Latisemenia longshania, gen. et sp. nov., a new Late Devonian seed plant from China.
The earliest known ovules in the Late Devonian (Famennian) are borne terminally on fertile branches and are typically enclosed in a cupule. Among these ovules are some that have terete integumentary lobes with little or no fusion. Here, we report a new taxon, Latisemenia longshania, from the Famennian of South China, which bears cupulate ovules that are terminal as well as opposite on the fertile axis. Each ovule has four broad integumentary lobes, which are extensively fused to each other and also to the nucellus. The cupule is uniovulate, and the five flattened cupule segments of each terminal ovule are elongate cuneate and shorter than the ovule. Associated but not attached pinnules are laminate and Sphenopteris-like, with an entire or lobate margin. Latisemenia is the earliest known plant with ovules borne on the side of the fertile axis and may foreshadow the diverse ovule arrangements found among younger seed plant lineages that emerge in the Carboniferous. Following the telome theory, Latisemenia demonstrates derived features in both ovules and cupules, and the shape and fusion of integumentary lobes suggest effective pollination and protection to the nucellus. Along with other recent discoveries from China, Latisemenia extends the palaeogeographic range of the earliest seed plants.


Helicobacter pylori Outer Membrane Protein-Related Pathogenesis.
Helicobacter pylori colonizes the human stomach and induces inflammation, and in some cases persistent infection can result in gastric cancer. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and outer membrane proteins (OMPs) play a pivotal role in binding to human cells. Some OMP interaction molecules are known in H. pylori, and their associated host cell responses have been gradually clarified. Many studies have demonstrated that OMPs are essential to CagA translocation into gastric cells via the Type IV secretion system of H. pylori. This review summarizes the mechanisms through which H. pylori utilizes OMPs to colonize the human stomach and how OMPs cooperate with the Type IV secretion system.


Multiplex and simultaneous measurement of displacement and temperature using tapered fiber and fiber Bragg grating.
A simple method to work out the multiplexing of tapered fiber based sensors is proposed and demonstrated. By cascading a tapered fiber with a fiber Bragg grating (FBG), the sensor head is provided with a wavelength identification, different FBGs provide the sensor heads with different reflective peaks and they can be distinguished in optical spectrum. By compositing several such sensor heads with a multi-channel beam splitter, a star-style topological structure sensor for multipoint sensing is achieved. At the same time, the output intensity at the peak wavelength is sensitive to one external physical parameter applied on the related FBG-cascaded tapered fiber and the central wavelength of the peak is only sensitive to temperature, so that that parameter and temperature can be measured simultaneously. A sensor for dual-point measurement of the displacement and temperature simultaneously is experimentally demonstrated by using a 2 × 2 coupler in this paper. Experiment results show that the sensor works well and the largest sensitivities reach to 0.11 dB/μm for displacement in the range of 0-400 μm, and ∼0.0097 nm/°C for temperature between 20 °C and 70 °C.


[Psychopathology in parents of children with school phobia].
In children, what is referred to as school phobia is usually avoidant behavior secondary to separation anxiety. The purpose of this study was to examine the psychopathology in parents of children with school phobia. The study compared 2 groups of parents: 1) parents of children with school phobia (n = 50); 2) parents of children free of any psychiatric diagnosis (n = 50). Parents were assessed with the Structured Clinical Interview for DSM-IV (SCID-I) to determine rates of overall psychopathology by a second clinician blind to the diagnostic status of their children, and they were also administered the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and Liebowitz Social Anxiety Scale (LSAS) to determine the presence of anxiety and mood disorders. Children with school phobia (n = 25), aged 6-12 years, and an age-and gender-matched control group (n= 25) were assessed based on the criteria of the DSM-IV. Parents completed the Child Behavior Checklist (CBCL) 4-18. All of the children with school phobia met the criteria for an anxiety disorder. Parental psychopathology was higher in parents of children with school phobia than in parents of normal children. BDI, BAI, and fear and anxiety subscale scores of the LSAS were significantly higher in the parents of school phobic children than in the control group parents. The high rates of psychopathology in parents of children with school phobia suggested that treatment of children diagnosed as anxiety disorder should include the treatment of parents as well.


[An experiment on the pathogenesis of early biotrauma in ventilator-induced lung injury].
To investigate the pathogenesis of early biotrauma in ventilator-induced lung injury (VILI). Twenty-four 8-week-old male specific-pathogen-free Sprague-Dawley (SD) rats weighing 250-300 g were randomly divided into sham group (S group), conventional mechanical ventilation group (L group) and high tidal volume (VT) mechanical ventilation group (H group) with 8 rats in each group. All rats received tracheostomy after anesthesia. Rats in S group received no mechanical ventilation but breathe room air spontaneously. All other parameters of the ventilator were the same in both mechanical ventilation groups, and the fraction of oxygen was set to 0.21, the rats in L group received 7 mL/kg VT, and those in H group received 28 mL/kg VT. Four hours after ventilation all rats were sacrificed and the lung tissues were harvested for wet/dry (W/D) ratio. Pathological injury score was evaluated by hematoxylin and eosin (HE) staining. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling stain (TUNEL) was performed to count the apoptosis cell in lung epithelial. Western Blot was performed to evaluate hemi-channel protein Pannexin-1 expression in lung homogenate. Bronchoalveolar lavage fluid (BALF) was collected, and the concentration of lactate dehydrogenase (LDH), isoprostane, adenosine triphosphate (ATP) and white cell count in BALF were measured. Yo-pro-1/propidium iodide (PI) double stain was performed to evaluate early apoptosis cell in BALF. There was no significant difference in lung injury between S group and L group. Compared with S group and L group, rats in H group showed significant lung injury, represented as alveolar rupture, inflammatory cell infiltration, interstitial edema and airway epithelial exfoliation, and the lung W/D ratio was increased significantly (5.1±0.2 vs. 4.4±0.2, 4.3±0.4, both P < 0.01), pathological score was significantly increased [4.00 (4.00, 8.00) vs. 1.00 (0, 4.00), 2.00 (0, 4.75), both P < 0.01], the white cell in BALF was significantly increased (×106/L: 2.97±0.46 vs. 1.03±0.26, 0.79±0.19, both P < 0.01), the level of LDH was significantly increased (U/L: 148.6±38.2 vs. 34.4±13.5, 78.6±13.9, both P < 0.01), and the expression of Pannexin-1 in lung homogenate was significantly increased (Pannexin-1/GAPDH: 0.89±0.21 vs. 0.48±0.25, 0.61±0.17, both P < 0.01), the ATP concentration in BALF was also significantly increased (nmol/L: 456.84±148.72 vs. 19.23±13.34, 113.26±57.90, both P < 0.01). There was no significant difference in the apoptosis cell in lung tissue or the apoptosis cell rate, isoprostane level in BALF among the three groups [apoptosis cell in lung (cells/HP): 4.00 (3.00, 5.00) vs. 5.00 (4.00, 6.00), 4.00 (3.25, 6.00); apoptosis cell rate in BALF: (0.57±0.20)% vs. (0.42±0.16)%, (0.58±0.19)%; isoprostane in BALF (μg/L): 3.85±0.46 vs. 3.83±0.60, 3.59±0.69, all P > 0.05]. The early pathogenesis of biotrauma in VILI is related to the release of inflammation mediator via membrane channel after activating by pressure stress, but not apoptosis and lipid peroxidation.


Metagenomics approaches in systems microbiology.
The world of microorganisms comprises a vast diversity of live organisms, each with its individual set of genes, cellular components and metabolic reactions that interact within the cell and communicate with the environment in many different ways. There is a strong imperative to gain a broader view of the wired and interconnected cellular and environmental processes as a whole via the systems microbiology approach in order to understand and predict ecosystem functioning. On the other hand, currently we experience a rise of metagenomics as an emerging tool to study communities of uncultured microorganisms. In this review, we conducted a survey of important methodologies in metagenomics and describe systems microbiology-like approaches for gaining a mechanistic understanding of complex microbial systems to interrogate compositional, evolutionary and metabolic properties. The review also discusses how metagenomics can be used as a holistic indicator for ecosystem response in terms of matter, nutrient and energy sources and functional networking.


Induction and rejoining of gamma-ray-induced DNA single- and double-strand breaks in Chinese hamster AA8 cells and in two radiosensitive clones.
The induction and rejoining of gamma-ray-induced DNA strand breaks were measured in a Chinese hamster ovary cell line, AA8, and in two radiosensitive clones (EM9 and NM2) derived from it. The kinetics of recovery from sublethal damage (SLD) and potentially lethal damage (PLD) has previously been characterized in each of these lines [vanAnkeren et al., Radiat. Res., 115, 223-237 (1988)]. No significant differences were observed among the cell lines in the yields of either DNA single-strand breaks (SSBs) or double-strand breaks (DSBs) as assayed by filter elution. Data for SSB rejoining in AA8 and NM2 cells irradiated with 7.5 Gy were fit by a biexponential process (t1/2 values of approximately 4 and 80 min). In comparison, SSB rejoining in EM9 cells was initially slower (t1/2 = 10 min) and a higher level of SSBs was unrejoined 6 h after irradiation. DSB rejoining in AA8 cells assayed at pH 9.6 was also biphasic (t1/2 values of 15 and 93 min), although when assayed at pH 7.0, most (approximately 80%) of the damage was rejoined at a constant rate (t1/2 = 45 min) during the first 2 h. EM9 cells exhibited a slower initial rate of DSB rejoining when assayed at pH 9.6 but showed no difference compared with AA8 cells in DSB rejoining when assayed at pH 7.0. These results indicate that radiosensitive EM9 cells, whose kinetics of recovery from SLD and PLD was the same as that of AA8 cells, have a defect in the fast phase of SSB rejoining but no measurable defect in DSB rejoining. Conversely, NM2 cells, which displayed a reduced shoulder width on their survival curve and decreased recovery from SLD, had no demonstrable defects in the rate or extent of rejoining of DSBs or SSBs. When compared with the SLD and PLD data reported previously, these results suggest that there is no direct correlation between either of these recovery processes and the rejoining of SSBs or DSBs as assayed here.


