Effects of oral salbutamol and pirbuterol on FEV1, heart rate and blood pressure in asthmatics.
In a double-blind trial the effects on ventilatory function (FEV1), heart rate and blood pressure of oral pirbuterol and oral salbutamol in various single doses were studied in ten patients with chronic asthma. Pirbuterol (15 mg) and salbutamol (4 mg) produced equal peak levels of bronchodilatation. There was no significant difference in the mean rise in heart rates caused by the two drugs, and no other significant side-effects were noted.


Opioid therapy pharmacogenomics for noncancer pain: efficacy, adverse events, and costs.
Chronic non-cancer pain is a debilitating condition associated with high individual and societal costs. While opioid treatment for pain has been available for centuries, it is associated with high variability in outcome, and a considerable proportion of patients is unable to attain relief from symptoms while suffering adverse events and developing medication dependence. We performed a review of the efficacy of pharmacogenomic markers and their abilities to predict adverse events, dependence, and associated economic costs, focusing on two genes: OPRM1 and CYP2D6. Data sources were articles indexed by PubMed on or before August 6, 2013. Articles were first selected after review of their titles and abstracts, and full papers were read to confirm eligibility. Initially, fifty-two articles were identified. Of these, 17 were relevant to biological actions of pharmacogenomic markers and their effect on therapeutic efficacy, 16 to adverse events, 15 to opioid dependence, and eight to economic costs. In conclusion, increasing costs of opioid therapy have made the advances in pharmacogenomics an attractive solution to personalize care with unclear repercussions related to the impact on costs, morbidity, and outcomes. This intersection of pharmacoeconomics and pharmacogenomics presents a unique platform to further examine current advances in clinical medicine and their utility in cost-effective treatment of chronic pain.


The introduction of a paediatric nutrition support program led by a clinical dietitian at a low-resource hospital setting in Malawi.
In low- and middle-income countries, nutrition support strategies are often suboptimal or non-existent in hospital settings. This is further compounded by high rates of malnutrition in these countries. The first four dietitians graduated in Malawi in 2017 providing a new opportunity to build capacity to introduce nutrition support in an acute care setting. A paediatric nutrition support program was implemented at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi including the hiring of a local dietitian. This capacity building paper explains the development and introduction of the nutrition support program including a description of perceptions of health professionals at QECH working alongside the dietitian. In the first four months of the program at QECH, the dietitian provided nutrition support to 183 different patients across paediatric wards. Nutritional interventions predominantly included infant formula and breastmilk fortification, provision of therapeutic feeds orally or via nasogastric tubes, increased dietary protein intake for children identified to be at high risk, and nutritional counselling to caregivers. More complex nutritional interventions were also given such as the insertion of gastrostomy tubes to deliver nutrition directly to the stomach. Following the introduction of the program, qualitative interviews were done with health professionals at QECH including nurses (n = 5) and physicians (n = 11). All participants emphasized the importance and impact of the nutrition support program in enhancing the care of hospitalized children, therefore improving outcomes such as tolerability of clinical interventions, decreased duration of stay, and reduced risk of hospital readmission. In conclusion, there is a need for nutrition support provided by a dietitian for different paediatric patients which was corroborated by positive feedback from health professionals at QECH. Integration of dietitians into the healthcare system by respective Ministries of Health will require advocacy around the potential for nutrition support to strengthen the quality of care of vulnerable children. A Chichewa abstract for this paper is available in a supplementary file.


A double-blind group comparative study of nedocromil sodium in the treatment of seasonal allergic rhinitis.
Thirty-eight patients with seasonal rhinitis due to grass pollen allergy took part in this double-blind study comparing 1% nedocromil sodium and placebo. Treatment was allocated by randomised coding sheet and consisted of 1% nedocromil sodium nasal spray or placebo given four times daily for four weeks during the peak pollen season. Highly significant (p less than 0.001) differences in favour of nedocromil sodium were seen for all signs and symptoms recorded at clinical assessments, and for diary card assessments of symptoms. In addition, time to effect and patient and clinician opinions of treatment significantly (p less than 0.001) favoured nedocromil sodium. Laboratory data on blood and urine samples taken before and after treatment showed no significant effects, and both treatments were well tolerated. Nedocromil sodium 1% nasal spray taken four times daily was shown to be an effective treatment for grass pollen rhinitis.


An Escherichia coli gene in search of a function: phenotypic effects of the gene recently identified as murI.
Earlier we reported that an open reading frame located at 89.5 min of the Escherichia coli map (ORFI) codes for a protein of unknown function that could be overexpressed and purified to homogeneity (G. Balikó, A. Raukas, I. Boros, and P. Venetianer, Mol. Gen. Genet. 211:326-331, 1988). In the work described here, we attempted to learn the function of this protein by inactivating the chromosomal gene and providing it or its deletion derivatives on temperature-sensitive plasmids. We found that the presence of the functional ORFI gene is essential; cells are not viable at the nonpermissive temperature or when the region coding for the C-terminal 50 amino acids of the protein is deleted. At intermediate temperatures or when the gene is overexpressed, characteristic changes occur in cell morphology, nucleoid separation during cell division, and supercoiling of plasmids. The possible mechanisms of these effects are discussed in view of the fact that Doublet et al. (P. Doublet, J. van Heijenoort, and D. Mengin-Lecreulx, J. Bacteriol. 174:5772-5779, 1992) recently identified the ORFI gene as murI, involved in D-glutamic acid biosynthesis.


Screening of hybridoma supernatants raised against membrane fractions from breast cancer using an immunodot assay.
Membranes were prepared from mammary tumors and fractionized using gel filtration and gradient polyacrylamide gel electrophoresis. To obtain monoclonal antibodies against tumor-associated antigens, mice were immunized against membrane fraction 2a. After hybridization, we obtained 746 hybridoma cell lines. We performed the immunodot assay for screening. Every supernatant was tested against 15 antigens. Eight antigens were purified fractions from tumor membrane preparation, and five were crude membrane preparations from benign and malignant breast cell lines. Additionally, the Thomsen-Friedenreich antigen of erythrocytes was tested. We selected 83 hybridomas for further characterization.


New window for cochlear implant insertion.
Nine patients with profound bilateral hearing loss received a cochlear implant via the middle fossa. Subjects presented with a bilateral radical mastoidectomy cavity, fibroadhesive otitis media, otosclerosis, autoimmune inner ear disease, previous cranial trauma and genetic prelingual deafness. A classic middle fossa approach was adopted. A small cochleostomy was performed on the most superficial part of the basal turn. A Nucleus CI24M cochlear implant system (Cochlear Corporation) was inserted in four patients, a Lauraflex implant (Philips Hearing Implants) in three patients and a Combi 40 + (Med-el) with double electrode array in two. The receiver-stimulator was positioned in a bone well drilled in the temporal squama and the electrode carrier was inserted in the fenestrated cochlea. Speech perception tests, performed over a period of time ranging from 1 to 6 months after cochlear implant activation, yielded better results than those obtained in postlingually deaf patients operated on via the traditional transmastoid route. Cochlear implant insertion via the middle fossa approach is a technique which is suitable for auditory rehabilitation of subjects with a bilateral radical mastoidectomy cavity, chronic middle ear disease, patients suffering from middle ear malformations, and patients with partial obliteration of the cochlea in the basal turn. However, the main advantage of middle fossa cochleostomy consists in the possibility of stimulating areas of the cochlea, i.e. middle and apical turns, where a greater survival rate of spiral ganglion cells is known to occur. This new approach led to major improvements in speech perception in all patients compared with patients operated on with the transmastoid approach and thus, given the present state of the art, it is the only approach which allows stimulation of the entire cochlea and enables the best auditory outcomes to be achieved in patients with a cochlear implant.


Angiography with epinephrine and beta receptor blocker in diagnosis of sigmoid lesions.
Various sigmoid lesions, seen on barium enema of 39 patients, were investigated with angiography of the inferior mesenteric artery using three series. The first was performed with contrast medium only, the second after use of epinephrine, and the third after a beta-blocking agent (propranolol) combined with epinephrine. The patients were followed for more than three years. Eleven carcinomas were detected, all diagnosed angiographically. Carcinoma, radiation fibrosis, and diverticulitis with fibrosis may appear similar on pharmacoangiography, but the inflammatory reaction seen, for example in diverticulitis, is different. These findings are important because they can have an influence on the indications and selection of the most suitable operation to be performed.


Recombinant bovine growth hormone identification and the kinetic of elimination in rainbow trout treated by LC-MS/MS.
The efficiency of the administration of recombinant bovine growth hormone (rbGH) to enhance fish growth has been widely reported in the literature. Although its use is probable and has been described in several countries, rbGH is prohibited in the European Union (Council Decisions 1994/936/EC, 1999/879/EC). In this context, an analytical strategy was optimised in order to identify rbGH-treated fish. Currently, one of the most difficult challenges for the detection of rbGH in fish is probably the choice of the matrix and the corresponding available quantity for analysis. Therefore, based on a previous efficient protocol developed for mammalian species, a method was adapted for very limited serum volume (50 µl) and was successfully implemented to analyse serum collected from seven trout treated with rbGH. The detection of rbGH was possible from the very first day after administration and the hormone could easily be identified at least for 1 month with levels in the range 5-10 µg ml(-1). The limits of detection (LODs) estimated around 0.5 µg ml(-1) rbGH in fish serum are far below observed concentrations in incurred samples and therefore attest to the relevance of the developed protocol.


Evaluation of predicted knee-joint muscle forces during gait using an instrumented knee implant.
Musculoskeletal modeling and optimization theory are often used to determine muscle forces in vivo. However, convincing quantitative evaluation of these predictions has been limited to date. The present study evaluated model predictions of knee muscle forces during walking using in vivo measurements of joint contact loading acquired from an instrumented implant. Joint motion, ground reaction force, and tibial contact force data were recorded simultaneously from a single subject walking at slow, normal, and fast speeds. The body was modeled as an 8-segment, 21-degree-of-freedom articulated linkage, actuated by 58 muscles. Joint moments obtained from inverse dynamics were decomposed into leg-muscle forces by solving an optimization problem that minimized the sum of the squares of the muscle activations. The predicted knee muscle forces were input into a 3D knee implant contact model to calculate tibial contact forces. Calculated and measured tibial contact forces were in good agreement for all three walking speeds. The average RMS errors for the medial, lateral, and total contact forces over the entire gait cycle and across all trials were 140 +/- 40 N, 115 +/- 32 N, and 183 +/- 45 N, respectively. Muscle coordination predicted by the model was also consistent with EMG measurements reported for normal walking. The combined experimental and modeling approach used in this study provides a quantitative framework for evaluating model predictions of muscle forces in human movement.


