Effect of different carbon sources on aerobic storage by activated sludge.
A study of substrate removal by real activated sludge with several synthetic substrates (acetate, ethanol, glutamic acid) and wastewater (raw and filtered) was carried out. Substrate, stored compounds (polyhydroxyalkanoates, PHA and internal carbohydrates), ammonia and oxygen uptake rate (OUR) were analytically determined. Polyhydroxybutyrate (PHB) was stored when the substrate was acetate or ethanol, while no appreciable formation of storage compound was detected using glutamic acid. A low amount of PHB was also formed in tests with raw and filtered wastewater which was probably mainly due to its acetate content. As far as the sum of storage and growth (indirectly estimated through ammonia consumption) did not match the overall solids formation, other unidentified mechanisms of substrate removal were likely to occur (biosorption, accumulation and/or storage of unidentified compounds). ASM3 and two derived models were used in the interpretation of experimental data with reference to synthetic substrates. With reference to synthetic substrates ASM3 can well describe the experimental data only assuming a stored product formation much higher than the analytically detected one, whereas the model that assumes a parallel growth and storage on the substrate can well describe the observed stored product profile only assuming a direct contribution of growth much higher than estimated from ammonia consumption. The model that assumes an accumulation/biosorption stage as first step of substrate removal can better describe the whole experimentally observed behaviour. However as well as in ASM3 this implies that some fraction of removed COD is still unidentified. With reference to real wastewater where the different phenomena were mixed up due to the presence of several substrates, the different models gave similar results.


Does recurrent acute pancreatitis lead to chronic pancreatitis? Sequential morphological and biochemical studies.
The pathogenesis of chronic pancreatitis (CP) has been debated as to whether it is a de novo process or the consequence of acute pancreatitis (AP). We investigated whether recurrent AP in rats leads to CP, by sequential morphological and biochemical studies. Thirty male Wistar rats were fed a choline-deficient diet with intraperitoneal ethionine injections twice daily at a dose of 60 mg/100 g body weight twice weekly, and six rats were killed at 4, 6, and 8 weeks; the remaining 12 rats, followed without further treatment, were killed at 12 and 16 weeks. The pancreata from study and control groups were examined by histology, immunohistochemistry, and bio- and immunoassays. Histologically, moderate to severe intra- and perilobular fibrosis and other CP-like lesions appeared maximally at 8 weeks. Immunohistochemically, the earliest extracellular matrix change was strong fibronectin staining at 4 weeks, with a progressive increase to 8 weeks. Collagens I and III came to show strong, and collagen IV moderate, interstitial staining at 6-8 weeks. These morphological changes, however, returned to nearly normal at 16 weeks. Prolyl hydroxylase was significantly elevated at 4 and 6 weeks and normalized after 8 weeks, with no significant change in collagenase. In conclusion, our results suggest that even severe CP-like lesions induced by recurrent AP are reversible in the absence of persistently elevated prolyl hydroxylase and/or suppressed collagenase. The mechanism regulating these changes remains to be studied further.


Prebiotic potential of new sweeteners based on the simultaneous biosynthesis of galactooligosaccharides and enzymatically modified steviol glycosides.
Prebiotics are known for their health-promoting functions associated with the modulation of the colonic microbiota and the products of fermentation. Recently, single-pot syntheses of galactooligosaccharides in combination with steviol glycosides (mSG-GOS) have been developed. This work was conducted to evaluate their prebiotic effect by using faecal inoculum from healthy human donors during in vitro batch fermentations. Additionally, their relative sweetness was evaluated to determine their suitability as food ingredients. The results showed a significant growth (p < 0.05) of bacteria, including the genera Bifidobacterium, Bacteroides and Clostridium, and a corresponding increase in short-chain fatty acids (SCFA) in comparison to either positive and negative controls. The sweetness equivalence to 1 % w:v of SG-GOS was 0.8 % w:v when compared to sucrose. Considering the bacteria and organic acids analyses and their sweetness values of these new biosynthesized compounds, SG-GOS could act as a prebiotic sweetener with potential health benefits warranting further evaluation through human studies.


Short communication: Effect of whey protein addition and transglutaminase treatment on the physical and sensory properties of reduced-fat ice cream.
The effects of whey protein addition and transglutaminase treatment, alone and in combination, on the physical and sensory properties of reduced-fat ice cream were investigated. Adding whey protein with or without enzyme treatment decreased melting rate, overrun, and hardness of the reduced-fat ice cream; however, the enzyme-treated sample had a higher melting rate and overrun and softer texture. Whey protein-fortified samples showed higher melting resistance, but lower overrun and firmer texture compared with the enzyme-treated sample without added whey protein. Whey protein addition with or without transglutaminase treatment caused an increase in apparent viscosity and a decrease in flow index of the reduced-fat ice cream; nevertheless, the flow behavior of full-fat sample was most similar to the enzyme-treated reduced-fat sample with no added whey protein. Descriptive sensory analyses showed that neither whey protein addition nor transglutaminase treatment significantly influenced the flavor and odor of reduced-fat ice cream, but they both noticeably improved the color and texture of the final product. The results of this study suggest that whey protein addition with transglutaminase treatment improves the physical and sensory properties of reduced-fat ice cream more favorably than does whey protein addition or transglutaminase treatment alone.


An experimental investigation into the colonization of concealed cadavers by necrophagous blowflies.
We used seven baited boxes with different combinations of access holes and odor diffusion surfaces to study the arrival of necrophagous flies. During laboratory experiments, 30 gravid Lucilia sericata females were kept in a chamber with one of the boxes. The box with the largest odor diffusion surface (99 cm(2)) combined with the lowest accessibility (one 1 cm(2) entrance hole) was entered least (5 ± 3.7 flies per run). In contrast, the most frequently entered box (one 9 cm(2) entrance hole with no additional odor diffusion surface) caught a mean of 24.6 ± 3.4 flies per run. These results indicate that 1) L. sericata entered nearly inaccessible places and 2) both odor diffusion and accessibility impacted the number of flies caught. During field experiments, the seven boxes were placed together outdoors. The box with the most entrances (ten 9-cm(2) holes) caught the most flies (55.6-99.4% of the total). Only a few flies entered the other boxes. Access to the less accessible boxes (poor odor diffusion and small entrances) was also delayed. The major conclusions of the field experiments are that 1) boxes with low accessibility took longer to be accessed; 2) larger odor diffusion surfaces were more attractive to flies; and 3) flies accessed boxes more readily through larger holes than through an equivalent surface area made up of smaller holes. With these conclusions in mind, attempts to quantify the preappearance interval or to interpret the number of flies observed in indoor forensic entomology cases should be approached with caution.


Effects of different media on the in vivo chondrogenesis of sheep bone marrow stem cells: histological assessment.
This study aimed to compare the effects of three different media on the in vivo chondrogenesis of sheep bone marrow stem cells (BMSC). Sheep BMSC were cultured in F12:DMEM + 10% FBS, chondrogenic medium containing 5ng/ml TGF,3 + 50ng/ml IGF-1 and UKM-MECC for three weeks. The cultured cells were then harvested for construct formation with fibrin. Constructed tissues were implanted subcutaneously into nude mice for in vivo development. Cell aggregates were formed in both chondrogenic medium and UKM-MECC demonstrated the early chondrogenesis process. After five weeks of in vivo development, both chondrogenic medium and UKM-MECC promoted cartilage matrix synthesis confirmed by Safranin O staining.


A review on the use of membrane technology and fouling control for olive mill wastewater treatment.
Olive mill effluents (OME) by-produced have significantly increased in the last decades as a result of the boost of the olive oil agro-industrial sector and due to the conversion into continuous operation centrifugation technologies. In these effluents, the presence of phytotoxic recalcitrant pollutants makes them resistant to biological degradation and thus inhibits the efficiency of biological and conventional processes. Many reclamation treatments as well as integrated processes for OME have already been proposed and developed but not led to completely satisfactory and cost-effective results. Olive oil industries in its current status, typically small mills dispersed, cannot afford such high treatment costs. Furthermore, conventional treatments are not able to abate the significant dissolved monovalent and divalent ions concentration present in OME. Within this framework, membrane technology offers high efficiency and moderate investment and maintenance expenses. Wastewater treatment by membrane technologies is growing in the recent years. This trend is owed to the fact of the availability of new membrane materials, membrane designs, membrane module concepts and general know-how, which have promoted credibility among investors. However, fouling reduces the membrane performances in time and leads to premature substitution of the membrane modules, and this is a problem of cost efficiency since wastewater treatment must imply low operating costs. Appropriate fouling inhibition methods should assure this result, thus making membrane processes for wastewater stream treatment both technically and economically feasible. In this paper, the treatment of the effluents by-produced in olive mills, generally called olive mill wastewaters, will be addressed. Within this context, the state of the art of the different pretreatments and integral membrane processes proposed up to today will be gathered and discussed, with an insight in the problem of fouling.


Robust model benchmarking and bias-imbalance in data-driven materials science: a case study on MODNet.
As the number of novel data-driven approaches to material science continues to grow, it is crucial to perform consistent quality, reliability and applicability assessments of model performance. In this paper, we benchmark the Materials Optimal Descriptor Network (MODNet) method and architecture against the recently released MatBench v0.1, a curated test suite of materials datasets. MODNet is shown to outperform current leaders on 6 of the 13 tasks, while closely matching the current leaders on a further 2 tasks; MODNet performs particularly well when the number of samples is below 10 000. Attention is paid to two topics of concern when benchmarking models. First, we encourage the reporting of a more diverse set of metrics as it leads to a more comprehensive and holistic comparison of model performance. Second, an equally important task is the uncertainty assessment of a model towards a target domain. Significant variations in validation errors can be observed, depending on the imbalance and bias in the training set (i.e., similarity between training and application space). By using an ensemble MODNet model, confidence intervals can be built and the uncertainty on individual predictions can be quantified. Imbalance and bias issues are often overlooked, and yet are important for successful real-world applications of machine learning in materials science and condensed matter.


