Prevalence and regional differences in overweight in 2001 and trends in BMI distribution in Swedish children from 1987 to 2001.
This study was undertaken to assess current prevalence and regional differences of overweight in 2001 and changes in body mass index (BMI) distribution between 1987 and 2001 in Swedish adolescents. Comparison was made of two independent samples. For assessment of prevalence and regional differences in 2001, a total of 1732 subjects were used. For trend analyses a total of 1,949 children (516 and 1,470 in 1987 and 2001, respectively), aged 10, 13, and 16 years. The prevalence of overweight in 2001 was between 21.7% and 13.3% for boys and girls aged 10 to 16 years and the prevalence of obesity was between 2.9% and 6.2%. Mean BMI as well as prevalence of overweight and obesity was higher in subjects from schools in smaller towns or from the countryside. Median BMI among adolescents changed from 1987 to 2001, most notably in 13- and 16-year-old children. The prevalence of overweight and obesity combined has changed more than 2.5-fold in children aged 10 to 16 years. In this study, the most pronounced elevation in BMI is found in the upper part of the BMI spectrum. This change is especially apparent in girls. The change in mean BMI and prevalence of overweight and obesity in children in this study is mainly due to the pronounced change in BMI at the upper end of the spectrum, indicating that the factors leading to overweight or obesity have changed in only a subgroup of the child population.


Pathogenic mechanisms of congenital heart disease.
Congenital heart disease (CHD) is the most common type of birth defect. Despite the many advances in the understanding of cardiac development and the identification of many genes related to cardiac development, the fundamental etiology for the majority of cases of congenital heart disease remains unknown. This review summarizes normal cardiac development, and outlines the recent discoveries of the genetic causes of congenital heart disease and provides possible strategies for exploring genetic causes.


Genomic and Pathogenic Diversity of Barley Yellow Mosaic Virus and Barley Mild Mosaic Virus Isolates in Fields of China and Their Compatibility with Resistance Genes of Cultivated Barley.
Plant viruses transmitted by the soilborne plasmodiophorid Polymyxa graminis constantly threaten global production of cereal crops. Although the yellow mosaic virus disease of barley has been known to be present for a long time in China, the understanding of the diversity of the viral pathogens and their interactions with host resistance remains limited. In this study, we conducted a nationwide survey of P. graminis and the barley yellow mosaic virus (BaYMV) and barley mild mosaic virus (BaMMV) it transmits, followed by genomic and pathogenic diversity analyses of both viruses. BaYMV and BaMMV were found exclusively in the region downstream of the Yangtze River, despite the national distribution of its transmission vector P. graminis. Analysis of the genomic variations of BaYMV and BaMMV revealed an elevated rate of nonsynonymous substitutions in the viral genome-linked protein (VPg), in which most substitutions were located in its interaction surface with the host eukaryotic translation initiation factor 4E (eIF4E). VPg sequence diversity was associated with the divergence in virus pathogenicity that was identified through multiple field trials. The majority of the resistance genes, including the widely applied rym4 and rym5 (alleles of eIF4E), as well as the combination of rym1/11 and rym5, are not sufficient to protect cultivated barley against viruses in China. Collectively, these results provide insights into virulence specificity and interaction mode with host resistance in cultivated barley, which has significant implications in breeding for the broad-spectrum resistance barley varieties.


[Two cases of recurrent, massive hemoptysis with contralateral, concurrent hemoptysis].
Bilateral, concurrent massive hemoptysis with respiratory failure is rare and difficult to manage. We encountered two patients with this condition. One was a 51-year-old woman and one was a 63-year-old woman. Both had inactive pulmonary tuberculosis and episodes of hemoptysis. Home oxygen therapy was prescribed to the former patient and bronchial artery embolization was done in the latter. The sites of initial bleeding were in the left basal segment and in the lingular segment. Bleeding was well controlled by endobronchial tamponade with a Fogarty balloon catheter in the left main bronchus, contralateral intubation, and systemic artery embolization. Use of water instead of air in the balloon was more effective in over the long term. Concurrent bleeding from the contralateral upper lobe bronchus was controlled by compression with a tracheal tube cuff at the bronchial orifice. Afterward, an infiltrative shadow was seen on the chest X-ray film and hemoptysis occurred in case 2 occurred in case 2. Treatment with erythromycin and antituberculosis drugs brought about improvement of chest X-ray findings and disappearance of the hemoptysis.


Localization of eight additional genes in the human major histocompatibility complex, including the gene encoding the casein kinase II beta subunit (CSNK2B).
A wide range of autoimmune and other diseases are known to be associated with the major histocompatibility complex. Many of these diseases are linked to the genes encoding the polymorphic histocompatibility antigens in the class I and class II regions, but some appear to be more strongly associated with genes in the central 1100-kb class III region, making it important to characterize this region fully for the presence of novel genes. An approximately 220-kb segment of DNA in the class III region separating the Hsp70 (HSPA1L) and BAT1 (D6S8IE) genes, which was previously known to contain 14 genes, has been analyzed for the presence of additional genes. Genomic DNA fragments spanning the gaps between the known genes were used as probes to isolate cDNAs corresponding to five new genes within this region. Evidence from Northern blot analysis and exon trapping experiments that suggested the presence of at least two more new genes was also obtained. Partial cDNA and complete exonic genomic sequencing of one of the new genes has identified it as the casein kinase II beta subunit (CSNK2B). Two of the other novel genes lie within a region syntenic to that implicated in susceptibility to experimental allergic orchitis in the mouse, an autoimmune disease of the testis, and represent additional candidates for the Orch-1 locus associated with this disease. In addition, characterization of the 13-kb intergenic gap separating the RD (D6545) and G11 (D6S60E) genes has revealed the presence of a gene encoding a 1246-amino-acid polypeptide that shows significant sequence similarity to the yeast anti-viral Ski2p gene product.


Schizosaccharomyces pombe NIMA-related kinase, Fin1, regulates spindle formation and an affinity of Polo for the SPB.
The Aspergillus nidulans protein kinase NIMA regulates mitotic commitment, while the human and Xenopus equivalents influence centrosome function. Two recessive, temperature-sensitive mutations in the Schizosaccharomyces pombe NIMA homologue, Fin1, blocked spindle formation at 37 degrees C. One of the two spindle pole bodies (SPBs) failed to nucleate microtubules. This phenotype was reduced by accelerating mitotic commitment through genetic inhibition of Wee1 or activation of either Cdc25 or Cdc2. Polo kinase (Plo1) normally associates with the SPB of mitotic, but not interphase cells. cut12.s11 is a dominant mutation in an SPB component that both suppresses cdc25 mutants and promotes Plo1 association with the interphase SPB. Both cut12.s11 phenotypes were abolished by removing Fin1 function. Elevating Fin1 levels promoted Plo1 recruitment to the interphase SPB of wild-type cells and reduced the severity of the cdc25.22 phenotype. These data are consistent with Fin1 regulating Plo1 function during mitotic commitment. The fin1 mitotic commitment and spindle phenotypes resemble distinct nimA phenotypes in different systems and suggest that the function of this family of kinases may be conserved across species.


Twist-Stabilized, Coiled Carbon Nanotube Yarns with Enhanced Capacitance.
Coil-structured carbon nanotube (CNT) yarns have recently attracted considerable attention. However, structural instability due to heavy twist insertion, and inherent hydrophobicity restrict its wider application. We report a twist-stable and hydrophilic coiled CNT yarn produced by the facile electrochemical oxidation (ECO) method. The ECO-treated coiled CNT yarn is prepared by applying low potentiostatic voltages (3.0-4.5 V vs Ag/AgCl) between the coiled CNT yarn and a counter electrode immersed in an electrolyte for 10-30 s. Notably, a large volume expansion of the coiled CNT yarns prepared by electrochemical charge injection produces morphological changes, such as surface microbuckling and large reductions in the yarn bias angle and diameter, resulting in the twist-stability of the dried ECO-treated coiled CNT yarns with increased yarn density. The resulting yarns are well functionalized with oxygen-containing groups; they exhibit extrinsic hydrophilicity and significantly improved capacitance (approximately 17-fold). We quantitatively explain the origin of the capacitance improvement using theoretical simulations and experimental observations. Stretchable supercapacitors fabricated with the ECO-treated coiled CNT yarns show high capacitance (12.48 mF/cm and 172.93 mF/cm2, respectively) and great stretchability (80%). Moreover, the ECO-treated coiled CNT yarns are strong enough to be woven into a mask as wearable supercapacitors.


The effects of malnutrition on the motor, perceptual, and cognitive functions of Filipino children.
The motor, perceptual, and cognitive abilities of 99 Filipino children, aged 4-6 years with a documented history of malnutrition from a nutritionally depressed area of Manila were determined using the Revised Manila Motor-Perceptual Screening Test. They were classified into four groups of: (1) normal; (2) acutely malnourished; (3) stunted but not malnourished; and (4) chronically malnourished using the Waterlow classification. Thirty-one normal children of comparable ages and background from a nationwide pool were similarly tested and served as the control group. Motor (p = 0.001) and perceptual skill (p less than 0.03 to less than 0.001) scores were significantly lower than in their normal counterparts, especially in the chronically malnourished children. Cognitive abilities were not evidently affected by malnutrition.


A multicentre study on LMW-heparin effectiveness in preventing postsurgical thrombosis.
A multicentric study was carried out involving six italian departments of general surgery to assess the efficacy of a low molecular weight (LMW) heparin called Fluxum compared to standard calcium heparin in low doses for prevention of postoperative thromboembolic complications (deep vein thrombosis and pulmonary embolism). 610 patients were treated; 308 (50.5%) of whom were treated with Fluxum at doses of 4,000 or 8,000 I.U. Axa once a day by subcutaneous injection and 302 (49.5%) with heparin calcium at doses of 5,000 I.U. two or three times a day by subcutaneous injection. We observed a total of 29 deep vein thrombosis (4.7%); 10 (3.2%) from the group treated with LMW heparin and 19 (6.3%) from the comparative group. During the study 4 (0.65%) pulmonary embolism were found, 1 (0.32%) in the group treated with LMW heparin and 3 (1%) in the group treated with calcium heparin. None serious hemorrhagic accident was reported during the study. The antithrombotic prophy laxis carried out with Fluxum was on the whole better tolerated than the treatment of the other group, registering a lower frequency of hematomas at the injection and surgical wound sites.