Effects of single-peak vs polywave light-emitting diode curing lights on the polymerization of resin cement.
This study examined the effect of selecting a single-peak blue vs a polywave blue/violet emission LED curing light on the degree of conversion (DC) and Knoop microhardness (KHN) of resin cements when light cured through a ceramic disk. Two shades (A1 and A4) of resin cement (Variolink II) were placed in a 0.5-mm-thick ring. The top surfaces were covered with a Mylar strip and further covered with a disk of 1-mm-thick Empress Esthetic ceramic, shade A2. The specimens were light cured by means of an Elipar-S10 (3M ESPE, single-peak blue LED) or BluePhase-G2 (Ivoclar Vivadent, polywave blue/violet LED) curing light, both for 20 s, directly on the surface of an attenuated total reflectance FT-IR plate at 30°C. The DC of the resin was calculated after 100 s. The specimens were removed, and the Knoop microhardness was tested immediately and again after 24-h storage in the dark at 37°C and 100% humidity. Five specimens were made in each group. The DC and Knoop microhardness results were analyzed with ANOVA and Fisher's PLSD at α = 0.05. The choice of curing light had no significant effect on the DC and only a small effect on the immediate and 24-h KHN values. Shade A4 of the resin cement was harder and had a higher DC than shade A1. When light cured for 20 s, Variolink II resin cement can be light cured with either the single-peak or the polywave curing light. Shade A4 of the cement was slightly harder than A1.


Late Migration of Amplatzer Septal Occluder Device to the Descending Thoracic Aorta.
Percutaneous closure of atrial septal defect (ASD) has become an increasingly common procedure. Serious complications of the procedure, such as cardiac migration, are rare, and usually occur <72 hours after device placement. In this report, we present the case of a patient who underwent successful surgical treatment for the migration of an ASD occluder device to the thoracic aorta 12 months after ASD closure.


Endogenous cytokine expression profiles in retinoic acid-induced IgA production by LPS-stimulated murine splenocytes.
All-trans-retinoic acid (RA) enhances IgA production by LPS-stimulated murine splenocytes. After stimulation by RA and LPS, or by LPS alone, total RNA was extracted from cultured cells on Days 1 to 4, and the kinetics of expression of various cytokine mRNAs were analyzed by the RT-PCR method. RA induced the expression of IL-5 and TGF-beta 2 mRNAs in the LPS-stimulated cells. In addition, the expression of IL-6 and IL-2 mRNAs was more intensive in RA-stimulated cells than in unstimulated cells. TGF-beta 1 and TGF-beta 3 mRNAs were constitutively expressed in both culture groups. RA enhanced IgA production by LPS-stimulated spleen cells but not that by LPS-stimulated mu(+) naive splenic B-cells. For RA-induced IgA production, the B-cells required T-cells or the culture supernatant from RA-stimulated T-cells. Furthermore, exogenous IL-5 replaced the T-cell requirement, at least in part, in RA-induced IgA production by LPS-stimulated B-cells. This reaction was partially inhibited by anti-TGF-beta-neutralizing antibodies. These findings suggest that RA induces IgA production by (IL-5 + LPS)-stimulated B-cells in TGF-beta-independent and TGF-beta-dependent manners.


The small molecule NSC676914A is cytotoxic and differentially affects NFκB signaling in ovarian cancer cells and HEK293 cells.
The small molecule NSC676914A was previously identified as an NF-κB inhibitor in TPA-stimulated HEK293 cells (Mol Can Ther 8:571-581, 2009). We hypothesized that this effect would also be seen in ovarian cancer cells, and serve as its mechanism of cytotoxicity. OVCAR3 and HEK293 cell lines stably containing a NF-κB luciferase reporter gene were generated. Levels of NF-κB activity were assessed by luciferase reporter assays, after stimulation with LPA, LPS, TPA, and TNFα, in the presence or absence of a known NF-κB inhibitor or NSC676914A, and cytotoxicity was measured. NSC676914A was toxic to both OVCAR3 and HEK293 cells. We also investigated the cytotoxicity of NSC676914A on a panel of lymphoma cell lines with well characterized mutations previously shown to determine sensitivity or resistance to NF-κB inhibition. The compound did not show predicted patterns of effects on NF-κB activity in either lymphoma, ovarian or HEK293 cell lines. In HEK293 cells, the small molecule inhibited NF-κB when cells were stimulated, while in OVCAR3 cells it only partially inhibited NF-κB. Interestingly, we observed rescue of cell death with ROS inhibition. The current study suggests that the effect of NSC676914A on NF-κB depends on cell type and the manner in which the pathway is stimulated. Furthermore, as it is similarly toxic to lymphoma, OVCAR3 and HEK293 cells, NSC676914A shows promising NF-κB-independent anti-cancer activity in ovarian tumor cells.


Photoconversion of riboflavin to lumichrome in plant tissues.
Free flavins have been extracted from shoots of etiolated corn (Zea mays L., var. Burpee Snowcross) and from yeast cells and separated from other substances by absorption on resorcinol-formaldehyde resin and talc columns and by thin layer chromatography. Riboflavin was the only free flavin present. Extracts of etiolated shoots of oats (Avena sativa L., var. Multiline E-69 and Clinford) yielded riboflavin plus a second free flavin previously demonstrated in oats. The areas of the chromatograms expected to contain lumichrome were completely clear. After illumination of any of the three organisms with artificial light (1100 ft-c) or sunlight for 6 hours, lumichrome (7,8-dimethylalloxazine) was found. In corn shoots after irradiation by sunlight, the amount of lumichrome present was equivalent to 2.5% of the total free flavin. Lumichrome was identified by thin layer chromatography in six solvent systems (including two two-dimensional systems), by its characteristic fluorescence in acetic acid, by its absorption spectrum, and by formation of a characteristic hydrate in ammonia-containing solutions. A comparison was made with in vitro photolysis of riboflavin and the possible role of photolysis of riboflavin (either free or bound) and of lumichrome formation in photo-responses of plants is discussed. Placing the shoots in the dark for 4 hours after irradiation in sunlight for 6 hours led to no detectable loss of the lumichrome which had been formed.


The Liquid Biopsy in the Management of Colorectal Cancer: An Overview.
Currently, there is a crucial need for novel diagnostic and prognostic biomarkers with high specificity and sensitivity in patients with colorectal cancer. A "liquid biopsy" is characterized by the isolation of cancer-derived components, such as circulating tumor cells, circulating tumor DNA, microRNAs, long non-coding RNAs, and proteins, from peripheral blood or other body fluids and their genomic or proteomic assessment. The liquid biopsy is a minimally invasive and repeatable technique that could play a significant role in screening and diagnosis, and predict relapse and metastasis, as well as monitoring minimal residual disease and chemotherapy resistance in colorectal cancer patients. However, there are still some practical issues that need to be addressed before liquid biopsy can be widely used in clinical practice. Potential challenges may include low amounts of circulating tumor cells and circulating tumor DNA in samples, lack of pre-analytical and analytical consensus, clinical validation, and regulatory endorsement. The aim of this review was to summarize the current knowledge of the role of liquid biopsy in the management of colorectal cancer.


Mast Cell Degranulation and Adenosine Release:Acupoint Specificity for Effect of Electroacupuncture on Pituitrin-Induced Acute Heart Bradycardia in Rabbits.
Acupuncture is a medical modality based on the theory of traditional Chinese medicine, and its effect is relatively dependent on acupoint specificity. However, there is little knowledge on acupoint specificity versus acupuncture outcomes because of the deficiency of rigorous investigation on this topic, which has impeded the growing legitimacy of acupuncture in the mainstream of medicine as an evidence-based therapy. Therefore, it is of utmost importance to clarify this critical issue. The present study aims to verify the phenomenon of acupoint specificity in acupuncture-induced cardiovascular regulation and explore the biological mechanism by measuring mast cells' degranulation and adenosine release. This study was conducted to explore the specificity of acupoints in an acute bradycardia rabbit model. After electroacupuncture (EA) stimulation at PC6, PC control (con) 1, PC con 2, LU7, LI11, and nonacupoint, only the PC6 group showed a significant improvement in relative heart rate as compared to that of the model group. There was no significant difference between the relative heart rate of other EA groups and that of the model group. Historical results also showed that the ratio of degranulated mast cells in PC6 was significantly higher than other acupoints and control points. From the results of high-performance liquid chromatography (HPLC), a transient elevation of adenosine concentration during EA was only observed on acupoints and control points (P < 0.05) along the pericardium meridian. The EA-induced adjustment on acute bradycardia exhibits a relative specificity of acupoints, which may be related to mast cell degranulation and adenosine release in local acupoint areas. Increased degranulation of mast cells and augmentation of adenosine release during EA may be the mechanisms for PC6 having significantly better acupuncture effects than other acupoints and nonacupoints.


[Therapeutic management of primary digestive lymphomas at Yaoundé: analysis of a series of 46 cases].
The aim of this study was to identify the principal deficiencies and difficulties associated with the treatment of primary digestive lymphomas at Yaounde. We analyzed the medical records of 46 patients treated at Yaounde General Hospital over a period of 7 years (January 1989 to December 1996). The study population consisted of 24 men (52%) and 22 women (48%), giving a sex ratio of 1.08. The mean age of the patients was 49 years (range: 18 to 80 years). The treatment of these patients was not always optimal, due largely to socioeconomic and technical factors. We observed cases of very late diagnosis in which the histological data were imprecise or incomplete, in the absence of modern histological techniques. Assessment of the expansion of tumors was frequently inadequate, due to the absence of scanners or the inability to pay for their use. These problems, and the high cost of chemotherapy and radiotherapy, have severely limited the efficacy of treatment, resulting in poorer responses to treatment than reported elsewhere. In conclusion, national solidarity and cooperation at the regional and international levels seem to be necessary in these clinical conditions, to overcome these obstacles and to improve the quality of treatment for patients in general, and for those with primary digestive lymphomas in particular.


