Quantitative Interpretations of Break Junction Conductance Histograms in Molecular Electron Transport.
We develop theoretical and computational tools for extracting quantitative molecular information from experimental conductance histograms for electron transport through single-molecule break junctions. These experimental setups always measure a combination of molecular conductance and direct electrode-electrode tunneling; our derivations explicitly incorporate the effects of such background tunneling. Validation of our models to simulated data shows that background tunneling is crucial for quantitative analyses (even in cases where it appears to be qualitatively negligible), and comparison to experimental data is favorable. Finally, we generalize these ideas to the case of molecules with a destructive interference feature and discuss potential signatures for interference in a conductance histogram.


Rare diseases and the assessment of intervention: what sorts of clinical trials can we use?
There is increasing emphasis on the importance of practising evidence-based medicine. Randomized controlled trials are the standard way to assess the benefits of an intervention, and observational studies are not usually accorded much weight; the results are likely to be considered misleading. For rare diseases, there are great difficulties in obtaining adequate evidence for interventions or for the benefits of early diagnosis. This is because the disorders are not only very rare but also have variable expression, may have very long courses, and have incompletely known late effects; and surrogate end-points often have to be used. Randomized controlled trials are usually impossible because of inadequate power, and because there are preconceived notions of the effects of treatments already in use. The adoption of the best possible design for observational trials, formation of a central registry of such trials, and a greater general appreciation of the problems that rare diseases pose will help in obtaining the best possible evidence for the effects of interventions.


Downregulated ABCG2 enhances sensitivity to topoisomerase I inhibitor in epidermal growth factor receptor tyrosine kinase inhibitor-resistant non-small cell lung cancer.
Understanding the mechanisms of drug resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is essential to develop novel chemotherapies for non-small cell lung cancer (NSCLC). Therefore, we analyzed the expression and function of ATP-binding cassette (ABC) transporters in EGFR TKI-resistant NSCLC. In three newly established AG1478-resistant NSCLC cell lines, we evaluated the expression profile of ABC transporters and genotyping of ABCG2 by real-time polymerase chain reaction and elucidated their function by Hoechst dye efflux analyses. The growth-inhibitory effect of the topoisomerase I inhibitor Hoechst 33342, which is extruded by ABCG2, was also investigated in these cells using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. In AG1478-resistant cells, significantly less ABCG2 was expressed, and the ratios of the cells with a strong ability to extrude Hoechst dye were remarkably smaller than in the parent cells. Because of the ABCG2 downregulation and loss of function due to C421A/C421A homozygosity, PC-14AG50R was thus considered to be more sensitive to Hoechst 33342 than the parental cells. All AG1478-resistant cells were more sensitive to the combination of Hoechst 33342 and AG1478 than to single agent. Resistance to EGFR TKI in NSCLC is associated with the downregulation of ABCG2 expression. A topoisomerase I inhibitor alone or in combination with EGFR TKI might offer a promising strategy for treating NSCLC that is resistant to EGFR TKI.


Microwave-Assisted Cp*CoIII-Catalyzed C-H Activation/Double C-N Bond Formation Reactions to Thiadiazine 1-Oxides.
A microwave-assisted, Cp*CoIII-catalyzed direct C-H activation/double C-N bond formation reaction of simple NH-sulfoximines with 1,4,2-dioxazol-5-ones to produce diverse thiadiazine-1-oxides is reported. The reaction tolerates a broad range of functional groups under external oxidant-free conditions and only releases CO2 and H2O as the sole byproducts. The preliminary mechanistic studies revealed an electrophilic metalation pathway is likely involved in the reaction.


[Pulmonary abscesses and bronchiectasis].
Both primary and secondary pulmonary abscesses are increasingly observed in thoracic surgery units. Primary pulmonary abscesses are related to necrotising pneumonia or aspiration due to alcoholism, drug abuse, dysphagia or gastrointestinal reflux disease. Secondary poststenotic abscesses are related to bronchial obstruction (endobronchial tumour or foreign body aspiration) or to superinfection of pulmonary neoplasia or infarction pneumonia. Bronchoscopy is mandatory if a pulmonary abscess is suspected, to exclude endobronchial obstruction and obtain bacteriological examination by bronchial lavage or transbronchial fine needle aspiration. Transthoracic fine needle aspiration may be helpful for bacteriological examination, since germs found in sputum do not necessarily correlate with those found in the abscess. Pulmonary abscesses are primarily treated by administration of appropriate antibiotics with a remission rate of 80%. In the presence of complications of the abscess or if conservative management fails, percutaneous transthoracic drainage or surgical resection may be indicated. Bronchiectasis is also increasingly seen, especially in refugees and immigrants. The disease is characterised by chronic dilatation of bronchi with paroxysmal cough, mucopurulent secretion and recurrent pulmonary infections. Bronchiectasis is most commonly caused by recurrent bronchial infections during childhood or behind bronchial obstruction. Congenital bronchiectasis is very rare. Viral and bacterial pulmonary infections during childhood are by far the most common causes of bronchiectasis, leading to destruction of the mucociliary apparatus and the cartilage of the segmental bronchi. Bronchiectasis should be treated by an appropriate antibiotic regimen. Resection should only be considered in situations where a conservative regimen fails. Segmentectomy of all involved segments is the surgical treatment of choice in situations with well-localised bronchiectasis and results in long-lasting remission in over 80% of those patients. Patients with bilateral bronchiectasis may be considered for bilateral surgical resection if diffuse and congenital disease has been ruled out.


Tip-growing cells of the moss Ceratodon purpureus Are gravitropic in high-density media.
Gravity sensing in plants and algae is hypothesized to rely upon either the mass of the entire cell or that of sedimenting organelles (statoliths). Protonemata of the moss Ceratodon purpureus show upward gravitropism and contain amyloplasts that sediment. If moss sensing were whole-cell based, then media denser than the cell should prevent gravitropism or reverse its direction. Cells that were inverted or reoriented to the horizontal displayed distinct negative gravitropism in solutions of iodixanol with densities of 1.052 to 1.320 as well as in bovine serum albumin solutions with densities of 1.037 to 1.184 g cm(-3). Studies using tagged molecules of different sizes and calculations of diffusion times suggest that both types of media penetrate through the apical cell wall. Estimates of the density of the apical cell range from 1.004 to 1.085. Because protonemata grow upward when the cells have a density that is lower than the surrounding medium, gravitropic sensing probably utilizes an intracellular mass in moss protonemata. These data provide additional support for the idea that sedimenting amyloplasts function as statoliths in gravitropism.


Evaluation of the physical and antimicrobial properties of silver doped hydroxyapatite depending on the preparation method.
In the present study, the effect of the preparation method on the physical and antibacterial properties of silver doped hydroxyapatite (HAp/Ag) samples was investigated. HAp/Ag with 0.1-5 % of silver was prepared using two different modified wet chemical precipitation methods. A comparison of thermal stability and thermodynamical properties indicated that the thermal stability and sintering temperature of HAp/Ag were higher than those of pure hydroxyapatite if Ca(NO3)2·4H2O, AgNO3, NH4OH and (NH4)2HPO4 were used as raw materials. Phase composition and silver release were determined by XRD and ICP-MS. The study showed that, after 50 h in simulated body fluid 0.8-1.8 % of silver of the total silver amount was released from compact HAp/Ag scaffolds, and release kinetics strongly depended on the HAp/Ag preparation method. In vitro antibacterial activity of samples from each method against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa was approved. Results showed that, in the case of using Ca(OH)2, H3PO4 and AgNO3 as raw materials for HAp/Ag synthesis, higher antibacterial activity towards both bacterial strains could be obtained.


[T2*-contrast perfusion study--principles, theory and clinical utility in evaluating cerebral hemodynamics].
Contrast-enhanced dynamic study is easily feasible with a clinical MR system, for evaluating cerebral perfusion. A bolus of the paramagnetic contrast agents such as Gd-DTPA produces inhomogenity of the regional magnetic field between the capillaries and extravascular proton, and causes a decrease of signal intensity in the perfused region with T2*-weighted sequences. Echo planar imaging (EPI) is suitable for contrast-enhanced dynamic study, because it is markedly susceptible and provides high temporal-resolution. Tracer kinetic approaches are used for analysis of the dynamic data to acquire various perfusion parameters such as time delta R2* curve, rCBF, rCBV and MTT. T2*-weighted contrast-enhanced perfusion imaging is useful, especially, for detecting hyperacute ischemia and its therapeutic window, and depicting vasculature and ability of the brain tumors.


Hepatitis C testing: interpretation, implications, and counseling.
New molecular biology techniques recently identified hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis. Serologic assays for HCV specific antibodies are a significant advance, but they require cautious interpretation due to problems with the tests' sensitivity and specificity. Patients with suspected HCV infection should be thoroughly evaluated to verify the presence of infection, to exclude other forms of chronic liver disease, and to determine the extent of liver damage prior to considering treatment.


Ripening and in vitro retention of respiratory control by avocado and pear mitochondria.
The retention of respiratory control ("survival") by mitochondria held at 25 C was studied in relation to the ripening of two varieties of avocado (Persea americana Mill. var. ;Fuerte' and ;Hass') and one variety of pear (Pyrus communis. L. var. ;Bartlett') fruit. The survival of avocado mitochondria increased from 8 to 10 hours when isolated from unripe, preclimacteric fruit, to 48 hours when isolated from fully ripe, postclimacteric fruits. Although rates of alpha-ketoglutarate oxidation, respiratory control, and ADP/O decreased somewhat in the postclimacteric phase, survival per se was not affected. Pear mitochondria survived for more than 30 hours regardless of the physiological age of the source.Exposure of postclimacteric avocado mitochondria to a preclimacteric supernatant fraction curtailed their survival. The harmful effect of some unknown substance(s) in the preclimacteric avocado supernatant fraction was confirmed by utilizing pear mitochondria as an independent test system.


Caries classification and management in the context of the CariesCare International (CCI™) consensus: a clinical case study.
The objective of this clinical case study is to illustrate the caries management four-step structured process, leading to personalised interventions specific for each individual patient's risks and needs, according to CariesCare International, derived from the International Caries Classification and Management System (ICCMS) for clinical practice. An 18-year-old female was diagnosed with higher caries risk at the individual level, and with several caries lesions at different severity stages, some likely active and others likely inactive. A care plan was co-created with the patient and delivered to obtain optimal health outcomes. Several issues pertinent to patient-centred care are discussed, including caries management at the individual and the tooth surface level, the preservation of tooth structure, patient's caries risk management, and prevention and control of caries lesions. The patient's perspective is taken into account and the health outcome focus of the system is highlighted.


