separate datasets that employ a biological motion perception task. We demonstrate that the functional networks learned by the LSTM model are more strongly associated with the task activity and dynamics compared to other approaches. Furthermore, the patterns of network association are more closely replicated across subjects within the same dataset as well as across datasets. More reproducible functional networks are essential for better characterizing the neural correlates of a target task.


Comparison of growth performance and zinc absorption, retention, and excretion in weanling pigs fed diets supplemented with zinc-polysaccharide or zinc oxide.
Fifty weanling crossbred pigs averaging 6.2 kg of initial BW and 21 d of age were used in a 5-wk experiment to evaluate lower dietary concentrations of an organic source of Zn as a Zn-polysaccharide (Zn-PS) compared with 2,000 ppm of inorganic Zn as ZnO, with growth performance, plasma concentrations of Zn and Cu, and Zn and Cu balance as the criteria. The pigs were fed individually in metabolism crates, and Zn and Cu balance were measured on individual pigs (10 replications per treatment) from d 22 to 26. The basal Phase 1 (d 0 to 14) and Phase 2 (d 14 to 35) diets contained 125 or 100 ppm added Zn as Zn sulfate, respectively, and met all nutrient requirements. Treatments were the basal Phase 1 and 2 diets supplemented with 0, 150, 300, or 450 ppm of Zn as Zn-PS or 2,000 ppm Zn as ZnO. Blood samples were collected from all pigs on d 7, 14, and 28. For pigs fed increasing Zn as Zn-PS, there were no linear or quadratic responses (P > or = 0.16) in ADG, ADFI, or G:F for Phases 1 or 2 or overall. For single degree of freedom treatment comparisons, Phase 1 ADG and G:F were greater (P < or = 0.05) for pigs fed 2,000 ppm Zn as ZnO than for pigs fed the control diet or the diet containing 150 ppm Zn as Zn-PS. For Phase 2 and overall, ADG and G:F for pigs fed the diets containing 300 or 450 ppm of Zn as Zn-PS did not differ (P > or = 0.29) from pigs fed the diet containing ZnO. Pigs fed the diet containing ZnO also had a greater Phase 2 (P < or = 0.10) and overall (P < or = 0.05) ADG and G:F than pigs fed the control diet. There were no differences (P > or = 0.46) in ADFI for any planned comparison. There were linear increases (P < 0.001) in the Zn excreted (mg/d) with increasing dietary Zn-PS. Pigs fed the diet containing ZnO absorbed, retained, and excreted more Zn (P < 0.001) than pigs fed the control diet or any of the diets containing Zn-PS. In conclusion, Phase 2 and overall growth performance by pigs fed diets containing 300 or 450 ppm Zn as Zn-PS did not differ from that of pigs fed 2,000 ppm Zn as ZnO; however, feeding 300 ppm Zn as Zn-PS decreased Zn excretion by 76% compared with feeding 2,000 ppm Zn as ZnO.


Neuromuscular response to resistive unloading: helium vs. bronchodilation.
To evaluate the neuromuscular response to resistive unloading, we compared the ventilatory and occlusion pressure (P100) response of normal subjects breathing 20.9% O2 in helium (He-O2) with their response to unloading produced by inhaled atropine sulfate. During He-O2 breathing airway resistance (Raw) fell by 49% of the base-line value on air, and P100 decreased by 20.8%. Minute ventilation, tidal volume, respiratory frequency, end-tidal Pco2, inspiratory and expiratory duration, and mean inspiratory flow were not significantly different when air was replaced by He-O2. In contrast, although atropine reduced Raw by an equivalent amount, there was no change in P100. Atropine had no significant effect on other respiratory variables, although a trend toward higher minute ventilation was noted. Fowler dead space increased after atropine but was not affected by He-O2. We conclude that, unlike He-O2 unloading, atropine unloading does not cause a reduction in occlusion pressure. This may be due to the effect of atropine on anatomical dead space which stimulates ventilation sufficiently to offset the fall in neuromuscular output due to resistive unloading.