Localization of cloned invertase in Saccharomyces cerevisiae directed by the SUC2 and MFalpha1 signal sequences.
Protein localization in Saccharomyces cerevisiae was studied with two plasmid systems used as a model: one containing the SUC2 structural gene fused with the MFalpha1 (alpha-factor) promoter and signal-sequence, the other containing the entire SUC2 gene. Special emphasis was placed on the effect of promoter/signal-sequence (SUC2 vs. MFalpha1) on the efficiency of invertase transport. The MFalpha 1 and SUC2 signal sequences were capable of transporting, respectively, 83% and 77% of cloned invertase out of the cytoplasm. However, the SUC2 promoter was easier to control since a six-fold enhancement of the transported invertase activity associated with derepression was achieved in response to a glucose concentration change from 10 to 2 g/L Cloning on a multicopy plasmid resulted in a four-fold increase in total specific invertase activity over the wild type yeast strain (which harbors a single copy of the SUC2 gene on the chromosome), whereas the chromosomal site was more efficient for invertase localization yielding over 90% of the invertase transported out of the cytoplasm. Transient experiments done with the SUC2 signal-sequence-containing plasmid showed that the specific invertase activity in the periplasmic space reached a maximum three hours after derepression, then decreased very slowly with an accompanying gradual increase in invertase activity in the growth medium.


Imaging aspects of the diagnosis of sarcoidosis.
Sarcoidosis is a systemic granulomatous disorder of unknown aetiology with a wide spectrum of radiological appearances and almost invariably pulmonary involvement. Lung involvement accounts for most of the morbidity and much of the mortality associated with sarcoidosis. Imaging contributes significantly to the diagnosis and management of patients with sarcoidosis. In typical cases, chest radiography may be sufficient to establish the diagnosis with little margin of error and CT is not necessary. However, CT can play a critical role in several clinical settings: atypical clinical and/or radiographic findings; normal or near-normal chest radiograph but clinical suspicion of sarcoidosis; and detection of complications. Moreover, in many patients, CT findings are atypical and unfamiliar to most radiologists (e.g. sarcoidosis mimicking other lung diseases and vice versa), and in these cases histological confirmation of the diagnosis is recommended. CT is also useful in assessing disease extent and may help to discriminate between reversible and irreversible lung disease, thus providing critical prognostic information. This review concentrates on the more difficult imaging aspects of sarcoidosis, in particular differential diagnosis and disease complications. •Sarcoidosis is characterized by a wide spectrum of radiological appearances. •In typical cases, imaging substantially contributes to the diagnosis of sarcoidosis. •CT plays a critical role in atypical and complicated cases. •CT may discriminate between reversible and irreversible lung disease.


Failure to correlate ampicillin and amoxicillin resistance by standard disk susceptibility tests and minimal inhibitory concentration in Haemophilus species.
22 Haemophilus strains, isolated from lower respiratory tract infections, were tested for their susceptibility to ampicillin and amoxicillin using both MIC and Kirby Bauer methods. Ampicillin and amoxicillin resistance tested with MIC method was not exactly correlated with Kirby Bauer standard (10 mcg ampicillin and 25 mcg amoxicillin disks) inhibition zones method (error rate: 52.6%). Yet using a 2 mcg ampicillin and 5 mcg amoxicillin handmade disk, error range decreased to 14.8%. Beta-lactamase production on whole cells were for 6 strains of the 22 tested. After breaking the cell wall, 19 on the 22 strains were beta-lactamase producers, confirming the results obtained with the MIC method.


Barriers and Facilitators to the Implementation of the Pathways to Comorbidity Care (PCC) Training Package for the Management of Comorbid Mental Disorders in Drug and Alcohol Settings.
Background: We have previously reported that the Pathways to Comorbidity Care (PCC) training program for alcohol and other drug (AOD) clinicians improved identification of comorbidity, self-efficacy, and attitudes toward screening and monitoring of comorbidity. We aimed to identify barriers and facilitators of implementation of the PCC training program in drug and alcohol settings. Methods: The PCC training program was implemented across 6 matched sites in Australia as per (1), and 20 clinicians received training. PCC training included seminar presentations, workshops conducted by local "clinical champions," individual clinical supervision, and access to an online information portal. We examined barriers and facilitators of implementation according to the Consolidated Framework for Implementation Research. Results: Barriers included inner setting (e.g., allocated time for learning) and characteristics of individuals (e.g., resistance). Facilitators included intervention characteristics (e.g., credible sources), inner setting (e.g., leadership), and outer setting domains (e.g., patient needs). Clinical champions were identified as an important component of the implementation process. Conclusions: Barriers included limited specific allocated time for learning. A credible clinical supervisor, strong leadership engagement and an active clinical champion were found to be facilitators of the PCC training program.


Utility of biphasic calcium phosphate cement as a seal for root-end filling.
The recently developed biphasic calcium phosphate cement (BCPC) consists of α-tricalcium phosphate-tetracalcium phosphate as the solid phase and calcium phosphate solution as the liquid phase. BCPC powder is composed of a single solid solution with a monomodal size distribution. Here, we used a bacterial leakage model to examine the utility of BCPC as a seal for root-end filling. We prepared large (median particle size=9.96 µm; BCPC-L) and small (median particle size=4.84 µm; BCPC-S) BCPC powders. In total, 45 single-rooted teeth were instrumented, resected at the root-end, and retrofilled with experimental materials. Mineral trioxide aggregate (MTA) was used as the control. After visual confirmation of BCPC powder size and retrofilling quality by microscopy, bacterial leakage tests were conducted using Enterococcus faecalis. The bacterial leakage tests did not reveal any significant differences between BCPC-S and MTA. Our findings suggest that BCPC-S is useful for root-end filling.


A Painless Bump: A Case Report of Cemento-Ossifying Fibroma of the Anterior Maxilla.
Cemento-ossifying fibroma (COF) is a benign odontogenic neoplasm. It is considered an ossifying fibroma with traces of interspersed cementum fragments. Here we present a case report of the occurrence of COF in the maxillary anterior region of an elderly woman. A 61-year-old female reported with a painless, progressive, slow-growing swelling on the upper front jaw region for the past five years. A single, localized, swelling on the anterior region of the maxilla which was non-tender and bony hard in consistency. Radiological examination consisting of orthopantomagram (OPG) and cone-beam computed tomography (CBCT) revealed increased thickness of bone over frontal, parietal and maxilla with alteration of trabecular pattern - cotton wool/ground glass. Serum alkaline phosphatase level was found to be 865 U/l, however, serum calcium level and other routine blood investigations (hemogram) were within normal limits. The above radiological and laboratory findings are more in favour of primary bone pathology and with a biopsy later correlating with histopathological findings; it was diagnosed as COF. Under conscious sedation, surgical excision of the bony mass was done along with extraction of associated teeth. The patient is currently on regular follow-up and planning for a dental prosthesis is in progress.


Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14.
The ubiquitin-specific processing protease (UBP) family of deubiquitinating enzymes plays an essential role in numerous cellular processes. Mammalian USP14 (Ubp6 in yeast) is unique among known UBP enzymes in that it is activated catalytically upon specific association with the 26S proteasome. Here, we report the crystal structures of the 45-kDa catalytic domain of USP14 in isolation and in a complex with ubiquitin aldehyde, which reveal distinct structural features. In the absence of ubiquitin binding, the catalytic cleft leading to the active site of USP14 is blocked by two surface loops. Binding by ubiquitin induces a significant conformational change that translocates the two surface loops thereby allowing access of the ubiquitin C-terminus to the active site. These structural observations, in conjunction with biochemical characterization, identify important regulatory mechanisms for USP14.


Uniformly-aligned gelatin/polycaprolactone fibers promote proliferation in adipose-derived stem cells and have distinct effects on cardiac cell differentiation.
Cardiac tissue engineering is a promising technique to regenerate cardiac tissue and treat cardiovascular disease. Here we applied a modified method to generate ultrafine uniformly-aligned composite gelatin/polycaprolactone fibers that mimic functional heart tissue. We tested the physical properties of these fibers and analyzed how these composite fibrous scaffolds affected growth and cardiac lineage differentiation in rat adipose-derived stem cells (rADSCs). We found that uniformly aligned composite fiber scaffolds had an anisotropic arrangement, functional mechanical properties, and strong hydrophilicity. The anisotropic scaffolds improved cell attachment, viability, and proliferative capacity of ADSCs over randomly-aligned scaffolds. Furthermore, uniformly aligned composite fiber scaffolds increased the efficiency of cardiomyogenic differentiation, but might reduce the efficiency of cardiac conduction system cell differentiation in ADSCs compared to randomly-oriented scaffolds and tissue culture polystyrene. However, the randomly-oriented composite scaffolds showed no obviously facilitated effects over tissue culture polystyrene on the two cells' differentiation process. The above results indicate that the scaffold fiber alignment has a greater effect on cell differentiation than the composition of the scaffold. Together, the uniformly-aligned composite fibers displayed excellent physical and biocompatible properties, promoted ADSC proliferation, and played distinct roles in the differentiation of cardiomyogenic cells and cardiac conduction system cells from ADSCs. These results provide new insight for the application of anisotropic fibrous scaffolds in cardiac tissue engineering for both in vitro and in vivo research.


Association between aluminum in drinking water and incident Alzheimer's disease in the Canadian Study of Health and Aging cohort.
Epidemiological evidence linking aluminum in drinking water and Alzheimer's disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants' residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 μg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p = 0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.


Pain sensitivity in posttraumatic stress disorder and other anxiety disorders: a preliminary case control study.
Despite substantial research on the comorbidity of anxiety disorders including posttraumatic stress disorder (PTSD) and chronic pain, little is known about the mechanisms underlying these conditions that might be potentially similar. Evoked pain sensitivity is one factor that has been associated with several pain conditions which might also have relevance to anxiety disorders and PTSD. The aim of this preliminary study was to examine evoked pain sensitivity in PTSD compared to other anxiety disorders and in control participants. The study used a cross-sectional case-control design in which participants completed a battery of questionnaires and structured interview and underwent cold pressor testing. Of 61 total participants, those in the PTSD (n =16) and other anxiety groups (n =12) endorsed significantly higher levels of psychological symptoms and poorer health functioning than control participants (n =33). The linear trend across baseline, threshold, and tolerance pain ratings from the cold pressor task significantly differed between participants with PTSD and the other anxiety and control groups suggesting lower pain sensitivity to a standardized stimulus of pain in individuals with PTSD. These findings are similar to some of the prior research and suggest that individuals with PTSD may exhibit lower cold pain sensitivity compared to those with other anxiety disorders. There is a need for future research to determine explanatory mechanisms.


