Structure of natural polyelectrolyte solutions: role of the hydrophilic/hydrophobic interaction balance.
A method allowing the evaluation of the solvophilic/solvophobic character of polyelectrolytes from their conformation in solution is discussed. Analyzed systems are salt-free aqueous solutions of natural copolysaccharides with controlled chemical structures. Small-angle X-ray scattering diagrams revealed their conformation by the "polyelectrolyte peak". The study of this peak allowed the determination of cb, the crossover concentration associated with the transition between the two structural organization regimes predicted by the scaling model of hydrophobic polyelectrolytes developed by Dobrynin and Rubinstein. A structural law of behavior as a function of the chain primary structure is built for chitosan, showing an increasing hydrophobic character when the fraction of N-acetyl-D-glucosamine residues (DA) increases. The results concerning this random copolymer are compared with those obtained for hyaluronan. Consistently, in the case of alginates, the relative content of the constitutive units is shown not to influence the polymer hydrophobicity.


[Correlation between the mRNA levels of carcinoembryonic antigen and cytokeratin 19 in peripheral blood with staging, treatment response and prognosis in patients with lung cancer].
To investigate the expression of carcinoembryonic antigen (CEA) and cytokeratin19 (CK19) mRNAs in peripheral blood of patients with lung cancer and their correlation with staging, treatment response and prognosis. CEA and CK19 mRNAs in peripheral blood were detected by Taq Man reverse transcriptase-polymerase chain reaction (RT-PCR) in 78 patients with lung cancer before and after treatment, 30 patients with benign lung diseases and 30 healthy subjects. Serum CEA and CYFRA21-1 levels were also measured by enzyme linked immunosorbent assay (ELISA) in the 78 patients with lung cancer before treatment. The patients were followed for 2 years. The positive rates of CEA mRNA and CK19 mRNA in patients with lung cancer were 69.2% (54/78) and 62.8% (49/78), respectively, which were significantly higher than those in patients with benign lung diseases and the healthy controls (P < 0.01). The positive rate of CEA mRNA was the highest in adenocarcinoma, while the positive rate of CK19 mRNA was the highest in squamous cell carcinoma. There was no statistically significant difference among different stages (P > 0.05), The positive rates of CEA mRNA and CK19 mRNA were higher than those of serum CEA and CYFRA21-1. The positive rates of CEA mRNA and CK19 mRNA decreased significantly after surgical operation, but there was no significant change after chemotherapy. The median survival time (MST) for patients with a positive CEA mRNA before chemotherapy was shorter than those with a negative CEA mRNA (8.5 month and 11.7 month, respectively). The MST for patients with a positive CK19 mRNA before chemotherapy was shorter than those with a negative CK19 mRNA (8.9 month and 12.3 month, respectively). The rate of relapse and metastasis was higher in patients (29.4%) with a positive CEA mRNA preoperatively than those with a negative CEA mRNA (7.7%). The rate of relapse and metastasis was also higher in patients with a positive CK19 mRNA preoperatively (18.8%) as compared to those with a negative PCR result (7.1%). CEA and CK19 mRNAs can be used as markers in the detection of tumor micrometastases in lung cancer, and in evaluating surgical response and prognosis. The results suggest that the gene markers are better than the serum ones, and therefore may be useful for the early diagnosis of lung cancer.


Capture of Electrochemically Generated Fleeting Carbazole Radical Cations and Elucidation of Carbazole Dimerization Mechanism by Mass Spectrometry.
The capture of reactive intermediates is important for the elucidation of reaction mechanisms. We report the first observation of electrochemically generated, short-lived radical cations of carbazole (t1/2 ≈ 97 μs) and two N-substituted carbazole derivatives by mass spectrometry. In addition, online investigation of the reactivity of electrochemically generated carbazole radical cations supports that the carbazole dimerization mechanism involves the reaction of one radical cation with one neutral molecule rather than the previously proposed coupling of two radical cations.


Phenological match drives pollen-mediated gene flow in a temporally dimorphic tree.
Variation in flowering phenology is common in natural populations, and is expected to be, together with inter-mate distance, an important driver of effective pollen dispersal. In populations composed of plants with temporally separated sexual phases (i.e. dichogamous or heterodichogamous populations), pollen-mediated gene flow is assumed to reflect phenological overlap between complementary sexual phases. In this study, we conducted paternity analyses to test this hypothesis in the temporally dimorphic tree Acer opalus. We performed spatially explicit analyses based on categorical and fractional paternity assignment, and included tree size, pair-wise genetic relatedness and morph type as additional predictors. Because differences between morphs in flowering phenology may also influence pollination distances, we modelled separate pollen dispersal kernels for the two morphs. Extended phenological overlap between male and female phases (mainly associated with inter-morph crosses) resulted in higher siring success after accounting for the effects of genetic relatedness, morph type and tree size, while reduced phenological overlap (mainly associated with intra-morph crosses) resulted in longer pollination distances achieved. Siring success also increased in larger trees. Mating patterns could not be predicted by phenology alone. However, as heterogeneity in flowering phenology was the single morph-specific predictor of siring success, it is expected to be key in maintaining the temporal dimorphism in A. opalus, by promoting not only a prevalent pattern of inter-morph mating, but also long-distance pollination resulting from intra-morph mating events.


ZooArchNet: Connecting zooarchaeological specimens to the biodiversity and archaeology data networks.
Interdisciplinary collaborations and data sharing are essential to addressing the long history of human-environmental interactions underlying the modern biodiversity crisis. Such collaborations are increasingly facilitated by, and dependent upon, sharing open access data from a variety of disciplinary communities and data sources, including those within biology, paleontology, and archaeology. Significant advances in biodiversity open data sharing have focused on neontological and paleontological specimen records, making available over a billion records through the Global Biodiversity Information Facility. But to date, less effort has been placed on the integration of important archaeological sources of biodiversity, such as zooarchaeological specimens. Zooarchaeological specimens are rich with both biological and cultural heritage data documenting nearly all phases of human interaction with animals and the surrounding environment through time, filling a critical gap between paleontological and neontological sources of data within biodiversity networks. Here we describe technical advances for mobilizing zooarchaeological specimen-specific biological and cultural data. In particular, we demonstrate adaptations in the workflow used by biodiversity publisher VertNet to mobilize Darwin Core formatted zooarchaeological data to the GBIF network. We also show how a linked open data approach can be used to connect existing biodiversity publishing mechanisms with archaeoinformatics publishing mechanisms through collaboration with the Open Context platform. Examples of ZooArchNet published datasets are used to show the efficacy of creating this critically needed bridge between biological and archaeological sources of open access data. These technical advances and efforts to support data publication are placed in the larger context of ZooarchNet, a new project meant to build community around new approaches to interconnect zoorchaeological data and knowledge across disciplines.


Oral Leiomyomatous Hamartoma of the Anterior Maxillary Gingiva.
Oral leiomyomatous hamartoma (OLH) is a rare developmental tumor-like anomaly of the oral cavity. This report documents a 4-year-old female who was diagnosed with an OLH of the palatal gingiva between the maxillary central incisors. This lesion was treated successfully by local surgical excision. Because many of the reported cases of this lesion have developed on the anterior maxillary gingiva, it is important for the periodontist to be aware of this entity.


Association of upper and lower airway eosinophilic inflammation with response to omalizumab in patients with severe asthma.
Background: The anti-immunoglobulin E monoclonal antibody, omalizumab, is used to treat severe asthma and has the potential to ameliorate airway inflammation. However, the effect of omalizumab in ameliorating upper airway inflammation has not been fully elucidated. Objective: We investigated the association of upper and lower airway inflammation with the response to omalizumab treatment. Methods: We used the Global Evaluation of Treatment Effectiveness to assess the efficacy of omalizumab in treating 16 patients with severe asthma. We also investigated the symptom score, short-acting β-agonist inhaler use, pulmonary function, biomarkers, computed tomography scans, and nasal mucosa pathology at omalizumab initiation and after four months of treatment. Results: When the fraction of exhaled nitric oxide (FeNO) and the percentage of sputum eosinophil were used as indicators of lower airway inflammation, positive correlations were found between CD20 B-cell, mast cell, and eosinophil counts in the nasal mucosa. Improved asthma symptoms were observed in 12 of the 16 severe asthma cases. The FeNO and eosinophil levels in the nasal tissue, prior to the administration of omalizumab were predictors of the response to asthma treatment. Conclusions: These findings suggest heterogeneity among people with severe asthma. In addition, the phenotype associated with response to omalizumab, leading to improvement in asthma symptoms, comprises upper airway eosinophilia and high FeNO levels.


Knowledge of preventive measures against occupational risks and spread of healthcare-associated infections among nursing students. An epidemiological prevalence study from Ferrara, Italy.
Exposure to biological agents is the most common occupational risk for nursing staff. This study verified changes in attitudes and knowledge occurred in the nursing students after the first year of degree. The survey was conducted in academic year 2006/07 among the students of the Professional Nursing Course at University of Ferrara (Italy) using a structured questionnaire. Students were 85 at the beginning and 80 at the end of the courses. The rate of subjects using gloves for intramuscular injections and fingertip puncture was unsatisfactory. A high percentage of students performed recap of needles. The use of gloves in case of washing of surgical instruments was high. The compliance in the use of gloves in handling test tubes remained low. Only 2/3 of the students washes their hands coming in ward. Incorrect attitudes have been observed in changing or wearing gloves. The students considered vaccination against hepatitis-B necessary, vaccination against flu unnecessary. A high percentage of students had not performed any prophylaxis for tuberculosis. Students intend the use of gloves mainly to perform self-protection. The concept of self-protection is contradicted by the large percentage of students that recap used needles. A significant percentage of students have not yet gained the critical thinking necessary to consider the importance of universal precautions as a means not only of self-protection but also of prevention of hospital infections. Students consider the basic standard measures for the control of infectious diseases only like self-protection and not to prevent hospital infections.


