The Effect of Humidity and Temperature Variations on the Behavior of Wire-to-Plane Coronas.
The effect of temperature and humidity on the current-voltage relationship and uniformity of positive and negative air coronas has been studied. Variations in temperature and absolute humidity seem to have a comparatively small effect on the behavior of coronas. By contrast, variations in the relative humidity have readily noticeable effects on the current-voltage relationship. At high voltages (positive or negative) the corona current decreases as the relative humidity increases due to ion and electron hydration effects. By contrast, both positive and negative coronas are initiated at lower voltages at high relative humidities, presumably due to the formation of miniscule water droplets with low ionization potential. The relative humidity also affects the uniformity of negative corona but not positive corona. Presumably the electron emitting properties of a negative wire are altered by moisture adsorbed on the wire surface at high relative humidities. By contrast, positive corona is not grossly affected because it is primarily a gas phase phenomena while negative corona is also sensitive to the electron emitting properties of the wire.


Field emission properties of AIN nanostructures.
AIN with different morphologies, including thin film, nanowires, nanoneedles and nanochilies, depending on the controlled growth parameters, have been successfully synthesized by chemical vapor deposition technique. Field emission properties have been systematically studied. The experimental results show that all AIN nanostructures have good field emission properties. In comparison, AIN nano-chilies possess the best field emission properties with a low turn-on and threshold fields of 1.8 V/microm and 3.1 V/microm, respectively. The results suggest that the morphological modulation is an effective way to optimize field emission performance of nanostructures.


Nickel-catalyzed reductive defunctionalization of esters in the absence of an external reductant: activation of C-O bonds.
The nickel-catalyzed reductive cleavage of esters in the absence of an external reductant, which involves the cleavage of an inert acyl C-O bond in O-alkyl esters is reported. Various groups, such as N-containing heterocycles, esters, amides, and even arene rings can function as a directing group.


Distinct cellular mechanisms of blood vessel fusion in the zebrafish embryo.
Although many of the cellular and molecular mechanisms of angiogenesis have been intensely studied [1], little is known about the processes that underlie vascular anastomosis. We have generated transgenic fish lines expressing an EGFP-tagged version of the junctional protein zona occludens 1 (ZO1) to visualize individual cell behaviors that occur during vessel fusion and lumen formation in vivo. These life observations show that endothelial cells (ECs) use two distinct morphogenetic mechanisms, cell membrane invagination and cord hollowing to generate different types of vascular tubes. During initial steps of anastomosis, cell junctions that have formed at the initial site of cell contacts expand into rings, generating a cellular interface of apical membrane compartments, as defined by the localization of the apical marker podocalyxin-2 (Pdxl2). During the cord hollowing process, these apical membrane compartments are brought together via cell rearrangements and extensive junctional remodeling, resulting in lumen coalescence and formation of a multicellular tube. Vessel fusion by membrane invagination occurs adjacent to a preexisting lumen in a proximal to distal direction and is blood-flow dependent. Here, the invaginating inner cell membrane undergoes concomitant apicobasal polarization and the vascular lumen is formed by the extension of a transcellular lumen through the EC, which forms a unicellular or seamless tube.


Multifocal leucoencephalopathy presenting as antidepressant induced mania.
A male patient presented with tricyclic induced hypomania after treatment for chronic depression. On follow up the patient deteriorated towards dementia with multifocal leucoencephalopathy. The possible role of brain lesions in the causation of affective syndromes and the neurobiological hypothesis of bipolar syndromes are discussed. The authors propose that chronic depression should be thoroughly investigated for a probable Axis III diagnosis.


Endovascular Aneurysm Repair for Abdominal Aortic Aneurysm: A Comprehensive Review.
Abdominal aortic aneurysm (AAA) can be defined as an abnormal, progressive dilatation of the abdominal aorta, carrying a substantial risk for fatal aneurysmal rupture. Endovascular aneurysmal repair (EVAR) for AAA is a minimally invasive endovascular procedure that involves the placement of a bifurcated or tubular stent-graft over the AAA to exclude the aneurysm from arterial circulation. In contrast to open surgical repair, EVAR only requires a stab incision, shorter procedure time, and early recovery. Although EVAR seems to be an attractive solution with many advantages for AAA repair, there are detailed requirements and many important aspects should be understood before the procedure. In this comprehensive review, fundamental information regarding AAA and EVAR is presented.


Dtar-Finder: program for drug target identification and characterization in bacteria.
The drug target identification is the primary step for drug discovery. Recent development of computational techniques and availability of sequencing data has provided numerous opportunities for target identification but very few of them are fully automated. Here, we have developed a Perl program named Dtar-Finder for drug target identification and its characterization. Dtar-Finder predicts the drug targets which are essential to pathogen and non homologous to human, essential human anti-targets and gut microflora. This program is divided in 6 modules where modules 1-4 extract drug targets while module 5-6 predicts druggability and broad spectrum ability of identified candidates. The performance of this program in terms of sensitivity and specificity is calculated where specificity score was better compare to sensitivity score. Further, we have tested our script on C. botulinum (3572 proteins) and 35 potential drug targets have been identified. Out of which 16 broad spectrums candidates were predicted whereas 8 candidates are found to be druggable whiles remaining are considered to be 'novel'. These drug targets were cross-validated through literature showing 77.14% accuracy. Thus, the idea behind this work was to develop a fast, robust and generic program capable of finding drug targets in bacteria, which has been fulfilled satisfactorily.


Fibrillary glomerulonephritis: presenting as crescentic glomerulonephritis causing rapidly progressive renal failure.
We report an unusual case of fibrillary glomerulonephritis (FGN) presenting as rapidly progressive renal failure and extensive crescent formation along with linear staining of capillary walls of the glomeruli on immunofluorescence, mimicking anti-glomerular basement membrane (anti-GBM) antibody-mediated disease. Laboratory results for circulating anti-GBM antibodies were negative. The subsequent electron microscopic findings were that of presence of electron-dense deposits in the glomerular mesangium and capillary walls, comprising of non-branching fibrils with an average diameter of 16 nm consistent with a diagnosis of FGN. This case illustrates the crucial role of electron microscopy in differential diagnosis of crescentic glomerulonephritis.


[Psychotherapy and forensic psychiatry].
Psychotherapists in the forensic field are in an uncomfortable position. The reluctance of patients to be subjected to such obligatory treatments and to face their own violence contributes to this difficult position. The mission of public safety assigned to these treatments, their assessment through risk of recidivism rather than therapeutic effectiveness as well as misconception by lawyers and authorities of what psychotherapy really is reinforce the difficulty of such a practice. However, a clarification of the nature of each type of interventions allows the establishment of viable psychotherapeutic framework adapted to penal constraints. The developments of approaches specifically tailored to prison settings as well as to sexual offenders are illustrations of this point.


Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake.
Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference. The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding. To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals. Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen. The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.


A case of chloroplast heteroplasmy in kiwifruit (Actinidia deliciosa) that is not transmitted during sexual reproduction.
We report the first case of plastid chimera within the Actinidia genus, where plastid inheritance was believed to be paternal. The heterogeneity of chloroplast DNA observed in the hexaploid Actinidia deliciosa cultivar D uno involves the presence or absence of a particular MspI restriction site in the region between the psbC gene and the tRNA-Ser(UGA) gene. The heterogeneity was first observed using restriction fragment length polymorphism and then confirmed through cloning and sequencing. The analysis of the cloned fragments revealed the presence of two haplotypes: the most frequent type was found in 123 (88.5%) out of a total of 139 colonies screened. Partial sequences of the psbC-trnS fragment from both haplotypes revealed that the polymorphism occurs within the coding region of the psbC gene and consists of a synonymous transition. A contamination-free cross involving D uno as the male parent produced only plants characterized by the most frequent haplotype, indicating either selection bias against the rare type or more likely fixation of the frequent type in tissues leading to the formation of the male gametes. The MspI restriction profiles performed on various tissues suggest that the rarer type is absent from the histogenic layer LII and that D uno is a periclinal plastid chimera.


[Clinicopathological and prognostic significance of PD-L1 expression in oral squamous cell carcinoma: a meta analysis].
To determine the prognostic role of high PD-L1 in patients with oral squamous cell carcinoma. Electronic databases, such as PubMed, Embase and Cochrane library, were searched to identify studies evaluating PD-L1 expression and overall survival (OS) in these patients. RevMan 5.3 software was used for meta-analysis. A total of 12 studies that involved 1595 patients were included. Pooled hazard ratio (HR) 1.02 (95%CI= 0.93-1.11,P=0.71) indicated that the association between PD-L1 expression and overall survival (OS) was not significant. The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with gender (OR=0.64, 95%CI=0.48-0.85, P=0.002), differentiation (OR=0.58, 95%CI=0.37-0.90, P=0.01) and HPV infection (OR=1.91, 95%CI=1.13-3.23, P=0.02). However, PD-L1 had no correlation with tumour size, and lymph node status. PD-L1 expression may not be an independent predictor of prognosis of patients with OSCC. Well-designed large cohort studies are needed to confirm these findings.