Design and development of a low-cost optical current sensor.
In this paper we demonstrate the design of a low-cost optical current sensor. The sensor principle is the Faraday rotation of a light beam through a magneto-optical material, SF2, when a magnetic field is present. The prototype has a high sensitivity and a high linearity for currents ranging from 0 up to 800 A. The error of the optical fibre sensor is smaller than 1% for electric currents over 175 A.


Restriction fragment length polymorphism of 16S-23S rDNA intergenic spacer of Aeromonas spp.
We analyzed restriction fragment length polymorphism (RFLP) of 16S-23S rDNA intergenic spacer region (ISR) of Aeromonas species. A total of 69 isolates belonging to 18 DNA hybridization groups (HG; equivalent of genomic species) were used in this study. ISRs were amplified by PCR and the products were digested with four restriction endonucleases: Hin6I, Csp6I, TaqI, and TasI. The RFLP patterns obtained after digesting by particular enzymes revealed ISR polymorphism of isolates allocated to individual genomic species. The combined Hin6I, Csp6I, TaqI, and TasI restriction profiles were examined by Dice coefficient (SD) and unweighted pair group method of clustering (UPGMA). The isolates were allocated into 15 groups, three strains were unclustered. The strains belonging to the following genomic species: A. hydrophila, A. bestiarum, A. salmonicida, A. caviae, A. media, A. schubertii, A. allosaccharophila, A. popoffii, and A. culicicola formed distinct clusters. Strains belonging to HG 6, HG 7, HG 11, and HG 16 revealed similar combined RFLP patterns and constituted one group. Similarly, the strains of A. jandaei (HG 9) and the type strain of A. trota were allocated into one cluster. Two isolates of HG 14 formed distinct cluster. We noticed a genetic diversity among A. veronii isolates, the strains were clustered in two groups. Our study showed that combined ISR-RFLP analysis may be used for identification of some species of Aeromonas.


Multidimensional quadratic extrapolation method for the correction of aberrations in lens systems.
An interactive optical design tool that is based on multidimensional quadratic extrapolation is described. This technique extends the radius of convergence of the aberration manipulation process, provides strategic information about the correctability of the aberrations at each stage in iteration, and is computationally simple. A quadratic approximation to each of the nonlinearly varying aberrations, which are initially based on one relatively remote linearly predicted point in solution space, allows the step length of this differential improvement method to be extended over that which is possible with local derivative techniques. The basic mathematical method works with an equal number of defects and variables, and to involve all the relevant constructional parameters of an optical system these are grouped or linked together on the basis of an assumption about their combined ability to correct the chosen aberrations. Examples are given.


Arthrobacter cupressi sp. nov., an actinomycete isolated from the rhizosphere soil of Cupressus sempervirens.
An actinobacterial strain, designated D48(T), was isolated from the rhizosphere soil of a cypress tree collected from Mianyang in Sichuan province, China. The strain was Gram-stain-positive, catalase-positive, oxidase-negative and non-motile, with lysine as the peptidoglycan diagnostic diamino acid and acetyl as the peptidoglycan acyl type. The predominant menaquinone was MK-9(H(2)); small amounts of MK-7(H(2)), MK-10(H(2)) and MK-6 were also present. The major fatty acids were anteiso-C(15:0), anteiso-C(17:0) and iso-C(16:0). The isolate underwent a rod-coccus morphological cycle, had a high DNA G+C content, was aerobic and grew between 12 and 37 °C (optimum, 28 °C). On the basis of the phenotypic and chemotaxonomic analyses, 16S rRNA gene sequence comparisons and DNA-DNA hybridization data, the isolate represents a novel species of the genus Arthrobacter, for which the name Arthrobacter cupressi sp. nov. is proposed. The type strain is D48(T) (=DSM 24664(T)=CGMCC 1.10783(T)).


Goldenhar Syndrome: A rare case report.
Goldenhar Syndrome or oculoauriculovertebral spectrum is a complex syndrome characterized by an association of maxillomandibular hypoplasia, deformity of the ear, ocular dermoid and vertebral anomalies and the most severe form of hemifacial microsomia. Here, we describe a 26-year-old male patient with unilateral hemifacial microsomia, preauricular ear tags, macrosomia on the right side of the face.


Spin-component-scaling second-order Møller-Plesset theory and its variants for economical correlation energies: unified theoretical interpretation and use for quartet N3.
The spin-component-scaling second-order Møller-Plesset theory proposed by Grimme, the scaled opposite-spin variant of Head-Gordon and co-workers, and other variants of the theory to treat the electron correlation energy are examined. A refinement of scaled opposite-spin theory for strong chemical interactions is suggested where the scaled correlation contribution is chosen such as to mimic closely the one obtained by more sophisticated methods of the coupled cluster type. With the scaling factor chosen to vary in a simple statistical manner with the number of opposite-spin electron pairs of the system, the parameters have been calibrated from standard coupled cluster type calculations for a chosen ab initio test data set. The new approach, termed as variable-scaling opposite spin, aims to be applicable at any regions of the molecule configuration space where second-order Møller-Plesset perturbation theory converges. It thus benefits of all advantages inherent to the original theory, which makes it an attractive approach on a computational cost basis. Because the method in one of its formats fails size-extensivity, the consequences and remedies of this are analyzed. Illustrations are presented for many molecules utilizing Dunning-type basis sets, in particular, for a detailed analysis of N(3) in its lowest quartet state, which does not belong to the test set. Extrapolations of the calculated raw energies to the complete one-electron basis set limit are also reported, giving the most reliable estimates available thus far of the energetics for the N((4)S)+N(2) exchange reaction. All spin-component-scaling schemes are known to show difficulties in dealing with weak interactions of the van der Waals type, which has justified the design of specific variants of the theory according to the property and regime of interactions. Several variants of the theory are then examined using a second test set of molecules, and shown to be linked via a coordinate that evolves gradually between two known extreme regimes. It is further shown that such a coordinate can be specified via a constrained Feenberg-type scaling approach, a theory whose merits are also explored.


A Z-type PGeP pincer germylene ligand in a T-shaped palladium(0) complex.
A dipyrromethane-based germylene decorated with two phosphane groups has been used to prepare an unusual T-shaped palladium(0) containing a PGeP pincer germylene that acts as a Z-type ligand. This compound is a strong reducing reagent, as it has been easily oxidized to germyl-palladium(ii) derivatives with a gold(i) complex, HCl and Ph2S2 through processes that involve formal addition of a bond of the oxidant across the Ge-Pd bond.


Targeted somatic mutagenesis in the mouse epidermis.
The efficient introduction of somatic mutations in a given gene at a given time and in specific cell types of the skin will greatly facilitate the studies of a number of genes expressed in the skin and the production of animal models for skin diseases. We describe here strategies and techniques to create spatiotemporally controlled somatic mutations of target genes in the skin using a conditional Cre/LoxP system. They are based on cell-specific expression of the chimeric Cre recombinase Cre-ERT2, whose activity is induced by antiestrogens such as Tamoxifen (Tam), and which is obtained by fusing the Cre recombinase with a mutated ligand binding domain of the human estrogen receptor ERalpha. As an example, we present ablation of the retinoid receptor RXRalpha in epidermal basal keratinocytes of adult mice.


High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes.
Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a-1c and 3-hydroxy-4-thiopyridones 1d-1f as well as their Ru(η6-p-cymene)Cl complexes 2a-2f, and report here the molecular structures of 1b and 1d as determined by X-ray diffraction analysis. Detailed cell biological investigations revealed potent cytotoxic activity, in particular of the 3-hydroxy-4-thiopyridones 1d-1f, while the Ru complexes of both compound types were less potent, despite still showing antiproliferative activity in the low μM range. The compounds did not modulate the cell cycle distribution of cancer cells but were cytostatic in A549 and cytotoxic in NCI-H522 non-small lung cancer cells, among other effects on cancer cells.


Relationship of histamine-releasing factors and histamine-releasing inhibitory factors to chemokine group of cytokine.
The release of mediators from mast cells and basophils represents the central event in the development of immediate hypersensitivity reactions with release of substances such as histamine, Leukotrienes C4/D4, Platelet Activating Factor (PAF), and Prostaglandin D2. Cytokines such as IL-1, TNF alpha, and IL-4 may also be secreted. Histamine Releasing Factors (HRF) are cytokine-like molecules that interact with basophils and/or mast cells to cause cell activation and secretion of mediators. Histamine release is the best characterized of these and has been used as the assay for HRFs, but a wide variety of inflammatory mediators can potentially be secreted. We believe this type of cell to cell communication to be important in tissue inflammation, in which infiltrating cells may produce HRFs in proximity to infiltrating basophils and/or mast cells and cause them to degranulate. Such a reaction appears to be independent of IgE antibody, may no longer require the presence of any inciting antigen, and appears to be pertinent to the allergic late phase reaction as it occurs in the nose, lungs, and skin. It is thought that an ongoing antigenic stimulus, as seen in seasonal or perennial allergic rhinitis and asthma, or in certain types of urticaria, or in atopic dermatitis, leads to a perpetuating inflammatory reaction that persists for many weeks or months. A chronic inflammatory reaction of this sort appears to be required for an allergic reaction (IgE mediated) to manifest as an allergic disease. The relationship of HRF to the chemokine group of cytokine-like molecules and the importance of HRF in the pathogenesis of bronchial hyperreactivity and asthma has been reviewed in this paper.


Accurate assessment of tissue expansion in the lower face and anterior neck by a simple measurement technique.
A simple, precise method of clinical estimation for the accurate assessment of tissue expansion in the lower face and anterior neck is described using fixed anatomical reference points. The method makes it possible to select the most suitable size of tissue expander and to decide the optimal timing of operation. By recording the baseline data before expansion and repeating measurements as expansion proceeds, the discrepancy of the expectation between the surgeon and patient concerning the postoperative result can also be minimised.


