The patients' perspective of sustaining a fall in hospital: A qualitative study.
To understand the patient's perspective of falling in hospital. A fall in hospital can affect a patient physically and psychologically, increasing their hospital length of stay and potentially putting them at risk of further complications. Despite a wealth of literature on falls that focuses on risk assessment, preventive interventions and cost, very little research has focused on the experience of the patient that has fallen, particularly within the acute hospital setting. A qualitative phenomenological design was used to investigate the experience of falling in hospital. Twelve hospital inpatients that had recently fallen were interviewed while in hospital using unstructured interviews. The methodology was guided by Van Manen's approach to data collection and analysis. Three key themes emerged from the analysis: Feeling safe, Realising the risk and Recovering independence and identity. These themes describe a continuum whereby falling was not initially a concern to participants, who trusted staff to keep them safe, and tended to not seek assistance. As participants began to appreciate the reality of their falls risk, they felt disempowered by their loss of independence but were more receptive to receiving assistance. Finally, as participants recovered, their desire to regain independence increased. They wanted others to perceive them as physically competent, rather than as a frail older person, meaning they were more willing to take risks with mobility. The participants' perspective of falling describes a continuum of responses with participants positioned at different psychosocial standpoints: from initial denial of their risk of falling to realisation of the importance of their fall and acceptance of its repercussions. By understanding the patient's perspective of falling, nurses and other health professionals conducting risk assessment can tailor their discussions and interventions to the patient's perceptions and needs.


A visual framework for sequence analysis using n-grams and spectral rearrangement.
Protein sequences are often composed of regions that have distinct evolutionary histories as a consequence of domain shuffling, recombination or gene conversion. New approaches are required to discover, visualize and analyze these sequence regions and thus enable a better understanding of protein evolution. Here, we have developed an alignment-free and visual approach to analyze sequence relationships. We use the number of shared n-grams between sequences as a measure of sequence similarity and rearrange the resulting affinity matrix applying a spectral technique. Heat maps of the affinity matrix are employed to identify and visualize clusters of related sequences or outliers, while n-gram-based dot plots and conservation profiles allow detailed analysis of similarities among selected sequences. Using this approach, we have identified signatures of domain shuffling in an otherwise poorly characterized family, and homology clusters in another. We conclude that this approach may be generally useful as a framework to analyze related, but highly divergent protein sequences. It is particularly useful as a fast method to study sequence relationships prior to much more time-consuming multiple sequence alignment and phylogenetic analysis. A software implementation (MOSAIC) of the framework described here can be downloaded from http://bioinformatics.org.au/mosaic/ firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


CYP2C19 genotype and the PPIs--focus on rabeprazole.
Amongst all the proton pump inhibitors (PPI), the hepatic metabolism of rabeprazole is least dependent on the CYP4502C19 system. Rabeprazole is therefore the PPI least affected by CYP4502C19 genetic polymorphism. This unique feature of rabeprazole complements rabeprazole's fast onset of action, and may lead to profound and consistent inhibition of gastric acid secretion in the treatment of acid-related disorders.


Stronger shared taste for natural aesthetic domains than for artifacts of human culture.
Individuals can be aesthetically engaged by a diverse array of visual experiences (paintings, mountain vistas, etc.), yet the processes that support this fundamental mode of interaction with the world are poorly understood. We tested whether there are systematic differences in the degree of shared taste across visual aesthetic domains. In Experiment 1, preferences were measured for five different visual aesthetic domains using a between-subjects design. The degree of agreement amongst participants differed by domain, with preferences for images of faces and landscapes containing a high proportion of shared taste, while preferences for images of exterior architecture, interior architecture and artworks reflected strong individual differences. Experiment 2 used a more powerful within-subjects design to compare the two most well matched domains-natural landscapes and exterior architecture. Agreement across individuals was significantly higher for natural landscapes than exterior architecture, with no differences in reliability. These results show that the degree of shared versus individual aesthetic preference differs systematically across visual domains, even for photographic images of real-world content. The findings suggest that the distinction between naturally occurring domains (e.g. faces and landscape) versus artifacts of human culture (e.g. architecture and artwork) is a general organizational principle governing the presence of shared aesthetic taste. We suggest that the behavioral relevance of naturally occurring domains results in information processing, and hence aesthetic experience, that is highly conserved across individuals; artifacts of human culture, which lack uniform behavioral relevance for most individuals, require the use of more individual aesthetic sensibilities that reflect varying experiences and different sources of information.


Phylogenetic relationship of Ornithobacterium rhinotracheale strains.
The bacterium Ornithobacterium rhinotracheale is associated with respiratory disease in wild birds and poultry. In this study, the phylogenetic analysis of nine reference strains of O. rhinotracheale belonging to serovars A to I, and eight Mexican isolates belonging to serovar A, was performed. The analysis was extended to include sequences from another 23 strains available in the public domain. The analysis showed that the 40 sequences formed six clusters, I to VI. All eight Mexican field isolates were placed in cluster I. One of the reference strains appears to present genetic diversity not previously recognized and was placed in a new genetic cluster. In conclusion, the phylogenetic analysis of O. rhinotracheale strains, based on the 16S rRNA gene, is a suitable tool for epidemiologic studies.


Association of the Respiratory Severity Score with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension in Infants Born Extremely Preterm.
To test the hypothesis that elevations in the respiratory severity score (RSS) are associated with increased risk of bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH). Retrospective cohort study of infants born extremely preterm admitted to a BPD center between 2010-2018. Echocardiograms obtained ≥36 weeks' post-menstrual age (PMA) were independently adjudicated by two blinded cardiologists to determine the presence/absence of BPD-PH. Multivariable logistic regression estimated the association between RSS with BPD-PH. BPD-PH was observed in 68/223 (36%) of subjects. The median RSS at time of echocardiography was 3.04 (Range 0-18.3). A one-point increase in RSS was associated with BPD-PH, aOR 1.3 (95% CI 1.2-1.4), after adjustment for gestational age and PMA at time of echocardiography. Elevations in the RSS were associated with a greater risk of BPD-PH. Prospective studies are needed to determine the validity and performance of RSS as a clinical susceptibility/risk biomarker for BPD-PH.


Effect of interseed spacing, tissue perfusion, thermoseed temperatures and catheters in ferromagnetic hyperthermia: results from simulations using finite element models of thermoseeds and catheters.
Finite element heat-transfer models of ferromagnetic thermoseeds and catheters are developed for simulating ferromagnetic hyperthermia. These models are implemented into a general purpose, finite element computer program to solve the bioheat transfer equation. The seed and catheter models are unique in that they have fewer modeling constraints than other previously developed thermal models. Simulations are conducted with a 4 x 4 array of seeds in a multicompartment tissue model. The heat transfer model predicts that fractions of tumor greater than 43 degrees C are between 8 and 40% lower when seed temperatures depend on power versus models which assume a constant seed temperature. Fractions of tumor greater than 42 degrees C, in simulations using seed and catheter models, are between 3.3 and 25% lower than in simulations with bare seeds. It is demonstrated that an array of seeds with Curie points of 62.6 degrees C heats the tumor very well over nearly all blood perfusion cases studied. In summary, results herein suggest that thermal models simulating ferromagnetic hyperthermia should consider the power-temperature dependence of seeds and include explicit models of catheters.


Platelet gel for the treatment of traumatic loss of finger substance.
Autologous or allogenic platelet gel is a blood component that exploits the effects of the cytokines contained in platelet α granules to stimulate repair processes. The properties of platelet gel were first tested on chronic ulcers to accelerate healing and later in orthopaedic, dental, vascular and cardiothoracic surgery. In our centre, we have been using platelet gel for 5 years, first for surgical patients with difficult wounds, then for orthopaedic patients undergoing osteosynthesis surgery and patients with ulcers not responding to traditional therapies. Subsequently we decided to extend the use of platelet gel also to amputations or traumatic loss of tissue of fingers. In this article we present the results obtained over 5 years concerning 115 patients with finger amputations or wounds treated with platelet gel in our Service of Transfusion Medicine. Platelets were obtained fom allogeneic buffy coats (10 mL) and the gel was produced by adding thrombin to concentrated platelets. The decision to use homologous platelet gel was based on its limited cost, ease of preparation, almost unlimited availability, the fact that the number of platelets that can be collected is much higher than the therapeutic range and so able to replace the losses due to secondary medication, and last, but not least, it causes no discomfort to patients. The safety of the product was ensured by virology tests including molecular biology studies. The recovery of soft tissue in all patients ranged from 80 to 100%; the median time for this recovery was 3 weeks (range, 10 days - 6 weeks). Approximately 60% of the patients complained of local hypoaesthesia for some weeks; 30% of the patients developed hyperaesthesia, which resolved completely within 6-8 weeks from starting treatment. Loss of bone tissue represented an obstacle to total tissue recovery, but the aesthetic results were satisfactory in nearly all cases. All patients showed good compliance, both because of the low frequency of medications (at most, twice a week) and because of the painless platelet gel applications. The only negative aspect was abnormal nail growth in a case of distal partial amputation of a finger. In conclusion, we believe that platelet gel can be very useful in patients with traumatic or surgical loss of finger tissue, since it can resolve critical situations thus avoiding amputation of residual tissue and compromised joint function.


Split-liver transplantation in 2 adults: significance of caudate lobe outflow reconstruction in left lobe recipient: case report.
Split-liver transplantation is a well-known procedure for increasing the donor pool. The procedure is commonly used in 1 adult and 1 child, but is less commonly performed in 2 adults because of technical difficulty and poor outcome in left-lobe recipients. Preservation of caudate lobe function is important in recipients with borderline graft-recipient weight ratio to achieve better results. Herein, we report a case in which caudate lobe outflow was reconstructed in a left lobe with a caudate lobe graft in split-liver transplantation in 2 adults.


Design of a cellular-uptake-shielding magnetic catcher for cancer cell separation.
Fluorescent-magnetic-biotargeting multifunctional microcapsules (FMBMMs) are designed and fabricated via layer-by-layer assembly. It is found that the arginine-glycine-aspartate-modified FMBMMs were capable of sensitively detecting and efficiently isolating approximately 80% target cancer cells within 20 min. More importantly, FMBMMs present a general template for identifying and separating multiple types of cancer cells simply by altering the recognition motif.


