Comparison of 27-gauge beveled-tip and 25-gauge flat-tip microincision vitrectomy surgery in the treatment of proliferative diabetic retinopathy: a randomized controlled trial.
To compare the effectiveness and safety of a 27-gauge (27G) beveled-tip microincision vitrectomy surgery (MIVS) with a 25-gauge (25G) flat-tip MIVS for the treatment of proliferative diabetic retinopathy (PDR). A prospective, single-masked, randomized, controlled clinical trial included 52 eyes (52 patients) with PDR requiring proliferative membrane removal. They were randomly assigned in a 1:1 ratio to undergo the 27G beveled-tip and or 25G flat-tip MIVS (the 27G group and the 25G group, respectively). During surgery, the productivity of cutting the membrane, the number of vitrectomy probe (VP) exchanges to microforceps, total operation time, vitrectomy time and intraoperative complications were measured. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) and postoperative complications were also assessed to month 6. Forty-seven eyes (47 patients) completed the follow-up, including 25 in the 27G group and 22 in the 25G group. During surgery in the 27G group, cutting the membrane was more efficient (P = 0.001), and the number of VP exchanges to microforceps was lower (P = 0.026). The occurrences of intraoperative hemorrhages and electrocoagulation also decreased significantly (P = 0.004 and P = 0.022). There were no statistical differences in the total operation time or vitrectomy time between the two groups (P = 0.275 and P = 0.372), but the former was slightly lower in the 27G group. Additionally, the 27G group required fewer wound sutures (P = 0.044). All the follow-up results revealed no significant difference between the two groups. Compared with the 25G flat-tip MIVS, the 27G beveled-tip MIVS could be more efficient in removing the proliferative membrane while reducing the occurrence of intraoperative hemorrhages and electrocoagulation using appropriate surgical techniques and instrument parameters. Its vitreous removal performance was not inferior to that of the 25G MIVS and might offer potential advantages in total operation time. In terms of patient outcomes, advanced MIVS demonstrates equal effectiveness and safety to 25G flat-tip MIVS. The clinical trial has been registered at Clinicaltrials.gov (NCT0544694) on 07/07/2022. And all patients in the article were enrolled after registration.


A new interpretation of the structure and solvent dependence of the far UV circular dichroism spectrum of short oligopeptides.
UV circular dichroism (UVCD) spectroscopy is a prominent tool for exploring secondary structures of polypeptides and proteins. In the unfolded state of these biomolecules, most of the individual residues primarily sample a conformation called polyproline II. Its CD spectrum contains a negatively biased positive couplet with a pronounced negative maximum below and a weak positive maximum above 200 nm. It is traditionally rationalized in terms of an excitonic coupling mechanism augmented by polarization effects. In this work, we carry out new time-dependent density functional theory calculations on the cationic tripeptide GAG in implicit and explicit water to determine the transitions that give rise to the observed CD signals of polyproline II and β-strand conformations. Our results reveal a plethora of electronic transitions that are governed by configurational interactions between multiple molecular orbital transitions of comparable energy. We also show that reproducing the CD spectra of polyproline II and β-strand conformations requires the explicit consideration of water molecules. The structure dependence of delocalized occupied orbitals contributes to the experimentally-observed invalidation of Flory's isolated pair hypothesis.


Origin of anomalous lattice expansion in oxide nanoparticles
Anomalous lattice expansions have been measured for the first time in monodisperse CeO2-x nanoparticles and in BaTiO3 single nanoparticles by electron diffraction. X-ray photoelectron spectroscopy studies on CeO2-x nanoparticles and ab initio computer simulation on BaTiO3 clusters show that the origin of expansion is the decrease of electrostatic force caused by valence reduction of Ce ions and the increase in ionicity of Ti ions, respectively. The lattice constant change of oxide (ionic) nanoparticles with the increase in ionicity would depend on the structure of the particles. Hence, first-principles calculations of large ionic clusters are indispensable.


Amodiaquine-induced toxicity in isolated rat hepatocytes and the cytoprotective effects of taurine and/or N-acetyl cysteine.
Amodiaquine is an antimalarial drug used in the prophylaxis and treatment of this disease. However, hepatotoxicity as a life-threatening adverse effect is associated with its clinical use. We evaluated amodiaquine-induced toxicity in isolated rat hepatocytes as an in vitro model for studying drug-induced hepatotoxicity. This study attempts to investigate the protective effects of taurine and N-acetyl cysteine against the cytotoxicity induced by amodiaquine. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. This technique is based on liver perfusion with collagenase after removal of calcium ion (Ca(2+)) with a chelator (ethylene glycol tetraacetic acid (EGTA) 0.5 mM). Cells were treated with different concentrations of amodiaquine, taurine and N-acetyl cysteine. Cell death, protein carbonylation, reactive oxygen species formation, lipid peroxidation, and mitochondrial depolarization were assessed as toxicity markers. Amodiaquine cytotoxic mechanism involved protein carbonylation as well as reactive oxygen species formation and lipid peroxidation. In addition, mitochondria seem to be a target for amodiaquine to induce cellular damage. Administration of taurine (200 μM) and/or N-acetyl cysteine (200 μM) reduced oxidative stress, lipid peroxidation and protein carbonylation caused by amodiaquine. Furthermore, amodiaquine-induced mitochondrial injury was significantly mitigated by taurine and/or N-acetyl cysteine. In glutathione-depleted cells, only N-acetyl cysteine protected hepatocytes against amodiaquine, and taurine showed no protective properties in this situation. Taurine and N-acetyl cysteine protect hepatocytes against amodiaquine probably via their antioxidant properties and counteracting oxidative stress.