Alternative proteolytic processing of hepatocyte growth factor during wound repair.
Wound healing is a crucial regenerative process in all organisms. We examined expression, integrity, and function of the proteins in the hepatocyte growth factor (HGF)/c-Met signaling pathway in normally healing and non-healing human skin wounds. Whereas in normally healing wounds phosphorylation of c-Met was most prominent in keratinocytes and dermal cells, in non-healing wounds phosphorylation of c-Met was barely detectable, suggesting reduced c-Met activation. In wound exudates obtained from non-healing, but not from healing wounds, HGF protein was a target of substantial proteolytic processing that was different from the classical activation by known serine proteases. Western blot analysis and protease inhibitor studies revealed that HGF is a target of neutrophil elastase and plasma kallikrein during skin repair. Proteolytic processing of HGF by each of these proteases significantly attenuated keratinocyte proliferation, wound closure capacity in vitro, and c-Met signal transduction. Our findings reveal a novel pathway of HGF processing during skin repair. Conditions in which proteases are imbalanced and tend toward increased proteolytic activity, as in chronic non-healing wounds, might therefore compromise HGF activity due to the inactivation of the HGF protein and/or the generation of HGF fragments that ultimately mediate a dominant negative effect and limit c-Met activation.


An Acute Cervical Subdural Hematoma as the Complication of Acupuncture: Case Report and Literature Review.
Several injuries in the cervical region as complications of acupuncture have been previously reported in the literature, including cord and medulla oblongata injuries, subdural empyema, and cervical hematoma. Spinal cord subdural hematoma is a rare condition mainly associated with coagulopathy, trauma, and iatrogenic procedures. We herein report an acute cervical subdural hematoma after cervical acupuncture for neck and shoulder pain. A 74-year-old woman presented with progressive quadriparesis and sensory deficit after receiving acupuncture in the neck and shoulder. Magnetic resonance imaging of the cervical spine showed a subdural lesion that was a hyperintense mass in the T1-weighted and hypointense in T2-weighted images at the C4-C6 level, which proved to be an early subacute subdural hematoma. After surgical evacuation of the hematoma, the patient had significant neurologic improvement. Although rare, cervical spinal cord hematomas are disastrous complications of cervical acupuncture. These procedures should be performed under direct observation of trained physicians with appropriate knowledge of cervical anatomy to avoid these complications.


The Construction of an Aqueous Two-Phase System to Solve Weak-Aggregation of Gigaporous Poly(Styrene-Divinyl Benzene) Microspheres.
Gigaporous poly(styrene-divinyl benzene) microspheres made via the surfactant reverse micelles swelling method had a controllable pore size of 100⁻500 nm. These microspheres had unique advantages in biomacromolecule separation and enzymes immobilization. However, the obtained microspheres adhered to each other in the preparation process. Though the weak aggregation could be re-dispersed easily by mechanical force, it will be difficult to scale up. By analyzing the formation mechanism of the aggregates, a method was presented to rebuild the interface between the internal aqueous channel and the external continuous phase by constructing an aqueous two-phase system (ATPS). Based on the ATPS, the method of emulsification, stirring speed, and surfactant concentration in oil phase were optimized. Under the optimum condition (screen emulsification method, 120 rpm for polymerization and 55% surfactant), the microspheres with a controllable particle size of 10⁻40 μm and a pore size of about 150 nm were obtained. This new method could significantly decrease the weak-aggregation of microspheres.


Biochemical analysis of the major vaccinia virus envelope antigen.
The major envelope antigen of vaccinia virus is an acylated protein of M(r) 37,000 (p37K) which is required for the formation of extracellular enveloped virions (EEV). Despite its important role in the wrapping process, p37K has not been studied in much detail. In order to better characterize this protein we have undertaken a detailed biochemical analysis. Sodium carbonate treatment showed that p37K is tightly bound to the viral envelope. Its resistance to proteinase K digestion indicates that it is not exposed on the surface of EEV but lines the inner side of the envelope. Since p37K does not contain a signal peptide characteristic of most membrane proteins, we examined the possibility that the protein acquires its membrane affinity through the addition of fatty acids. Indeed, Triton X-114 phase partitioning experiments demonstrated that p37K is hydrophobic when acylated, but hydrophilic in the absence of fatty acids. Three other viral proteins have been shown to be required for virus envelopment and release from the host cell and we therefore tested whether p37K interacts with viral proteins. In EEV and in absence of reducing agents, an 80-kDa complex reacting with an anti-37K antiserum was found. Analysis of this complex showed that it most likely consists of a p37K homodimer. Interestingly, only a small amount of p37K occurs as a complex, most of it is present in the viral envelope as monomers.


Water-soluble monodispersed lanthanide oxide submicrospheres: PVP-assisted hydrothermal synthesis, size-control and luminescence properties.
We report a facile hydrothermal synthetic route to prepare a class of monodispersed lanthanide-based compound submicrospheres with controllable size, which employs raw lanthanide oxides as starting material, urea as precipitator and poly(N-vinyl-2-pyrrolidone) (PVP) as surfactant. Dependent on the intrinsic properties of respective lanthanide, the resulting products could be in the form of oxide, hydroxide or basic carbonate. These lanthanide hydroxides or basic carbonates can be easily transformed into their corresponding oxides by calcination, retaining the same morphology and size dispersion. The formation mechanism of these lanthanide-based compound submicrospheres is investigated and PVP plays a critical role in forming uniform and well-dispersed products. Furthermore, this method could be extended to a binary system by using two kinds of lanthanide oxides as starting material, resulting in doped-type lanthanide oxide submicrospheres (such as Y(2)O(3):Eu(3+)). The Y(2)O(3):Eu(3+) submicrospheres exhibit nearly uniform spherical morphology and narrow size distribution as well as good water solubility and sharp spectral emission at 610 nm (corresponding to the 5D(0)-7F(2) transition of Eu(3+)). This makes them attractive materials for applications in fields such as fluorescent lamps, field emission displays (FEDs) or LCDs, or as biomedical labels and molecular probes.


Renal artery stenosis and ischemic nephropathy.
Renal artery stenosis (RAS), in its most severe form, can result in diminished renal function and loss of kidney mass. The prevalence of ischemic nephropathy is greatly under-appreciated in the elderly population and is the source of substantial morbidity and mortality. Diagnostic tests for RAS in patients with renal insufficiency are problematic, and medical therapy does little to slow the natural progression of the disease. Renal artery stenting can achieve long-term vessel patency and has been shown to preserve renal function. Proper technique and careful case selection are critical to the success of such procedures. Large-scale trials are needed to clearly identify groups of patients who will benefit most from percutaneous revascularization.


The non-adrenergic non-cholinergic innervation of the esophagus and the lower esophageal sphincter.
Electrical stimulation of the vagus nerve causes the relaxation of the lower esophageal sphincter (LES), followed by the sequential contraction of the esophageal body smooth muscle. These responses are similar to those in response to swallowing. The nature of the inhibitory neurotransmitter responsible for the LES relaxation is not exactly known. Following the preliminary criteria, we systematically examined the possibility of different candidate substances as the inhibitory neurotransmitter. We ruled out the role of different neurotransmitter substances including the cholinergic and adrenergic ones. Finally, we examined the possibility of VIP as the inhibitory neurotransmitter of non-adrenergic non-cholinergic intramural neurons of the LES, responsible for LES relaxation. VIP caused relaxation of the LES by its action directly at the muscle. VIP antiserum, which antagonized the action of VIP, caused a significant antagonism of LES relaxation caused by vagal stimulation and local stimulation. These results suggest that VIP acts as an inhibitory neurotransmitter for LES relaxation. The exact nature of the neurotransmitter responsible for the esophageal peristalsis is also not known. It is suggested that the contraction of the longitudinal smooth muscle of the esophagus is mediated by acetylcholine and substance P, while the circular smooth muscle contraction is mediated through the release of acetylcholine and an unknown non-adrenergic non-cholinergic neurotransmitter. Whether the latter neurotransmitter is VIP remains to be seen.


Layer- and gate-tunable spin-orbit coupling in a high-mobility few-layer semiconductor.
Spin-orbit coupling (SOC) is a relativistic effect, where an electron moving in an electric field experiences an effective magnetic field in its rest frame. In crystals without inversion symmetry, it lifts the spin degeneracy and leads to many magnetic, spintronic, and topological phenomena and applications. In bulk materials, SOC strength is a constant. Here, we demonstrate SOC and intrinsic spin splitting in atomically thin InSe, which can be modified over a broad range. From quantum oscillations, we establish that the SOC parameter α is thickness dependent; it can be continuously modulated by an out-of-plane electric field, achieving intrinsic spin splitting tunable between 0 and 20 meV. Unexpectedly, α could be enhanced by an order of magnitude in some devices, suggesting that SOC can be further manipulated. Our work highlights the extraordinary tunability of SOC in 2D materials, which can be harnessed for in operando spintronic and topological devices and applications.


Psychological Outcomes, Health-Related Quality of Life, and Neurocognitive Functioning in Survivors of Childhood Cancer and Their Parents.
Childhood cancer disrupts the lives of patients and their families and affects acute and long-term psychological health. This article summarizes (1) psychological challenges, including depression, anxiety, worries, and posttraumatic stress, as well as positive outcomes such as benefit finding and posttraumatic growth in young survivors and parents; (2) health-related quality of life; (3) interventions to support survivors and parents with psychological difficulties; and (4) neurocognitive problems and interventions to help alleviate them. Although many survivors and parents fare well in the long term, many survivors may benefit from interventions. Interventions should be further evaluated and integrated into routine clinical care.


Exopolysaccharide producing rhizobacteria and their impact on growth and drought tolerance of wheat grown under rainfed conditions.
The demand for agricultural crops continues to escalate with an increasing population. To meet this demand, marginal land can be used as a sustainable source for increased plant productivity. However, moisture stress not only affects crop growth and productivity but also induces plants' susceptibility to various diseases. The positive role of plant growth hormone, salicylic acid (SA), on the defence systems of plants has been well documented. With this in mind, a combination of plant growth promoting rhizobacteria (PGPR) and SA was used to evaluate its performance on wheat grown under rainfed conditions (average moisture 10-14%). The selected bacterial strains were characterized for proline production, indole-3-acetic acid (IAA), hydrogen cyanide (HCN), ammonia (NH3), and exopolysaccharides (EPS). Wheat seeds of two genotypes, Inqilab-91 (drought tolerant) and Shahkar-2013 (drought sensitive), which differed in terms of their sensitivity to drought stress, were soaked for three hours prior to sowing in 24-hour old cultures of the bacterial strains Planomicrobium chinense strain P1 (accession no. MF616408) and Bacillus cereus strain P2 (accession no. MF616406). SA was applied (150 mg/L), as a foliar spray on one-month-old wheat seedlings. A significant reduction in the physiological parameters was noted in the plants grown in rainfed conditions but the PGPR and SA treatment effectively ameliorated the adverse effects of moisture stress. The wheat plants treated with PGPR and SA showed significant increases in leaf protein and sugar contents and maintained higher chlorophyll content, chlorophyll fluorescence (fv/fm) and performance index (PI) under rainfed conditions. Leaf proline content, lipid peroxidation, and antioxidant enzyme activity were higher in the non-inoculated plants grown in rainfed conditions but significantly reduced in the inoculated plants of both genotypes. Integrative use of a combination of PGPR strains and SA appears to be a promising and eco-friendly strategy for reducing moisture stress in plants.