OMARU: a robust and multifaceted pipeline for metagenome-wide association study.
Microbiome is an essential omics layer to elucidate disease pathophysiology. However, we face a challenge of low reproducibility in microbiome studies, partly due to a lack of standard analytical pipelines. Here, we developed OMARU (Omnibus metagenome-wide association study with robustness), a new end-to-end analysis workflow that covers a wide range of microbiome analysis from phylogenetic and functional profiling to case-control metagenome-wide association studies (MWAS). OMARU rigorously controls the statistical significance of the analysis results, including correction of hidden confounding factors and application of multiple testing comparisons. Furthermore, OMARU can evaluate pathway-level links between the metagenome and the germline genome-wide association study (i.e. MWAS-GWAS pathway interaction), as well as links between taxa and genes in the metagenome. OMARU is publicly available (https://github.com/toshi-kishikawa/OMARU), with a flexible workflow that can be customized by users. We applied OMARU to publicly available type 2 diabetes (T2D) and schizophrenia (SCZ) metagenomic data (n = 171 and 344, respectively), identifying disease biomarkers through comprehensive, multilateral, and unbiased case-control comparisons of metagenome (e.g. increased Streptococcus vestibularis in SCZ and disrupted diversity in T2D). OMARU improves accessibility and reproducibility in the microbiome research community. Robust and multifaceted results of OMARU reflect the dynamics of the microbiome authentically relevant to disease pathophysiology.


A valley-filtering switch based on strained graphene.
We investigate valley-dependent transport through a graphene sheet modulated by both the substrate strain and the fringe field of two parallel ferromagnetic metal (FM) stripes. When the magnetizations of the two FM stripes are switched from the parallel to the antiparallel alignment, the total conductance, valley polarization and valley conductance excess change greatly over a wide range of Fermi energy, which results from the dependence of the valley-related transmission suppression on the polarity configuration of inhomogeneous magnetic fields. Thus the proposed structure exhibits the significant features of a valley-filtering switch and a magnetoresistance device.


Chemical identification and ethological function of soldier-specific secretion in Japanese subterranean termite Reticulitermes speratus (Rhinotermitidae).
We identified the soldier-specific compounds in the Japanese subterranean termite, Reticulitermes speratus, to clarify their ethological roles. Silica gel column chromatography separated one major soldier-specific compound in the hexane fraction accounting for 70-80% of the total amount of the fraction, while cuticular hydrocarbons constituted the rest. We identified the compound as β-selinene by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparative GC analyses of the major exocrine glands detected the compound in the soldier's frontal gland. Both soldiers and workers made aggregation to the hexane fraction, as well as to the crushed heads and head extract of the soldiers. They did not aggregate to cuticular hydrocarbons, making it likely that β-selinene was the aggregation pheromone in this species. The opportunistic predator of this termite, Lasius japonicus, was also attracted to the compounds. The ant workers, therefore, would use the termite aggregation pheromone as a kairomone for hunting them.


Age and QT variability index during free breathing, controlled breathing and tilt in patients with chronic heart failure and healthy control subjects.
The QT variability index (QTVI) indicates temporal dispersion in myocardial repolarization, and a high QTVI is associated with a propensity for sudden death from malignant ventricular arrhythmias in subjects at high risk. In this study, the authors assessed the effects of free breathing, controlled breathing, and sympathetic stress (tilt) on the QTVI in patients with chronic heart failure (CHF) and healthy control subjects. The authors also examined the influence of age on the same variables. To obtain normative data, they calculated 95% confidence intervals for healthy subjects grouped according to age. Under all experimental conditions, the QTVI was larger in the CHF group overall and in the age subsets than in controls. In patients and controls, the QTVI increased significantly during tilt, although no differences were found between the QTVI measured during free and controlled breathing. In healthy controls, the following variables correlated significantly with the QTVI: age and baseline heart rate (P < 0.001). In patients with CHF, aging had no influence on the QTVI. Age, sympathetic stress, and CHF all tend to increase the QTVI and could potentially induce sudden death. Further studies should assess the usefulness of the QTVI as a marker predicting sudden cardiac death under the various conditions of risk.


Effect of fucoidan on fibroblast growth factor-2-induced angiogenesis in vitro.
Fucoidans are sulfated polysaccharides extracted from brown marine algae. A purified fucoidan fraction exhibits the same venous antithrombotic activity as heparin in rabbits, but with a lower anticoagulant effect. Because of its heparin-like structure, we postulated that fucoidan might modulate heparin-binding angiogenic growth factor activity. We thus studied its effect, at antithrombotic concentrations, on fibroblast growth factor (FGF)-2-induced proliferation and differentiation of human umbilical vein endothelial cells. The fucoidan effect on endothelial cell differentiation was evaluated by studying the expression of surface proteins (i.e. integrin, adhesion molecule) known to be modulated by FGF-2 and involved in angiogenesis, and by quantifying closed areas delimited by vascular tubes formed on reconstituted basement membrane. Fucoidan had no modulatory effect on the mitogenic activity of FGF-2, but significantly increased tubular structure density induced by FGF-2. Fucoidan alone increased alpha(6) integrin subunit expression with only partially organized tubular structure. In the presence of FGF-2, fucoidan enhanced alpha(6), beta(1) and PECAM-1 and inhibited alpha(v)beta(3) integrin expression. Heparin had no effect in these systems. The most striking effect of fucoidan was observed on alpha(6) expression and tube formation was abolished by monoclonal anti-alpha(6) antibodies. Fucoidan plus FGF-2 effect on alpha(6) expression was markedly decreased by monoclonal anti-FGF-2 antibodies, indicating that fucoidan acts mainly via FGF-2. These results show that, at antithrombotic concentrations, contrary to heparin, fucoidan can enhance vascular tube formation induced by FGF-2 with a modulation of the expression of surface proteins (mainly alpha(6)) involved in angiogenesis.


Clinical analysis of multiple primary malignancies of the hypopharynx and esophagus.
Because the capability to control squamous cell carcinomas of the head and neck has improved recently, the phenomenon of multiple primary malignancies of that region is now recognized with increasing frequency. We reviewed cases of multiple primary squamous cell carcinomas of the hypopharynx and esophagus with regard to their frequency, incidence, and prognosis. We reviewed 104 cases of hypopharyngeal cancer to determine (1) if and when esophageal cancer occurred, (2) the classification of multiple tumors as metachronous or synchronous, and (3) tumor histology. In most cases of the metachronous type, esophageal cancer followed hypopharyngeal cancer within less than 3 years. Most cases of hypopharyngeal cancer were at an advanced stage, in contrast to esophageal cancer, which were all early stage. These cases had a poor prognosis despite various treatments causing local disease to be well controlled. Endoscopic esophageal mucosal resection was found to be an effective treatment for esophageal cancer, especially in superficial types. The prognosis and mild systemic damage after endoscopic esophageal mucosal resection compare favorably with surgery, radiation, or systemic chemotherapy.


Inkjet Printable and Self-Curable Disperse Dyes/P(St-BA-MAA) Nanosphere Inks for Both Hydrophilic and Hydrophobic Fabrics.
Low-water-soluble disperse dyes possess a broad color gamut and good durability, but they need chemical or physical modification before being used in inks and can only be applied to several kinds of hydrophobic fabrics. In this work, disperse dyes/P(St-BA-MAA) nanospheres (known as DPN) absorbed by sodium nitrilotriacetate (known as NTA@DPN) were prepared and applied into ink formulations, which exhibited high dye fixation, long-term stability and self-curable ability without addition of any binder. Transmission electron microscopy (TEM) images showed the nanospheres have homogeneous core-shell spherical shape and the average diameter increased by 20.6 nm after coloration. X-ray diffraction (XRD), Fourier transform infrared spectrum (FTIR), and differential scanning calorimetry (DSC) measurements illustrated the interaction between dyes and nanospheres and indicated that the colored nanospheres contained both dye molecules and crystalline dyes. The Zeta potential and particle size measurements demonstrated that the dispersion stability was improved when sodium nitrilotriacetate (NTA) was absorbed onto DPN. The rheological behavior of the NTA@DPN inks was Newtonian and desired droplet formation was achieved at the viscosity of 4.23 mPa·s. Both hydrophilic cotton and hydrophobic polyester fabrics were cationic modified before used, which had an excellent image quality and desired rubbing fastness after inkjet printing. Scanning electron microscope (SEM) images showed NTA@DPN formed stable deposits on the surface of modified fibers and could self-cure to form continuous film coating on the fiber surface after being baked at 150 °C without addition of any binder.


Ventral Caudate and Anterior Insula Recruitment During Value Estimation of Passionate Rewarding Cues.
"Wanting", a component of reward processing, is a motivational property that guides decision making in goal-oriented behavior. This includes behavior aiming at supporting relational bonds, even at the group level. Accordingly, group belongingness works as this motivational property, which is fundamentally different from romantic or maternal love. While primary rewards (or learned associations, such as money) have been largely used to study the conceptual framework associated with "wanting," other cues triggering behavior, such as passionate motives, are less well-studied. We investigated the neural correlates of value estimation of a passion-driven incentive in neuropsychologically defined football fans. We asked the participants (n = 57) to compute the value of football tickets (the cues that trigger passionate behavior in this "tribal love" context). The trials were all different, comprising tickets for different matches. The participants had no restrictions on the amount to be introduced. This enabled a parametric functional magnetic resonance imaging design based on the explicit estimated value given by the participants in a trial-by-trial approach. Using a whole-brain approach (to prevent biased focus on value-related regions), only the activity in the ventral caudate and left anterior insula showed a critical relationship with the reported value. Higher normalized values led to more activity in the striatum and left insula. The parametric map shows that these regions encode the magnitude of incentive by indexing self-relevant value. Other regions were involved in value computation, such as the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex, but did not exhibit parametric patterns. The involvement of the nucleus accumbens in value estimation was only found in region of interest -based analysis, which emphasizes the role of the ventral caudate for the presently studied social "reinforcer" cue.


Schistosomiasis: an unusual finding of the cervix.
Schistosomiasis remains a major threat to women's health in many resource-poor countries and is being seen with increasing frequency in developed countries among immigrants and tourists who have a history of freshwater exposure in endemic areas. A 28-year-old asymptomatic African immigrant presented with an abnormal Pap test result showing rare atypical squamous cells. Colposcopy examination showed pale-yellow, finely granular cervical lesions. Calcified Schistosoma hematobium eggs were identified by histology but were absent in urine and stool specimens. Praziquantel treatment was initiated promptly, avoiding significant morbidity. The differential diagnosis of female genital schistosomiasis should be considered for patients who have a history of residence in or travel to endemic areas, including asymptomatic patients and patients presenting a long time after exposure.