Recurrence of Hallux Valgus Can Be Predicted from Immediate Postoperative Non-Weight-Bearing Radiographs.
The aims of this study were to identify risk factors for the recurrence of hallux valgus deformity and to clarify whether recurrence after surgery to treat hallux valgus can be predicted using radiographic parameters assessed on immediate postoperative non-weight-bearing radiographs. A proximal chevron osteotomy combined with a distal soft-tissue procedure was performed by a single surgeon to treat moderate to severe hallux valgus deformity in 93 patients (117 feet). The feet were grouped according to nonrecurrence or recurrence. Changes in the hallux valgus angle, the intermetatarsal angle, and sesamoid position over time were analyzed by comparing values measured during each postoperative period. The relative risks of recurrence as indicated by preoperative and postoperative radiographic parameters were determined. Twenty (17.1%) of the 117 feet showed hallux valgus recurrence at the time of the last follow-up. The hallux valgus angle and the intermetatarsal angle stabilized at 6 months after surgery in the nonrecurrence group. An immediate postoperative hallux valgus angle of ≥8°, an immediate postoperative sesamoid position of grade 4 or greater, a preoperative metatarsus adductus angle of ≥23°, and a preoperative hallux valgus angle of ≥40° were significantly associated with recurrence. Recurrence of hallux valgus after a proximal chevron osteotomy can be reliably predicted from immediate postoperative non-weight-bearing radiographs. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Impact of one-layer assumption on diffuse reflectance spectroscopy of skin.
Diffuse reflectance spectroscopy (DRS) can be used to noninvasively measure skin properties. To extract skin properties from DRS spectra, you need a model that relates the reflectance to the tissue properties. Most models are based on the assumption that skin is homogenous. In reality, skin is composed of multiple layers, and the homogeneity assumption can lead to errors. In this study, we analyze the errors caused by the homogeneity assumption. This is accomplished by creating realistic skin spectra using a computational model, then extracting properties from those spectra using a one-layer model. The extracted parameters are then compared to the parameters used to create the modeled spectra. We used a wavelength range of 400 to 750 nm and a source detector separation of 250 μm. Our results show that use of a one-layer skin model causes underestimation of hemoglobin concentration [Hb] and melanin concentration [mel]. Additionally, the magnitude of the error is dependent on epidermal thickness. The one-layer assumption also causes [Hb] and [mel] to be correlated. Oxygen saturation is overestimated when it is below 50% and underestimated when it is above 50%. We also found that the vessel radius factor used to account for pigment packaging is correlated with epidermal thickness.


In situ relationships between microbiota and potential pathobiota in Arabidopsis thaliana.
A current challenge in microbial pathogenesis is to identify biological control agents that may prevent and/or limit host invasion by microbial pathogens. In natura, hosts are often infected by multiple pathogens. However, most of the current studies have been performed under laboratory controlled conditions and by taking into account the interaction between a single commensal species and a single pathogenic species. The next step is therefore to explore the relationships between host-microbial communities (microbiota) and microbial members with potential pathogenic behavior (pathobiota) in a realistic ecological context. In the present study, we investigated such relationships within root-associated and leaf-associated bacterial communities of 163 ecologically contrasted Arabidopsis thaliana populations sampled across two seasons in southwest of France. In agreement with the theory of the invasion paradox, we observed a significant humped-back relationship between microbiota and pathobiota α-diversity that was robust between both seasons and plant organs. In most populations, we also observed a strong dynamics of microbiota composition between seasons. Accordingly, the potential pathobiota composition was explained by combinations of season-specific microbiota operational taxonomic units. This result suggests that the potential biomarkers controlling pathogen's invasion are highly dynamic.