Sociology and the nursing curriculum: a note of caution.
One of the consequences of the expansion of degree, and diploma level Project 2000 courses in nursing, has been that students are now exposed to a significant amount of material from academic disciplines other than nursing, at a relatively advanced level. In this paper, one such discipline, sociology, is considered, and its relevance to the nursing curriculum is assessed. Following a consideration of two theoretical models of the relationship between academic disciplines and professional practice (the 'personal education' and 'semantic conjunction' models), it is argued that whilst the implicit rationale for the inclusion of sociology in the nursing curriculum can best be understood in relation to the latter, neither model offers a convincing reason as to why we should teach sociology to nurses. It is argued instead that the nature of sociological knowledge is inherently multi-paradigmatic, and hence reflexive, and so cannot in principle provide a knowledge base for action-oriented conduct such as nursing work.


Depression, immune function, and early adrenarche in children.
Despite consistent findings of an association between depression and immunity in adult and adolescent populations, little is known about the nature of this relationship at earlier ages. Studies of children have yielded mixed results, suggesting methodological confounds and/or the presence of significant moderating factors. Timing of adrenarche, the first phase of puberty that occurs during late childhood, is a plausible moderator of the depression-immunity relationship in late childhood due to its associations with both the immune system and psychological wellbeing. We hypothesized that: (1) a depression-immunity association exists in children, (2) this association is moderated by adrenarcheal timing, and, (3) this association is also moderated by gender. Data were drawn from a nested study of 103 participants (62 females, Mage=9.5, age range: 8.67-10.21 years) participating in a population based cohort study of the transition from childhood to adolescence (across puberty). Participants in this nested study completed the Children's Depression Inventory 2 (CDI-2) and provided morning saliva samples to measure immune markers (i.e., C-reactive protein, CRP; and secretory immunoglobulin A, SIgA). Using hierarchical regression, inflammation measured by CRP was positively associated with the negative mood/physical symptoms (NM/PS) subscale (β=0.23, t=2.33, p=0.022) of the CDI-2. A significant interaction effect of SIgA x adrenarcheal timing was found for NM/PS (β=-0.39, t=-2.19, p=0.031) and Interpersonal Problems (β=-0.47, t=-2.71, p=0.008). SIgA and NM/PS were positively associated for relatively late developers. SIgA and Interpersonal Problems were positively associated for late developers, and negatively associated for early developers. We suggest that both sets of findings might be partially explained by the immunosuppressive effect of the hormonal changes associated with earlier adrenarche, namely testosterone. These results also suggest that adrenarcheal timing has an effect on the association between depression and immunity, and is therefore an important measure in research with younger populations. Future research should utilize longitudinal designs to demonstrate direction of influence of variables, and use a broader range of pro- and anti-inflammatory markers.


Survival after refusal of surgical treatment for locally advanced laryngeal cancer.
Survival of advanced laryngeal cancer is declining while the popularity of organ preservation protocols grows. This study assesses the survival impact of refusing surgical treatment for locally advanced, resectable laryngeal cancer. Adult patients with T3 and T4a non-metastatic laryngeal squamous cell carcinoma were identified from the Surveillance, Epidemiology and End Results 18 database from 2004 to 2013. Patients were stratified based on a recommendation for extirpative surgery and the refusal of surgery. Multivariate logistic regression modeling identified variables associated with refusal. A multivariate cox proportional hazard model produced adjusted Kaplan-Meier survival curves. Survival was compared using adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Of 5786 patients in the study, 2877 were recommended for surgical treatment and 138 (4.8%) refused. Refusal of surgery was associated with unmarried status (Single, odds ratio (OR) 1.79, CI 1.10-2.92), black race (OR 1.50, CI 1.00-2.22), T3 tumors (OR 1.80, CI 1.26-2.61) and N3 nodal disease (OR 3.50, CI 1.24-8.48). Compared to patients undergoing surgery, those who refused had lower 5-year cancer specific survival and increased hazard of cancer-specific mortality (aHR 1.60, CI 1.24-2.07) which resulted in decreased 5-year survival (50.0vs 60.1%), after controlling for other factors. Refusal of surgery for locally advanced laryngeal cancer is more common in patients without marital support and with T3 tumors. This decision results in a 10% survival decrease at 5-year. Future study is needed to understand patients' reasoning behind this decision and to investigate additional factors not available in this dataset.