Widespread secondary contact and new glacial refugia in the halophilic rotifer Brachionus plicatilis in the Iberian Peninsula.
Small aquatic organisms harbour deep phylogeographic patterns and highly structured populations even at local scales. These patterns indicate restricted gene flow, despite these organisms' high dispersal abilities, and have been explained by a combination of (1) strong founder effects due to rapidly growing populations and very large population sizes, and (2) the development of diapausing egg banks and local adaptation, resulting in low effective gene flow, what is known as the Monopolization hypothesis. In this study, we build up on our understanding of the mitochondrial phylogeography of the halophilic rotifer Brachionus plicatilis in the Iberian Peninsula by both increasing the number of sampled ponds in areas where secondary contact is likely and doubling sample sizes. We analyzed partial mitochondrial sequences of 252 individuals. We found two deep mitochondrial DNA lineages differing in both their genetic diversity and the complexity of their phylogeographic structure. Our analyses suggest that several events of secondary contact between clades occurred after their expansion from glacial refugia. We found a pattern of isolation-by-distance, which we interpret as being the result of historical colonization events. We propose the existence of at least one glacial refugium in the SE of the Iberian Peninsula. Our findings challenge predictions of the Monopolization hypothesis, since coexistence (i.e., secondary contact) of divergent lineages in some ponds in the Iberian Peninsula is common. Our results indicate that phylogeographic structures in small organisms can be very complex and that gene flow between diverse lineages after population establishment can indeed occur.


Hsp90 Inhibitor SNX-2112 Enhances TRAIL-Induced Apoptosis of Human Cervical Cancer Cells via the ROS-Mediated JNK-p53-Autophagy-DR5 Pathway.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent cancer cell apoptosis-inducing factor that can induce apoptosis in a variety of cancer cells. However, resistance to TRAIL in cancer cells is a huge obstacle in creating effective TRAIL-targeted clinical therapies. Thus, agents that can either enhance the effect of TRAIL or overcome its resistance are needed. In this study, we combined TRAIL with SNX-2112, an Hsp90 inhibitor we previously developed, to explore the effect and mechanism that SNX-2112 enhanced TRAIL-induced apoptosis in cervical cancer cells. Our results showed that SNX-2112 markedly enhanced TRAIL-induced cytotoxicity in HeLa cells, and this combination was found to be synergistic. Additionally, we found that SNX-2112 sensitized TRAIL-mediated apoptosis caspase-dependently in TRAIL-resistant HeLa cells. Mechanismly, SNX-2112 downregulated antiapoptosis proteins, including Bcl-2, Bcl-XL, and FLIP, promoted the accumulation of reactive oxygen species (ROS), and increased the expression levels of p-JNK and p53. ROS scavenger NAC rescued SNX-2112/TRAIL-induced apoptosis and suppressed SNX-2112-induced p-JNK and p53. Moreover, SNX-2112 induced the upregulation of death-receptor DR5 in HeLa cells. The silencing of DR5 by siRNA significantly decreased cell apoptosis by the combined effect of SNX-2112 and TRAIL. In addition, SNX-2112 inhibited the Akt/mTOR signaling pathway and induced autophagy in HeLa cells. The blockage of autophagy by bafilomycin A1 or Atg7 siRNA abolished SNX-2112-induced upregulation of DR5. Meanwhile, ROS scavenger NAC, JNK inhibitor SP600125, and p53 inhibitor PFTα were used to verify that autophagy-mediated upregulation of DR5 was regulated by the SNX-2112-stimulated activation of the ROS-JNK-p53 signaling pathway. Thus, the combination of SNX-2112 and TRAIL may provide a novel strategy for the treatment of human cervical cancer by overcoming cellular mechanisms of apoptosis resistance.


Glucose clamp algorithms and insulin time-action profiles.
Most current insulin pumps include an insulin-on-board (IOB) feature to help subjects avoid problems associated with "insulin stacking." In addition, many control algorithms proposed for a closed-loop artificial pancreas make use of IOB to reduce the probability of hypoglycemic events that often occur due to the integral action of the controller. The IOB curves are generated from the pharmacodynamic (time-activity profiles) actions of subcutaneous insulin, which are obtained from glycemic clamp studies. Glycemic clamp algorithms are reviewed and in silico studies are performed to analyze the effect of glucose meter bias and noise on glycemic control and the manipulated glucose infusion rates. The glucose infusion rates are used to obtain insulin time-activity profiles, which are then used to generate IOB curves. A model-based, three-step-ahead controller is shown to be equivalent to a proportional-integral control algorithm with time-delay compensation. A systematic glucose meter bias of +6 mg/dl results in a decrease in the glucose area under the curve of 3% but no change in the IOB profiles. Based on these preliminary simulation studies, a substantial amount of glucose meter bias and noise during a glycemic clamp can be tolerated with little net effect on the IOB curves. It is suggested that handheld glucose meters can therefore be used in clamp studies if the measurements are filtered (averaged) before processing by the control algorithm. Clinical studies are needed to confirm these preliminary results.


Liver histological structure in adult European bison. Bison bonasus (Linnaeus, 1758).
The histological structure of the liver in 12 European bison, 2-8 years old, was presented. The study of the hepatic lobule showed that in Bison bonasus there were no connective septa around the hepatic lobules. On the hepatic lobule territory, solitary bile ducts, respectively solitary arterioles, were sometimes observed. Every one of these vessels was isolated from the hepatic parenchyma by thick coats of collagen. In the adventitia of the hepatic sublobar vessels, capillaries of the vasa vasorum system were found. The thick capsule of Glisson presented an outer part lacking in blood vessels and an inner part vascularised with arterioles and capillaries originating from the subcapsular portal tracts. The ligament insertion in the liver parenchyma was described.


Screening and treating asymptomatic bacteriuria in pregnancy.
Asymptomatic bacteriuria (ASB) in pregnancy, if left undiagnosed and appropriately treated can lead to acute pyelonephritis in mothers and low birth weight in infants. Urine culture is the gold standard for diagnosing ASB. Unfortunately, urine culture is limitedly available. The present review aims at evaluating performance of various screening tests and effectiveness of antibiotic regimens for ASB. Positive dipslide test is very likely to have a definitive diagnosis of ASB, whereas a negative result effectively rules out ASB. Available evidences regarding the performance of urine dipstick are still conflicting, it is currently not appropriate to recommend urine dipstick for screening ASB in pregnancy. Choice of antibiotics should be guided by antimicrobial susceptibility testing whenever possible. Nitrofurantoin seems to be antibiotic of choice for ASB in pregnancy. Seven-day regimen of antibiotics gives a better microbiological cure rate but no difference in important clinical outcomes compared with 1-day regimen. Dipslide culture is a promising screening test for ASB. Pregnant women with ASB should be treated with 7-day regimen of antibiotics, although 1-day regimen might be appropriate in some settings. More research is needed for identifying appropriate screening tests for ASB.


Doppler optical coherence microscopy for studies of cochlear mechanics.
The possibility of measuring subnanometer motions with micron scale spatial resolution in the intact mammalian cochlea using Doppler optical coherence microscopy (DOCM) is demonstrated. A novel DOCM system is described that uses two acousto-optic modulators to generate a stable 500-kHz heterodyne frequency. Images and motion measurements are obtained using phase-resolved analysis of the interference signal. The DOCM system permits imaging with micron-scale resolution and 85-dB sensitivity and motion measurements with 100-kHz bandwidth, directional discrimination, and 30-pm/Hz(0.5) noise floor. Images and motion measurements are presented that demonstrate the ability to resolve motions of structures of interest in a mammalian cochlea in vitro including the basilar membrane, reticular lamina, tectorial membrane, and outer hair cells.


GameRank: R package for feature selection and construction.
Building calibrated and discriminating predictive models can be developed through the direct optimization of model performance metrics with combinatorial search algorithms. Often, predictive algorithms are desired in clinical settings to identify patients that may be high and low risk. However, due to the large combinatorial search space, these algorithms are slow and do not guarantee the global optimality of their selection. Here, we present a novel and quick maximum likelihood-based feature selection algorithm, named GameRank. The method is implemented into an R package composed of additional functions to build calibrated and discriminative predictive models. GameRank is available at https://github.com/Genentech/GameRank and released under the MIT License.


Total synthesis of (-)-domoic acid, a potent ionotropic glutamate receptor agonist and the key compound in oceanic harmful algal blooms.
The stereo-controlled total synthesis of (-)-domoic acid is described. The critical construction of the C1'-C2' Z-configuration was accomplished by taking advantage of an unsaturated lactam structure. The side chain fragment was introduced in the final stages of synthesis through a modified Julia-Kocieński reaction, aiming for its efficient derivatization.


[Drug therapy of chronic glaucoma with pilocarpine gel].
In an open clinical trial including 19 patients with chronic open-angle glaucoma, the efficacy, duration of action and tolerance of pilocarpine gel were investigated over a treatment period of a 4 weeks on the basis of one application once a day. The vehicle of pilocarpine gel is a highly viscous, cross-linked, hydrophilic polyacrylic acid which renders prolonged release of pilocarpine hydrochloride 4%, and for this reason insures a prolonged duration of action. After single-dose application pilocarpine gel caused a significant lowering of IOP over at least 18 hours, with a relative potency in the range of 23% of 31% on the first day of treatment, and between 13% and 25% on the 29th day of treatment. As the time interval following the preceding pilocarpine-gel application increased, there was a slight but significant rise in the treated pressure level, although therapeutic pressure levels were not exceeded. In the course of the 4 weeks of treatment, there was a small but significant decrease in response, which can be explained by a certain type of subsensitivity caused by the prolonged release of the active drug. The tolerance of pilocarpine gel was good; side-effects were minor and reversible. These results fulfill the expectations of the glaucoma therapists with respect to both efficacy and tolerance.