Dual role of tree florigen activation complex component FD in photoperiodic growth control and adaptive response pathways.
A complex consisting of evolutionarily conserved FD, flowering locus T (FT) proteins is a regulator of floral transition. Intriguingly, FT orthologs are also implicated in developmental transitions distinct from flowering, such as photoperiodic control of bulbing in onions, potato tuberization, and growth cessation in trees. However, whether an FT-FD complex participates in these transitions and, if so, its mode of action, are unknown. We identified two closely related FD homologs, FD-like 1 (FDL1) and FD-like 2 (FDL2), in the model tree hybrid aspen. Using gain of function and RNAi-suppressed FDL1 and FDL2 transgenic plants, we show that FDL1 and FDL2 have distinct functions and a complex consisting of FT and FDL1 mediates in photoperiodic control of seasonal growth. The downstream target of the FT-FD complex in photoperiodic control of growth is Like AP1 (LAP1), a tree ortholog of the floral meristem identity gene APETALA1. Intriguingly, FDL1 also participates in the transcriptional control of adaptive response and bud maturation pathways, independent of its interaction with FT, presumably via interaction with abscisic acid insensitive 3 (ABI3) transcription factor, a component of abscisic acid (ABA) signaling. Our data reveal that in contrast to its primary role in flowering, FD has dual roles in the photoperiodic control of seasonal growth and stress tolerance in trees. Thus, the functions of FT and FD have diversified during evolution, and FD homologs have acquired roles that are independent of their interaction with FT.


Alerta Rosa: Novel Alert and Navigation Breast Cancer Program in Nuevo Leon, Mexico, for Reducing Health System Interval Delays.
In Mexico, the median time between breast cancer (BC) symptom detection and treatment initiation is approximately 7 months. Alerta Rosa is a program that was developed with the intent of breaking down medical care barriers and reduce delays. Through several media campaigns, we reached out to patients with breast symptoms or abnormal imaging studies. Patients contacted our call center or Facebook page. A navigator recorded their main complaint and scheduled a medical consultation with a specialist. We prioritized patients according to clinical risk. Those diagnosed with BC were referred to their health affiliation unit for care. To date, 656 patients have contacted our program. Median age was 44 years (range, 7-82). Patients reported becoming aware of Alerta Rosa mainly by word of mouth and TV. A total of 446 medical consultations were scheduled, and 309 patients attended their appointments. A biopsy procedure was solicited for 39 patients, and 22 were diagnosed with BC. Most patients had stage II (45%) or stage III (32%) disease. The median time from alert activation to treatment initiation was 33 days (range, 19-56) and from first medical evaluation to treatment initiation was 28 days (range, 16-48). In low- or middle-income countries, where BC screening programs do not effectively reach the target population, it is crucial to focus efforts in identifying and prioritizing symptomatic patients or those with abnormal imaging studies to ultimately downstage BC. Alerta Rosa proved to be successful in reducing health system intervals and could be replicated and adapted for other limited resource settings. In countries such as Mexico, infrastructure and financial drawbacks limit the implementation of effective screening mammography programs. This article presents a novel and effective alternative to optimize resources and reduce health system intervals, so that patients in limited-resource settings can have access to prompt quality care. This strategy for early breast cancer detection focused efforts in prioritizing symptomatic women and those with abnormal breast imaging studies. This article presents novel information that will be useful for the development of effective early breast cancer detection with a focus on opportunistic rather than population-screening mammography in low-resource settings.


Biomarker discovery across annotated and unannotated microarray datasets using semi-supervised learning.
The growing body of DNA microarray data has the potential to advance our understanding of the molecular basis of disease. However annotating microarray datasets with clinically useful information is not always possible, as this often requires access to detailed patient records. In this study we introduce GLAD, a new Semi-Supervised Learning (SSL) method for combining independent annotated datasets and unannotated datasets with the aim of identifying more robust sample classifiers. In our method, independent models are developed using subsets of genes for the annotated and unannotated datasets. These models are evaluated according to a scoring function that incorporates terms for classification accuracy on annotated data, and relative cluster separation in unannotated data. Improved models are iteratively generated using a genetic algorithm feature selection technique. Our results show that the addition of unannotated data into training, significantly improves classifier robustness.


Intracellular accumulation of extracellular proteins by pleiotropic export mutants of Aeromonas hydrophila.
Pleiotropic export mutants of Aeromonas hydrophila were obtained which are unable to release protease, hemolysin, and glycerophospholipid:cholesterol acyltransferase. The synthesis of the proteins was not impaired; they were accumulated in active forms inside the mutant cells. The hemolysin could be isolated from cell contents by immunoprecipitation in a form with the same apparent molecular weight as the wild-type extracellular product, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Because both the protease and the hemolysin could be released from the mutant cells by osmotic shock, it was concluded that they were accumulated in the periplasmic space. Some mutants were missing two major outer membrane proteins, both of which reappeared in revertants with the wild-type excretory phenotype. Another mutant class had a normal outer membrane protein profile. That two different mutant classes could be obtained indicates that at least two gene products may be needed for export after protein translocation through the inner membrane. The accumulation of proteins which can be released by osmotic shock suggests that the periplasm may be part of the normal route for protein export.