The extent of the human odontoblast process as determined by transmission electron microscopy: the hypothesis of a retractable suspensor system.
After fixation of fully formed human permanent teeth in liquid nitrogen the extent of the odontoblast process has been studied in transmission electron microscopy. The odontoblast process, limited by a trilaminar plasma membrane, was found just under the dentine-enamel junction. In cross section, the cytoplasm contained a granular mass with light and/or dense core granules. Bare unmyelinated nerve-like fibrils were seen in close connection with the odontoblast process. In the periodontoblastic space non calcified collagen fibrils were occasionally present. Cytoplasmic globules and granules limited by a trilaminar membrane, with occasional myelinic figures were also noted in the peripheral tubular lumens. The hypothesis of a retractable suspensor system is advanced to explain why in normal fixation conditions the odontoblast processes associated with nerve fibrils have not been observed in the outer layers of dentine.


Body temperature of trauma patients on admission to hospital: a comparison of anaesthetised and non-anaesthetised patients.
Hypothermia at hospital admission has been found to independently predict increased mortality in trauma patients. Objectives To establish if patients anaesthetised in the prehospital phase of care had a higher rate of hypothermia than non-anaesthetised patients on admission to hospital. Retrospective review of admission body temperature in 1292 consecutive prehospital trauma patients attended by a physician-led prehospital trauma service admitted to The Royal London Hospital between 1 July 2005 and 31 December 2008. 38% had a temperature recorded on admission. There was a significant difference in body temperature between the anaesthetised group (N=207) and the non-anaesthetised group (N=287): mean (SD) 35.0 (2.1) vs 36.2 (1.0)°C, respectively (p<0.001). No significant seasonal body temperature variation was demonstrated. This study confirmed that patients anaesthetised in the prehospital phase of care had a significantly lower admission body temperature. This has led to a change in the author's prehospital practice. Anaesthetised patients are now actively surface heated and have whole body insulation to prevent further heat loss in an attempt to conserve body temperature and improve outcome. This is an example of best in-hospital anaesthetic practice being carried out in the prehospital phase.


Effects of estradiol on lipoprotein lipase activity and lipid availability in exercised male rats.
The effects of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1 x 100 g body wt-1) and exercise on tissue lipid content and lipoprotein lipase (LPL) activity were determined in male rats. Estradiol administration significantly (P < 0.05) increased fatty acid contents of resting adipose, plasma, and white and red vastus muscle tissues and red vastus muscle triacylglycerol. Adipose and plasma fatty acids and red and white vastus muscle triacylglycerol were significantly higher in exercised estradiol-administered animals than in exercised oil-administered animals. Estradiol administration significantly reduced resting adipocyte LPL activity by 71% and increased myocardial LPL activity by 96%. After exercise, red vastus LPL activity was significantly increased by 76% in estradiol-administered animals compared with oil-administered animals. Ratios of red vastus to adipose LPL activity and myocardial to adipose LPL activity at rest and after exercise were significantly greater in estradiol-administered than in oil-administered animals. Estradiol administration significantly increased the ratio of white vastus to adipose LPL activity of exercised animals. These data indicate that estradiol increases the availability of lipid substrate to exercising muscle from multiple sources, including adipose, plasma, and intracellular muscle triacylglycerol. The absolute increases in muscle LPL activity, combined with a greater ratio of muscle to adipose LPL activity, lead to increased distribution of plasma triacylglycerol-derived fatty acids toward muscle.


Comparison of the medial sural artery perforator flap with the radial forearm flap for head and neck reconstructions.
For a small to medium-sized defect in the head and neck region after cancer ablation, the free radial forearm flap is commonly used. More recently, the free medial sural artery perforator flap has been used as an alternative. The authors investigated the outcome and donor-site morbidity of the free radial forearm flap and the free medial sural artery perforator flap for head and neck reconstruction. Between July of 2004 and May of 2008, 47 patients (45 men and two women) underwent head and neck reconstruction, with a free radial forearm flap used in 29 cases and a free medial sural artery perforator flap used in 18 cases. Patient age ranged from 30 to 70 years (mean, 50.5 years). The success rate of free radial forearm and free medial sural artery perforator flaps was 100.0 percent. There was no significant difference in flap harvest time (57.5 minutes versus 60 minutes), hospital stay (24.5 days versus 19.7 days), or overall recipient-site complication rate (20.7 percent versus 11.1 percent). The free medial sural artery perforator flap group had a better subjective functional and cosmetic outcome in the donor site than the free radial forearm flap group (two-sided Fisher's exact test, p = 0.0002). The medial sural artery perforator flap is a good alternative for head and neck reconstruction of small defects. The medial sural artery perforator flap is advantageous with regard to less donor-site morbidity compared with the free radial forearm flap. The unfamiliarity of the pedicle anatomy of the medial sural artery perforator flap must be weighed against an easily harvested radial forearm flap.


Polyethylene subluxation: a radiographic sign of locking mechanism failure after modular total knee arthroplasty.
Tibial insert locking mechanisms are intended to limit interface motion and "backside" wear in modular total knee arthroplasty (TKA). Nevertheless, anterior polyethylene subluxation is occasionally apparent on lateral radiographs after TKA, suggesting locking mechanism failure. We retrospectively identified 10 modular posterior-stabilized implants of a single design that were found to have failure of the locking mechanism at the time of revision surgery for osteolysis. Operative reports were reviewed for the presence of backside wear, and preoperative radiographs were inspected for polyethylene subluxation. All 10 implants demonstrated significant backside wear. Nine had anterior polyethylene subluxation evident on preoperative radiographs. Anterior polyethylene subluxation on the lateral radiograph is a subtle sign of failure of the locking mechanism in this modular posterior-stabilized TKA.


Monitoring cell therapy using iron oxide MR contrast agents.
Given the remarkable progress that has recently been obtained in animal studies, the clinical use of stem and progenitor cells to correct or replace defective cell populations may soon become a reality. In order to develop effective cell therapies, the location and distribution of these cells must be determined in a non-invasive manner. Magnetic resonance (MR) tracking of magnetically labeled cells following transplantation or transfusion may fulfill this requirement. Indeed, a series of recent studies indicate that MRI cell tracking has great potential for further evaluation and optimization of cell therapy. Due to its biocompatibility and strong effects on T2(*) relaxation, iron oxide nanoparticles appear to be the contrast agent of choice, and several methods now exist to shuttle sufficient amount of these compounds into cells. Most of the tracking work has been carried out in disease models of the central nervous system, but, recently, the infarcted heart has also received attention. With its excellent spatial resolution and the ability to track labeled cells over prolonged periods of time, MR monitoring of cell therapy is likely to become an important technique in the foreseeable future.


Effects on inadvertent endplate fracture following lateral cage placement on range of motion and indirect spine decompression in lumbar spine fusion constructs: A cadaveric study.
The lateral transpsoas approach to interbody fusion is gaining popularity. Existing literature suggests that perioperative vertebra-related complications include endplate breach owing to aggressive enedplate preparation and poor bone quality. The acute effects of cage subsidence on stabilization and indirect decompression at the affected level are unknown. The purpose of this study was to compare the kinematics and radiographic metrics of indirect decompression in lumbar spines instrumented with laterally placed cages in the presence of inadvertent endplate fracture, which was determined radiographically, to specimens instrumented with lateral cages with intact endplates. Five levels in 5 specimens sustained endplate fracture during lateral cage implantation followed by supplementary fixation (pedicle screw/rod [PSR]: n = 1; anterolateral plate [ALP]: n = 4), as part of a larger laboratory-based study. Range of motion (ROM) in these specimens was compared with 13 instrumented specimens with intact endplates. All specimens were scanned using computed tomography (CT) in the intact, noninstrumented condition and after 2-level cage placement with internal fixation under a 400-N follower load. Changes in disc height, foraminal area, and canal area were measured and compared between specimens with intact endplates and fractured endplates. Subsidence in the single PSR specimen and 4 ALP specimens was 6.5 mm and 4.3 ± 2.7 mm (range: 2.2-8.3 mm), respectively. ROM was increased in the PSR and ALP specimens with endplate fracture when compared with instrumented specimens with intact endplates. In 3 ALP specimens with endplate fracture, ROM in some motion planes increased relative to the intact, noninstrumented spine. These increases in ROM were paralleled by increase in cage translations during cyclic loading (up to 3.3 mm) and an unpredictable radiographic outcome with increases or decreases in posterior disc height, foraminal area, and canal area when compared with instrumented specimens with intact endplates. Endplate fracture and cage subsidence noted radiographically intraoperatively or in the early postoperative period may be indicative of biomechanical instability at the affected level concomitant with a lack of neurologic decompression, which may require revision surgery.


Chemiluminescence detection of amino acids and related compounds using acidic potassium permanganate, manganese(IV) or tris(2,2'-bipyridine)ruthenium(III).
We have explored the chemiluminescence response of amino acids and related compounds (including the tripeptide glutathione, and disulfides: cystine, homocystine and glutathione disulfide) with several new adaptations of the permanganate and tris(2,2'-bipyridine)ruthenium(III) ([Ru(bipy)(3)](3+)) reagents and a recently developed colloidal manganese(IV) system. The selectivity of the permanganate reagent can be directed towards tyrosine or thiol compounds like cysteine, homocysteine and glutathione by manipulating reaction conditions (providing limits of detection of 4 nM tyrosine and 5 nM glutathione). Colloidal Mn(IV) produced measureable responses with all analytes, but was most suitable for tryptophan, tyrosine, thiols and disulfides, including α-lipoic acid and dihydrolipoic acid, for which the limits of detection were 30 nM and 20 nM, respectively. A stabilised form of [Ru(bipy)(3)](3+), prepared by oxidising [Ru(bipy)(3)](ClO(4))(2) in acetonitrile, exhibited similar selectivity to that of the conventional aqueous reagent. The [Ru(bipy)(3)](3+) reagent was effective for the detection of secondary amino acids such as proline and hydroxyproline, as well as the disulfide, homocystine.