A Dual Anchoring Strategy for the Directed Evolution of Improved Artificial Transfer Hydrogenases Based on Carbonic Anhydrase.
Artificial metalloenzymes result from anchoring a metal cofactor within a host protein. Such hybrid catalysts combine the selectivity and specificity of enzymes with the versatility of (abiotic) transition metals to catalyze new-to-nature reactions in an evolvable scaffold. With the aim of improving the localization of an arylsulfonamide-bearing iridium-pianostool catalyst within human carbonic anhydrase II (hCAII) for the enantioselective reduction of prochiral imines, we introduced a covalent linkage between the host and the guest. Herein, we show that a judiciously positioned cysteine residue reacts with a p-nitropicolinamide ligand bound to iridium to afford an additional sulfonamide covalent linkage. Three rounds of directed evolution, performed on the dually anchored cofactor, led to improved activity and selectivity for the enantioselective reduction of harmaline (up to 97% ee (R) and >350 turnovers on a preparative scale). To evaluate the substrate scope, the best hits of each generation were tested with eight substrates. X-ray analysis, carried out at various stages of the evolutionary trajectory, was used to scrutinize (i) the nature of the covalent linkage between the cofactor and the host as well as (ii) the remodeling of the substrate-binding pocket.


Noncovalent Immobilization of Yarrowia lipolytica Lipase on Dendritic-Like Amino Acid-Functionalized Silica Nanoparticles.
Immobilization of enzymes is a promising approach for the cost-effective application of enzymes. Among others, noncovalent but unleachable approaches for immobilization are one of the most favorable and crucial approaches. Herein, silica nanoparticles are modified by (3-aminopropyl)triethoxysilane (APTES) to generate amino-functionalized silica nanoparticles. Then, the amine functionalities are converted to bifunctional amino acid via post-modification that has zwitterionic properties. This nanostructure with the new functional theme is employed to immobilize Yarrowia lipolytica lipase at room temperature with no further post-modification or cross-linking. This immobilization method is further compared with the metal chelate-based immobilization approach on the same support. The biocatalytic activity of the immobilized lipase is examined under various conditions. The encapsulation of lipase through amino acid-functionalized silica nanoparticles exhibited enhanced stability for the immobilized lipase at higher temperatures and unneutral pHs.


[Kampo medicine in the pediatric surgical field].
Kampo medicine has been used for over 4,000 years. Recently, some Kampo formulas have been prescribed for postoperative pediatric patients with gastrointestinal anomalies and disease. However, it has been only 30 years since Kampo medicine has been widely used in the pediatric surgical field. Some of the principal Kampo formulas used for daily treatment in the pediatric surgical field are: Rikkunshito and Bukuryouin-Gou-Hangekoubokuto for patients after upper gastrointestinal surgery; Daikenchuto for patients after colorectal surgery; Inchinkoto for postoperative patients with biliary atresia; and Hainosankyuto for periproctal abscess. Kampo formulas according to the postoperative condition are reviewed from the viewpoint of evidence-based medicine, our experience, and experiments. The results of the Kampo treatments listed above were superior to the results when a Kampo formula was not administered in pediatric patients postoperatively.


Introduction to the Special Issue: Interplay of Family Factors and Cognitive-Affective Processes in Youth.
Substantial research suggests that caregivers and families are powerful socialization agents when it comes to how youth process and regulate cognitive-affective information, which in turn can be a risk or resilience factor for various forms of developmental psychopathology. To this end, Clinical Child and Family Psychology Review features this special journal issue on the "Interplay of Family Factors & Cognitive-Affective Processes in Youth." Featured articles review a wide array of methodologies and highlight numerous forms of cognitive-affective processing and family contextual factors. Multiple themes emerged across the twelve articles, emphasizing the need to examine (1) complex pathways within families, (2) the quality of cognitive-affective processes across individuals, (3) neurodevelopmental pathways linking socialization and cognitive-affective processes, (4) nuanced methods to assess "in-the-moment" cognitive-affective processes, (5) the impact of cultural background on how family factors intersect with youth cognitive-affective processes, and (6) the socialization of positive emotion. These papers showcase the applicability of this significant area of research for future efforts in prevention and intervention with youth at risk for, or already experiencing, some form of psychopathology.


Bimetal metal-organic framework domino micro-reactor for synergistic antibacterial starvation/chemodynamic therapy and robust wound healing.
Antibacterial chemodynamic therapy (aCDT) has captured considerable attention in the treatment of pathogen-induced infections due to its potential to inactivate bacteria through germicidal reactive oxygen species (ROS). However, the lifespan of ROS generated by CDT is too short to achieve the efficacy of complete sterilization; thus, residual bacteria inevitably reproduce and cause super-infections. To address this concern, we devise an innovative bimetal, metal-organic framework (BMOF) domino micro-reactor (BMOF-DMR), consisting of Cu/Zn-rich BMOF and glucose oxidase (GOx), via electrostatic self-assembly. GOx catalyzes conversion of glucose into H2O2, and the Cu2+ ions then convert H2O2 into ˙OH to kill bacteria, thereby showing a domino effect. Accordingly, the BMOF-DMR not only blocks the nutrient/energy supply for bacteria, but also triggers a Fenton(-like) reaction and glutathione (GSH) depletion in a self-generating H2O2 microenvironment, all leading to high-efficiency bactericidal performance through synergistic starvation/chemodynamic therapy. Remarkably, in vitro and in vivo assessments demonstrate that the BMOF-DMR has superior cytocompatibility and exhibits robust ability to accelerate infectious full-thickness cutaneous regeneration through eradicating bacteria, promoting epithelialization of the wound beds and facilitating angiogenesis from the antibacterial activity and delivery of bimetal elements. The advantage of this antibacterial platform is that it suppresses bacterial metabolism by blocking the energy supply, which might prevent secondary infections from residual bacteria. As envisaged, the use of such a micro-reactor with starvation/chemodynamic therapy is a promising approach for combating bacterial skin wounds.


Is meta-analysis clinically useful for perianesthesia nurses?
Meta-analyses can provide clinicians with the evidence-based information necessary to effect change in patient care delivery. Meta-analysis, the application of statistical techniques to condense data from a group of individual studies, is the most sophisticated summary of research evidence. An example meta-analysis study of inadvertent surgical hypothermia is used in this article to describe how nurses can locate, evaluate, and apply synthesized research data for perianesthesia clinical practice. Without data to support decisions, nurses will increasingly be faced with decisions made by others based on cost-cutting measures alone. Although meta-analysis may resolve a controversy or solve a clinical problem, it will not provide simple statistical answers for complex problems or obviate the need for sound and compassionate clinical judgment.


Sex steroid deficiency-associated bone loss is microbiota dependent and prevented by probiotics.
A eubiotic microbiota influences many physiological processes in the metazoan host, including development and intestinal homeostasis. Here, we have shown that the intestinal microbiota modulates inflammatory responses caused by sex steroid deficiency, leading to trabecular bone loss. In murine models, sex steroid deficiency increased gut permeability, expanded Th17 cells, and upregulated the osteoclastogenic cytokines TNFα (TNF), RANKL, and IL-17 in the small intestine and the BM. In germ-free (GF) mice, sex steroid deficiency failed to increase osteoclastogenic cytokine production, stimulate bone resorption, and cause trabecular bone loss, demonstrating that the gut microbiota is central in sex steroid deficiency-induced trabecular bone loss. Furthermore, we demonstrated that twice-weekly treatment of sex steroid-deficient mice with the probiotics Lactobacillus rhamnosus GG (LGG) or the commercially available probiotic supplement VSL#3 reduces gut permeability, dampens intestinal and BM inflammation, and completely protects against bone loss. In contrast, supplementation with a nonprobiotic strain of E. coli or a mutant LGG was not protective. Together, these data highlight the role that the gut luminal microbiota and increased gut permeability play in triggering inflammatory pathways that are critical for inducing bone loss in sex steroid-deficient mice. Our data further suggest that probiotics that decrease gut permeability have potential as a therapeutic strategy for postmenopausal osteoporosis.


Evaluation of a lyophilized platelet-derived hemostatic product.
Current limitations of platelet shelf life to 5 days have led to an increasingly greater demand for hemostatic agents with greater longevity. The objective of this study was to evaluate the function of a lyophilized platelet-derived hemostatic product (thrombosome [TS]) as a potential alternative to fresh platelets. Platelets were collected from whole blood from healthy donors. TSs were reconstituted with water and added to various configurations of reassembled whole blood (platelets, plasma, and RBCs); measures included rotational thromboelastometry (ROTEM), optical aggregometry, mitochondrial function, calibrated automated thrombogram, collagen adhesion under flow (shear flow assay), and flow cytometry. In ROTEM, no differences were observed between maximum clot formation values for contact pathway activation thromboelastometry tests with TSs or platelet samples. Significantly decreased aggregation was observed in the TSs versus platelets (p < 0.001 for all agonists). Flow cytometry measures demonstrated significant decreases in glycoprotein Ib expression and increases in phosphatidylserine expression in the TS group (p < 0.01). The calibrated automated thrombogram assay was suggestive (lag time and peak thrombin) that the TSs might have some thrombogenic properties. Measurements of mitochondrial function revealed that TSs had no functional mitochondria. In this study, TSs were shown to have nonfunctional mitochondria. ROTEM measures revealed that the TSs had no impact on clot strength. Likewise, compared to platelets, the TSs displayed minimal aggregation, had significantly more phosphatidylserine (measure of activation status), but had the ability to adhere to a collagen surface under flow conditions and contribute to clot formation and induced greater thrombin generation.


Survival of Bacillus cereus vegetative cells during Spanish-style fermentation of conservolea green olives.
The aim of this research was to investigate the survival of artificially inoculated Bacillus cereus during Spanish-style green olive fermentation. Olives were initially treated with lye and subjected to different fermentation procedures including (i) heat shock (85 degrees C for 10 min) and inoculation with Lactobacillus plantarum ACA-DC 287, (ii) heat shock and inoculation with L. plantarum ACA-DC 146, (iii) heat shock and inoculation with Lactobacillus pentosus isolated during previous studies, and (iv) fermentation by indigenous flora (control process). Microbial growth and survival, pH, titratable acidity, and organic acid evolution were monitored. Inactivation of B. cereus was observed during all processes. The pathogen population declined during all fermentations, but a tailing effect was observed in the brines when the population reached 2 log CFU/ml, at which point the pathogen does not pose a risk to human health. The rate of inactivation was higher in heat-shocked inoculated olives (mean of -2.21 log CFU/day) compared with control olives (-1.26 log/day), indicating an advantage of heat shock and inoculation over spontaneous fermentation. The production of organic acids (primarily lactic acid) during fermentation seemed to be the main factor that determined the behavior of the pathogen under stress conditions prevailing in the brine. Principal components analysis was useful for distinguishing among the different fermentation processes on the basis of the relevant organic acid profile.