Production of an Active, Human Membrane Protein in Saccharomyces cerevisiae: Full-Length FICD.
The human Fic domain-containing protein (FICD) is a type II endoplasmic reticulum (ER) membrane protein that is important for the maintenance of ER proteostasis. Structural and in vitro biochemical characterisation of FICD AMPylase and deAMPylase activity have been restricted to the soluble ER-luminal domain produced in Escherichia coli. Information about potentially important features, such as structural motifs, modulator binding sites or other regulatory elements, is therefore missing for the approximately 100 N-terminal residues including the transmembrane region of FICD. Expressing and purifying the required quantity and quality of membrane proteins is demanding because of the low yields and poor stability often observed. Here, we produce full-length FICD by combining a Saccharomyces cerevisiae-based platform with green fluorescent protein (GFP) tagging to optimise the conditions for expression, solubilisation and purification. We subsequently employ these conditions to purify milligram quantities of His-tagged FICD per litre of culture, and show that the purified, detergent-solubilised membrane protein is an active deAMPylating enzyme. Our work provides a straightforward methodology for producing not only full-length FICD, but also other membrane proteins in S. cerevisiae for structural and biochemical characterisation.


Computational Chemistry Meets Experiments for Explaining the Geometry, Electronic Structure, and Optical Properties of Ca10V6O25.
In this paper, we present a combined experimental and theoretical study to disclose, for the first time, the structural, electronic, and optical properties of Ca10V6O25 crystals. The microwave-assisted hydrothermal (MAH) method has been employed to synthesize these crystals with different morphologies, within a short reaction time at 120 °C. First-principle quantum mechanical calculations have been performed at the density functional theory level to obtain the geometry and electronic properties of Ca10V6O25 crystal in the fundamental and excited electronic states (singlet and triplet). These results, combined with the measurements of X-ray diffraction (XRD) and Rietveld refinements, confirm that the building blocks lattice of the Ca10V6O25 crystals consist of three types of distorted 6-fold coordination [CaO6] clusters: octahedral, prism and pentagonal pyramidal, and distorted tetrahedral [VO4] clusters. Theoretical and experimental results on the structure and vibrational frequencies are in agreement. Thus, it was possible to assign the Raman modes for the Ca10V6O25 superstructure, which will allow us to show the structure of the unit cell of the material, as well as the coordination of the Ca and V atoms. This also allowed us to understand the charge transfer process that happens in the singlet state (s) and the excited states, singlet (s*) and triplet (t*), generating the photoluminescence emissions of the Ca10V6O25 crystals.


Mental health and disabilities: what we know about racial and ethnic minority children.
The recognition that children and adolescents suffer from mental health problems and disabilities is a recent phenomenon, not arising until the late 19th century. Because of the increasing numbers and importance of ethnic minority children and youth to the vitality of the United States, their mental health and disabilities can no longer be overlooked. Mental health is paramount for fostering social integration, unity, and inclusiveness within and between ethnic groups. Thus the significance of changing demographics and the disparity in mental health indicators make this a key issue for the future. Nursing research in this area has been limited, in spite of the fact that mental health problems and disabilities exert a disproportionate negative effect on racial and ethnic minority children (NIMH, 2001a). The purpose of this chapter is to critique the available nursing research on mental health and disabilities in racial and ethnic minority children, including how such research has been conceptualized, conducted, and interpreted.


Immunological response to parenteral vaccination with recombinant hepatitis B virus surface antigen virus-like particles expressing Helicobacter pylori KatA epitopes in a murine H. pylori challenge model.
Virus-like particles (VLPs) based on the small envelope protein of hepatitis B virus (HBsAg-S) are immunogenic at the B- and T-cell level. In this study, we inserted overlapping sequences encoding the carboxy terminus of the Helicobacter pylori katA gene product into HBsAg-S. The HBsAg-S-KatA fusion proteins were able to assemble into secretion-competent VLPs (VLP-KatA). The VLP-KatA proteins were able to induce KatA-specific antibodies in immunized mice. The mean total IgG antibody titers 41 days post-primary immunization with VLP-KatA (2.3 × 10(3)) were significantly greater (P < 0.05) than those observed for vaccination with VLP alone (5.2 × 10(2)). Measurement of IgG isotypes revealed responses to both IgG1 and IgG2a (mean titers, 9.0 × 10(4) and 2.6 × 10(4), respectively), with the IgG2a response to vaccination with VLP-KatA being significantly higher than that for mice immunized with KatA alone (P < 0.05). Following challenge of mice with H. pylori, a significantly reduced bacterial load in the gastric mucosa was observed (P < 0.05). This is the first report describing the use of VLPs as a delivery vehicle for H. pylori antigens.


Co-infection of market-age turkeys with Escherichia coli and Listeria monocytogenes in two stress models.
We have hypothesized that stress-induced subclinical infection of turkeys with Listeria monocytogenes may be an overlooked source of processing plant contamination, and we have shown that concurrent Escherichia coli challenge can increase L. monocytogenes colonization. The objective of this study was to determine the effects of dexamethasone (Dex) immunosuppressive treatment and transport stress on the isolation of L. monocytogenes in an E. coli-L. monocytogenes challenge model. Thirteen-week-old male turkeys housed in floor pens were either nonchallenged (NCH) or challenged (CH) by environmental exposure to E. coli and L. monocytogenes Scott A, using both a coarse spray and feed inclusion. One group of both NCH and CH birds was not stressed (NCH-Con and CH-Con, respectively), a second group was treated with Dex during challenge (NCH-Dex and CH-Dex, respectively), and a third group was subjected to a 12-hour transport (Trans) stress protocol at 15 wk of age (NCH-Trans and CH-Trans, respectively). All birds were bled and necropsied the morning after transport. Dexamethasone treatment increased mortality and disease incidence. The CH-Con, CH-Trans, and CH-Dex birds, as well as the NCH-Dex birds, had lowered body weights compared to the NCH-Con. The relative liver and heart weights were increased, and the relative bursal weights were decreased by both NCH-Dex and CH-Dex treatments. The heterophil:lymphocyte ratio, a measure of the stress response, was increased by CH-Trans, NCH-Dex, and CH-Dex. Total erythrocyte counts and hematocrit were decreased by NCH-Trans, CH-Trans, NCH-Dex and CH-Dex. The challenge strain of E. coli was isolated from the organs of a significant number of CH-Dex birds using direct plating and occasionally from CH-Trans birds. Listeria monocytogenes was not isolated from significant numbers of birds using direct plating, but was isolated from the knee or hip synovial tissues of a significant percentage of CH-Dex birds using pre-enrichment cultural methods, and from CH-Trans and CH-Dex birds using real-time PCR detection. These data suggest that L. monocytogenes colonization of processing-age turkeys can be increased by stress, and the organism may be harbored within inapparent infections of turkey synovial tissue.


Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries.
A theoretical model is developed to simulate the flow of blood through the capillary network in a single alveolar septum. The objective is to study the influence of random variability in capillary dimension and compliance on flow patterns and pressures within the network. The capillary bed is represented as an interconnected rectangular grid of capillary segments and junctions; blood flow is produced by applying a pressure gradient across the network. Preferred flow channels are shown to be a natural consequence of random anatomic variability, the effect of which is accentuated at low transcapillary pressures. The distribution of pressure drops across single capillary segments widens with increasing network variability and decreasing capillary transmural pressure. Blockage of one capillary segment causes the pressure drop across that segment to increase by 60%, but the increase falls to < 10% at a distance of three segments. The factors that cause nonuniform capillary blood flow through the capillary network are discussed.


[Medication overuse headache].
Rebound headache (RH) is a chronic daily headache which occurs when analgesics, triptans, ergotamines are taken frequently (more than 15 days/month for more than 3 months) to relieve headaches. The prevalence of RH is 1 to 4% in the general population. RH commonly occurs in patients with migraine and tension-type headache. The deficit of central sensitization and psychological factors play an important role in initiating and maintaining of RH. Treatment of noofen for 2 months is effective in 75% of patients with RH.


Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients.
Isotretinoin has been successfully used for the treatment of acne vulgaris. To investigate the effects of isotretinoin on body mass index (BMI), to determine whether isotretinoin causes any changes in serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients, and to correlate variables. Thirty-two patients were included in this study. Oral isotretinoin was begun at a dose of 0.5-0.6 mg/kg and raised to 0.6-0.75 mg/kg. Pretreatment and posttreatment third-month BMI and adiponectin, leptin, and ghrelin serum levels were measured. The pre- and posttreatment BMI values were not significantly different. In addition, serum adiponectin and leptin levels were significantly increased following isotretinoin therapy while serum ghrelin levels were not different. Isotretinoin may exert its anti-inflammatory activity by increasing leptin and adiponectin levels.