Reprogramming of myeloid cells and their progenitors in patients with non-medullary thyroid carcinoma.
Myeloid cells, crucial players in antitumoral defense, are affected by tumor-derived factors and treatment. The role of myeloid cells and their progenitors prior to tumor infiltration is poorly understood. Here we show single-cell transcriptomics and functional analyses of the myeloid cell lineage in patients with non-medullary thyroid carcinoma (TC) and multinodular goiter, before and after treatment with radioactive iodine compared to healthy controls. Integrative data analysis indicates that monocytes of TC patients have transcriptional upregulation of antigen presentation, reduced cytokine production capacity, and overproduction of reactive oxygen species. Interestingly, these cancer-related pathological changes are partially removed upon treatment. In bone marrow, TC patients tend to shift from myelopoiesis towards lymphopoiesis, reflected in transcriptional differences. Taken together, distinct transcriptional and functional changes in myeloid cells arise before their infiltration of the tumor and are already initiated in bone marrow, which suggests an active role in forming the tumor immune microenvironment.


Mutations of two lysine residues in the CDR loops of a recombinant immunotoxin that reduce its sensitivity to chemical derivatization.
B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of monoclonal antibody B3 is connected to a truncated form of Pseudomonas exotoxin. It would be desirable to use the lysine residues of the molecule for chemical modification so that it can be derivatized with poly(ethylene glycol) to achieve reduced immunogenicity or with the Bolton-Hunter reagent for biodistribution studies. We found that derivatizing lysine residues of B3(Fv)-PE38 causes a marked loss of specific target cell cytotoxicity and/or immunoreactivity. Here we show that two lysine residues in the antibody-combining region of B3(Fv)-PE38 can be replaced with arginines, with only a small loss of cytotoxicity and no change in specificity. This mutant molecule is 3-fold more resistant to inactivation by derivatization with succinimidyl 4-(N-maleimidomethyl)cyclohexane 1-carboxylate (SMCC) or Bolton-Hunter reagent.


Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells.
Activation of telomerase is crucial for cells to gain immortality. Most normal human somatic cells have a limited proliferative life span, and expression of the rate-limiting telomerase catalytic subunit, known as human telomerase reverse transcriptase (hTERT), has been believed to be tightly repressed. This model of hTERT regulation is challenged by the recent identification of the induction of hTERT in normal cycling human fibroblasts during their transit through S phase. Here we show the small-molecule-based identification of the assembly and disassembly of E2F-pocket protein-histone deacetylase (HDAC) complex as a key mechanistic basis for the repression and activation of hTERT in normal human cells. A cell-based chemical screen was used to identify a small molecule, CGK1026, that derepresses hTERT expression. CGK1026 inhibits the recruitment of HDAC into E2F-pocket protein complexes assembled on the hTERT promoter. Chromatin immunoprecipitation analysis reveals dynamic alterations in hTERT promoter occupancy by E2F and pocket proteins according to the cell cycle-dependent regulation of hTERT. Dominant-negative or protein-knockout strategies to disrupt the assembly of E2F-pocket protein-HDAC complex derepress hTERT and telomerase activity. Taken together with the results on the regulatory function of these complexes in cellular senescence and tumorigenesis, our findings suggest that dynamic assembly of E2F-pocket protein-HDAC complex plays a central role in the regulation of hTERT in a variety of proliferative conditions (e.g., normal cycling, senescent, and tumor cells).


[Vertebral artery dissection following manipulation of the cervical vertebrae].
We report on two patients who developed symptoms and signs of infarction of dorsolateral medulla oblongata (Wallenberg's syndrome) and the cerebellum respectively, following cervical manipulation for slight neck pain. Subsequent vertebral artery angiography and MRI showed the typical signs of vertebral artery dissection of the atlantoaxial and intracranial segment in one patient, and of the intertransverse segment in the second. The pathogenesis of vertebral artery injury following cervical manipulation is discussed and the literature is reviewed. The practical implications of this rare complication are discussed.


Characterization of two unrelated satellite DNA families in the Colorado potato beetle Leptinotarsa decemlineata (Coleoptera, Chrysomelidae).
The Colorado potato beetle (Leptinotarsa decemlineata, family Chrysomelidae),a phytophagous insect, which feeds preferably on potatoes, constitutes a serious pest of this crop and causes extensive damage to tomatoes and egg plants. It has a remarkable ability to develop resistance quickly against insecticides and shows a diversified and flexible life history. Consequently, the control of this pest has become difficult, requiring the development of new alternative biotechnology-based strategies. Such strategies require a thorough knowledge of the beetle's genome,including the repetitive DNA. Satellite DNA (stDNA), composed of long arrays of tandemly arranged repeat units, constitutes the major component of heterochromatin and is located mainly in centromeric and telomeric chromosomal regions. We have studied two different unrelated satellite-DNA families of which the consensus sequences were 295 and 109bp in length, named LEDE-I and LEDE-II, respectively.Both were AT-rich (70.8% and 71.6%, respectively). Predictive models of sequence-dependent DNA bending and the study of electrophoretic mobility on non-denaturing polyacrylamide gels have shown that the DNA was curved in both satellite-DNA families. Among other features, the chromosome localization of both stDNAs has been studied. In situ hybridization performed on meiotic and mitoticnuclei showed chromosomes, including the X chromosome, with zero, one, or two stDNAs. In recent years, it has been proposed that the repetitive DNA may play a key role in biological diversification processes. This is the first molecular and cytogenetic study conducted on L. decemlineata repetitive DNA and specifically on stDNA, which is one of the important constituents of eukaryotic genomes.


Antiviral activity of sulfated Chuanmingshen violaceum polysaccharide against Newcastle disease virus.
Newcastle disease virus (NDV) is a member of Paramyxovirinae subfamily and can infect most species of birds causing severe economic losses. The current control measure is vaccination, but infections cannot be completely prevented. It remains a constant threat to the poultry industry and new control measures are urgently needed. This study demonstrates that sulfated Chuanmingshen violaceum polysaccharides (sCVPSs) were potent inhibitors of NDV, with 50 % inhibitory concentrations (IC50) ranging from 62.55 to 76.31 µg ml(-1) in Baby hamster kidney fibroblasts clone 21 (BHK-21) and from 101.57 to 125.90 µg ml(-1) in chicken embryo fibroblasts (CEF). sCVPS is more effective than heparan sulfate (HS; as a positive control) with IC50 values of 99.28 µg ml(-1) in BHK-21 and 118.79 µg ml(-1) in CEF. sCVPSs and HS exhibit anti-NDV activity by prevention of the early stages of viral life. The mechanism of action study indicated that virus adsorption in BHK-21, and both virus adsorption and penetration in CEF were inhibited by sCVPSs. When the number of viruses was increased to an m.o.i. of 0.1 in the immunofluorescence study and to an m.o.i. of 1 in the fluorescent quantitative PCR study, viral infection was also significantly suppressed; the antiviral activity of sCVPSs was independent of the m.o.i. sCVPSs also prevented the cell-to-cell spread of NDV. In vivo tests carried out on specific pathogen-free (SPF) chickens showed that sCVPSs also inhibited virus multiplication in heart, liver, spleen, lung and kidney. These results indicated that sCVPSs perform more effectively than HS as antiviral agents against NDV, and can be further examined for their potential as an alternative control measure for NDV infection.


Sensorimotor gating impairments induced by MK-801 treatment may be reduced by tolerance effect and by familiarization in monkeys.
Dizocilpine (MK-801) is a non-competitive NMDA antagonist that induces schizophreniclike effects. It is therefore widely used in experimental models of schizophrenia including prepulse inhibition (PPI) impairments in rodents. Nevertheless, MK-801 has never been tested in monkeys on a PPI paradigm. In order to evaluate MK-801 effects on monkeys' PPI, we tested eight capuchin monkeys (Sapajus spp.) using three different doses of MK-801 (0.01; 0.02; 0.03 mg/kg). Results show PPI impairment in acute administration of the highest dose (0.03 mg/kg). PPI impairment induced by MK-801 was reversed by re-exposure to the PPI test throughout treatment trials, in contrast with rodent studies. These results indicate that tolerance effect and familiarization with PPI test may reduce the sensorimotor gating deficits induced by MK-801 in monkeys, suggesting a drug-training interaction.


Effective temperature in nonequilibrium steady states of Langevin systems with a tilted periodic potential.
We theoretically study Langevin systems with a tilted periodic potential. It is known that the ratio Theta of the diffusion constant D to the differential mobility mu(d) is not equal to the temperature of the environment (multiplied by the Boltzmann constant), except in the linear response regime, where the fluctuation dissipation theorem holds. In order to elucidate the physical meaning of Theta far from equilibrium, we analyze a modulated system with a slowly varying potential. We derive a large scale description of the probability density for the modulated system by use of a perturbation method. The expressions we obtain show that Theta plays the role of the temperature in the large scale description of the system and that Theta can be determined directly in experiments, without measurements of the diffusion constant and the differential mobility. Hence the relation D= mu(d) Theta among the independent measurable quantities D, mu(d), and Theta can be interpreted as an extension of the Einstein relation.