Cytokeratin patterns of human oral epithelia: differences in cytokeratin synthesis in gingival epithelium and the adjacent alveolar mucosa.
Human oral mucosa includes various epithelia that are commonly classified as lining, masticatory, and specialized epithelia. Although adjacent tissues, the gingiva and alveolar mucosa represent two different types of epithelia: the gingiva is cornified and exhibits high rate ridges, whereas the mucosa does not normally cornify and exhibits a relatively smooth-contoured borderline between the epithelium and the underlying connective tissue. We examined the cytokeratin patterns of both epithelia using one- and two-dimensional gel electrophoresis. The gingiva expresses a great complexity of cytokeratins, including significant amounts of components nos. 1, 2, 5, 6, 10, 11, 13, 14, 16, and 17, as well as traces of cytokeratins nos. 4 and 15, i.e., a pattern similar to those of vaginal mucosa and epidermis containing proliferative keratinocytes. In contrast, the alveolar mucosa contains only two major cytokeratins, i.e., nos. 4 and 13, together with two minor amounts of cytokeratins nos. 5, 6, 14, and 17, thus resembling the patterns of certain other stratified, noncornified epithelia, such as the esophagus. Immunofluorescence microscopy using monoclonal antibodies to cytokeratins nos. 4 and 13 revealed the presence of these proteins in the suprabasal layers of alveolar mucosa, whereas in the gingiva, only certain small, suprabasal clusters of cells appeared to contain these cytokeratins. The cytoskeletal differences between gingival and alveolar mucosa are discussed in relation to the differences in their morphology and function, and with respect to pathological processes characteristic of these epithelia.


Pathoanatomy, biomechanics, and treatment of upper cervical ligamentous instability: A literature review.
Cervical spine instability broadly refers to compromise of the articular congruity. It can be stratified according to spinal level, functional compromise, and mechanism of instability. Conventional wisdom advocates for use of bracing and physical therapy with only a subset of patients proceeding to obtain surgical treatment. The purpose of this review article is to summarize the current state of knowledge on upper cervical ligamentous instability. The literature search was performed in Mendeley. Search fields were varied until redundant. All articles were screened by title and abstract and a preliminary decision to include an article was made. The full-text screening was performed on the selected articles. Any question regarding the inclusion of an article was discussed by 3 authors until an agreement was reached. Many articles report on the etiological factors including ligamentous laxity, traumatic injury, syndrome instability, iatrogenic instability, congenital, and inflammatory causes. A few recent studies elucidate new findings regarding pathoanatomy through the use of finite element analysis. A few articles demonstrate the diagnosis and show that radiographs alone have a low diagnostic rate and that functional MRI may be able to better quantify instability. Conservative treatment has been described, but there are no outcome studies in the literature. Surgical treatment has been described in many different populations with good radiologic and clinical outcomes. Recently the use of preoperative 3D CT reconstruction has been described with radiographic and immediate postoperative patient-reported outcomes. The presentation of upper cervical spinal instability can be asymptomatic, symptoms of isolated instability, symptoms of nerve irritation, vertebrobasilar insufficiency, or severe neurologic compromise. 3D fine element analysis models and motion-capture systems have the potential to increase our understanding of the pathoanatomic cascade in both traumatic and non-traumatic cases of upper cervical spinal instability. A few modalities on the horizon could increase diagnostic potential. More efforts are needed regarding the use of fine element analysis in understanding the pathoanatomic cascade, the long-term outcomes of children over a spectrum of syndromic causes, and the potential of preoperative virtual simulation to improve surgical outcomes.


Expression and stabilization of the MCT-1 protein by DNA damaging agents.
The contribution of oncogene amplification and/or overexpression to T-cell lymphoid neoplasms has only of late been established with the implication of the TCL1 and MTCP1 genes in T-cell malignancies. Our laboratory has recently discovered a novel oncogene, MCT-1, amplified in a T-cell lymphoma and mapped to chromosome Xq22-24. MCT-1 has been shown to decrease cell-doubling time, dramatically shortening the duration of G(1) transit time and/or G1-S transition, and transforms NIH3T3 fibroblasts. Constitutive expression of MCT-1 results in a strong proliferative signal and is associated with deregulation of protein kinase-mediated G1/S phase checkpoints. In this study we analysed the level and subcellular localization of this novel cell cycle regulatory molecule as a function of cell cycle phase. In human lymphoid tumors expression of MCT-1 is constant throughout the cell cycle and remains cytoplasmic. Cells overexpressing MCT-1 have increased expression of cyclin D1 with dysregulation of the G(1)-S checkpoint. Both cyclin D1 and MCT-1 are involved in regulating passage of cells through the G1 phase of the cell cycle. Since prior work has shown that gamma irradiation induces cyclin D1 expression we investigated the induction of MCT-1 to DNA damaging agents. We demonstrate that increases in MCT-1 protein in irradiated human lymphoid cells do not occur at the mRNA level and do not require new protein synthesis.


Nucleation rates in a new phenomenological model.
In this paper we develop a new theory to evaluate the nucleation rate in the framework of the EMLD-DNT model. Beyond the model, our theory deals with cluster translation and exclusion, effects that have been virtually ignored in classical nucleation theory. We apply the model to the case of 1-pentanol, and compare the predictions with experimental results. We find an excellent agreement between the nucleation rate predicted by our theory and experimental data. The distinguishing feature of the model is its ability to predict successfully the rate of formation of the critical nucleus without the use of an intermolecular potential, employing only macroscopic thermodynamic properties.


[Endogenous fungal endophthalmitis: results of antifungal treatment with and without vitrectomy].
Fungal endophthalmitis represents a significant cause of ocular morbidity, affecting in the majority of cases patients in poor general conditions. The eye is typically involved by hematogen dissemination, and the germ induces a chorioretinitis associated with an important panuveitis. Four patients were examined. They complained of a progressive reduction of vision, associated with photophobia. Ophthalmologic examination disclosed an important panuveitis. Investigations showed a fungal chorio-retinitis in all cases. Risk factors were intra-venous toxicomania, longterm parenteral nutrition and traumatism of the sinuses. Vitreous cultures were positive for Candida albicans (3 patients) and for Aspergillus fumigatus (1 patient). Blood cultures were negative in the four cases. Three patients were treated with anti-fungal medication (fluconazole, itraconazole) associated with a vitrectomy by pars plana. One patient was treated by anti-fungal therapy only. Clinical evolution was satisfactory in all cases. Final vision was 10/10 in three cases and 5/10 in one. One patient developed a retinal detachment and an epiretinal membrane. Follow-up was 7 months (2-16 months). The evolution of these four cases suggests that a rapid anti-fungal therapy associated with or without a vitrectomy represent a favourable therapeutic option when a fungal infection is suspected.


A versatile Trichoderma reesei expression system for the production of heterologous proteins.
To develop a versatile Trichoderma reesei (teleomorph Hypocrea jecorina) expression system for the high-purity production of heterologous proteins. The versatile T. reesei expression system is based on xyn1 and xyn2 promoters, A824V transition in XYRI, and a bicomponent carbon source strategy. Red fluorescent protein gene rfp and alkaline endoglucanase EGV gene egv3 from Humicola insolens were used as reporter genes to test our versatile expression system CONCLUSIONS: The versatile T. reesei expression system can be applied to produce heterologous proteins with high purity and high yield.


Effectiveness of Exogenous Fe2+ on Nutrient Removal in Gravel-Based Constructed Wetlands.
A group of microcosm-scale unplanted constructed wetlands (CWs) were established to evaluate the effectiveness of exogenous Fe2+ addition on ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3--N), and total phosphorus (TP) removal. The addition of Fe2+ concentrations were 5 mg/L (CW-Fe5), 10 mg/L (CW-Fe10), 20 mg/L (CW-Fe20), 30 mg/L (CW-Fe30), and 0 mg/L (CW-CK). The microbial community in CWs was also analyzed to reveal the enhancement mechanism of pollutant removal. The results showed that the addition of Fe2+ could significantly (p < 0.05) reduce the NO3--N concentration in the CWs. When 10 mg/L Fe2+ was added and the hydraulic retention time (HRT) was 8 h, the highest removal rate of NO3--N was 88.66%. For NH4+-N, when the HRT was 8-24 h, the removal rate of CW-Fe5 was the highest (35.23% at 8 h and 59.24% at 24 h). When the HRT was 48-72 h, the removal rate of NH4+-N in CWs with 10 mg/L Fe2+ addition was the highest (85.19% at 48 h and 88.66% and 72 h). The removal rate of TP in all CWs was higher than 57.06%, compared with CW-CK, it increased 0.63-31.62% in CWs with Fe2+ addition; the final effluent TP concentration in CW-Fe5 (0.13 mg/L) and CW-Fe10 (0.16 mg/L) met the class III water standards in Surface Water Environmental Quality Standards of China (GB3838-2002). Microbical diversity indexes, including Shannon and Chao1, were significantly lower (p < 0.05) in Fe2+ amended treatment than that in CW-CK treatment. Furthermore, phylum Firmicutes, family Carnobacteriaceae, and genus Trichococcus in Fe2+ amended treatments was significantly (p < 0.05) higher than that in CW-CK treatment. Fe3+ reducing bacteria, such as Trichococcus genus, belonging to the Carnobacteriaceae in family-level, and Lactobacillales order affiliated to Firmicutes in the phylum-level, can reduce the oxidized Fe3+ to Fe2+ and continue to provide electrons for nitrate. It is recommended to consider adding an appropriate amount of iron into the water to strengthen its purifying capacity effect for constructed artificial wetlands in the future.


[Thoracic x-ray computed tomography in pneumology].
Computerized tomography (CT) of the chest is now widely used in pneumological practice. It has completely superseded conventional tomography and reduced the number of bronchographies and pulmonary angiographies. CT is superior to conventional examinations in detecting lymph node enlargements, solid tumours, granulomas, fat deposits, calcifications, pulmonary necrosis and pleural plaques and in demonstrating tumoral limits. In the lung itself, the information provided by CT is of subsegmental accuracy. The new method is capable of diagnosing bronchiectasis and emphysema and evaluating their extension; it also gives a good visualization of chronic interstitial lung lesions.