Population coding of figure and ground in natural image patches by V4 neurons.
Segmentation of a natural scene into objects and background is a fundamental but challenging task for recognizing objects. Investigating intermediate-level visual cortical areas with a focus on local information is a crucial step towards understanding the formation of the cortical representations of figure and ground. We examined the activity of a population of macaque V4 neurons during the presentation of natural image patches and their respective variations. The natural image patches were optimized to exclude the influence of global context but included various characteristics of local stimulus. Around one fourth of the patch-responsive V4 neurons exhibited significant modulation of firing activity that was dependent on the positional relation between the figural region of the stimulus and the classical receptive field of the neuron. However, the individual neurons showed low consistency in figure-ground modulation across a variety of image patches (55-62%), indicating that individual neurons were capable of correctly signaling figure and ground only for a limited number of stimuli. We examined whether integration of the activity of multiple neurons enabled higher consistency across a variety of natural patches by training a support vector machine to classify figure and ground of the stimuli from the population firing activity. The integration of the activity of a few tens of neurons yielded discrimination accuracy much greater than that of single neurons (up to 85%), suggesting a crucial role of population coding for figure-ground discrimination in natural images.


Efficacy of combined liver-lung scintillation imaging.
Of 116 patients who had undergone combined liver-lung scintillation imaging, 23 with negative studies had abnormal subphrenic spaces at operation, and 5 with positive studies had abnormal subphrenic spaces at laparotomy (hematomas, bile spillage, serous fluid or abscess); 4 of 6 nonexplored positive studdies showed resolution of defects on serial imaging. Other information obtained included abnormalities intrinsic to liver, lungs or spleen; evidence suggestive of left subphrenic pathology; and reliable information about the right subphrenic space even in the presence of intrathoracic pathology, including effusions.


Feshbach Resonances in p-Wave Three-Body Recombination within Fermi-Fermi Mixtures of Open-Shell 6Li and Closed-Shell 173Yb Atoms.
We report on the observation of magnetic Feshbach resonances in a Fermi-Fermi mixture of ultracold atoms with extreme mass imbalance and on their unique p-wave dominated three-body recombination processes. Our system consists of open-shell alkali-metal 6Li and closed-shell 173Yb atoms, both spin polarized and held at various temperatures between 1 and 20 μK. We confirm that Feshbach resonances in this system are solely the result of a weak separation-dependent hyperfine coupling between the electronic spin of 6Li and the nuclear spin of 173Yb. Our analysis also shows that three-body recombination rates are controlled by the identical fermion nature of the mixture, even in the presence of s-wave collisions between the two species and with recombination rate coefficients outside the Wigner threshold regime at our lowest temperature. Specifically, a comparison of experimental and theoretical line shapes of the recombination process indicates that the characteristic asymmetric line shape as a function of applied magnetic field and a maximum recombination rate coefficient that is independent of temperature can only be explained by triatomic collisions with nonzero, p-wave total orbital angular momentum. The resonances can be used to form ultracold doublet ground-state molecules and to simulate quantum superfluidity in mass-imbalanced mixtures.


Phytochemical analysis and antioxidant activity of the seed of Telfairia occidentalis Hook (Cucurbitaceae).
The 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical, nitric oxide, reducing power, hydrogen peroxide scavenging, and total antioxidant activities of the methanol extract, n-hexane, dichloromethane, ethyl acetate, butanol and aqueous fractions of the seed of Telfairia occidentalis were evaluated. Total phenolic content was determined using the Folin-Ciocalteu method. The dichloromethane fraction exhibited the highest DPPH radical scavenging, reducing power and total antioxidant activities. Two pure compounds which were identified by FTIR, H-and 2D NMR and Mass spectroscopy as 9-octadecenoic acid (TOS B) and 10-hydroxyoctadecanoic acid (TOS C) and four oily isolates, TOS A, TOS D, TOS E and TOS F were obtained from the dichloromethane fraction. TOS E had the highest DPPH radical scavening activity comparable to that of ascorbic acid. GC-MS analysis revealed the major compounds in TOS E as 4-(2,2-Dimethyl-6-methylene cyclohexylidene)-2-butanol; 3-(3-hydroxybutyl)-2,4,4-trimethyl-2-cyclohexene-1-one and 1,2-Benzenedicarboxylic acid disooctyl ester. Thus, the seed of T. occidentalis can be consumed for its antioxidant property.


Comparative effects of meals high in protein, sucrose, or starch on human mineral metabolism and insulin secretion.
Protein, carbohydrates, and amino acids produce calciuria by decreasing renal calcium reabsorption. This study compared the postprandial calciuretic and serum insulin responses of 12 adults to isocaloric meals: Control, High Protein, High Sucrose, and High Starch. In 3 h 60% more Ca was excreted after High Protein than after other meals; renal Ca reabsorption was lower after High Protein than after High Sucrose at 2.5 h and after High Starch and High Sucrose at 3 h (p less than 0.01). Insulin was higher after High Starch and High Sucrose than after High Protein. Urinary phosphorus excretion was lower 1-3 h after High Protein than after other meals (p less than 0.01). High Protein increased urinary potassium and zinc. Urinary Ca correlated significantly with urinary Zn (r = 0.64) and sodium (r = 0.62), peak serum P (r = -0.29), and serum insulin increase for Control (r = 0.70) and High Protein (r = 0.68) only. Insulin inhibition of Ca reabsorption is not the sole explanation of macronutrient-induced calciuria.


Contiguous multiple π-coordination of π-conjugated polyenes: bonding nature and charge delocalization behaviour of polyene-(palladium chain) sandwich clusters.
The contiguous multiple π-coordination (CMπC) bonds are formed at the molecular interface between the extended π-conjugated sp2-carbon framework and metal-metal moieties. However, the static properties including the bonding nature of the CMπC bonds have not been well-understood. Here we report the charge delocalization behavior and bonding nature of the polyene-(palladium chain) sandwich clusters. We observed the chain-length dependent 13C NMR chemical shifts of the terminal phenyl groups in [Pdm{Ph(CH[double bond, length as m-dash]CH)m+1Ph}2][B(ArF)4]2 (m = 3, 4, 5, 6), showing the efficient delocalization of positive charge over the polyene ligands. Furthermore, the detailed molecular orbital analysis of several model clusters provides insights into the bonding nature of the μ-η2:(η2:)nη2- and μ-η3:(η2:)nη3-poylene palladium chain sandwich clusters, where the former type is attributed to the corner-sharing Pd array and the latter to the edge-sharing/corner-sharing hybrid Pd array. The analogy of the μ-η3:(η2:)nη3-type with the carbonyl-bridge coordination is discussed. The Pd string in each mode of sandwich chain clusters has a weak M-M bonding interaction.


A re-analysis of the long-term effects on life expectancy of the Great Finnish Famine of 1866-68.
The results of studies exploring the long-term consequences of famine during foetal or infant development are inconsistent. We tested the hypothesis that selection forces occurring during a famine change the distribution of frailty in the affected cohorts, possibly hiding negative long-term effects. Using mortality data for Finland, gathered from the Human Mortality Database, we explored the effect of being born during the Great Finnish Famine of 1866-68 by comparing mortality at age 60 and over for the 1850-89 births, taking into account unobserved cohort heterogeneity. Contemporaneous Swedish cohorts, unexposed to the famine, were used as an additional control group. When cohort heterogeneity is accounted for, a lower life expectancy at age 60 for male cohorts in Finland born during the famine is observed. The results for females are less conclusive. No substantial changes are seen in the Swedish cohorts. In order to provide consistent estimates of the long-run effects of famines, selection forces need to be considered.


Improving Patient's Primary Medication Adherence: The Value of Pharmaceutical Counseling.
Quality of transitions of care is one of the first concerns in patient safety. Redesigning the discharge process to incorporate clinical pharmacy activities could reduce the incidence of postdischarge adverse events by improving medication adherence. The present study investigated the value of pharmacist counseling sessions on primary medication adherence after hospital discharge.This study was conducted in a 1844-bed hospital in France. It was divided in an observational period and an interventional period of 3 months each. In both periods, ward-based clinical pharmacists performed medication reconciliation and inpatient follow-up. In interventional period, initial counseling and discharge counseling sessions were added to pharmaceutical care. The primary medication adherence was assessed by calling community pharmacists 7 days after patient discharge.We compared the measure of adherence between the patients from the observational period (n = 201) and the interventional period (n = 193). The rate of patients who were adherent increased from 51.0% to 66.7% between both periods (P < 0.01). When discharge counseling was performed (n = 78), this rate rose to 79.7% (P < 0.001). The multivariate regression performed on data from both periods showed that age of at least 78 years old, and 3 or less new medications on discharge order were predictive factors of adherence. New medications ordered at discharge represented 42.0% (n = 1018/2426) of all medications on discharge order. The rate of unfilled new medications decreased from 50.2% in the observational period to 32.5% in the interventional period (P < 10). However, patients included in the observational period were not significantly more often readmitted or visited the emergency department than the patients who experienced discharge counseling during the interventional period (45.3% vs. 46.2%; P = 0.89).This study highlights that discharge counseling sessions are essential to improve outpatients' primary medication adherence. We identified predictive factors of primary nonadherence in order to target the most eligible patients for discharge counseling sessions. Moreover, implementation of discharge counseling could be facilitated by using Health Information Technology to adapt human resources and select patients at risk of nonadherence.


On the Neotropical spider Subfamily Masteriinae (Araneae, Dipluridae).
The Neotropical species of the diplurid subfamily Masteriinae are revised and redefined. Masteriinae now comprises four genera, Masteria L. Koch, 1893, Striamea Raven, 1981, a new genus, Siremata n. gen. and Edwa Raven, 2015, a fossil genus. The type species, Masteria hirsuta L. Koch, 1893, was used as basis for comparison and the knowledge of the genus has increased. Twelve species of Masteria are redescribed and eight new species are described: M. amarumayu n. sp. and M. mutum n. sp., from Brazil; M. yacambu n. sp., from Venezuela; M. sabrinae n. sp., from Martinique; M. tayrona n. sp., from Colombia; M. aguaruna n. sp., from Peru, M. soucouyant n. sp., from Trinidad and Tobago; and M. galipote n. sp., from the Dominican Republic. Females of Masteria aimeae (Alayón, 1995) and M. golovatchi Alayón, 1995 are described for the first time. Females of M. spinosa (Petrunkevitch, 1925), M. petrunkevitchi (Chickering, 1964), M. lewisi (Chickering, 1964), M. barona (Chickering, 1966), M. downeyi (Chickering, 1966), M. simla (Chickering, 1966), M. colombiensis Raven, 1981 and M. pecki Gertsch, 1982 are illustrated for the first time and rediagnosed. Masteria tovarensis (Simon, 1889) and M. cyclops (Simon, 1889) are synonymized with M. lucifuga (Simon, 1889). Masteria modesta (Simon, 1892) is considered as species inquirendae and M. emboaba Pedroso, Baptista Bertani, 2015 is considered as incertae sedis, as the type is lost. Both species of Striamea are revised and redescribed. A new genus, Siremata n. gen., is described and includes three Amazonian species: S. valteri n. sp., S. juruti n. sp., S. lucasae n. sp. Knowledge of the distribution ranges of the Neotropical Masteriinae are increased.