Impact of Family Caregiver Training on Care of Burn Patients.
The purpose of this study was to investigate the impact of a family caregiver training program on care provision to burn patients. A quasi-experimental study was conducted with 96 family caregivers of burn patients admitted to a burn hospital in Iran. The caregivers' knowledge and training needs were measured at baseline. Four training sessions were provided for the experimental group and caregivers' practices were measured 6 weeks after discharge. Comparing the scores of knowledge and total care with its subdomains (i.e., diet and medication, wound care, itch decrease, wound scar healing, pain management, use of mobility assistive devices, and follow-up considerations) revealed a significant difference between the two groups of caregivers after the intervention (p < 0.01). The caregivers' practices regarding provision of care to burn patients were improved after attending the training program. Receiving sufficient and continuous information from admission to discharge can empower family members.


Prevalence of esophageal disorders in patients with chest pain newly referred to the cardiologist.
The prevalence of esophageal disorders (dysmotility and/or gastroesophageal reflux) in patients with chest pain newly referred to a cardiologic clinic is unknown. The aims of our study were to investigate the prevalence of esophageal abnormalities in these patients and to assess the value of medical history in predicting the origin of the patient's chest pain. We evaluated 28 consecutive patients who were newly referred to the cardiologist because of angina-like chest pain. Patients with evidence of severe myocardial ischemia were excluded. Cardiologic evaluation included medical history, physical examination, ECG, and exercise testing; further cardiologic workup was carried out only when considered necessary. Gastroenterologic evaluation consisted of medical history, esophageal manometry, endoscopy, and 24-h ambulatory monitoring of esophageal pH and pressure. In five patients a diagnosis of ischemic coronary artery disease was made. In only two of these five patients, the cardiologic history strongly suggested a cardiac origin of the pain. Twelve patients had a pathologic 24-h pH profile, four of whom also had reflux esophagitis. Ten patients had symptomatic reflux. In only three of these ten patients, the history was judged to be indicative of an esophageal origin of the chest pain. No motility disorders were found. Thirty-six percent of the patients with chest pain newly referred to a cardiologic out-patient clinic have symptomatic gastroesophageal reflux. Neither cardiologic nor gastroenterologic history data have a high predictive value with respect to the origin of the chest pain.


Intracluster ion molecule reactions following the generation of Mg+ within polar clusters.
In this work we investigated the intracluster ion molecule reactions following the generation of Mg(+) within the polar clusters (water, methanol, ether and acetonitrile), using time of flight mass spectrometry. In the case of Mg(+)/water and Mg(+)/methanol, dehydrogenation reactions are observed after the addition of five molecules. However, no dehydrogenation reactions are observed in the case of Mg(+)/ether or Mg(+)/acetonitrile clusters. This confirms the role of the H atom in (O-H) in the dehydrogenation reaction, and rules out any contribution from the H atom in the CH(3) group. In addition, the magic numbers in the time of flight (TOF) mass spectra of the Mg(+)X(n) clusters (X = H(2)O, CH(3)OH, CH(3)OCH(3) and CH(3)CN) have been investigated. Finally, the role of ground electronic magnesium ion Mg(+)((2)S(1/2)), and excited electronic magnesium ion Mg(+)((2)P(1/2)) in the dehydrogenation reaction were investigated using Ion Mobility Mass spectrometry. The results offer direct evidence confirming the absence of the electronically excited, Mg(+)((2)P(1/2)).


Temporal self-organization of the cyclin/Cdk network driving the mammalian cell cycle.
We propose an integrated computational model for the network of cyclin-dependent kinases (Cdks) that controls the dynamics of the mammalian cell cycle. The model contains four Cdk modules regulated by reversible phosphorylation, Cdk inhibitors, and protein synthesis or degradation. Growth factors (GFs) trigger the transition from a quiescent, stable steady state to self-sustained oscillations in the Cdk network. These oscillations correspond to the repetitive, transient activation of cyclin D/Cdk4-6 in G(1), cyclin E/Cdk2 at the G(1)/S transition, cyclin A/Cdk2 in S and at the S/G(2) transition, and cyclin B/Cdk1 at the G(2)/M transition. The model accounts for the following major properties of the mammalian cell cycle: (i) repetitive cell cycling in the presence of suprathreshold amounts of GF; (ii) control of cell-cycle progression by the balance between antagonistic effects of the tumor suppressor retinoblastoma protein (pRB) and the transcription factor E2F; and (iii) existence of a restriction point in G(1), beyond which completion of the cell cycle becomes independent of GF. The model also accounts for endoreplication. Incorporating the DNA replication checkpoint mediated by kinases ATR and Chk1 slows down the dynamics of the cell cycle without altering its oscillatory nature and leads to better separation of the S and M phases. The model for the mammalian cell cycle shows how the regulatory structure of the Cdk network results in its temporal self-organization, leading to the repetitive, sequential activation of the four Cdk modules that brings about the orderly progression along cell-cycle phases.


Restoration of renal function in shock by perfusion of the renal artery with venous blood: a counterintuitive approach.
Acute renal failure (ARF) in low-flow states may be reversed by increasing renal perfusion. When hemodynamics are maximized, renal perfusion can only be improved by shunting a higher proportion of cardiac output to the kidney; however, in low-flow states, this reduces already compromised systemic pressure and perfusion to other organs. Increasing perfusion using venous blood (VB) would be an attractive option because decreased systemic pressure and perfusion to other organs could be avoided. However, it is not known whether VB can provide adequate oxygen delivery to restore or maintain renal function. We studied whether antegrade VB perfusion of the kidney via the renal artery would restore urine output (UO) and glomerular filtration rate (GFR) in hypoperfused ARF. Shock was induced in six dogs via a hemorrhagic protocol resulting in a systolic blood pressure of 50-70 mm Hg, a mixed venous oxygen saturation of 25% to 40%, and a UO <10% of baseline. After 60 mins of shock, the left renal artery was cannulated under fluoroscopy and perfused at pressures of 100-150 mm Hg for 30 mins with VB drawn from the vena cava and delivered by an extracorporeal pump system. The right kidneys were controls and remained hypoperfused. All VB-perfused kidneys recovered renal function after a sustained period of shock and marked oliguria: UO from 0.7 +/- 1.6 mL/hr to 101 +/- 58 mL/hr (p <.01); GFR from approximately 0 to 70.3 +/- 55 mL/min (p =.04). The control kidneys' UO (0.7 +/- 1.6 mL/hr) and GFR (0 mL/min) remained unchanged throughout the study. The experimental kidneys were able to extract oxygen from VB (O2 saturation, 31 +/- 7% to 16 +/- 4%; p =.01). When flow is controlled, kidneys in hypoperfused ARF can extract sufficient oxygen from antegrade VB perfusion to restore renal function (UO and GFR).


Canertinib pfizer.
Canertinib, a water-soluble, orally available analog of PD-169414 (Pfizer Inc), is an EGFR tyrosine kinase inhibitor under development by Pfizer Inc as a potential treatment for cancer.


A Novel 3D Cultured Model for Studying Early Changes in Age-Related Macular Degeneration.
Various in vitro culture systems have been used to investigate the pathogenesis of age-related macular degeneration (AMD). However, many still rely on oversimplified monolayer culture models. AMD is a complex disease, associated with the pathological changes to multiple structural components such as the Bruch's membrane, retinal pigment epithelium (RPE), and choroidal endothelial cells. This study aims to construct a novel 3D coculture model using the polycaprolactone (PCL)-gelatin electrospun scaffold, with human RPE cells (hRPE) and primate choroidal cells (RF-6A). Results from this study show that PCL-gelatin scaffolds have a highly porous ultrastructure that supports the attachment, proliferation, differentiation, and migration of the hRPEs and choroidal endothelial cells. It is also demonstrated that the PCL-gelatin 3D coculture model may be useful in exploring the molecular interplay between the hPRE and the choroidal endothelial cells, and their effects on growth factor modulation, which may be important in the pathogenesis of AMD.


Thermally Induced Solid-Phase Quasi-Intramolecular Redox Reactions of [Hexakis(urea-O)iron(III)] Permanganate: An Easy Reaction Route to Prepare Potential (Fe,Mn)Ox Catalysts for CO2 Hydrogenation.
Research on new reaction routes and precursors to prepare catalysts for CO2 hydrogenation has enormous importance. Here, we report on the preparation of the permanganate salt of the urea-coordinated iron(III), [hexakis(urea-O)iron(III)]permanganate ([Fe(urea-O)6](MnO4)3) via an affordable synthesis route and preliminarily demonstrate the catalytic activity of its (Fe,Mn)Ox thermal decomposition products in CO2 hydrogenation. [Fe(urea-O)6](MnO4)3 contains O-coordinated urea ligands in octahedral propeller-like arrangement around the Fe3+ cation. There are extended hydrogen bond interactions between the permanganate ions and the hydrogen atoms of the urea ligands. These hydrogen bonds serve as reaction centers and have unique roles in the solid-phase quasi-intramolecular redox reaction of the urea ligand and the permanganate anion below the temperature of ligand loss of the complex cation. The decomposition mechanism of the urea ligand (ammonia elimination with the formation of isocyanuric acid and biuret) has been clarified. In an inert atmosphere, the final thermal decomposition product was manganese-containing wuestite, (Fe,Mn)O, at 800 °C, whereas in ambient air, two types of bixbyite (Fe,Mn)2O3 as well as jacobsite (Fe,Mn)T-4(Fe,Mn)OC-62O4), with overall Fe to Mn stoichiometry of 1:3, were formed. These final products were obtained regardless of the different atmospheres applied during thermal treatments up to 350 °C. Disordered bixbyite formed first with inhomogeneous Fe and Mn distribution and double-size supercell and then transformed gradually into common bixbyite with regular structure (and with 1:3 Fe to Mn ratio) upon increasing the temperature and heating time. The (Fe,Mn)Ox intermediates formed under various conditions showed catalytic effect in the CO2 hydrogenation reaction with <57.6% CO2 conversions and <39.3% hydrocarbon yields. As a mild solid-phase oxidant, hexakis(urea-O)iron(III) permanganate, was found to be selective in the transformation of (un)substituted benzylic alcohols into benzaldehydes and benzonitriles.


Clinical features and genetic analysis of a Chinese kindred with Fabry's disease.
Fabry's disease is an X-linked recessive inborn error of glycosphingolipid catabolism resulting from deficient activity of lysosomal enzyme alpha-galactosidase A causing occlusive microvascular diseases affecting the kidney, heart, peripheral nerves and brain. It is an uncommon disease in the Oriental population. We report a Chinese kindred of Fabry's disease and the relevant clinical features are discussed. The diagnosis of Fabry's disease was based on serum alpha-galactosidase A activity and typical histological features from renal biopsy in the index patient. Genetic analysis of two hemizygous male patients revealed a missense mutation predicting a leucine to proline substitution (L14P) in the alpha-galactosidase gene causing classical Fabry's disease in this family. This is a novel point mutation not described previously in the literature and the second report describing novel genetic mutations for Fabry's disease in Chinese patients. Fabry's disease is rare in Chinese patients but this diagnosis should be considered in patients with positive family history of kidney disease and relevant clinical features.