Structure of the chromosomal gene and cDNAs coding for lactase-phlorizin hydrolase in humans with adult-type hypolactasia or persistence of lactase.
Lactase-phlorizin hydrolase (LPH) splits lactose in the small intestine. LPH activity is high in the suckling; in many human populations the activity declines in adults, leading to adult-type hypolactasia, whereas in other populations the high LPH activity persists in adults. In the present work, we compared LPH sequences at the gene and cDNA level among adult subjects with high and low LPH activity. The complete intron-exon organization, including the sequences of all 17 exons and of the borders of all introns (as well as about 1,000 bp of 5' flanking region), was established for the cloned chromosomal LPH gene of a subject with persistence of lactase. Using PCR, we directly sequenced the exons of a hypolactasic subject. Except for silent mutations and the unknown linkage phase at two heterozygous positions, both coding sequences were identical. We further examined the LPH mRNA of a hypolactasic subject by S1 mapping and by sequencing a set of overlapping PCR products produced from cDNA templates. Except for allelic differences, the LPH sequence of the hypolactasic subject was identical to that of the LPH cDNAs of three subjects with persistence of lactase (one cDNA isolated previously by cloning and two characterized in the present work by PCR). No allele was peculiar to the hypolactasic subject. We conclude that humans with high or low levels of lactase can code for identical LPH enzymes.


Thiol-dependent metal-catalyzed oxidation of bovine lens aldose reductase. I. Studies on the modification process.
Bovine lens aldose reductase (alditol: NADP+ oxido-reductase, EC 220.127.116.11) undergoes a thiol-dependent oxidative modification catalyzed by the Fe(II)/Fe(III) redox system. The enzyme is inactivated by various oxygen radical generating systems. However, addition of 2-mercaptoethanol to the oxygen radical generating systems resulted in an initial increase followed by a decrease in the activity of aldose reductase. The net maximal increase in the enzyme activity was observed with 3 mM 2-mercaptoethanol, 0.3 mM FeSO4, and 0.9 mM EDTA, either with or without 1 mM hypoxanthine and 37 mU/ml of xanthine oxidase. The formation of the stable, activated intermediate, ARa, appears to proceed through the reaction between the enzyme and the oxidized form of 2-mercaptoethanol which in the presence of iron, forms a mixed disulfide with a cysteine residue. Reduction of ARa with dithiothreitol released 0.7 mol of 2-mercaptoethanol per mole of enzyme and converted it to a form that resembled the native aldose reductase.


Implications of interconnection theory for optical digital computing.
Heat removal, rather than finite interconnect density, is the major mechanism that limits how densely we can pack three-dimensional computing systems of increasing numbers of elements. Thus highly interconnected approaches can be employed without a further increase in system size. The use of optical interconnections for implementing the longer connections of such systems is advantageous. In fact, if the optical communication energy is sufficiently low and large-bit repetition rates are employed, conductors are useful for only the shortest connections and can be dispensed with altogether with little disadvantage. This justifies consideration of an optical digital computer.


Instrumentation for posterior stabilisation of cervical traumatic and degenerative disorders: bullet-shaped implant and titanium cable.
Numerous implants for posterior stabilisation of cervical spine have been described so far. The aims of all these implants and techniques are rigid spinal stabilisation without neurologic damage, restoration of neuroanatomy and excellent radiological studies in postoperative period. The objective of this study was to determine the effectively and clinical safety of this system. We conducted a retrospective analysis of patients treated with posterior stabilisation system for the stabilisation of traumatic and osteodegerative disorders of lower cervical spine in our department. This posterior cervical stabilisation system consist of titanium bullet-shaped implant (Ti-Frame) and titanium cables (sof' wire). All patients underwent only posterior fixation except 2 (anterior decompression and posterior stabilisation in 2 stages) and postoperative early immobilisation was allowed with Philadelphia collar in all patients. At the follow-up period 15.2 months (9-25 months), none of the patients had superficial or deep infection, implant resection or failure. In conclusion, this system (Ti-frame and titanium cables) is a simple, safe and effective system for posterior cervical stabilisation in patients with traumatic and osteodegenerative disorders due to provide rigid fixation and allow CT and MR imaging without the significant artifact.


Engineering three-dimensional labyrinthine fractal acoustic metamaterials with low-frequency multi-band sound suppression.
Acoustic metamaterials are a class of artificially periodic structures with extraordinary elastic properties that cannot be easily found in naturally occurring materials and can be applied to regulate the sound propagation behavior. The fractal configuration can be widely found in the acoustic system, like characterizing the broadband or multi-band sound propagation. This work will engineer three-dimensional (3D) labyrinthine fractal acoustic metamaterials (LFAMs) to regulate the sound propagation on subwavelength scales. The dispersion relations of LFAMs are systematically analyzed by the Bloch theory and the finite element method (FEM). The multi-bands, acoustic modes, and isotropic properties characterize their acoustic wave properties in the low-frequency regime. The effective bulk modulus and mass density of the LFAMs are numerically calculated to explain the low-frequency bandgap behaviors in specific frequencies. The transmissions and pressure field distributions of 3D LFAMs have been used to measure the ability for sound suppression. Furthermore, when considering the thermo-viscous loss on the transmission properties, the high absorptions occur within the multi-band range for low-frequency sound. Hence, this research contributes to potential applications on 3D LFAMs for multi-bands blocking and/or absorption on deep-subwavelength scales.


How to build distylous flowers: comparative floral development and evolution of distylous species across the angiosperms.
Distyly, a plant breeding system characterized by two floral morphs that have reciprocal positioning of anthers and stigmas, is known from at least 27 angiosperm families, making it an excellent example of convergent evolution. The various manners in which patterns of floral development produce the distinct anther and stigma heights in each morph remain largely unexplored from developmental and evolutionary perspectives. In 15 species representing at least 12 origins of distyly, heights and lengths of floral organs in each morph throughout development were examined using light microscopy. Patterns of floral organ development were determined and compared among species. Family-level phylogenies of distylous species and relatives were reconstructed, and patterns of ancestral herkogamy were resolved. Differences in floral development between morphs resulted in 12 patterns leading to the anther and stigma positions characterizing distyly. Distylous species evolved from ancestors with different types of herkogamy, with approach herkogamy and lack of herkogamy resolved most frequently. Seven of the 12 patterns of floral development are known from only one species, with three other patterns described among pairs of close relatives. The most common pattern of floral development, described from at least seven genera, involves for anther heights, distinct intermorph growth rates and for stigma heights, growth rates that differ between morphs only during later development. This pattern is common among subclass Lamiidae, suggesting canalized development within the taxon. Among distylous species, the same type of ancestral herkogamy can give rise to different patterns of floral development.


Development of the adrenal gland in the tropical lizard Calotes versicolor.
The development of the adrenal gland in the lizard Calotes versicolor was studied histologically and histochemically from the day of oviposition (stage 27) to 60 days after hatching. At stage 27, the adrenocortical cells are found in association with the genital ridge (primordial gonad). The separation of adrenocortical cells from the gonad takes place at stage 31. Organization of adrenocortical cells into cords takes place at stage 34. The catecholamine-secreting chromaffin cells can be seen distinctly on the dorsal region of the adrenal at stage 36, indicating the presence of biologically active catecholamines; the noradrenaline-secreting chromaffin cells appear first at stage 36 and the adrenaline-secreting cells appear later at stage 41. The cortico-medullary ratio of 6:1 during early embryonic development decreases with the increase in age and is 3:1 in posthatching lizards. The histochemical localization of Delta(5)-3beta-hydroxysteroid dehydrogenase (3beta-HSD) and glucose-6-phosphate dehydrogenase in the adrenocortical cells as early as at stage 27 (prior to the gonadal differentiation) indicates the capability of these cells to synthesize steroids. The intensity of the enzyme activity is maximum on the day of hatching and remains more or less the same in the posthatching lizards. The localization of 17beta-HSD enzyme activity observed in the adrenocortical cells at stage 34 is suggestive of their ability to synthesize sex steroids during embryonic life. The intense 3beta-HSD activity on the day of hatching in C. versicolor suggests high production of steroids which may be corticoids. The results of the present work also suggest that the onset of steroid secretion occurs prior to catecholamine secretion during embryogenesis of the adrenal gland in C. versicolor. In addition, there is a significant relationship between ontogenic steroidogenesis of the adrenal gland and sexual differentiation of the gonad.


mRNAs coding for neurotransmitter receptors in rabbit and rat visual areas.
Levels of mRNAs encoding neurotransmitter receptors in the visual cortex, lateral geniculate nucleus, and superior colliculus of the rabbit and rat, and properties of the receptors expressed, were studied using Xenopus laevis oocytes. mRNA extracted from these areas was injected into the oocytes, which then acquired functional receptors. Electrical recordings of neurotransmitter-induced membrane currents reflect the relative amounts of mRNAs encoding the corresponding receptors. Receptors to gamma aminobutyric acid (GABA), kainate, glutamate, and serotonin exhibited uniformly high levels of expression, whereas expression of receptors to glycine and N-methyl-D-aspartate was uniformly low. In contrast, the expression of receptors to acetylcholine and substance P was highly non-uniform. Expression of acetylcholine receptors was high in oocytes injected with mRNA from the visual cortex, low for the lateral geniculate nucleus, and very low or absent for the superior colliculus. Conversely, the currents elicited by substance P were large in oocytes injected with superior colliculus mRNA, but were small or absent in oocytes injected with mRNAs from the other regions. Immunohistochemical analysis, at the light and electron microscopic levels, was used to localize choline acetyltransferase, the acetylcholine-synthesizing enzyme, and substance P-containing synaptic boutons in the three visual areas. Their presence closely paralleled the potency of mRNAs coding for acetylcholine and substance P receptors. The ability of rat mRNA, from each visual area, to induce neurotransmitter receptors was similar to that observed in the corresponding rabbit mRNAs. In addition to the marked differential distribution of mRNA encoding neurotransmitter receptors in the visual system, our findings reveal the probable existence of as yet uncharacterized receptors, whose new molecular forms may be revealed by further study. Our results also provide the basic information required for subsequent studies on the effect of monocular deprivation on the expression of neurotransmitter receptors in the visual system.