Evaluation of use patterns of psychotropic drugs in an Italian geriatric hospital.
This study is a survey of psychotropic drug use patterns among 934 elderly patients admitted to the Padua Geriatric Hospital. 34% of the patients took psychotropic drugs during their stay in hospital. The drugs most commonly used are anxiolytics and hypnotics of the benzodiazepine class. Women subjects living alone, and to a lesser extent those suffering from particular disorders, as of the central nervous system and the musculoskeletal apparatus, seem to be at higher risk in the use of psychotropic drugs. Moreover, the results show that psychotropic drugs are prescribed during the stay in hospital and even on discharge to a high percentage of subjects who did not use such drugs before admission to the hospital.


Synthesis and insecticidal activities of 2,3-dihydroquinazolin-4(1H)-one derivatives targeting calcium channel.
A series of compounds containing dihydroquinazolinone moiety was designed and synthesized. Amine bridge part was changed in comparison with known anthranilic diamides insecticides. Their insecticidal activities against oriental armyworm (Mythimna separata) indicated that most of the compounds showed moderate to high activities at the tested concentrations. In particular, compounds 5a and 5k showed 80% larvicidal activities against oriental armyworm at the concentration of 5mg/L. The present study also explored the possible effects of target compounds on the high voltage-gated calcium channel and the calcium channels in the endoplasmic reticulum in the central neurons isolated from the third instar larvae of Spodoptera exigua using whole-cell patch clamp and calcium imaging technique. The results showed that compound 5a activated the high voltage-gated calcium channel in the central neurons of S. exigua weakly. The peak currents only increased by 6% of the initial value at the end of the 10-min recording after treated with 0.22μM 5a, while chlorantraniliprole has an opposite effect. The effects of 5a on the intracellular calcium ion concentration ([Ca(2+)]i) in neurons were well investigated. The experimental results indicated that these novel compounds have different mechanism compared with chlorantraniliprole.


Novel single nucleotide polymorphisms in the 3'-UTR of the TGFbetaRI and TGFbetaRIII genes.
Transforming growth factor beta (TGFbeta) family members are multifunctional cytokines that play a key role in cellular growth, proliferation and differentiation. Transmembrane signalling by TGFbeta occurs via a complex of the serine/threonine kinases TGFbeta type 1 (TGFbetaRI), type 2 (TGFbetaRII), and type 3 (TGFbetaRIII) receptors. Previous studies have implicated TGFbeta receptors (TGFbetaR) in a variety of important hereditary clinical disorders. Mutations of the TGFbetaR genes have been observed in several human cancers. The aim of this study was to identify and confirm novel single nucleotide polymorphisms (SNPs) in TGFbetaRI and RIII and to determine the relative allele and genotype frequencies of these SNPs. SNPs were identified from the examination of sequence alignments held in databases and were confirmed by DNA sequencing. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was devised for genotyping TGFbeta receptor polymorphisms. DNA samples from 91 controls were examined. The observed heterozygosities of TGFbetaRI and TGFbetaRIII gene polymorphisms in the control population were 43 and 33%, respectively, suggesting these SNPs could be useful markers in disease association studies.


Surface density expression of the leukocyte-associated Ig-like receptor-1 is directly related to inhibition of human T-cell functions.
The relevance of inhibitory receptors that downregulate T-cell functions, such as CD152 (CTLA-4) and CD85j, have been extensively analyzed. This study will show that leukocyte-associated Ig-like receptor-1 (LAIR-1) acts as an inhibitory receptor for antigen-specific human effector T cells. To this end 28 CD8(+) and 22 CD4(+) T-cell clones were analyzed. LAIR-1 activity appears to be clonally distributed among T-cell clones and inhibition of T lymphocyte functions ranges from 4% to 49% in a redirected killing assay. This inhibitory function, although less efficient than that exerted by other inhibitory receptors expressed by T cells (i.e., CD152 and CD85j), downregulates the cytotoxic activity of CD8(+) T lymphocytes, both in a CD3-mediated and in an antigen-specific system. Furthermore, LAIR-1 inhibits the proliferative response of CD4(+) T lymphocytes to recall antigens and in CD3 stimulation. LAIR-1 also modulates cytokine production, downregulating IL-2 and IFN-gamma production. In contrast, LAIR-1 crosslinking induces secretion of transforming growth factor beta. This study will also demonstrate that a direct relationship exists between surface density expression of LAIR-1 molecules and their ability to modulate CD3-mediated activation of both CD8(+) and CD4(+) T-cell clones.


Dermoscopic features of a black hairy tongue in 2 Japanese patients.
Dermoscopic features of a black hairy tongue have never been reported. Dermoscopy might be useful in speculating pathologic features of oral lesions. The objective was to identify additional dermoscopic criteria. Two Japanese patients who were clinically given a diagnosis of "black hairy tongue" were evaluated for dermoscopic features. We have shown characteristic dermoscopic features of brownish hair-like elongation of filiform papillae with whitish lingual papillae. Dermoscopic examination seemed useful as an adjunct to the diagnosis of this benign disorder of the tongue, demonstrating exact changes in shape and color of filiform papillae. It might also be helpful in more objective observation of the therapeutic efficacy.


The mechanisms of stone fragmentation in ESWL.
Currently, several mechanisms of kidney stone fragmentation in extracorporal shockwave lithotripsy (ESWL) are under discussion. As a new mechanism, the circumferential quasistatic compression or "squeezing" by evanescent waves in the stone has been introduced. In fragmentation experiments with self-focussing electromagnetic shock-wave generators with focal diameters comparable to or larger than the stone diameter, we observed first cleavage surfaces either parallel or perpendicular to the wave propagation direction. This is in agreement with the expectation of the "squeezing" mechanism. Because, for positive pulse pressures below 35 MPa and stones with radii of 15 mm or smaller, cleavage into only two fragments was observed, we developed a quantitative model of binary fragmentation by "quasistatic squeezing." This model predicts the ratio of the number of pulses for the fragmentation to 2-mm size and of the number of pulses required for the first cleavage into two parts. This "fragmentation-ratio" depends linearly alone on the stone radius and on the final size of the fragments. The experimental results for spherical artificial stones of 5 mm, 12 mm and 15 mm diameter at a pulse pressure of 11 MPa are in good agreement with the theoretical prediction. Thus, binary fragmentation by quasistatic squeezing in ESWL as a new efficient fragmentation mechanism is also quantitatively verified.


Aripiprazole: profile on efficacy and safety.
Aripiprazole (Abilitat, Bristol-Myers Squibb) is the most recent addition to the new class of atypical antipsychotic medications, following the release of clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Aripiprazole exhibits typical antagonism at dopamine (D2) receptors in the mesolimbic pathway, as well as having unique partial agonist activity at D2 receptors in the mesocortical pathway. As exemplified by other atypical antipsychotics, it displays strong 5-HT(2a) receptor antagonism and is similar to ziprasidone in also having agonistic activity at the 5-HT(1a) receptor. Among the atypical antipsychotics, aripiprazole displays the lowest affinity for alpha(1)adrenergic (alpha(1)), histamine (H1) and muscarinic (M1) receptors. This combination of effects may be responsible for its efficacy in positive and negative symptoms of schizophrenia and in bipolar disorder. Similarly, this profile may be the reason for the low rates of reported side effects observed. This includes general adverse events, a low incidence of reported weight gain and a low liability for inducing movement disorders. Other early data suggest that aripiprazole may induce reductions in plasma prolactin, as well as in plasma glucose and lipid profiles. Finally, results also support the proposition that aripiprazole may lead to reductions in corrected QT interval and have minimal drug interactions.


Effects of HOX homeobox genes in blood cell differentiation.
The burgeoning number of articles concerning the role of HOX genes and hematopoiesis ensures that this will continue to be an area of very active research. It seems clear that HOX genes are expressed in stage- and lineage-specific patterns during early stages of hematopoietic development and differentiation. Several lines of evidence suggest that multiple genes of the HOXB (B2, B4, B6-B9), HOXC (C6, C8), and HOXA (A5) are involved in erythropoiesis. Similarly, a number of genes of the HOXA, HOXB, and HOXC appear to play a role in lymphoid cells. Furthermore, several genes, such as A9, A10, B3, B7, and B8, may control myelomonocytic differentiation. The question arises as to whether such a multiplicity of HOX genes reflects redundancy or indicates subtlety of the regulatory machinary. A similar complexity has been observed for hematopoietic cytokines, and the current view is that, although multiple molecules may have similar or overlapping effects, each factor has a specific function and regulatory combinations appear to play a critical role in controlling hematopoietic cell processes (99). One challenge for the future is to delineate in more detail the precise expression patterns of these genes in the many distinct subpopulations of blood cells and during fetal development. Overexpression of HOX genes in hematopoietic cells can dramatically perturb the differentiation of various cell lineages and can contribute to leukemogenesis. Future studies may involve the overexpression of alternatively spliced versions of different HOX genes or of truncated versions of HOX genes to ascertain the functional domains of the proteins that mediate the biologic effects. The findings in HOX knockout mice confirm a role for these genes in normal blood cell development. Further work in this area will require careful examination of fetal hematopoiesis and of animals bearing multiple HOX gene knockouts. Involvement of HOX genes in leukemia is just beginning to be appreciated. Establishing the true extent of HOX gene mutations in human disease will require strategies such as comparative genomic hybridization (100) and analysis of high density oligonucleotide arrays (101). The holy grail of homeobox work is to discover the physiologic processes and specific target genes regulated by HOX proteins. Given the broad range of tissues in which HOX genes are expressed, they would appear to be involved in very basic cellular processes, e.g., cell proliferation and death, adhesion, and migration, etc., rather than the direct regulation of tissue-specific genes. The search for target genes may be made easier by the further characterization of cooperative DNA binding between HOX proteins and other transcription factors. We speculate that HOX proteins do not behave as conventional transcriptional activators or inhibitors but rather may mark genes for potential future activation, i.e., they may establish competency to execute specific differentiation programs, with the actual activation being accomplished by transcriptional pathways triggered by exogenous signals. This proposed function may be an architectural one, involving changes in the conformation of DNA and/or altering interactions between DNA and histones, thus making areas of the genome more or less accessible to other protein factors (102). If this is the case, we may need to develop new assays to discern the molecular action of HOX proteins. The ease of manipulating the hematopoietic systems would appear to make it a very attractive model for explicating the general functions of this remarkable family of genes.