Vasculitis in a patient with mixed cryoglobulinemia treated with rituximab biosimilar CT-P10: a case report.
Rituximab represents a milestone in the treatment of mixed cryoglobulinemic vasculitis. Despite usually well-tolerated, rituximab may induce different types of adverse drug reactions, including exacerbation of vasculitis. Rituximab biosimilar have been recently approved in Europe in the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of rituximab biosimilar in the treatment of mixed cryoglobulinemic vasculitis. We describe a severe skin vasculitis reactivation in a patient affected by rheumatoid arthritis and mixed cryoglobulinemic vasculitis treated with rituximab biosimilar. After 7 days from the first infusion, a severe purpuric rash at lower limbs appeared, that resolved in about 2 weeks with high dose-corticosteroid. Rituximab-induced vasculitis has also been described since 2001, but its pathophysiology is still controversial due to the anecdotical descriptions in literature and the variability of the time between the rituximab infusion and the onset of skin lesions. Up to date, this is the first report describing a vasculitic flare in a patient affected by mixed cryoglobulinemic vasculitis treated with rituximab biosimilar.


[Significance of L-asparaginase activity and biochemical parameters evaluation in children with acute lymphoblastic leukemia].
L-asparaginase is one of the most important agent used in multidrug chemotherapy regimens in the treatment of malignancies which derive from lymphoid system (acute lymhoblastic leukemias and non-hodgkin lymphoma). L-asparaginase leads to enzymatic cleavage of L-asparagine (amino acid essential for lymphoblasts' growth) to ammonia and L-aspartic acid, what results in depletion of L-asparagine in a serum and cerebrospinal fluid, and finally leads to destruction of lymphoblasts, which lack ability of endogenic L-asparagine production. In the course of L-asparaginase therapy severe side effects could be observed such as: coagulation disturbances, acute pancreatitis, anaphilactic shock and other types of allergic reaction, as well as liver and CNS failure. Monitoring of L-asparaginase activity in serum is recomended in order to optimalize therapy with L-asparaginase and reducing risk of severe side effects. Continuous assessment of L-asparaginase activity during therapy gives also opportunity to detect asymptomatic inactivation of L-ASPA - so called "silent inactivation", which is cused by production of antibodies against xenogenic protein, especcialy in IgG class. This process leads to shortening of half-life of L-ASPA. The paper shows presently available monitoring methods during therapy with L-ASPA, with all their pros and cons.


Nuclear plasticity and timing mechanisms of the initiation of alkaline phosphatase expression in cytoplasm-transferred blastomeres of ascidians.
Egg cytoplasm containing endoderm determinants was transferred to presumptive-muscle or presumptive-epidermis blastomeres isolated from cleavage-stage embryos of the ascidian Halocynthia roretzi. We investigated three aspects of the expression of endoderm-specific alkaline phosphatase (ALP) activity. First, we examined whether ectopic ALP expression, an indication of ectopic endoderm formation, was promoted in cytoplasm-transferred blastomeres isolated at late-cleavage stage. The results showed that the cell fate was converted by the introduced cytoplasm, even in recipient blastomeres in which the cell fate was already restricted to muscle or epidermis, and in those where expression of the muscle- or epidermis-specific genes was already initiated. Next, we examined the formation of endoderm and other tissue in embryos by double staining for ALP and muscle- or epidermis-specific marker. Regions positive for ALP and positive for muscle or epidermis marker were mutually exclusive. These results suggested that muscle- or epidermis-specific genes that were already expressed in the recipient blastomeres were down-regulated in ectopically forming endoderm cells. This is evidence for nuclear plasticity during ascidian embryogenesis. In the last series of experiments, we investigated the timing of the appearance of ALP activity in cytoplasm-transferred embryos. In the partial embryos that were derived from various combination of recipient blastomeres and donor cytoplasm obtained from various staged eggs and embryos, the timing seemed to coincide with the time that starts when cell fusion for cytoplasmic transfer was done. Therefore, the clock that determines the timing of the initiation of ALP expression is likely to start at the moment of cell fusion. Several possible hypotheses for the timing mechanism are discussed.


Geographic variation in health services use in Nova Scotia.
To further our understanding of factors underlying geographic variation in health and the potential role of availability of and access to health services, we sought to quantify the geographic variation in health services use in the province of Nova Scotia. For the period 1996 to 1999 we examined the variation in the use of health services across 64 geographic areas in conjunction with health and socio-economic factors, using multilevel methods and empirical Bayesian estimates based on provincial physician billings and hospital separation records. We revealed moderate geographic variation in the use of family physician services and large variation in specialist and hospital services. In the two urban centres, Metropolitan Halifax and the Cape Breton Regional Municipality, use of specialist services was respectively 26.24% and 15.59% higher than the provincial average, and use of hospital services was respectively 21.55% and 37.67% higher. Geographic areas in which residents had better health were characterized by more use of family physician services and reduced use of specialist and hospital services. These associations seem to support policy strategies that aim to improve health and to reduce health care costs by investing in prevention and primary health care, and they highlight the potential implications of the shortage of family physicians across Canada.


Stromal cells and integrins: conforming to the needs of the tumor microenvironment.
The microenvironment of a tumor is constituted of a heterogenous population of stromal cells, extracellular matrix components, and secreted factors, all of which make the tumor microenvironment distinct from that of normal tissue. Unlike healthy cells, tumor cells require these unique surroundings to metastasize, spread, and form a secondary tumor at a distant site. In this review, we discuss that stromal cells such as fibroblasts and immune cells including macrophages, their secreted factors, such as vascular endothelial growth factor, transforming growth factor beta, and various chemokines, and the integrins that connect the various cell types play a particularly vital role in the survival of a growing tumor mass. Macrophages and fibroblasts are uniquely plastic cells because they are not only able to switch from tumor suppressing to tumor supporting phenotypes but also able to adopt various tumor-supporting functions based on their location within the microenvironment. Integrins serve as the backbone for all of these prometastatic operations because their function as cell-cell and cell-matrix signal transducers are important for the heterogenous components of the microenvironment to communicate.


Effect of Phosphatidic Acid on Biomembrane: Experimental and Molecular Dynamics Simulations Study.
We consider the impact of phosphatidic acid (namely, 1,2-dioleoyl-sn-glycero-3-phosphate, DOPA) on the properties of a zwitterionic (1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) bilayer used as a model system for protein-free cell membranes. For this purpose, experimental measurements were performed using differential scanning calorimetry and the Langmuir monolayer technique at physiological pH. Moreover, atomistic-scale molecular dynamics (MD) simulations were performed to gain information on the mixed bilayer's molecular organization. The results of the monolayer studies clearly showed that the DPPC/DOPA mixtures are nonideal and the interactions between lipid species change from attractive, at low contents of DOPA, to repulsive, at higher contents of that component. In accordance with these results, the MD simulations demonstrated that both monoanionic and dianionic forms of DOPA have an ordering and condensing effect on the mixed bilayer at low concentrations. For the DOPA monoanions, this is the result of both (i) strong electrostatic interactions between the negatively charged oxygen of DOPA and the positively charged choline groups of DPPC and (ii) conformational changes of the lipid acyl chains, leading to their tight packing according to the so-called "umbrella model", in which large headgroups of DPPC shield the hydrophobic part of DOPA (the conical shape lipid) from contact with water. In the case of the DOPA dianions, cation-mediated clustering was observed. Our results provide a detailed molecular-level description of the lipid organization inside the mixed zwitterionic/PA membranes, which is fully supported by the experimental data.


Evaluation of a newly developed visual shade-matching apparatus.
This study evaluated a newly developed visual shade-matching apparatus, Shademat Visual+, as well as the influence of tab arrangement, clinician gender, and years in practice on shade-matching quality. A group of 129 color-normal evaluators-dental students and general dentists-matched the shade of four ceramometal crowns using the Vitapan Classical shade guide. Crowns were positioned onto the upper member of an artificial head and fastened to the headrest of the dental chair or Shademat Visual+. Shade tabs were arranged according to the manufacturer's suggestion or according to deltaE* in relation to the "lightest" tab and divided into groups (alternative arrangement). The evaluators matched the shade of four ceramometal crowns both in daylight and using the Shademat Visual+ artificial light source. The color coordinates were determined using digital image analysis. Based on deltaE* values, each shade-matching result was ranked from 1 (the worst match) to 16 (the best match) points. The evaluators achieved a better result in Shademat Visual+ trials than in daylight trials (13.2 points vs 12.4 points; P < .001). For the same ceramometal crown, 12.7 points were recorded in daylight trials with the manufacturer-suggested arrangement, and 13.7 were recorded with the alternative arrangement (P< .001). Corresponding values for Shademat Visual+ trials were 13.6 points and 14.6 points, respectively (P< .001). Female-male and student-dentist evaluator differences were not significant. The Shademat Visual+ apparatus enabled better shade-matching results than daylight. The alternative tab arrangement enabled better results than the manufacturer-suggested one. Gender and years in practice did not influence shade-matching quality.


Ascorbic acid and total vitamin C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation.
Epidemiological evidence suggests that high dietary ascorbic acid reduces gastric cancer risk. It may do this by either reducing N-nitroso compound formation in gastric juice, or by scavenging reactive oxygen species in gastric mucosa. The aim of this study was to discover if potential ascorbic acid protection might be increased by supplementation. Thirty two patients were supplemented with ascorbic acid, 500 mg twice daily for two weeks. Gastric juice, plasma, and upper gastrointestinal biopsy ascorbate concentrations were measured and compared with values in 48 unsupplemented patients. It was found that ascorbic acid and total vitamin C concentrations were considerably higher in biopsy specimens from oesophagus, body, antrum, duodenum, and rectum, compared with values in plasma or gastric juice. Plasma and mucosal concentrations were unaffected by the presence of chronic gastritis but gastric juice concentrations were substantially lower in patients with chronic gastritis than in patients with normal histological assessment (p < 0.01). Patients receiving ascorbic acid supplements had higher ascorbic acid concentrations in plasma (p < 0.001), gastric juice (p < 0.001), and at all biopsy sites in the upper gastrointestinal tract (p < 0.05). Gastric juice ascorbic acid and total vitamin C concentrations in gastritic patients, however, were still less after supplementation than in normal subjects (p < 0.01). These data suggest that high ascorbic acid intake could reduce gastric cancer risk, but its protective effect might be greater if gastritis is treated (for example, by Helicobacter pylori eradication).