Development of the Spence Children's Anxiety Scale - Short Version (SCAS-S).
The literature provides several examples of anxiety symptoms questionnaires for children. However, these questionnaires generally contain many items, and might not be ideal for screening in large populations, or repeated testing in clinical settings. The Spence Children's Anxiety Scale (SCAS) is an extensively used and evaluated 44-item questionnaire developed to assess anxiety symptoms in children, and provides a sound base for the development of an abbreviated anxiety symptoms questionnaire. Although methodological standards have been presented in how to develop abbreviated questionnaires, previous studies have often suffered from several limitations regarding validating procedures. Guided by these methodological standards, the current study aimed at developing an abbreviated version of the SCAS, while retaining the content, convergent, and divergent validity of the original scale. A school-based sample (n = 750) was used to reduce the number of items, and an independent school-based sample (n = 371) together with a clinical sample (n = 93), were used to validate the abbreviated scale. The abbreviated version of the SCAS contained 19 items, it showed a clear factor structure as evaluated in the independent sample, and it performed as good as the original questionnaire regarding classification accuracy, convergent, and divergent validity. In our view, the abbreviated version is a very good alternative to the original scale especially for younger children, in initial screening, or in order to reduce response burden.


Comparison of RTPS and Monte Carlo dose distributions in heterogeneous phantoms for photon beams.
The purpose of this study was to compare dose distributions from three different RTPS with those from Monte Carlo (MC) calculations and measurements, in heterogeneous phantoms for photon beams. This study used four algorithms for RTPS: AAA (analytical anisotropic algorithm) implemented in the Eclipse (Varian Medical Systems) treatment planning system, CC (collapsed cone) superposition from the Pinnacle (Philips), and MGS (multigrid superposition) and FFT (fast Fourier transform) convolution from XiO (CMS). The dose distributions from these algorithms were compared with those from MC and measurements in a set of heterogeneous phantoms. Eclipse/AAA underestimated the dose inside the lung region for low energies of 4 and 6 MV. This is because Eclipse/AAA do not adequately account for a scaling of the spread of the pencil (lateral electron transport) based on changes in the electron density at low photon energies. The dose distributions from Pinnacle/CC and XiO/MGS almost agree with those of MC and measurements at low photon energies, but increase errors at high energy of 15 MV, especially for a small field of 3x3 cm(2). The FFT convolution extremely overestimated the dose inside the lung slab compared to MC. The dose distributions from the superposition algorithms almost agree with those from MC as well as measured values at 4 and 6 MV. The dose errors for Eclipse/AAA are lager in lung model phantoms for 4 and 6 MV. It is necessary to use the algorithms comparable to superposition for accuracy of dose calculations in heterogeneous regions.


Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts.
GLUT2 is a facilitative glucose transporter, expressed in polarized epithelial cells of the liver, intestine, kidney and pancreas, where it plays a critical role in glucose homeostasis. Together with SGLT1/2, it mediates glucose absorption in metabolic epithelial tissues, where it can be translocated apically upon high glucose exposure. To track the subcellular localization and dynamics of GLUT2, we created an mCherry-hGLUT2 fusion protein and expressed it in multicellular kidney cysts, a major site of glucose reabsorption. Live imaging of GLUT2 enabled us to avoid the artefactual localization of GLUT2 in fixed cells and to confirm the apical GLUT2 model. Live cell imaging showed a rapid 15 ± 3 min PKC-dependent basal-to-apical translocation of GLUT2 in response to glucose stimulation and a fourfold slower basolateral translocation under starvation. These results mark the physiological importance of responding quickly to rising glucose levels. Importantly, we show that phloretin, an apple polyphenol, inhibits GLUT2 translocation in both directions, suggesting that it exerts its effect by PKC inhibition. Subcellular localization studies demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, and that it is at least partly recovered in Rab11A-positive recycling endosome. Our work illuminates GLUT2 dynamics, providing a platform for drug development for diabetes and hyperglycaemia.


Introduction of mutations into the non-structural genes or 3' untranslated region of an attenuated dengue virus type 4 vaccine candidate further decreases replication in rhesus monkeys while retaining protective immunity.
A dengue virus vaccine candidate, rDEN4Delta30, has been previously reported to be safe and immunogenic in humans, but a subset of vaccinees developed asymptomatic rash, elevation of liver enzymes and/or mild neutropenia. In the current study, mutations that had previously been shown to reduce replication of DEN4 virus in suckling mice and/or in SCID mice engrafted with human liver cells (SCID-HuH-7 mice) were introduced into rDEN4Delta30 in an attempt to further attenuate this virus. Three of the five resulting modified rDEN4Delta30 viruses showed decreased replication in SCID-HuH-7 mice relative to rDEN4Delta30. Moreover, in rhesus monkeys, two of the modified rDEN4Delta30 viruses showed a decrease in replication relative to rDEN4Delta30 while generating levels of neutralizing antibody similar to rDEN4Delta30 virus. All of the modified rDEN4Delta30 viruses completely protected immunized rhesus monkeys from challenge with wild-type DEN4 virus. Based on their attenuation for both human liver cells and rhesus monkeys, two of the modified rDEN4Delta30 vaccine candidates are currently being prepared for use in clinical trials. The application of these attenuating mutations to flavivirus vaccine development is discussed.