A case of adrenoleukodystrophy presenting with manic symptoms in a patient on steroids for Addison's disease.
Adrenoleukodystrophy (ALD) is an X-linked disorder with diverse clinical presentations. A 30-year-old male, previously diagnosed with Addison's disease, on steroid supplementation for 18 years, presented to us with manic symptoms for 4 years. He was found to have white matter hypodensities in computed tomography head and had white matter signal changes in magnetic resonance imaging, and therefore a diagnosis of ALD was made.


Separation and characterization of endopolygalacturonase and exopolygalacturonase from peaches.
Two polygalacturonases (PG I and PG II) have been separated from extracts of ripe peaches (Prunus persica) by chromatography on Sephadex G-100. PG I hydrolyzes polygalacturonic acid from the nonreducing ends of the molecules, releasing galacturonic acid as the product. It functions optimally at pH 5.5, requires Ca(2+) for activity, and hydrolyzes low molecular weight substrates most rapidly. In contrast, PG II cleaves the molecular chain of the substrate randomly with a pH optimum at about 4. This enzyme is most reactive with substrates of intermediate molecular weight. It catalyzes the release of water-soluble, but 70% ethanol-insoluble, pectin from washed peach cell walls.


SRP-RNA sequence alignment and secondary structure.
The secondary structures of the RNAs from the signal recognition particle, termed SRP-RNA, were derived buy comparative analyses of an alignment of 39 sequences. The models are minimal in that only base pairs are included for which there is comparative evidence. The structures represent refinements of earlier versions and include a new short helix.


TSH stimulates 32P-labeling of thyroid nuclear HMG 14, a protein associated with actively transcribed chromatin.
Thyroid slices were incubated with 32Pi with or without TSH. 32P-labeling of acid-soluble nuclear proteins was then examined by two-dimensional polyacrylamide gel electrophoresis and autoradiography. We found that TSH enhanced the labeling of the high mobility group protein HMG 14, a protein that is preferentially associated with actively transcribed chromatin. This observation suggests that changes in HMG 14 phosphorylation may be involved in mediating TSH-induced effects on the structure and function of active chromatin.


Relationship between urinary amino acids and diets in Spanish Cardiovascular Diseases and Alimentary Comparison Study.
A randomized, cross-sectional study was carried out to examine dietary pattern and urinary amino acids excretion in two Spanish free-living populations. A total of 288 adults (50-54 years old; 50% men and 50% women), randomly selected from the census, took part in the study; of these, 146 were living in an urban district of Madrid and 142 in a rural area. Dietary intakes by 7-day recall questionnaires, smoking habits, and alcohol intake were examined in each participant, and 24-h urine was collected in aliquot cups designed for the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. All amino acid excretions averaged higher in men than in women in both areas, and higher in the urban than in the rural population. Main dietary differences between urban and rural populations were higher consumption of fish in urban than in rural populations and higher consumption of bread in rural than in urban populations. Urinary taurine excretion as well as 3-methylhistidine or histidine were significantly associated with fish and meat consumptions, respectively, estimated by 7-day dietary recall questionnaires.


Democratic Systems Increase Outgroup Tolerance Through Opinion Sharing and Voting: An International Perspective.
Democracy may contribute to friendly attitudes and positive attitudes toward outgroups (i.e., outgroup tolerance) because members of democratic societies learn to exercise their rights (i.e., cast a vote) and, in the process, listen to different opinions. Study 1 was a survey study with representative samples from 33 countries (N = 45,070, 53.6% female) and it showed a positive association between the levels of democracy and outgroup tolerance after controlling for gender, age and the rate of immigrants influx from 2010 to 2013. Study 1 demonstrated that members in countries with higher political participation and civil liberty showed greater tolerance toward immigrants. In Study 2, we conducted an experimental study in Taiwan (N = 93, 67.7% female) to further examine two potential mediators (opinion sharing and voting) of the effect of democratic system on tolerance toward outgroups (i.e., attitudes toward mental patients) after controlling for gender and age. We found that when individuals were allowed to share opinions and vote, they had the highest positive other-oriented emotions toward mental patients, which in turn led to greater tolerance toward outgroups compared to those who were not allowed to share opinions or vote. In general, these results demonstrated that the democratic system plays a critical role in increasing outgroup tolerance. Limitations of the two studies and implications regarding opinion sharing, voting, democratic systems, and effects on outgroup tolerance are discussed.


Hydrostatic reduction of intussusception in children: a single centre experience.
intussusception is a common surgical emergency in children especially in infants. Treatment of intussusception could be non-operative or operative. Non-operative treatment (hydrostatic reduction) of intussusception is increasingly being practiced in developing countries. this was a review of our experience in the hydrostatic reduction of intussusception in children at a teaching hospital in Enugu, Nigeria. This study covered an 18-months period, October 2017 to March 2019. Patients on presentation were resuscitated, appropriate investigations done and prepared for surgery before the hydrostatic reduction (using normal saline) was carried out. Patients with features of peritonitis and marked abdominal distension were excluded from hydrostatic reduction. twenty patients who had 21 episodes of intussusception were analyzed. One patient had a recurrence that necessitated repeat hydrostatic reduction. Eighty percent of the patients were male. The mean and peak age of the patients was 8 months and 6 months respectively. Significant number of the patients presented after 48 hours of onset of their symptoms. Abdominal pain was the predominant presenting symptom. Twenty percent and fifteen percent of the patients had a history of preceding gastrointestinal and respiratory infections preceding the intussusception respectively. Ileocolic intussusception was the most common type and the most distal end of the intussusception was at the transverse colon. Hydrostatic reduction was successful in 13 patients (65%). hydrostatic reduction is a simple and effective method of treatment of intussusception. However, early presentation and proper patient selection is necessary for optimal outcome.


Effect of water-soluble fraction from lysozyme-treated Enterococcus faecalis FK-23 on mortality caused by influenza A virus in mice.
To maintain homeostasis of the immune system is considered important for the prevention of influenza A virus infection. Aberrant systemic inflammation is frequently induced by influenza A virus infection, and the severity of the symptoms is associated with pathogenicity of the virus. Lactic acid bacteria are known to have a positive effect in maintaining the immune system. Furthermore, preparations of a lactic acid bacteria strain, Enterococcus faecalis FK-23 (FK-23), have been reported to exert preferable homeostatic effects on immune diseases such as allergic rhinitis and early asthmatic responses. In this study, we examined the efficacy of the water-soluble fraction of lysed and heat-treated FK-23 (SLFK) against a lethal influenza A virus challenge. Mice were orally administered SLFK from day -7 to day 20, and intranasally infected with influenza virus A/Puerto Rico/8/34 (H1N1) at 10(3) PFU on day 0. The survival rate of SLFK-administered mice after influenza A virus infection was significantly improved compared with that of control mice. In addition, the mRNA expression level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lung tissues was enhanced by the oral administration of SLFK after influenza A virus infection. These observations suggest that the oral administration of SLFK exerts a protective effect against influenza virus infection through the activation of the anti-inflammatory response.


S1-bZIP Transcription Factors Play Important Roles in the Regulation of Fruit Quality and Stress Response.
Sugar metabolism not only determines fruit sweetness and quality but also acts as signaling molecules to substantially connect with other primary metabolic processes and, therefore, modulates plant growth and development, fruit ripening, and stress response. The basic region/leucine zipper motif (bZIP) transcription factor family is ubiquitous in eukaryotes and plays a diverse array of biological functions in plants. Among the bZIP family members, the smallest bZIP subgroup, S1-bZIP, is a unique one, due to the conserved upstream open reading frames (uORFs) in the 5' leader region of their mRNA. The translated small peptides from these uORFs are suggested to mediate Sucrose-Induced Repression of Translation (SIRT), an important mechanism to maintain sucrose homeostasis in plants. Here, we review recent research on the evolution, sequence features, and biological functions of this bZIP subgroup. S1-bZIPs play important roles in fruit quality, abiotic and biotic stress responses, plant growth and development, and other metabolite biosynthesis by acting as signaling hubs through dimerization with the subgroup C-bZIPs and other cofactors like SnRK1 to coordinate the expression of downstream genes. Direction for further research and genetic engineering of S1-bZIPs in plants is suggested for the improvement of quality and safety traits of fruit.


Quality of Life and Job Loss during the COVID-19 Pandemic: Mediation by Hopelessness and Moderation by Trait Emotional Intelligence.
This study contributes to the knowledge on the effects of the COVID-19 pandemic by examining a moderated mediation model in which the impact of job loss over quality of life (QoL) is mediated by hopelessness and moderated by trait emotional intelligence (trait EI). Data were collected from a large nationally representative Italian sample of adult workers (N = 1610), who completed a series of anonymous online questionnaires. Total, direct and indirect effects were estimated through bootstrapped mediated moderation analyses providing 95% bias corrected bootstrap confidence intervals. After controlling for the effects of gender and age range, job loss was found to be negatively associated with QoL, and hopelessness partially mediated such relationship. These relationships were in turn moderated by trait EI. Our study suggests that trait EI levels act as protective factor for a good QoL, mitigating the impact of both job loss and hopelessness over QoL levels during the COVID-19 pandemic. Identifying psychological protective and/or risk factors for a better QoL is crucial for the development of interventions aimed at reducing the emotional impact of the pandemic and of its negative real-life consequences.


Nutrition and alcoholic encephalopathies.
An assessment has been made of metabolic factors possibly causing or contributing to the brain damage associated with chronic alcoholism, especially thiamin lack or disturbance of amino acid metabolism. Abnormalities in the thiamin-dependent enzyme, transketolase, provide evidence of a high incidence of thiamin deficiency as well as of disturbed thiamin metabolism in chronic alcoholics, which are likely to be caused by reduced vitamin intake as well as impaired absorption. A grossly disturbed pattern of amino acids in the blood of patients undergoing treatment for alcohol withdrawal syndromes is likely to be caused by loss of hepatic function and may well aggravate brain damage caused by B group vitamin deficiency. A hypothesis is proposed of how chronic thiamin lack can lead to brain damage.