Glorisa superba Hydroalcoholic Extract from Tubers Attenuates Experimental Arthritis by Downregulating Inflammatory Mediators, and Phosphorylation of ERK/JNK/p-38.
Glorisa superba (GS) is a medicinal plant that has been traditionally used in the treatment of joint pain and rheumatoid arthritis (RA). The present study was carried out to investigate the antiarthritic activity of Glorisa superba hydroalcoholic extract (GSHE) in an adjuvant-induced arthritis (AIA) rat model. Arthritis was induced by sub-plantar administration of complete Freund's adjuvant (CFA) and GSHE (25, 50, or 100 mg/kg/day) was administered orally for 21 consecutive days. Joint diameter was measured on Days 0, 3, 7, 14, and 21. GSHE dose dependently attenuates the increased joint diameter and serum tumor necrosis factor (TNF)-α level following induction of arthritis by adjuvant. This attenuation was well substantiated with reduced mRNA expression of interleukin (IL)-1β, IL-6, TNF-α, and NF-κB. Additionally, GSHE inhibited phosphorylation of the mitogen-activated protein kinases (MAPK) signaling pathway as there was decreased protein expression of MAPK (p-p38/p38 and p-ERK/ERK p-JNK/JNK ratio). Moreover, GSHE in a dose-dependent fashion normalized the redox status of ankle joint (GSH, malonaldialdehyde [MDA], and NO levels and superoxide dismutase [SOD] and catalase [CAT] activities) and displayed decreased inflammatory cell infiltration in histopathological findings. Taken together, these findings indicate that GSHE protects against AIA by modulating MAPK.


The MHC class II-associated invariant chain interacts with the neonatal Fc gamma receptor and modulates its trafficking to endosomal/lysosomal compartments.
The neonatal Fc receptor for IgG (FcRn) transfers maternal IgG to the offspring and protects IgG from degradation. The FcRn resides in an acidic intracellular compartment, allowing it to bind IgG. In this study, we found the association of FcRn and invariant chain (Ii). The interaction was initiated within the endoplasmic reticulum by Ii binding to either the FcRn H chain alone or FcRn H chain-beta(2)-microglobulin complex and appeared to be maintained throughout the endocytic pathway. The CLIP in Ii was not required for FcRn-Ii association. The interaction was also detected in IFN-gamma-treated THP-1, epithelial and endothelial cells, and immature mouse DCs. A truncated FcRn without the cytoplasmic tail was unable to traffic to early endosomes; however, its location in early endosomes was restored by Ii expression. FcRn was also detected in the late endosome/lysosome only in the presence of Ii or on exposure to IFN-gamma. In immature human or mouse DCs, FcRn was barely detected in the late endosome/lysosome in the absence of Ii. Furthermore, the cytoplasmic tail of Ii conferred tailless FcRn to route to both the early endosome and late endosome/lysosome in a hybrid molecule. Because the FcRn is expressed in macrophages and DCs or epithelial and endothelial cells where Ii is induced under inflammation and infection, these results reveal the complexity of FcRn trafficking in which Ii is capable of expanding the boundary of FcRn trafficking. Taken together, the intracellular trafficking of FcRn is regulated by its intrinsic sorting information and/or an interaction with Ii chain.


Chloride channels and their functional roles in smooth muscle tone in the vasculature.
Although evidence of important contributions by Cl- channels to agonist-induced currents have been reported in vascular smooth muscle cells, the functional roles played by Cl- channels in the smooth muscle contraction and in setting the membrane potential remain essentially obscure. All of the admittedly few papers published have focused on the physiological roles of Cl- channels in the contraction and membrane depolarization elicited by agonists. At present, it seems likely that in vascular cells: a) Cl- conductance contributes to membrane depolarization, with the subsequent contraction being due to Ca2+ release from the intracellular store sites, and b) Cl- movements through the membrane of the Ca2+ store sites also regulate Ca2+ release and Ca2+ uptake from/into the store sites. As a Ca2+-dependent Cl- current is most easily demonstrated under quasi-physiological conditions (by the perforated patch-clamp method), the contribution made by Cl- channels to smooth muscle function may be more important than previously thought. The development of the new, selective Cl--channel blockers as well as the identification and gene engineering of the channel molecules are essential if we are to advance our knowledge of the physiology and pharmacology of the Cl- channels residing in vascular smooth muscle cells.


Controlled release of fibroblast growth factor-2 from an injectable 6-O-desulfated heparin hydrogel and subsequent effect on in vivo vascularization.
We prepared a 6-O-desulfated (DS-) heparin (Hep) hydrogel as an excellent carrier for the controlled release of Hep-binding growth factors, such as fibroblast growth factor (FGF)-2. This material, which is partially derived from photoreactive groups, such as cinnamate, is easily crosslinked upon ultraviolet light (UV)-irradiation, resulting in a water-insoluble, viscous, and injectable hydrogel. In the present study, we examined the capacity of 6-O-DS-Hep hydrogel to immobilize FGF-2, as well as the controlled release of FGF-2 molecules from this hydrogel in vitro and in vivo. Only 10% of FGF-2 was gradually released from the FGF-2-containing 6-O-DS-Hep hydrogel (photocrosslinked 6-O-DS-Hep (4%; w/w) hydrogel containing 50 microg/mL FGF-2) into PBS (phosphate-buffered saline) within first 7 days. The 6-O-DS-Hep hydrogel in vitro maintained the original form through 1 weeks incubation in PBS, but it was gradually fragmented and could not maintain the original form by 2-3 week-washing. When the FGF-2-containing 6-O-DS-Hep hydrogel was subcutaneously injected into the back of rats, significant neovascularization and fibrous tissue formation were induced near the injected site from day 3 after the injection. And, the hydrogel had been biodegraded and completely disappeared from the injected sites in vivo within about 15-20 days after the injection. These findings indicate a controlled release of biologically active FGF-2 molecules together with fragmentation and biodegradation of 6-O-DS-Hep hydrogel and the subsequent induction of neovascularization in vivo.


A feedback mechanism regulates monoallelic odorant receptor expression.
In olfactory neurons, expression of a single odorant receptor (OR) from a repertoire of >1000 genes is required for odor coding and axonal targeting. Here, we demonstrate a role for OR protein as an essential regulator in the establishment of monoallelic OR expression. An OR-promoter-driven reporter expresses in a receptor-like pattern but, unlike a native OR, is coexpressed with an additional OR allele. Expression of a functional OR from the identical promoter eliminates expression of other OR alleles. The presence of an untranslatable OR coding sequence in the mRNA is insufficient to exclude expression of a second OR. Together, these data identify the OR protein as a critical element in a feedback pathway that regulates OR selection.


Solitary sclerotic fibroma.
Sclerotic fibroma is a rare skin neoplasm that can be seen sporadically or in association with disorders such as Cowden's disease. We present a case of solitary sclerotic fibroma that presented as an asymptomatic nodule in a 40-year-old man with no evidence of Cowden's disease. Histopathologically, the lesion was consistent with a sclerotic fibroma displaying hypocellular collagen bundles with clefts.


DL-3-n-butylphthalide therapy for Parkinson's disease: A randomized controlled trial.
Currently available treatments for Parkinson's disease (PD) do not delay or prevent disease development and progression. DL-3-n-butylphthalide (NBP), isolated from Apium graveolens seeds, alleviates oxidative damage and mitochondrial dysfunction. It has been revealed to reduce the loss of dopamine neurons in pre-clinical PD models, and has been approved for the treatment of ischemic stroke patients. The purpose of the present study was to examine whether NBP has the capacity provide a benefit for PD patients and to slow disease progression. A randomized, controlled trial was performed between September 2014 and December 2016. Pairs of patients matched by age, gender and off-medication Unified PD Rating Scale motor subscale (UPDRS-III) scores, were randomly assigned to an NBP treatment group and a control group. All patients continued their originally prescribed medication regimen and those in the NBP group were administered NBP at 200 mg three times daily for 24 weeks. Primary outcome measures were changes in UPDRS-III, including tremor score and non-tremor score, the Pittsburgh sleep quality index (PSQI) and the PD 39-items questionnaire (PDQ) scores. Assessments were completed by blinded evaluators at baseline and 12, 24 and 48 weeks after randomization. All patients were monitored for adverse events (AEs). A total of 103 patients were enrolled in the present study. The NBP group exhibited significantly greater improvements in the non-tremor, PSQI and PDQ-39 scores than the control group, which generally exhibited no improvement. NBP-associated AEs were uncommon and primarily consisted of mild gastrointestinal symptoms. In conclusion, over the 6-month treatment period, NBP was safe and effective for improving the symptoms and impairing the progression of patients with PD (Trial registry number, ChiCTR1800018892).


Cytochrome b5, cytochrome c, and cytochrome P-450 interactions with NADPH-cytochrome P-450 reductase in phospholipid vesicles.
Upon incubation of detergent-solubilized NADPH-cytochrome P-450 reductase and either cytochrome b5 or cytochrome c in the presence of a water-soluble carbodiimide, a 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), covalently cross-linked complex was formed. The cross-linked derivative was a heterodimer consisting of one molecule each of flavoprotein and cytochrome, and it was purified to 90% or more homogeneity. The binary covalent complex between the flavoprotein and cytochrome b5 was exclusively observed following incubation of all three proteins including NADPH-cytochrome P-450 reductase, cytochrome b5, and cytochrome c in L-alpha-dimyristoylphosphatidylcholine vesicles, and no heterotrimer could be identified. The isolated reductase-cytochrome b5 complex was incapable of covalent binding with cytochrome c in the presence of EDC. No clear band for covalent complex formation between PB-1 and reductase was seen with the present EDC cross-linking technique. More than 90% of the cross-linked cytochrome c in the purified derivative was rapidly reduced upon addition of an NADPH-generating system, whereas approximately 80% of the cross-linked cytochrome b5 was rapidly reduced. These results showed that in the greater part of the complexes, the flavin-mediated pathway for reduction of cytochrome c or cytochrome b5 by pyridine nucleotide was intact. When reconstituted into phospholipid vesicles, the purified amphipathic derivative could hardly reduce exogenously added cytochrome c, cytochrome b5, or PB-1, indicating that the cross-linked cytochrome shields the single-electron-transferring interface of the flavoprotein. These results suggest that the covalent cross-linked derivative is a valid model of the noncovalent functional electron-transfer complex.