Spinning convincing stories for both true and false association signals.
When interpreting genome-wide association peaks, it is common to annotate each peak by searching for genes with plausible relationships to the trait. However, "all that glitters is not gold"-one might interpret apparent patterns in the data as plausible even when the peak is a false positive. Accordingly, we sought to see how human annotators interpreted association results containing a mixture of peaks from both the original trait and a genetically uncorrelated "synthetic" trait. Two of us prepared a mix of original and synthetic peaks of three significance categories from five different scans along with relevant literature search results and then we all annotated these regions. Three annotators also scored the strength of evidence connecting each peak to the scanned trait and the likelihood of further studying that region. While annotators found original peaks to have stronger evidence (p Bonferroni = 0.017) and higher likelihood of further study ( p Bonferroni = 0.006) than synthetic peaks, annotators often made convincing connections between the synthetic peaks and the original trait, finding these connections 55% of the time. These results show that it is not difficult for annotators to make convincing connections between synthetic association signals and genes found in those regions.


The effects of hyperbaric oxygen treatment on lipid peroxidation of pregnant rabbits and their fetus during late pregnancy.
To measure the effects of hyperbaric oxygen on lipid peroxidation of pregnant and fetal rabbits during late pregnancy. Sixteen pregnant rabbits were randomly and equally divided into two groups. One, the HBO2 group, was exposed to 2-atm oxygen for 60 min a day from the 21st to the 30th day of gestation, and the other group, non-HBO2 group, did not obtain any hyperbaric oxygen treatment. On the 30th day of pregnant period, the activity of antioxidant enzyme SOD in plasma of the pregnant rabbits of the HBO2 group was significantly higher than that of the non-HBO2 group, but there was no significant difference in the level of oxidative stress marker 8-iso-PG-F2 alpha between the two groups. As for the fetal rabbits, the SOD activity in umbilical plasma, placenta tissue and fetal brain tissue of HBO2 group was significantly higher than that of the non-HBO2 group, while there was no statistical difference between the concentrations of 8-iso-PG-F2 alpha of HBO2 and non-HBO2 group. HBO2 treatment during the late pregnancy up-regulates the activity of antioxidant enzyme in plasma of pregnant rabbits, placenta, umbilical plasma, and fetal brain. This does not have significant effect on the oxidative stress in these tissues.


[Mastoid osteosarcoma].
A case of osteogenic sarcoma of the mastoid region of the temporal bone in a 28-year-old male is reported. The rarity of the site is emphasized and the fundamental clinical and therapeutic features are discussed. The literature is reviewed.


DNA Aptamer Raised against Advanced Glycation End Products Prevents Abnormalities in Electroretinograms of Experimental Diabetic Retinopathy.
Abnormalities in electroretinograms (ERG), such as reduced amplitudes and delayed implicit times of a- and b-wave and oscillatory potentials (OPs), are one of the earliest features of diabetic retinopathy prior to obvious vascular changes in diabetic retinas. We have previously shown that serum levels of advanced glycation end products (AGEs) are correlated with a delayed latency of OPs in type 2 diabetic rats. However, the pathological role of AGEs in ERG abnormalities remains unclear. We examined here whether high-affinity DNA aptamer directed against AGEs (AGE-aptamer) prevents ERG abnormalities in experimental type 1 diabetic retinopathy. Streptozotocin-induced diabetic rats or control rats received continuous intraperitoneal infusion of either AGE-aptamer or control aptamer via an osmotic mini pump for 16 weeks. Anthropometric, metabolic, and hemodynamic variables were measured, and an ERG was performed. Although AGE-aptamer did not affect body weight, fasting and random blood glucose, HbA1c, blood pressure, or lipid parameters, it completely prevented the increase in serum AGE levels as well as the reduction of a- and b-wave and OP amplitudes in diabetic rats. The present study demonstrated for the first time that AGE-aptamer prevents abnormalities in ERG in experimental diabetic retinopathy probably by blocking the harmful effects of AGEs.