Cohort study of cardiovascular risk in asymptomatic young adults: subclinical atherosclerosis and coronary calcium score.
Coronary artery calcification is an early marker of subclinical atherosclerosis, but little research has been done in asymptomatic individuals under 45 years. In this cohort study with 17 years of follow-up, 155 participants were assessed in 2016 with a coronary calcium score for the association with cardiovascular risk factors. During follow-up, there was a significant increase in anthropometric measurements, cholesterol and fractions, and diastolic pressure. Participants who gained 1 cm in waist circumference had a mean reduction of 0.36 mg/dL in HDL-cholesterol and those who gained 1 kg/m2 in body mass index had a reduction of 0.72 mg/dL in HDL-cholesterol. Married participants had a 4.78 mg/dL reduction in HDL-cholesterol levels compared to singles. There was an increase of 2.09 mg/dL in HDL-cholesterol at each higher level of self-perceived health. One single case, a 32-year-old male, smoker, sedentary individual with a family history of cardiovascular disease, presented coronary calcification (0.6%). His HDL-cholesterol was reduced by 43.4%, with levels of less than 25 mg/dL at the time of coronary calcium scoring. Our findings may prompt broader studies of populations under 35 years with HDL-C levels below 25 mg/dL and family histories of cardiovascular disease, associated with obesity, sedentary lifestyle and smoking.


Temperature stability of proteins: Analysis of irreversible denaturation using isothermal calorimetry.
The structural stability of proteins has been traditionally studied under conditions in which the folding/unfolding reaction is reversible, since thermodynamic parameters can only be determined under these conditions. Achieving reversibility conditions in temperature stability experiments has often required performing the experiments at acidic pH or other nonphysiological solvent conditions. With the rapid development of protein drugs, the fastest growing segment in the pharmaceutical industry, the need to evaluate protein stability under formulation conditions has acquired renewed urgency. Under formulation conditions and the required high protein concentration (∼100 mg/mL), protein denaturation is irreversible and frequently coupled to aggregation and precipitation. In this article, we examine the thermal denaturation of hen egg white lysozyme (HEWL) under irreversible conditions and concentrations up to 100 mg/mL using several techniques, especially isothermal calorimetry which has been used to measure the enthalpy and kinetics of the unfolding and aggregation/precipitation at 12°C below the transition temperature measured by DSC. At those temperatures the rate of irreversible protein denaturation and aggregation of HEWL is measured to be on the order of 1 day-1 . Isothermal calorimetry appears a suitable technique to identify buffer formulation conditions that maximize the long term stability of protein drugs.


Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study.
Several of the known risk factors for ovarian cancer are thought to act through their effects on ovulation and the menstrual cycle, such as parity, breastfeeding, and use of oral contraceptives. We aimed to assess the effect of these three risk factors, and of tubal ligation, on the risk of ovarian cancer in women who carry a mutation in the BRCA1 or BRCA2 genes. We did a matched case-control study in women who were found to carry a pathogenetic mutation in BRCA1 or BRCA2. Participants were derived from a population-based study of ovarian cancer in Ontario, Canada, and from an international registry of mutation carriers based in Toronto, ON, Canada. All participants completed a written questionnaire that detailed their reproductive history. Women with invasive ovarian cancer and controls were matched on year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of breast cancer. The odds ratios and 95% CI for ovarian cancer were estimated with respect to use of oral contraceptives, parity, breastfeeding, and tubal ligation. Questionnaires were completed by 799 women with a history of invasive ovarian cancer (670 with BRCA1 mutations, 128 with BRCA2 mutations, and one with a mutation in both genes), and controls were 2424 women without ovarian cancer (2043 with BRCA1 mutations, 380 with BRCA2 mutations, and one with a mutation in both genes). Use of oral contraceptives reduced the risk of ovarian cancer in carriers of BRCA1 mutations (odds ratio 0.56 [95% CI 0.45-0.71]; p<0.0001) and carriers of BRCA2 mutations (0.39 [0.23-0.66]; p=0.0004). Parity was associated with a reduced risk for carriers of BRCA1 mutations (0.67 [0.46-0.96]; p=0.03), but with an increased risk for those with BRCA2 mutations (2.74 [1.18-6.41]; p=0.02). Breastfeeding was associated with a reduced risk for carriers of BRCA1 mutations (0.74 [0.56-0.97]; p=0.03). An effect of similar magnitude was seen for carriers of BRCA2 mutations (0.72 [0.41-1.29]; p=0.27), but this was not statistically significant. The association with tubal ligation was not significant for carriers of BRCA1 mutations (0.80 [0.59-1.08]; p=0.15), or for carriers of BRCA2 mutations (0.63 [0.34-1.15]; p=0.13). Oral contraceptives could be used as a means to prevent ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The possible adverse effect of parity on ovarian-cancer risk in women with a BRCA2 mutation needs further study.


Eradication of Biofilm-Mediated Methicillin-Resistant Staphylococcus aureus Infections In Vitro: Bacteriophage-Antibiotic Combination.
Bacterial biofilms are difficult to eradicate and can complicate many infections by forming on tissues and medical devices. Phage+antibiotic combinations (PAC) may be more active on biofilms than either type of agent alone, but it is difficult to predict which PAC regimens will be reliably effective. To establish a method for screening PAC combinations against Staphylococcus aureus biofilms, we conducted biofilm time-kill analyses (TKA) using various combinations of phage Sb-1 with clinically relevant antibiotics. We determined the activity of PAC against biofilm versus planktonic bacteria and investigated the emergence of resistance during (24 h) exposure to PAC. As expected, fewer treatment regimens were effective against biofilm than planktonic bacteria. In experiments with isogenic strain pairs, we also saw less activity of PACs against DNS-VISA mutants versus their respective parentals. The most effective treatment against both biofilm and planktonic bacteria was the phage+daptomycin+ceftaroline regimen, which met our stringent definition of bactericidal activity (>3 log10 CFU/mL reduction). With the VISA-DNS strain 8015 and DNS strain 684, we detected anti-biofilm synergy between Sb-1 and DAP in the phage+daptomycin regimen (>2 log10 CFU/mL reduction versus best single agent). We did not observe any bacterial resensitization to antibiotics following treatment, but phage resistance was avoided after exposure to PAC regimens for all tested strains. The release of bacterial membrane vesicles tended to be either unaffected or reduced by the various treatment regimens. Interestingly, phage yields from certain biofilm experiments were greater than from similar planktonic experiments, suggesting that Sb-1 might be more efficiently propagated on biofilm. IMPORTANCE Biofilm-associated multidrug-resistant infections pose significant challenges for antibiotic therapy. The extracellular polymeric matrix of biofilms presents an impediment for antibiotic diffusion, facilitating the emergence of multidrug-resistant populations. Some bacteriophages (phages) can move across the biofilm matrix, degrade it, and support antibiotic penetration. However, little is known about how phages and their hosts interact in the biofilm environment or how different phage+antibiotic combinations (PACs) impact biofilms in comparison to the planktonic state of bacteria, though scattered data suggest that phage+antibiotic synergy occurs more readily under biofilm-like conditions. Our results demonstrated that phage Sb-1 can infect MRSA strains both in biofilm and planktonic states and suggested PAC regimens worthy of further investigation as adjuncts to antibiotics.


Early effect of inbreeding as revealed by microsatellite analyses on Ostrea edulis larvae.
This paper reports new experimental evidence on the effect of inbreeding on growth and survival in the early developmental phase of a marine bivalve, the flat oyster Ostrea edulis. Two crosses between full sibs were analyzed using four microsatellite markers. Samples of 96 individuals were taken just after spawning (day 1), at the end of the larval stage before metamorphosis (day 10) and at the postlarval stage (day 70). Significant departure from Mendelian expectation was observed at two loci in the first cross and two loci in the second. Departure from 1:1 segregation occurred in one parent of the first cross at three loci and genotypic selection, which resulted in highly significant heterozygote excesses, was recorded at three out of four loci in cross C1 and at two out of three loci in cross C2. Across the four markers, there were similar significant excesses of multilocus heterozygosity, and significant multilocus heterozygosity-growth correlations were recorded for both crosses at all stages. These results suggest that microsatellite markers, often assumed to be neutral, cosegregated with fitness-associated genes, the number of which is estimated to be between 15 and 38 in the whole genome, and that there is a potentially high genetic load in Ostrea edulis genome. This load provides a genetic basis for heterosis in marine bivalves.


Influence of Dirichlet boundary conditions on dissipative solitons in the cubic-quintic complex Ginzburg-Landau equation.
We investigate the influence of Dirichlet boundary conditions on various types of localized solutions of the cubic-quintic complex Ginzburg-Landau equation as it arises as an envelope equation near the weakly inverted onset of traveling waves. We find that various types of nonmoving pulses and holes can accommodate Dirichlet boundary conditions by having, for holes, two halves of a pi hole at each end of the box. Moving pulses of fixed shape as they arise for periodic boundary conditions are replaced by a nonmoving asymmetric pulse, which has half a pi hole at the end of the box in the original moving direction to guarantee that Dirichlet boundary conditions are met. Moving breathing pulses as they arise for periodic boundary conditions propagate toward one end of the container and stop moving while the breathing persists indefinitely. Finally breathing and moving holes are replaced by two (nonbreathing) half pi holes at each end of the container and one hump in the bulk.