Short-term passive smoking causes endothelial dysfunction via oxidative stress in nonsmokers.
Recent studies have shown that passive smoking impairs vascular endothelial function and induces oxidative stress in humans. However, in most of the previous human data regarding tobacco-induced pathophysiology, vascular endothelial dysfunction and oxidative stress have been separately assessed. This study was designed to determine the association between the acute effect of passive smoking on vascular endothelial function and in-vivo oxidative stress status. We studied 30 healthy male Japanese volunteers (32 +/- 7 years) including 15 habitual smokers and 15 nonsmokers. After baseline echocardiographic, hemodynamic recording, and blood sampling, subjects were exposed to passive smoking for 30 min. Endothelium-dependent vasodilation was measured by using % flow-mediated vasodilation (%FMD) of the brachial artery and plasma levels of 8-isoprostane was measured by enzyme immunoassay before and after the passive smoking exposure. Baseline %FMD was lower (4.3% +/- 1.2% vs. 10.9% +/- 3.1%, p < 0.001) and baseline plasma 8-isoprostane level was higher (41.5 +/- 5.8 pg/mL vs. 26.9 +/- 5.4 pg/mL, p < 0.001) in smokers than those in nonsmokers. The %FMD and 8-isoprostane level did not change after passive smoking in smokers. In nonsmokers, however, the %FMD decreased (to 5.0% +/- 1.9%, p < 0.001) and the 8-isoprostane level increased (to 37.8 +/- 9.6 pg/mL, p < 0.001) significantly after 30 min passive smoking exposure, equivalently to the levels of smokers. Sixty corrected samples before and after passive smoking exposure in all patients showed a significant negative correlation between the % FMD and the plasma 8-isoprostane levels (n = 60, r = -0.69, p < 0.001). Even 30 min of passive smoking rapidly impairs vascular endothelial function, which is associated with oxidative stress. Our data provide the pathophysiological insight for the recent epidemiological evidence about the increased risk of coronary heart disease among nonsmokers exposed to passive smoking.


Role of surgical intervention in the management of intestinal metastases from malignant melanoma.
Malignant melanoma is the most common metastatic lesion of the intestine. Surgical consultation is often sought when bowel metastases become symptomatic. To determine the role of surgical intervention in such cases, a database of 6,000 melanoma patients was examined, and a subset of 102 patients with small intestinal or colonic metastases were identified premortem. Common presenting features included abdominal pain with or without acute symptoms (29% of patients), obstruction or intussusception (27%), and bleeding (26%). The presence of metastatic lesions was confirmed by surgical exploration in 80% of patients, endoscopic procedures in 11%, and percutaneous biopsy in 5%. Cure was achieved in 36 patients by resection, which resulted in the removal of all demonstrable disease. The subsequent mean length of survival in this group was 31 +/- 5.2 months. Forty-two patients underwent palliative enteric bypass or debulking procedures, and 24 patients received either chemotherapy alone or symptomatic treatment. The average length of survival in these latter groups was 9.6 +/- 15.9 and 9.6 +/- 3.6 months, respectively, both of which were significantly less than the duration of survival in the complete resection group (p less than 0.05). Small or large bowel resection for bleeding or obstruction and enteric bypass for obstruction provided symptomatic relief in 92% of patients thus treated. There was no operative mortality in the series. An aggressive search for resectable disease in patients with symptoms secondary to intestinal metastases from malignant melanoma should be performed. Surgical intervention may then allow the palliation of pain, obstruction, and bleeding. Survival can be significantly prolonged if it is possible to remove all demonstrable disease.


In patients with a positive family history of familial adenomatous polyposis can the condition be diagnosed from the presence of congenital hypertrophy of the retinal pigment epithelium detected via an eye examination: A systematic review.
In classic familial adenomatous polyposis (FAP) adenomas become malignant. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is a retinal pigmented lesion and is the earliest and most common potential extraintestinal manifestation of FAP. This review aims to summarize and analyse all of the published data on CHRPE in patients with classic FAP and then ascertain whether these patients should undergo a relatively cheap and non-invasive dilated fundus examination to screen for CHRPE. Adhering to Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines our database search identified 102 relevant articles of which 13 were selected for further analysis. The percentage of FAP patients with CHRPE was found to be 80.00%, whereas the percentage of at-risk patients with CHRPE was 31.12%. Despite various statistically significant findings, CHRPE alone cannot be used as a surrogate for diagnosing FAP in those with a positive family history. The authors advocate a combined approach of eye examinations, colonoscopy and genetic testing.


Impairment of endothelium-dependent aorta relaxation by phospholipid components of oxidized low-density lipoprotein.
Oxidized low-density lipoprotein (LDL) is a major component in the pathophysiology of atherosclerosis and plays a role in the changes of vascular reactivity observed in this disease. Herein the authors investigate the potential involvement of platelet-activating factor (PAF)-like phospholipid components of oxidized LDL in rabbit aorta reactivity. Aortic rings were precontracted with noradrenaline (0.5 microM) and relaxation was induced by subsequent stimulation with sequential additions of acetylcholine (1 nM to 3 microM). High-performance liquid chromatography (HPLC) fractions (6- and 7-min) obtained from phospholipids extracted from oxidized LDL inhibited relaxation evoked by acetylcholine, but not the relaxation induced by sodium nitroprusside. This effect was not antagonized either by incubation of the fractions with PAF acetylhydrolase or by incubation of the aortic rings with a PAF receptor antagonist. Authentic PAF or C4-PAF, a PAF mimetic previously found in fractions 6 and 7 did not inhibit acetylcholine-induced relaxation. In contrast, lyso-PAF inhibited acetylcholine, but not sodium nitroprusside-induced relaxation. The authors conclude that phospholipids of oxidized LDL impair vascular reactivity to endothelium-dependent agonists. This effect is not due to oxidatively generated proinflammatory PAF mimetics, but rather to a metabolite of these phospholipids, lysoPAF.


Patient-reported QoL in anal cancer survivors 3 and 6 years after treatment-results from the Swedish national ANCA study.
The impact of anal cancer treatment for the patients is best evaluated by the patients themselves. The purpose of this study was to investigate quality of life (QoL) in patients with anal cancer at 3 and 6 years after treatment. A Swedish national cross-sectional prospective cohort study with patients diagnosed with anal cancer between 2011 and 2013. Patients were invited to respond to a QoL questionnaire at 3 and 6 years, with focus on bowel, urinary and sexual function, social and mental function, co-morbidity, lifestyle, daily activities, personal characteristics, and perceived QoL. It also contained questions on the severity of the symptoms regarding occurrence, frequency, and duration and the level of "bother" experienced related to functional symptoms. QoL and prevalence of bother with urinary, sexual, bowel dysfunction, and anal pain were described. The prevalence of impaired QoL was compared with a healthy reference population. The association between QoL and experiencing bother was quantified by regression models. From an original cohort of 464 patients with anal cancer, 264 (57%) were alive and contacted at 3 years and 230 (50%) at 6 years. One hundred ninety-five (74%) patients responded to the 3-year and 152 (66%) to the 6-year questionnaire. Sixty percent reported low QoL at both 3 and 6 years. Impaired QoL was more prevalent among patients with major bother due to bowel dysfunction (at 3 years RR 1.42, 95% CI (1.06-1.9) p-value 0.020, at 6 years RR 1.52, 95% CI (1.03-2.24) p-value 0.034) and urinary dysfunction (at 6 years RR 1.44, 95% CI (1.08-1.91) p-value 0.013). There was a tendency to a positive relationship between the number of bodily functions causing bother and risk for impaired QoL. Patients treated for anal cancer reported bother regarding several bodily functions as well as poor QoL both at 3 and 6 years without much improvement. Bother was also associated with low QoL indicating that function-related bother should be addressed.


Acoustic schwannoma: MR findings in 84 tumors.
MR imaging is the study of choice for the examination of patients with suspected acoustic schwannoma, because of its high sensitivity, especially after the use of contrast material. This essay illustrates the common MR features of acoustic schwannomas as seen in a study of 84 tumors. We pay special attention to the role of MR imaging in the distinction between acoustic schwannoma and meningioma.


[Immediate results of surgical treatment of proximal aortic dissection].
From 1984 to 1997, 112 patients have been operated at the Department of Cardiac Surgery of the Azienda Ospedaliera of Parma for acute dissection of ascending aorta. They were 73 males and 39 females of mean age 59.2 years (range 19-79); in the majority they presented a history of essential hypertension and atherosclerotic disease: the first diagnostic suspicion has been confirmed either by angio-CT scan or by CT scan plus aorthography and, from 1994, with transesophageal color doppler echocardiography that is becoming a valuable and precise tool wich can be used in emergency room. Bentall type composite repair or modified Bentall technique has been possible in 37 patients, while in the remaning 75, surgical aortic repair has been achieved by interposition of a dacron vascular prosthesis. Cardiac procedures that were performed in addition were coronary bypass grafthing, resuspension of the aortic valve, AVR. Total arch replacement with reimplantation of brachiocephalic vessels were performed in 6 patients and partial in 10, when intimal tear extended into the arc. Thirthythree in hospital deaths (29.4%) occurred (15 in S.O. and 18 in UCI). Follow up of the hospital survivors was conducted at a mean postoperative interval of 55 months (range 2 to 149 months with 6 late death related to aortic dissection). Our experience shows an increased incidence hypertension and aortic atherosclerosis, compared with marfan's syndrome as a source of acute aortic dissection in the late years, transesophageal echocardiography is a excellent tool for aortic dissection but it may miss dissection localized in other aortic portion, the need of an individualized and conservative surgical approach tailored to the pathology encountered.


Cyclooxygenase-2 inhibition provides lasting protection against neonatal hypoxic-ischemic brain injury.
To investigate whether inhibition of cyclooxygenase-2, a critical component of the inflammatory pathway, is neuroprotective in a neonatal rat model of cerebral hypoxia-ischemia. The development of brain inflammation largely contributes to neonatal brain injury that may lead to a lifetime of neurologic deficits. Laboratory investigation. University research laboratory. Postnatal day ten Sprague-Dawley rats. Neonatal hypoxia-ischemia was induced by ligation of the right common carotid artery followed by 2 hrs of hypoxia (8% oxygen). The pups in treatment groups were administered 10 mg/kg (low dose) or 30 mg/kg (high dose) of a known selective cyclooxygenase-2 inhibitor (NS398). Animals were euthanized at three time points: 72 hrs, 2 wks, or 6 wks. Inflammation outcomes were assessed at 72 hrs; brain damage was assessed at 2 wks and 6 wks along with other organs (heart, spleen). Detailed neurobehavioral examination was performed at 6 wks. Pharmacologic inhibition of cyclooxygenase-2 markedly increased survivability within the first 72 hrs compared with untreated rats (100% vs. 72%). Low- and high-dose NS398 significantly attenuated the loss of brain and body weights observed after hypoxia-ischemia. Neurobehavioral outcomes were significantly improved in some parameters with low-dose treatment, whereas high-dose treatment consistently improved all neurologic deficits. Immunohistochemical results showed a marked decrease in macrophage, microglial, and neutrophil abundance in ipsilateral hemisphere of the NS398-treated group along with a reduction in interleukin-6 expression. Selective cyclooxygenase-2 inhibition protected neonatal rats against death, progression of brain injury, growth retardation, and neurobehavioral deficits after a hypoxic-ischemic insult.