A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity.
Though simple and attractive, the role of hydration for the prophylaxis of contrast nephrotoxicity has not been definitively established. We prospectively evaluated the role of deliberate saline hydration in patients undergoing nonemergency cardiac catheterization. Patients (n = 53) were randomized on the day prior to scheduled catheterization to one of two groups - group 1 (n = 27) received normal saline for 24 h (at a rate of 1 ml/kg/h) beginning 12 h prior to scheduled catheterization, and group 2 (n = 26) were allowed unrestricted oral fluids. Serum creatinine measured 24 and 48 h postcardiac catheterization was compared to the pre-randomization baseline value. The mean baseline calculated creatinine clearance was 79.6 +/- 31.9 ml/min and the mean baseline creatinine was 106 +/- 28 micromol/l. An increase in serum creatinine by at least 44.2 micromol/l (0.5 mg/dl), within 48 h of contrast exposure, was considered to represent clinically significant acute renal insufficiency. Ten subjects (18.9%) developed acute renal insufficiency. The incidence of acute renal insufficiency was significantly lower in group 1 (1 out of 27) as compared to group 2 (9 out of 26; p = 0.005 for comparison between groups; relative risk 0.11, 95% confidence interval 0.015 to 0.79). Twenty-four hours after contrast exposure, the mean increase in creatinine was less in group 1 vs. group 2 (8 +/- 11 vs. 20 +/- 21 micromol/l, p = 0.02). The increase in creatinine was not significantly different in group 1 vs. group 2 48 h after contrast exposure (12 +/- 21 vs. 29 +/- 40 micromol/l, p = 0.17). Deliberate saline hydration decreases the incidence of contrast-related acute renal failure and the severity of contrast-induced renal dysfunction in patients undergoing non-emergency cardiac catheterization.


[Venous thromboembolic complications in oncological patients: present-day possibilities of effective and safe anticoagulant therapy].
Cancer-associated thromboembolic complications in malignant neoplasms are commonly encountered. They deteriorate the course of the underlying disease and are frequent causes of death. The oncological patient is at high risk of not only thrombosis but haemorrhage during anticoagulant therapy. Recent randomized clinical trials have positively appreciated the possibilities of direct oral anticoagulants in treatment and prevention of thromboses in oncological patients. Analysing subgroups in these studies demonstrated that direct oral anticoagulants during long-term administration were at least as effective and safe as vitamin K antagonists. The most significant by the number of cases, duration of therapy, and methodology of analysis are the reports regarding rivaroxaban - an oral, direct factor Xa inhibitor. There are also findings obtained in a separate randomized study, confirming efficacy and safety of rivaroxaban in treatment of patients with cancer-associated venous thromboembolic complications as compared with therapy with low-molecular-weight heparins. Namely these results formed the basis for the guidelines of the International Society on Thrombosis and Hemostasis (SSC ISTH), according to which rivaroxaban may be regarded as an alternative to low-molecular-weight heparins in certain clinical situations.


Experimental degeneration of motor and sensory cortical terminals in the cuneate nucleus of the monkey (Macaca fascicularis).
A total of nine monkeys (Macaca fascicularis) of both sexes was used for the present study. Eight monkeys were used for either motor or sensory cortical lesions, and were allowed to survive for 1--7 days post-operatively. No degenerating nerve terminals were observed 1 day following either motor or sensory cortical lesions. After a motor cortical lesion, most degenerating terminals were seen on the third and only a few on the fifth day. Following a sensory cortical lesion, most degenerating terminals were seen on the fifth and fewer on the third and seventh days. Two types of degenerative changes were observed: granular and electron-dense. Granular change was more evident after the shorter survival periods, while the electron-dense type of degeneration was more commonly seen in animals which were allowed to survive longer after operation. The cortical axon terminals were small and contained either round or flattened synaptic vesicles. Most of those axons containing flattened vesicles originated from the sensory cortex, but a few came from the motor cortex. Vice versa, most of those axons containing round vesicles appeared to arise from the motor cortex and only a few from the sensory cortex. Cortical axon terminals containing round synaptic vesicles formed asymmetrical synapses with small to medium-sized dendrites poor in organelles. In a few instances such cortical terminals were observed to be postsynaptic to other axon terminals containing flattened vesicles. No cortical axon terminal was observed to terminate presynaptically on another axon terminal. Cortical terminals containing flattened vesicles formed symmetrical synapses with dendritic profiles of varying diameters, some of which were the proximal dendrites of Group II neurons. No cortical axon terminals containing flattened vesicles have been observed to form axo-axonal synapses in the cuneate neuropil.


A new species of the genus Attheyella (Copepoda: Harpacticoida: Canthocamptidae) from Gosu cave in Korea.
A new species, Attheyella namkungi sp. nov., is described from Gosu cave at Danyang, Chungcheongbuk-do, South Korea. This species bears a superficial resemblance to A. coreana Miura, 1969 in having a 2-segmented mandibular palp with only four smooth apical setae, and in the armature formulae of the antennary exopod and thoracic legs. However the new species is clearly distinguishable by the non-sexually dimorphic caudal rami, two long plumose setae and a short seta on leg 6, and the absence of the setular row at the inner lateral margin of each caudal ramus. The new species is characterized from other congeners by having two adjacent inner spines on female leg 3 endopod-2, the caudal ramus twice as long as its width, absence of a barbed apophysis on male leg 3 endopod-2, and the seta number of legs 5 and 6. A key to the Korean species of the genus Attheyella is provided.


Direct phase determination from neutron diffraction data of the structure of melampodin.
The structure of a large complex molecule, C(21)H(24)O(9), has been solved directly from neutron diffraction data by using sigma-2 and tangent refinement methods. As a consequence, the neutron diffraction technique must be reevaluated as a possible primary tool for crystal structure determination.


Content of transfluthrin in indoor air during the use of electro-vaporizers.
The quality of indoor air evokes increasing interest; however, no standards have been developed which determine the content of pesticides in the air of living space. At present, insecticides are increasingly more frequently applied to control household pests, flies, mosquitoes, termites and other harmful insects. In this study, the content of transfluthrin was measured indoors after the application of two consumer products containing this active substance, using commercially available electro-vaporizers. It was found that during the application of insecticides in the form of gel and liquid the mean concentration of transfluthrin in the air was 1.295-2.422 ug/m(3) and 3.817-5.227 ug/m(3), respectively. The concentration of an active agent in the air did not depend on the day of application. The concentration of transfluthrin was higher when used in the form of a liquid than a gel preparation. 18-24 hours after the discontinuation of the use of the preparation no active agent was found in the air. As long as the standards are developed regulating the content of insecticides in the air of living spaces and utility rooms, the most important method of preventing their potential hazardous effect is informing the users of these preparations about the occurrence of active substances in indoor air, and eventual risk of exposure to the effect of pesticides during their application at home.


Protic additives determine the pathway of CdSe nanocrystal growth.
The formation of semiconductor nanocrystals by hot-injection synthesis follows complex reaction mechanisms that are not yet fully understood. In particular the occurrence of intermediate species indicated by sharp, stationary spectral lines poses an important deviation from the predictions of classical nucleation theory. We show that trace amounts of water and other protic additives strongly impact the structure of these reaction intermediates, forming either coordination polymers under dry conditions or small clusters in the presence of moisture. These intermediates bind monomer during the initial nucleation phase. The structure of the intermediate determines the monomer release rate, either continuously or in a rapid dissolution event, and hence controls the reaction kinetics. From this we propose a kinetic model that allows us to predict secondary nucleation events. By directing the type of intermediate formed, protic additives provide a lever to manipulate this equilibrium and control nanocrystal synthesis in a rational fashion.


Iron-induced Hypophosphatemic Osteomalacia-An Atypical Case of Bilateral Femoral Stress Fractures.
We present a case of a 61-year-old healthy man who had bilateral femoral neck insufficiency fractures attributed to repeated iron transfusions, causing iron-induced hypophosphatemic rickets, requiring surgical intervention. Atraumatic insufficiency fractures present a diagnostic dilemma in orthopaedics. Chronic fractures with no acute precipitating trigger can often go unrecognized until complete fracturing or displacement occurs. Early identification of the risk factors in conjunction with a comprehensive history, clinical examination, and imaging can potentially avoid these serious complications. Atraumatic femoral neck insufficiency fractures have been sporadically reported in the literature, often unilateral and attributed to the use of long-term bisphosphonates. Through this case, we elaborate on the relatively unknown link between iron transfusions and insufficiency fractures. This case highlights the importance of early detection and imaging of such fractures from an orthopaedic perspective.


Differential expression of beta 2-integrins and cytokine production between gammadelta and alphabeta T cells in experimental autoimmune encephalomyelitis.
The expression of beta 2-integrins on gammadelta T cells in naïve mice or those with experimental autoimmune encephalomyelitis (EAE) remains poorly characterized. We compared beta 2-integrin expression and cytokine production between gammadelta and alphabeta T cells over the acute course of EAE. We observed that unlike in alphabeta T cells, beta 2-integrin expression on gammadelta T cells increased significantly from baseline, peaked at Day 10, and remained unchanged in the draining lymph nodes or declined in the spleen and CNS by Day 15. In addition, IFN-gamma- and TNF-alpha-producing gammadelta T cells infiltrated the CNS rapidly and produced significantly more of these cytokines than alphabeta T cells throughout the course of EAE. These results suggest unique roles for beta 2-integrins in the trafficking of gammadelta versus alphabeta T cells during EAE and that gammadelta T cells infiltrate the CNS rapidly, producing cytokines, which modulate acute disease.