Sequence analysis of the human fucosyltransferase 1 and 2 genes in Tibetan blood donors: identification of three novel alleles.
The α(1,2)-fucosyltransferase gene 1 (FUT1) and 2 (FUT2), respectively, regulate H antigen synthesis in red blood cells and body fluids. Genetic polymorphisms of FUT1 and FUT2 are ethnically and geographically specific. Healthy unrelated Tibetan blood donors (n = 200) from the Tibet Autonomous Region of China were recruited for this study. The entire FUT1 and FUT2 coding regions were amplified and sequenced. The haplotypes including novel single-nucleotide polymorphisms (SNPs) were determined by clone sequencing. In Tibetans, the major FUT1 allele was wild-type allele with a frequency of 97.75%. One novel FUT1 allele was defined by a novel synonymous mutation (846T>G). The two most common FUT2 alleles were functional allele Se(357) with a frequency of 32.75% and nonfunctional allele se(357,385) with a frequency of 55%. Two new FUT2 alleles were found at low frequency. They were characterized by two novel SNPs on the basis of se(357,385) : 617 T>G (V206G) and 841 G>A (G281R). Three new alleles in FUT1 and FUT2 genes were identified in the study. The allelic polymorphisms of FUT1 and FUT2 in Tibetans show a population-specific manner.


Axoneme Structure from Motile Cilia.
The axoneme is the main extracellular part of cilia and flagella in eukaryotes. It consists of a microtubule cytoskeleton, which normally comprises nine doublets. In motile cilia, dynein ATPase motor proteins generate sliding motions between adjacent microtubules, which are integrated into a well-orchestrated beating or rotational motion. In primary cilia, there are a number of sensory proteins functioning on membranes surrounding the axoneme. In both cases, as the study of proteomics has elucidated, hundreds of proteins exist in this compartmentalized biomolecular system. In this article, we review the recent progress of structural studies of the axoneme and its components using electron microscopy and X-ray crystallography, mainly focusing on motile cilia. Structural biology presents snapshots (but not live imaging) of dynamic structural change and gives insights into the force generation mechanism of dynein, ciliary bending mechanism, ciliogenesis, and evolution of the axoneme.


The impact of the COVID-19 pandemic on illicit drug supply, drug-related behaviour of people who use drugs and provision of drug related services in Georgia: results of a mixed methods prospective cohort study.
This study examines the effects of COVID-19 related restrictions on the supply of illicit drugs, drug-use behaviour among people who use drugs (PWUD) regularly (at least weekly), and drug-related service provision in Tbilisi, Georgia. In this mixed methods study, a cohort of 50 Georgian PWUD recruited through a snow-ball sampling participated in a bi-weekly online survey in April-September, 2020. They also took part in the qualitative telephone interviews at 12- and 24-week follow-up time points. In addition, four key informants (field experts) were interviewed monthly to assess their perceptions of changes in the illicit drug market and drug service delivery. Mean age in the sample was 36 (range 18-60); 39 (78%) were males. Perceived availability of drugs was reduced during the lockdown, and many PWUD switched to alternative substances when preferred drugs were not available. On average, participants used significantly fewer substances over the course of the study, from 3.5 substances in the preceding 14 days to 2.1 (aOR 0.92; 95% CI 0.90-0.94). Consumption of cannabis products declined significantly (aOR 0.89; 95% CI 0.84-0.95), likewise alcohol (aOR 0.94; 95% CI 0.88-1.0), diverted medicinal methadone (aOR 0.85; 95% CI 0.8-0.9) and diverted medicinal buprenorphine (aOR 0.91; 95% CI 0.84-0.99). PWUD cited fewer contacts with drug dealers, the lack of transportation, and the lack of conventional recreational environment as the main reasons for these changes. When access to sterile injection equipment was limited, PWUD exercised risk-containing injection behaviours, such as buying drugs in pre-filled syringes (aOR 0.88; 95% CI 0.80-0.96). Harm reduction and treatment programs managed to adopt flexible strategies to recover services that were affected during the initial stage of the pandemic. COVID-19-related restrictive measures mediated specific changes in supply models and drug-use behaviours. While adjusting to the new environment, many PWUD would engage in activities that put them under increased risk of overdose and blood-borne infections. Harm reduction and treatment services need to develop and implement protocols for ensuring uninterrupted service delivery during lockdowns, in anticipation of the similar epidemics or other emergency situations.


N:P stoichiometry and protein:RNA ratios in vascular plants: an evaluation of the growth-rate hypothesis.
The growth-rate hypothesis states that fast-growing organisms need relatively more phosphorus-rich RNA to support rapid rates of protein synthesis, and therefore predicts, within and among taxa, increases in RNA and phosphorus content (relative to protein and nitrogen content) with increased growth rate. Here, we present a test of this hypothesis in vascular plants. We determined nitrogen : phosphorus ratios and protein:RNA ratios in pines growing at different rates due to nutrient conditions. In general, when comparing leaves of the same species at low and high growth rates, the faster-growing plants had higher RNA content, higher %N and %P, and lower protein:RNA ratios, but not consistently lower N:P ratios. We found no link between growth rate and foliar N:P or protein:RNA when comparing multiple species of different inherent growth rates. We conclude that plants adjust the balance of protein and RNA to favour either speed or efficiency of protein synthesis, but this balance does not alone dictate leaf stoichiometry.


Empty pericarp2 encodes a negative regulator of the heat shock response and is required for maize embryogenesis.
The heat shock response (HSR) is an evolutionarily conserved molecular/biochemical reaction to thermal stress that is essential to the survival of eukaryotic organisms. Recessive Mutator transposon mutations at the maize empty pericarp2 (emp2) locus led to dramatically increased expression of heat shock genes, retarded embryo development, and early-stage abortion of embryogenesis. The developmental timing of emp2 mutant embryo lethality was correlated with the initial competence of maize kernels to invoke the HSR. Cloning and sequence analyses revealed that the emp2 gene encoded a predicted protein with high similarity to HEAT SHOCK BINDING PROTEIN1, which was first described in animals as a negative regulator of the HSR. emp2 is a loss-of-function mutation of an HSR-negative regulator in plants. Despite the recessive emp2 phenotype, steady state levels of emp2 transcripts were abundant in mutant kernels, and the predicted coding region was unaffected. These expression data suggest that emp2 transcription is feedback regulated, whereas S1 nuclease mapping suggests that emp2 mutant transcripts are 5' truncated and nontranslatable. In support of this model, immunoblot assays revealed that EMP2 protein did not accumulate in mutant kernels. These data support a model whereby an unattenuated HSR results in the early abortion of emp2 mutant embryos. Furthermore, the developmental retardation of emp2 mutant kernels before the HSR suggests an additional role for EMP2 during embryo development distinct from the HSR.


Network motifs and their origins.
Modern network science is a new and exciting research field that has transformed the study of complex systems over the last 2 decades. Of particular interest is the identification of small "network motifs" that might be embedded in a larger network and that indicate the presence of evolutionary design principles or have an overly influential role on system-wide dynamics. Motifs are patterns of interconnections, or subgraphs, that appear in an observed network significantly more often than in compatible randomized networks. The concept of network motifs was introduced into Systems Biology by Milo, Alon and colleagues in 2002, quickly revolutionized the field, and it has had a huge impact in wider scientific domains ever since. Here, we argue that the same concept and tools for the detection of motifs were well known in the ecological literature decades into the last century, a fact that is generally not recognized. We review the early history of network motifs, their evolution in the mathematics literature, and their recent rediscoveries.


[Prevalence and features of pre-B-cell acute lymphoblastic leukemia in Mexico: description of 9 patients].
A group of 9 patients with pre-B cell acute lymphoblastic leukaemia (pre-B ALL) was identified prospectively within 209 patients with ALL. This variant of leukaemia was defined by the presence of heavy mu-chains in the cytoplasm of the malignant cells, and no surface immunoglobulins. Four patients displayed the CD10 (CALLA) antigen, in addition to cytoplasmic mu chains. A G-0 acute leukaemia (no blast cells in S-phase) was identified in two cases. Response to treatment of the patients was poor: Only four achieved complete remission; median survival was 24 weeks and the 40-week disease free survival was 20%. These figures are significantly worse than those obtained in patients with early-pre-B (CD10+) ALL. We conclude that the prevalence of pre-B ALL is low in our experience (4.6% of all patients with ALL) and that a poor outcome of treatment was related to it.


Intestinal Infarction in COVID-19 Pandemic: A Case Series.
Novel coronavirus disease 2019 (COVID-19) as a potential health risk factor continues to spread worldwide. Although common symptoms include headache and respiratory symptoms, some studies have suggested that COVID-19 may cause coagulation disorders and thrombolytic events, disrupt blood flow to the visceral organs, and cause some complications such as mesenteric ischemia. The authors reported four cases of acute mesenteric ischemia associated with COVID-19 confirmed in patients hospitalized in Imam Reza Hospital (a COVID-19 referral center in Mashhad University of Medical Sciences, Mashhad, Iran). The authors described the pathological findings that may be associated with this infection. The authors collected clinical data, imaging, microscopic, and operative findings of four patients with severe COVID-19 infection and evidence of intestinal necrosis. These four cases of severe COVID-19 pneumonia simultaneously showed intestinal necrosis during the infection process, indicating a relationship between coronavirus and mesenteric vascular events. Physicians should be aware of thrombosis symptoms in the digestive system in patients with severe COVID-19.