Colloid-polymer mixtures under slit confinement.
We report a NVT molecular dynamic study of colloid-polymer mixtures under slit confinement. For this purpose, we are employing the Asakura-Oosawa model for studying colloidal particles, polymer coils, and hard walls as the external confining field. The colloid-polymer size ratio, q, is varied in the range 1⩾q⩾0.4 and the confinement distance, H, in 10σc⩾H⩾3σc, σc being the colloidal diameter. Vapor-liquid coexistence properties are assessed, from which phase diagrams are built. The obtained data fulfill the corresponding states law for a constant H when q is varied. The shift of the polymer and colloidal chemical potentials of coexistence follows a linear relationship with (H-σc)-1 for H≳4σc. The confined vapor-liquid interfaces can be fitted with a semicircular line of curvature (H-σc)-1, from which the contact angle can be obtained. We observe complete wetting of the confining walls for reservoir polymer concentrations above and close to the critical value, and partial wetting for reservoir polymer concentrations above and far from it.


A new species of Antherospora supports the systematic placement of its host plant.
The morphology and phylogeny of anther smut specimens on Tractema verna collected in the United Kingdom were investigated using light microscopy, scanning electron microscopy and partial rDNA sequence analyses. The anther smut of Tractema verna shows similarity to Antherospora eucomis, A. scillae, A. tourneuxii, A. urgineae, A. vaillantii, and A. vindobonensis but differs in spore size range, spore wall thickness, host plant genera and considerable divergences of ITS and LSU sequences. Consequently, the smut is described here as a new species, Antherospora tractemae. The host plant was formerly included in the genus Scilla (S. verna), but recently moved to a distinct genus Tractema. Molecular phylogenetic analyses reveal that Antherospora tractemae is sister to the lineage of Muscari-parasitizing Antherospora and only distantly related to the Scilla-parasitizing Antherospora species. Thus, the phylogenetic placement of the smut fungus supports the systematic placement of its host plant.


SAW-LC coupled resonator wideband VCO for medical telemetry.
Wireless links with implantable devices can help in real-time monitoring of symptoms, irregularities, implanted device efficacy and their reconfiguration. We present the design of a low-power wideband voltage controlled oscillator (VCO) to facilitate implantable wireless telemetry. A coupled SAW-LC resonator design combines high Q and spectral purity of a SAW element and tunability of an LC-tank. The designed 2.7 MHz bandwidth VCO is suitable for full duplex communication protocols in the MedRadio band with frequency agility and higher duty cycles, in conformance with FCC regulations. Output power at the fundamental frequency is above -7.5 dBm for a wide range of load impedances. Output power load insensitivity provides a wide margin for selection of communication system parameters, variability in device placement, temporal variation in tissue properties and flexibility for implants at different locations (e.g. heart, gastrointestinal tract, brain). The maximum output power variation in the entire 2.7 MHz band is limited to 1.3 dBm. Sensitivity of oscillation frequency to loading can be addressed by individual device calibration. The small size, component count and low DC power consumption (1.9 V, ~1.95 mW) is favorable for including in a miniaturized and integrated design assembly with a battery-powered implanted device.


Evaluation of the human immunodeficiency virus type 1 and 2 antibodies detection in dried whole blood spots (DBS) samples.
Human Immunodeficiency Virus Type 1 and 2 antibodies detection was performed in 457 dried whole blood spots samples (S&S 903). Q-Preven HIV 1+2 was the screening test used. The results were compared with the gold standard serum tests by ELISA (Cobas Core e Axsym HIV1/2 gO) and immunofluorescence was the definitive confirmatory test. The samples were obtained from the Hospital Nossa Senhora da Conceição in Porto Alegre, RS - Brazil, through whole blood transfer to filter paper card and sent to Caxias do Sul, RS-Brazil where the tests were performed. The dried whole blood spot stability was evaluated with two different panels. The first one was composed of five negative and five positive samples stored at room temperature, 4 degrees C, -20 degrees C and -70 degrees C, while the second was composed of two negative and three positive samples stored at 37 degrees C (humidity <50%). Each sample was screened every week for six weeks. These measurement results didn't show variation during the study period. The detected sensibility was 100%, specificity was 99.6%, the positive predictive value was 99.5% and negative predictive values were 100%. The results demonstrated high performance characteristics, opening a new perspective of dried whole blood spot utilization in HIV screening diagnosis.


Compliance with guidelines for ADHD: a pilot study of an evaluation tool.
The investigators developed a 1-page chart abstraction tool to evaluate compliance with practice guidelines for attention deficit hyperactivity disorder. The tool had strong inter-rater reliability, with kappa of 0.81. Pilot testing for 57 children with attention deficit hyperactivity disorder showed only 12% documented full compliance with assessment guidelines and 44% with treatment guidelines.


Postsynaptic alpha-adrenoceptors in the perfused canine saphenous vein in vitro.
To study the relative localization of alpha 1 and alpha 2-adrenoceptors in relation to the intima and the adventitia of canine saphenous vein, a comparison was made of the potency of alpha 1- and alpha 2-adrenoceptor agonists applied by intraluminal and extraluminal route of perfused segments of that vessel. Noradrenaline was the most potent of the agonists used and was approximately as potent by intraluminal as by extraluminal route. Cocaine (12 mumol/l) caused supersensitivity to noradrenaline which was of about the same magnitude (threefold) irrespective of the route of administration of noradrenaline. The selective alpha 1-agonist phenylephrine was about 10 times less potent than noradrenaline and was also equieffective by both routes. The selective alpha 2-agonist UK-14,304, at concentrations lower than 0.3 mumol/l, caused very small responses and only in 3 out of 14 experiments. In all cases it caused responses at concentrations higher than 0.3 mumol/l. Cocaine did not change the sensitivity to either phenylephrine or UK-14,304. Thus, it is concluded that the results obtained with cocaine agreed with expectations for a homogeneously innervated tissue. Furthermore, alpha 1-adrenoceptors seem to predominate and to be evenly distributed throughout the media. The lack of responses to the low concentrations of UK-14,304--those selectively acting on alpha 2-adrenoceptors--was ascribed to the very low efficacy of this agonist on the distal part of the canine saphenous vein and to the tone created by the perfusion pressure which might be high enough to mask this small response.


[A case of extrahepatic bile duct metastasis from gastric cancer].
A 56-year-old man was admitted with obstructive jaundice. Abdominal computed tomography and endoscopic retrograde cholangiopancreatography showed circumferential stenosis with irregular wall in lower bile duct, but the cytology of biliary brushing was no malignancy. The patient was given a diagnosis of gastric carcinoma with bone and skin metastasis. He died 2 months after the first hospital admission and autopsy was performed. The histological findings of gastric and bile duct tumor revealed signet ring cell carcinoma. The immunohistological findings of both tumors were identical. We definitively diagnosed this case as metastasis of gastric carcinoma to the bile duct.


North and South Indian populations share a common ancestral origin of Friedreich's ataxia but vary in age of GAA repeat expansion.
Friedreich's ataxia (FRDA) is caused by expansion of GAA repeats in the frataxin (FXN) gene on chromosome 9q13-q21.1. We analysed the origin of FRDA in 21 North Indian (NI) and eight South Indian (SI) families using five single nucleotide polymorphisms (SNPs) and a microsatellite marker spanning the GAA repeats. The NI and SI families were derived from Indo-European and Dravidian linguistic backgrounds respectively. The frequency of large normal (LNs) alleles of the GAA repeat correlate with the overall lower prevalence of FRDA in India compared to the European population. All of the expanded alleles in the Indian population share a common core haplotype suggesting a founder effect. The expanded alleles in the NI population demonstrate more similarity to those of Europeans in terms of age of GAA repeat expansion (15975 +/- 2850 years) and association of LNs with expanded alleles. FRDA seems to have been introduced recently in the South Indian population since the average estimated age of the mutation in SI is 5425 +/- 1750 years and unlike NI some of the haplotypes of LNs are not associated with the expanded alleles.


A novel mitochondrial membrane protein, Ohmm, limits fungal oxidative stress resistance and virulence in the insect fungal pathogen Beauveria bassiana.
The Hog1 mitogen-activated protein (MAP) kinase regulates environmental stress responses and virulence in the entomopathogenic fungus Beauveria bassiana. To further characterize this pathway, we constructed a subtraction library enriched for genes regulated by Hog1. One targeted gene, encoding a novel membrane protein, Ohmm (oxidative homeostasis membrane-protein-mitochondria), was uniquely identified as being downregulated in the ΔHog1 background during growth under non-stress and osmotic stress conditions, but upregulated under oxidative stress. Ohmm was an experimentally validated flavin-binding protein and targeted to the mitochondria. Deletion of Ohmm resulted in increased oxidative stress resistance, whereas overexpression caused an opposite phenotype. The ΔOhmm showed accumulation of reactive oxygen species with alterations in cell wall composition and compatible solute accumulation evident as compared with the wild type parent. Conidiation was reduced > 80%; however, conidia produced by the ΔOhmm strain germinated significantly faster than wild type cells. Insect bioassays using the greater wax moth revealed increased virulence for the ΔOhmm strain in both topical and intrahemocoel injection assays, indicating a negative effect of the presence of Ohmm with respect to pathogenesis. As predicted from our characterization, deletion of Ohmm in a ΔHog1 background rescued its oxidative sensitivity phenotype, confirming that Ohmm acts downstream of the Hog1 MAP-kinase.