AtPDS overexpression in tomato: exposing unique patterns of carotenoid self-regulation and an alternative strategy for the enhancement of fruit carotenoid content.
The regulation of plant carotenogenesis is an active research area for both biological discovery and practical implementation. In tomato (Solanum lycopersicum), we demonstrate additional bottlenecks exist in the poly-cis-transformation of phytoene to lycopene in the context of ripening-induced PSY1 expression and activity and reveal phytoene desaturase (PDS), as a target for manipulation towards elevated lycopene content in maturing tomato fruit. Overexpression of Arabidopsis PDS, AtPDS, elevated PDS transcript abundance in all aerial tissues resulting in both altered carotenoid accumulation and associated pathway gene expression in a tissue-specific manner. Significant increases in downstream carotenoids (all-trans-lycopene and β-carotene) and minimal changes in carotenogenic gene expression (carotenoid isomerase-like 1, CRTIL1) suggest overexpression of heterologous AtPDS in tomato circumvents endogenous regulatory mechanism observed with previous strategies. In transgenic leaves, depletion of the PDS substrate, phytoene, was accompanied by minor, but significant increases in xanthophyll production. Alterations in the leaf carotenogenic transcript profile, including the upstream MEP pathway, were observed revealing unique feedback and feedforward regulatory mechanisms in response to AtPDS overexpression. AtPDS overexpression in the background of the tangerine (carotenoid isomerase, CRTISO) mutant exposes its potential in elevating downstream cis-lycopene accumulation in ripe tomato fruit, as cis-lycopene is more bioavailable yet less abundant than all-trans-lycopene in the wild-type control. In summary, we demonstrate the limitation of PDS in ripening fruit, its utility in modifying carotenoid profiles towards improved quality, and reveal novel carotenoid pathway feedback regulation.


Nicardipine versus nifedipine: multicentre controlled trial in essential hypertension.
Ninety-five hypertensive outpatients of both sexes, aged 23 to 65 years with diastolic blood pressures above 105 but below 120 mmHg (greater than 14.0 but less than 16.0 kPa), after one week on a placebo were randomly assigned either to nicardipine plus a placebo (40 mg/day - 48 patients) or nifedipine sustained-release plus a placebo (20 mg/day - 47 patients) for an additional six weeks. The study groups were homogeneous and comparable. After the run-in period the average blood pressure was 181 +/- 17/116 +/- 9 mmHg (24.1 +/- 2.3/15.5 +/- 1.2 kPa) in the nicardipine and 177 +/- 22/116 +/- 9 mmHg (23.6 +/- 2.9/15.5 +/- 1.2 kPa) in the nifedipine group (p greater than 0.10). In the acute oral test (nicardipine 40 mg to all the subjects; blood pressure measured at 30 min intervals during two hours) almost identical hypotensive effects within and between groups were observed (mean arterial pressure decrease of 11%, after 120 min; p less than 0.05). At the end of this trial blood pressure decreased further to 152 +/- 12/94 +/- 11 mgHg (20.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nicardipine and to 145 +/- 12/94 +/- 11 mmHg (19.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nifedipine. There were no significant changes in pulse rate. The observed between-group differences were trivial (p greater than 0.10). The laboratory data did not alter appreciably during this study. Three patients on nicardipine and four on nifedipine reported headache, palpitations and flushing: one patient on nicardipine and two on nifedipine were as a result excluded from the trial. It was concluded that nicardipine and nifedipine sustained-release were comparably effective and well-tolerated drugs suitable as the first-line agents for the management of mild to moderate hypertension.


Synaptic mechanisms in auditory cortex function.
Neurons in the auditory cortex (AC) respond to acoustic stimuli in diverse ways. Short latency responses code for the physical properties of stimuli, i.e., their frequency and intensity, whereas longer latency potentials may code for behavioral significance or other features. Despite a huge number of studies that, over the years, have reported on acoustic-evoked short and long-latency potentials, remarkably little is understood regarding the cellular mechanisms underlying these responses. Such information is critical to a full understanding of auditory information processing. This review summarizes the available data on synaptic and cellular mechanisms in AC neurons that have been obtained using electrophysiological methods with in vivo and in vitro preparations. It is apparent that the fundamental mechanisms identified in recent studies can be used in the near future to develop an integrated understanding of the cellular bases of information processing in auditory cortex.