Differentiation of soft-tissue lymphoma from undifferentiated sarcoma: apparent diffusion coefficient histogram analysis.
Making the preoperative diagnosis of soft-tissue lymphoma is important because the treatments for lymphoma and sarcoma are different. To determine the reliability and accuracy of single-slice and whole-tumor apparent diffusion coefficient (ADC) histogram analysis when differentiating soft-tissue lymphoma from undifferentiated sarcoma. Patients with confirmed soft-tissue lymphoma or undifferentiated sarcoma who underwent 3-T magnetic resonance imaging (MRI), including diffusion-weighted imaging, were included. Single-slice and whole-tumor ADC histogram analyses were performed using software. Mean, standard deviation (SD), 5th and 95th percentiles, skewness, and kurtosis were compared between groups, and a receiver operating characteristic curve with area under the curve (AUC) was obtained. Thirteen patients with soft-tissue lymphoma and 12 patients with undifferentiated sarcoma were included. ADC histogram analysis of single-slice and whole-tumor, mean, SD, and 5th and 95th percentiles was significantly lower in lymphoma than in undifferentiated sarcoma. Whole-tumor analysis kurtosis was significantly higher in lymphoma than in undifferentiated sarcoma. All AUCs were high in single-slice and whole-tumor analysis: 0.987 vs. 1.000 in mean; 0.821 vs. 0.782 in SD; 0.949 vs. 0.949 in 5th percentile; and 1.000 vs. 1.000 in 95th percentile without significant difference. AUC of kurtosis in whole-tumor ADC histogram analysis was 0.750. Single-slice and whole-tumor ADC histogram analysis seems to be reliable and accurate for differentiating soft-tissue lymphoma from undifferentiated sarcoma.


Do metformin a real anticarcinogen? A critical reappraisal of experimental data.
Evidence has emerged that antidiabetic biguanides [phenformin (PF), buformin (BF) and metformin (MF)] are promising candidates for prevention of cancer. It was shown that antidiabetic biguanides postpone spontaneous carcinogenesis as well as inhibit carcinogenesis induced by chemical, radiation and biological factors (virus, transgene, genetic modifications, special diet, etc.) in a number of organs and tissues in various strains of mice and rats. The present review focused on some details of experiments such as design of studies, dose and route of administration of biguanide, and age of animals at start of treatment etc. Conclusion may be done that there are rather sufficient evidence of cancer-preventive activity of antidiabetic biguanides in experimental animals.


De Novo Drug Design of Targeted Chemical Libraries Based on Artificial Intelligence and Pair-Based Multiobjective Optimization.
Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical and biological landscapes by addressing the automated de novo design of compounds as a result of a humanlike creative process. In the present study, we conceived a novel pair-based multiobjective approach implemented in an adapted SMILES generative algorithm based on recurrent neural networks for the automated de novo design of new molecules whose overall features are optimized by finding the best trade-offs among relevant physicochemical properties (MW, logP, HBA, HBD) and additional similarity-based constraints biasing specific biological targets. In this respect, we carried out the de novo design of chemical libraries targeting neuraminidase, acetylcholinesterase, and the main protease of severe acute respiratory syndrome coronavirus 2. Several quality metrics were employed to assess drug-likeness, chemical feasibility, diversity content, and validity. Molecular docking was finally carried out to better evaluate the scoring and posing of the de novo generated molecules with respect to X-ray cognate ligands of the corresponding molecular counterparts. Our results indicate that artificial intelligence and multiobjective optimization allow us to capture the latent links joining chemical and biological aspects, thus providing easy-to-use options for customizable design strategies, which are especially effective for both lead generation and lead optimization. The algorithm is freely downloadable at https://github.com/alberdom88/moo-denovo and all of the data are available as Supporting Information.


Electrospray Ionization Mass Spectrometric Study of the Gas-Phase Coordination Chemistry of Be2+ Ions with 1,2- and 1,3-Diketone Ligands.
Electrospray ionization mass spectrometry (ESI MS) is a powerful technique for the study of coordination complexes because of its ability to analyze solution systems involving very low concentrations of metal complexes. In this work, the coordination chemistry of Be ions with a selection of well-known 1,3-diketone and related 1,2-diketone ligands has been investigated using ESI MS. With acetylacetone (Hacac), a range of acac-containing ions is observed, including [Be(acac)2H]+, [Be(acac)(MeOH) n]+ ( n = 1, 2), and polynuclear species such as the dinuclear [Be2(acac)3]+ and trinuclear [Be3O(acac)3]+. Density functional theory calculations indicate that the latter species has a central Be3(μ3-O) core, with each Be chelated (as opposed to being bridged) by an acac ligand. The effect of changing the substituents on 1,3-diketone was explored by an investigation of mixtures of Be2+ with other 1,3-diketones such as dibenzoylmethane (Hdbm), where the [Be(dbm)2H]+ ion showed a lesser tendency to undergo fragmentation and aggregation processes. Comparisons with the corresponding aluminum acetylacetone system were also made. In contrast, mixtures of Be2+ and the 1,2-diketones diacetyl and phenanthrenequinone showed poor metal-ligand interactions. Be2+ interacted with the 1,2-diketone benzil [PhC(O)C(O)Ph], forming the [Be(benzil) n]2+ ( n = 2-4) ions. The synthesis (from BeCl2) and X-ray structures of the dibenzoylmethanato (dbm) complex Be(dbm)2 and the benzil complex [BeCl2(benzil)] are also reported.


The 2008 WHO classification of lymphomas: implications for clinical practice and translational research.
The 4(th) edition of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues published in 2008 builds upon the success of the 2001 3(rd) edition; new entities are defined, and solutions for problematic categories are sought. Recent studies have drawn attention to the biological overlap between classical Hodgkin lymphoma (CHL) and diffuse large B-cell lymphomas (DLBCL). Similarly, there is a greater appreciation of the borderlands between Burkitt lymphoma and DLBCL. Strategies for the management of these borderline lesions are proposed. Additionally, age-specific and site-specific factors play an important role in the definition of several new entities, which also have biological underpinnings. Among the peripheral T-cell lymphomas (PTCL), more precise definitions were introduced for several entities, including anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and subcutaneous panniculitis-like T-cell lymphoma. Several new variants of primary cutaneous T-cell lymphomas are proposed. Finally, the subclassification and categorization of the most common lymphoma subtypes, follicular lymphoma (FL) and DLBCL, were altered to enhance diagnostic accuracy and aid in clinical management. The 2008 WHO classification also draws attention to early events in lymphomagenesis. These lesions help delineate the earliest steps in neoplastic transformation and generally mandate a conservative therapeutic approach. The 2001 classification was rapidly adopted for clinical trials and successfully served as a common language for scientists comparing genetic and functional data. The modifications made in the 2008 classification are the result of this successful partnership among pathologists, clinicians, and biologists, but are only a stepping stone to the future.


Reliability of PEDOT-PSS Strain Gauge on foam structure.
Reliability is one important issue in using PEDOT: PSS as a strain gauge for large strain measurements. In our research, PEDOT: PSS strain gauge is fabricated on the polyurethane and porous substrate, which enhances the mechanical property when large strain and cyclic loads are applied to it. Our result shows that with the polyurethane as the substrate adhesion layer, the strain of PEDOT: PSS can go up to 17.7% and stabilize without reference resistance drifting.


When should the evaluation of erectile function be done before radical prostatectomy?
The aim of this study is to assess the erectile function of patients before and after transrectal ultrasound prostate biopsy comparatively in order to determine the appropriate time to evaluate erectile function before radical prostatectomy. A total of 44 patients underwent transrectal ultrasound biopsy. We used the International Index of Erectile Function-5 questionnaire to assess all the patients. In total, 44 volunteered patients were included in this study. All patients were evaluated with the International Index of Erectile Function-5 questionnaire before the biopsy and at 4 weeks after the transrectal ultrasound biopsy. A total of 50% of patients were potent before the biopsy was done. A month after the biopsies, erectile dysfunction was reported by 29 of 44 patients (66%) as mild in 10 (22.7%), as mild-moderate in 14 (31.8%), as moderate in 4 (9.1%), and severe in 1 (2.3%). The differences were statistically significant in the first month of the biopsy (p < 0.05). The effect of prostate biopsy upon the erectile function is non-negligible. However, this situation is temporary and transient. Therefore, it is recommended that the International Index of Erectile Function-5 questionnaire is to be administered prior to prostate biopsy rather than before surgical treatment.


Anti-S1 MERS-COV IgY Specific Antibodies Decreases Lung Inflammation and Viral Antigen Positive Cells in the Human Transgenic Mouse Model.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 and causes severe and often fatal acute respiratory illness in humans. No approved prophylactic and therapeutic interventions are currently available. In this study, we have developed egg yolk antibodies (immunoglobulin Y (IgY)) specific for MERS-CoV spike protein (S1) in order to evaluate their neutralizing efficiency against MERS-CoV infection. S1-specific immunoglobulins were produced by injecting chickens with purified recombinant S1 protein of MERS-CoV at a high titer (5.7 mg/mL egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated that the IgY antibody specifically bound to the MERS-CoV S1 protein. Anti-S1 antibodies were also able to recognize MERS-COV inside cells, as demonstrated by an immunofluorescence assay. Plaque reduction and microneutralization assays showed the neutralization of MERS-COV in Vero cells by anti-S1 IgY antibodies and non-significantly reduced virus titers in the lungs of MERS-CoV-infected mice during early infection, with a nonsignificant decrease in weight loss. However, a statistically significant (p = 0.0196) quantitative reduction in viral antigen expression and marked reduction in inflammation were observed in lung tissue. Collectively, our data suggest that the anti-MERS-CoV S1 IgY could serve as a potential candidate for the passive treatment of MERS-CoV infection.


Cancer and lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations.
This article provides an overview of the current literature on seven cancer sites that may disproportionately affect lesbian, gay, bisexual, transgender/transsexual, and queer/questioning (LGBTQ) populations. For each cancer site, the authors present and discuss the descriptive statistics, primary prevention, secondary prevention and preclinical disease, tertiary prevention and late-stage disease, and clinical implications. Finally, an overview of psychosocial factors related to cancer survivorship is offered as well as strategies for improving access to care.


The effect of music versus nonmusic on behavioral signs of distress and self-report of pain in pediatric injection patients.
Receiving vaccinations is a part of growing up; however, as necessary as vaccinations are, many children find them to be frightening and painful. Music has been examined as a potential distraction during pediatric medical procedures, but research findings have been mixed, due, in part, to the fact that children were primarily instructed to merely "listen to the music." The present study sought to determine if a focus of attention activity involving music would affect levels of distress and perceptions of pain in pediatric injection patients. Sixty-four 4- to 6(1/2) -year old children receiving routine immunizations were randomly assigned to one of three conditions: musical story, spoken story, or standard care/control. Children in the two treatment conditions listened to a recorded story and pointed at corresponding pictures throughout the injection process. Observational data on distress and pain were collected, in addition to the child's self-rating of pain. Participants in the musical story condition tended to be less distressed and report less pain than participants in the other two conditions, although these differences were not statistically significant. Subsequent analysis indicated that children who received more injections tended to benefit more from the music intervention, in terms of their perceived pain.