OutKnocker: a web tool for rapid and simple genotyping of designer nuclease edited cell lines.
The application of designer nucleases allows the induction of DNA double-strand breaks (DSBs) at user-defined genomic loci. Due to imperfect DNA repair mechanisms, DSBs can lead to alterations in the genomic architecture, such as the disruption of the reading frame of a critical exon. This can be exploited to generate somatic knockout cell lines. While high genome editing activities can be achieved in various cellular systems, obtaining cell clones that contain all-allelic frameshift mutations at the target locus of interest remains a laborious task. To this end, we have developed an easy-to-follow deep sequencing workflow and the evaluation tool OutKnocker (www.OutKnocker.org), which allows convenient, reliable, and cost-effective identification of knockout cell lines.


Chitosan cross-linking with a water-soluble, blocked diisocyanate. 1. Solid state.
The present investigation focuses on the synthesis and application of a cross-linking agent that is compatible with the solubility characteristics of chitosan. A water-soluble, blocked-diisocyanate was prepared as a bisulfite adduct to 1,6-hexamethylene diisocyanate, which proved to be stable for several weeks in aqueous, acidic chitosan solutions at room temperature. Thermal cross-linking of chitosan as cast, dried films was investigated by varying the NCO/NH(2) ratio from 0.0 to 1.2. Spectroscopic (IR), thermal (TGA), swelling, and structural (WAXD) studies indicated that chitosan was cross-linked in a concentration-dependent manner under mild thermal conditions: 60 degrees C for 24 h. Cross-linking inefficiency was concluded to be due to lack of mobility of the reacting species in the solid state. In a preliminary study, the enzymatic degradation with Chitinase (E. C. 184.108.40.206) from Streptomyces griseus was found to be the greatest for non-crosslinked chitosan, followed by chitin, and then by cross-linked samples.


Clinical characteristics and outcomes of invasively ventilated patients with COVID-19 in Argentina (SATICOVID): a prospective, multicentre cohort study.
Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country. In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete. Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52-70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7-22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0-7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8-12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111-218), respiratory system compliance 36 mL/cm H2O (29-44), driving pressure 12 cm H2O (10-14), and FiO2 0·60 (0·45-0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01-1·03]), Charlson score (1·16 [1·11-1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10-1·71]), vasopressor use on day 1 (1·29 [1·07-1·55]), D-dimer concentration (1·02 [1·01-1·03]), PaO2/FiO2 on day 1 (0·998 [0·997-0·999]), arterial pH on day 1 (1·01 [1·00-1·01]), driving pressure on day 1 (1·05 [1·03-1·08]), acute kidney injury (1·66 [1·36-2·03]), and month of admission (1·10 [1·03-1·18]) as independent predictors of mortality. In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere. None. For the Spanish translation of the Summary see Supplementary Materials section.


Lifetime excess cancer risk due to carcinogens in food and beverages: Urban versus rural differences in Canada.
To explore differences in urban versus rural lifetime excess risk of cancer from five specific contaminants found in food and beverages. Probable contaminant intake is estimated using Monte Carlo simulations of contaminant concentrations in combination with dietary patterns. Contaminant concentrations for arsenic, benzene, lead, polychlorinated biphenyls (PCBs) and tetrachloroethylene (PERC) were derived from government dietary studies. The dietary patterns of 34 944 Canadians from 10 provinces were available from Health Canada's Canadian Community Health Survey, Cycle 2.2, Nutrition (2004). Associated lifetime excess cancer risk (LECR) was subsequently calculated from the results of the simulations. In the calculation of LECR from food and beverages for the five selected substances, two (lead and PERC) were shown to have excess risk below 10 per million; whereas for the remaining three (arsenic, benzene and PCBs), it was shown that at least 50% of the population were above 10 per million excess cancers. Arsenic residues, ingested via rice and rice cereal, registered the greatest disparity between urban and rural intake, with LECR per million levels well above 1000 per million at the upper bound. The majority of PCBs ingestion comes from meat, with values slightly higher for urban populations and LECR per million estimates between 50 and 400. Drinking water is the primary contributor of benzene intake in both urban and rural populations, with LECR per million estimates of 35 extra cancers in the top 1% of sampled population. Overall, there are few disparities between urban and rural lifetime excess cancer risk from contaminants found in food and beverages. Estimates could be improved with more complete Canadian dietary intake and concentration data in support of detailed exposure assessments in estimating LECR.


Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine.
Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia. The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg). The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups. We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine.


Opiate modulating properties of nociceptin/orphanin FQ.
The recently discovered peptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOR share many structural similarities with the opioid peptides and their receptors. The anatomical distributions of N/OFQ and NOR are similar to those of opioid peptides and receptors. In addition, NOR and opiate receptors couple via the same G-proteins to similar effectors, such as Ca(2+) channels, K(+) channels, adenylyl cyclase, and several protein kinases. Thus, the behavioral effects of N/OFQ have been investigated in the context of known opiate effects, and a possible connection has been sought between the effects of these two homologous signaling systems. Originally characterized as a nociception-producing peptide, N/OFQ has now been shown to have diverse effects on nociception, as well as effects on many other behaviors. With regard to nociception, the peptide has been reported to produce hyperalgesia, reversal of opioid-mediated analgesia, analgesia, and allodynia. N/OFQ also has effects on other behaviors, such as locomotion, feeding, anxiety, spatial attention, reproductive behaviors, and opiate tolerance. The relationship between opiates and N/OFQ is strengthened by the fact that opiates also affect these behaviors. However, the exact nature of the relationship of N/OFQ with opiates-opiate-like versus antiopiate-remains controversial. This review will detail the diverse effects of N/OFQ and suggest that this peptide, like other putative antiopiate peptides, can be described as 'opiate modulating. '


BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA.
Members of the BCL-2-related antiapoptotic family of proteins have been shown previously to regulate ATP/ADP exchange across the mitochondrial membranes and to prevent the loss of coupled mitochondrial respiration during apoptosis. We have found that BCL-2/BCL-x(L) can also improve mitochondrial oxidative phosphorylation in cells harboring pathogenic mutations in mitochondrial tRNA genes. The effect of BCL-2 overexpression in mutated cells was independent from apoptosis and was presumably associated with a modulation of adenine nucleotide exchange between mitochondria and cytosol. These results suggest that BCL-2 can regulate respiratory functions in response to mitochondrial distress by regulating the levels of adenine nucleotides.


Mixed stitching interferometry with correction from one-dimensional profile measurements for high-precision X-ray mirrors.
This work presents a mixed stitching interferometry method with correction from one-dimensional profile measurements. This method can correct the error of stitching angles among different subapertures using the relatively accurate one-dimensional profiles of the mirror, e.g., provided by the contact profilometer. The measurement accuracy is simulated and analyzed. The repeatability error is decreased by averaging multiple measurements of the one-dimensional profile and using multiple profiles at different measurement positions. Finally, the measurement result of an elliptical mirror is presented and compared with the global algorithm-based stitching, and the error of the original profiles is reduced to one-third. This result shows that this method can effectively suppress the accumulation of stitching angle errors in classic global algorithm-based stitching. The accuracy of this method can be further improved by using high-precision one-dimensional profile measurements such as the nanometer optical component measuring machine (NOM).


Selective Potassium Chloride Recognition, Sensing, Extraction, and Transport Using a Chalcogen-Bonding Heteroditopic Receptor.
Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M+ (M+ = K+, Rb+, Cs+) sandwich complex and bidentate ChB···X- formation. Extensive quantitative 1H NMR ion-pair affinity titration experiments, solid-liquid and liquid-liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor's ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation-anion ion-pair binding observations for halides and oxoanions.


Enhanced expression of Fc alpha receptor I on blood phagocytes of patients with gram-negative bacteremia is associated with tyrosine phosphorylation of the FcR-gamma subunit.
Sepsis caused by gram-negative bacteria is a common finding having high incidence and mortality. Fc alpha RI (CD89), a receptor for immunoglobulin A (IgA), has been shown to mediate bacterial phagocytosis, which might play a role in the pathogenesis of sepsis. In this study the expression and function of Fc alpha RI were analyzed on blood monocytes and neutrophils of patients with bacteremia. We found a marked increased in expression of the alpha- and gamma-subunits of the Fc alpha RI on both types of cells in patients with gram-negative bacteremia, but not in patients with gram-positive bacteremia. This increase was independent of serum IgA levels. Fc alpha RI M(r) was lower on cells from gram-negative patients than on cells from controls (50-65 kDa versus 55-75 kDa), despite a similar 32-kDa backbone, indicating altered glycosylation. Increased levels of Fc alpha RI on blood phagocytes correlated with enhanced serum IL-6 levels, but not with IFN gamma or TNF-alpha. FcR-gamma chain associated with Fc alpha RI was phosphorylated in patients neutrophils, indicating functional engagement of this receptor during gram-negative sepsis. Increased expression and activation of Fc alpha RI-gamma 2 complexes following gram-negative infections suggests its involvement in host defense against bacteria.


Prism adaptation and spatial neglect: the need for dose-finding studies.
Spatial neglect is a devastating disorder in 50-70% of right-brain stroke survivors, who have problems attending to, or making movements towards, left-sided stimuli, and experience a high risk of chronic dependence. Prism adaptation is a promising treatment for neglect that involves brief, daily visuo-motor training sessions while wearing optical prisms. Its benefits extend to functional behaviors such as dressing, with effects lasting 6 months or longer. Because one to two sessions of prism adaptation induce adaptive changes in both spatial-motor behavior (Fortis et al., 2011) and brain function (Saj et al., 2013), it is possible stroke patients may benefit from treatment periods shorter than the standard, intensive protocol of ten sessions over two weeks-a protocol that is impractical for either US inpatient or outpatient rehabilitation. Demonstrating the effectiveness of a lower dose will maximize the availability of neglect treatment. We present preliminary data suggesting that four to six sessions of prism treatment may induce a large treatment effect, maintained three to four weeks post-treatment. We call for a systematic, randomized clinical trial to establish the minimal effective dose suitable for stroke intervention.