Binaural electric-acoustic interactions recorded from the inferior colliculus of Guinea pigs: the effect of masking observed in the central nucleus of the inferior colliculus.
To investigate the electric-acoustic interactions within the inferior colliculus of guinea pigs and to observe how central masking appears in invasive neural recordings of the inferior colliculus (IC). A platinum-iridium wire was inserted to scala tympani through cochleostomy with a depth no greater than 1 mm for intracochlear stimulation of electric pulse train. A 5 mm 100 µm, single-shank, thin-film, penetrating recording probe was inserted perpendicularly to the surface of the IC in the coronal plane at an angle of 30-40° off the parasagittal plane with a depth of 2.0-2.5 mm. The peripheral and central masking effects were compared using electric pulse trains to the left ear and acoustic noise to the left ear (ipsilateral) and to the right ear (contralateral). Binaural acoustic stimuli were presented with different time delays and compared with combined electric and acoustic stimuli. The averaged evoked potentials and total spike numbers were measured using thin-film electrodes inserted into the central nucleus of the IC. Ipsilateral noise had more obvious effects on the electric response than did contralateral noise. Contralateral noise decreased slightly the response amplitude to the electric pulse train stimuli. Immediately after the onset of acoustic noise, the response pattern changed transiently with shorter response intervals. The effects of contralateral noise were evident at the beginning of the continuous noise. The total spike number decreased when the binaural stimuli reached the IC most simultaneously. These results suggest that central masking is quite different from peripheral masking and occurs within the binaural auditory system, and this study showed that the effect of masking could be observed in the IC recording. These effects are more evident and consistent with the psychophysical data from spike number analyses than with the previously reported gross potential data.


Combined enzymatic degradation of proteoglycans and collagen significantly alters intratissue strains in articular cartilage during cyclic compression.
As degenerative joint diseases such as osteoarthritis (OA) progress, the matrix constituents, particularly collagen fibrils and proteoglycans, become damaged, therefore deteriorating the tissue's mechanical properties. This study aims to further the understanding of the effect of degradation of the different cartilage constituents on the mechanical loading environment in early stage OA. To this end, intact, collagen- and proteoglycan-depleted cartilage plugs were cyclically loaded in axial compression using an experimental model simulating in vivo cartilage-on-cartilage contact conditions in a micro-MRI scanner. Depletion of collagen and proteoglycans was achieved through enzymatic degradation with collagenase and chondroitinase ABC, respectively. Using a displacement-encoded imaging sequence (DENSE), strains were computed and compared in intact and degraded samples. The results revealed that, while degradation with one or the other enzyme had little effect on the contact strains, degradation with a combination of both enzymes caused an increase in the means and variance of the transverse, axial and shear strains, particularly in the superficial zone of the cartilage. This effect indicates that the balance between cartilage matrix constituents plays an essential role in maintaining the mechanical properties of the tissue, and a disturbance in this balance leads to a decrease of the load bearing capacity associated with degenerative joint diseases such as OA.


Japanese sisters associated with pseudohomozygous familial hypercholesterolemia and sitosterolemia.
Pseudohomozygous familial hypercholesterolemia is a rare condition of unknown etiology. Sitosterolemia is a rare autosomal recessively inherited disorder that is characterized by premature coronary artery disease, cutaneous xanthomas, and increased plasma plant sterols and 5alpha-stanols. Only a few cases of both sitosterolemia and pseudohomozygous familial hypercholesterolemia have been reported. In this study, we report two sisters with both conditions. With a low-cholesterol diet (< 250 mg/day), serum cholesterol concentration decreased rapidly to an almost normal level and cutaneous xanthomas gradually regressed and finally disappeared; however, plant sterol levels did not change during the period. Plant sterols should be measured in patients considered to have pseudohomozygous familial hypercholesterolemia. The two conditions in this family may have been the results of a single gene mutation. The findings also indicate that low cholesterol diet therapy is effective for the treatment of hypercholesterolemia but not of sitosterolemia in this family.


Management and complications of anesthesia for transvenous electrical cardioversion of atrial fibrillation in horses: 62 cases (2002-2006).
To describe management of anesthesia for transvenous electrical cardioversion (TVEC) in horses and report perianesthetic complications. Retrospective case series. 62 horses with atrial fibrillation and without underlying cardiac disease and 60 horses without atrial fibrillation. Medical records of horses with atrial fibrillation anesthetized for TVEC were reviewed, as were records of horses without atrial fibrillation anesthetized for magnetic resonance imaging (MRI). The TVEC group horses were compared with MRI group horses for incidence of intraoperative bradycardia and use of inotropic drugs. Data obtained included patient signalment, weight, duration of anesthesia, heart rate and arterial blood pressure during anesthesia, anesthetic drugs administered, mode of ventilation, perioperative complications, and quality of recovery. The TVEC group horses were > 1 year of age and were predominantly Standardbreds. The TVEC group horses underwent a total of 76 anesthetic episodes. For 40 (52.6%) anesthetic episodes, horses received xylazine only for premedication, and for 26 (34.2%) anesthetic episodes, horses received xylazine and butorphanol. Induction of anesthesia consisted of ketamine administration in various combinations with diazepam and guaifenesin for 74 (97.4%) anesthetic episodes and ketamine alone for 2 (2.6%). Bradycardia in horses was encountered during 15 of 76 (19.7%) anesthetic episodes. Minor signs of possible postanesthetic myopathy occurred following 6 (7.9%) anesthetic episodes. No significant difference was found between TVEC and MRI group horses regarding incidence of bradycardia and inotropic drug administration. Short-duration anesthesia for TVEC of atrial fibrillation in horses without underlying cardiac disease was a safe procedure.


Predictors of the longitudinal course of major depression in a Canadian population sample.
Most psychiatric epidemiologic studies have used cross-sectional methods, resulting in a lack of information about the longitudinal course of depressive disorders. The objective of our study was to describe the longitudinal epidemiology of major depressive episodes (MDEs) in a Canadian sample using data from the National Population Health Survey (NPHS). The NPHS started data collection in 1994 and has evaluated past-year MDE using repeat interviews of the same cohort every 2 years since then. In our study, we examined the number of weeks depressed during years when MDEs occurred, the proportion of respondents having MDEs at consecutive cycles, and MDE counts during follow-up. A sizable proportion of MDEs were brief: about one-half of respondents with past-year MDE reported 8 or fewer weeks of depression during that year. Less than 10% reported that they were depressed for the entire year. However, a larger proportion (19.1%) fulfilled criteria for MDE on consecutive interview cycles, suggesting either persistence or rapid recurrence. The mean number of detected MDEs among those with at least 1 detected MDE up to 2006 was 2. Positive family history, evidence of comorbidity, negative cognitive style, stress, pain, and smoking were associated with a more negative course. The longitudinal course of MDE in the general population is heterogeneous, including a mixture of brief and more protracted MDEs. Many risk factors for MDE are also associated with a negative course, exceptions being (younger) age and sex. These epidemiologic observations may assist with identification of patients requiring more intensive management in clinical practice.


The cytotoxic effects of preserved and preservative-free prostaglandin analogs on human corneal and conjunctival epithelium in vitro and the distribution of benzalkonium chloride homologs in ocular surface tissues in vivo.
To investigate the cytotoxicity of benzalkonium chloride (BAC)-containing ophthalmic solutions of prostaglandin analogs (latanoprost, travoprost, bimatoprost, and preservative-free (PF) tafluprost), BAC mixture (BACmix) and BAC homologs with different alkyl chain lengths using human corneal epithelial (HCE) and conjunctival epithelial (IOBA-NHC) cell cultures. The distribution of BAC homologs in rabbit ocular surface tissues in vivo was examined. The cells were exposed for one hour to prostaglandin analogs, BACmix and three homologs. Cytotoxicity was assessed with the WST-1 and lactate dehydrogenase (LDH) assays for cellular viability and cell membrane integrity. BAC 0.02% solution was instilled on the rabbit eye daily for 14 days and the concentrations of BAC homologs in external ocular tissues were determined. The order of decreasing cytotoxicity in the WST-1 test was latanoprost ≥ travoprost > bimatoprost ≥ PF tafluprost. IOBA-NHC cells were more sensitive than HCE cells. In HCE, only latanoprost diluted to 10% increased LDH leakage. In IOBA-NHC, LDH leakage was statistically significant with 3-10% travoprost and 10% latanoprost. The order of decreasing cytotoxicity of preservatives was C14 > C12 > BACmix > C16 in HCE and C12 > C14 > BACmix > C16 in IOBA-NHC. Following treatment with BAC 0.02% solution, the amounts of BAC-C12, -C14 and -C16 in rabbit cornea and conjunctiva, respectively were: 0.37 ± 0.08 and 2.64 ± 0.27 ng/mg; 0.42 ± 0.07 and 4.77 ± 0.43 ng/mg; 0.04 ± 0.01 and 0.54 ± 0.05 ng/mg. The cytotoxic effects of latanoprost, travoprost, and bimatoprost were dependent on the BAC concentration in their formulations. BACmix was cytotoxic at the concentrations above those corresponding to 0.001% BAC in ophthalmic medications. PF tafluprost was the least toxic of the drugs tested. Within studied BAC homologs, those with longer alkyl chain and higher lipophility penetrated effectively into rabbit external ocular tissues.


Regulatory variation within and between species.
Understanding how individuals differ from one another and from closely related species is a fundamental problem in biology. Recent evidence suggests that much of the variation both within and between species is due to differential gene regulation. Here we review differential gene regulation focusing on evolutionary-developmental (evo-devo) biology, global comparison of genomic sequences, whole-genome gene expression, and transcription factor (TF) binding profiles. We also explore the relationship between divergence rate of regulatory sequences, coding sequences, and TF binding events using several different measures and discuss their implications in the context of evolution of regulatory networks. Finally, we discuss the current status and future challenges in relating regulatory variation to the divergence across and within species.


sn-Glycerol-3-phosphate acyltransferases in plants.
sn-Glycerol-3-phosphate acyltransferase (GPAT) catalyzes the acylation at sn-1 position of glycerol-3-phosphate to produce lysophosphatidic acid (LPA). LPA is an important intermediate for the formation of different types of acyl-lipids, such as extracellular lipid polyesters, storage and membrane lipids. Three types of GPAT have been found in plants, localizing to the plastid, endoplasmic reticulum, and mitochondria. These GPATs are involved in several lipid biosynthetic pathways and play important biological roles in plant development. In the present review, we will focus on the recent progress in studying the physiological functions of GPATs and their metabolic roles in glycerolipid biosynthesis.