First determination of the rate constant for ring-closure of an azahexenoyl radical: 6-aza-7-ethyl-5-hexenoyl.
Competitive kinetic experiments utilising free radical carbonylation chemistry provide a first estimate for the rate constant for 6-endo cyclization of the 6-aza-7-ethyl-5-hexenoyl radical of (4.8 +/- 2.4) x 10(6) s(-1) at 90 degrees C in benzene, in good agreement with ONIOM-G3(MP2)-CC+COSMO-RS calculations (6.8 x 10(6) s(-1)).


Auto-oscillation of surface tension: effect of pH on fatty acid systems.
Spontaneous nonlinear oscillations of surface tension produced by transfer of either octanoic or nonanoic acids from a droplet situated in the bulk water to the air/water interface are studied experimentally. It is shown that the oscillation amplitude decreases significantly with the increase of pH of aqueous phase. At pH > 6.5, detectable oscillations for the two fatty acids studied do not exist. The results are discussed in terms of the mechanism proposed recently for spontaneous oscillations produced by transfer of nonionic surfactants.


Stress and decision making: a few minutes make all the difference.
Stress has been shown to impair decision making. However the temporal development of this phenomenon remains poorly understood. We speculated that the rapid stress induced increase in norepinephrine and the delayed increase in cortisol might exert opposing effects on decision making under risk. Therefore, three different experimental groups underwent the Trier Social Stress Test (TSST) and performed the Game of Dice Task (GDT) at different time points in relation to the stressor, which lasted approximately 18min. The first group performed the GDT 5min after stress onset, the second and third group performed the GDT either 18 or 28min after TSST onset. Decision-making performance of the control group was measured after a respective resting time. Results confirmed a rapid activation of the sympathetic nervous system and a somewhat slower response of the hypothalamic pituitary adrenal axis. In the GDT an improvement of decision-making performance in the 5 and 18min stress groups compared to controls and the 28min stress group occurred. Descriptively, decision making of the 28min after stress group was more risky than decision making of the control group. Our findings are in line with the idea that a moderate increase in catecholamines enhances decision-making performance, while elevated cortisol concentrations may negatively affect decision making presumably via rapid nongenomic mechanisms.


Direct Detection of Uranyl in Urine by Dissociation from Aptamer-Modified Nanosensor Arrays.
An ever-growing demand for uranium in various industries raises concern for human health of both occupationally exposed personnel and the general population. Toxicological effects related to uranium (natural, enriched, or depleted uranium) intake involve renal, pulmonary, neurological, skeletal, and hepatic damage. Absorbed uranium is filtered by the kidneys and excreted in the urine, thus making uranium detection in urine a primary indication for exposure and body burden assessment. Therefore, the detection of uranium contamination in bio-samples (urine, blood, saliva, etc.,) is of crucial importance in the field of occupational exposure and human health-related applications, as well as in nuclear forensics. However, the direct determination of uranium in bio-samples is challenging because of "ultra-low" concentrations of uranium, inherent matrix complexity, and sample diversity, which pose a great analytical challenge to existing detection methods. Here, we report on the direct, real-time, sensitive, and selective detection of uranyl ions in unprocessed and undiluted urine samples using a uranyl-binding aptamer-modified silicon nanowire-based field-effect transistor (SiNW-FET) biosensor, with a detection limit in the picomolar concentration range. The aptamer-modified SiNW-FET presented in this work enables the simple and sensitive detection of uranyl in urine samples. The experimental approach has a straight-forward implementation to other metals and toxic elements, given the availability of target-specific aptamers. Combining the high surface-to-volume ratio of SiNWs, the high affinity and selectivity of the uranyl-binding aptamer, and the distinctive sensing methodology gives rise to a practical platform, offering simple and straightforward sensing of uranyl levels in urine, suitable for field deployment and point-of-care applications.


Blue-light hazard from CO2 arc welding of mild steel.
The objective was to quantify the blue-light hazard from CO(2) arc welding of mild steel. The spectral radiance of arcs in CO(2) arc welding of mild steel was measured for solid and flux-cored wires at welding currents of 120-480 A. Effective blue-light radiance and the maximum acceptable exposure duration were calculated from the spectral radiance using their definitions in American Conference of Governmental Industrial Hygienists guidelines. The effective blue-light radiance ranged from 22.9 to 213.1 Wcm(-2)sr(-1). The corresponding maximum acceptable exposure duration was only 0.47-4.36 s, meaning that the total daily exposure to the welding arc without eye protection should not exceed this duration. It is very hazardous to view the arcs in CO(2) arc welding of mild steel. Welders and their helpers should use appropriate eye protectors in these arc-welding operations. Also, they should avoid direct light exposure when starting an arc-welding operation.


Communicating mild and borderline abnormal cervical smear results: how and what are women told?
The way in which women are informed about borderline or mild smear results can have a significant psychological impact. By means of a questionnaire survey of general practices in Nottingham, England, this study audited the means by which abnormal smear results were normally communicated to subjects and analysed the content of these communications. Transmitting abnormal smear results, either by letter or by telephone call, was typically the responsibility of the practice nurse, and communications varied widely in informational content. We conclude that the method and content of communications imparting mild or borderline smear results differs between general practices, even within a small geographical area.


Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics.
Immunohistology and in situ hybridization were used to evaluate the presence, activation status, and cytokine mRNA profile of cells in the bronchial mucosa during human allergen-induced asthma. Fifteen atopic asthmatic subjects underwent inhalation challenge with allergen and with allergen diluent, performed in random order separated by an interval of at least 3 wk. Bronchial biopsies were obtained 24 h after challenge. Immunostaining revealed increases in the numbers of secreting eosinophils (EG2+; P < 0.05) and in interleukin-2 receptor (IL-2R)-positive cells (CD25+; P < 0.01) after allergen compared with diluent challenge. No differences were observed in the numbers of total leukocytes (CD45+), T lymphocytes (CD3+, CD4+, and CD8+), elastase-positive neutrophils, macrophages (CD68+), or mast cell subtypes (MCT+ or MCTC+). In situ hybridization revealed significant increases in the numbers of cells expressing mRNA for IL-5 (P < 0.02) and granulocyte/macrophage colony-stimulating factor (P < 0.01) after allergen compared with diluent challenge. A significant inverse relationship was observed between the number of cells expressing mRNA for IL-4 and for interferon-gamma (r = -0.75, P < 0.02). The results support the view that cytokines possibly from activated T lymphocytes may contribute to local eosinophil accumulation during allergen-induced asthma.


Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms.
Measure acceptance and use of extending the number of active oral contraceptive (OC) pills beyond 21 days and/or shortening the hormone-free interval to reduce the frequency and severity of hormone withdrawal symptoms. A retrospective review was performed of patients on OCs with unwanted hormone withdrawal symptoms who were counseled by one osbtetrician-gynecologist (P. J. S.) on altering their standard 21/7 regimen. All patients used a monophasic 30 to 35 microg pill and underwent an initial counseling visit between December 1993 and October 2000. Of 318 patients counseled on "extending the number of active pills," 292 (92%) had documented follow-up after the initial counseling session. The primary reason for extending the number of active pills was to decrease symptoms of headache (35%), dysmenorrhea (21%), hypermenorrhea (19%), and premenstrual symptoms (13%). The remaining 12% of patients cited convenience, endometriosis, and other reasons such as menstrual-associated acne. Twenty-five (9%) of 292 chose not to extend, with a preference for monthly menses as the most common reason (40%) followed by a concern that symptoms were not severe enough to warrant extension (32%). Of 267 patients who initiated an extended regimen, 57 discontinued OCs, 38 returned to a standard regimen, and 172 were extending use at the time of last follow-up. Using survival analysis methods, at 5 years 46% +/- 5% (mean +/- SE) of patients continued an extended OC pattern. The regimen of OC use by patients continuing an extended pattern was 12 +/- 12 (mean +/- SD) weeks of active pills (median of 9 weeks and range to 104 weeks) with pill-free interval of 6 +/- 2 days (median of 5 days and range of 0-7 days). The majority of patients with hormone withdrawal symptoms on OCs will initiate a regimen of extending active pills, often with a shortened hormone-free interval to reduce frequency and severity of associated symptoms.


Adenosine A2A receptor ligand recognition and signaling is blocked by A2B receptors.
The adenosine receptor (AR) subtypes A2A and A2B are rhodopsin-like Gs protein-coupled receptors whose expression is highly regulated under pathological, e.g. hypoxic, ischemic and inflammatory conditions. Both receptors play important roles in inflammatory and neurodegenerative diseases, are blocked by caffeine, and have now become major drug targets in immuno-oncology. By Förster resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET), bimolecular fluorescence complementation (BiFC) and proximity ligation assays (PLA) we demonstrated A2A-A2BAR heteromeric complex formation. Moreover we observed a dramatically altered pharmacology of the A2AAR when co-expressed with the A2BAR (A2B ≥ A2A) in recombinant as well as in native cells. In the presence of A2BARs, A2A-selective ligands lost high affinity binding to A2AARs and displayed strongly reduced potency in cAMP accumulation and dynamic mass redistribution (DMR) assays. These results have major implications for the use of A2AAR ligands as drugs as they will fail to modulate the receptor in an A2A-A2B heteromer context. Accordingly, A2A-A2BAR heteromers represent novel pharmacological targets.


Wetting behavior of water droplets on hydrophobic microtextures of comparable size.
The wetting behavior of water droplets on periodically structured hydrophobic surfaces was investigated. The effect of structure geometry, roughness, and relative pore fraction on the contact angles was investigated experimentally for droplets of size comparable to the size of the structures. It was found that surface geometry may induce a transition from groove-filling and Wenzel-like behavior to nonfilling of surface grooves and consequential Cassie-Baxter behavior. Numerical calculations of the free energy of these systems suggest that the equilibrium behavior is in line with the experimental observations. The observations may serve as guidelines for the design of surfaces with the desired wetting behavior.