Mechanism, Kinetics, and Potential of Mean Force of Evaporation of Water from Aqueous Sodium Chloride Solutions of Varying Concentrations.
The mechanism, kinetics, and potential of mean force of evaporation of water from aqueous NaCl solutions are investigated through both unbiased molecular dynamics simulations and also biased simulations using the umbrella sampling method. The results are obtained for aqueous solutions of three different NaCl concentrations ranging from 0.6 to 6.0 m and also for pure water. The rate of evaporation is found to decrease in the presence of ions. It is found that the process of evaporation of a surface water molecule from ionic solutions can be triggered through its collision with another water or chloride ion. Such collisions provide the additional kinetic energy that is required for evaporation. However, when the collision takes place with a Cl- ion, the evaporation of the escaping water also involves a collision with water in the vicinity of the ion at the same time along with the ion-water collision. These two collisions together provide the required kinetic energy for escape of the evaporating water molecule. Thus, the mechanism of evaporation process of ionic solutions can be more complex than that of pure water. The potential of mean force (PMF) of evaporation is found to be positive and it increases with increasing ion concentration. Also, no barrier in the PMF is found to be present for the condensation of water from vapor phase to the surfaces of the solutions. A detailed analysis of the unsuccessful evaporation attempts by surface water molecules is also made in the current study.


The last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) plays a central role in insulin signaling and the Golgi/endosomes protein network.
Insulin is internalized with its cognate receptor into the endosomal apparatus rapidly after binding to hepatocytes. We performed a bioinformatic screen of Golgi/endosome hepatic protein fractions and found that ATIC, which is a rate-limiting enzyme in the de novo purine biosynthesis pathway, and PTPLAD1 are associated with insulin receptor (IR) internalization. The IR interactome (IRGEN) connects ATIC to AMPK within the Golgi/endosome protein network (GEN). Forty-five percent of the IR Golgi/endosome protein network have common heritable variants associated with type 2 diabetes, including ATIC and AMPK. We show that PTPLAD1 and AMPK are rapidly compartmentalized within the plasma membrane (PM) and Golgi/endosome fractions after insulin stimulation and that ATIC later accumulates in the Golgi/endosome fraction. Using an in vitro reconstitution system and siRNA-mediated partial knockdown of ATIC and PTPLAD1 in HEK293 cells, we show that both ATIC and PTPLAD1 affect IR tyrosine phosphorylation and endocytosis. We further show that insulin stimulation and ATIC knockdown readily increase the level of AMPK-Thr172 phosphorylation in IR complexes. We observed that IR internalization was markedly decreased after AMPKα2 knockdown, and treatment with the ATIC substrate AICAR, which is an allosteric activator of AMPK, increased IR endocytosis in cultured cells and in the liver. These results suggest the presence of a signaling mechanism that senses adenylate synthesis, ATP levels, and IR activation states and that acts in regulating IR autophosphorylation and endocytosis.


Mitochondrial disease in flies.
The Drosophila mutant technical knockout (tko), affecting the mitochondrial protein synthetic apparatus, exhibits respiratory chain deficiency and a phenotype resembling various features of mitochondrial disease in humans (paralytic seizures, deafness, developmental retardation). We are using this mutant to analyse the cellular and genomic targets of mitochondrial dysfunction, and to identify ways in which the phenotype can be alleviated. Transgenic expression of wild-type tko in different patterns in the mutant background reveals critical times and cell-types for production of components of the mitochondrial disease-like phenotype. Mitochondrial bioenergy deficit during the period of maximal growth, as well as in specific parts of the nervous system, appears to be most deleterious. Inbreeding of tko mutant lines results in a systematic improvement in all phenotypic parameters tested. The resulting sub-lines can be used for genetic mapping and transcriptomic analysis, revealing clues as to the genes and pathways that can modify mitochondrial disease-like phenotypes in a model metazoan.


[Deficits in adherence on all levels. Current need of interventions in primary, secondary, and tertiary prevention of cardiovascular diseases].
Previous studies often lack any differentiation between target groups for primary, secondary and tertiary prevention of cardiovascular disease (CVD). The aim of this study was to investigate the target group-specific adherence with lifestyle recommendations in different risk groups. This information may be useful in identifying better starting points for future CVD interventions. 2,002 men and women aged 50 to 70 years were selected by random and interviewed about their health status, health behavior and health locus of control. Adherence was defined as regular physical activity, healthy diet, non-smoking, and moderate alcohol consumption. Differences between risk groups were determined using Chi-square tests and stratified logistic regression. Health behavior only varied to a limited extent between the risk groups: physical activity (77.8%), healthy diet (62.2%), moderate alcohol consumption (74.4%), non-smoking (total: 75.7%; healthy respondents 70.9%; risk group 79.1%; CVD patients 74.7%). 29.6% were adherent to lifestyle recommendations. Women were more likely to be adherent than men (35.4% vs. 23.5%). In CVD patients, those living together with a partner were also more likely to have a healthy lifestyle (32.2% vs. 20.0%). Furthermore, health locus of control seems to be an important factor. In the age group 50-70 adherence with lifestyle recommendations of almost 30% is rather low and not optimal. Health locus of control as motivational barrier should be taken into account particularly in secondary prevention. There is a need of health behavior interventions not only for persons at increased risk and CVD patients, but also for the (still) healthy. Men, singles and persons with external health locus of control should be particularly addressed by these interventions.


The application of bone graft substitutes for alveolar ridge preservation after orthodontic extractions and for augmentation of residual cleft defects.
The use of bone substitute materials in orthodontics is to be considered prior to orthodontic space closure after tooth extraction during the treatment of marked crowding as well as for treatment of residual defects in cleft-lip-and-palate children. In both cases the common objective is structure preservation or augmentation of the alveolar ridge. The demands to be made on the synthetic bone graft substitute comprise not just complication-free and safe use but also the chance of early tooth movement into the treated defect area with sufficient stability of the new tooth position.


The complexity of oral physiology and its impact on salivary diagnostics.
Saliva contains biomarkers for systemic as well as oral diseases. This study was undertaken to assess the variability in the sources of such biomarkers (plasma, cells) and attempted to identify saliva deterioration markers in order to improve saliva diagnostic outcomes. Inter- and intrasubject variations in salivary gingival crevicular fluid levels were determined by measuring salivary albumin and transferrin levels. The purity of collected glandular secretions was determined by bacterial culture, and the variability in epithelial cell numbers by cell counting and optical density measurement. Saliva sample deterioration markers were identified by RP-HPLC and LC-ESI-MS/MS. Tenfold variations were observed in plasma-derived albumin and transferrin levels, emphasizing the need for biomarker normalization with respect to plasma contributions to saliva. Epithelial cell levels varied 50-fold in samples collected before and after a meal. Salivary fungal levels varied within subjects and among subjects from 0 to >1,000 colony-forming units per milliliter. In saliva samples incubated for various time intervals at 37°C, five peptides were identified that steadily increased in intensity over time and which could be explored as "deterioration markers." Taking saliva characteristics appropriately into account will help realize the promise that this body fluid is suitable to be exploited for reliable healthcare monitoring and surveillance.


Confocal microscopy of corneal flap microfolds after LASIK.
To describe the morphological characteristics of microfolds that appear at the corneal flap after LASIK, as seen under confocal microscopy. Twenty-one eyes that had undergone LASIK were examined, all within 3 weeks to 1 month after surgery. A central scan of the total corneal thickness was obtained by using confocal microscopy in vivo. Confocal images were captured and digitized. The longitudinal orientation (vertical, horizontal, and oblique) and morphological characteristics of the microfolds were described and recorded. Six eyes had folds at the central corneal flap, visible as linear distortions in the confocal images: one fold had a vertical orientation, two were horizontal, and three were oblique. The folds were visible from the epithelial basal cell layer to the stromal portion of the flap and were deeper than Bowman's layer. Confocal microscopy allowed visualization of microfolds after LASIK. With the appropriate software, it is possible to analyze the morphological characteristics of these folds. Flap microfolds after LASIK are deeper than Bowman's layer.


Adenoid cystic carcinoma associated with mucous retention cyst of the parotid gland.
Mucous retention cysts of the parotid gland are rare, and a coexistent adenoid cystic carcinoma is even an unusual occurrence. Such coexistent adenoid cystic carcinomas with mucous retention cyst of the parotid gland are difficult to diagnose clinically and, at times, stage difficulty in their management. We report a rare case of adenoid cystic carcinoma associated with mucous retention cyst of the parotid gland with its diagnostic and management dilemma in a 14-year-old adolescent girl.