Crucial role of iron in epigenetic rewriting during adipocyte differentiation mediated by JMJD1A and TET2 activity.
Iron metabolism is closely associated with the pathogenesis of obesity. However, the mechanism of the iron-dependent regulation of adipocyte differentiation remains unclear. Here, we show that iron is essential for rewriting of epigenetic marks during adipocyte differentiation. Iron supply through lysosome-mediated ferritinophagy was found to be crucial during the early stage of adipocyte differentiation, and iron deficiency during this period suppressed subsequent terminal differentiation. This was associated with demethylation of both repressive histone marks and DNA in the genomic regions of adipocyte differentiation-associated genes, including Pparg, which encodes PPARγ, the master regulator of adipocyte differentiation. In addition, we identified several epigenetic demethylases to be responsible for iron-dependent adipocyte differentiation, with the histone demethylase jumonji domain-containing 1A and the DNA demethylase ten-eleven translocation 2 as the major enzymes. The interrelationship between repressive histone marks and DNA methylation was indicated by an integrated genome-wide association analysis, and was also supported by the findings that both histone and DNA demethylation were suppressed by either the inhibition of lysosomal ferritin flux or the knockdown of iron chaperone poly(rC)-binding protein 2. In summary, epigenetic regulations through iron-dependent control of epigenetic enzyme activities play an important role in the organized gene expression mechanisms of adipogenesis.


Electrical and magnetic properties of La(0.35)Sr(0.65)Ti(1-x)Fe(x)O(3) thin films.
We report that the La(0.35)Sr(0.65)Ti(1-x)Fe(x)O(3) system forms a solid solution within the composition range 0≤x≤0.5 and a room temperature magnetic semiconductor phase exists at x = 0.20. This system shows an anomalous Hall effect and is ferromagnetic with a large moment per Fe ion. The results show that the strong La doping provides sufficient carriers to the system to maintain carrier-mediated ferromagnetism for low Fe doping. Furthermore, the presence of ferromagnetism within this phase space raises the possibility that the conduction, and hence the magnetism, could be electronically controlled.


Species dependent impact of helminth-derived antigens on human macrophages infected with Mycobacterium tuberculosis: Direct effect on the innate anti-mycobacterial response.
In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.


Graph topology plays a determinant role in the evolution of cooperation.
We study the evolution of cooperation in communities described in terms of graphs, such that individuals occupy the vertices and engage in single rounds of the Prisoner's Dilemma with those individuals with whom they are connected through the edges of those graphs. We find an overwhelming dominance of cooperation whenever graphs are dynamically generated through the mechanisms of growth and preferential attachment. These mechanisms lead to the appearance of direct links between hubs, which constitute sufficient conditions to sustain cooperation. We show that cooperation dominates from large population sizes down to communities with nearly 100 individuals, even when extrinsic factors set a limit on the number of interactions that each individual may engage in.


Improving policy responses to the risk of air pollution.
This paper offers a brief review of the need for cost-benefit analysis (CBA) and the available policy instruments for air pollution. To prioritize different possible actions, one needs to know which source of pollution causes how much damage. This requires an impact pathway analysis, that is, an analysis of the chain emission --> dispersion --> dose-response function --> monetary valuation. The methodology for this is described and illustrated with the results of the ExternE (External Costs of Energy) project series of the European Commission. Two examples of an application to CBA are shown: one where a proposed reduction of emission limits is justified, and one where it is not. It is advisable to subject any proposed regulation to a CBA, including an analysis of the uncertainties. Even if the uncertainties are large and a policy decision may have to take other considerations into account, a well-documented CBA clarifies the issues and provides a basis for rational discussion. One of the main sources of uncertainty lies in the monetary valuation of premature mortality, the dominant contribution to the damage cost of air pollution. As an alternative, an innovative policy tool is described, the Life Quality Index (LQI), a compound indicator comprising societal wealth and life expectancy. It is applied to the Canada-wide standards for particulate matter and ozone. Regardless of monetary valuation, a 50% reduction of PM10 concentrations in Europe and North America has been shown to yield a population-average life expectancy increase on the order of 4 to 5 mo.


Interlayer Excitons with Large Optical Amplitudes in Layered van der Waals Materials.
Vertically stacked two-dimensional materials form an ideal platform for controlling and exploiting light-matter interactions at the nanoscale. As a unique feature, these materials host electronic excitations of both intra- and interlayer type with distinctly different properties. In this Letter, using first-principles many-body calculations, we provide a detailed picture of the most prominent excitons in bilayer MoS2, a prototypical van der Waals material. By applying an electric field perpendicular to the bilayer, we explore the evolution of the excitonic states as the band alignment is varied from perfect line-up to staggered (Type II) alignment. For moderate field strengths, the lowest exciton has intralayer character and is almost independent of the electric field. However, we find higher lying excitons that have interlayer character. They can be described as linear combinations of the intralayer B exciton and optically dark charge transfer excitons, and interestingly, these mixed interlayer excitons have strong optical amplitude and can be easily tuned by the electric field. The first-principles results can be accurately reproduced by a simple excitonic model Hamiltonian that can be straightforwardly generalized to more complex van der Waals materials.


Beacon immunoreactivity in the rat hypothalamus.
Beacon (BC) is a peptide of 73 amino acids, whose gene expression was first reported in the hypothalamus of Psammomys obesus (or Israeli sand rat). To appreciate better the functional role of BC in normal rats and sand rats, the distribution of BC immunoreactivity (irBC) and its subcellular localization were studied in the brain of Sprague-Dawley rats. In the hypothalamus, intense staining was present in neurons of the supraoptic (SO), paraventricular (PVH), and accessory neurosecretory nuclei and in cell processes of median eminence. Double labeling of the hypothalamic sections with mouse monoclonal oxytocin (OT) antibody and rabbit polyclonal BC antiserum revealed that nearly all OT-immunoreactive cells from SO, PVH, and accessory neurosecretory nuclei were irBC. Double labeling of the sections with guinea pig vasopressin (VP) antiserum and BC antiserum showed that a population of VP-immunoreactive neurons was irBC. By immunoelectron microscopy, immunoreactive product was associated with mitochondrial membranes or appeared as electron-dense bodies in many PVH and SO neurons. Most of the neurosecretory granules were unstained for BC. Taken together, our results indicate the presence of beacon in the OT-containing neurons and a population of VP-containing neurons, mostly associated with mitochondrial membrane. Insofar as the amino acids sequence of beacon is identical to that of ubiquitin-like 5, it is possible that the distribution of BC immunoreactivity noted in our study is that of ubiquitin-like 5 peptide in the rat hypothalamus.


Imaging of physeal injury: overuse.
As the intensity of youth participation in athletic activities continues to rise, the number of overuse injuries has also increased. A subset of overuse injuries involves the physis, which is extremely susceptible to injury. This paper aims to review the utility of the various imaging modalities in the diagnosis and management of physeal injuries in the skeletally immature population. A search for the keywords pediatric, physis, growth plate, x-ray, computed tomography, magnetic resonance imaging, and overuse injury was performed using the PubMed database. No limits were set for the years of publication. Articles were reviewed for relevance with an emphasis on the imaging of growth plate injuries. Retrospective literature review. Level 4. Three major imaging modalities (radiographs, computed tomography, and magnetic resonance imaging) complement each other in the evaluation of pediatric patients with overuse injuries. However, magnetic resonance imaging is the only modality that offers direct visualization of the physis, and it also offers the best soft tissue contrast for evaluating the other periarticular structures for concomitant injury. Imaging has an important role in the diagnosis of physeal injuries, and the information it provides has a tremendous impact on the subsequent management of these patients.


Associations Among Self-rated Oral Health, Subjective Oral Conditions, Oral Health Behaviours, and Oral Healthrelated Quality of Life (OHRQoL).
To evaluate the relationship between self-rated oral health, subjective oral conditions, oral health behaviours, and oral health-related quality of life (OHRQoL) in Chinese college students. An online cross-sectional survey was conducted, inviting college students from eastern China to participate. A total of 1708 participants were included. A structural equation model was constructed to explain and assess the associations among self-rated oral health, subjective oral conditions, oral health behaviours, and OHRQoL. Self-rated oral health had a direct positive effect on subjective oral conditions and OHRQoL. Oral health behaviours had direct negative impacts on subjective oral conditions and OHRQoL as well as on tooth condition perception and oral health interventions. Subjective oral conditions had a direct positive effect on OHRQoL. There was a positive correlation between oral health behaviours and self-rated oral health. In addition, subjective oral conditions partially mediated both the effect of oral health behaviours on OHRQoL and the effect of self-rated oral health on OHRQoL. There were influential associations between self-rated oral health, subjective oral conditions, oral health behaviours, and OHRQoL among college students in eastern China. Making the most of their association can be a guide to radically improving the oral health of college students.


Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma.
Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy. We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival 4+, 10 and 16 months), respectively; 3 patients had a partial response lasting 4, 6 and 8 months (survival 6+, 11+ and 14 months), respectively. Overall response was 27% (95% confidence interval 11-50%). Toxicity was relatively mild and mainly due to nausea. In 3 patients the dose of carboplatin was reduced because of grade 4 haematological toxicity. This described easy outpatient regimen shows comparable results as other polychemotherapeutic regimens in disseminated melanoma, but with a relatively mild toxicity profile.


[Consensus and controversy of endoscopic diagnosis and treatment of gastroenteropancreatic neuroendocrine tumors].
Neuroendocrine neoplasms(NENs) are relatively rare tumors originating from the diffuse neuroendocrine system, and gastrointestinal tract is one of the most common location of the tumors. Currently, the European Neuroendocrine Neoplasm Society (ENETS) and the National Comprehensive Cancer Network (NCCN) have released the international guidelines for NENs management. And also, experts from Chinese Society of Clinical Oncology (CSCO) have proposed "The Consensus on Gastroenteropancreatic Neuroendocrine Neoplasm in China" in 2016, which is also one of the most important reference standard for the diagnosis and treatment of gastroenteropancreatic(GEP) NENs in China. Here we will interpret these three guidelines or consensus. There are few controversies about endoscopic management principle for GEP-NEN of different locations and sizes among these three guidelines or consensus, but for small NENs without involving intrinsic muscularis, endoscopic resection is recommended and considered. We hope that this interpretation may help clinicians for clinical decision making.