Stimulation by atropine of acetylcholine release and synthesis in cortical slices from rat brain.
1. Cortical slices from rat brain were incubated in media containing the irreversible cholinesterase inhibitor soman and a high KCl concentration, and the release and synthesis of acetylcholine (ACh) were determined.2. Atropine enhanced the release and synthesis of ACh.3. Tetrodotoxin, a substance which blocks nervous conduction, did not influence the release and synthesis of ACh, in the absence or in the presence of atropine. Therefore the nerve endings are probably the site at which atropine acts when stimulating the release and synthesis of ACh.4. Pretreatment of the slices with botulinum type A toxin partially blocked the release and synthesis of ACh and reduced the extra amounts of ACh released and synthesized under the influence of atropine.5. Lowering the calcium or raising the magnesium concentration in the incubation medium reduced the release and synthesis of ACh and their enhancement by atropine.6. Physostigmine decreased the total extractable ACh content of the slices during incubation in a 25 mM KCl containing medium. This decrease was nearly prevented when the release and synthesis of ACh were inhibited by omission of the calcium ions from the medium, but was enhanced by atropine.7. The observations made with pretreatment by botulinum type A toxin, with changes in the calcium and magnesium concentration as well as with physostigmine, all support the theory that it is primarily the release of ACh which is enhanced by atropine and that its stimulating action on the synthesis results from the increased release.


Shear wave elastography of the liver - review on normal values.
Shear wave elastography (SWE) has been developed to non-invasively estimate liver stiffness. Different techniques are available and they are described in detail in the EFSUMB guidelines on elastography. However, there are only a few published studies investigating normal ranges in healthy subjects by comparing different equipment and analysing influencing factors. In the present review, we summarize the impact factors on liver stiffness measurement (LSM) using SWE, report its reproducibility, and define normal range tables of LSM in healthy subjects for clinical practice according to the published literature.


Effect of sleep deprivation on spike-wave discharges in idiopathic generalised epilepsy: a 4 x 24 h continuous long term EEG monitoring study.
The aim of the study was to investigate the effect of sleep and sleep deprivation on spike-wave discharges (SWD) in an idiopathic generalised epileptic patient population by continuous long term cassette EEG monitoring for 4 x 24 h. In ten patients with idiopathic generalised epilepsy, showing SWD during awake state and in sleep as well, EEG and sleep polygraphy was recorded for 4 x 24 h. Sleep was deprived during the second 24 h. Awake state, NREM1, NREM2, NREM3+4 and REM sleep duration and number of SWD episodes were evaluated in 4 min intervals by visual scoring. For analysing the effect of 'day' and 'night', 'vigilance' and 'sleep deprivation' (SD) on the density variables multi-way ANOVAs were carried out in different designs. SWD densities for different vigilance states were not significantly different during 'day' and 'night' in 24 h without SD or rebound after SD. Sleep had an activating effect SWD densities being the highest during NREM1 and NREM2. There was an increase of SWD densities in all vigilance states after SD, but SWD densities remained the highest in NREM1 andNREM2. Our results support the view that sleep dependent rather than sleep independent mechanisms cause activation of SWD after SD in generalised epilepsy. We assume that fine graded vigilance fluctuations, that are more frequent after SD, have an essential role in SWD activation in superficial sleep or even in wakefulness.


Neutrophil activation by the tissue factor/Factor VIIa/PAR2 axis mediates fetal death in a mouse model of antiphospholipid syndrome.
Women with antiphospholipid syndrome (APS), a condition characterized by the presence of antiphospholipid antibodies (aPL), often suffer pregnancy-related complications, including miscarriage. We have previously shown that C5a induction of tissue factor (TF) expression in neutrophils contributes to respiratory burst, trophoblast injury, and pregnancy loss in mice treated with aPL. Here we analyzed how TF contributes to neutrophil activation and trophoblast injury in this model. Neutrophils from aPL-treated mice expressed protease-activated receptor 2 (PAR2), and stimulation of this receptor led to neutrophil activation, trophoblast injury, and fetal death. An antibody specific for human TF that has little impact on coagulation, but potently inhibits TF/Factor VIIa (FVIIa) signaling through PAR2, inhibited aPL-induced neutrophil activation in mice that expressed human TF. Genetic deletion of the TF cytoplasmic domain, which allows interaction between TF and PAR2, reduced aPL-induced neutrophil activation in aPL-treated mice. Par2-/- mice treated with aPL exhibited reduced neutrophil activation and normal pregnancies, which indicates that PAR2 plays an important role in the pathogenesis of aPL-induced fetal injury. We also demonstrated that simvastatin and pravastatin decreased TF and PAR2 expression on neutrophils and prevented pregnancy loss. Our results suggest that TF/FVIIa/PAR2 signaling mediates neutrophil activation and fetal death in APS and that statins may be a good treatment for women with aPL-induced pregnancy complications.


A group adaptation of Interpersonal Psychotherapy for depressed adolescents.
This paper presents an overview of the adaptation of Interpersonal Psychotherapy for depressed adolescents (IPT-A) to be delivered in a group format (IPT-AG) for the treatment of depressed, nonbipolar outpatient adolescents. The model has been modified to address the challenges of working with several adolescents in a group context. It takes advantage of the group as a laboratory environment for experimenting with new ways of communicating and interacting with others. The IPT-AG manual, described in this paper, provides guidelines for working with multiple interpersonal issues and keeping the group discussion relevant to the group as a whole. These adaptations are discussed in the context of the interpersonal framework with respect to each phase of treatment. Preliminary data about the feasibility and acceptability of conducting IPT-AG are discussed.


Handedness inversion of chiral amphiphilic molecular assemblies evidenced by supramolecular chiral imprinting in mesoporous silica assemblies.
Antipodal twisted helical ribbons with lamellar bilayer structure were obtained by self-assembly of chiral amphiphilic molecules in water and water/ethanol. The handedness inversion of the molecular arrangement in these antipodal helical ribbons was investigated by using chiroptical spectroscopy and molecular probes in their antipodal mesoporous silica assemblies synthesized through pairing interaction between the head group of the chiral amphiphilic molecules and a co-structure-directing agent. The supramolecular chirality is imprinted in the pore surface through the organic group of the co-structure-directing agent. The mirror-image diffuse-reflectance circular dichroism spectra of the conjugated discotic probing molecule introduced into their supramolecular chiral imprinted mesoporous silica demonstrated the origin of inverse chirality from the antipodal helical stacking of the molecules.


Evaluation of liver function tests in neonatal calves.
To evaluate the efficacy of tests for hepatic disease in young calves. Prospective case-control study. 28 clinically normal calves and 47 calves with histologically proven hepatic disease. Liver function tests and serum activity of liver-derived enzymes were determined on 28 clinically normal calves at birth and at 2 weeks of age. These values were compared with the results from 47 calves with hepatic disease verified by histologic examination. Upper limit of confidence interval was determined for the results on the clinically normal calves, and Student's t-test was used to identify significant differences in the data from calves of various age-groups. None of the results of the common tests for liver damage or function (measurement of bilirubin, gamma-glutamyltransferase, glutamate dehydrogenase [GMD], alkaline phosphatase, L-lactate dehydrogenase, aspartate transaminase, or alanine transaminase) were clinically useful when used alone for detection of hepatic disease in calves less than 6 weeks old. Sensitivity of gamma-glutamyltransferase, GMD, aspartate transaminase, and alkaline phosphatase as indicators of hepatic disease in this population of calves was 0, 59, 80, and 9%, respectively. Direct bilirubin (sensitivity, 87%) was more sensitive than total bilirubin (sensitivity, 66%). Serum enzyme activity of most enzymes (P < 0.01), total bilirubin concentration (P < 0.001), and sulfobromophthalein sodium clearance half-life were significantly higher (P < 0.001) in newborn calves than in 2-week-old calves. Clinical findings that indicate hepatic disease in calves that are less than 6 weeks old could be confirmed by measurement of serum activity of GMD or concentrations of total serum bile acids or direct bilirubin. Percutaneous liver biopsy may still be needed and may provide the most information.


Frequency of neutrophil alloantigens by polymerase chain reaction.
Neutrophil alloantigens are responsible for a number of immune clinical disorders such as neonatal alloimmune neutropenia, febrile transfusion reaction and transfusion related acute lung injury. Recent progress enabled typing of neutrophil antigens by deoxyribose nucleic acid based techniques. In this study we report for the first time the frequency distribution of human neutrophil antigen system-one in Saudis. Blood samples were collected from 100 successive healthy Saudi male blood donors presenting to Regional Laboratory and Blood Bank, Dammam, Kingdom of Saudi Arabia in 1997. Human neutrophil antigen typing was carried out using polymerase chain reaction-sequence specific primer method. Our results show that human neutrophil antigen system-one is highly polymorphic in this population and similar in its distribution to the Hispanic and Native Americans but different from the Caucasians, Indians and Africans. We found the polymerase chain reaction-sequence specific primer method to be a practical technique for neutrophil alloantigen typing. We recommend introducing this technology in tertiary care hospitals to allow easier diagnosis of immune neutropenias.


Studies on azaspiracid biotoxins. I. Ultrafast high-resolution liquid chromatography/mass spectrometry separations using monolithic columns.
In this study, the performance of monolithic columns was evaluated for ultrafast liquid chromatography/mass spectrometry (LC/MS) analyses and for high-resolution separations of several azaspiracid biotoxin analogs. Because of their high permeability, monolithic columns offer a number of advantages over conventional packed columns; viz., very low backpressures and relatively flat van Deemter curves at high flow rates. That is, very high flow rates can be used for ultrafast analyses or, by using longer than normal columns, high-resolution separations are possible. In a series of experiments, we varied the mobile phase flow rates between 1 and 8 mL/min, and studied their impact on chromatographic parameters such as retention time, resolution, number of plates and pressure. The chromatographic run times could be reduced to ca. 30 s without a significant change in the separation efficiency. A signal intensity comparison revealed interesting differences between atmospheric-pressure chemical ionization (APCI) and electrospray ionization (ESI) in their flow-rate dependency. An explanation with respect to the behavior as of a mass-flow or a concentration-dependent device is given in the paper. Additionally, the column length was varied between 10 and 70 cm. As a result, the number of theoretical plates increased substantially. In the example shown in the report, an increase from 13 000 plates for a 10-cm column to 80 000 for a 70-cm column is demonstrated. In addition, the potential of the monolithic columns for high-resolution LC/MS separations is shown for a complex biotoxin mixture, which was separated on a 40-cm-long column.