Acute flaccid paralysis: Do not forget beriberi neuropathy.
We aimed to elucidate characteristics of beriberi neuropathy (BB) in a general hospital (GH) setting. Nerve conduction studies (NCS), cross-referenced with clinical records of patients admitted to a GH (May 2011-July 2017), were reviewed for diagnosis of BB. Thirteen patients (age range 23-64 years; five women) were diagnosed with BB. Eleven were incarcerated (2-24 months) at time of index event. Eleven reported prior, severe anorexia (2-6 months); five reported significant weight loss, three had recurrent vomiting, and three reported alcohol misuse. Commonest presentation was weakness (12/13); nine had symptom evolution over ≥3 weeks. At nadir, 11/13 could not walk independently. Other features included numbness/paraesthesiae (10/13), dysautonomia (6/13), vocal cord dysfunction/dysphagia (4/13), nystagmus (3/13). Pain was not prominent. Cerebrospinal fluid, tested in five patients, was acellular; one showed mildly increased protein. NCS showed predominantly sensorimotor, axonal polyneuropathy, rarely asymmetric. Only one patient had sural-sparing pattern. All received high dose thiamine. Two of the thirteen received intravenous immunoglobulin for suspicion of Guillain-Barré syndrome (GBS). Eleven improved to independent ambulation. One patient died from pulmonary embolism; one was lost to follow-up. Two of the thirteen had residual neurocognitive effects; both misused alcohol. Besides GBS, BB is an important cause of acute to subacute flaccid paralysis, especially in incarcerated patients and those with significant dietary deprivation. Features favoring BB over GBS are ≥3 weeks of symptoms, nystagmus, confusion, vocal cord dysfunction, volume overload, normal spinal fluid, elevated lactate, and absence of sural-sparing pattern in NCS.


Kawasaki disease: update on pathogenesis.
This review will highlight recent advances in our understanding of the pathogenesis of Kawasaki disease, highlighting the molecular players involved in regulation of T-cell activation and their affect on disease incidence and outcome in both humans and mouse. Kawasaki disease is the most common cause of multisystem vasculitis in childhood. The vessels most commonly damaged are the coronary arteries, making Kawasaki disease the number one cause of acquired heart disease in children from the developed world. The contribution of genetics to disease predisposition is clearly implicated, but the mechanisms involved in regulating predisposition to disease susceptibility and outcome are not clearly understood. Two independent approaches have recently identified regulation of T-cell activation as the critical factor in determining susceptibility and severity of Kawasaki disease. Firstly, genetic analysis of affected Japanese children identified ITPKC, 1,4,5-triphosphate 3-kinase C, a kinase involved in regulation of T-cell activation, to be significantly associated with susceptibility to and increased severity of Kawasaki disease. A second independent approach using an animal model of Kawasaki disease has also identified regulation of T-cell activation, specifically costimulation, the second signal regulating optimal T-cell activation as the critical regulator of susceptibility to and severity of disease. Understanding the molecular players responsible for dysregulation of the immune response in Kawasaki disease will foster development of improved diagnostic/predictive tools and more rational use of therapeutic agents to improve outcome in affected children.


Design and scaling of monocentric multiscale imagers.
Monocentric multi-scale (MMS) lenses are a new approach to high-resolution wide-angle imaging, where a monocentric objective lens is shared by an array of identical rotationally symmetric secondary imagers that each acquire one overlapping segment of a mosaic. This allows gigapixel images to be computationally integrated from conventional image sensors and relatively simple optics. Here we describe the MMS design space, introducing constraints on image continuity and uniformity, and show how paraxial system analysis can provide both volume scaling and a systematic design methodology for MMS imagers. We provide the detailed design of a 120° field of viewimager (currently under construction) resolving 2 gigapixels at 41.5 μrad instantaneous field of view, and demonstrate reasonable agreement with the first-order scaling calculation.


New reactive polymer for protein immobilisation on sensor surfaces.
Immobilisation of biorecognition elements on transducer surfaces is a key step in the development of biosensors. The immobilisation needs to be fast, cheap and most importantly should not affect the biorecognition activity of the immobilised receptor. A novel protocol for the covalent immobilisation of biomolecules containing primary amines using an inexpensive and simple polymer is presented. This tri-dimensional (3D) network leads to a random immobilisation of antibodies on the polymer and ensures the availability of a high percentage of antibody binding sites. The reactivity of the polymer is based on the reaction between primary amines and thioacetal groups included in the polymer network. These functional groups (thioacetal) do not need any further activation in order to react with proteins, making it attractive for sensor fabrication. The novel polymer also contains thiol derivative groups (disulphide groups or thioethers) that promote self-assembling on a metal transducer surface. For demonstration purposes the polymer was immobilised on Au Biacore chips. The resulting polymer layer was characterised using contact angle meter, atomic force microscopy (AFM) and ellipsometry. A general protocol suitable for the immobilisation of bovine serum albumin (BSA), enzymes and antibodies such as polyclonal anti-microcystin-LR antibody and monoclonal anti-prostate specific antigen (anti-PSA) antibody was then optimised. The affinity characteristics of developed immunosensors were investigated in reaction with microcystin-LR, and PSA. The calculated detection limit for analytes depended on the properties of antibodies. The detection limit for microcystin-LR was 10 ngmL(-1) and for PSA 0.01 ngmL(-1). The non-specific binding of analytes to synthesised polymers was very low. The polymer-coated chips were stored for up to 2 months without any noticeable deterioration in their ability to react with proteins. These findings make this new polymer very promising for the development of low-cost, easy to prepare and sensitive biosensors.