Anatomical Predictors of Flared Limb Complications in Endovascular Aneurysm Repair.
Purpose: To evaluate possible predictors of complications with flared iliac stent-graft limbs for ectatic common iliac arteries (CIAs) associated with abdominal aortic aneurysms treated with endovascular aneurysm repair (EVAR). Materials and Methods: A retrospective comparative analysis was conducted of 533 EVAR patients (mean age 75 years; 442 men) treated between 2012 and 2017 who had complications associated with the stent-graft limbs (n=1066). Complications, including type Ib endoleak, type IIIa endoleak, and limb occlusion, were compared between patients with nondilated (<16 mm) CIAs treated with standard iliac limbs (SLs, n=808) vs patients with ectatic CIAs treated with flared limbs (FLs, n=258). Follow-up included a duplex scan at 3, 6, and 12 months and yearly thereafter; computed tomography angiography was performed in case of iliac complications. Risk factors for iliac complications in FLs were investigated using Cox regression and Kaplan-Meier analyses; results of the regression analysis are presented as the hazard ratio (HR) and 95% confidence interval (CI). Results: Overall, no iliac complications occurred at 30 days, but over a mean follow-up of 38±8 months, there were 10 (1%) events (4 limb occlusions, 6 type Ib endoleaks): 7 (3%) in FLs and 3 (0.4%) in SLs (p=0.20). Kaplan-Meier analysis found no differences at 5 years in SLs vs FLs for freedom from limb occlusion (99%±1% vs 98%±1%, respectively; p=0.30) or type Ib endoleak (96%±3% vs 97%±1%, respectively; p=0.44). Similarly, the overall 5-year iliac complication rates were similar in SLs vs FLs (96%±3% vs 95%±2%, p=0.21). Regression analysis found CIA length ≤30 mm (HR 4.7, 95% CI 1.02 to 21.6, p=0.04) and a diameter ≥20 mm (HR 7.8, 95% CI 1.05 to 64.8, p=0.03) to be independent predictors of iliac complications in FLs. Kaplan-Meier estimates of iliac complication-free survival in FLs were significantly worse when the CIA length was ≤30 mm (79%±9% vs 98%±1%, p=0.003) or the diameter was ≥20 mm (85%±7% vs 99%±1%, p=0.02). The combination of both risk factors produced significantly poorer iliac complication-free survival compared with cases in which there was one or no risk factor (67%±19% vs 96%±2% vs 99%±1%, respectively; p<0.001). Conclusion: Iliac limb complications are infrequent in EVAR, regardless of the type of iliac limb chosen; however, CIAs ≤30 mm in length or ≥20 mm in diameter significantly increased the risk of late iliac complications in FLs. If both characteristics were present, this risk was further elevated.


Sympathetic nervous adjustments in man to simulated weightlessness induced by water immersion.
To clarify the role of the sympathetic nervous system to adjust the fluid shift under weightlessness, muscle and skin sympathetic activities were recorded microneurographically in human subjects under simulated weightlessness induced by water immersion up to the levels of the knee, the navel, the breast and the neck. The muscle and skin sympathetic activities were reduced in proportion to rise of immersion level up to the neck. These changes of sympathetic activities were almost concomitant with those of simultaneously recorded soleus electromyograms and heart rate. Reductions of the thigh and the leg circumference were also confirmed by strain gauge plethysmogram recorded under the same experimental condition. Based on these findings, it is concluded that the sympathetic nervous system is suppressed under weightlessness simulated by water immersion. This suppression might depend mainly on the activation of intrathoracic low pressure receptors, due to the fluid shift toward the upper part of the body. The suppression of the sympathetic nervous system seems to be important to compensate the fluid shift under weightlessness.


Bioactive glass/polymer composite materials with mechanical properties matching those of cortical bone.
Stress shielding resulting from mismatch in dynamic mechanical properties contributes to the reduced stability of osseous implants. Our objective was to develop biocompatible composites having mechanical properties similar to those of cortical bone. Polymers of urethane dimethacrylate (UDMA) and 2-hydroxyethyl methacrylate (HEMA, 0-20%) and composites containing bioactive glass particles (70% SiO(2), 25% CaO, and 5% P(2)O(5)), with or without silane treatment were prepared. Young's moduli of composites containing silane-treated glass (16 GPa) were significantly greater than those of composites containing untreated glass (12-13 GPa) or of unfilled polymers (5-6 GPa). Bioactive glass reduced water sorption by the composites and incorporation of silane-treated glass prevented HEMA-induced increases in water sorption. Osteoblast-like cells attached equally well to UDMA polymer and composite containing silane-treated bioactive glass. Thus, silane treatment improved the mechanical properties of bioactive glass composites without compromising biocompatibility. This material has a Young's modulus comparable to that of cortical bone. Therefore, silane-treated bioactive glass composites, when used as implant or cement materials, would reduce stress shielding and improve implant stability.


Soft Rot Enterobacteriaceae Are Carried by a Large Range of Insect Species in Potato Fields.
Pathogenic soft rot Enterobacteriaceae (SRE) belonging to the genera Pectobacterium and Dickeya cause diseases in potato and numerous other crops. Seed potatoes are the most important source of infection, but how pathogen-free tubers initially become infected remains an enigma. Since the 1920s, insects have been hypothesized to contribute to SRE transmission. To validate this hypothesis and to map the insect species potentially involved in SRE dispersal, we have analyzed the occurrence of SRE in insects recovered from potato fields over a period of 2 years. Twenty-eight yellow sticky traps were set up in 10 potato fields throughout Norway to attract and trap insects. Total DNA recovered from over 2,000 randomly chosen trapped insects was tested for SRE, using a specific quantitative PCR (qPCR) TaqMan assay, and insects that tested positive were identified by DNA barcoding. Although the occurrence of SRE-carrying insects varied, they were found in all the tested fields. While Delia species were dominant among the insects that carried the largest amount of SRE, more than 80 other SRE-carrying insect species were identified, and they had different levels of abundance. Additionally, the occurrence of SRE in three laboratory-reared insect species was analyzed, and this suggested that SRE are natural members of some insect microbiomes, with herbivorous Delia floralis carrying more SRE than the cabbage moth (Plutella xylostella) and carnivorous green lacewing larvae (Chrysoperla carnea). In summary, the high proportion, variety, and ubiquity of insects that carried SRE show the need to address this source of the pathogens to reduce the initial infection of seed material.IMPORTANCE Soft rot Enterobacteriaceae are among the most important pathogens of a wide range of vegetables and fruits. The bacteria cause severe rots in the field and in storage, leading to considerable harvest losses. In potato, efforts to understand how soft rot bacteria infect and spread between healthy plants have been made for over a century. Early on, fly larvae were implicated in the transmission of these bacteria. This work aimed at investigating the occurrence of soft rot bacteria in insects present in potato fields and at identifying the species of these insects to better understand the potential of this suspected source of transmission. In all tested potato fields, a large proportion of insects were found to carry soft rot bacteria. This suggests a need to give more weight to the role of insects in soft rot ecology and epidemiology to design more effective pest management strategies that integrate this factor.


Trends in speciated fine particulate matter and visibility across monitoring networks in the Southeastern United States.
Trends in fine particulate matter <2.5 microm in diameter (PM2.5) and visibility in the Southeastern United States were evaluated for sites in the Interagency Monitoring of Protected Visual Environments, Speciated Trends Network, and Southeastern Aerosol Research and Characterization Study networks. These analyses are part of the technical assessment by Visibility Improvement-State and Tribal Association of the Southeast (VISTAS), the regional planning organization for the southeastern states, in support of State Implementation Plans for the regional haze rule. At all of the VISTAS IMPROVE sites, ammonium sulfate and organic carbon (OC) are the largest and second largest contributors, respectively, to light extinction on both the 20% haziest and 20% clearest days. Ammonium nitrate, elemental carbon (EC), soils, and coarse particles make comparatively small contributions to PM2.5 mass and light extinction on most days at the Class I areas. At Southern Appalachian sites, the 20% haziest days occur primarily in the late spring to fall, whereas at coastal sites, the 20% haziest days can occur through out the year. Levels of ammonium sulfate in Class I areas are similar to those in nearby urban areas and are generally higher at the interior sites than the coastal sites. Concentrations of OC, ammonium nitrate, and, sometimes, EC, tend to be higher in the urban areas than in nearby Class I areas, although differences in measurement methods complicate comparisons between networks. Results support regional controls of sulfur dioxide for both regional haze and PM2.5 implementation and suggest that controls of local sources of OC, EC, or nitrogen oxides might also be considered for urban areas that are not attaining the annual National Ambient Air Quality Standard for PM2.5.


[Screening bioactive compounds inhibiting influenza virus from isatidis radix by ultrafiltration mass spectrometry].
In vitro neuraminidase inhibition assays and ultrafiltration liquid chromatography with diodearray detector coupled to time of flight mass spectrometer (UPLC-DAD-TOF-MS) were combined to screen bioactive compounds inhibiting neuraminidase from Isatidis Radix. By comparing the compounds from Isatidis Radix before and after ultrafiltration, we found that arginine, goitrin and adenosinea can bind with neuraminidase, and the binding degree of the three compounds were (36.23 +/- 1.12)%, (32.54 +/- 1.02)% and (9.38 +/- 0.47)%, respectively. The IC50 of arginine and goitrin were (1.16 +/- 0.02), (1.20 +/- 0.02) g x L(-1), respectively. While the IC50 of adenosinea was higher than 500 g x L(-1). The results showed that arginine and goitrin might be the main compounds with antiviral activity of Isatidis Radix. This study may provide a useful method for the screening of bioactive compounds and quality control of Isatidis Radix.