MapSplice: accurate mapping of RNA-seq reads for splice junction discovery.
The accurate mapping of reads that span splice junctions is a critical component of all analytic techniques that work with RNA-seq data. We introduce a second generation splice detection algorithm, MapSplice, whose focus is high sensitivity and specificity in the detection of splices as well as CPU and memory efficiency. MapSplice can be applied to both short (<75 bp) and long reads (≥ 75 bp). MapSplice is not dependent on splice site features or intron length, consequently it can detect novel canonical as well as non-canonical splices. MapSplice leverages the quality and diversity of read alignments of a given splice to increase accuracy. We demonstrate that MapSplice achieves higher sensitivity and specificity than TopHat and SpliceMap on a set of simulated RNA-seq data. Experimental studies also support the accuracy of the algorithm. Splice junctions derived from eight breast cancer RNA-seq datasets recapitulated the extensiveness of alternative splicing on a global level as well as the differences between molecular subtypes of breast cancer. These combined results indicate that MapSplice is a highly accurate algorithm for the alignment of RNA-seq reads to splice junctions. Software download URL: http://www.netlab.uky.edu/p/bioinfo/MapSplice.


Factors influencing injury severity score regarding Thai military personnel injured in mass casualty incident April 10, 2010: lessons learned from armed conflict casualties: a retrospective study.
Political conflicts in Bangkok, Thailand have caused mass casualties, especially the latest event April 10, 2010, in which many military personnel were injured. Most of them were transferred to Phramongkutklao Hospital, the largest military hospital in Thailand. The current study aimed to assess factors influencing Injury Severity Score (ISS) regarding Thai military personnel injured in the mass casualty incident (MCI) April 10, 2010. A total of 728 injured soldiers transferred to Phramongkutklao Hospital were reviewed. Descriptive statistics was used to display characteristics of the injuries, relationship between mechanism of injury and injured body regions. Multiple logistic regressions were used to calculate the adjusted odds ratio (adjusted OR) of ISS comparing injured body region categories. In all, 153 subjects defined as major data category were enrolled in this study. Blast injury was the most common mechanism of injury (90.2%). These victims displayed 276 injured body regions. The most common injured body region was the extremities (48.5%). A total of 18 patients (11.7%) had an ISS revealing more than 16 points. Three victims who died were expected to die due to high Trauma and Injury Severity Score (TRISS). However, one with high TRISS survived. Factors influencing ISS were age (p = 0.04), abdomen injury (adjusted OR = 29.9; 95% CI, 5.8-153.5; P < 0.01), head & neck injury (adjusted OR = 13.8; 95% CI, 2.4-80.4; P < 0.01) and chest injury (adjusted OR = 9.9; 95% CI, 2.1-47.3; P < 0.01). Blast injury was the most common mechanism of injury among Thai military personnel injured in the MCI April 10, 2010. Age and injured body region such as head & neck, chest and abdomen significantly influenced ISS. These factors should be investigated for effective medical treatment and preparing protective equipment to prevent such injuries in the future.


[The efficacy of OM85-BV in the treatment of recurrent upper respiratory tract infection with adenoid hypertrophy and the preliminary exploration of potential therapeutic mechanism].
Objective:To observe the efficacy of OM85-BV in the treatment of recurrent upper respiratory tract infection with adenoid hypertrophy and to explore its possible mechanism. Method:Four hundred and forty-eight children with recurrent upper respiratory tract infection and adenoid hypertrophy were collected. Three hundred and twenty-six patients in the control group were treated with conventional drugs, and one hundred and twenty-two patients in the observation group were treated with OM85-BV+conventional drugs, and the treatment lasted 12 weeks. The sleep obstructive symptoms of adenoid hypertrophy were scored according to OSA-18 before and after the treatment respectively(0, 6, 12 weeks). The symptoms scores and effective rate of treatment between the study and the control group were compared. The patients in the control group and the observation group who were unresponsive to drug treatment received surgery after 12 weeks of drug treatment. The levels of serum IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ and IgE, the ratio of serum CD3, CD4, CD8 in lymphocytes and the ratio of CD4/CD8 were compared between the study and the control group before operation. The levels of HBD-2, IFN-γ, IL-4, IL-6 cytokines in the adenoid were compared between the control group and the observation group. The expression and distribution of adenoid HBD-2, IFN-γ, IL-4, IL-6 were compared between the control group and the observation group. Result:After 12 weeks of treatment, the total effective rate of the observation group was significantly higher than that of the control group, and the improvement of sleep respiratory obstruction symptoms of children with recurrent upper respiratory tract infection and adenoid hypertrophy was also much better than that of the control group. The serum IFN-γ of the observation group was significantly higher than that of the control group, and there was no significant difference in serum IL-2, IL-4, IL-6, IL-10, TNF, IgE between the observation group and the control group. There was no significant difference in serum CD3, CD4, CD8 and CD4/CD8 between the observation group and the control group. In the observation group, the adenoid HBD-2 was significantly higher but IL-4, IFN-γ were significantly lower than that in the control group, and IL-6 had no significant difference compared with the control group. Conclusion:OM85-BV can significantly improve the sleep apnea symptoms but can not rise the level of immune lymphocytes in children with adenoid hypertrophy and recurrent upper respiratory tract infection.OM85-BV can improve the Th1 immune response, enhancing the ability of human body to fight against pathogens and induce the release of HBD-2, increasing the resistance to microorganisms, reducing the bacteria aggregation, weakening the local inflammatory response in adenoids.


Risk of depression in patients with acromegaly in Korea (2006-2016): a nationwide population-based study.
An increased prevalence of depression has been reported in patients with acromegaly. However, most studies included a relatively small sample size owing to the rarity of acromegaly. We aimed to investigate the risk of depression in patients with acromegaly using the Korean National Health Information Database (NHID). The data of patients with acromegaly in 2006-2016 were collected from the rare incurable disease registry of the NHID. Patients with acromegaly were matched with control participants without acromegaly for age and sex in a 1:5 ratio. Patients who did not receive treatment for acromegaly had a significantly increased risk of depression (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.12-1.82). However, the risk of depression did not increase in patients who received treatment for acromegaly. The multiple Cox regression analysis showed that the risk of depression was significantly higher in the untreated group than in the control group during the first 3 years of observation (HR: 1.829, 95% CI: 1.305-2.563). However, after a time lag of over 3 years, the risk of depression decreased in the untreated group, which is similar to that in the control group. Our nationwide study suggests that patients who did not receive treatment for acromegaly have a higher risk of depression compared with controls. The untreated acromegaly patients should be monitored for the development of depression, especially in the early years after diagnosis. These results could serve as a basis for developing screening strategies to mitigate depression in acromegaly patients.


Effects of nocturnal oxygen therapy on heart function in SDB patients undergoing dialysis.
There is a close relationship between sleep disordered breathing (SDB) and heart failure. We performed home oxygen therapy (HOT) in patients with SAS undergoing dialysis, and investigated its effects on the heart function. The subjects were 10 SDB patients on dialysis. On retiring at night, oxygen was transnasally administered at 1.0 L/min. The human atrial natriuretic peptide (hANP), brain natriuretic peptide (BNP), total protein, Alb, cholesterol and phosphorus levels were measured before the start of oxygen therapy and after 6 weeks. The mean SpO2 increased from 93.5% [91.5, 97.0] to 96.3% [94.8, 97.4] (median [interquartile range]) (p = 0.015). The hANP (p = 0.0039), BNP (p = 0.0098) and serum Alb (p = 0.015) levels significantly improved. There were no significant changes in the cholesterol, phosphorus or total protein levels. These results suggest that nocturnal oxygen therapy improves indices of heart failure, contributing to the prevention and treatment of heart failure in dialysis patients with SDB.


Reactive surface coatings based on polysilsesquioxanes: controlled functionalization for specific protein immobilization.
The key designing in reliable biosensors is the preparation of thin films in which biomolecular functions may be immobilized and addressed in a controlled and reproducible manner. This requires the controlled preparation of specific binding sites on planar surfaces. Poly(methylsilsesquioxane)-poly(pentafluorophenyl acrylates) (PMSSQ-PFPA) are promising materials to produce stable and adherent thin reactive coatings on various substrates. Those reactive surface coatings could be applied onto various materials, for example, gold, polycarbonate (PC), poly(tetrafluoroethylene) (PTFE), and glass. By dipping those substrates in a solution of a desired amine, specific binding sites for protein adsorption could be immobilized on the surface. The versatile strategy allowed the attachment of various linkers, for example, biotin, l-thyroxine, and folic acid. The adsorption processes of streptavidin, pre-albumin, and folate-binding protein were monitored using surface plasmon resonance (SPR), Fourier transform infrared (FTIR) spectroscopy, fluorescence spectroscopy, and atomic force microscopy (AFM). The presented protein immobilization strategy, consisting of four steps (a) spin-coating of PMSSQ-PFPA hybrid polymer from tetrahydrofuran (THF) solution, (b) annealing at 130 degrees C for 2 h to induce thermal cross-linking of the PMSSQ part, (c) surface analogues reaction with different amino-functionalized specific binding sites for proteins, and (d) controlled assembly of proteins on the surface, may find various applications in future biosensor design.


Role of nectin in organization of tight junctions in epithelial cells.
In polarized epithelial cells, cell-cell adhesion forms specialized membrane structures comprised of claudin-based tight junctions (TJs) and of E-cadherin-based adherens junctions (AJs). These structures are aligned from the apical to the basal side of the lateral membrane, but the mechanism of this organization remains unknown. Nectin is a Ca2+ independent immunoglobulin-like cell-cell adhesion molecule which localizes at AJs. Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs in cooperation with E-cadherin. We show here that nectin is also involved in the formation of TJs. During the formation of the junctional complex consisting of AJs and TJs in Madin-Darby canine kidney (MDCK) cells, claudin and occludin accumulated at the apical sites of the nectin-based cell-cell adhesion sites. This accumulation of claudin and occludin was inhibited by inhibitors acting on the trans interaction of nectin. The barrier function of TJs was also impaired by the nectin inhibitors. It has been shown that a phorbol ester promotes the formation of a TJ-like structure in an E-cadherin-independent manner. This phorbol ester-induced formation of the TJ-like structure was also inhibited by the nectin inhibitors. These results suggest a role of the nectin-afadin system in the organization of TJs as well as AJs in epithelial cells.