Noncontrast computed tomography in obstructive anuria: a prospective study.
To evaluate the role of noncontrast computed tomography (NCCT) in the determination of the cause of obstructive anuria and to compare its accuracy with that of the traditional methods of combined plain abdominal x-ray (KUB) and gray-scale abdominal ultrasonography (US). The study included 40 consecutive patients with obstructive anuria. In addition to the routine evaluation, which included history, clinical examination, biochemical profile, KUB, and US, all patients underwent NCCT. The study patients were tested against an age and sex-matched control group that included the normal contralateral kidneys of 57 consecutive patients who underwent KUB, US, and NCCT for acute flank pain during the same study period. The reference standard for the determination of the cause of obstruction was retrograde or antegrade ureterography with or without ureteroscopy or open surgery. The absence of obstruction in the control group was confirmed by nonequivocal normal intravenous urography of the side free of flank pain. Both NCCT and combined KUB and US were compared regarding the sensitivity, specificity, and overall accuracy. The study group had 48 renal units, because obstruction was bilateral in 8 patients and of a solitary kidney in 32. Of the 42 renal units with calculus obstruction, the site of stone impaction was identified in all renal units by NCCT (sensitivity 100%) and in only 25 by combined KUB and US (sensitivity 59.5%)-a significant difference (P = 0.0001). Of the 6 renal units with noncalcular obstruction, both NCCT and US diagnosed the cause of obstruction in 3. The overall sensitivity of NCCT in the determination of the cause of obstructive anuria was 94% and that of combined KUB and US was 58%-a significant difference (P = 0.0001). The specificity of NCCT was not significantly different from that of combined KUB and US (96.5% versus 93%, respectively). The overall accuracy of NCCT was 95% and that of combined KUB and US was 77%-a significant difference (P = 0.0003). In patients with obstructive anuria, conventional KUB and US could not identify the cause of ureteral obstruction in about 40% of the patients. Under such conditions, NCCT can accurately provide the diagnosis, obviating the need of invasive and expensive diagnostic procedures.


Occurrence of 7-methylguanine in nucleic acids of rat liver.
1. Microsomal and soluble RNA of rat liver have been studied by column and paper chromatography after administration of [Me-(14)C]methionine; evidence was obtained for the occurrence of 7-methylguanine, the methyl group being derived from methionine. 2. No evidence was obtained for the occurrence of 7-methylguanine in DNA.


Drug hypersensitivity: insights into pathomechanisms.
In adverse reactions to drugs with an immunological basis (ADRIB) specific IgE antibodies or sensitised effector T cells take part. Each type of response induces well defined clinical entities. For T cell reactions, classically known as Type IV Gel and Coomb responses, different subtypes have been classified. These correspond to different clinical entitles and each have characteristically histopathological findings. Advanced in vitro studies by development of T cell liens and T cell clones to different drugs compounds and the monitorisation of the immunological response during the course of these diseases has provided new insights for a better understanding and evaluation of ADRIB.


Progress and challenges in the development of a cell-based therapy for hemophilia A.
Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review, we discuss the possibilities, progress, and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific induced pluripotent stem cells.


Collaboration of antibody and inflammation in clearance of rabies virus from the central nervous system.
To investigate the involvement of various cellular and humoral aspects of immunity in the clearance of rabies virus from the central nervous system, (CNS), we studied the development of clinical signs and virus clearance from the CNS in knockout mice lacking either B and T cells, CD8+ cytotoxic T cells, B cells, alpha/beta interferon (IFN-alpha/beta) receptors, IFN-gamma receptors, or complement components C3 and C4. Following intranasal infection with the attenuated rabies virus CVS-F3, normal adult mice of different genetic backgrounds developed a transient disease characterized by loss of body weight and appetite depression which peaked at 13 days postinfection (p.i.). While these animals had completely recovered by day 21 p.i., mice lacking either B and T cells or B cells alone developed a progressive disease and succumbed to infection. Mice lacking either CD8+ T cells, IFN receptors, or complement components C3 and C4 showed no significant differences in the development of clinical signs by comparison with intact counterparts having the same genetic background. However, while infectious virus and viral RNA could be detected in normal control mice only until day 8 p.i., in all of the gene knockout mice studied except those lacking C3 and C4, virus infection persisted through day 21 p.i. Analysis of rabies virus-specific antibody production together with histological assessment of brain inflammation in infected animals revealed that clearance of CVS-F3 by 21 days p.i. correlated with both a strong inflammatory response in the CNS early in the infection (day 8 p.i.), and the rapid (day 10 p.i.) production of significant levels of virus-neutralizing antibody (VNA). These studies confirm that rabies VNA is an absolute requirement for clearance of an established rabies virus infection. However, for the latter to occur in a timely fashion, collaboration between VNA and inflammatory mechanisms is necessary.


Human P450scc gene transcription is induced by cyclic AMP and repressed by 12-O-tetradecanoylphorbol-13-acetate and A23187 through independent cis elements.
Long-term regulation of mammalian steroid hormone synthesis occurs principally by transcriptional regulation of the gene for the rate-limiting cholesterol side-chain cleavage enzyme P450scc. Adrenal steroidogenesis is regulated primarily by two hormones: adrenocorticotropin, which works via cyclic AMP (cAMP) and protein kinase A, and angiotensin II, which works via Ca2+ and protein kinase C. Forskolin and 8-bromo-cAMP stimulated, while prolonged treatment with a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) and a calcium ionophore (A23187) additively suppressed accumulation of endogenous P450scc mRNA in transformed murine adrenal Y1 cells. In Y1 cells transfected with 2,327 base pairs of the human P450scc promoter fused to the bacterial gene for chloramphenicol acetyltransferase (CAT), forskolin increased CAT activity 900% while combined TPA plus A23187 reduced CAT activity to 15% of the control level. Forskolin induced the P450scc promoter as rapidly as a promoter containing two cAMP-responsive elements fused to a simian virus 40 promoter, a system known to respond directly to cAMP. Basal expression was increased by sequences between -89 and -152 and was increased further by sequences between -605 and -2327. This upstream region also conferred inducibility by cAMP. TPA plus A23187 transiently increased CAT activity before repressing it, reflecting the complex actions of angiotensin II in vivo. Repression by prolonged treatment with TPA plus A23187 was mediated by multiple elements between -89 and -343. Induction of CAT activity by forskolin was not diminished by treatment with TPA plus A23187, nor were the regions of the promoter responsible for regulation by the two pathways coisolated. Thus, the human gene for P450scc is repressed by TPA plus A23187 by mechanisms and sequences independent of those that mediate induction by cAMP.


Calcium-dependent stability studies of domains 1 and 2 of epithelial cadherin.
Epithelial cadherin is important in establishing and maintaining cell to cell interactions in epithelial cells, thereby playing an important role during morphogenesis. The epithelial cadherin molecules have three main regions: the N-terminal extracellular region, the transmembrane region that spans the cell membrane once, and the C-terminal cytoplasmic region that communicates with the cytoskeletal actin filaments through catenins. We report studies of the calcium-dependent stability of extracellular domains 1 and 2 of epithelial cadherin as a two-domain construct (MECAD12). Circular dichroism (CD) spectra of MECAD12 indicated a typical beta-sheet conformation in all solution conditions. Thermal- and denaturant-induced unfolding was monitored by CD. Distinct calcium stabilization was observed as a shift in T(m) from 40 (apo) to 65 degrees C (10 mM Ca2+). Spectroscopic experiments agreed well with calorimetric (DSC). In the absence of calcium, the unfolding transition was shallow (deltaH(m) = 40 kcal/mol) but not obviously three state. Model-dependent analysis indicated that a second transition could be assigned to the unfolding of domain 2. A calcium-binding constant was derived from the calcium-dependent shift in temperature denaturation profiles. The Kd that was obtained (55 microM) was consistent with literature values. Thus, the modular domains of epithelial cadherin exhibit context-dependent behavior in both the apo and calcium-bound states. This cooperativity between the modules is consistent with the physiological role of epithelial cadherin in signal transduction through cell-adhesive contacts.


The computational study of the γ-Fe2O3 nanoparticle as Carmustine drug delivery system: DFT approach.
In the present study, it is attempted to scrutinize the properties of the maghemite nanoparticle as a Carmustine drug delivery system by means of the density functional theory calculations regarding their geometries, adsorption energies, vibrational frequencies, and topological features of the electron density. Based on the density functional theory results, it is found that the interaction between Carmustine drug molecule and maghemite nanoparticle is weak; so that, the adsorption of the Carmustine drug is typically physisorption. It is also found that the intermolecular hydrogen bonds between the drug and the nanoparticle play the significant role in the stability of the physisorption configurations. The nature of the intermolecular interactions has been explored by calculation of the electron densities and their Laplacian at the bond critical points using Atoms-in-Molecule theory. Moreover, natural bond orbital analysis indicates that the Carmustine molecule can be adsorbed on the nanoparticle surface with a charge transfer from the Carmustine drug to the nanoparticle.


Mucopolysaccharidosis type II: skeletal-muscle system involvement.
Mucopolysaccharidosis type II (MPS-II) is a rare lysosomal storage disorder caused by deficiency in the activity of the enzyme iduronate-2-sulphatase. This enzyme is responsible for the catabolism of two different glycosaminoglycans (GAGs), dermatan sulfate and heparan sulfate. Lysosomal accumulation of these GAG molecules results in cell, tissue, and organ dysfunction. The skeletal-muscle system involvement is because of essential accumulated GAGs in joints and connective tissue. MPS-II has many clinical features and includes two recognized clinical entities, mild and severe, that represent two ends of a wide spectrum of clinical severity. The aim of this study is to review the involvement of the skeletal-muscle system in MPS-II.


[Proglumetacin for the treatment of inflammatory and degenerative arthropathies].
Twenty patients with inflammatory (15) or degenerative (5) joint disorders had been treated with 450 mg/day of proglumetacin during 35 +/- 18 days. Articular symptoms showed a definite and continued improvement, particularly evident during the initial 15 days of treatment on both painful and inflammatory components. The final physician's evaluation rated 75% of results as excellent or good, versus 15% of poor (3 patients, one of whom already refractory to diclofenac). The tolerance was defined as excellent to good in 90% of patients: one (5%) was dropped out upon the onset of sweating and palpitation, already observed with other drugs. Overall, only one case each of heartburn, anorexia and diarrhoea were considered as possibly related to the treatment. Laboratory tests did not show any variation that could be attributed to the drug. Proglumetacin therefore, by force of its efficacy and safety, appears to be particularly suited as a first-choice drug for the management of both inflammatory and degenerative joint disorders.