The mycotoxin ochratoxin-A impairs protein uptake in cells derived from the proximal tubule of the kidney (opossum kidney cells).
Proximal tubule-derived opossum kidney (OK) cells are a suitable model to study proximal tubular protein endocytosis by using fluorescein-isothiocyanate-albumin as substrate. We used OK cells to investigate several steps of the endocytotic process in control cells and in ochratoxin A (OTA)-treated cells. OTA is a mycotoxin which causes proteinuria. When OTA was present only during the 15-min period in which uptake was studied, it had no effect on albumin endocytosis. Preincubation of OK cells with OTA (10 mumol/l) for 24 hr led to a reduction of transport capacity (Jmax to approximately 50% of control) and of apparent affinity (Km to approximately 200% of control). Specific binding of albumin to the apical cell surface was reduced also. Maximum binding capacity was reduced to 72% of control. By contrast, endocytotic uptake of the fluid-phase marker dextran was not affected by OTA. Preincubation of OK cells for 24 hr with 10 mumol/l of OTA reduced degradation of fluorescein-isothiocyanate-albumin to trichloroacetic acid-soluble fluorescence to 59% of control. We could not detect any difference in endosomal pH (6.13 +/- 0.05 in controls vs. 6.04 +/- 0.10 in OTA-treated cells). Furthermore, the rate of re-exocytosis of albumin taken up was significantly greater in OTA-treated cells. We conclude that: 1) OK cells are a suitable model to study several steps of the endocytotic process separately and thus to investigate the pathophysiology of reduced tubular protein reabsorption and 2) 24-hr exposure to OTA reduces protein uptake because of a decrease of specific binding sites and of enhanced exocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Morphological and immunohistochemical support for the interstitial cell origin of oestrogen-induced kidney tumours in the Syrian golden hamster.
The oestrogen-induced kidney tumour of the Syrian golden hamster has been extensively used not only as a model for renal carcinogenesis, but also for hormonal carcinogenetic studies. In spite of all the different approaches, its histogenesis remains unresolved. The two classical hypotheses are an epithelial origin (in the proximal convoluted tubules) or a mesenchymal-blastemal origin (in the interstitial cells). In the present study two types of preneoplastic lesions were seen: tubular dysplasia and interstitial cell hyperplasia. The first neoplastic stage consisted of interstitial or blastemal cells aggregated in the form of microscopic nodules (tumourlets). In the more advanced tumours the blastemal pattern was the more predominant, but we also observed other patterns of epithelial, mesenchymal or neural types. These findings were confirmed by ultrastructural analysis, which revealed blastemal-epithelial transitions and mesenchymal and mesonephric features, as well as the presence of neurosecretory granules. The paucity of immunohistochemical studies on these tumours led us to apply a panel of the most frequently used antibodies in diagnostic pathology to 36 cases of our series. There was co-expression of cytokeratins and vimentin, which were the most intensely stained, together with S-100 protein. Further positivities were seen for carcinoembryonic antigen, desmin, neuron-specific enolase and HNK-1. These results lend support to the revised, new histological classification confirmed by the ultrastructural findings, allowing us to postulate a tumoural origin in the renal interstitial cells, which may be nephrogenic undifferentiated cells that possess an epithelial, mesenchymal and neuroectodermal phenotype.


[Experimental study of fast formation of biomimetic apatite coatings on pure titanium surface].
To investigate calcium-phosphate coating on commercial pure titanium substrate using a fast biomimetic procedure. The titanium specimens were divided into two groups, group A and group B. The specimens of group A were only treated with the mixture of H2SO4/HCl for 30 min. The specimens of group B were treated with the mixture of H2SO4/HCl for 30 min, immersed into 5 mol/L NaOH solution at 60 degrees C for 24 h, and then heated to 600 degrees C and maintained for 1 h. All specimens were soaked into simulated body fluid-A (SBF) and SBF-B for each day. The surface morphology was observed by field scanning electron microscopy. Dense calcium-phosphate coating deposited on all the titanium surfaces of two groups. The calcium-phosphate coating consisted of spheric structure with a diameter of 1 approximately 3 microm, which was proved to be hydroxycarbonate apatite with the analysis of X-ray diffraction. Thin hydroxycarbonate apatite coating can deposited on pure titanium using a fast biomimetic procedure.


tert-Butylhydroquinone mobilizes intracellular-bound zinc to stabilize Nrf2 through inhibiting phosphatase activity.
The nuclear factor erythroid 2-related factor 2 (Nrf2) is required to combat increases in oxidative stress. The chemical compound tert-butylhydroquinone (tBHQ) can downregulate Kelch-like ECH-associated protein 1 (Keap1), a repressor of Nrf2, thus maintaining the stability of Nrf2. tBHQ can also increase intracellular "free" zinc in human bronchial epithelial (16HBE) cells. We aim to investigate whether the intracellular free zinc change plays a role in Nrf2 activation. tBHQ exposure dose-dependently increases intracellular free zinc concentrations within 30 min in 16HBE cells by mobilizing intracellular zinc pools. Active Nrf2 and the antioxidant enzyme heme oxygenase-1 (HO-1) increase at 3 h after tBHQ treatment. Chelating intracellular free zinc with tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN) during tBHQ exposure partially abrogates the tBHQ-induced activation of Nrf2 and HO-1 expression, while Keap1 is further decreased. These results indicate that tBHQ-induced stability of Nrf2 is associated with the intracellular free zinc level. Because the activated Nrf2 is phosphorylated, the serine/threonine protein phosphatase activity, which is known to be inhibited by zinc, is assayed. The results showed that tBHQ treatment can suppress cellular protein phosphatase-2A (PP2A) and protein phosphatase-2C (PP2C) activity, which can be abrogated by adding TPEN. This finding is verified in a cell-free protein extract experiment by supplying zinc or by chelating zinc with TPEN. These results provide a novel mechanistic insight into Nrf2 activation in antioxidant enzyme induction involving zinc signaling. The increase of intracellular free zinc may be one mechanism for Nrf2 activation. The inhibition of PP2A and PP2C activity may be involved in Nrf2 phosphorylation modulation.


Influence of polyhedron distortions on calculated bond-valence sums for cations with one lone electron pair.
In the present bond-valence model (BVM), the bond-valence parameters r(0) and b are, in general, supposed to be constant for each A-X pair and equal to 0.37 A for all A-X pairs, respectively. For [A(i)(X(j))(n)] coordination polyhedra that do not deviate strongly from regularity, these suppositions are well fulfilled and calculated values for the bond-valence sums (BVS)(i) are nearly equal to the whole-number values of the stoichiometric valence. However, application of the BVM to 2591 [L(i)(X(j))(n)] polyhedra, where L are p-block cations, i.e. cations of the 13th to 17th group of the periodic system of elements, with one lone electron pair and X = O(-II), S(-II) and Se(-II), shows that r(0i) values of individual [LX(n)] polyhedra are correlated with the absolute value /Phi(i)/ of an eccentricity parameter, Phi(i), which is higher for more distorted [LX(n)] polyhedra. As a consequence, calculated (BVS)(i) values for these polyhedra are also correlated with /Phi(i)/, rather than being numerically equal to the stoichiometric valence of L. This is interpreted as the stereochemical influence of the lone electron pair of L. It is shown that the values of the correlation parameters and the R(2) values of the correlation equations depend on the position of the L cation in the periodic system of elements, if the correlations are assumed to be linear. This observation suggests that (BVS)(L) describes a chemical quantity that is different from the stoichiometric valence of L.


Protumoral role of monocytes in human B-cell precursor acute lymphoblastic leukemia: involvement of the chemokine CXCL10.
Myelomonocytic cells play a key role in the progression of many solid tumors. However, very little is known about their contribution to the progression of hematopoietic cancers. We investigated the role of monocytes in the progression of human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). We demonstrated that coculturing human monocytes in vitro with CD19+ BCP-ALL blasts from patients "conditioned" them to an inflammatory phenotype characterized by significant up-regulation of the chemokine, CXCL10. This phenotype was also observable ex vivo in monocytes isolated from BCP-ALL patients, which show elevated CXCL10 production compared with monocytes from healthy donors. Functionally, the "conditioned" monocytes promoted migration and invasive capacity of BCP-ALL cells. Increased invasion was mediated by matrix metalloproteinase 9 expression and activity in the BCP-ALL cells induced by the monocyte-derived CXCL10. However, neither the "conditioned" monocytes nor the CXCL10 produced by these cells had any effect on the proliferation/viability of BCP-ALL cells and angiogenesis. Collectively, our results strongly suggest a protumoral role for human monocytes in BCP-ALL, orchestrated by CXCL10 and its effect on tumor cell migration and invasion. These observations highlight the importance of the CXCL10/CXCR3 chemokine circuit in BCP-ALL progression.


Innate immunity modulates adipokines in humans.
Chronic inflammation converges in type 2 diabetes and atherosclerosis. Modulation of adipokine signaling by innate immunity in humans is of considerable interest given the role of adipokines in insulin resistance and atherosclerosis. The aim of the study was to examine effects of low-grade endotoxemia, a model of human inflammation, on adipokines in vivo. An open-label, placebo-controlled, fixed-sequence clinical study was conducted at a General Clinical Research Center. There were 20 healthy male (50%) and female volunteers aged 18-40 yr. Serial blood sampling and adipose biopsies were performed for 24 h before and after iv bolus endotoxin [lipopolysaccharide (LPS), 3 ng/kg]. We measured plasma leptin, adiponectin, resistin, soluble leptin receptor, cytokines, insulin, and glucose; distribution of adiponectin among multimeric complexes; whole blood, monocyte and adipose mRNA for adipokines and their receptors. LPS induced fever, blood, and adipose TNF and IL-6 and increased homeostasis model assessment of insulin resistance. These were associated with increases in plasma leptin (from 4.1 +/- 1.1 to 6.1 +/- 1.9 ng/ml in men; 21.1 +/- 4.4 to 27.4 +/- 4.7 ng/ml in women; P < 0.005), doubling of the leptin:soluble leptin receptor ratio, and marked induction of whole blood resistin mRNA (13.7 +/- 7.3-fold; P < 0.001) and plasma resistin (8.5 +/- 2.75 to 43.2 +/- 15.3 ng/ml; P < 0.001). Although total adiponectin levels and low and high molecular weight adiponectin complexes were unaltered by LPS treatment, whole blood mRNA for adiponectin receptors 1 (49%; P < 0.005) and 2 (65%; P < 0.001) was suppressed. Modulation of adipokine signaling may contribute to the insulin resistant, atherogenic state associated with human inflammatory syndromes. Targeting of individual adipokines or their upstream regulation may prove effective in preventing acute and chronic inflammation-related metabolic complications.