The effect of weight correction on risk calculations for Down's syndrome screening.
Recent advances in prenatal screening have led to the possibility that the risk of Down's syndrome associated pregnancy may be assessed by blood tests for maternal serum alphafetoprotein, human chorionic gonadotrophin (and possibly unconjugated oestriol) taken at 15-18 weeks of gestation. In neural tube defect screening correction of maternal serum alphafetoprotein for maternal weight has been recommended, although the precise method for weight correction is still under debate. We report an assessment of weight correction for maternal serum alphafetoprotein and human chorionic gonadotrophin based on 1408 singleton pregnancies and for unconjugated oestriol based on 197 singleton pregnancies. We demonstrate that weight correction of maternal serum alphafetoprotein and human chorionic gonadotrophin is statistically valid but that correction of unconjugated oestriol is not.


Comparison of NaCl-induced programmed cell death in the obligate halophyte Cakile maritima and the glycophyte Arabidopsis thaliana.
Salinity represents one of the most important constraints that adversely affect plants growth and productivity. In this study, we aimed at determining possible differences between salt tolerant and salt sensitive species in early salt stress response. To this purpose, we subjected suspension-cultured cells from the halophyte Cakile maritima and the glycophyte Arabidopsis thaliana, two Brassicaceae, to salt stress and compared their behavior. In both species we could observe a time and dose dependent programmed cell death requiring an active metabolism, a dysfunction of mitochondria and caspase-like activation although C. maritima cells appeared less sensitive than A. thaliana cells. This capacity to mitigate salt stress could be due to a higher ascorbate pool that could allow C. maritima reducing the oxidative stress generated in response to NaCl. It further appeared that a higher number of C. maritima cultured cells when compared to A. thaliana could efficiently manage the Na(+) accumulation into the cytoplasm through non selective cation channels allowing also reducing the ROS generation and the subsequent cell death.


Vaccination uptake among Australian early childhood education staff: assessing perceptions, behaviours and workplace practices.
Early Childhood Education Centre (ECEC) staff are strongly recommended to receive several immunizations including influenza and pertussis. However, evidence regarding the uptake is either old or lacking across all Australian States/Territories. This study aimed to explore the attitudes and barriers around ECEC staff vaccination and the immunisation policy/practices employed at their workplaces. An online cross-sectional survey was undertaken of staff members (administrators and childcare center staff) in early 2017. We compared the individual's knowledge, attitude and practices as well as the centre's policy and practice variables between the vaccinated and unvaccinated respondents. A logistic model was used to identify the factors associated with uptake of the different vaccines. A total of 575 ECEC staff completed the survey. Sixty percent reported being aware of the recommendations about staff immunisation. While participants did acknowledge that they could spread diseases if unvaccinated (86%), 30% could not recall receiving a dTpa in the last 10 years. Private centres were less likely to provide free or onsite vaccination compared to other categories of centres. Less than half reported receiving any encouragement to get the influenza vaccine and only 33% reported that their centre provides onsite influenza vaccination. Regarding the introduction of mandatory policies, 69% stated that they would support a policy. Employers should consider supporting methods to maximize vaccination of their employees including providing free onsite vaccination. Participants were open to idea of mandatory vaccination; however, this needs to be explored further to determine how vaccine costs and access issues could be resolved.


Whole Health in the Veterans Health Administration.
The Whole Health System being developed and implemented at the Veterans Health Administration is an approach to care which aims to shift the discussion from "What's the Matter With You?" to "What Matters to You?" This article describes some of the progress and future challenges in the implementation of this approach across the VHA.


Prose Fiction as a Narrative Companion for a Vegetable Parenting Videogame.
The purpose of this research is to explore the capacity of story to connect to a health-related videogame, as well as the qualities that may increase efficacy by making the story compelling. Parents of 3-5-year-old children often report difficulty getting their children to eat vegetables, which are protective against chronic illnesses. Videogames may be vehicles for training parenting practices for successful vegetable consumption outcomes but often rely on stories to provide context and details. Unfortunately, storytelling may interrupt immersion and player agency. Delivering stories outside of gameplay may provide an understanding of game situations while maintaining immersion. Two companion storylines (one a romantic adventure and the other a suspenseful fantasy) were generated for a vegetable parenting game, "Mommio," targeting mothers of preschool children. Mothers of 3-5-year-old children (n=18) read both storylines and completed semistructured interviews. Mothers preferred the romantic adventure, which featured strong characters, relatable issues, and an engaging plot. Most mothers were interested in playing the "Mommio" videogame after reading the stories. Results suggest that it is possible for prose literature to both motivate gameplay and be an immersive narrative companion to, but separate from, games for health. This literature should include engaging, realistic stories and relatable strong characters.


[Surgical treatment of adrenocortical cancer: significance of systematic lymphodissection].
Comparative efficacy of radical methods of surgical intervention for adrenocortical cancer (ACC) with lymphodissection (LD) and without it was studied. There were operated on 280 patients for primary ACC. Adrenalectomy (AE) with en bloc excision of tumor and systematic lymph nodes dissection (paranephral, left-side paraaortal and the right-side paracaval collectors) constitutes the optimal surgical procedure. AE with retroperitoneal space lymph nodes dissection is the method of choice for ACC. AE with the tumor en bloc excision without performance of LD may give the same expected efficacy only for I-II stages tumor, when it is impossible to confirm malignancy intraoperatively.


Effects of palmitoylation of Cys(415) in helix 8 of the CB(1) cannabinoid receptor on membrane localization and signalling.
The CB(1) cannabinoid receptor is regulated by its association with membrane microdomains such as lipid rafts. Here, we investigated the role of palmitoylation of the CB(1) receptor by analysing the functional consequences of site-specific mutation of Cys(415) , the likely site of palmitoylation at the end of helix 8, in terms of membrane association, raft targeting and signalling. The palmitoylation state of CB(1) receptors in rat forebrain was assessed by depalmitoylation/repalmitoylation experiments. Cys(415) was replaced with alanine by site-directed mutagenesis. Green fluorescence protein chimeras of both wild-type and mutant receptors were transiently expressed and functionally characterized in SH-SY5Y cells and HEK-293 cells by means of confocal microscopy, cytofluorimetry and competitive binding assays. Confocal fluorescence recovery after photobleaching was used to assess receptor membrane dynamics, whereas signalling activity was assessed by [(35) S]GTPγS, cAMP and co-immunoprecipitation assays. Endogenous CB(1) receptors in rat brain were palmitoylated. Mutation of Cys(415) prevented the palmitoylation of the receptor in transfected cells and reduced its recruitment to plasma membrane and lipid rafts; it also increased protein diffusional mobility. The same mutation markedly reduced the functional coupling of CB(1) receptors with G-proteins and adenylyl cyclase, whereas depalmitoylation abolished receptor association with a specific subset of G-proteins. CB(1) receptors were post-translationally modified by palmitoylation. Mutation of Cys(415) provides a receptor that is functionally impaired in terms of membrane targeting and signalling. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.


Abdominal ultrasound image acquisition and interpretation by novice practitioners after minimal training on a simulated patient model.
The Focused Assessment with Sonography in Trauma (FAST) exam is a rapid ultrasound test to identify evidence of hemorrhage within the abdomen. Few studies examine the accuracy of paramedic performed FAST examinations. The duration of an ultrasound training program remains controversial. This study's purpose was to assess the accuracy of paramedic FAST exam interpretation following a one hour didactic training session. The interpretation of paramedic performed FAST exams was compared to the interpretation of physician performed FAST examinations on a mannequin model containing 300ml of free fluid following a one hour didactic training course. Results were compared using the Chi-square test. Differences in accuracy rate were deemed significant if p < 0.05. Fourteen critical care flight paramedics and four emergency physicians were voluntarily recruited. The critical care paramedics were mostly ultrasound-naive whereas the emergency physicians all had ultrasound training. The correct interpretation of FAST scans was comparable between the two groups with accuracy of 85.6% and 87.5% (∆1.79 95%CI -33.85 to 21.82, p = 0.90) for paramedics and emergency physicians respectively. This study determined that critical care paramedics were able to use ultrasound to detect free fluid on a simulated mannequin model and interpret the FAST exam with a similar accuracy as experienced emergency physicians following a one hour training course. This suggests the potential use of prehospital ultrasound to aid in the triage and transport decisions of trauma patients while limiting the financial and logistical burden of ultrasound training.


Comorbidity of late life depression: an opportunity for research on mechanisms and treatment.
Late life depression principally affects individuals with other medical and psychosocial problems, including cognitive dysfunction, disability, medical illnesses, and social isolation. The clinical associations of late life depression have guided the development of hypotheses on mechanisms predisposing, initiating, and perpetuating specific mood syndromes. Comorbidity studies have demonstrated a relationship between frontostriatal impairment and late life depression. Further research has the potential to identify dysfunctions of specific frontostriatal systems critical for antidepressant response and to lead to novel pharmacological treatments and targeted psychosocial interventions. The reciprocal interactions of depression with disability, medical illnesses, treatment adherence, and other psychosocial factors complicate the care of depressed older adults. Growing knowledge of the clinical complexity introduced by the comorbidity of late life depression can guide the development of comprehensive treatment models. Targeting the interacting clinical characteristics associated with poor outcomes has the potential to interrupt the spiral of deterioration of depressed elderly patients. Treatment models can be most effective if they focus on amelioration of depressive symptoms, but also on treatment adherence, prevention of relapse and recurrence, reduction of medical burden and disability, and improvement of the quality of life of patients and their families.