Construction, characterization, and use of two Listeria monocytogenes site-specific phage integration vectors.
Two site-specific shuttle integration vectors were developed with two different chromosomal bacteriophage integration sites to facilitate strain construction in Listeria monocytogenes. The first vector, pPL1, utilizes the listeriophage U153 integrase and attachment site within the comK gene for chromosomal insertion. pPL1 contains a useful polylinker, can be directly conjugated from Escherichia coli into L. monocytogenes, forms stable, single-copy integrants at a frequency of approximately 10(-4) per donor cell, and can be used in the L. monocytogenes 1/2 and 4b serogroups. Methods for curing endogenous prophages from the comK attachment site in 10403S-derived strains were developed. pPL1 was used to introduce the hly and actA genes at comK-attBB' in deletion strains derived from 10403S and SLCC-5764. These strains were tested for second-site complementation in hemolysin assays, plaquing assays, and cell extract motility assays. Unlike plasmid-complemented strains, integrated pPL1-complemented strains were fully virulent in the mouse 50% lethal dose assay. Additionally, the PSA phage attachment site on the L. monocytogenes chromosome was characterized, and pPL1 was modified to integrate at this site. The listeriophage PSA integrates in the 3' end of an arginine tRNA gene. There are 17 bp of DNA identity between the bacterial and phage attachment sites. The PSA prophage DNA sequence reconstitutes a complete tRNA(Arg) gene. The modified vector, pPL2, was integration proficient at the same frequency as pPL1 in common laboratory serotype 1/2 strains as well as serotype 4b strains.


[Relation of a suicidal behaviour with the heliogeophysical factors].
Heliogeophysical parameters of the environment at the time of realization of suicidal behaviours using the data of four independent cohorts from different Ukrainian regions, separately for men (totally 7585 cases) and women (totally 4023 cases) for interval of 1989-2008 were analysed. A suicidal behaviour of men is actualized when geomagnetic activity decreases after its maximum. Heliogeophysical factors have smaller influence on women's suicidal behaviour. Suicide bombing attacks in Israel, Iraq and Afghanistan (for the period from 1994 to 2008) tend to take place by the maximal values of geomagnetic activity or during changes in interplanetary magnetic field polarity from negative to positive. These findings promote future discussion regarding unifying psychological or psycho-physiological mechanisms in suicides and suicidal terroristic acts and have some predicting potential.


Model predictive control using fuzzy decision functions.
Fuzzy predictive control integrates conventional model predictive control with techniques from fuzzy multicriteria decision making, translating the goals and the constraints to predictive control in a transparent way. The information regarding the (fuzzy) goals and the (fuzzy) constraints of the control problem is combined by using a decision function from the theory of fuzzy sets. This paper investigates the use of fuzzy decision making (FDM) in model predictive control (MPG), and compares the results to those obtained from conventional MPG. Attention is also paid to the choice of aggregation operators for fuzzy decision making in control. Experiments on a nonminimum phase, unstable linear system, and on an air-conditioning system with nonlinear dynamics are studied. It is shown that the performance of the model predictive controller can be improved by the use of fuzzy criteria in a fuzzy decision making framework.