Persistence of the fetal cardiopulmonary circulatory pathway: survival of an infant after a prolonged course;.
The first case of "idiopathic" persistence of the fetal cardiopulmonary circulatory pathway with survival after a prolonged course is documented by serial cardiac catheterizations. All previously reported infants have either markedly improved within the first week of life or subsequently died. This entity has been described in term infants with prenatal or perinatal distress who present with tachypnea and cyanosis from birth. The chest radiograph is remarkable for the absence of pulmonary parenchymal pathology and the hemoglobin and hematocrit are normal. Blood gas determinations indicate hypoxia and acidosis with or without hypercarbia. Cardiac catheterization and angiography reveal an anatomically normal heart with severe pulmonary hypertension, left ventricular pressure lower than right ventricular pressure, and right-to-left venoarterial shunting through the fetal channels (atrial and or ductal levels). It is postulated that this entity may result from antenatal factors that affect the pulmonary vasculature and its subsequent adjustment to extrauterine life. These factors may include abnormal intrauterine stress resulting in excessive hypertrophy of the pulmonary arteriolar smooth muscle, or abnormal pulmonary vascular responsiveness to the usual vasoactive stimuli before or after birth, or an immature or dysfunctioning enzyme system necessary for the normal decrease in pulmonary artery pressure.


[The concept and definition of locomotive syndrome in a super-aged society].
The population of elderly individuals who need nursing care is rapidly increasing in Japan. Locomotive syndrome involves a decrease in mobility due to locomotive organ dysfunction, and increases risk for dependency on nursing care service. Because gait speed and chair stand time are correlated with such risks, patients with locomotive syndrome are assessed using brief methods such as the two-step test, which involves dividing the maximum stride length by the height of the patient, and the stand-up test, which involves standing on one or both legs at different heights. One leg standing and squatting are recommended as beneficial locomotive home exercises. Locomotive syndrome has been recognized widely in Japan, and included in the National Health Promotion Movement (2013-2022).


Identification of c.1531C>T Pathogenic Variant in the CDH1 Gene as a Novel Germline Mutation of Hereditary Diffuse Gastric Cancer.
Germline pathogenic variants in the CDH1 gene are a well-established cause of hereditary diffuse gastric cancer (HDGC) syndrome. The aim of this study was to characterize CDH1 mutations associated with HDGC from Chile, a country with one of the highest incidence and mortality rates in the world for gastric cancer (GC). Here, we prospectively include probands with family history/early onset of diffuse-type of GC. The whole coding sequence of the CDH1 gene was sequenced from genomic DNA in all patients, and a multidisciplinary team managed each family member with a pathogenic sequence variant. Thirty-six cases were included (median age 44 years/male 50%). Twenty-seven (75%) patients had diffuse-type GC at ≤50 years of age and 19 (53%) had first or second-degree family members with a history of HDGC. Two cases (5.5%) carried a non-synonymous germline sequence variant in the CDH1 gene: (a) The c.88C>A missense variant was found in a family with three diffuse-type GC cases; and (b) c.1531C>T a nonsense pathogenic variant was identified in a 22-year-old proband with no previous family history of HDGC. Of note, six family members carry the same nonsense pathogenic variant. Prophylactic gastrectomy in the proband's sister revealed stage I signet-ring cell carcinoma. The finding of 1531C>T pathogenic variant in the CDH1 in proband with no previous family history of HDGC warrants further study to uncover familial clustering of disease in CDH1 negative patients. This finding may be particularly relevant in high incidence countries, such as the case in this report.


Fiber-Optic Skew Ray Sensors.
The evanescent fields along multimode fibers are usually relatively weak. To enhance the sensitivity of the resulting sensors, skew rays have been exploited for their larger number of total internal reflections and their more comprehensive spread over the fiber surface. The uniform distribution of light-matter interactions across the fiber surface facilitates high sensitivity through an increased interaction area, while mitigating the risk of laser-induced coating-material damage and photobleaching. Power-dependent measurements are less susceptible to temperature effects than interferometric techniques, and place loose requirements on the laser source. This review highlights the key developments in this area, while discussing the benefits, challenges as well as future development.


"We and the nurses are now working with one voice": How community leaders and health committee members describe their role in Sierra Leone's Ebola response.
Across low-income settings, community volunteers and health committee members support the formal health system - both routinely and amid emergencies - by engaging in health services such as referrals and health education. During the 2014-2015 Ebola epidemic, emerging reports suggest that community engagement was instrumental in interrupting transmission. Nevertheless, literature regarding community volunteers' roles during emergencies generally, and Ebola specifically, is scarce. This research outlines what this cadre of the workforce did, how they coped, and the facilitators and barriers they faced to providing care in Sierra Leone. Thirteen focus group discussions (FGD) were conducted with community members (including members of Health Management Committees (HMC)) near the height of the Ebola epidemic in two districts of Sierra Leone: Bo and Kenema. Conducted in either Krio or Mende, each FGD lasted an average of two hours and was led by a trained moderator who was accompanied by a note taker. All FGDs were audio recorded, transcribed, and translated into English by the data collection team. Analysis followed a modified framework approach, which entailed coding (both inductive and deductive), arrangement of codes into themes, and drafting, distribution and discussion of analytic summaries across the study team. Community volunteers and HMC members described engaging in labor-related tasks (e.g. building isolation structures, digging graves) and administrative/community-outreach tasks (e.g. screening, contact tracing, and encouraging care seeking within facilities). Through their dual orientation as community members and as individuals linked to the health system, respondents described building community trust and support for Ebola prevention and treatment, while also enabling formal health workers to better understand and address people's fears and needs. Community volunteers' main concerns included inadequate communication with - and a sense of being forgotten by - the health system, negative perceptions of their role within their communities, and concerns regarding the amount and nature of their compensation. Respondents described commitment to supporting their health system and their communities during the Ebola crisis. The health system could more effectively harness the potential of local responders by recognizing community strengths and weaknesses, as well as community volunteers' motivations and limitations. Clarifying the roles, responsibilities, and remuneration of health volunteers to the recipients themselves, facility-based staff, and the wider community will enable organizations that partner with health committees to bolster trust, manage expectations, and reinforce collaboration.


Effect of a whey-predominant starter formula containing LCPUFAs and oligosaccharides (FOS/GOS) on gastrointestinal comfort in infants.
Development of new infant formulas aims to replicate the benefits of breast milk. One benefit of breast milk over infant formulas is greater gastrointestinal comfort. We compared indicators of gastrointestinal comfort in infants fed a whey-predominant formula containing long-chain polyunsaturated fatty acids, galacto-oligo-saccharides and fructo-oligosaccharides, and infants fed a control casein-predominant formula without additional ingredients. The single-centre, prospective, double-blind, controlled trial randomly assigned healthy, full-term infants (n=144) to receive exclusively either experimental or control formula from 30 days to 4 months of age. A group of exclusively breast-fed infants served as reference (n=80). At 1, 2, 3, and 4 months, infants' growth parameters were measured and their health assessed. Parents recorded frequency and physical characteristics of infants' stool, frequency of regurgitation, vomiting, crying and colic. At 2-months, gastric emptying (ultrasound) and intestinal transit time (H2 breath test) were measured, and stool samples collected for bacterial analysis. Compared to the control (n=69), fewer of the experimental group (n=67) had hard stools (0.7 vs 7.5%, p<0.001) and more had soft stools (90.8 vs 82.3%, p<0.05). Also compared to the control, the experimental group's stool microbiota composition (mean % bifidobacteria: 78.1 (experimental, n=17), 63.7 (control, n=16), 74.3 (breast-fed, n=20), gastric transit times (59.6 (experimental, n=53), 61.4 (control, n=62), 55.9 (breast-fed, n=67) minutes) and intestinal transit times (data not shown) were closer to that of the breast-fed group. Growth parameter values were similar for all groups. The data suggest that, in infants, the prebiotic-containing whey-based formula provides superior gastrointestinal comfort than a control formula.


Stopping power of dense plasmas: The collisional method and limitations of the dielectric formalism.
We present a study of the stopping power of plasmas using two main approaches: the collisional (scattering theory) and the dielectric formalisms. In the former case, we use a semiclassical method based on quantum scattering theory. In the latter case, we use the full description given by the extension of the Lindhard dielectric function for plasmas of all degeneracies. We compare these two theories and show that the dielectric formalism has limitations when it is used for slow heavy ions or atoms in dense plasmas. We present a study of these limitations and show the regimes where the dielectric formalism can be used, with appropriate corrections to include the usual quantum and classical limits. On the other hand, the semiclassical method shows the correct behavior for all plasma conditions and projectile velocity and charge. We consider different models for the ion charge distributions, including bare and dressed ions as well as neutral atoms.


[Dual mediating effects of positive and negative emotions on fertility stress and fertility quality of life among infertile men in China].
To explore the effects of fertility stress on the quality of life (QOL) of infertile men and the dual mediating roles of positive and negative emotions in fertility stress and fertility QOL. Using the Fertility Problem Inventory, Fertility Quality of Life Questionnaire and Positive and Negative Affect Scale, we conducted a cross-sectional survey among 304 infertile men. We established a structural equation model for analysis of the relationship between the four variables of fertility stress, fertility QOL, positive emotion and negative emotion. The scores of the patients in fertility stress, fertility QOL, positive emotion and negative emotion were (158.42 ± 21.725), (60.72 ± 10.926), (32.15 ± 6.294) and (19.48 ± 6.378), respectively. The root mean square error approximation (RMSEA) of the direct effect model, positive emotion separate mediation model and negative emotion separate mediation model was >0.08, and the dual mediation model showed optimum fit indexes, with χ2 / df = 1.959, goodness of fit index (GFI) = 0.950, adjusted GFI (AGFI) = 0.919, normed fit index (NFI) = 0.899, incremental fit index (IFI) = 0.948, Tucker-Lewis index (TLI) = 0.926, comparative fit index (CFI) = 0.947, and RMSEA = 0.056. The results of bootstrap test indicated that the positive and negative emotions had significant mediating effects, both incomplete, on fertility stress and fertility QOL. Moreover, the separate mediation of positive emotion exhibited no statistically significant difference from that of negative emotion (95% CI: -0.063 to 0.028). Positive emotion and negative emotions are part of the intermediary in fertility stress and fertility QOL. Fertility stress can affect fertility QOL through the dual mediating effect of positive emotion and negative emotions in infertile men.