Solvothermal one-step synthesis of Ni-Al layered double hydroxide/carbon nanotube/reduced graphene oxide sheet ternary nanocomposite with ultrahigh capacitance for supercapacitors.
A Ni-Al layered double hydroxide (LDH), mutil-wall carbon nanotube (CNT), and reduced graphene oxide sheet (GNS) ternary nanocomposite electrode material has been developed by a facile one-step ethanol solvothermal method. The obtained LDH/CNT/GNS composite displayed a three-dimensional (3D) architecture with flowerlike Ni-Al LDH/CNT nanocrystallites gradually self-assembled on GNS nanosheets. GNS was used as building blocks to construct 3D nanostructure, and the LDH/CNT nanoflowers in turn separated the two-dimensional (2D) GNS sheets, which preserved the high surface area of GNSs. Furthermore, the generated porous networks with a narrow pore size distribution in the LDH/CNT/GNS composite were also demonstrated by the N2 adsorption/desorption experiment. Such morphology would be favorable to improve the mass transfer and electrochemical action of the electrode. As supercapacitor electrode material, the LDH/CNT/GNS hybrid exhibited excellent electrochemical performance, including ultrahigh specific capacitance (1562 F/g at 5 mA/cm(2)), excellent rate capability, and long-term cycling performance, which could be a promising energy storage/conversion material for supercapacitor application.


The complete chloroplast genome of Castanopsis mekongensis A. Camus (Fagaceae).
Castanopsis mekongensis is highly valued in the furniture industry for its good wood texture, an endemic species in Yunnan province, southwest China. In our study, the chloroplast genome of C. mekongensis was assembled and characterized based on Illumina pair-end sequencing data. The total genome size of C. mekongensis was 160,699 bp, displayed a typical quadripartite structure including a pair of inverted repeat (IRs, 25,714 bp) regions separated by a large single-copy (LSC, 90,278 bp) region and a small single-copy (SSC, 18,963 bp) region. The overall guanine-cytosine (GC) content was 36.8%. We annotated 130 genes in the genome, containing 85 protein-coding genes, 37 tRNA genes, and eight rRNA genes, 12 genes contain a single intron, and two genes have two introns. The result of phylogenetic analysis based on maximum-likelihood (ML) phylogenetic tree indicated that C. mekongensis was most closely related to C. hainanensis.


O-acetylserine(thiol)lyase from spinach (Spinacia oleracea L.) leaf: cDNA cloning, characterization, and overexpression in Escherichia coli of the chloroplast isoform.
The last enzymatic step for L-cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL, EC 184.108.40.206) which synthesizes L-cysteine from O-acetylserine and "sulfide." We have isolated and characterized a full-length cDNA (1432 bp) from a lambda gt11 library of spinach leaf encoding the complete precursor of the chloroplast isoform. The 1149-nucleotide open reading frame coding for O-acetylserine(thiol)lyase was in the direction opposite that of the lambda gt11 beta-galactosidase gene. The derived amino acid sequence indicates that the protein precursor consists of 383 amino acid residues including a N-terminal presequence peptide of 52 residues. The amino acid sequence of mature spinach chloroplast O-acetylserine(thiol)lyase shows 40 and 57% homology with its bacterial counterparts. Sequence comparison with several pyridoxal 5'-phosphate-containing proteins reveals the presence of a lysine residue assumed to be involved in cofactor binding. A synthetic cDNA was constructed, coding for the entire 331-amino-acid mature O-acetylserine(thiol)lyase and for an initiating methionine. A high level of expression of the active mature chloroplast isoform was achieved in an Escherichia coli strain carrying the T7 RNA polymerase system (F. W. Studier, A. H. Rosenberg, J. J. Dunn, and J. W. Dubendorff, 1990, in Methods in Enzymology, D. V. Goeddel, Ed., Vol. 185, pp. 60-89, Academic Press, San Diego, CA). Addition of pyridoxine to the bacterial growth medium enhanced the enzyme activity due to the recombinant protein. The extent of production is 25-fold higher than in chloroplast from spinach leaves and the recombinant protein presents the relative molecular mass and immunological properties of the natural enzyme from spinach leaf chloroplast. This work, together with our previous biochemical studies, are in accordance with a prokaryotic type enzyme for L-cysteine biosynthesis in higher plant chloroplasts. Southern blot analysis indicated that O-acetylserine(thiol)lyase is encoded by multiple genes in the spinach leaf genomic DNA.


Milia-like calcinosis cutis in a girl with Down syndrome.
Milia-like idiopathic calcinosis cutis (MICC) is a very rare dermatological disorder characterized by multiple whitish to skin colored, milia-like papules, mostly found on the hands. MICC can disappear spontaneously by adulthood; therefore, its early recognition is crucial to avoiding unnecessary interventions. Herein, we present a case of MICC in a 6-year-old girl with Down syndrome.


Emergency Radiobioassay Method for Determination of ⁹⁰Sr and ²²⁶Ra in a Spot Urine Sample.
A new radiobioassay method has been developed for simultaneous determination of (90)Sr and (226)Ra in a spot urine sample. The method is based on a matrix removal procedure to purify the target radionuclides from a urine sample followed by an automated high performance ion chromatographic (HPIC) separation of (90)Sr and (226)Ra and offline radiometric detection by liquid scintillation counting (LSC). A Sr-resin extraction chromatographic cartridge was used for matrix removal and purification of (90)Sr and (226)Ra from a urine sample prior to its introduction to the HPIC system. The HPIC separation was carried out through cation exchange chromatography using methanesulfonic acid (75 mM) as the mobile phase at 0.25 mL/min flow rate. The performance criteria of the method was evaluated against the American National Standard Institute ANSI/HPS N13.30-2011 standard for the root mean squared error (RMSE) of relative bias (Br) and relative precision (SB) at two different spiked activity levels. The RMSE of Br and SB for (90)Sr and (226)Ra were found to be satisfactory (≤0.25). The minimum detectable activity (MDA) of the method for (90)Sr and (226)Ra are 2 Bq/L and 0.2 Bq/L, respectively. The MDA values are at least 1/10th of the concentrations of (90)Sr (190 Bq/L) and (226)Ra (2 Bq/L) excreted in urine on the third day following an acute exposure (inhalation) that would lead to an effective dose of 0.1 Sv in the first year. The sample turnaround time is less than 8 h for simultaneous determination of (90)Sr and (226)Ra.


Breath-hold device for laboratory rodents undergoing imaging procedures.
The increased use in noninvasive imaging of laboratory rodents has prompted innovative techniques in animal handling. Lung imaging of rodents can be a difficult task because of tissue motion caused by breathing, which affects image quality. The use of a prototype flat-panel computed tomography unit allows the acquisition of images in as little as 2, 4, or 8 s. This short acquisition time has allowed us to improve the image quality of this instrument by performing a breath-hold during image acquisition. We designed an inexpensive and safe method for performing a constant-pressure breath-hold in intubated rodents. Initially a prototypic manual 3-way valve system, consisting of a 3-way valve, an air pressure regulator, and a manometer, was used to manually toggle between the ventilator and the constant-pressure breath-hold equipment. The success of the manual 3-way valve system prompted the design of an electronically actuated valve system. In the electronic system, the manual 3-way valve was replaced with a custom designed 3-way valve operated by an electrical solenoid. The electrical solenoid is triggered by using a hand-held push button or a foot pedal that is several feet away from the gantry of the scanner. This system has provided improved image quality and is safe for the animals, easy to use, and reliable.


Cofactor-apoprotein hydrogen bonding in oxidized and fully reduced flavodoxin monitored by trans-hydrogen-bond scalar couplings.
Hydrogen bonding plays a key role in the tight binding of the FMN cofactor and the regulation of its redox properties in flavodoxins. Hydrogen bonding interactions can be directly observed in solution by multidimensional heteronuclear NMR spectroscopy through the scalar couplings between donor and acceptor nuclei. Here we report on the detection of intermolecular trans-hydrogen-bond couplings ((h)J) between the flavin ring system and the backbone of Desulfovibrio vulgaris flavodoxin in the oxidized and the two-electron reduced states. For this purpose, experiments are adapted from pulse sequences previously applied to determining (h)J coupling constants in nucleic acid-base pairs and proteins. The resulting (h2)J(N,N), (h4)J(N,N), (h3)J(C,N), and (h1)J(H,N) couplings involve the (15)N(1), (13)C(2), and (15)N(3) nuclei of the pyrimidine moiety of FMN, whereas no such interactions are detectable for (13)C(4) and (15)N(5). Several long-range (15)N-(15)N, (13)C-(15)N, and (1)H-(15)N J-coupling constants within the flavin are obtained as "by-products". The magnitudes of both (h)J and regular J couplings are found to be dependent on the redox state. In general, good correlations between (h)J coupling constants and donor-group (1)H chemical shifts and also crystallographic donor-acceptor distances are observed.


PVO / NGO initiatives, Latin America. Grupo pela VIDDA, Brazil.
"VIDDA" is a Portuguese acronym representing enhancement, integration, and dignity of people living with HIV/AIDS (PWAs). The groups are composed of people infected with HIV, their friends, relatives, lovers, and anyone who feels that his or her everyday life has been affected by the epidemic. They hope that through solidarity they can respond to the difficult situation facing people who are HIV positive in Brazil. Grupo pela VIDDA seeks to raise the consciousness of the government and the society and force them to take responsibility for the epidemic. Their fundamental objective is to fight for PWAs to have a full range of civil rights. "This is a fight that we have in common with all the Brazilian people who are searching for democracy, the right to work, and access to good health services," states a Grupo pela VIDDA brochure. Through their network they provide accurate and current information, counseling, legal assistance, and sponsor support groups. For more information, please contact Grupo pela VIDDA, Rua General Jardim, 556 CEP 01223-010, Cx Postal 54063, CEP 01296, Sao Paulo SP, tel/fax: +55 11 258 7729; or Rua 7 de Setembro, 48 12 andar CEP 20050-000, tel: +55 21 224 1654, fax: +55 21 294 5602. There are also offices in Curitiba, Goiania, Niteroi, Recife, and Vitoria.


Porcine sperm factor supports activation and development of bovine nuclear transfer embryos.
A study was undertaken to determine whether injection of porcine sperm factors (pSF), which trigger oscillations in intracellular calcium concentration ([Ca(2+)](i)) in mammalian oocytes, could be used to activate bovine oocytes during nuclear transfer. To date, only combined treatments that induce a monotonic rise in [Ca(2+)](i) and inhibit either phosphorylation or protein synthesis have been utilized in nuclear transfer. Several doses of pSF were tested. Injection of 5 mg/ml pSF triggered [Ca(2+)](i) oscillations that resembled those associated with fertilization with respect to amplitude and periodicity, and as a result, a high percentage of oocytes underwent activation. Furthermore, this concentration of pSF supported in vitro and in vivo development up to 60-90 days of gestation, comparable to development in control nuclear transfer embryos. Nevertheless, neither activation procedure supported development as well as did fertilization. The effectiveness of pSF as an activating agent in bovine oocytes may have been compromised because pSF was unable to support oscillations past 3-5 h postinjection and a second injection was necessary to extend the [Ca(2+)](i) oscillations. Likewise, a single injection of pSF failed to trigger downregulation of the inositol 1,4,5-trisphosphate receptor 1 subtype, whereas a second injection downregulated the receptor in a manner similar to that seen in fertilized oocytes. These results demonstrate that soluble factor(s) from porcine sperm can support early development in bovine nuclear transfer embryos; however, the efficacy may be limited because of the premature cessation of the induced oscillations.