Surface engineering of gold nanoparticles for in vitro siRNA delivery.
Cellular uptake, endosomal/lysosomal escape, and the effective dissociation from the carrier are a series of hurdles for specific genes to be delivered both in vitro and in vivo. To construct siRNA delivery systems, poly(allylamine hydrochloride) (PAH) and siRNA were alternately assembled on the surface of 11.8 ± 0.9 nm Au nanoparticles (GNP), stabilized by denatured bovine serum albumin, by the ionic layer-by-layer (LbL) self-assembly method. By manipulating the outmost PAH layer, GNP-PAH vectors with different surface electric potentials were prepared. Then, the surface potential-dependent cytotoxicity of the resultant GNP-PAH particles was evaluated via sulforhodamine B (SRB) assay, while the surface potential-dependent cellular uptake efficiency was quantitatively analyzed by using the flow cytometry method based on carboxyfluorescein (FAM)-labeled siRNA. It was revealed that the GNP-PAH particles with surface potential of +25 mV exhibited the optimal cellular uptake efficiency and cytotoxicity for human breast cancer MCF-7 cells. Following these results, two more positively charged polyelectrolytes with different protonating abilities in comparison with PAH, i.e., polyethylenimine (PEI), and poly(diallyl dimethyl ammonium chloride) (PDDA), were chosen to fabricate similarly structured vectors. Confocal fluorescence microscopy studies indicated that siRNA delivered by GNP-PAH and GNP-PEI systems was better released than that delivered by the GNP-PDDA system. Further flow cytometric assays based on immunofluorescence staining of the epidermal growth factor receptor (EGFR) revealed that EGFR siRNA delivered by GNP-PAH and GNP-PEI exhibited similar down-regulation effects on EGFR expression in MCF-7 cells. The following dual fluorescence flow cytometry assays by co-staining phosphatidylserine and DNA suggested the EGFR siRNA delivered by GNP-PAH exhibited an improved silencing effect in comparison with that delivered by the commercial transfection reagent Lipofectamine 2000.


Improving cyclodextrin complexation of a new antihepatitis drug with glacial acetic acid.
The purpose of this study was to develop and evaluate a solid nonaqueous oral dosage form for a new hepatitis C drug, PG301029, which is insoluble and unstable in water. Hydroxypropyl-beta-cyclodextrin (HPbetaCD) and PG301029 were dissolved in glacial acetic acid. The acetic acid was removed by rotoevaporation such that the drug exists primarily in the complexed form. The stability of formulated PG301029 was determined upon dry storage and after reconstitution in simulated intestinal fluid (SIF), simulated gastric fluid (SGF), and water. Formulated PG301029 was found to be stable upon storage and can be reconstituted with water to a concentration 200 times that of the intrinsic solubility. Once reconstituted, the powder dissolves rapidly and PG301029 remains stable for 21 hours in SGF, SIF, and water. The unique use of acetic acid and HPbetaCD results in a solid dosage form of PG301029 that is both soluble and stable in water.


Mobbing in the workplace by peers and managers: mobbing experienced by nurses working in healthcare facilities in Turkey and its effect on nurses.
This research was conducted as a descriptive and cross-sectional study with the purpose of determining the mobbing experienced by nurses who work in healthcare facilities in Turkey, its emotional, social and physiological effects on the nurses and the actions that the individuals take to escape from the mobbing. The term 'mobbing', which includes workplace terrorizing, pressure, frightening, belittling and psycho-terror, is defined as the presence of systematic, directed, unethical communication and antagonistic behaviour by one or more individuals. These actions that occur frequently and continue for a long time are the most serious and effective causes of workplace stress. The person who is the target of the mobbing is left without help, without protection and alone in the workplace. Individuals who are exposed to psychological abuse experience physiological, psychological and social problems that are related to high levels of stress and anxiety. The research participants were 505 nurses of whom 325 (64%) worked in public and 180 (36%) in private hospitals. All of the participants were female. A questionnaire developed by the researchers in the light of information in the literature was used for data collection and had four sections including the participants' demographic characteristics and questions asking about mobbing behaviours, reaction to mobbing incidents and actions taken to escape from the mobbing. The data were collected between October and December 2005 by giving an envelope to the participants and then collecting the responses in the closed envelope. The overwhelming majority (86.5%) of the nurses participating in the research reported facing mobbing behaviour in the workplace in the last 12 months. The nurses working at private hospitals faced statistically significantly more mobbing behaviours than those at public hospitals (p<or=0.02). It was determined that the nurses who faced mobbing behaviours gave various physiological, emotional and social reactions to these incidents. The most common behaviours exhibited by the participants to escape mobbing was 'to work harder and be more organized' and 'to work more carefully to avoid criticism'. In addition 10% of the participants stated that they 'consider committing suicide sometimes.' Mobbing behaviours in the workplace need to be defined and appropriate policies and procedures need to be developed and shared with all employees to prevent the development of these behaviours. In addition, managers should adopt an open managerial approach to prevent the development of these behaviours.


Investment in HIV/AIDS programs: does it help strengthen health systems in developing countries?
There is increasing debate about whether the scaled-up investment in HIV/AIDS programs is strengthening or weakening the fragile health systems of many developing countries. This article examines and assesses the evidence and proposes ways forward. Considerably increased resources have been brought into countries for HIV/AIDS programs by major Global Health Initiatives. Among the positive impacts are the increased awareness of and priority given to public health by governments. In addition, services to people living with HIV/AIDS have rapidly expanded. In many countries infrastructure and laboratories have been strengthened, and in some, primary health care services have been improved. The effect of AIDS on the health work force has been lessened by the provision of antiretroviral treatment to HIV-infected health care workers, by training, and, to an extent, by task-shifting. However, there are reports of concerns, too - among them, a temporal association between increasing AIDS funding and stagnant reproductive health funding, and accusations that scarce personnel are siphoned off from other health care services by offers of better-paying jobs in HIV/AIDS programs. Unfortunately, there is limited hard evidence of these health system impacts. Because service delivery for AIDS has not yet reached a level that could conceivably be considered "as close to Universal Access as possible," countries and development partners must maintain the momentum of investment in HIV/AIDS programs. At the same time, it should be recognized that global action for health is even more underfunded than is the response to the HIV epidemic. The real issue is therefore not whether to fund AIDS or health systems, but how to increase funding for both. The evidence is mixed - mostly positive but some negative - as to the impact on health systems of the scaled-up responses to HIV/AIDS driven primarily by global health partnerships. Current scaled-up responses to HIV/AIDS must be maintained and strengthened. Instead of endless debate about the comparative advantages of vertical and horizontal approaches, partners should focus on the best ways for investments in response to HIV to also broadly strengthen the primary health care systems.