12-O-tetradecanoylphorbol-13-acetate and EZH2 inhibition: A novel approach for promoting myogenic differentiation in embryonal rhabdomyosarcoma cells.
Rhabdomyosarcoma (RMS) is a soft tissue sarcoma that arises from muscle precursors affecting predominately children and young adults. It can be divided into two main classes: embryonal (eRMS) and alveolar rhabodomyosarcomas (aRMS). Despite the expression of early muscle specific genes, RMS cells fail to complete myogenesis even in differentiation conditions. We previously demonstrated that Enhancer Zeste of Homolog 2 (EZH2), the catalytic subunits of PRC2 complex, contributes to inhibit muscle differentiation in eRMS and its down-regulation causes a partial recovery of myogenesis. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a molecule able to induce differentiation in eRMS with a mechanism that involves the protein kinase C (PKC). In this paper we report that treatment with TPA reduces the expression of EZH2 without affecting levels of H3K27me3. The combination of TPA with GSK126, an inhibitor of the catalytic activity of EZH2, has a synergic effect on the induction of muscle differentiation in RD rhabdomyosarcoma cells, suggesting a new therapeutic combinatory approach for RMS treatment.


Heterometallic MIIRuIII2 compounds constructed from trans-[Ru(Salen)(CN)2]- and trans-[Ru(Acac)2(CN)2]-. Synthesis, structures, magnetic properties, and density functional theoretical study.
The synthesis, structures, and magnetic properties of four cyano-bridged M(II)Ru(III)2 compounds prepared from the paramagnetic Ru(III) building blocks, trans-[Ru(salen)(CN)2]- 1 [H2salen = N,N'-ethylenebis(salicylideneimine)] and trans-[Ru(acac)2(CN)2]- (Hacac = acetylacetone), are described. Compound 2, {Mn(CH3OH)4[Ru(salen)(CN)2]2}.6CH3OH.2H2O, is a trinuclear complex that exhibits antiferromagnetic coupling between Mn(II) and Ru(III) centers. Compound 3, {Mn(H2O)2[Ru(salen)(CN)2]2.H2O}n, has a 2-D sheetlike structure that exhibits antiferromagnetic coupling between Mn and Ru, leading to ferrimagnetic-like behavior. Compound 4, {Ni(cyclam)[Ru(acac)2(CN)2]2}.2CH3OH.2H2O (cyclam = 1,4,8,11-tetraazacyclotetradecane), is a trinuclear complex that exhibits ferromagnetic coupling. Compound 5, {Co[Ru(acac)2(CN)2]2}n, has a 3-D diamond-like interpenetrating network that exhibits ferromagnetic ordering below 4.6 K. The density functional theory (DFT) method was used to calculate the molecular magnetic orbitals and the magnetic exchange interaction between Ru(III) and M(II) (Mn(II), Ni(II)) ions.


Compact oligomers and nucleosome phasing.
Micrococcal nuclease (EC 18.104.22.168) digestion of histone H1- and H5-depleted chicken erythrocyte chromatin yields, in addition to 140-base-pair (bp) core particles, a series of nucleosome oligomers containing about 260 bp (compact dimer), 380 bp (compact trimer), etc. of DNA. These are postulated to represent members of a class of oligomers in which the DNA is tightly wound on stacked protein cores. The physical properties (melting, circular dichroism) as well as DNase I (EC 126.96.36.199) digestion patterns support this view. DNase I digestion of tight oligomers in which the 5' ends of the DNA have been labeled yields results consistent with this model and inconsistent with some other possible models. Several classes of such particles are postulated to exist, differing in DNA length by 10-bp increments. This may be an explanation of the 10-bp nucleosome "phasing" that has been observed in some nuclei.


Hospital admission rates for lower respiratory tract infections in infants in the Northwest Territories and the Kitikmeot region of Nunavut between 2000 and 2004.
Health care workers have long observed increased rates of hospital admissions for respiratory illness in infants from the northern regions of Canada. Particularly high rates have been reported in the Inuit population. The purpose of the present study was to compare rates of hospital admission in Inuit versus non-Inuit infants from the perspective of a single northern health region. A retrospective review of all hospital admissions for lower respiratory tract infections (LRTIs) in infants from the Northwest Territories and the Kitikmeot region of Nunavut between 2000 and 2004 was completed and admission rates were compared by health region. Hospital admission rates for LRTIs in infants were above the Canadian rate for all regions. The rate of hospital admission for LRTIs in infants from the Kitikmeot region of Nunavut was dramatically high at 590 hospital admissions/1000 live births in the first 12 months of life. The majority of hospitalized infants were previously healthy, non-breastfed term infants with no underlying disease. The rate of hospital admission in the Kitikmeot region of Nunavut is the highest reported in the current literature. The reason for such significant morbidity is difficult to explain and raises the question of an underlying predisposition to severe disease in this infant population. The question warrants further study to gain a better understanding of risk factors as well as the role of prevention.


[Ultrasonic-guided fine-needle biopsy of osteolytic lesions].
Percutaneous biopsy of lytic lesions of the bone, in the past pertaining to orthopedic surgeons, has now become a part of interventional radiology. Fluoroscopic guidance has simplified its execution. US does not, under normal conditions, allow an accurate examination of the skeleton; on the other hand, when the bone tissue is replaced by soft tissue, US can easily demonstrate the presence of a tumefaction, caused by a lytic lesion, and determine its characteristics. Eleven patients with lytic lesions (recognized on plain film) underwent US. The lesions were demonstrated. In such cases, biopsy is essential to define their benign or malignant nature, in the latter case if primitive or metastatic, and their histology as well. US is a simple guide to the biopsy of noncorticalized lytic lesions, and it offers consistent advantages over fluoroscopic guidance--i.e. it is easier to perform, it requires no X-ray exposure, it provides with three-dimensional images, the guide is performed in real time, and a choice of the most appropriate (non-necrotic) areas is possible.


DNA sequence characterisation and phylogeography of Lymnaea cousini and related species, vectors of fascioliasis in northern Andean countries, with description of L. meridensis n. sp. (Gastropoda: Lymnaeidae).
Livestock fascioliasis is a problem throughout Ecuador, Colombia and Venezuela, mainly in Andean areas where the disease also appears to affect humans. Transmission patterns and epidemiological scenarios of liver fluke infection have shown to differ according to the lymnaeid vector snail species involved. These Andean countries present the vectors Lymnaea cousini, L. bogotensis and L. ubaquensis, unknown in the rest of Latin America. An exhaustive combined haplotype study of these species is performed by means of DNA sequencing of the nuclear ribosomal 18S RNA gene, ITS-2 and ITS-1, and mitochondrial DNA cox1 gene. The conserved 5.8S rDNA sequence corroborated that no pseudogenes are involved in the numerous non-microsatellite/minisatellite-related indels appearing between the ITS-2 and ITS-1 sequences when comparing different L. cousini--L. bogotensis populations. Sequence analyses and phylogenetic reconstruction methods including other lymnaeid vector species show that (i) L. bogotensis is a synonym of L. cousini, (ii) L. ubaquensis is a synonym of Pseudosuccinea columella, and (iii) populations of L. cousini hitherto known from Venezuelan highlands indeed belong to a new species for which the name L. meridensis n. sp. is proposed. This new species is described and a complete phenotypic differentiation provided. ITS-2, ITS-1 and cox1 prove to be good markers for specimen classification and haplotype characterisation of these morphologically similar lymnaeids in endemic areas. Analysis of the 18S gene and phylogenetic reconstructions indicate that L. cousini and L. meridensis n. sp. cluster in an evolutionary line different from the one of P. columella, despite their external resemblance. This suggests an evolutionary phenotypic convergence related to similar environments and which has given rise to frequent specimen misclassification. Body size and phylogenetic relationships of L. meridensis n. sp. with well-known vectors as Lymnaea cousini and P. columella, as well as with Galba/Fossaria species, suggest that the new species may participate in disease transmission to both animals and humans in altitude areas during the yearly window in which temperatures are higher than the F. hepatica minimum development threshold. The involvement of L. cousini and P. columella in the transmission and geographical/altitudinal distribution of fascioliasis in these Andean countries is analysed.


LCT-EF258 with S17I Mutation in DprA Exhibits Horizontal Gene Transfer Deficiency After Spaceflight.
BACKGROUND: Space is a special environment in which microgravity and cosmic rays are the primary factors that induce gene mutations of microorganisms. In our previous studies, a single point mutation in the gene dprA was found in an Enterococcus faecium strain of LCT-EF258 after spaceflight. DNA processing protein A (DprA) plays a prominent role in the horizontal transfer of genes among bacteria (such as Streptococcus pneumoniae, Helicobacter pylori, Bacillus subtilis, and Rhodobacter capsulatus). However, the function of DprA in E. faecium remains unknown. Furthermore, E. faecium could acquire antibiotic resistance through the horizontal transfer of antibiotic resistance genes, but it is unclear whether dprA mutants could affect this process in E. faecium.METHODS: In this study, we constructed a plasmid containing the vancomycin resistance gene vanA and then transferred the gene vanA into the dprA-mutant strain LCT-EF258 and the control strain LCT-EF90 using the electroporation technique. We then used Discovery StudioTM software to construct the 3D protein structure.RESULTS: The results showed that the horizontal transfer efficiency of the vancomycin resistance gene vanA in the dprA-mutant E. faecium decreased. And the hydrophobic core of the mutant DprA became stable and the binding affinity between the mutant DprA and ssDNA reduced.DISCUSSION: This study is an exploration of bacterial gene mutation after spaceflight. The dprA mutant could affect the ability of E. faecium to acquire exogenous resistance gene vanA, which offered us an interesting path to block the dissemination of resistance genes between strains.Yu Y, Chang D, Guo Q, Wang J, Liu C. LCT-EF258 with S171 mutation in DprA exhibits horizontal gene transfer deficiency after spaceflight. Aerosp Med Hum Perform. 2019; 90(2):116-122.


The alpha1beta1 integrin and TNF receptor II protect airway CD8+ effector T cells from apoptosis during influenza infection.
Primary viral infections of the lung induce potent effector CD8 T cell responses. To function in the influenza-infected airways, CD8 T cells must be able to resist cell death. The majority of the CD8 T cells in the airways and lung parenchyma expressed CD49a, the alpha-chain of the type IV collagen receptor VLA-1, and these cells were highly activated, producing both IFN-gamma and TNF-alpha. In the airways, where type IV collagen is abundant, but not the spleen, the CD49a(+) CD8 cells had reduced proportions of annexin V and caspase 8, and >80% expressed the TNF-alpha receptor II, while Fas, TNFR-I, and CD27 expression were similar to CD49a(-) cells. Furthermore, the CD49a(+), but not CD49a(-), CD8 T cells from the airways were resistant to active induction of apoptosis in the presence of type IV collagen and TNF-alpha in vitro. We propose that TNFR-II and the VLA-1 synergize to protect effector CD8 T cells in the infected airways from apoptosis during the acute infection.