Functional asymmetries in the rodent barrel cortex.
Neurophysiological and 2-deoxyglucose (2DG) studies of the rodent whisker barrel cortex have demonstrated asymmetries in its functional organization. To examine the possibility that the activity gradients observed in metabolic studies can be attributed to subtle rostral-caudal and dorsal-ventral asymmetries in electrophysiologically measured surround or cross-whisker inhibition, we compared 2DG results with predictions generated from quantitative single-cell receptive field data. Despite differences in the two experimental approaches, there is remarkable agreement between the findings. (1) The distribution of 2DG activity declines across the barrel cortex of the behaving animal from anteromedial barrels to posterolateral barrels, and is qualitatively and quantitatively similar to the values predicted from neurophysiology. (2) The strength of surround inhibition in barrel neurons predicts the twofold increase in activation of the C3 barrel following acute clipping of adjacent whiskers. And (3) within a cortical column, the decrease in metabolic activity associated with adjacent whisker stimulation is greatest in layer IV and least in the infragranular layers; this corresponds to the laminar distribution of inhibitory interactions observed electrophysiologically.


Differential activation of NF-κB and nitric oxide in lymphocytes regulates in vitro and in vivo radiosensitivity.
Lymphocytes are more sensitive to radiation in vivo than in vitro. However, the mechanism of this differential response is poorly understood. In the present study, it was found that the lipid peroxidation and cell death were significantly higher in lymphocytes following whole body irradiation (WBI) as compared to lymphocytes exposed to radiation in vitro. EL-4 cells transplanted in mice were also more sensitive to radiation than EL-4 cells irradiated in vitro. DNA repair, as assessed by comet assay, was significantly faster in lymphocytes exposed to 4Gy radiation in vitro as compared to that in lymphocytes obtained from whole body irradiated mice exposed to the same dose of radiation. This was associated with increased NF-κB activation in response to genotoxic stress and lesser activation of caspase in lymphocytes in vitro compared to in vivo. To explain the differential radiosensitivity, we postulated a role of nitric oxide, an extrinsic diffusible mediator of radiosensitivity that has also been implicated in DNA repair inhibition. Nitric oxide levels were significantly elevated in the plasma of whole body irradiated mice but not in the supernatant of cells irradiated in vitro. Addition of sodium nitroprusside (SNP), a nitric oxide donor to cells irradiated in vitro inhibited the repair of DNA damage and enhanced apoptosis (increased Bax to Bcl-2 ratio). Administration of l-NAME, a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. These results confirm that the observed differential radiosensitivity of lymphocytes was due to slow repair of DNA due to nitric oxide production in vivo.


β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.
Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in mitochondria. We showed that mice with a global loss of SIRT4 [SIRT4-knockout (KO) mice] developed an increase in glucose- and leucine-stimulated insulin secretion, and this was followed by accelerated age-induced glucose intolerance and insulin resistance. Because whole body SIRT4-KO mice had alterations to nutrient-stimulated insulin secretion, we hypothesized that SIRT4 plays a direct role in regulating pancreatic β-cell function. Thus, we tested whether β-cell-specific ablation of SIRT4 would recapitulate the elevated insulin secretion seen in mice with a global loss of SIRT4. Tamoxifen-inducible β-cell-specific SIRT4-KO mice were generated, and their glucose tolerance and glucose- and leucine-stimulated insulin secretion were measured over time. These mice exhibited normal glucose- and leucine-stimulated insulin secretion and maintained normal glucose tolerance even as they aged. Furthermore, 832/13 β-cells with a CRISPR/Cas9n-mediated loss of SIRT4 did not show any alterations in nutrient-stimulated insulin secretion. Despite the fact that whole body SIRT4-KO mice demonstrated an age-induced increase in glucose- and leucine-stimulated insulin secretion, our current data indicate that the loss of SIRT4 specifically in pancreatic β-cells, both in vivo and in vitro, does not have a significant impact on nutrient-stimulated insulin secretion. These data suggest that SIRT4 controls nutrient-stimulated insulin secretion during aging by acting on tissues external to the β-cell, which warrants further study.


Catheter closure of the persistent foramen ovale: mid-term results in 162 patients.
Four different types of occluder systems were used to close a persistent foramen ovale (PFO) in 162 patients with paradoxical embolic events. Ninety-eight patients had ischemic stroke, 60 transient ischemic attacks (TIA) or prolonged reversible ischemic neurological deficit (PRIND), and 4 had peripheral arterial embolism. The age of the patients was 40.2 +/- 11.9 years and the ischemic event had happened 7 +/- 10 months before device closure. CardioSeal and Amplatzer occluders were the most commonly used devices (73 and 77 cases, respectively). Implantations were successful in all patients. Serious catheter-related complications included two device embolizations and two venous bleedings. Six patients had documented supraventricular arrhythmias within the first month after implantation, which disappeared spontaneously within some weeks without therapy in three patients; the other three patients with atrial fibrillation needed conversion to sinus rhythm. Residual leaks were found in 5 out of 116 patients who had been followed by transesophageal echocardiography (TEE) and one leak was closed by a second device. During a follow-up period of 19.4 +/- 16.2 months per patient, TIA and PRIND occurred in 3 of 116 patients. Interventional closure of PFO is a simple, effective and quick method that is superior to surgery and avoids the problems of life-long anticoagulation.


Characterization of the pleural microenvironment niche and cancer transition using single-cell RNA sequencing in EGFR-mutated lung cancer.
Background: Lung cancer is associated with a high mortality rate and often complicated with malignant pleural effusion (MPE), which has a very poor clinical outcome with a short life expectancy. However, our understanding of cell-specific mechanisms underlying the pathobiology of pleural metastasis remains incomplete. Methods: We analyzed single-cell transcriptomes of cells in pleural effusion collected from patients with lung cancer and congestive heart failure (as a control), respectively. Soluble and complement factors were measured using a multiplex cytokine bead assay. The role of ferroptosis was evaluated by GPX4 small interfering RNA (siRNA) transfection and overexpression. Results: We found that the mesothelial-mesenchymal transition (MesoMT) of the pleural mesothelial cells contributed to pleural metastasis, which was validated by lung cancer/mesothelial cell co-culture experiments. The ferroptosis resistance that protected cancer from death which was secondary to extracellular matrix detachment was critical for pleural metastasis. We found a universal presence of immune-suppressive lipid-associated tumor-associated macrophages (LA-TAMs) with complement cascade alteration in the MPE of the lung cancer patients. Specifically, upregulated complement factors were also found in the MPE, and C5 was associated with poor overall survival in the lung cancer patients with epidermal growth factor receptor mutation. Plasmacytoid dendritic cells (pDCs) exhibited a dysfunctional phenotype and pro-tumorigenic feature in the primary cancer. High expression of the gene set extracted from pDCs was associated with a poor prognosis in the lung cancer patients. Receptor-ligand interaction analysis revealed that the pleural metastatic niche was aggravated by cross-talk between mesothelial cells-cancer cells/immune cells via TNC and ICAM1. Conclusions: Taken together, our results highlight cell-specific mechanisms involved in the pathobiological development of pleural metastasis in lung cancer. These results provide a large-scale and high-dimensional characterization of the pleural microenvironment and offer a useful resource for the future development of therapeutic drugs in lung cancer.


2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event.
We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified compounds were designed to possess the binding affinity of an RNA molecule towards a complementary RNA target with an enhanced stability against nucleases. The 2'-O-methyl and 2'-O-ethyl antisense compounds function as potent inhibitors of the reaction at 1-10 nM, approximately 5-fold more effective than a natural antisense RNA molecule and requiring an approximate 5-fold excess over the target RNA for 80% inhibition of the processing reaction.


[Behavior and mental activity disorders after carbon monoxide poisoning. Bilateral pallidal lesions].
Two patients who had suffered severe carbon monoxide intoxication showed lasting neuropsychologic sequelae: 1) deep inertia involving the whole behaviour and expressed by an almost complete lack of activity if not induced by someone else; a mental gap when the patients were left to themselves and a tendency to give up the mental activity when stimuli ceased; an apparent affective indifference connected with a lack of spontaneous expression of the affects; 2) pseudo-obsessionnal activities: coprolalia with sexual themes in one patient, obsessive collecting and tidying up activities in the other one. Neurologic examination was normal, particularly no parkinsonian syndrome was present. CT scans showed bilateral pallidal low density areas. Both patients had moderate intellectual impairment in psychometric tests and amnestic disorders. There is a possible relationship between memory and cognitive impairment and mental inertia. The onset of pseudo-obsessional signs following basal ganglia lesions is emphasized. The central semeiological fact seems to be a disorder of the initiation and the carrying on of any external action as well as mental activity itself. This may be related with the activity disorders represented at a more elementary level by motion impairment in parkinsonian akinesia.


Measuring the thickness of vertebral endplate and shell using digital tomosynthesis.
The vertebral endplate and cortical shell play an important structural role and contribute to the overall strength of the vertebral body, are at highest risk of initial failure, and are involved in degenerative disease of the spine. The ability to accurately measure the thickness of these structures is therefore important, even if difficult due to relatively low resolution clinical imaging. We posit that digital tomosynthesis (DTS) may be a suitable imaging modality for measurement of endplate and cortical shell thickness owing to the ability to reconstruct multiplanar images with good spatial resolution at low radiation dose. In this study, for 25 cadaveric L1 vertebrae, average and standard deviation of endplate and cortical shell thickness were measured using images from DTS and microcomputed tomography (μCT). For endplate thickness measurements, significant correlations between DTS and μCT were found for all variables when comparing thicknesses measured in both the overall endplate volume (R2 = 0.25-0.54) and when measurements were limited to a central range of coronal or sagittal slices (R2 = 0.24-0.62). When compared to reference values from the overall shell volume, DTS thickness measurements were generally nonsignificant. However, when measurement of cortical shell thickness was limited to a range of central slices, DTS outcomes were significantly correlated with reference values for both sagittal and coronal central regions (R2 = 0.21-0.49). DTS may therefore offer a means for measurement of endplate thickness and, within a limited sagittal or coronal measurement volume, for measurement of cortical shell thickness.