Inhibition of miRNA-29a regulates intestinal barrier function in diarrhea-predominant irritable bowel syndrome by upregulating ZO-1 and CLDN1.
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder. MicroRNAs (miRNAs) have been identified to be involved in different physiological and pathological processes. In this study, the role of miRNA-29a in the potential mechanism underlying the function of the intestinal mucosal barrier in IBS-D was analyzed. Human intestinal mucosal epithelia from patients with IBS-D (diagnosed as meeting the Rome IV criteria) and healthy volunteers were collected. An IBS-D mouse model was established via induction with trinitro-benzene-sulfonic acid (TNBS), and the mice were injected with miRNA-29a inhibitor. Using transmission electron microscopy (TEM), the epithelial ultrastructure of the human intestinal mucosa was examined. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, the expression level of miRNA-29a was assessed. ELISA was used to analyze the activity of D-lactate (D-LA) and diamine oxidase (DAO). Through immunohistochemistry, RT-qPCR and western blotting, the expression of tight junction protein ZO-1 (ZO-1) and claudin-1 (CLDN1) was examined. In the human intestinal mucosal epithelia from patients with IBS-D, miRNA-29a was upregulated, ZO-1 and CLDN1 were downregulated, and the junctional complex (JC) was faint and discontinuous. In the IBS-D mouse model, treatment with miRNA-29a inhibitor downregulated D-LA and DAO activity, and increased the expression of ZO-1 and CLDN1 in the intestinal mucosal epithelium. In conclusion, the present study revealed that miRNA-29a is involved in the pathogenesis of IBS-D, probably by downregulating ZO-1 and CLDN1 expression, suggesting that miRNA-29a is likely to be an important regulator of intestinal barrier function and could be a possible therapeutic target for IBS-D.


Value of technetium 99m sestamibi iodine 123 imaging in reoperative parathyroid surgery.
The purpose of this study was to assess the contribution of technetium 99m sestamibi iodine 123 (T/S) imaging to preoperative and intraoperative management of patients with persistent hyperparathyroidism. During a period of 10 months, all patients being prepared for reoperative parathyroid surgery (n = 10), two patients deemed significant operative risks (one patient with severe chronic obstructive pulmonary disease and one patient with severe cervical spine ankylosing spondylitis), and two patients who had undergone prior thyroid operation were studied with T/S imaging. Six patients undergoing reoperative surgery had undergone one, three had undergone two, and one had undergone three prior procedures. T/S imaging correctly localized 14 of 16 parathyroid tumors. By comparison, only 1 of 6 thallium technetium and 3 of 12 computed tomography (CT) scans (in seven patients) were positive. T/S imaging guided the reoperative surgical approach accurately in 12 of 14 patients, including one case of an undescended left lower gland at the level of the mandible and identification of a third gland on the left in another case. Sternal split was required to remove three lesions localized by T/S imaging, two beneath the aortic arch and one nestled in the aortopulmonary window in a patient who had undergone two prior procedures including a sternal split. In these three cases T/S imaging was particularly useful, because CT scans, thallium technetium scans, magnetic resonance imaging, and arteriography were not diagnostic. The outcome after operation was favorable in all 14 cases, with correction of hypercalcemia and no permanent laryngeal nerve injuries or hypocalcemia. We concluded that T/S imaging is more accurate than thallium technetium and CT scans in evaluation of patients with persistent hyperparathyroidism.


Predicting clinical responses in major depression using intrinsic functional connectivity.
There has been increasing interest in multivariate pattern analysis (MVPA) as a means of distinguishing psychiatric patients from healthy controls using brain imaging. However, it remains unclear whether MVPA methods can accurately estimate the medication status of psychiatric patients. This study aims to develop an MVPA approach to accurately predict the antidepressant medication status of individuals with major depression on the basis of whole-brain resting-state functional connectivity MRI (rs-fcMRI). We investigated data from rs-fcMRI of 24 medication-naive depressed patients, 16 out of whom subsequently underwent antidepressant treatment and achieved clinical recovery, and 29 demographically similar controls. By training a linear support vector machine classifier and combining it with principal component analysis, the medication-naive patients were identified from the healthy controls with 100% accuracy. In addition, we found reliable correlations between MVPA prediction scores and clinical symptom severity. Moreover, the most discriminative functional connections were located within or across the cerebellum and default mode, affective, and sensorimotor networks, indicating that these networks may play important roles in major depression. Most importantly, only ∼30% of these discriminative connections were normalized in clinically recovered patients after antidepressant treatment. The current study may not only show the feasibility of estimating medication status by MVPA of whole-brain rs-fcMRI data in major depression but also shed new light on the pathological mechanism of this disorder.


Interleukin-22 deficiency alleviates doxorubicin-induced oxidative stress and cardiac injury via the p38 MAPK/macrophage/Fizz3 axis in mice.
Several interleukin (IL) family members have been demonstrated to be involved in doxorubicin (DOX)-induced cardiac injury. This study aimed to investigate the role of IL-22 in DOX-induced cardiac injury and explore its possible mechanisms. In this study, mice were given DOX, and the cardiac expression and sources of IL-22 were determined. Then, IL-22 was knocked out to observe the effects on DOX-induced cardiac injury in mice. In addition, the p38 mitogen-activated protein kinase (MAPK) pathway was inhibited, macrophages were depleted and adoptively transferred, and Fizz3 was up-regulated in mice to explore the mechanisms. The results showed that cardiac IL-22 expression was significantly increased by DOX treatment and was mostly derived from cardiac macrophages. IL-22 knockout significantly reduced cardiac vacuolization and the expression of cardiomyocyte injury markers in both serum and left ventricular tissue and improved cardiac function in DOX-treated mice. In addition, IL-22 knockout reversed DOX-induced cardiac M1 macrophage/M2 macrophage imbalance, reduced oxidative stress and protected against cardiomyocyte apoptosis. p38 MAPK pathway inhibition with SB203580 and macrophage depletion further alleviated the above effects in DOX-treated IL-22-knockout mice. The effects were stronger IL-22-knockout mice with adoptive transfer of WT macrophages than in those with adoptive transfer of IL-22-knockout macrophages. Furthermore, increasing the expression of Fizz3 reduced cardiomyocyte apoptosis and alleviated cardiac dysfunction. Our results may suggest that IL-22 knockout alleviate DOX-induced oxidative stress and cardiac injury by inhibiting macrophage differentiation and thereby increasing the expression of Fizz3. Reductions in IL-22 expression may be beneficial for clinical chemotherapy in tumor patients.


Low Density Nanocellular Polymers Based on PMMA Produced by Gas Dissolution Foaming: Fabrication and Cellular Structure Characterization.
This paper describes the processing conditions needed to produce low density nanocellular polymers based on polymethylmethacrylate (PMMA) with relative densities between 0.45 and 0.25, cell sizes between 200 and 250 nm and cell densities higher than 1014 cells/cm³. To produce these nanocellular polymers, the foaming parameters of the gas dissolution foaming technique using CO₂ as blowing agent have been optimized. Taking into account previous works, the amount of CO₂ uptake was maintained constant (31% by weight) for all the materials. Foaming parameters were modified between 40 °C and 110 °C for the foaming temperature and from 1 to 5 min for the foaming time. Foaming temperatures in the range of 80 to 100 °C and foaming times of 2 min allow for production of nanocellular polymers with relative densities as low as 0.25. Cellular structure has been studied in-depth to obtain the processing-cellular structure relationship. In addition, it has been proved that the glass transition temperature depends on the cellular structure. This effect is associated with a confinement of the polymer in the cell walls, and is one of the key reasons for the improved properties of nanocellular polymers.


Extracts of the rat tapeworm, Hymenolepis diminuta, suppress macrophage activation in vitro and alleviate chemically induced colitis in mice.
Analysis of parasite-host interactions can reveal the intricacies of immunity and identify ways to modulate immunopathological reactions. We assessed the ability of a phosphate-buffered saline-soluble extract of adult Hymenolepis diminuta to suppress macrophage (human THP-1 cell line, murine peritoneal macrophages) activity in vitro and the impact of treating mice with this extract on colitis induced by dinitrobenzene sulfonic acid (DNBS). A high-molecular-mass fraction of adult H. diminuta (HdHMW) or excretory/secretory products reduced macrophage activation: lipopolysaccharide (LPS)-induced interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) and poly(I:C)-induced TNF-alpha and IL-6 were suppressed by HdHMW. The active component in the HdHMW extract was minimally sensitive to boiling and trypsin digestion, whereas the use of sodium metaperiodate, as a general deglycosylation strategy, indicated that the immunosuppressive effect of HdHMW was at least partially dependent on a glycan: treating the HdHMW with neuraminidase and alpha-mannosidase failed to inhibit its blockade of LPS-induced TNF-alpha production by THP-1 macrophages. Mice treated with DNBS developed colitis, as typified by wasting, shortening of the colon, macroscopic and microscopic tissue damage, and an inflammatory infiltrate. Mice cotreated with HdHMW (three intraperitoneal injections) displayed significantly less inflammatory disease, and this was accompanied by reduced TNF-alpha production and increased IL-10 and IL-4 production by mitogen-stimulated spleen cells. However, cotreatment of mice with neutralizing anti-IL-10 antibodies had only a minor impact on the anticolitic effect of the HdHMW. We speculate that purification of the immunosuppressive factor(s) from H. diminuta has the potential to lead to the development of novel immunomodulatory drugs to treat inflammatory disease.


Immunohistochemical localization of lysozyme, lactoferrin, alpha 1-antichymotrypsin, and alpha 1-antitrypsin in salivary gland of human fetuses.
26 human fetuses were examined to elucidate the immunohistochemical distributions of lysozyme, lactoferrin, alpha 1-antichymotrypsin, and alpha 1-antitrypsin in prenatal salivary glands. Development of fetal salivary glands was divided into 4 stages: The early developmental stage (EDS), the early intermediate developmental stage (EIDS), the late intermediate developmental stage (LIDS), and the late developmental stage (LDS) and were used to compare antigen localization during salivary gland development. Lysozyme (LY) staining was prominent in serous or demilune cells of the mucous acinar compartment. Lactoferrin (LF) was rarely seen in the fetal glands; only trace amounts were seen in serous cells, alpha 1-antichymotrypsin (alpha 1-ACT) was diffusely positive particularly in glandular ducts, alpha 1-antitrypsin (alpha 1-AT) was also diffusely distributed in all salivary gland elements and was more abundant in ductal cells than acinar cells. During the EDS, immunohistochemical staining of LY, LF, alpha 1-ACT, and alpha 1-AT could be observed with glandular intensity increases corresponding to the advance of cytodifferentiation of granular epithelium occurring in the subsequent EIDS and LIDS. Staining intensities were continuous during the LDS even though the amount of those materials in the fetal salivary glands was not of the extent seen in the adult salivary gland. These results suggest that production of LY, LF, alpha 1-ACT, and alpha 1-AT was positive during prenatal development of human salivary glands. The present study discusses the protective roles and defense mechanisms of LY, LF, alpha 1-ACT, and alpha 1-AT in developing human salivary glands.