Neuraminidase activity in middle ear effusions.
Analyses of Streptococcus pneumoniae culture filtrates and middle ear effusions (MEE) containing S pneumoniae for various hydrolytic enzymes have demonstrated substantial levels of neuraminidase activity when measured employing a sensitive fluorometric assay. S pneumoniae neuraminidase exhibits optimum activity near neutral pH (6.0 to 6.5), and catalyzes the cleavage of sialic acid residues from glycoproteins, gangliosides and mucopolysaccharides. S pneumoniae begins secreting large amounts of neutral neuraminidase (mean [means] = 43.3 units/mL culture filtrate) when cells enter the stationary phase. Nearly all (96%) human chronic MEEs yielding positive cultures for S pneumoniae contain neuraminidase activity (means = 0.200 units/mg protein), while only 21.1% to 45.5% of all other effusions contain the enzyme. Middle ear effusions obtained from S pneumoniae infected-chinchillas contained large amounts of neuraminidase activity (approximately 200 units/mL), which decayed exponentially in vivo with an apparent half-life of 8 1/2 days. Three neuraminidase isoenzymes (designated I-III) were identified in S pneumoniae culture filtrates, as well as in MEEs from chinchillas infected with the organism, using a combination of ion-exchange and gel filtration chromatography. With 4-methylumbelliferyl-N-acetylneuraminic acid serving as substrate, preparation I from both culture filtrates and MEEs was characterized by a high Michaelis constant (Km), while forms II and III had low Km values. Preferred substrates were orosomucoid and neuramin-lactose; gangliosides, thyroglobulin, and bovine submaxillary mucin were poorer substrates.


Virus Surveys in Olive Orchards in Greece Identify Olive Virus T, a Novel Member of the Genus Tepovirus.
Field surveys were conducted in Greek olive orchards from 2017 to 2020 to collect information on the sanitary status of the trees. Using a high-throughput sequencing approach, viral sequences were identified in total RNA extracts from several trees and assembled to reconstruct the complete genomes of two isolates of a new viral species of the genus Tepovirus (Betaflexiviridae), for which the name olive virus T (OlVT) is proposed. A reverse transcription-polymerase chain reaction assay was developed which detected OlVT in samples collected in olive growing regions in Central and Northern Greece, showing a virus prevalence of 4.4% in the olive trees screened. Sequences of amplified fragments from the movement-coat protein region of OlVT isolates varied from 75.64% to 99.35%. Three olive varieties (Koroneiki, Arbequina and Frantoio) were infected with OlVT via grafting to confirm a graft-transmissible agent, but virus infections remained latent. In addition, cucumber mosaic virus, olive leaf yellowing-associated virus and cherry leaf roll virus were identified.


[Genetic diversity of Citrus succosa Hort. Ex Tanaka from seven provinces as revealed by AFLP analysis].
Using 28 selected primer combinations, 12 accessions of Bendizao tangerine from seven provinces were investigated by AFLP analysis. A total of 882 genetic sites were detected, among which 192 were polymorphic. Using Huangyan Bendizao as contrast, the polymorphic sites of the other 11 accessions from seven provinces are not very high (3.5%-10.54%), and the number of different sites between accessions from other provinces is higher than that from Zhejiang province, which indicates that the ecological difference can partially contribute the formation of the genetic diversity. Genetic distance and dendrogram showed considerably close relatedness among the 12 accessions, and the max genetic distance was 0.229. The genetic analysis of the 12 accessions from seven provinces can provide useful information for the relationship between the formation of genetic variation and environmental difference and can facilitate the genetic improvement of this cultivar.


Atomistic simulations of electroporation in water preembedded membranes.
Atomistic simulations of electroporation were conducted on water/membrane/water systems, in which the membranes initially contained randomly distributed water molecules that might be introduced by acoustic treatment. The simulation results indicate that the critical strength of an applied electric field to induce electroporation is greatly reduced due to the initially embedded water molecules in the membranes. A lower applied electric field will significantly enhance the viability of cells in electroporation.


Muscle fatigue during dynamic contractions assessed by new spectral indices.
The aim of the present study was to test the applicability and sensitivity of new electromyography (EMG) spectral indices in assessing peripheral muscle fatigue during dynamic knee-extension exercise. Seven subjects completed 10 sets of 15 repetitions of right knee-extension exercise lifting 50% of their one-repetition maximum. Torque (T), knee-joint angle, and the interference EMG of rectus femoris muscle were recorded simultaneously. Maximal voluntary isometric contraction (MVC) was tested before and after exercise. Median spectral frequency (Fmed) and new spectral indices of muscle fatigue (FInsmk) were calculated for each repetition. The rate and range of FInsmk- and Fmed-relative changes against the first repetition of the corresponding set increased gradually across successive repetitions within the set, reflecting accumulation of peripheral muscle fatigue. The maximal change of FInsmk observed in the present experiment was approximately eightfold, whereas that of Fmed was only 32%. Significant between-subject variability in the range of FInsmk changes (P < 0.0001) was found, so a hierarchical cluster analysis of muscle fatigue indices was conducted. Three distinct subgroups of subjects were identified: high (N = 1, FInsmk change > 400%), medium (N = 4, 200% < FInsmk change < 400%), and low (N = 2, FInsmk change < 200%) muscle fatigability. The changes in muscle performance during (last vs first repetition peak T, P = 0.03) and after (post- vs preexercise MVC, P = 0.012) exercise were significantly different between clusters (one-way ANOVA). The rate of fatigue development was also significantly different between clusters (linear regression analysis of Fmed and FInsmk changes). The new spectral indices are a valid and reliable tool for assessment of muscle fatigability irrespective of EMG signal variability caused by dynamic muscle contractions, and these indices are more sensitive than those traditionally used.


Transient Global Ischemia-Induced Brain Inflammatory Cascades Attenuated by Targeted Temperature Management.
Sudden cardiac arrest leads to a significantly increased risk of severe neurological impairment and higher mortality rates in survivors due to global brain tissue injury caused by prolonged whole-body ischemia and reperfusion. The brain undergoes various deleterious cascading events. Among these damaging mechanisms, neuroinflammation plays an especially crucial role in the exacerbation of brain damage. Clinical guidelines indicate that 33 °C and 36 °C are both beneficial for targeted temperature management (TTM) after cardiac arrest. To clarify the mechanistic relationship between TTM and inflammation in transient global ischemia (TGI) and determine whether 36 °C produces a neuroprotective effect comparable to 33 °C, we performed an experiment using a rat model. We found that TTM at 36 °C and at 33 °C attenuated neuronal cell death and apoptosis, with significant improvements in behavioral function that lasted for up to 72 h. TTM at 33 °C and 36 °C suppressed the propagation of inflammation including the release of high mobility group box 1 from damaged cells, the activation and polarization of the microglia, and the excessive release of activated microglia-induced inflammatory cytokines. There were equal neuroprotective effects for TTM at 36 °C and 33 °C. In addition, hypothermic complications and should be considered safe and effective after cardiac arrest.


Wheat bran layers: composition, structure, fractionation, and potential uses in foods.
Wheat bran, the main by-product of dry milling of wheat, is currently mainly used in the animal feed industry, but has attracted attention as a food ingredient owing to its high dietary fiber and phytochemical contents, providing excellent physiological effects. The bran layers (aleurone layer, outer pericarp and intermediate layer) contain different compositions, structures, and nutrients, and have different properties. Each layer, when separated and isolated, potentially could find more extensive applications in foods. This triggered interest in isolating the bran layers using milling and wet- or dry-fractionation techniques based on their chemical or physical properties. The recent progress has allowed the production of commercial products from wheat bran layers, particularly aleurone-rich products, enhancing the value of wheat bran layers and their applications in food. The present review highlights the recent advances in studying the chemical composition including distribution of chemical components, physical structure, biopolymer matrix, and physicochemical properties of each wheat bran layer. Technologies to fractionate wheat bran layers and utilization of different bran layers in foods are discussed and reviewed, providing new strategies for improving the value of wheat bran and utilization of wheat bran in foods.


Extracellular laccase from Monilinia fructicola: isolation, primary characterization and application.
Laccases are enzymes belonging to the family of blue copper oxidases. Due to their broad substrate specificity, they are widely used in many industrial processes and environmental bioremediations for removal of a large number of pollutants. During last decades, laccases attracted scientific interest also as highly promising enzymes to be used in bioanalytics. The aim of this study is to obtain a highly purified laccase from an efficient fungal producer and to demonstrate the applicability of this enzyme for analytics and bioremediation. To select the best microbial source of laccase, a screening of fungal strains was carried out and the fungus Monilinia fructicola was chosen as a producer of an extracellular enzyme. Optimal cultivation conditions for the highest yield of laccase were established; the enzyme was purified by a column chromatography and partially characterized. Molecular mass of the laccase subunit was determined to be near 35 kDa; the optimal pH ranges for the highest activity and stability are 4.5-5.0 and 3.0-5.0, respectively; the optimal temperature for laccase activity is 30°C. Laccase preparation was successfully used as a biocatalyst in the amperometric biosensor for bisphenol A assay and in the bioreactor for bioremediation of some xenobiotics.


Efficacy of up-front treatment with a double stem cell transplantation in multiple myeloma.
We report the outcome of 53 patients with multiple myeloma (MM), who received autologous stem cell transplantation (ASCT) from April 1996 to September 2004 at our institution and who survived for more than 3 months after the transplant. Following the first ASCT, 36 patients underwent an up-front second SCT, which consisted of either an ASCT (n = 24) or a reduced-intensity conditioning allogeneic stem cell transplant (RIST) (n = 12). Seventeen patients were given maintenance treatment. Seventy-seven percent of the patients (n = 41) showed an objective response to the initial therapy prior to the first ASCT. Overall, 60.4% (32 out of 53) and 32.1% (17 out of 53) of the patients had a complete response (CR) and partial response (PR) after the first ASCT, respectively. At the time of analysis, 34 patients (64.2%) were still alive. With a median follow-up of 32 months (range 9-98), the estimated progression-free survival (PFS) and overall survival (OS) at 5 years were 17.0 and 34.9%, respectively. Multivariate analysis revealed that the second SCT, normal hemoglobin and <50% marrow plasma cells were associated with an improved PFS. A second SCT, CR to the first SCT, female gender and an absence of advanced bone lesions were associated with a better OS. A second SCT is the most significant factor for an improved PFS and OS after the first ASCT (P < 0.001, respectively). Up-front double SCT is needed to improve the OS and PFS in patients with MM.