High extinction ratio terahertz wire-grid polarizers with connecting bridges on quartz substrates.
A terahertz (THz) wire-grid polarizer with metallic bridges on a quartz substrate was simulated, fabricated, and tested. The device functions as a wide-band polarizer to incident THz radiation. In addition, the metallic bridges permit the device to function as a transparent electrode when a DC bias is applied to it. Three design variations of the polarizer with bridges and a polarizer without bridges were studied. Results show the devices with bridges have average s-polarization transmittance of less than -3 dB and average extinction ratios of approximately 40 dB across a frequency range of 220-990 GHz and thus are comparable to a polarizer without bridges.


Soil ascomycetes from Spain. XIII. Two new species of Apiosordaria.
Apiosordaria hispanica sp. nov. and Apiosordaria globosa sp. nov. isolated from soil samples collected in Tarragona, Catalonia, Spain, are described and illustrated. Both species are morphologically close to A. otanii. The ascospores of A. hispanica have tuberculate walls, while those of A. otanii have small warts. Apiosordaria globosa differs from those species by the globose upper cell of the ascospores, which has a small apical protrusion with sub-apical germ pore when young. In A. hispanica and A. globosa the lower cells of the ascospores are slightly warted, while in A. otanii the lower cell of the ascospores is smooth-walled.


Body mass index and body fat percentage in assessment of obesity prevalence in saudi adults.
To assess the obesity prevalence in Saudi adults according to the international standards of body mass index (BMI) and body fat percentage (BF%). Five hundred and thirty healthy Saudi adults aged 18-72 years (mean 36.91 ± 15.22 years) were enrolled in this study. Their body composition was assessed by bioelectrical impendence analysis with a commercially available body composition analyzer. Standard BMI and BF% values were used to define obesity. The prevalence of underweight, normal underweight, overweight and obesity in Saudi adults according to the BMI criteria (<18.5 kg/m², 18.5-24.4 kg/m², 25-29.9 kg/m², 30 kg/m² and above, respectively) was 2.5%, 30.2%, 33.6%, and 33.8%, respectively, whereas the obesity prevalence was 60% (n=318) in Saudi adults according to the BF% criteria (25% for males and 30% for females), which was significantly higher than that according to BMI criteria. However, it was 50.6% (n=268) when the BMI cutoff point was 27.5 kg/m², proposed by WHO for the Asian population. Kappa analysis showed that the obesity prevalence defined by BMI and BF% was higher in females than in males (k=0.530 vs k=0.418, P<0.0001). The sensitivity and specificity of BMI (30 kg/m² and 27.5 kg/m²) were 54.1% and 96.7% and 76.4% and 88.2%, respectively, for obesity. A lower BMI cutoff point (26.60 kg/m²) was proposed in this study, which gave the maximum sensitivity (84.3%) and specificity (85.4%), with a moderate kappa agreement (k=0.686). Moreover, the obesity prevalence at this cutoff point (56.4%) was significantly higher than that recommended by WHO. The specificity of BMI for obesity is high and its sensitivity is low in both sexes. Its sensitivity can be increased by changing BMI cutoff to a lower value. The choice of BF% reference is of great influence for the assessment of obesity prevalence according to the BMI.


Protein kinase C delta inhibits the proliferation of vascular smooth muscle cells by suppressing G1 cyclin expression.
To elucidate the physiological role of protein kinase C (PKC) delta, a ubiquitously expressed isoform in vascular smooth muscle cells (VSMC), PKC delta was stably overexpressed in A7r5 cells, rat clonal VSMC. The [3H]thymidine incorporation in A7r5 overexpressed with PKC delta (DVs) was suppressed to 37.1 +/- 16.3% (mean +/- S.D.) of the level in control or A7r5 transfected with vector alone (EVs). The reduction of [3H]thymidine incorporation was strongly correlated with overexpressed PKC levels. Moreover, transient transfection of a dominant negative mutant of PKC delta restored the reduced proliferation in DVs. Flow cytometry analysis demonstrated that DVs were arrested in the G0/G1 phase of the cell cycle. Expression of cyclins D1 and E and retinoblastoma protein phosphorylation were reduced, while the protein levels of p27 were elevated in DVs as compared with EVs. There were no significant differences in the expression of c-fos, c-jun, c-myc, cyclin D2, D3, cyclin-dependent kinase 2, cyclin-dependent kinase 4, and p21 among the clones. We conclude that PKC delta inhibits the proliferation of VSMC by arresting cells in G1 via mainly inhibiting the expression of cyclin D1 and cyclin E.


[How often and what type of control tests should be done during long- term anti-epileptic treatment?].
During long-term epileptic treatment, it is essential to monitor the efficacy of the drugs used. Any adverse effects of this treatment must be detected early or preferably avoided. However, the type of control and the frequency with which this should be carried out are controversial. All anti-epileptic drugs are potentially liable to provoke adverse reactions of different types and degrees. Determinations of the blood-levels of anti-epileptic drugs are useful to attain optimus drug levels, and to identify any relationship there might be between these drugs and possible adverse effects. However, this usefulness varies, depending on the particular anti-epileptic drug concerned. Therefore measurement as a routine is not justified, but should be undertaken to obtain the answer to specific questions. Laboratory analysis of blood to determine liver function, blood cell counts, coagulation, etc. is necessary in some cases. This may imply problems of interpretation and of cost. Is most cases it is of little help in the early detection or prevention of the most serious adverse reactions, which cause the greatest mortality. Therefore although such measures are necessary, attention should be paid to clinical methods for the early detection of symptoms and signs which may indicate the presence of adverse effects. Similarly, EEG should not be done as a routine for the assessment of the effect of treatment, but should be used when indicated for the follow-up of specific epileptic syndromes. An EEG may be useful for prognosis before suspending long-term epileptic treatment.


A large outbreak of influenza B-associated benign acute childhood myositis in Germany, 2007/2008.
Benign acute childhood myositis (BACM) is a rare syndrome associated with various viral infections. Bilateral calve pain may lead to inability to walk. During winter 2007/2008, we investigated a nationwide outbreak of influenza-associated BACM (IA-BACM) to identify etiologic (sub)type, describe the course of disease, and explore how well the syndrome is known among physicians. We performed retrospective and prospective case finding in all German federal states. Physicians returned patient-based questionnaires containing information about sex, age, disease progression, patient-management, and number of BACM cases treated previously. We compared IA-BACM cases with influenza cases from the German virologic sentinel surveillance system for influenza. We investigated 219 children with IA-BACM. They coincided with the curve of influenza B of the German virologic sentinel surveillance system for influenza. Median age was 7 years, 74% (160/216) of cases were male, median time between the onset of fever and onset of BACM-symptoms was 3 days lasting for a median of 4 days. Almost half of the affected children had presented at hospitals. One case with beginning renal impairment occurred, but the patient recovered completely. Most reporting physicians had not seen BACM-patients previously. Multivariable analysis showed IA-BACM's strong association with influenza B, male sex, and age between 6 and 9 years. Influenza B caused a large BACM outbreak in Germany. Onset of BACM symptoms followed shortly after the onset of influenza symptoms. The course of this disease was almost exclusively mild and self-limiting. Diagnosis of this rare but distinct clinical entity by the alert physician can spare the patient potentially unneeded invasive testing and hospital admission.


Mentoring and its impact on intellectual capital: through the eyes of the mentee.
Recently, the concept of mentoring, and the use of mentorship programs, is being touted as a strategic means within healthcare organizations to address the nursing shortage that promises to continue well into the future. Mentoring, on the surface, could also be considered as an excellent means of supporting the development and retention of intellectual capital and succession planning within nursing. However, without a better understanding of the concept of mentoring, nurse leaders can never really know the full impact of mentoring in order to achieve such goals within the organization. Several key results from a study of mentorship in nursing support the concept of ongoing knowledge sharing within the discipline, as seen through the eyes of the mentee. The implications for nurse leaders shift the focus from formal mentoring programs to the creation of practice settings that foster the development of mentoring relationships.


[Organ donation: A treatment option in end-of life intensive care?]
A newly issued policy statement of the German Medical Association considers organ donation as an integral part of end-of-life intensive care in patients with devastating brain afflictions. Hence, patients' wishes towards organ donation and medical suitability should be evaluated when prognosis is considered futile and goals of treatment need to be reconsidered. Continuation of intensive care treatment towards the (mandatory) diagnosis of "brain death" and subsequently towards organ donation has to be legitimatized by patients' explicit wishes (organ donor card, advanced directive) or by surrogate decisions makers. Intensive care facilitating organ donation should be goal-directed and follow established guidelines. Thus, a potential recovery of transplantable organs is supported by appropriate intensive care treatment. Decisions to employ extended intensive care options (like extracorporeal circulatory support or cardiopulmonary resuscitation) in potential organ donors should be carefully outbalanced with patients' wishes, organ donation being considered an achievable goal and even potential frictions in medical teams.


Prognostic factors and outcome for patients with esophageal squamous cell carcinoma underwent surgical resection alone: evaluation of the seventh edition of the American Joint Committee on Cancer staging system for esophageal squamous cell carcinoma.
More data are essential to test the efficacy of the seventh edition of the American Joint Committee on Cancer (AJCC) staging system for esophageal squamous cell carcinoma (ESCC). This retrospective study was designed to identify the prognostic factors for survival of patients with ESCC who underwent surgical resection alone and to evaluate the new AJCC staging system for ESCC. Data of a single-center cohort of 2011 patients with ESCC who underwent surgical resection alone according to the new staging system were reviewed. Univariate and multivariate analyses were performed to identify prognostic factors. The 1-, 3-, and 5-year overall survival rates were 83.5, 57.4, and 47.4%, respectively, with a median survival time of 51.0 months. Age, histologic grade, R-category, pT category, pN category, pM category, pTNM stage, and the extent of lymph node metastasis were independent prognostic factors (p < 0.05). In separate subgroup analyses, the survival differences were not significant for pN2 versus pN3 category (p = 0.159) and stages IA versus IB (p = 0.922). Subdivisions by depth of infiltration rather than tumor grade for pT1N0M0 cancers and modified nodal categories (0, 1, 2-3, and ≥4 positive lymph nodes) better represented a survival advantage. The seventh edition of the AJCC staging system for ESCC is acceptable in predicting survival. However, tumor location does not influence survival in our study. Subdivisions of pT1N0M0 cancers and the N-classification may need to be modified.