Electron cloud migration effect-induced lithiophobicity/lithiophilicity transformation for dendrite-free lithium metal anodes.
Enabling stable lithium metal anodes is significant for developing electrochemical energy storage systems with higher energy density. However, safety hazards, infinite volume expansion, and low coulombic efficiency (CE) of lithium metal anodes always hinder their practical application. Herein, a nano-thickness lithiophilic Cu-Ni bimetallic coating was synthesized to prepare dendrite-free lithium metal anodes. The electron cloud migration effect caused by the different electronegativities of Cu and Ni can achieve lithiophobicity/lithiophilicity transformation and thus promote uniform Li deposition/dissolution. By changing the ratio of Cu to Ni, the electron cloud migration can be reasonably adjusted for obtaining dendrite-free lithium anodes. As a result, the as-obtained Cu-Ni bimetallic coating is able to guarantee dendrite-free lithium metal anodes with a stable long cycling time (>1500 hours) and a small voltage hysteresis (∼26 mV). In addition, full cells with LiFePO4 as a cathode present excellent cycling stability and high coulombic efficiency. This work can open a new avenue for optimizing the lithiophilicity of materials and realizing dendrite-free anodes.


Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male mice.
Low to moderate doses of alcohol consumption induce heightened aggressive behavior in some, but not all individuals. Individual vulnerability for this nonadaptive behavior may be determined by an interaction of genetic and environmental factors with the sensitivity of alcohol's effects on brain and behavior. We used a previously established protocol for alcohol oral self-administration and characterized alcohol-heightened aggressive (AHA) mice as compared with alcohol non-heightened (ANA) counterparts. A week later, we quantified mRNA steady state levels of several candidate genes in the serotonin [5-hydroxytryptamine (5-HT)] system in different brain areas. We report a regionally selective and significant reduction of all 5-HT receptor subtype transcripts, except for 5-HT(3), in the prefrontal cortex of AHA mice. Comparable gene expression profile was previously observed in aggressive mice induced by social isolation or by an anabolic androgenic steroid. Additional change in the 5-HT(1B) receptor transcripts was seen in the amygdala and hypothalamus of AHA mice. In both these areas, 5-HT(1B) mRNA was elevated when compared with ANA mice. In the hypothalamus, AHA mice also showed increased transcripts for 5-HT(2A) receptor. In the midbrain, 5-HT synthetic enzyme, 5-HT transporter and 5-HT receptors mRNA levels were similar between groups. Our results emphasize a role for postsynaptic over presynaptic 5-HT receptors in mice which showed escalated aggression after the consumption of a moderate dose of alcohol. This gene expression profile of 5-HT neurotransmission components in the brain of mice may suggest a vulnerability trait for alcohol-heightened aggression.


The mediating effects of stress and coping on depression among adolescents in China.
To explore gender differences in Chinese adolescent depression related to the mediating effects of stress and coping. The data were collected using a cross-sectional design from a multisite follow-up investigation of adolescent physical and psychological study carried out in China. The study population consisted of 17,622 students aged from 11 to 22 years of age in junior high, senior high schools, and colleges/universities from eight large cities in China. Overall, 44.3% of the sample reported depression during the past week. Male adolescents were more likely to have depression than female counterparts (46.8% versus 41.7%), especially those aged <15 and >17 years of age. Overall, stress in boys was statistically higher than that of girls. Boys experienced high levels of stress from school, family, health, and romantic domains, while girls suffered a higher level of peer stress. A multivariate logistic regression model showed that a high level of total stress was significantly associated with increased risk for depression, while peer stress and positive coping style were protective factors for depression in both boys and girls in China. Unlike their Western counterparts, Chinese boys suffered more depression than girls, which is partly due to more stressful life events and less positive coping style. Our study has important implications for health officers and public health professionals to pay much attention to the relationship between stress and coping style in prevention on adolescent depression.


Nurses' job satisfaction: a meta-analysis of related variables.
The purpose of this study was to describe the magnitude of the relationships between nurses' job satisfaction and the variables most frequently associated with it. A meta-analysis of data from 48 studies with a total of 15,048 subjects revealed that job satisfaction was most strongly associated with stress (-.609) and organizational commitment (.526). Seven variables had correlations between .20 and .50: communication with supervisor, autonomy, recognition, routinization, communication with peers, fairness, and locus of control. Four other variables frequently included in these studies had low correlations (less than .20): age, education, tenure, and professionalization. The influence of employment site, date of study, and measures used on the size and consistency of estimates was described.


Significant increase of blood alcohol by cimetidine after repetitive drinking of small alcohol doses.
To assess effects of repetitive alcohol drinking and pre-existing first-pass metabolism on the cimetidine-induced increase in blood alcohol concentrations, 20 healthy men (aged 20 to 40) of varied ethnicity and consuming less than 60 g alcohol per week underwent baseline quantitation of first-pass metabolism of alcohol. This was followed by oral administration of 0.6 g/kg ethanol given postprandially in 3 to 4 drinks spread over 135 min, before and after cimetidine (400 mg twice a day for 7 days). Blood alcohol concentrations were determined by breath analysis. First-pass metabolism was quantified by applying Michaelis-Menten kinetics to blood alcohol curves after intravenous or oral administration of equal alcohol doses. At baseline, 15 subjects had a substantial first-pass metabolism (over one sixth of the dose); their alcohol levels increased with repeated doses with a mean peak of 27 +/- 3 mg/dl before and 39 +/- 5 after cimetidine (P < 0.01), an effect much greater and longer than after a single alcohol dose. Three subjects exceeded 50 mg/dl, the legal limit for driving in several countries. By contrast, in the five subjects with minimal first-pass metabolism, cimetidine did not increase alcohol levels. Thus, under conditions mimicking social drinking, cimetidine increased blood alcohol to concentrations known to impair psychomotor skills and they persisted at those levels over prolonged periods of time. In a minority of subjects, no such interaction was found, but their first-pass metabolism at baseline was absent or minimal and thus no inhibition by the drug was to be expected.


Influence of vasoconstriction, temperature, and flow on the kinetics of serotonin uptake in rabbit lungs.
In the process of estimating the kinetic parameters of the pulmonary endothelial serotonin (5-HT) uptake, it is critically important to distinguish the effects of hemodynamic changes from endothelial injury. Therefore, the effects of changes in flow rate (1.7-5.0 ml/s), hemodynamics (vasoconstriction by norepinephrine), and temperature (39 vs. 33 degrees C) were investigated in isolated rabbit lungs. Indicator-dilution data were expressed in terms of the Michaelis-Menten equation for the two 5-HT uptake pathways in the preparation. The maximum uptake velocity (Vmax1) and the 5-HT concentration at half-maximum velocity (Km1) of the first pathway as well as the first-order constant (Vmax2/Km2) of the linear part of the second pathway were determined. Neither vasoconstriction nor flow variations had any effect on Km1, whereas increasing the flow rate caused extensive recruitment, with a concomitant increase in Vmax1 and Vmax2/Km2. Furthermore, all the kinetic parameters were significantly decreased at the lower temperature. We conclude that Km1 is independent of organ hemodynamics (vasoconstriction and flow) but susceptible to changes in 5-HT uptake capacity caused by a change in temperature. Vmax1 and Vmax2/Km2 respond to alterations in 5-HT uptake capacity and perfused organ volume. These are prerequisites to apply kinetic modeling as a method for the investigation of pulmonary endothelial function and integrity.


High frequency of methotrexate intolerance in longstanding rheumatoid arthritis: using the methotrexate intolerance severity score (MISS).
Methotrexate (MTX) intolerance is frequent, and its early identification may impact treatment, leading to timely changes in medication that may promote patient compliance and better control of rheumatoid arthritis (RA). The objective of this study was to identify the frequency of, and risk factors for, MTX intolerance using the Brazilian Portuguese version of the Methotrexate Intolerance Severity Score (MISS) questionnaire in patients with RA. This cross-sectional study was performed between April 2018 and April 2019 and enrolled patients with RA in regular use of oral or subcutaneous MTX for at least 3 months. Patients were invited to answer the Brazilian Portuguese version of the MISS questionnaire, and MTX intolerance was defined by a score ≥ 6 points. Age, sex, disease duration, time of MTX use, dose, route of administration, concomitant medications, comorbidities, smoking, and Disease Activity Score for 28joint (DAS28) data were collected from institutional medical records. Among 120 patients, 103 (85.8%) were female, the mean age was 61 (±12.5) years, the mean duration of disease was 16 (±10.3) years, and the average duration of MTX use was 7 (±5.5) years. The frequency of MTX intolerance was 21.6%. The most frequent symptoms reported after the use of MTX were nausea (92.3%), abdominal pain (46.1%), and vomiting (30.7%). Behavioral symptoms occurred in 96.1% of patients with MTX intolerance, the most frequent being restlessness and irritability. Patients who used corticosteroids were more likely to develop MTX intolerance than those not using corticosteroids (odds ratio = 2.73; 95% confidence interval, 1.06 to 7.06; p = 0.038). Conversely, increasing age showed marginally significant association with decreased risk of MTX intolerance (p = 0.059). The use of the MISS questionnaire disclosed high frequencies of anticipatory, associative, and behavioral symptoms in MTX-intolerant patients, and the use of corticosteroid increases the risk of MTX intolerance. We suggest that the MISS questionnaire be used routinely in clinical practice.


Cytologic features of blastic plasmacytoid dendritic cell neoplasm involving liver: A case report and literature review.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare but clinically aggressive hematologic malignancy, believed to originate from plasmacytoid dendritic cells (PDCs) although it possesses multilineage potentials. Due to the dismal prognosis, accurate and rapid diagnosis is critical for early management. The disease usually initially involves skin and bone marrow. Here we report the cytopathologic findings in a case of BPDCN involving the liver in a patient previously diagnosed with BPDCN from skin and lymph node biopsies. The fine-needle aspiration specimen from the liver lesion demonstrates a hypercellular smear of atypical epithelioid cells dispersed singly or in loose groups. These cells have enlarged, eccentric, round to irregular nuclei with fine chromatin. The agranular gray-blue cytoplasm shows delicate wispy cytoplasmic extensions and cytoplasmic microvacuoles. Binucleation is common. The concurrent core biopsy shows that the neoplastic plasmacytoid cells with eccentric nuclei were positive for CD4, CD7, CD43, CD56, and CD68, confirming the diagnosis of BPDCN. Mutations of ASXL1 and TET2, classic for BPDCN, and a complex karyotype were detected in skin, bone marrow, and lymph node specimens. We catalog the heterogeneous pathologic features of this rare disease, emphasizing the clinical and histopathological correlation. The differential diagnoses and review of literature are also included. Awareness of this disease and accurate diagnosis are emphasized to aid early management and potentially produce a better clinical outcome.