Singaporeans' perceptions of and attitudes toward long-term care services.
Use of long-term care (LTC) services among older adults in Asia has emerged as an important issue in light of rapidly aging countries and changing family structures. Simply building more LTC facilities will not result in higher usage rates, and more insight is needed on the usage of existing services. Few studies have been conducted among Asian populations outside Western settings on this topic. The multi-ethnic population in Singapore is useful for understanding the factors influencing the use of long-term care services in Asia. We present our qualitative findings on long-term care service usage in the older population (50+ years) over time. We highlight caregivers' needs as an important determinant of LTC use. Although preferences of the care recipients were considered, caregiver needs, the availability of formal and informal care support, attitudes, perceived control, and social norms surrounding family caregiving governed the use of formal LTC services in Singapore.


[Essential diet in extensive cervico-facial surgery].
A prospective nutritional study was undertaken on 26 patients submitted to pharyngo-laryngectomy with pre-operative irradiation. Three diets were compared, given through a naso-gastric Levine tube. The first diet being the hospital blenderized diet, the second one Flexical, and the third one, Flexical Control. There was no significant difference between Flexical and Flexical Control, but the biological parameters and the clinical evolution militate in favor of a widespread use of the Flexical method. The authors recommend the use of controlled defined diet as compared to the hospital blenderized diet and the more sophisticated and more expensive method as the intravenous hyperalimentation.


Orbital Floor Fracture.
The medial wall and floor of the bony orbit are frequently fractured because of the delicate anatomy. To optimize functional and aesthetic results, reconstructive surgeons should understand the anatomy and pathophysiology of orbital fractures. Appropriate treatment involves optimal timing of intervention, proper indications for operative repair, incision and dissection, release of herniated tissue, implant material and placement, and wound closure. The following review will discuss the management of orbital floor fractures, with the operative method preferred by the author. Special considerations in operation technique and the complication are also present in this article.


Purification and characterization of the 30S ribosomal proteins from the bacterium Thermus thermophilus.
The total protein mixture of the 30S subunit (TP-30) of the bacterium Thermus thermophilus has been purified using reverse-phase HPLC and the proteins obtained were identified both by means of two-dimensional polyacrylamide gel electrophoresis as well as by amino-terminal amino acid microsequence analysis. The proteins are numbered according to their primary structural similarity with known prokaryotic ribosomal proteins. Eight of them, namely proteins S6, S7, S9, S10, S14, S15, S16 and S17 run at different positions in the two-dimensional gel electrophoresis system to those suggested [Sedelnikova, S. C., Agalarov, M. B., Garber, M. & Yusupov, M. M. (1987) FEBS Lett. 220, 227-230]. All characterized proteins are homologous to known ribosomal proteins from other species, except for a small basic protein which shows homology only to a ribosomal protein from spinach chloroplasts [Choli, T., Franceschi, F., Yonath, A. & Wittmann-Leibold, B. (1993) Biol. Chem. Hoppe-Seyler 374, 377-383; Subramanian, A.-R. (1984) Trends Biochem. Sci. 9, 491-494].


What Happens When an Intersex Baby Happens.
Psychoanalytic efforts to think sexual difference beyond the restrictions of binary notions about anatomy and gender continue to prove challenging in both clinical practice and theory building. Claims that such binary notions are no longer applicable fail to take seriously the ongoing power of binary processes as they manifest both consciously and unconsciously. Without a capacity to think sexual difference as more than two, a capacity that resists the lure of spectrum modeling, efforts to conceptualize intersexuality and other nonbinary forms of anatomy and gender falter. An exploration into the challenges faced by two parents of an intersex baby, especially regarding the dilemma of pursuing genital surgery or not, shows some of the difficulties inherent in thinking sexual difference when the profound inadequacy of binary notions cannot be ignored.


Prevalence of dental anxiety among 5- to 8-year-old Taiwanese children.
Many people experience discomfort to a greater or lesser degree about the prospect of dental treatment. Dental treatment can be a terrible experience, especially for children with dental anxiety. This study estimated the prevalence of dental anxiety among 5- to 8-year-old children in Kaohsiung City, Taiwan. The Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) was translated into Chinese, and a receiver operating characteristic (ROC) curve was made based on criteria determined from pretest clinical observations of a sample population to set a cutoff score. Then, the parental CFSS-DS was used as a screening tool to survey the dental anxiety levels of 5- to 8-year-old children at kindergartens and elementary schools in Kaohsiung City, Taiwan. Participants were selected by stratified random sampling. The stratification was done by geographic district, age group, and sex. A total of 3,597 valid questionnaires were collected. The Chinese version of the CFSS-DS had an optimal cutoff score of 38/39 (sensitivity was 0.857, specificity was 0.882) with an area under the ROC curve of 0.912. The estimated prevalence of dental anxiety among 5- to 8-year-old children in Kaohsiung City was 20.6 percent. The dental anxiety score was found to decrease as age increased; primary school boys had significantly lower scores. The prevalence of dental anxiety was found to be high for 5- to 8-year-old Taiwanese children. The study's findings point to the urgent need for preventive health education and intervention programs in Taiwan to promote children's oral health and reduce dental anxiety.


Hepatocellular carcinoma: a review of the surgical approaches to management.
Hepatocellular carcinoma (HCC) is increasing in incidence in the United States and is strongly associated with chronic liver disease and cirrhosis. Surgical therapy with liver transplantation or resection remains the mainstay of curative therapy for patients with HCC. Therapeutic decisions in patients with HCC are complex and are best approached via a multidisciplinary group of liver transplant and hepatobiliary surgeons, oncologists, and hepatologists. In this manuscript, we review the current surgical management of HCC.


Adenocarcinoma of the esophagogastric junction and its background mucosal pathology: A comparative analysis according to Siewert classification in a Japanese cohort.
Adenocarcinoma of the esophagogastric junction (AEG) has heterogeneous carcinogenic process due to its location straddling the esophagogastric junction. We assessed background mucosal pathology and its correlation with clinicopathological features of each Siewert type of AEG. Clinicopathological and immunohistochemical analyses of 103 AEGs and 58 gastric cancers (GCs) were conducted. Background mucosal features were evaluated according to the updated Sydney System. Siewert classification divided 103 AEGs into three type I, 75 type II, and 25 type III tumors, respectively. Two type I, 9 type II AEGs, and none of type III AEGs were Barrett-related and were excluded from further analysis. Background mucosa of type III AEGs more frequently showed moderate to marked degree of atrophy and intestinal metaplasia than those of type II AEGs and was very similar to those of GCs. Among type II AEGs, tumors with atrophic background were significantly associated with higher patient age and intestinal-type histology. Type II AEGs with nonatrophic background, but not those with atrophic background, showed more frequent mismatch repair deficiency, TP53 overexpression, and less frequent intestinal phenotypic markers expression than type III AEG or GC. Type II AEGs with atrophic background involved suprapancreatic nodes more frequently than those without. We demonstrated that chronic atrophic gastritis was a major precancerous condition of AEG in the Japanese population, especially Siewert type III which had background mucosal pathology similar to that of GC. Type II AEGs with and without atrophic background showed some clinicopathological differences, and these observations might represent heterogeneous carcinogenic process within type II AEGs.


Local Health Department and Hospital Collaboration Around Community Health Needs Assessment to Improve Health Outcomes.
The objectives of this study were to examine the relationships between local health department (LHD) and nonprofit hospital collaboration around community health needs assessment (CHNA), levels of collaboration, and selected community health outcomes. Data were obtained from multiple sources including the National Profile of Local Health Departments. Results showed that high levels of LHD-hospital collaboration around CHNA were associated with lower self-reported poor or fair health, lower years of potential life lost per 100 000 population, and lower premature age-adjusted mortality per 100 000 population. More research is needed to examine the influence of collaboration around CHNA on community health.


Chernobyl fallout in southern and central Finland.
To study the levels and distributions of radionuclides released in the Chernobyl accident, we sampled surface peat from 62 sites in Southern and Central Finland and measured 131I, 134Cs, 137Cs, 132Te, 140Ba, 103Ru, 90Sr, 141Ce, and 95Zr. The distribution of fallout activities was highly uneven, depending on movement of the contaminated air mass and rainfall distribution during the critical days. The highest values observed were 420 kBq m-2 of 131I and 70 kBq m-2 of 137Cs. The nuclide ratios showed wide and partly unexpected variations. The high-boiling-point, or nonvolatile, elements Ce and Zr were spread mostly on a 200-km-wide zone extending across Finland from southwest to northeast. The more volatile elements, I, Ce, and Te, showed quite a different, more widespread, fallout distribution, while an intermediate behavior was observed for Ba, Ru, and possibly Sr. These results can be explained by assuming that pulverized nuclear fuel material released in the reactor explosion on 26 April reached Finland via Poland and the Baltic Sea and traversed the country along the above-mentioned narrow zone, while volatile material, evaporated in the reactor fire from 26 April to 5 May, arrived in several waves and was consequently more widely and evenly spread. From their elemental melting and boiling points, Ru and Mo would appear to belong to the nonvolatile group and Sr to the volatile. Yet, their actual behaviors were opposite; Ru in particular was found in the nonvolatile as well as the volatile fallout, possibly because Ru activities were present in the fuel partly in the metallic state and partly as volatile oxides.