Presence of integrons in isolates of different biotypes of Acinetobacter baumannii from Chilean hospitals.
Class 1 and class 2 integrons were investigated by hybridisation in 100 isolates of multiresistant biotypes of Acinetobacter baumannii from Chilean hospitals. Most isolates of A. baumannii biotype 9, the prevalent biotype, harboured integrons of class 2 (Tn7-like) whereas no integrons were detected in infrequent biotypes. Integron-carrying isolates exhibited broader antibiotic resistance patterns as well as higher resistance levels to various antimicrobials.


Most probable distance between the nucleus and HOMO electron: the latent meaning of atomic radius from the product of chemical hardness and polarizability.
The simple relationship between size of an atom, the Pearson hardness, and electronic polarizability is described. The estimated atomic radius correlates well with experimental as well as theoretical covalent radii reported in the literature. Furthermore, the direct connection of atomic radius to HOMO electron density and important notions of conceptual DFT (such as frontier molecular orbitals and Fukui function) has been shown and interpreted. The radial maximum of HOMO density distribution at (αη)(1/2) minimizes the system energy. Eventually, the knowledge of the Fukui function of an atom is sufficient to estimate its electronic polarizability, chemical potential, and hardness.


[A case of atypical malignant hyperthermia which presented a typical rise in Ca-induced Ca release after the operation].
A 61-year-old man showed clinical findings which suggest atypical malignant hyperthermia after pancreatoduodenectomy. He showed no abnormal findings in preoperative examinations. General anesthesia was induced with thiopental, fentanyl, and vecuronium, and epidural anesthesia was also used for the perioperative management. The surgery went on uneventfully and the patient returned to the ward. The laboratory data after the surgery showed extremely high creatine kinase and myoglobin. The patient's body temperature rose up and showed rigidity. We suspected atypical malignant hyperthermia and began its treatment. Four months later, we performed muscle biopsy and Ca-induced Ca release (CICR) test, which presented a typical rising pattern. This is the first case of malignant hyperthermia which occurred after the surgery and accompanied by a typical rise in CICR.


'State-of-the-heart' of cardiac laminopathies.
LMNA gene encodes the nuclear A-type lamins. LMNA mutations are associated with more than 10 clinical entities and represent one of the first causes of inherited dilated cardiomyopathy. LMNA-dilated cardiomyopathy is associated with conduction disease (DCM-CD) and is a severe and aggressive form of DCM. However, pathogenesis remains largely unknown and no specific treatment is currently available for the patients. In this review, we present recent discoveries that improve the understanding of the cardiac pathophysiological roles of A-type lamins and shed light on potential therapeutic targets. In the last decade, many efforts have been made to elucidate how mutations in A-type lamins, ubiquitous proteins, lead to DCM-CD. No clear genotype/phenotype correlations have been found to help in elucidating those mechanisms. Analysis of several mouse models has helped in deciphering critical pathomechanisms. Among those, Mitogen-activated protein kinases (MAPK) and Akt/mTOR appear to be key early-activated signaling pathways in LMNA DCM-CD in both humans and mice. Inhibition of these signaling pathways has shown encouraging beneficial effects upon cardiac evolution of DCM-CD. These recent findings suggest that targeting MAPK and Akt/mTOR pathways with potent and specific compounds represents a promising intervention for the treatment of LMNA DCM-CD.


Human X-chromosomal lineages in Europe reveal Middle Eastern and Asiatic contacts.
Within Europe, classical genetic markers, nuclear autosomal and Y-chromosome DNA polymorphisms display an east-west frequency gradient. This has been taken as evidence for the westward migration of Neolithic farmers from the Middle East. In contrast, most studies of mtDNA variation in Europe and the Middle East have not revealed clinal distributions. Here we report an analysis of dys44 haplotypes, consisting of 35 polymorphisms on an 8 kb segment of the dystrophin gene on Xp21, in a sample of 1203 Eurasian chromosomes. Our results do not show a significant genetic structure in Europe, though when Middle Eastern samples are included a very low but significant genetic structure, rooted in Middle Eastern heterogeneity, is observed. This structure was not correlated to either geography or language, indicating that neither of these factors are a barrier to gene flow within Europe and/or the Middle East. Spatial autocorrelation analysis did not show clinal variation from the Middle East to Europe, though an underlying and ancient east-west cline across the Eurasian continent was detected. Clines provide a strong signal of ancient major population migration(s), and we suggest that the observed cline likely resulted from an ancient, bifurcating migration out of Africa that influenced the colonizing of Europe, Asia and the Americas. Our study reveals that, in addition to settlements from the Near East, Europe has been influenced by other major population movements, such as expansion(s) from Asia, as well as by recent gene flow from within Europe and the Middle East.


Validation of a Simple HPLC-UV Method for the Determination of Monomers Released from Dental Resin Composites in Artificial Saliva.
Bisphenol-A (BPA), bisphenol A glycerolate dimethacrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), and urethane dimethacrylate (UDMA) are organic monomers that can be released from dental composites into the oral cavity. Over specific concentrations, they can act as endocrine disruptors or cause toxic effects. The purpose of this work is to develop and validate an analytical method to determine BPA, Bis-GMA, TEGDMA, and UDMA monomers released from synthetic dental resins in artificial saliva. The method was validated before its application to new hybrid ceramic materials used in computer-aided design and computer-aided manufacturing (CAD/CAM) restorations to determine the release of monomers in various time intervals (e.g., 24 h, and 7, 14, 30, and 60 days), both in methanolic solutions, as well as in artificial saliva. Chromatographic analysis was performed isocratically on a Perfect Sil Target ODS-3 analytical column (250 mm × 4.6 mm, 5 µm) with CH3CN/H2O, 58/42% v/v as mobile phase within 23 min. The developed method was validated in terms of selectivity, linearity, accuracy, and precision.


A modified vaccination technique for the prevention and treatment of an experimental autoimmune kidney disease.
The main purpose of this article is to introduce a promising new vaccination technique and to outline its efficacy and safety as demonstrated in an experimental autoimmune kidney disease. We have found that antigen (AG)-specific downregulation and/or upregulation of immune responses can be achieved by injections of immune complexes (ICs) which contain prepackaged information. This result is attained with the new vaccination method, a method developed in our laboratory which we have called "modified vaccination technique" (MVT). This MVT not only enables the prevention of pathogenic autoimmune events leading to the development of an experimental autoimmune kidney disease; it also allows, with equal effectiveness, therapeutic intervention to terminate the disease. With an injected IC containing predetermined immune response-inducing components, the process effectuates a specific antibody information transfer conferring advantages that go beyond its prophylactic and therapeutic applicability. Its specificity can induce a precise immune response to correct mishaps, for example, in conditions where the immune system overreacts to an autologous antigen or fails to recognize unwanted self (as in autoimmune disorders, cancer, etc.) Preformed ICs are nontoxic and nonirritant, evoke a predetermined antibody response without the use of adjuvants, cause no disturbance in the overall regulatory function of the immune system, and produce no side effects. We firmly believe that proper implementation of the MVT will be able to induce and maintain specific preventive and/or curative responses in a way that is both natural and more effective in patients with chronic ailments presently treatable only with drugs.


Breeding sex ratio and population size of loggerhead turtles from Southwestern Florida.
Species that display temperature-dependent sex determination are at risk as a result of increasing global temperatures. For marine turtles, high incubation temperatures can skew sex ratios towards females. There are concerns that temperature increases may result in highly female-biased offspring sex ratios, which would drive a future sex ratio skew. Studying the sex ratios of adults in the ocean is logistically very difficult because individuals are widely distributed and males are inaccessible because they remain in the ocean. Breeding sex ratios (BSR) are sought as a functional alternative to study adult sex ratios. One way to examine BSR is to determine the number of males that contribute to nests. Our goal was to evaluate the BSR for loggerhead turtles (Caretta caretta) nesting along the eastern Gulf of Mexico in Florida, from 2013-2015, encompassing three nesting seasons. We genotyped 64 nesting females (approximately 28% of all turtles nesting at that time) and up to 20 hatchlings from their nests (n = 989) using 7 polymorphic microsatellite markers. We identified multiple paternal contributions in 70% of the nests analyzed and 126 individual males. The breeding sex ratio was approximately 1 female for every 2.5 males. We did not find repeat males in any of our nests. The sex ratio and lack of repeating males was surprising because of female-biased primary sex ratios. We hypothesize that females mate offshore of their nesting beaches as well as en route. We recommend further comparisons of subsequent nesting events and of other beaches as it is imperative to establish baseline breeding sex ratios to understand how growing populations behave before extreme environmental effects are evident.


Correlation between sleep disorder screening and executive dysfunction in children with attention deficit-hyperactivity disorder.
To compare frequency of sleep disorders (SD) and executive dysfunction (ED) in children with attention deficit-hyperactivity disorder (ADHD) and a control group. We studied 156 children with ADHD with a mean age of 8.5 years, and a control group with 111 children with a mean age of 8.3 years. We utilized the Pediatric Sleep Questionnaire (PSQ) to screen SD and the working memory measurement from the Wechsler intelligence scale for children (WISC-IV) to screen ED. We did not observe an increased frequency of SD in children with ADHD compared with the controls. However, we did identify ED in children with ADHD; additionally a significant correlation was observed between the type of ADHD and SD and among ED, WISC-IV measurements, and type of SD in children with ADHD. An increase of SD frequency in children with ADHD was not observed, but we did identify ED in children with ADHD. Additionally, a correlation among ADHD types, SD, ED, and WISC-IV measurements was observed in children with ADHD.