In vivo fertilizing capacity of deep frozen boar semen packaged in plastic bags and maxi-straws.
Pooled ejaculates from six fertile boars were frozen under controlled conditions in Teflon FEP-film plastic bags (5 ml) and maxi-straws (2.5 ml) using 3% glycerol as cryoprotectant. The percentages of both post-thaw motility and normal apical ridges were significantly higher (P less than 0.001) for the bags (54.5 and 75%) than for the maxi-straws (40.1 and 59.4%) respectively. For evaluation of the in vivo fertilizing capacity of the frozen-thawed spermatozoa, 26 gilts were inseminated once 24 h after the first observation of standing reflex in their second oestrus, with 5 ml of semen (containing 5 billion spermatozoa) reconstituted in 80 ml of BTS from either bags or maxi-straws. Ova were recovered from the oviducts/uteri 2-4 days following insemination and examined for cleavage and sperm binding to the zona pellucida (ZP). Significantly higher rates (P less than 0.02) of fertilized ova were found in the bag-inseminated (75%) than in maxi-straw inseminated gilts (63%); and similarly their ova had significantly more spermatozoa in the ZP, irrespective of whether they were fertilized or nonfertilized. This study confirmed that the plastic bags are suitable and may be used for packaging single insemination doses of deep frozen boar semen for routine A.I. work.


Anabolic androgenic steroids: a survey of 500 users.
The use of anabolic androgenic steroids (AAS) to increase muscle size and strength is widespread. Information regarding self-administered AAS used nonmedically to enhance athletic performance or improve physical appearance is sparse and poorly documented. The purpose of this study is to identify current trends in the drug-taking habits of AAS users. An anonymous self-administered questionnaire was posted on the message boards of Internet Web sites popular among AAS users. Of the 500 AAS users who participated in the survey, 78.4% (392/500) were noncompetitive bodybuilders and nonathletes; 59.6% (298/500) of the respondents reported using at least 1000 mg of testosterone or its equivalent per week. The majority (99.2%) of AAS users (496/500) self-administer injectable AAS formulations, and up to 13% (65/500) report unsafe injection practices such as reusing needles, sharing needles, and sharing multidose vials. In addition to using AAS, 25% of users admitted to the adjuvant use of growth hormone and insulin for anabolic effect, and 99.2% (496/500) of users reported subjective side effects from AAS use. This survey reveals several trends in the nonmedical use of AAS. Nearly four out of five AAS users are nonathletes who take these drugs for cosmetic reasons. AAS users in this sample are taking larger doses than previously recorded, with more than half of the respondents using a weekly AAS dose in excess of 1000 mg. The majority of steroid users self-administer AAS by intramuscular injection, and approximately 1 in 10 users report hazardous injection techniques. Polypharmacy is practiced by more than 95% of AAS users, with one in four users taking growth hormone and insulin. Nearly 100% of AAS users reported subjective side effects.


Cryptorchidism and increased risk of neurodevelopmental disorders.
Male congenital malformations as cryptorchidism may contribute to the development of neurodevelopmental disorders directly or via shared familial genetic and/or environmental factors, but the evidence is sparse. Using population-based health registries, we conducted a cohort study of all liveborn singleton boys in Denmark during 1979-2008. Boys with a diagnosis of cryptorchidism were categorized into the exposed cohort and the other boys into the unexposed comparison cohort. The outcomes were diagnoses of any neurodevelopmental disorders and their subtypes. We used Cox proportional hazards regression to compute hazard ratios (HRs), taking into consideration several potential confounders. Among 884,083 male infants, 27,505 received a diagnosis of cryptorchidism during follow-up. Boys with cryptorchidism were more likely to be diagnosed with intellectual disability (HR = 1.77; 95%confidence interval [CI]:1.59,1.97), autism spectrum disorders (ASD) (HR = 1.24; 95% CI:1.13,1.35), attention-deficit hyperactivity disorder (ADHD) (HR = 1.17; 95% CI: 1.08,1.26), anxiety (HR = 1.09; 95% CI: 1.01,1.17), and other behavioral/emotional disorders (HR = 1.16; 95% CI: 1.08,1.26) compared to boys without cryptorchidism. The observed risks of intellectual disability, ASD, and ADHD were increased further in boys with bilateral cryptorchidism. Except for anxiety, cryptorchid boys had higher risks of neurodevelopmental disorders than their non-cryptorchid full brothers. The observed increased risks were similar among boys who underwent orchiopexy, as well as among those with shorter waiting times for this surgery. Cryptorchidism may be associated with increased risks of intellectual disability, ASD, ADHD, and other behavioral/emotional disorders. Cryptorchidism and neurodevelopmental disorders may have shared genetic or in-utero/early postnatal risk factors, which need to be further investigated.


Brain Abnormalities in Congenital Fibrosis of the Extraocular Muscles Type 1: A Multimodal MRI Imaging Study.
To explore the possible brain structural and functional alterations in congenital fibrosis of extraocular muscles type 1 (CFEOM1) patients using multimodal MRI imaging. T1-weighted, diffusion tensor images and functional MRI data were obtained from 9 KIF21A positive patients and 19 age- and gender-matched healthy controls. Voxel based morphometry and tract based spatial statistics were applied to the T1-weighted and diffusion tensor images, respectively. Amplitude of low frequency fluctuations and regional homogeneity were used to process the functional MRI data. We then compared these multimodal characteristics between CFEOM1 patients and healthy controls. Compared with healthy controls, CFEOM1 patients demonstrated increased grey matter volume in bilateral frontal orbital cortex and in the right temporal pole. No diffusion indices changes were detected, indicating unaffected white matter microstructure. In addition, from resting state functional MRI data, trend of amplitude of low-frequency fluctuations increases were noted in the right inferior parietal lobe and in the right frontal cortex, and a trend of ReHo increase (p<0.001 uncorrected) in the left precentral gyrus, left orbital frontal cortex, temporal pole and cingulate gyrus. CFEOM1 patients had structural and functional changes in grey matter, but the white matter was unaffected. These alterations in the brain may be due to the abnormality of extraocular muscles and their innervating nerves. Future studies should consider the possible correlations between brain morphological/functional findings and clinical data, especially pertaining to eye movements, to obtain more precise answers about the role of brain area changes and their functional consequence in CFEOM1.


Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression--a double-blind, randomized, placebo controlled long-term trial.
The efficacy and safety of Hypericum extract WS 5570 in preventing relapse during 6 months' continuation treatment and 12 months' long-term maintenance treatment after recovery from an episode of recurrent depression were investigated in a double-blind, placebo controlled multicenter trial. Adult out-patients with a recurrent episode of moderate major depression, a 17-item Hamilton Depression Rating Scale (HAMD) total score > or =20 and > or =3 previous episodes in 5 years participated. After 6 weeks of single-blind treatment with 3 x 300 mg/day WS 5570 patients with score < or =2 on item 'Improvement' of the Clinical Global Impressions (CGI) scale and a HAMD total score decrease > or =50% versus baseline were randomized to 3 x 300 mg/day WS 5570 or placebo for 26 weeks. 426 patients were evaluated for efficacy. Relapse rates during continuation treatment were 51/282 (18.1%) for WS 5570 and 37/144 (25.7%) for placebo. Average time to relapse was 177+/-2.8 and 163+/-4.4 days for WS 5570 and placebo, respectively (time-to-event analysis; p=0.034; alpha=0.025 one-sided). Patients treated with WS 5570 showed more favorable HAMD and Beck Depression Inventory time courses and greater over-all improvement (CGI) than those randomized to placebo. In long-term maintenance treatment a pronounced prophylactic effect of WS 5570 was observed in patients with an early onset of depression as well as in those with a high degree of chronicity. Adverse event rates under WS 5570 were comparable to placebo. WS 5570 showed a beneficial effect in preventing relapse after recovery from acute depression. Tolerability in continuation and long-term maintenance treatment was on the placebo level.


Conversion of tricoordinate to hexacoordinate phosphorus. Formation of a phosphorane-phosphatrane system.
Reaction of RPCl(2) with tris(2-hydroxy-3-tert-butyl-5-methylbenzyl)amine (4) led to the formation of a tricoordinated phosphonite (1) when R = Ph and to a hexacoordinated phosphorane-phosphatrane (2) when R = Et. The X-ray structures showed that the unreacted hydroxyl group in 1 oxidatively added to phosphorus in 2 leading to the formation of three additional bonds, a P[bond]O, a P[bond]H, and a P[bond]N linkage. In solution, (31)P measurements assisted by solid-state (31)P measurements revealed that each of the compounds existed in both structural forms. VT (31)P established equilibria where the solid-state structures predominated in each case. This is the first example of a conversion of three-coordinate to six-coordinate phosphorus on going from the solid to the solution state and the existence of these two disparate geometries in equilibrium with one another in solution. In the absence of steric protection with the use of an analogous amine (5) without tert-butyl groups, a hydrolysis reaction occurred with PhPCl(2). X-ray analysis revealed an anionic phenylphosphinate structure (3) hydrogen bonded in a cage-like arrangement with the protonated amine. Similar hydrolysis reactions take place with 1 and 2 but much more slowly.


The arrangement of Brachypodium distachyon chromosomes in interphase nuclei.
The spatial organization of chromatin within the interphase nucleus and the interactions between chromosome territories (CTs) are essential for various biological processes, such as DNA replication, transcription, and repair. However, detailed data about the CT arrangement in monocotyledonous plants are scarce. In this study, chromosome painting was used to analyse the distribution and associations of individual chromosomes in the 3-D preserved nuclei of Brachypodium distachyon root cells in order to determine the factors that may have an impact on the homologous CT arrangement. It was shown that the frequency of CT association is linked to the steric constraints imposed by the limited space within the nucleus and may depend on chromosome size and morphology as well as on the nuclear shape. Furthermore, in order to assess whether the distribution of interphase chromosomes is random or is subject to certain patterns, a comparison between the experimental data and the results of a computer simulation (ChroTeMo), which was based on a fully probabilistic distribution of the CTs, was performed. This comparison revealed that homologous chromosome arm CTs associate more often than if they were randomly arranged inside the interphase nucleus.