C4 Bacterial Volatiles Improve Plant Health.
Plant growth-promoting rhizobacteria (PGPR) associated with plant roots can trigger plant growth promotion and induced systemic resistance. Several bacterial determinants including cell-wall components and secreted compounds have been identified to date. Here, we review a group of low-molecular-weight volatile compounds released by PGPR, which improve plant health, mostly by protecting plants against pathogen attack under greenhouse and field conditions. We particularly focus on C4 bacterial volatile compounds (BVCs), such as 2,3-butanediol and acetoin, which have been shown to activate the plant immune response and to promote plant growth at the molecular level as well as in large-scale field applications. We also disc/ uss the potential applications, metabolic engineering, and large-scale fermentation of C4 BVCs. The C4 bacterial volatiles act as airborne signals and therefore represent a new type of biocontrol agent. Further advances in the encapsulation procedure, together with the development of standards and guidelines, will promote the application of C4 volatiles in the field.


Classification of 5-HT(1A) receptor agonists and antagonists using GA-SVM method.
To construct a reliable computational model for the classification of agonists and antagonists of 5-HT(1A) receptor. Support vector machine (SVM), a well-known machine learning method, was employed to build a prediction model, and genetic algorithm (GA) was used to select the most relevant descriptors and to optimize two important parameters, C and r of the SVM model. The overall dataset used in this study comprised 284 ligands of the 5-HT(1A) receptor with diverse structures reported in the literatures. A SVM model was successfully developed that could be used to predict the probability of a ligand being an agonist or antagonist of the 5-HT(1A) receptor. The predictive accuracy for training and test sets was 0.942 and 0.865, respectively. For compounds with probability estimate higher than 0.7, the predictive accuracy of the model for training and test sets was 0.954 and 0.927, respectively. To further validate our model, the receiver operating characteristic (ROC) curve was plotted, and the Area-Under-the-ROC- Curve (AUC) value was calculated to be 0.883 for training set and 0.906 for test set. A reliable SVM model was successfully developed that could effectively distinguish agonists and antagonists among the ligands of the 5-HT(1A) receptor. To our knowledge, this is the first effort for the classification of 5-HT(1A) receptor agonists and antagonists based on a diverse dataset. This method may be used to classify the ligands of other members of the GPCR family.


[Aspiration and ingestion of dental instruments--diagnosis, treatment and prevention].
Aspiration and ingestion of foreign bodies of dental origin during treatment may cause a gastrointestinal and airway obstruction or perforation, and may constitute a life threatening situation. Ingestion occurs more often than aspiration and usually does not cause any clinical signs or symptoms. Most often it will spontaneously rejected from the gastrointestinal tract by peristaltic movement without any coimplication. However aspiration always requires treatment since foreign bodies there may cause inflammatory reaction and even severe obstruction and death. This article describes one case of aspiration and 3 cases of ingestion of dental instruments and materials. We discuss the diagnostic procedure: evidence of clinical signs and plain radiography, CT and the use of contrast material in case of radiolucent foreign bodies. The modern technique of endoscopy is successfully performed for diagnosis and treatment of foreign bodies in case of aspiration with minimal complications. We suggest a step by step protocol of treatment at the dental clinic in the case of ingestion/aspiration of foreign body and discuss several prevention techniques.


Prelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear.
In the medial prefrontal cortex, the prelimbic area is emerging as a major modulator of fear behavior, but the mechanisms remain unclear. Using a selective neocortical knockout mouse, virally mediated prelimbic cortical-specific gene deletion, and pharmacological rescue with a TrkB agonist, we examined the role of a primary candidate mechanism, BDNF, in conditioned fear. We found consistently robust deficits in consolidation of cued fear but no effects on acquisition, expression of unlearned fear, sensorimotor function, and spatial learning. This deficit in learned fear in the BDNF knockout mice was rescued with systemic administration of a TrkB receptor agonist, 7,8-dihydroxyflavone. These data indicate that prelimbic BDNF is critical for consolidation of learned fear memories, but it is not required for innate fear or extinction of fear. Moreover, use of site-specific, inducible BDNF deletions shows a powerful mechanism that may further our understanding of the pathophysiology of fear-related disorders.


Difference in effects of stretch on depressive effect of endothelium-derived nitric oxide on noradrenaline- and high-K+-induced contractions between the aortae from normotensive and spontaneously hypertensive rats.
Difference in effects of stretch tension on endothelium-derived nitric oxide (EDNO)-dependent depression of noradrenaline (NA)- and high-K+-induced contraction between the aortae from normotensive Wistar Kyoto rats (WKY) a nd stroke-pronespontaneously hypertensive rats (SHRSP) was studied. NA-induced contraction in preparations both from WKY and SHRSP was augmented in the presence of N(omega)-nitro-L-arginine (L-NNA). This augmentation was minimized when the spontaneous tone, which was more prominent in preparations from SHRSP, was subtracted and the effects of L-NNA became less prominent in preparations from SHRSP. The effects of L-NNA were maximal at the stretch tension of 15 mN and, then, decreased as stretch tension increased in both preparations when the spontaneous tone was subtracted. The effects of L-NNA were less prominent when the contraction was initiated by high-K+, although the effects of stretch on high-K+-induced contraction were similar to that of NA-induced contraction. These results suggested 1) that both NA- and high-K+-induced contractions are depressed by EDNO, 2) that the release of EDNO induced by high-K+ is less than that by NA, 3) that increase in stretch tension decreases the release of EDNO, and 4) that the depressive effect of EDNO on contraction is impaired in the aorta of SHRSP.


Dietary Supplementation of Bacillus sp. PM8313 with β-glucan Modulates the Intestinal Microbiota of Red Sea Bream (Pagrus major) to Increase Growth, Immunity, and Disease Resistance.
A 56-day feeding trial was conducted to determine the effect of dietary supplementation with Bacillus sp. isolated from the intestines of red sea bream on the growth performance, immunity, and gut microbiome composition of red sea bream. Three diets (a control diet and two treatments) were formulated without Bacillus sp. PM8313 or β-glucan (control, CD), 1 × 108 CFU g-1 PM8313 (BSD), and 1 × 108 CFU g-1 PM8313 + 0.1% β-glucan (BGSD). At the end of the experiment, the weight, specific growth rate, feed conversion ratio, and protein efficiency ratio of the fish in the BSD and BGSD diet groups were significantly improved than those of the control group (P < 0.05). Additionally, amylase and trypsin activities were significantly higher (P < 0.05) in both groups compared to the control. Superoxide dismutase and lysozyme activity, which are serum non-specific immune responses, only increased in the BGSD group. The two treatment groups exhibited a marked difference in the intestinal microbiota composition compared to the control group. Furthermore, the treatment groups exhibited an upregulation of IL-6 and NF-κb, coupled with high survival rates when challenged with Edwardsiella tarda. Therefore, dietary supplementation with PM8313 improved the growth performance, digestive enzyme activity, non-specific immunity, and pathogen resistance of red sea bream, in addition to affecting the composition of its intestinal microflora.


Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feedback regulation.
Streptomyces peucetius self-resistance genes drrA and drrB encode membrane-associated proteins that function like an ABC transporter for the efflux of daunorubicin and to maintain a constant subinhibitory physiological concentration of the drug within the cell. In this study, the drrA and drrB operons were disrupted for investigating drug production, self-resistance and regulation. The drrA-drrB null mutant was highly sensitive to daunorubicin. A 10-fold decrease in drug production was observed in the null mutant compared with the wild-type strain. We propose that the absence of a drug-specific efflux pump increases the intracellular concentration of daunorubicin, which is sensed by the organism to turn down drug production. Quantitative real-time PCR analysis of the mutant showed a drastic reduction in the expression of the key regulator dnrI and polyketide synthase gene dpsA. However, the expression of regulatory genes dnrO and dnrN was increased. Feedback regulation based on the intracellular daunorubicin concentration is discussed.


VEGF-C promotes survival in podocytes.
Vascular endothelial growth factor (VEGF)-A is an autocrine survival factor for podocytes, which express two VEGF receptors, VEGF-R1 and VEGF-R3. As VEGF-A is not a known ligand for VEGF-R3, the aim of this investigation was to examine whether VEGF-C, a known ligand for VEGF-R3, served a function in podocyte biology and whether this was VEGF-R3 dependent. VEGF-C protein expression was localized to podocytes in contrast to VEGF-D, which was expressed in parietal epithelial cells. Intracellular calcium ([Ca2+]i) experiments demonstrated that VEGF-C induced a 0.74+/-0.09-fold reduction in [Ca2+]i compared with baseline in human conditionally immortalized podocytes (hCIPs; P<0.05, one sample t-test, n=8). Cytotoxicity experiments revealed that in hCIPs VEGF-C reduced cytotoxicity to 81.4+/-1.9% of serum-starved conditions (P<0.001, paired t-test, n=16), similar to VEGF-A (82.8+/-4.5% of serum-starved conditions, P<0.05, paired t-test). MAZ51 (a VEGF-R3 kinase inhibitor) inhibited the VEGF-C-induced reduction in cytotoxicity (106.2+/-2.1% of serum-starved conditions), whereas MAZ51 by itself had no cytotoxic effects on hCIPs. VEGF-C was also shown to induce a 0.5+/-0.13-fold reduction in levels of MAPK phosphorylation compared with VEGF-A and VEGF-A-Mab treatment (P<0.05, ANOVA, n=4), yet had no effect on Akt phosphorylation. Surprisingly, immunoprecipitation studies detected no VEGF-C-induced autophosphorylation of VEGF-R3 in hCIPs but did so in HMVECs. Moreover, SU-5416, a tyrosine kinase inhibitor, blocked the VEGF-C-induced reduction in cytotoxicity (106+/-2.8% of serum-starved conditions) at concentrations specific for VEGF-R1. Together, these results suggest for the first time that VEGF-C acts in an autocrine manner in cultured podocytes to promote survival, although the receptor or receptor complex activated has yet to be elucidated.