Production of tense marking in successive bilingual children: when do they converge with their monolingual peers?
Children with English as a second language (L2) with exposure of 18 months or less exhibit similar difficulties to children with Specific Language Impairment in tense marking, a marker of language impairment for English. This paper examines whether L2 children with longer exposure converge with their monolingual peers in the production of tense marking. Thirty-eight successive bilingual Turkish-English speaking (L2) children with a mean age of 7;8 and 33 monolingual English-speaking (L1) age-matched controls completed the screening test of the Test of Early Grammatical Impairment (TEGI). The L2 children as a group were as accurate as the controls in the production of -ed, but performed significantly lower than the controls in the production of third person -s. Age and years of exposure (YoE) affected the children's performance. The highest age-expected performance on the TEGI was attested in 8- and 9-year-old children who had 4-6 YoE. L1 and L2 children performed better in regular compared to irregular verbs, but L2 children overregularized more than L1 children and were less sensitive to the phonological properties of verbs. The results show that tense marking and the screening test of the TEGI may be promising for differential diagnosis in 8- and 9-year-old L2 children with at least four YoE.


Growth propagation of yeast in linear arrays of microfluidic chambers over many generations.
The growth of microorganisms is often confined in restricting geometries. In this work, we designed a device to study the growth propagation of budding yeast along linear arrays of microfluidic chambers. Vacuum assisted cell loading was used to seed cells of limited numbers in the up-most chambers of each linear array. Once loaded, cells grow until confluent and then overgrow, pushing some of the newborns into the neighboring downstream chamber through connection channels. Such a scenario repeats sequentially along the whole linear chamber arrays. We observed that the propagation speed of yeast population along the linear arrays was strongly channel geometry dependent. When the connection channel is narrow and long, the amount of cells delivered into the downstream chamber is small so that cells grow over several generations in the same chamber before passing into the next chamber. Consequently, a population growth of more than 50 generations could be observed along a single linear array. We also provided a mathematical model to quantitatively interpret the observed growth dynamics.


Do collectivists know themselves better than individualists? Cross-cultural studies of the holier than thou phenomenon.
Collectivists know themselves better than individualists do, in that collectivists provide more accurate self-predictions of future behavior in situations with moral or altruistic overtones. In 3 studies, respondents from individualist cultures overestimated the likelihood that they would act generously in situations involving redistributing a reward (Study 1), donating money (Study 2), or avoiding rude behavior (Study 3), whereas collectivists were, in general, more accurate in their self-predictions. Both groups were roughly accurate in predicting the behavior of their peers. Collectivists were more accurate in their self-predictions than were individualists, even when both groups were sampled from the same cultural group (Study 4). Discussion centers on culturally specific motivations that may bias the accuracy of self-insight and social insight.


Effect of Inter-Fragmentary Gap Size on Neovascularization During Bone Healing: A Micro-CT Imaging Study.
Introduction: Neovascularization of the fracture site is of great importance for bone healing and could be influenced by local mechanical environment such as fixation stability and inter-fragmentary gap size. This study aims to reconstruct the neovascularization of the fracture site and explore the effect of inter-fragmentary gap size on the spatiotemporal structure of vascularity during bone healing. Methods: Osteotomy was performed on 36 Sprague-Dawley (SD) rats on the right tibial diaphysis, and the fracture was given stable fixation with two different inter-fragmentary gap sizes. SD rats received stable fixation with either a small-sized inter-fragmentary gap (FSF1, 1 mm, n = 18) or a large-sized one (FSF3, 3 mm, n = 18). The left hind limbs were treated as the control group (CON). The animals were killed at different time points (2, 4, and 6 weeks postoperatively, n = 6, respectively) for vascular perfusion and micro-CT imaging. Results: (a) At week 2 and 4, FSF1 group showed significantly higher vessel volume ratio (VV/TV) and vessel surface density (VS/TV) values than both CON and FSF3 group; there was no significant difference in either VV/TV or VS/TV values between CON and FSF3 groups. (b) At week 6, both FSF1 and FSF3 groups showed significantly higher VV/TV and VS/TV values than CON group; FSF3 group had a significantly higher VV/TV value than FSF1 group. Conclusion: Different inter-fragmentary gap sizes greatly affect the timing of angiogenesis at the fracture site. Stable fixation with a small inter-fragmentary gap (1 mm) benefits neovascularization at the early stages during bone healing and reconstruction, while stable fixation with a large inter-fragmentary gap (3 mm) delays the occurrence of angiogenesis to a later phase.