Influence of narrow-band UVB phototherapy on cutaneous microbiota of children with atopic dermatitis.
In the present work, the effect of narrow-band ultraviolet B (UVB) phototherapy on a cutaneous microbial population was evaluated in patients with atopic dermatitis (AD) and compared with control patients (vitiligo). Count, isolation and identification of cutaneous microbiota from anticubital fossa were performed in 10 controls and 10 AD patients, both submitted to similar levels (P > 0.05) of UVB phototherapy (4.3 +/- 0.9 and 4.3 +/- 0.8 accumulated joules, respectively). Additionally, Staphylococcus aureus isolates were screened for the production of exotoxins. The total and staphylococcal cutaneous microbial population levels were higher (P < 0.05) in AD patients than in the controls. All these population levels decreased (P < 0.05) for both AD and control patients after UVB phototherapy, which also decreased the SCORAD for AD patients. All patients with AD and 50% of controls were carriers of S. aureus, and harboured the bacteria simultaneously on skin and anterior nares. All of the S. aureus strains recovered from AD patient skin produced toxin and the B type was the most frequently detected (70%), followed by C (20%) and A (10%) toxins. Only 40% of the S. aureus isolates from control patients produced toxin. After UVB treatment, microbial population levels of AD patients were similar (P > 0.05) to the ones found in control patients before phototherapy, and toxin production ability of S. aureus isolates decreased drastically. The results of the present study show the beneficial effect of UVB phototherapy on AD and suggest that this may be attributable not only to reduction of skin surface bacteria but also to the suppression of superantigen production from S. aureus.


Association of abnormal serum lipids in elderly persons with atherosclerotic vascular disease and dementia, atherosclerotic vascular disease without dementia, dementia without atherosclerotic vascular disease, and no dementia or atherosclerotic vascular disease.
Observational data have shown that the use of statins was associated with a lower prevalence of vascular dementia and of Alzheimer's disease. We investigated in an academic nursing home the association of dyslipidemia with atherosclerotic vascular disease (group 1), atherosclerotic vascular disease without dementia (group 2), dementia without atherosclerotic vascular disease (group 3), and no dementia or atherosclerotic vascular disease (group 4). Increased serum low-density lipoprotein (LDL) cholesterol was present in 36 of 50 group 1 patients (72%), in 34 of 50 group 2 patients (68%), in 34 of 50 group 3 patients (68%), and in 18 of 50 group 4 patients (36%) (p =.0003 for 1 versus 4; p = 0.001 for 2 versus 4 and 3 versus 4). Decreased serum high-density lipoprotein (HDL) cholesterol was present in 34 of 50 group 1 patients (68%), in 35 of 50 group 2 patients (70%), in 32 of 50 group 3 patients (64%), and in 16 of 50 group 4 patients (32%) (p =.0003 for 1 versus 4; p =.0001 for 2 versus 4; p =.001 for 3 versus 4). Hypertriglyceridemia was not significantly different in the 4 groups. The prevalence of increased serum LDL cholesterol and decreased serum HDL cholesterol were significantly higher in elderly patients with atherosclerotic vascular disease plus dementia, atherosclerotic vascular disease without dementia, and dementia without atherosclerotic vascular disease than in patients with no dementia or atherosclerotic vascular disease.


Toxoplasmosis and the compromised host.
A high percentage of population shows antibodies to Toxoplasma gondii yet clinical manifestations of primary infestations are rare. Congenital and secondary forms (chorioretinitis) are serious medical conditions. An outburst in a compromised host is always serious and may be fatal. Therefore, patients subjected to immunosuppressive therapy or with pathologic immune suppression should be clinically and serologically screened and, when toxoplasmosis is diagnosed, treated for the entire period of immunosuppression.


Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study.
Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN.


The enantioseparation of amino acids on a teicoplanin chiral stationary phase using non-aqueous mobile phases after pre-column derivatization with sulfur-containing reagents: the considerations of mobile phase composition and analyte structure variation on resolution enhancement.
Amino acids were derivatized with sulfur-containing reagents in alkaline medium and enantioresolved by HPLC on a teicoplanin chiral stationary phase. Much better resolution was achieved using methanol-based mobile phase compared with elution with acetonitrile-based solvent mixture. The value of selectivity factor for many derivatives examined in the study can be easily several tenths of 100 or even exceed 100 in some cases. This magnitude of resolution is suitable for the preparative-scale application of isolating alpha-amino acid enantiomers in the derivatized form using a short column. The resolution is believed to be a result of the hydrogen bonding and steric hindrance by the nitrogen and sulfur atoms from the isothiocyanatyl fragment of the reagent, respectively, and is enhanced as the fragment is structurally phenylated (e.g. 2,4-difluorophenyl isothiocyanate and others examined in this study). The enhancement is even more significant if the aromatic moiety of the reagent becomes more acidic through halogenation with chlorine or fluorine for the stronger pi-pi interaction. However, this type of enhancement is offset to some extent and sometimes obscured by a chlorinated reagent that is relatively large in size as compared with the fluorinated one. Judging from the chromatographic data and the elution profile, the mechanisms leading to the resolutions are believed to be different under the elution of polar-organic mobile phases (i.e. methanol- and acetonitrile-based mobile phases).


Identification of patients with childhood moyamoya diseases showing temporary hypertension after anesthesia by preoperative multifractal Hurst analysis of heart rate variability.
This study was performed to determine whether the preoperative multifractal Hurst analysis of heart rate variability might identify and characterize childhood patients with moyamoya disease (MMD) who showed temporary postoperative hypertension. We studied 59 childhood patients with MMD. Thirty were classified as hypertensive group when the mean arterial pressure in the postoperative recovery room was 120% or greater than that during the preoperative period and 29 were classified as normotensive group. The 2 groups were compared with respect to preoperative indices of heart rate variability including frequency-domain measures, approximate entropy, and very short-term multifractal Hurst exponents of RR intervals (RRI). Using preoperative indices that showed significant differences, discriminant analysis was performed to identify postoperative hypertensive patients. Only exponents of the order > or =3 (H3alpha, H4alpha, and H5alpha) were significantly lower in the hypertensive group than in the normotensive group. Frequency-domain measures, approximate entropy, and the exponents of the order < or =2 were not significantly different in the 2 groups. Discriminant analysis using all of the three exponents correctly identified 27/30 (90%) of the postoperative hypertensive patients. Preoperative very short-term multifractal Hurst analysis of RRI variability identified 90% of childhood MMD patients who developed postoperative hypertension. The preoperative characteristic of RRI variability was the reduced smoothness at the 8-second-long, local RRI regions within which a very large change of RRI occurs.


The impact of stage and cell type on the prognosis of pulmonary neuroendocrine tumors.
In pulmonary neuroendocrine tumors the realization that the extent of nodal disease is related to cell type has led to a controversy as to which is the dominant prognostic factor, stage or morphology. To clarify this relationship, we studied patients treated at our institution over a 23-year period. This is a historical cohort study of patients with confirmed pulmonary neuroendocrine tumors who underwent lung resection from 1980 through 2003. Survivors were contacted by telephone, and recurrences were confirmed by means of histopathology. Cox proportional hazards regression was used to ascertain the joint influence of several risk factors on survival. The mean age of the cohort was 54 years (standard deviation, 15 years), and 100 (57%) were men. The cell types for the 177 eligible patients were typical carcinoid in 89 (50%), atypical carcinoid in 15 (8%), large cell in 22 (13%), and small cell in 51 (29%). The median time to follow-up was 7 years (first to third quartile, 2-12 years), and overall 5- and 10-year survivals were 86% (79%-90%) and 81% (74%-87%), respectively. The univariable predictors of survival were age (P = .001), nodal stage (P = .01), and cell type (P < .001). In the final multivariable model only age (P = .04) and cell type (P < .001) remained as independent predictors. The hazard of death among patients with large cell or small cell lung cancer was highest in the first year and a half after diagnosis, reducing drastically thereafter. In pulmonary neuroendocrine tumors cell type is the predominant determinant of survival. The survival of patients with each cell type is sufficiently diverse to warrant different management strategies. Conservative resection is feasible for typical carcinoids, but the effects of adjuvant chemotherapy need to be evaluated for the other subgroups.


Efficacy of a potential trivalent vaccine based on Hc fragments of botulinum toxins A, B, and E produced in a cell-free expression system.
Botulinum toxins produced by the anaerobic bacterium Clostridium botulinum are the most potent biological toxins in nature. Traditionally, people at risk are immunized with a formaldehyde-inactivated toxin complex. Second generation vaccines are based on the recombinant carboxy-terminal heavy-chain (Hc) fragment of the neurotoxin. However, the materialization of this approach is challenging, mainly due to the high AT content of clostridial genes. Herein, we present an alternative strategy in which the native genes encoding Hc proteins of botulinum toxins A, B, and E were used to express the recombinant Hc fragments in a cell-free expression system. We used the unique property of this open system to introduce different combinations of chaperone systems, protein disulfide isomerase (PDI), and reducing/oxidizing environments directly to the expression reaction. Optimized expression conditions led to increased production of soluble Hc protein, which was successfully scaled up using a continuous exchange (CE) cell-free system. Hc proteins were produced at a concentration of more than 1 mg/ml and purified by one-step Ni(+) affinity chromatography. Mice immunized with three injections containing 5 microg of any of the in vitro-expressed, alum-absorbed, Hc vaccines generated a serum enzyme-linked immunosorbent assay (ELISA) titer of 10(5) against the native toxin complex, which enabled protection against a high-dose toxin challenge (10(3) to 10(6) mouse 50% lethal dose [MsLD(50)]). Finally, immunization with a trivalent HcA, HcB, and HcE vaccine protected mice against the corresponding trivalent 10(5) MsLD(50) toxin challenge. Our results together with the latest developments in scalability of the in vitro protein expression systems offer alternative routes for the preparation of botulinum vaccine.