Hunting the mechanisms of self-renewal of immortal cell populations by means of real-time imaging of living cells.
The causes of the indefinite propagation of immortalized cell populations remain insufficiently understood, that hinders the research of such fundamental processes as ageing and cancer. In this study the interrelations between clonal proliferation and abnormalities of mitotic divisions in the immortalized cell line established from the mouse embryo were investigated with the aid of computerized microscopy of living cells. 3 mitoses with three daughter cells and 7 asymmetric mitoses which generated two daughter cells of conspicuously different sizes were registered among 71 mitotic divisions in the individual cell genealogy. Abnormal mitotic divisions either did not slow the proliferation in cell clones compared with progenies of cells that divided by means of normal mitoses or were followed by the acceleration of divisions in consecutive cell generations. These data suggest that abnormal mitotic divisions may contribute to the maintenance of the immortalized state of cell populations by means of generating chromosomal instability.


[A case of unilateral and synchronous occurrence of oncocytoma and renal cell carcinoma].
A 45-year-old female, who had undergone an operation for rectal cancer 4 years previously was admitted to our hospital because of a left renal mass found by follow-up ultrasonography. Ultrasonography revealed two high echoic tumors. Enhanced computerized tomography (CT) showed relatively low density tumors measuring 3.8 x 3.8 cm and 0.8 x 0.8 cm in the upper and lower pole, respectively. Renal angiography demonstrated a spoke-wheel appearance in the upper pole. Left radical nephrectomy was performed. Histopathological diagnosis of the tumor in the upper pole was oncocytoma and that in the lower pole was renal cell carcinoma.


Ages at peak velocity and peak velocities for seven body dimensions in Japanese children.
Seven body dimensions of 37 Japanese children, 16 boys and 21 girls, were measured longitudinally at 6-monthly intervals from 9 through 15 years of age. Spline curves were fitted to the longitudinal data of each dimension to obtain age at peak velocity and magnitude of peak velocity for each child. Ages at peak velocity for each dimension occurred, on average, later in boys than in girls. Mean peak velocities were also larger in boys except for chest circumference. Ages at peak velocity occurred, on average, earlier in Japanese than in European and North American children.


Photoluminescent layered Y(III) and Tb(III) silicates doped with Ce(III).
The synthesis and structural characterization of new layered rare-earth silicates K(3)[M(1-a)Ce(a)Si(3)O(8)(OH)(2)], M = Y(3+), Tb(3+), a << 1 (AV-22 materials), have been reported. These materials combine the properties of layered silicates, such as intercalation chemistry, and photoluminescence and may find applications in new types of sensor devices. For mixed Tb/Ce-AV-22, evidence has been found for the energy transfer from the large Ce(3+) 4f( 1) --> 5d(1) broad band to the sharp Tb(3+) 4f (8) lines. This energy transfer allows the fine-tuning of the color emission in the blue-green region of the chromaticity diagram. Upon Ce(3+) excitation (342 nm), the radiance of Tb/Ce-AV-22 is approximately 2 times higher than that measured under direct Tb(3+) excitation, which reinforces the existence of effective room-temperature Ce(3+)-to-Tb(3+) energy transfer.


Predictor of Liver Biochemistry Improvement in Patients with Cytomegalovirus Cholestasis after Ganciclovir Treatment.
Cholestasis resulting from cytomegalovirus (CMV)-induced hepatitis manifests in 40% of patients with a CMV infection. Ganciclovir treatment in children with CMV infections has proven to be highly effective. Until now, there are very few studies have identified predictive factors for liver biochemistry improvement after ganciclovir therapy. This study aimed to identify the predictors of liver biochemistry improvement in patients with CMV cholestasis after ganciclovir treatment. A retrospective cohort study was conducted using medical records from Dr. Sardjito General Hospital Yogyakarta, Indonesia from 2013 to 2018. CMV cholestasis was confirmed based on serum CMV IgG and IgM positivity and/or blood and urine CMV antigenemia positivity. Incomplete medical records and other etiologies for cholestasis, such as biliary atresia, choledochal cyst, metabolic diseases, and Alagille syndrome, were excluded. Patient age at cholestasis diagnosis and ganciclovir treatment, duration of CMV cholestasis, history of prematurity, central nervous system involvement, and nutritional status were analyzed and presented as an odds ratio (OR) with a 95% confidence interval (95% CI). CMV cholestasis with ganciclovir therapy was found in 41 of 54 patients. Multivariate analysis showed that a shorter duration of CMV cholestasis (OR: 4.6, 95% CI: 1.00-21.07, p=0.04) was statistically significant for liver biochemistry improvement after 1 month of ganciclovir treatment. The remaining factors that were analyzed were not significant predictors of liver biochemistry improvement in patients with CMV cholestasis after ganciclovir treatment. A shorter duration of CMV cholestasis is the predictor of liver biochemistry improvement after 1 month gancyclovir treatment.


Which prescription for the illegible and unreadable DTC (direct-to-consumer) brief summary--major surgery or euthanasia?
Healthcare costs are rising, mostly because of increased prescription drug use, chiefly as the result of direct-to-consumer drug ads on television, newspapers, and magazines. However, the FDA's requirement for a brief summary in direct-to-consumer drug ads has produced summaries that are ineffective because they are illegible and unreadable, create information overload, and require literacy skills not possessed by most consumers. If the FDA wants brief summaries to be in a patient-friendly format, it should provide document design templates and plain language examples. Unless brief summaries are written so that they can be understood by the average patient, they should be overhauled or done away with.


A rare bacterial RNA motif is implicated in the regulation of the purF gene whose encoded enzyme synthesizes phosphoribosylamine.
The Fibro-purF motif is a putative structured noncoding RNA domain that was discovered previously in species of Fibrobacter by using comparative sequence analysis methods. An updated bioinformatics search yielded a total of only 30 unique-sequence representatives, exclusively found upstream of the purF gene that codes for the enzyme amidophosphoribosyltransferase. This enzyme synthesizes the compound 5-phospho-D-ribosylamine (PRA), which is the first committed step in purine biosynthesis. The consensus model for Fibro-purF motif RNAs includes a predicted three-stem junction that carries numerous conserved nucleotide positions within the regions joining the stems. This architecture appears to be of sufficient size and complexity for the formation of the ligand-binding aptamer portion of a riboswitch. In this study, we conducted biochemical analyses of a representative Fibro-purF motif RNA to confirm that the RNA generally folds according to the predicted consensus model. However, due to the instability of PRA, binding of this ligand candidate by the RNA could not be directly assessed. Genetic analyses were used to demonstrate that Fibro-purF motif RNAs regulate gene expression in accordance with predicted PRA concentrations. These findings indicate that Fibro-purF motif RNAs are genetic regulation elements that likely suppress PRA biosynthesis when sufficient levels of this purine precursor are present.


[Serotypes and genotypes of dengue virus circulating in Venezuela, 1990-1997].
Due to the increasing severity of hemorrhagic dengue epidemics during the last years in Venezuela, a retrospective analysis was conducted to identify the behaviour of the dengue virus serotypes circulating in the country and the molecular evolution of dengue virus serotype 2. The data presented here indicates that dengue virus serotypes 1, 2 and 4 are endemic in Venezuela, they circulate simultaneously around the year in the biggest urban cities, however, one particular serotype is predominant during an epidemic period and replaces the virus serotype dominant during the previous epidemic period. The increased severity of dengue fever since 1989 in Venezuela might be associated to the introduction of the Asiatic genotype of virus which replaced the autochthonous Caribbean genotype. The Asiatic genotype is recognised as a more virulent virus.


A probabilistic model for co-occurrence analysis in bibliometrics.
The co-occurrence analysis of Medical Subject Heading (MeSH) terms extracted from the PubMed database is popularly used in bibliometrics. Practically for making the result interpretable, it is necessary to apply a certain filter procedure of co-occurrence matrix for removing the low-frequency items due to their low representativeness. Unfortunately, there is rare research referring to determine a critical threshold to remove the noise of co-occurrence matrix. Here, we proposed a probabilistic model for co-occurrence analysis that can provide statistical inferences about whether the paired items co-occur randomly. With help of this model, the dimensionality of co-occurrence matrix could be reduced according to the selected threshold. The conceptual model framework, simulation and practical applications are illustrated in the manuscript. Further details (including all reproducible codes) can be downloaded from the project website: https://github.com/xizhou/co-occurrence-analysis.git.


Inhibition of apoptotic signalling in spermine-treated vascular smooth muscle cells by a novel glutathione precursor.
CKD (chronic kidney disease) is a public health problem, mediated by haemodynamic and non-haemodynamic events including oxidative stress. We investigated the effect of two GSH (glutathione) precursors, NAC (N-acetylcysteine) and cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1) in preventing spermine (uraemic toxin)-induced apoptosis in cultured human aortic VSMC (vascular smooth muscle cells). VSMCs exposed to spermine (15 microM) with or without antioxidants (doses 50, 100, 200 and 500 microg/ml) were assessed for apoptosis, JNK (c-Jun-NH2-terminal kinase) activation and iNOS (inducible nitric oxide synthase) induction and activation of intrinsic pathway signalling. Spermine exposure resulted in activation of JNK and iNOS induction and apoptosis. NAC and F1 (dose range 50-500 microg/ml) attenuated spermine-induced acceleration of VSMC apoptosis but only F1 (at 200 and 500 microg/ml) maintained spermine-induced apoptosis at control levels. Spermine-induced JNK activation was prevented by 200 microg/ml of both NAC and F1, while iNOS induction was blocked only by F1. Notably, the adverse effects of spermine on BAX/BCL-2 ratio, cytochrome c release and caspase activation was fully attenuated by F1. In conclusion, F1 was more effective than NAC in preventing spermine-induced apoptosis and downstream changes in related signal transduction pathways in VSMCs. Further studies are needed to examine the effect of these compounds in preventing CKD-associated vascular disease.