Colony formation and colony size do not reflect the onset of replicative senescence in human fibroblasts.
Replicative senescence of human fibroblasts in vitro has been used as a model for in vivo aging. The onset of replicative senescence varies between several months to years. A colony formation assay, critically dependent on growth speed, can be performed within weeks, and has been reported being an indicator for the onset of replicative senescence. Earlier we could not find a correlation between growth speed in mass cultures and onset of replicative senescence of human fibroblast strains. Therefore, we studied the colony formation assay in 23 fibroblast strains that varied widely in their replicative capacity. Neither the number nor the size of colonies was related to the onset of replicative senescence. The number of cells within the colonies was modestly correlated to the growth speed of the mass cultures. We conclude that the colony formation assay does not reflect the onset of replicative senescence in human fibroblasts.


Omicron variant susceptibility to neutralizing antibodies induced in children by natural SARS-CoV-2 infection or COVID-19 vaccine.
The novel SARS-CoV-2 Omicron variant may increase the risk of re-infection and vaccine breakthrough infections as it possesses key mutations in the spike protein that affect neutralizing antibody response. Most studies on neutralization susceptibility were conducted using specimens from adult COVID-19 patients or vaccine recipients. However, since the paediatric population has an antibody response to SARS-CoV-2 infection that is distinct from the adult population, it is critical to assess the neutralization susceptibility of pediatric serum specimens. This study compared the neutralization susceptibility of serum specimens collected from 49 individuals of <18 years old, including 34 adolescent BNT162b2 (Pfizer-BioNTech) vaccine recipients, and 15 recovered COVID-19 patients aged between 2 and 17. We demonstrated that only 38.2% of BNT162b2 vaccine recipients and 26.7% of recovered COVID-19 patients had their serum neutralization titre at or above the detection threshold in our live virus microneutralization assay. Furthermore, the neutralizing antibody titer against the Omicron variant was substantially lower than those against the ancestral virus or the Beta variant. Our results suggest that vaccine recipients and COVID-19 patients in the pediatric age group will likely be more susceptible to vaccine breakthrough infections or reinfections due to the Omicron variant than previous variants.


Delaunay tessellation of proteins: four body nearest-neighbor propensities of amino acid residues.
Delaunay tessellation is applied for the first time in the analysis of protein structure. By representing amino acid residues in protein chains by C alpha atoms, the protein is described as a set of points in three-dimensional space. Delaunay tessellation of a protein structure generates an aggregate of space-filling irregular tetrahedra, or Delaunay simplices. The vertices of each simplex define objectively four nearest neighbor C alpha atoms, i.e., four nearest-neighbor residues. A simplex classification scheme is introduced in which simplices are divided into five classes based on the relative positions of vertex residues in protein primary sequence. Statistical analysis of the residue composition of Delaunay simplices reveals nonrandom preferences for certain quadruplets of amino acids to be clustered together. This nonrandom preference may be used to develop a four-body potential that can be used in evaluating sequence-structure compatibility for the purpose of inverted structure prediction.


Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin.
As part of a screening programme for antibiotic-producing bacteria, a novel Actinomadura species was discovered from a soil sample collected in Santorini, Greece. Preliminary 16S rRNA gene sequence comparisons highlighted Actinomadura macra as the most similar characterised species. However, whole-genome sequencing revealed an average nucleotide identity (ANI) value of 89% with A. macra, the highest among related species. Further phenotypic and chemotaxonomic analyses confirmed that the isolate represents a previously uncharacterised species in the genus Actinomadura, for which the name Actinomadura graeca sp. nov. is proposed (type strain 32-07T). The G+C content of A. graeca 32-07 is 72.36%. The cell wall contains DL-diaminopimelic acid, intracellular sugars are glucose, ribose and galactose, the predominant menaquinone is MK-9(H6), the major cellular lipid is phosphatidylinositol and fatty acids consist mainly of hexadecanoic acid. No mycolic acid was detected. Furthermore, A. graeca 32-07 has been confirmed as a novel producer of the non-ribosomal peptide antibiotic zelkovamycin and we report herein a provisional description of the unique biosynthetic gene cluster.


Dietary Antioxidants in Age-Related Macular Degeneration and Glaucoma.
Age-related macular degeneration (AMD) and glaucoma are ophthalmic neurodegenerative diseases responsible for irreversible vision loss in the world population. Only a few therapies can be used to slow down the progression of these diseases and there are no available treatment strategies for reversing the degeneration of the neural retina. In AMD, the pathological process causes the malfunction and damage of the retinal pigmented epithelium and photoreceptors in the macula. In glaucoma, damage of the retinal ganglion cells and their axons is observed and treatment strategies are limited to intraocular pressure lowering. Therefore, other prophylactic and/or therapeutic methods are needed. Oxidative stress is involved in the neurodegenerative process accompanying both AMD and glaucoma; therefore, the use of antioxidant agents would clearly be beneficial, which is supported by the decreased prevalence and progression of AMD in patients adherent to a diet naturally rich in antioxidants. Dietary antioxidants are easily available and their use is based on the natural route of administration. Many preclinical studies both in vitro and using animal models of retinal degeneration showed the efficacy of dietary antioxidants, which was further proved in clinical trials. Resveratrol is beneficial both in AMD and glaucoma animal models, but confirmed only among AMD patients. For AMD, carotenoids and omega-3 fatty acids were also proved to be sufficient in preventing neurodegeneration. For glaucoma, coenzyme Q10 and alpha-lipoic acid showed efficacy for decreasing retinal ganglion cell loss and inhibiting the accompanying destructive processes. Interestingly, the benefits of vitamins, especially vitamin E was not confirmed, neither in preclinical nor in clinical studies.


Parental Home Vision Testing of Children During Covid-19 Pandemic.
The Covid-19 pandemic necessitated social distancing restrictions, which placed limitations on access to ophthalmic care to only those who had an imminent risk of sight loss. All other face-to-face consultations were converted to telephone consultations or were postponed. We investigated whether parents were able to test their child's vision using available home vision testing applications, with an aim to aid decision making during a telephone consultation. Families with follow-up consultations at Birmingham Children's Hospital were asked to test their child's vision at home. Instructions for the use of Peek acuity, or iSight Pro, were emailed to a parent. Parents chose to use a particular app based on available devices at home. Parents were asked to test uniocular visual acuity twice. Home versus hospital acuity was correlated. Home acuity test-retest reliability was acquired. Parental feedback was obtained through questionnaires. One hundred and three families were contacted, 15 families completed home vision testing. Ten families used Peek acuity, five families used iSight Pro. Uniocular visual acuity test-retest reliability was 0.03 LogMAR. Home-hospital acuity testing had a bias of 0.14 LogMAR, hospital acuity yielding a lower LogMAR score. Most families who completed testing found it easy to do; however, some struggled, and 81 families did not undertake home vision testing. Uptake of home vision testing was limited by parental engagement, most likely influenced by the current pandemic. Most families who undertook home vision testing were able to generate results that could be used for clinical decision making. Extending the impact of parental vision testing will require education by clinicians and further study to increase sample sizes and to improve confidence.


Glucosamine-6-phosphate synthase--the multi-facets enzyme.
L-Glutamine: D-fructose-6-phosphate amidotransferase, known under trivial name of glucosamine-6-phosphate synthase, as the only member of the amidotransferase subfamily of enzymes, does not display any ammonia-dependent activity. This enzyme, catalysing the first committed step in a pathway leading to the eventual formation of uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), is an important point of metabolic control in biosynthesis of amino sugar-containing macromolecules. The molecular mechanism of reaction catalysed by GlcN-6-P synthase is complex and involves both amino transfer and sugar isomerisation. Substantial alterations to the enzyme structure and properties have been detected in different neoplastic tissues. GlcN-6-P synthase is inflicted in phenomenon of hexosamine-induced insulin resistance in diabetes. Finally, this enzyme has been proposed as a promising target in antifungal chemotherapy. Most of these issues, especially their molecular aspects, have been extensively studied in recent years. This article provides a comprehensive overview of the present knowledge on this multi-facets enzyme.


Modulatory effects of black tea polyphenols on rat forestomach carcinogenesis.
ABSTRACT The present study was designed to evaluate the chemopreventive effects of black tea polyphenols (Polyphenon-B) on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in Wistar rats. Intragastric administration of MNNG induced well-differentiated squamous cell carcinomas that showed diminished mitochondrial lipid and protein oxidation and an increase in antioxidants. In contrast to tumor tissue, the liver mitochondria of tumor-bearing animals showed elevated lipid and protein oxidation with compromised antioxidant defenses. Dietary administration of Polyphenon-B effectively suppressed MNNG-induced stomach tumors, modulated mitochondrial lipid and protein oxidation, and enhanced antioxidant enzyme activities in the stomach and liver. Our results suggest that Polyphenon-B may exert its chemopreventive effects by modulating mitochondrial cellular redox status in the tumor as well as in the host liver.


Rough-fuzzy collaborative clustering.
In this study, we introduce a novel clustering architecture, in which several subsets of patterns can be processed together with an objective of finding a common structure. The structure revealed at the global level is determined by exchanging prototypes of the subsets of data and by moving prototypes of the corresponding clusters toward each other. Thereby, the required communication links are established at the level of cluster prototypes and partition matrices, without hampering the security concerns. A detailed clustering algorithm is developed by integrating the advantages of both fuzzy sets and rough sets, and a measure of quantitative analysis of the experimental results is provided for synthetic and real-world data.


How I do it: emergency nasal packing using an umbilical cord clamp to secure a Foley catheter for posterior epistaxis.
Posterior nasal balloon tamponade using a Foley catheter is a well-known, easy, and quick way to bring an end to a posterior epistaxis in emergency situations. To prevent loosening and displacement of the balloon away from the choana, some metallic devices that may crush or tear the catheter are often used. Being light and easy to install, a plastic umbilical cord clamp is a good alternative. While providing a stable double grip on the catheter, the Hollister umbilical clamp does not crush it. When the clamp is removed, saline can be aspirated from the balloon and the catheter left in place with the nasal packing. Afterward, if needed, the saline can be reinjected to restore the tamponade.