Community-based VHA clinics: effect on patient satisfaction and resource utilization.
This study was conducted to determine whether enrollment in a Veterans Healthcare Administration (VHA) Access Point (AP) community-based clinic would reduce hospital admissions and unplanned urgent care visits while maintaining patient satisfaction with medical care. Through use of a survey and a review of medical records, data were gathered on the following three patient groups: veterans receiving care at a VHA hospital-based clinic, veterans receiving care at an AP, and veterans receiving care from non-VHA sources. Results showed that the number of unplanned hospital admissions and urgent care visits decreased in the two groups receiving care at VHA facilities.


The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes mellitus patients ineffectively managed with metformin: a double-blind, randomized, placebo-controlled trial.
Type 2 diabetes mellitus (T2DM) is one of the major diseases confronting the health care systems. In diabetes mellitus (DM), combined use of oral hypoglycemic medications has been shown to be more effective than metformin (Met) alone in glycemic control. This study determined the effects of Ginkgo biloba (GKB) extract as an adjuvant to Met in patients with uncontrolled T2DM. Sixty T2DM patients were recruited in a randomized, placebo-controlled, double-blinded, and multicenter trial. The patients, currently using Met, were randomly grouped into those treated with either GKB extract (120 mg/day) or placebo (starch, 120 mg/day) for 90 days. Blood glycated hemoglobin (HbA1c), fasting serum glucose, serum insulin, body mass index (BMI), waist circumference (WC), insulin resistance, and visceral adiposity index (VAI) were determined before (baseline) and after 90 days of GKB extract treatment. GKB extract significantly decreased blood HbA1c (7.7%±1.2% vs baseline 8.6%±1.6%, P<0.001), fasting serum glucose (154.7±36.1 mg/dL vs baseline 194.4±66.1 mg/dL, P<0.001) and insulin (13.4±7.8 μU/mL vs baseline 18.5±8.9 μU/mL, P=0.006) levels, BMI (31.6±5.1 kg/m2 vs baseline 34.0±6.0 kg/m2, P<0.001), waist WC (102.6±10.5 cm vs baseline 106.0±10.9 cm, P<0.001), and VAI (158.9±67.2 vs baseline 192.0±86.2, P=0.007). GKB extract did not negatively impact the liver, kidney, or hematopoietic functions. GKB extract as an adjuvant was effective in improving Met treatment outcomes in T2DM patients. Thus, it is suggested that GKB extract is an effective dietary supplement for the control of DM in humans.


Safety and efficacy of pulmonary physiotherapy in hospitalized patients with severe COVID-19 pneumonia (PPTCOVID study): A prospective, randomised, single-blind, controlled trial.
Pulmonary physiotherapy (PPT) is an important treatment in the management of patients with different types of pulmonary disorders. We aimed to evaluate safety and efficacy of PPT in hospitalized patients with severe COVID-19 pneumonia. In this randomised, single-blind, controlled trial, we enrolled hospitalized, non-intubated patients (18 to 75 years with oxygen saturation (Spo2) in free-air breathing ≤90%) with COVID-19 pneumonia at a referral hospital. Participants were randomly assigned (1:1) to receive PPT (six sessions PPT with breathing exercises and airway clearance techniques) or basic care. The primary outcomes were venous blood O2 (pO2) and CO2 (pCO2) pressures, Spo2, and three-minute walking test (3MWT) that were assessed before and end of sixth session. Secondary outcomes included level of dyspnea, venous blood PH, one-month mortality, three-month mortality and short form-36 (SF-36) after one and three months. The assessor was blinded to the assignment. This trial is registered with ClinicalTrials.gov (NCT04357340). In April-May 2020, 40 participants were randomly assigned to PPT or basic care groups. While at the end of intervention, pO2 (adjusted mean difference to baseline measure (AMD) 6.43 mmHg [95%CI 2.8, 10.07], P<0.01), Spo2 (AMD 4.43% [95%CI 2.04, 6.83], P = 0.0011), and 3MTW (AMD 91.44 m [95%CI 68.88, 113.99], P<0.01) were higher in PPT group and basic care group, pCO2 was not improved (AMD -2.1 mmHg [95%CI-6.36, 2.21], P = 0.33). Based on the logistic model adjusted to baseline Spo2, the risks of mortality were reduced 81% ([95%CI: 97% reduction to 30% increase], P = .09) and 84% ([95%CI 74% reduction to 5% increase], P = .06) at one-month and three-month, respectively. There were no significant differences in most SF-36 domains scores after one and three months. No serious adverse event was observed during PPT sessions. Early PPT can be considered a safe and relatively effective therapeutic choice for patients with severe COVID-19.


A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene.
FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase and is implicated in autosomal recessive combined oxidative phosphorylation deficiency 14. The clinical manifestation can be divided into early onset epileptic phenotype and spastic paraplegia phenotype. The purpose of this study was to report a case of juvenile manifesting refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. Microscopic and histochemical examination as well as next-generation sequencing and reconstruction of the three-dimensional structure of FARS2 protein were performed. A 17-year-old man with no developmental delays suffered from generalized tonic-clonic convulsion since 12 years of age and developed refractory status epilepticus 5 years later. No specific etiology was found following brain imaging, muscle biopsy and metabolic studies. DNA sequencing identified two novel compound heterozygous mutations in FARS2, (p.V197M and p.F402S), derived from each parents, respectively. These mutations affected the structure or thermodynamic stability of the protein. This is a case report of juvenile-onset refractory epilepsy caused by two novel compound heterozygous mutations in the FARS2 gene. This case confirms and expands the clinicalphenotype and the genotypic spectrum of the FARS2 gene.


Accuracy issues involved in modeling in vivo protein structures using PM7.
Using the semiempirical method PM7, an attempt has been made to quantify the error in prediction of the in vivo structure of proteins relative to X-ray structures. Three important contributory factors are the experimental limitations of X-ray structures, the difference between the crystal and solution environments, and the errors due to PM7. The geometries of 19 proteins from the Protein Data Bank that had small R values, that is, high accuracy structures, were optimized and the resulting drop in heat of formation was calculated. Analysis of the changes showed that about 10% of this decrease in heat of formation was caused by faults in PM7, the balance being attributable to the X-ray structure and the difference between the crystal and solution environments. A previously unknown fault in PM7 was revealed during tests to validate the geometries generated using PM7. Clashscores generated by the Molprobity molecular mechanics structure validation program showed that PM7 was predicting unrealistically close contacts between nonbonding atoms in regions where the local geometry is dominated by very weak noncovalent interactions. The origin of this fault was traced to an underestimation of the core-core repulsion between atoms at distances smaller than the equilibrium distance.


Intramolecular proton transfer in calixphyrin derivatives.
Calix[4]phyrins are convenient models for porphyrin metabolism intermediates. They also attract attention as complexation agents in macromolecular chemistry. For the biological function and chemical properties, their flexibility plays an important role. In this study, we explore the inner hydrogen motion previously detected in some calix[4]phyrins as a slow chemical exchange in the NMR spectra (J. Am. Chem. Soc. 2004, 126, 13714). The potential energy surface of this motion is defined by two generalized coordinates and modeled at DFT levels. The transitional barriers thus obtained agree reasonably well with those calculated from dynamic (1)H NMR measurements. The transitions over both the sp(2) and sp(3) links are found to be possible. During the transfer, an intermediate is formed where the two hydrogen atoms are attached to the neighboring nitrogens. Surprisingly, the barriers channeling the sp(2) and sp(3) paths in significantly depend on the dispersion and other interactions between remote side chains. The results confirm the possibility of a fine-tuning of the calixphyrin core properties by distant substituents.


[Coronary angioplasty in diabetic patients. Current and future perspectives].
It has been estimated that 15-25% of patients who undergo percutaneous or surgical coronary angioplasty are diabetics. The indications for coronary revascularization and initial results of the procedure do not differ substantially between patients with diabetes mellitus and non-diabetics. However, the long-term results of both percutaneous and surgical coronary angioplasty are less favorable in diabetics in terms of mortality and the need for new revascularization procedures. The development and widespread use of stents and glycoprotein IIb/IIIa receptor inhibiting drugs have improved the clinical evolution of diabetics treated with angioplasty. Currently available data show that the administration of glycoprotein IIb/IIIa inhibitors to patients undergoing coronary angioplasty is especially useful in diabetics and improves short-term and long-term results, decreasing one-year mortality by 45%. There seem to be indications for the routine use of glycoprotein IIb/IIIa inhibitors in diabetics treated with angioplasty. While the use of stents has improved long-term and short-term results in diabetics, the success rates of angioplasty in diabetics are still lower than in non-diabetics. Diabetes is still an independent predictor of restenosis and long-term events after stenting interventions. Analysis of the studies comparing percutaneous and surgical revascularization in diabetic patients with multivessel disease shows that surgery is superior in terms of long-term mortality and need for new revascularization procedures. Stenting has improved, but not substantially, the results of multivessel angioplasty in diabetics. Therefore, the indications for angioplasty in multivessel diabetics should be evaluated individually. Factors that contribute to the less favorable post-angioplasty evolution of diabetic patients are more rapid progression of atherosclerosis and, especially, a higher rate of restenosis. New angioplasty techniques, such as brachytherapy and drug-eluting stents, are likely to significantly improve the results of percutaneous interventions in diabetics, thus allowing the indications for angioplasty in diabetics to be extended even further in the near future.


Genus Stathmopoda Herrich-Schäffer, 1853 (Lepidoptera: Stathmopodidae) from China: Descriptions of thirteen new species.
Thirteen new species of the genus Stathmopoda are described from China: S. atrifusca sp. nov., S. cellifaria sp. nov., S. cornuta sp. nov., S. digitiprocessa sp. nov., S. dolichantha sp. nov., S. falsistimulata sp. nov., S. guangxiensis sp. nov., S. ingena sp. nov., S. liberata sp. nov., S. purpurata sp. nov., S. serrifasciaria sp. nov., S. similatridorsalis sp. nov. and S. spinicornuta sp. nov. Images of both adults and genitalia of the new species are provided, along with a map showing the distribution of these species.