A simple derivation of the exact quasiparticle theory and its extension to arbitrary initial excited eigenstates.
The quasiparticle (QP) energies, which are minus of the energies required by removing or produced by adding one electron from/to the system, corresponding to the photoemission or inverse photoemission (PE/IPE) spectra, are determined together with the QP wave functions, which are not orthonormal and even not linearly independent but somewhat similar to the normal spin orbitals in the theory of the configuration interaction, by self-consistently solving the QP equation coupled with the equation for the self-energy. The electron density, kinetic, and all interaction energies can be calculated using the QP wave functions. We prove in a simple way that the PE/IPE spectroscopy and therefore this QP theory can be applied to an arbitrary initial excited eigenstate. In this proof, we show that the energy-dependence of the self-energy is not an essential difficulty, and the QP picture holds exactly if there is no relaxation mechanism in the system. The validity of the present theory for some initial excited eigenstates is tested using the one-shot GW approximation for several atoms and molecules.


Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis.
It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6-82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8-80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4-89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4-89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.


Lateralization of cognitive functions after stroke in childhood.
A child's brain shows a remarkable ability to recover from adverse events such as stroke. Language functions recover particularly well, while visuo-spatial skills are more affected by brain damage, regardless of its localization. This study investigated the lateralization of language and visual search after childhood stroke. Ten patients with unilateral stroke (aged 10-19 years, five left-, five right-sided lesion) and 20 healthy controls (aged 8-20 years) completed a neuropsychological test battery and functional magnetic resonance imaging (fMRI) intended to activate predominantly right (visual search) and left-sided functional networks (language). After stroke, patients demonstrated atypical lateralization of visual search functions (8/10 patients, left lateralization) more often than that of language (4/10 patients, right lateralization). There was a dissociation between the lateralization of productive and semantic language (4/10 patients, 1/20 controls) and between the lateralization of simple and complex visual search (3/10 patients, 3/20 controls). In patients, atypical contralateral activations occurred in the same areas that showed decreasing activation during development in healthy participants. The lateralization of functions depends upon the cognitive function measured. Dissociation between the lateralization of different language or visual search tasks can occur.


A look at a deviant group of medical school applicants.
A total of 246 physicians who either had graduated from or had matriculated without graduating from dental school prior to entering a medical school were identified, and a combination multiple-choice, open-ended questionnaire was mailed to the group. Completed questionnaires were recived from 194 subjects for a 79 percent response rate. The questionnaire was designed to elicit information about the decision to study dentistry and the subsequent decision to study medicine. The authors were also interested in the process of admission to medical school, in academic performance in both schools, in choice of medical specialty, and in attitudes toward dentistry and medicine.


Effect and mechanism of epigallocatechin-3-gallate (EGCG). against the hydrogen peroxide-induced oxidative damage in human dermal fibroblasts.
This study was conducted to investigate the protective effects of epigallocatechin-3-gallate (EGCG) on hydrogen peroxide (H2O2)-induced oxidative stress injury in human dermal fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and the use of Hoechst staining and terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptosis detection indicated that the administration of H2O2 to human dermal fibroblasts caused cell damage and apoptosis. The incubation of human dermal fibroblasts with EGCG markedly inhibited the human dermal fibroblast injury induced by H2O2. The assay for 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity indicated that EGCG had a direct, concentration-dependent antioxidant activity. Treatment of human dermal fibroblasts with EGCG significantly reversed the H2O2-induced decrease of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), and the inhibition of malondialdehyde (MDA) levels. These results showed that EGCG possessed antioxidant activity and was effective against H2O2-induced human dermal fibroblast injury by enhancing the activity of SOD and GSH-px, and by decreasing the MDA level. Our results suggested that EGCG should have the potential to be used further in cosmetics and in the prevention of aging-related skin injuries.


Hip flexion weakness is associated with impaired mobility in oculopharyngeal muscular dystrophy: a retrospective study with implications for trial design.
Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy for which validated outcome measures are lacking, posing a barrier to clinical trials. Our goal was to identify factors associated with impaired mobility in OPMD in order to guide development of surrogate endpoints in future clinical trials. One hundred forty-four individuals with OPMD were included in this retrospective, single-center study. We made novel use of parametric time-to-event analysis to model age at initial use of assistive device for ambulation. We hypothesized that limb weakness and other markers of disease severity are associated with earlier use of assistive devices. 23.6% of individuals (34/144) progressed to use of assistive devices (mean age 66.0 ± 9.6 y). Earlier age at assistive device was associated with hip flexion Medical Research Council grade ≤3 (p <0.0001), earlier disease onset (p <0.0001), and lack of blepharoptosis surgery (p = 0.011). Markers of dysphagia severity were not associated with earlier progression to assistive devices. Our study is the first to show a statistical association between hip flexion weakness and impaired mobility in OPMD, indicating that hip flexion strength could be explored as a surrogate endpoint for use in clinical trials. Since severity of disease features may be discordant within individuals, composite outcome measures are warranted.


Ethological approach to autism spectrum disorders.
The purpose of the study was to develop a new ethogram for the assessment of children and adolescents with autism spectrum disorders (ASD) and intellectual developmental disorder (IDD) and to test whether this instrument accurately distinguishes ASD participants (n = 61) from IDD participants (n = 61). An ethogram with 88 behavior elements was generated, including body postures, verbalizations, facial expressions, motor stereotypies, head postures, gaze behavior, gestures, and interpersonal distance. Significant differences were detected between both groups in classic ASD behaviors; in behaviors that are deficient in ASD according to established theoretical models, such as symbolic play, gaze direction, gaze following, and use of mental state language; in atypical behaviors that have also been described previously in ethological studies with ASD; and in the nonspecific behaviors of ASD, such as walk, look own body, explore, and cry. The predictive success of a diagnosis of ASD in the logistic regression model with the ethogram's factors was 98.4%. The results suggest that this ethogram is a powerful and useful tool for both the detailed study of the social behaviors of autistic children and adolescents, and for discriminating ASD and IDD.


Current therapy of small cell lung cancer.
This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated with initial versus delayed radiotherapy. No survival differences in the larger study of the two studies were detected, which compared alternating with sequential delivery of radiotherapy (n = 335). The optimal way to deliver radiotherapy still must be defined. Two small, randomized studies on dose intensity with the use of growth factor support in patients with extensive disease reached conflicting results. Two randomized trials including patients with poor prognosis were discontinued prematurely, owing to interim analyses reporting a significant disadvantage in survival associated with oral single-agent etoposide compared with intravenous multiagent treatment. Thus, oral etoposide has a very limited role as single-agent treatment in the palliative setting. Convincing data have emerged regarding the camptothecins. Randomized studies of both the camptothecins and the taxanes in combination with established drugs are awaited with interest. Unfortunately, too many studies still lack sufficient statistical power, and large randomized studies are needed.


A MYB coiled-coil transcription factor interacts with NSP2 and is involved in nodulation in Lotus japonicus.
Transcription factor complex formation is a central step in regulating gene expression. In this report, a novel MYB coiled-coil transcription factor referred to as IPN2, for Interacting Protein of NSP2, is described. The interaction between IPN2 and NSP2 was examined by protein pull-down assays and bimolecular fluorescence complementation (BiFC). Subcellular localization of proteins, gene expression and gene function were assessed in transgenic hairy roots expressing tagged recombinant proteins, promoter-reporter and RNA interference (RNAi) constructs, respectively. The GRAS domain of NSP2 and the coiled-coil domain of IPN2 were found to be responsible for the interaction between the two proteins. IPN2 had strong transcription activation activity, bound directly to the NIN gene promoter, and was localized to the nuclei of Lotus japonicus root cells. The expression of IPN2 was elevated during nodule development, coinciding with increased NSP2 gene expression during nodule organogenesis. RNAi-mediated knockdown expression of IPN2 did not affect arbuscular mycorrhizal development, but had deleterious effects on rhizobial infection and nodule formation in L. japonicus. These results demonstrate an important role of IPN2 in nodule organogenesis and place a new MYB transcription factor in the Nod signaling pathway.


Apoptotic Cell Clearance in Development.
Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology.


[Risk factor of intestinal colonization with vancomycin resistant Enterococcus spp in hospitalized pediatric patients with oncological disease].
The isolation of vancomycin-resistant Enterococcus spp (ERV) has increased significantly within the last few years, along with the risk of infection and dissemination of these bacteria. Our aim was to determine risk factors (RF) for intestinal colonization in hospitalized pediatric patients with oncological disease at Hospital de Niños Roberto del Río. Between January 2012 and December 2013 a transversal study was performed with 107 rectal swabs and processed with a PCR for ERV. The patients were classified as "colonized with ERV" and "not colonized with ERV" and we evaluated possible RF for intestinal colonization in both groups. VRE colonization was found in 51 patients (52%). The median of time elapsed between oncological diagnosis and VRE colonization was 35 days. The significant RF associated with VRE colonization were days of hospitalization prior to study, neutropenia and treatment with antibiotics within 30 days prior to study and mucositis. According to the RF revealed in this study we may suggest prevention standards to avoid ERV colonization. This is the first investigation in our country in hospitalized pediatric patients with oncological disease and processed with a multiplex PCR for ERV, therefore it is a great contribution about this subject in Chile.