Face, Content, and Construct Validity Evaluation of Simulation Models in General Surgery Laparoscopic Training and Education: A Systematic Review.
Laparoscopic technical surgical skills (LTS) are considered a fundamental competence for General Surgery residents. Several simulation tools (ST) have been explored to develop LTS. Although a plethora of systematic reviews evaluate the translation of LTS developed in simulation to real surgery, there is a lack of evidence that clarifies effectiveness of different validated ST in acquisition of LTS in surgical residents. The aim of this systematic review (SR) is to summarize published evidence on ST validation used for surgery education and training. A protocol was published in PROSPERO. A SR was carried out following PRISMA guidelines. Complete published articles in English or Spanish that validate either content or construct, plus another form of validation of ST to acquire LTS in general surgery were included. Articles that used only one validation or did not validate an ST were excluded. 1052 publications were initially identified across all searched databases. Title review identified 204 studies eligible for full text screening. 10 studies were included for final review. Two studies assessed both face and content, 4 face and construct, and 4 face, content and construct validity. None of the studies presented comparable outcomes due to metrics variation and scores used for the validation strategies. This study assessed validated laparoscopic simulation models, particularly in content and construct validity. Articles reported an increased use of simulation models in laparoscopic training with positive feedback from trainees, but few studies reported validation of training model. Validation strategies are not standardized, limiting comparability between them.


Combinations of Independent Dominant Loci Conferring Clubroot Resistance in All Four Turnip Accessions (Brassica rapa) From the European Clubroot Differential Set.
Clubroot disease is devastating to Brassica crop production when susceptible cultivars are planted in infected fields. European turnips are the most resistant sources and their resistance genes have been introduced into other crops such oilseed rape (Brassica napus L.), Chinese cabbage and other Brassica vegetables. The European clubroot differential (ECD) set contains four turnip accessions (ECD1-4). These ECD turnips exhibited high levels of resistance to clubroot when they were tested under controlled environmental conditions with Canadian field isolates. Gene mapping of the clubroot resistance genes in ECD1-4 were performed and three independent dominant resistance loci were identified. Two resistance loci were mapped on chromosome A03 and the third on chromosome A08. Each ECD turnip accession contained two of these three resistance loci. Some resistance loci were homozygous in ECD accessions while others showed heterozygosity based on the segregation of clubroot resistance in 20 BC1 families derived from ECD1 to 4. Molecular markers were developed linked to each clubroot resistance loci for the resistance gene introgression in different germplasm.


Revisiting monomeric HIV-1 protease. Characterization and redesign for improved properties.
Interactions between the C-terminal interface residues (96-99) of the mature HIV-1 protease were shown to be essential for dimerization, whereas the N-terminal residues () and Arg(87) contribute to dimer stability (Ishima, R., Ghirlando, R., Tozser, J., Gronenborn, A. M., Torchia, D. A., and Louis, J. M. (2001) J. Biol. Chem. 276, 49110-49116). Here we show that the intramonomer interaction between the side chains of Asp(29) and Arg(87) influences dimerization significantly more than the intermonomer interaction between Asp(29) and Arg(8'). Several mutants, including T26A, destablize the dimer, exhibit a monomer fold, and are prone to aggregation. To alleviate this undesirable property, we designed proteins in which the N- and C-terminal regions can be linked intramolecularly by disulfide bonds. In particular, cysteine residues were introduced at positions 2 and 97 or 98. A procedure for the efficient preparation of intrachain-linked polypeptides is presented, and it is demonstrated that the Q2C/L97C variant exhibits a native-like single subunit fold. It is anticipated that monomeric proteases of this kind will aid in the discovery of novel inhibitors aimed at binding to the monomer at the dimerization interface. This extends the target area of current inhibitors, all of which bind across the active site formed by both subunits in the active dimer.


The intelligibility of interrupted speech depends upon its uninterrupted intelligibility.
Recognition of sentences containing periodic, 5-Hz, silent interruptions of differing duty cycles was assessed for three types of processed speech. Processing conditions employed different combinations of spectral resolution and the availability of fundamental frequency (F0) information, chosen to yield similar, below-ceiling performance for uninterrupted speech. Performance declined with decreasing duty cycle similarly for each processing condition, suggesting that, at least for certain forms of speech processing and interruption rates, performance with interrupted speech may reflect that obtained with uninterrupted speech. This highlights the difficulty in interpreting differences in interrupted speech performance across conditions for which uninterrupted performance is at ceiling.


Distribution of rotavirus antigen in intestinal lymphoid tissues: potential role in development of the mucosal immune response to rotavirus.
Groups of suckling BALB/c mice were inoculated with murine rotavirus (MRV) at 5 days of age and sequentially tested for the presence of MRV antigen (Ag) in intestinal villus epithelium (VE), Peyer's patch (PP), mesenteric lymph node (MLN), spleen, liver and lung, using indirect immunofluorescence techniques (IF). MRV Ag was first detected in VE 24 h after oral administration of the virus and remained in VE for as long as 10 days post-inoculation (pi). MRV Ag was observed in the epithelium overlying PP at 3-7 days pi and in subepithelial and interfollicular areas in the PP between 3 and 20 days pi. MRV Ag was also detected in MLN during the same period of time. Small numbers of MRV-Ag-containing cells were detected in the lamina propria (LP) of intestinal villi at 10 days pi. Most MRV-Ag-containing cells in PP and MLN were Ia-positive but negative for Lyt-1, Lyt-2 and MAC-1 cell surface markers. MRV-Ag-containing cells were negative for surface or cytoplasmic immunoglobulin. Intestinal antibody response to MRV indicated by the presence of MRV-specific IgA plasma cells in LP was first detectable 10 days pi. Highest density of MRV-specific plasma cells was observed in the duodenum, with a similar distribution to that of MRV-Ag-containing cells in PP. These observations suggest that MRV-Ag uptake is largely limited to the PP associated epithelium and the virus Ag is subsequently transported to the underlying lymphoid follicles and MLN. These findings suggest a close relationship between the availability of MRV Ag in the lymphoid follicles at different locations and the subsequent development of local antibody responses in different segments of small intestine.


Ataxic hemiparesis from small capsular hemorrhage. Computed tomography and somatosensory evoked potentials.
We studied three cases that fit the clinical syndrome of ataxic hemiparesis. Computed tomography revealed small hemorrhages of the posterior limb of the internal capsule in all the cases, and somatosensory evoked potential studies predicted a disturbance of the lemniscal pathway from the thalamus to the parietal sensory cortex without demonstrable sensory loss. These results suggested that ataxia of the contralateral limbs following capsular lesion might result from a disruption of the thalamocortical sensory projection. The site of the lesion, the pathologic cause, and the underlying mechanism of ataxia are not necessarily homogeneous within the syndrome.


Efficient Heterogeneous Copper-Catalyzed Alder-Ene Reaction of Allenynamides to Pyrrolines.
Herein, we describe an efficient nanocopper-catalyzed Alder-ene reaction of allenynamides. The copper nanoparticles were immobilized on amino-functionalized microcrystalline cellulose. A solvent-controlled chemoselectivity of the reaction was observed, leading to the chemodivergent synthesis of pyrrolines (2,5-dihydropyrroles) and pyrroles. The heterogeneous copper catalyst exhibits high efficiency and good recyclability in the Alder-ene reaction, constituting a highly attractive catalytic system from an economical and environmental point of view.


Accuracy of Self-Reported Items for the Screening of Depression in the General Population.
Though self-reported items (SRD, self-reported depression) are commonly used in health surveys and cohort studies, their metric properties as a depression indicator remain unclear. The aims were to evaluate the measurement properties of SRD using the Patient Health Questionnaire-8 (PHQ-8) as reference and to identify factors related to the agreement between both indicators. Data from the European Health Interview Survey in Spain in 2014/2015 (n = 22,065) were analyzed. Two indicators of depression were considered: SRD based on two items yes/no (positive: both yes), and the PHQ-8 (positive ≥ 10). Socioeconomic factors and use of health services were considered as independent variables. The prevalence of depression, sensitivity, specificity, global agreement, and positive and negative predictive values (PPV and NPV) of SRDs were evaluated using the PHQ-8 as a reference. Logistic regression models were fitted to determine factors associated with the agreement between indicators. The prevalence of depression was lower when assessed with PHQ-8 (5.9%) than with SRD (7.7%). SRD sensitivity and PPV were moderate-low (52.9% and 40.4%, respectively) whereas global agreement, specificity, and NPV were high (92.7%, 95.1%, and 97.0%, respectively). Positive agreement was associated with marital status, country of birth, employment status, and social class. Negative agreement was related to all independent variables except country of birth. SRD items tend to overestimate the current prevalence of depression. While its use in health surveys and cohorts may be appropriate as a quick assessment of possible depression, due to their low sensitivity, its use in clinical contexts is questionable.


Simplified rules for everyday delineation of lymph node areas for breast cancer radiotherapy.
The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas "Help of delineation for breast cancer treatment". In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.


Folding of epidermal growth factor-like repeats from human tenascin studied through a sequence frame-shift approach.
In order to investigate the factors that determine the correct folding of epidermal growth factor-like (EGF) repeats within a multidomain protein, we prepared a series of six peptides that, taken together, span the sequence of two EGF repeats of human tenascin, a large protein from the extracellular matrix. The peptides were selected by sliding a window of the average length of tenascin EGF repeats over the sequence of EGF repeats 13 and 14. We thus obtained six peptides, EGF-f1 to EGF-f6, that are 33 residues long, contain six cysteines each, and bear a partial overlap in the sequence. While EGF-f1 corresponds to the native EGF-14 repeat, the others are frame-shifted EGF repeats. We carried out the oxidative folding of these peptides in vitro, analyzed the reaction mixtures by acid trapping followed by LC-MS, and isolated some of the resulting products. The oxidative folding of the native EGF-14 peptide is fast, produces a single three-disulfide species with an EGF-like disulfide topology and a marked difference in the RP-HPLC retention time compared with the starting product. On the contrary, frame-shifted peptides fold more slowly and give mixtures of three-disulfide species displaying RP-HPLC retention times that are closer to those of the reduced peptides. In contrast to the native EGF-14, the three-disulfide products that could be isolated are mainly unstructured, as determined by CD and NMR spectroscopy. We conclude that both kinetics and thermodynamics drive the correct pairing of cysteines, and speculate about how cysteine mispairing could trigger disulfide reshuffling in vivo.