[Study on the immuno-effects and influencing factors of Chinese hamster ovary (CHO) cell hepatitis B vaccine among adults, under different dosages].
To evaluate the immuno-effect and related influencing factors on 10 µg and 20 µg Chinese hamster ovary (CHO) cell hepatitis B vaccine, using the randomized double-blind controlled trials in adult population. A total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis B, and negative on five blood indicators for hepatitis B, were selected as the study objects from four districts in Beijing. The study objects were randomly divided into two groups, and then accepted 10 µg and 20 µg recombinant CHO hepatitis B vaccination by 0 - 1 - 6 month schedule. Influencing factors were investigated by means of questionnaire. Blood samples were collected one month after the third dose of vaccination. Anti-HBs level was detected by Abott chemiluminescence detection method. For the anti-HBs negative person, fluorescent quantitative PCR method was used to find out if the person had been infected with HBV. Logistic regression analysis was used to find out the influencing factors of anti-HBs seroconversion on every studied subject. The anti-HBs seroconversion rates on 10 µg and 20 µg dose groups were 88.8% (95%CI: 85.4% - 92.2%) and 95.3% (95%CI: 93.0% - 97.6%) respectively. Taking the anti-HBs level < 100 mIU/ml as the low/non-response standard, the low response and non-response rates were 34.3% and 17.4% respectively. The geometric mean titers (GMT) of anti-HBs were 173.42 mIU/ml for the 10 µg dose group and 588.51 mIU/ml for the 20 µg dose group. Data from the Multivariate analysis showed that:diabetes, spouses infected with hepatitis B virus and old age were unfavorable factors for anti-HBs Seroconversion. 20 µg dose of the vaccine was conducive to seroconversion. 20 µg CHO hepatitis B vaccine seemed better than 10 µg CHO hepatitis B vaccine while many factors need to be taken into account for evaluation on hepatitis B vaccines.


A view of sur/KIR6.X, KATP channels.
ATP-sensitive potassium channels, termed KATP channels, link the electrical activity of cell membranes to cellular metabolism. These channels are heteromultimers of sulfonylurea receptor (SUR) and KIR6.X subunits associated with a 1:1 stoichiometry as a tetramer (SUR/KIR6.X forms the pores, whereas SUR regulates their activity. Changes in [ATP]i and [ADP]i gate the channel. The diversity of KATP channels results from the assembly of SUR and KIR6.X subtypes KIR6.1-based channels differ from KIR6.2 channels mainly by their smaller unitary conductance. SUR1- and SUR2-based channels are distinguished by their differential sensitivity to sulfonylureas, whereas SUR2A-based channels are distinguished from SUR2B channels by their differential sensitivity to diazoxide. Mutations that result in the loss of KATP channels in pancreatic beta-cells have been identified in SUR1 and KIR6.2. These mutations lead to familial hyperinsulinism. Understanding the mutations in SUR and KIR6.X is allowing insight into how these channels respond to nucleotides, sulfonylureas, and potassium channel openers, KCOs.


A Zebrafish Drug-Repurposing Screen Reveals sGC-Dependent and sGC-Independent Pro-Inflammatory Activities of Nitric Oxide.
Tissue injury and infection trigger innate immune responses. However, dysregulation may result in chronic inflammation and is commonly treated with corticosteroids and non-steroidal anti-inflammatory drugs. Unfortunately, long-term administration of both therapeutic classes can cause unwanted side effects. To identify alternative immune-modulatory compounds we have previously established a novel screening method using zebrafish larvae. Using this method we here present results of an in vivo high-content drug-repurposing screen, identifying 63 potent anti-inflammatory drugs that are in clinical use for other indications. Our approach reveals a novel pro-inflammatory role of nitric oxide. Nitric oxide affects leukocyte recruitment upon peripheral sensory nervous system or epithelial injury in zebrafish larvae both via soluble guanylate cyclase and in a soluble guanylate cyclase -independent manner through protein S-nitrosylation. Together, we show that our screening method can help to identify novel immune-modulatory activities and provide new mechanistic insights into the regulation of inflammatory processes.


Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a prospective study of factors associated with rebleeding.
In a previous randomized trial, we demonstrated that propranolol prevented recurrent gastrointestinal bleeding in patients with cirrhosis. We have undertaken the present study in a new group of patients to ascertain the factors associated with rebleeding. Among 232 patients with cirrhosis admitted for gastrointestinal bleeding, 127 were included. They received propranolol orally at a dose reducing the heart rate by 25%. The median follow-up period was 682 days. The following factors were studied: cause of cirrhosis; severity of cirrhosis; hepatocellular carcinoma recognized after inclusion; compliance; persistent decrease in heart rate; dose of propranolol; alcohol abstinence; previous history of hemorrhage; time interval from hemorrhage to onset of propranolol administration, and source of bleeding. The percentage of patients free of rebleeding was 71% at 1 year and 57% at 2 years. Only five factors were significantly and independently associated with rebleeding: occurrence of hepatocellular carcinoma; lack of compliance; lack of persistent decrease in heart rate; lack of abstinence, and previous history of bleeding. In conclusion, this study confirms the results of our previous trial and suggests that certain factors play a role in the mechanism of rebleeding in patients receiving propranolol.


Contribution of formant frequency information to vowel perception in steady-state noise by cochlear implant users.
Cochlear implant (CI) recipients have difficulty understanding speech in noise even at moderate signal-to-noise ratios. Knowing the mechanisms they use to understand speech in noise may facilitate the search for better speech processing algorithms. In the present study, a computational model is used to assess whether CI users' vowel identification in noise can be explained by formant frequency cues (F1 and F2). Vowel identification was tested with 12 unilateral CI users in quiet and in noise. Formant cues were measured from vowels in each condition, specific to each subject's speech processor. Noise distorted the location of vowels in the F2 vs F1 plane in comparison to quiet. The best fit model to subjects' data in quiet produced model predictions in noise that were within 8% of actual scores on average. Predictions in noise were much better when assuming that subjects used a priori knowledge regarding how formant information is degraded in noise (experiment 1). However, the model's best fit to subjects' confusion matrices in noise was worse than in quiet, suggesting that CI users utilize formant cues to identify vowels in noise, but to a different extent than how they identify vowels in quiet (experiment 2).


Distinct Roles of Perilipins in the Intramuscular Deposition of Lipids in Glutamine-Supplemented, Low-, and Normal-Birth-Weight Piglets.
Piglets with low birth weight (LBW) usually have reduced muscle mass and increased lipid deposition compared with their normal-birth-weight (NBW) littermates. Supplementation of piglets with amino acids during the first days of life may improve muscle growth and simultaneously alter the intramuscular lipid deposition. The aim of the current study was to investigate the influence of glutamine (Gln) supplementation during the early suckling period on lipid deposition in the longissimus muscle (MLD) and the role of different perilipin (PLIN) family members in this process. Four groups were generated consisting of 72 male LBW piglets and 72 NBW littermates. Piglets were supplemented with either 1 g Gln/kg body weight or an isonitrogenous amount of alanine (Ala) between days post natum (dpn) 1 and 12. Twelve piglets per group were slaughtered at 5, 12, and 26 dpn, and muscle tissue was collected. Perilipins were localized by immunohistochemistry in muscle sections. The mRNA and protein abundances of PLIN family members and related lipases were quantified by quantitative RT-PCR (qPCR) and western blots, respectively. While PLIN1 was localized around lipid droplets in mature and developing adipocytes, PLIN2 was localized at intramyocellular lipid droplets, PLIN3 and 4 at cell membranes of muscle fibers and adipocytes, and PLIN5 in the cytoplasm of undefined cells. The western blot results indicated higher protein abundances of PLIN2, 3, 4, and 5 in LBW piglets (p < 0.05) at 5 dpn compared with their NBW littermates independent of supplementation, while not directly reflecting the mRNA expression levels. The mRNA abundance of PLIN2 was lower while PLIN4 was higher in piglets at 26 dpn in comparison with piglets at 5 dpn (p < 0.01). Relative mRNA expression of LPL and CGI-58 was lowest in piglets at 5 dpn (p < 0.001). However, ATGL mRNA was not influenced by birth weight or supplementation, but the Spearman correlation coefficient analysis revealed close correlations with PLIN2, 4, and 5 mRNA at 5 and 26 dpn (r > 0.5, p < 0.001). The results indicated the importance of birth weight and age for intramuscular lipid deposition and different roles of PLIN family members in this process, but no clear modulating effect of Gln supplementation.


Characteristics of reduced fat milks as influenced by the incorporation of folic acid.
Folic acid plays an important role in the prevention of neural tube defects (e.g., spina bifida and anencephaly), heart defects, facial clefts, urinary abnormalities, and limb deficiencies. Milk and milk products serve as a potential source for folic acid fortification because of the presence of folate-binding proteins that seem to be involved in folate bioavailability. Although milk is not a good source of folic acid, fortification could help in the prevention of the above-mentioned defects. The objective of this study was to examine the physicochemical characteristics of reduced fat milks fortified with folic acid. Reduced fat milks were prepared using 25, 50, 75, and 100% of the recommended dietary allowance of 400 microg of folic acid. Treatments included addition of folic acid at these levels before and after pasteurization. Color, pH, fat, protein, viscosity, folic acid concentration, folate-binding protein concentration, folate-binding protein profile, standard plate count, and coliform counts were determined on d 1, 7, 14, and 21. A consumer acceptability test was conducted on d 7. Data from the consumer panel were analyzed using ANOVA (PROC GLM) with means separation to determine the differences among treatments. Data obtained from the color, pH, fat, protein, viscosity, folic acid concentration, folate-binding protein concentration, standard plate count, and coliform counts were analyzed using the GLM with a repeated measure in time. Significant differences were determined at P < 0.05 using Tukey's Studentized Range Test. There were no differences in the electrophoretic mobility of folate-binding protein in the samples. The concentration of folic acid was significantly higher in reduced fat milks fortified with folic acid after pasteurization compared with the treatments in which folic acid was added before pasteurization. The consumer panelists did not find any significant differences in flavor, appearance, or texture of folic acid fortified reduced fat milks compared with that of the control. Fortification of reduced fat milks with folic acid can be accomplished without adversely affecting the product characteristics.