Structural covariances of prefrontal subregions selectively associate with dopamine-related gene coexpression and schizophrenia.
Evidence highlights that dopamine (DA) system dysregulation and prefrontal cortex (PFC) dysfunction may underlie the pathophysiology of schizophrenia. However, the associations among DA genes, PFC morphometry, and schizophrenia have not yet been fully clarified. Based on the brain gene expression dataset from Allen Human Brain Atlas and structural magnetic resonance imaging data (NDIS = 1727, NREP = 408), we first identified 10 out of 22 PFC subregions whose gray matter volume (GMV) covariance profiles were reliably associated with their DA genes coexpression profiles, then four out of the identified 10 PFC subregions demonstrated abnormally increased GMV covariance with the hippocampus, insula, and medial frontal areas in schizophrenia patients (NCASE = 100; NCONTROL = 102). Moreover, based on a schizophrenia postmortem expression dataset, we found that the DA genes coexpression of schizophrenia was significantly reduced between the middle frontal gyrus and hippocampus, in which 21 DA genes showed significantly unsynchronized expression changes, and the 21 genes' brain expression were enriched in brain activity invoked by working memory, reward, speech production, and episodic memory. Our findings indicate the DA genes selectively regulate the structural covariance of PFC subregions by their coexpression profiles, which may underlie the disrupted GMV covariance and impaired cognitive functions in schizophrenia.


Tropical Drosophila pandora carry Wolbachia infections causing cytoplasmic incompatibility or male killing.
Wolbachia infections have been described in several Drosophila species, but relatively few have been assessed for phenotypic effects. Cytoplasmic incompatibility (CI) is the most common phenotypic effect that has been detected, while some infections cause male killing or feminization, and many Wolbachia infections have few host effects. Here, we describe two new infections in a recently described species, Drosophila pandora, one of which causes near-complete CI and near-perfect maternal transmission (the "CI" strain). The other infection is a male killer (the "MK" strain), which we confirm by observing reinitiation of male production following tetracycline treatment. No incompatibility was detected in crosses between CI strain males and MK strain females, and rare MK males do not cause CI. Molecular analyses indicate that the CI and MK infections are distantly related and the CI infection is closely related to the wRi infection of Drosophila simulans. Two population surveys indicate that all individuals are infected with Wolbachia, but the MK infection is uncommon. Given patterns of incompatibility among the strains, the infection dynamics is expected to be governed by the relative fitness of the females, suggesting that the CI infection should have a higher fitness. This was evidenced by changes in infection frequencies and sex ratios in population cages initiated at different starting frequencies of the infections.


[The necessity of the multidisciplinary comprehensive treatment of orthodontics].
The rapid development of orthodontics is based on the oral health. Healthy oral cavity includes teeth, alveolar bone, maxilla and mandible, periodontal tissue, dental body, temporomandibular joint and other structures, which should function with coordination, stability and esthetics. Based on the above requirements, the clinical treatment of orthodontics often needs multidisciplinary cooperation to obtain satisfactory results. This paper makes a review on the multidisciplinary collaborative treatment of orthodontics.


The role of the bone marrow examination in the diagnosis of immune thrombocytopenic purpura: case series and literature review.
The need for a bone marrow examination was assessed in patients with clinical and laboratory features consistent with ITP; the literature was reviewed. The records of all patients undergoing a bone marrow examination between January 1988 to January 1998 were retrospectively reviewed to determine which were motivated by the suspicion of ITP. Data were collected from hospital and outpatient medical and pathology records. Eighty-six patients with isolated thrombocytopenia (i.e., normal white blood cell count, hemoglobin, peripheral smear and clotting studies) were studied. The bone marrow was consistent with ITP in 82 patients, (i.e., normal or increased megakaryocytes and other hemopoietic lineages normal.) Four patients had decreased megakaryocytes, but all patients responded to corticosteroids. All 86 patients were followed up for a median of 22 months after bone marrow aspiration (range, 2-76 months.) During that time, none of the patients developed features to suggest an alternative diagnosis to ITP. The initial clinical and laboratory findings of 99 patients with acute leukemia were also reviewed; all had features atypical of ITP. These data suggest that routine performance of a bone marrow examination for the diagnosis of ITP is not necessary, provided that a thorough history and physical examination are performed and that the complete blood cell count, peripheral blood smear, and routine clotting studies show no abnormalities apart from thrombocytopenia. The findings of seven prior retrospective studies, two in adults and five in children are consistent with the previous findings. However, the value of marrow investigation in ITP remains unresolved and data from a large prospective study would be helpful.


PO2/TransformON, an ontology for data integration on food, feed, bioproducts and biowaste engineering.
We are witnessing an acceleration of the global drive to converge consumption and production patterns towards a more circular and sustainable approach to the food system. To address the challenge of reconnecting agriculture, environment, food and health, collections of large datasets must be exploited. However, building high-capacity data-sharing networks means unlocking the information silos that are caused by a multiplicity of local data dictionaries. To solve the data harmonization problem, we proposed an ontology on food, feed, bioproducts, and biowastes engineering for data integration in a circular bioeconomy and nexus-oriented approach. This ontology is based on a core model representing a generic process, the Process and Observation Ontology (PO2), which has been specialized to provide the vocabulary necessary to describe any biomass transformation process and to characterize the food, bioproducts, and wastes derived from these processes. Much of this vocabulary comes from transforming authoritative references such as the European food classification system (FoodEx2), the European Waste Catalogue, and other international nomenclatures into a semantic, world wide web consortium (W3C) format that provides system interoperability and software-driven intelligence. We showed the relevance of this new domain ontology PO2/TransformON through several concrete use cases in the fields of process engineering, bio-based composite making, food ecodesign, and relations with consumer's perception and preferences. Further works will aim to align with other ontologies to create an ontology network for bridging the gap between upstream and downstream processes in the food system.


Bee Stings and Chronic Pain Disorder.
Chronic pain is a major problem of public health, and patients seek manifold forms of help to find relief. Here we present and discuss the case of a middle-aged woman suffering from mental disorders who treated her headache with the self-application of bee stings on her back.


Validity, reliability, feasibility and satisfaction of the Mini-Clinical Evaluation Exercise (Mini-CEX) for cardiology residency training.
The purpose of the study was to determine the validity, reliability, feasibility and satisfaction of the Mini-CEX. From May 2003 to December 2004, 108 residents from 17 cardiology residency programs in Buenos Aires were monitored by the educational board of the Argentine Society of Cardiology. Validity was evaluated by the instrument's capability to discriminate between pre-existing levels of clinical seniority. For reliability, generalisability theory was used. Feasibility was defined by a minimum number of completed observations: 50% of the residents obtaining at least four Mini-CEX's. Satisfaction was evaluated through a one to nine rating scale from the evaluators, and residents' perspectives. The total number of encounters was 253. Regarding validity, Mini-CEX was able to discriminate significantly between residents of different seniority. Reliability analysis indicated that a minimum of ten evaluations are necessary to produce a minimally reliable inference, but more are preferable. Feasibility was poor: 15% of the residents were evaluated four or more times during the study period. High satisfaction ratings from evaluators' and residents' were achieved. Mini-CEX discriminates between pre-existing levels of seniority, requires considerable sampling to achieve sufficient reliability, and was not feasible within the current circumstances, but it was considered a valuable assessment tool as indicated by the evaluators' and residents' satisfaction ratings.


Life After Being a Pathology Department Chair: Issues and Opportunities.
Although there is a considerable literature on transition of faculty members to the position of department chair, there is a dearth of publications about transitioning from the chair to other activities including retirement. The Association of Pathology Chairs senior fellows (all of whom are former chairs of academic departments of pathology) made this topic a focus of discussion at the Association of Pathology Chairs 2016 Annual Meeting. Of the 33 senior fellows engaged in this discussion, following their time as chairs, a small majority (18) transitioned to other administrative posts within or outside the university, while the others either returned to the active faculty (7) or retired (8). The motivating factors and influences for transitioning from the chair were probed along with the processes used in executing the transition, such as the development of transition plans. The reasons for selecting the specific type of postchair activity were also investigated. There was extraordinary diversity in the type of post-chair activities pursued. To our knowledge, no other medical specialty has examined these issues, which may be potentially relevant for the career planning of active chairs.


Future considerations for clinical dermatology in the setting of 21st century American policy reform: The Medicare Access and Children's Health Insurance Program Reauthorization Act and the Merit-based Incentive Payment System.
As the implementation of the Medicare Access and Children's Health Insurance Program Reauthorization Act begins, many dermatologists who provide Medicare Part B services will be subject to the reporting requirements of the Merit-based Incentive Payment System (MIPS). Clinicians subject to MIPS will receive a composite score based on performance across 4 categories: quality, advancing care information, improvement activities, and cost. Depending on their overall MIPS score, clinicians will be eligible for a positive or negative payment adjustment. Quality will replace the Physician Quality Reporting System and clinicians will report on 6 measures from a list of over 250 options. Advancing care information will replace meaningful use and will assess clinicians on activities related to integration of electronic health record technology into their practice. Improvement activities will require clinicians to attest to completion of activities focused on improvements in care coordination, beneficiary engagement, and patient safety. Finally, cost will be determined automatically from Medicare claims data. In this article, we will provide a detailed review of the Medicare Access and Children's Health Insurance Program Reauthorization Act with a focus on MIPS and briefly discuss the potential implications for dermatologists.