Type I proatlantal artery with bilateral absence of the external carotid arteries.
During color Doppler examination of a 41-year-old man who presented with vertigo, a right vertebral artery could not be found. Both MR angiography and digital subtraction angiography revealed a large anastomotic vessel between the right internal carotid and vertebral artery. It was thought to be type I proatlantal artery. Furthermore, the external carotid arteries were bilaterally absent. Although each vascular anomaly mentioned above is rare, it even more rare for these variations to occur simultaneously.


[Treatment of fresh Achilles tendon ruptures with fibrin glue].
The surgeons of the accident hospital of the relevant professional association at Ludwigshafen have been increasingly resorting to treating fresh ruptures of the Achilles tendon with fibrin adhesive only. Initially the adhesion procedure was supplemented by and adaptational suture. The essential feature of this procedure is that no suturing material whatsoever is implanted into the tendon. The surgical procedure is quicker and simpler than by suturing the tendon rupture. Up to now 52 ruptures of the Achilles tendon have been treated with fibrin adhesive at the hospital under report. Curative results were very satisfactory with the exception of one complication where a renewed injury resulted in another rupture.


Alcohol and the nervous system.
Alcoholism is regarded as a multifactorial disorder, but the causes of alcoholism are poorly understood. The most important part of dealing with this widespread health and social problem is a prevention and early identification and treatment of those at risk. Therapeutic intervention should take place before development of cognitive impairment and physical dependence, otherwise treatment of developed alcoholism is notoriously unsatisfactory.


Oral exfoliative cytology in the diagnosis of paracoccidioidomycosis.
To assess the efficacy of conventional oral exfoliative cytology as a diagnostic tool in paracoccidioidomycosis. Cytologic smears and incisional biopsies were obtained from 10 patients with a clinical suspicion and oral manifestations of paracoccidioidomycosis. Cytologic smears and sections of the incisional biopsy underwent methenamine silver staining for fungi according to the Gomori-Grocott method. The dry glass slides were examined at 400 or 1,000 x magnification, and the presence and shape of yeasts of Paracoccidioides brasiliensis were investigated. Yeasts of the fungus P brasiliensis were clearly identified in cytologic smears and sections from incisional biopsies in all cases analyzed (100.0%). Cytology of oral samples proved an effective diagnostic method for the detection of paracoccidioidomycosis in humans.


Antimicrobial Sensitivity of Avibacterium paragallinarum Isolates from Four Latin American Countries.
The antimicrobial sensitivity of 11 reference strains and 66 Avibacterium paragallinarum isolates from four Latin American countries was investigated. All 11 reference strains were sensitive to amoxicillin-clavulanic acid, ampicillin, fosfomycin, gentamicin, kanamycin, neomycin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole. The 11 reference strains were all resistant to lincomycin. All isolates (100%) from Mexico, Panama, and Peru were sensitive to amoxicillin-clavulanic acid, ampicillin, and fosfomycin. The Ecuadorian isolates showed some level of resistance to all 16 agents tested. The Ecuadorian isolates were significantly more sensitive to erythromycin, lincomycin, and streptomycin, and significantly more resistant to gentamicin, kanamycin, penicillin, and tetracycline, than the Mexican isolates. A total of 57.5% (38/66) of tested isolates were multi-drug resistant (MDR), with 16 MDR patterns detected in 88.4% (23/26) of the antimicrobial-resistant isolates from Ecuador, and 8 MDR patterns detected in 42.8% (15/35) of the antimicrobial-resistant isolates from Mexico. In conclusion, the variation in antimicrobial sensitivity patterns between isolates from Ecuador and Mexico emphasizes the importance of active, ongoing monitoring of A. paragallinarum isolates.


Separation and quantitation of cholesterol "carriers" in bile.
On the basis of phase equilibria theory and experimental data, we discuss the identity, separation and quantitation of cholesterol-solubilizing lipid aggregates in bile, trivially known as cholesterol "carriers." We first describe analogies (as well as lack of correspondence) between equilibrium phase diagrams of aqueous bile salt, lecithin and cholesterol systems and phase equilibria in native biles. At equilibrium, the possible number and types of different cholesterol "carriers" are limited by constraints placed by the phase rule. These "carriers" include simple micelles (bile salts without lecithin), mixed micelles (bile salts plus lecithin), a lecithin plus cholesterol lamellar phase composed of single bilayer structures (vesicles) or multilamellar structures (liquid crystals) and possibly fragments of a hexagonal phase. Clearly, in this context, cholesterol monohydrate crystals, no matter how small, cannot be considered "carriers." We also use a metastable "phase diagram" for aqueous taurocholate-egg yolk lecithin-cholesterol systems to interpret physicochemical studies on the formation and stability of native biles. In biliary lipid systems, bile salt monomers with or without simple bile salt micelles are present in the aqueous "phase" in equilibrium with mixed micelles/or vesicles. This bile salt concentration is designated the intermicellar concentration but actually represents the total nonmixed micellar/nonvesicular concentration of bile salts (i.e., bile salt monomers and simple bile salt micelles when present) and may be a value that falls below, equal to or above the critical micellar concentration of the bile salts. Experimental estimates of the intermicellar-intervesicular bile salt concentration in model systems are compared with the range of bile salt concentrations that has been used in the literature to separate the presently accepted cholesterol "carriers" (mixed micelles and vesicles) in both model and native biles. We also reinterpret published lipid compositions of phases separated from human bile, using both a nonequilibrium "phase diagram" and an equilibrium phase diagram for the model system, taurocholate-egg yolk lecithin-cholesterol. From these analyses, we conclude that precise quantitation of cholesterol "carriers" in bile awaits methods to accurately determine the intermicellar-intervesicular concentration of bile salts in any individual bile, as well as advances in nonperturbing separatory procedures, and methods to control the thermal and temporal history of native bile samples.


Combined Effects of Irrigation Regime, Genotype, and Harvest Stage Determine Tomato Fruit Quality and Aptitude for Processing into Puree.
Industry tomatoes are produced under a range of climatic conditions and practices which significantly impact on main quality traits of harvested fruits. However, the quality of tomato intended for processing is currently addressed on delivery through color and Brix only, whereas other traits are overlooked. Very few works provided an integrated view of the management of tomato puree quality throughout the chain. To gain insights into pre- and post-harvest interactions, four genotypes, two water regimes, three maturity stages, and two processes were investigated. Field and glasshouse experiments were conducted near Avignon, France, from May to August 2016. Two irrigation regimes were applied: control plants were irrigated in order to match 100% of evapotranspiration (ETP); water deficit (WD) plants were irrigated as control plants until anthesis of the first flowers, then irrigation was reduced to 60 and 50% ETP in field, and glasshouse respectively. Fruits were collected at three stages during ripening. Their color, fresh weight, dry matter content, and metabolite contents were determined before processing. Pericarp cell size was evaluated in glasshouse only. Two laboratory-scaled processing methods were applied before structural and biochemical analyses of the purees. Results outlined interactive effects between crop and process management. WD hardly reduced yield, but increased dry matter content in the field, in contrast to the glasshouse. The puree viscosity strongly depended on the genotype and the maturity stage, but it was disconnected from fruit dry matter content or Brix. The process impact on puree viscosity strongly depended on water supply during fruit production. Moreover, the lycopene content of fresh fruit may influence puree viscosity. This work opens new perspectives for managing puree quality in the field showing that it was possible to reduce water supply without affecting yield and to improve puree quality.


VFDB 2022: a general classification scheme for bacterial virulence factors.
The virulence factor database (VFDB, http://www.mgc.ac.cn/VFs/) is dedicated to presenting a comprehensive knowledge base and a versatile analysis platform for bacterial virulence factors (VFs). Recent developments in sequencing technologies have led to increasing demands to analyze potential VFs within microbiome data that always consist of many different bacteria. Nevertheless, the current classification of VFs from various pathogens is based on different schemes, which create a chaotic situation and form a barrier for the easy application of the VFDB dataset for future panbacterial metagenomic analyses. Therefore, based on extensive literature mining, we recently proposed a general category of bacterial VFs in the database and reorganized the VFDB dataset accordingly. Thus, all known bacterial VFs from 32 genera of common bacterial pathogens collected in the VFDB are well grouped into 14 basal categories along with over 100 subcategories in a hierarchical architecture. The new coherent and well-defined VFDB dataset will be feasible and applicable for future panbacterial analysis in terms of virulence factors. In addition, we introduced a redesigned JavaScript-independent web interface for the VFDB website to make the database readily accessible to all users with various client settings worldwide.


Impact of preoperative sarcopenia on postoperative complications and survival outcomes of patients with esophageal cancer: a meta-analysis of cohort studies.
The effects of preoperative sarcopenia on postoperative complications and survival outcomes of patients undergoing esophageal cancer resection are controversial. From database establishment to 16 May 2021, we systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Chinese Biomedical Literature Database to collect relevant studies investigating the effects of preoperative sarcopenia on postoperative complications, survival outcomes, and the risk of a poor prognosis of patients undergoing esophagectomy. The Newcastle-Ottawa scale was used to evaluate the quality of the included literature, and RevMan 5.3 software was used for the meta-analysis. A total of 26 studies (3 prospective cohort studies and 23 retrospective cohort studies), involving 4,515 patients, were included. The meta-analysis showed that preoperative sarcopenia significantly increased the risk of overall complications (risk ratio [RR]: 1.15; 95% confidence interval [CI]: 1.08-1.22), pulmonary complications (RR: 1.78; 95% CI: 1.48-2.14), and anastomotic leakage (RR: 1.29; 95% CI: 1.04-1.59) and reduced the overall survival rate (hazard ratio: 1.12; 95% CI: 1.04-1.20) following esophageal cancer resection. Preoperative sarcopenia increased the risks of overall postoperative and pulmonary complications in patients undergoing esophageal cancer resection. For patients with esophageal cancer, assessing the preoperative risk of preoperative sarcopenia is necessary.