The culture of patient safety in an Iranian intensive care unit.
To explore nurses' and physicians' attitudes and perceptions relevant to safety culture and to elicit strategies to promote safety culture in an intensive care unit. A strong safety culture is essential to ensure patient safety in the intensive care unit. This case study adopted a mixed method design. The Safety Attitude Questionnaire (SAQ-ICU version), assessing the safety climate through six domains, was completed by nurses and physicians (n = 42) in an academic intensive care unit. Twenty semi-structured interviews and document analyses were conducted as well. Interviews were analysed using a framework analysis method. Mean scores across the six domains ranged from 52.3 to 72.4 on a 100-point scale. Further analysis indicated that there were statistically significant differences between physicians' and nurses' attitudes toward teamwork (mean scores: 64.5/100 vs. 52.6/100, d = 1.15, t = 3.69, P < 0.001) and job satisfaction (mean scores: 78.2/100 vs. 57.7/100, d = 1.5, t = 4.8, P < 0.001). Interviews revealed several safety challenges including underreporting, failure to learn from errors, lack of speaking up, low job satisfaction among nurses and ineffective nurse-physician communication. The results indicate that all the domains need improvements. However, further attention should be devoted to error reporting and analysis, communication and teamwork among professional groups, and nurses' job satisfaction. Nurse managers can contribute to promoting a safety culture by encouraging staff to report errors, fostering learning from errors and addressing inter-professional communication problems.


Effect of vaccination of the dam on rotavirus infection in young calves.
Vaccination of cows with a combined, inactivated, adjuvanted rotavirus and Escherichia coli vaccine resulted in increased neutralising antibody titres to rotavirus in serum and colostral whey. Evidence was obtained that vaccination resulted in a decreased incidence of rotavirus shedding and of abnormal faeces or diarrhoea in young calves fed colostrum and milk from the vaccinated dams. The E coli component of the vaccine was not evaluated because no natural challenge was evident.


Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies.
The phosphoinositide 3-kinase (PI3K)/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR) kinase is an important mediator for its signaling. Our recent in vitro studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop). The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models. Two studies prospectively enrolled adult patients with advanced pancreatic cancer, Eastern Cooperative Oncology Group performance status 0-1, adequate hematologic, hepatic and renal parameters and measurable disease. In Study A, temsirolimus was administered intravenously at 25 mg weekly. In Study B, everolimus was administered orally at 30 mg weekly and erlotinib was administered at 150 mg daily. The primary endpoint in both studies was overall survival at 6 months. Secondary endpoints included time to progression, progression-free survival, overall survival, response rate, safety and toxicity. Pretreatment tumor biopsies were analyzed by immunofluorescence and laser scanning cytometry for the expression of pmTOR/mTOR, pAkt/Akt, pErk/Erk, pS6, p4EBP-1 and PTEN. Five patients enrolled in Study A; Two patients died within a month (rapid disease progression and hemorrhagic stroke, respectively). One patient developed dehydration and another developed asthenia. Sixteen patients enrolled in Study B.: 12 males, all ECOG PS = 1. Median cycles = 1 (range 1-2). Grade 4 toxicity: hyponatremia (n = 1), Grade 3: diarrhea (n = 1), cholangitis (n = 3), hyperglycemia (n = 1), fatigue (n = 1). Grade 2: pneumonia (n = 2), dehydration (n = 2), nausea (n = 2), neutropenia (n = 1), mucositis (n = 2) & rash (n = 2). Four patients were hospitalized. Progressive disease occurred in 15 and 1 was non-evaluable. Pretreatment biopsies revealed a higher pAkt/Akt ratio in tumor specimens that in nonmalignant pancreatic tissue. No such trends were noted for the other biomarkers. Neither study with mTOR inhibitors demonstrated objective responses or disease stability. The negative feedback loop resulting from mTOR inhibition may account for the disease progression and toxicity noted in these studies. Future strategies should aim for a broader targeting of the PI3K pathway in pancreatic cancer. NCT 0075647. NCT00640978.


Quality assurance monitoring in psychiatry.
The implementation of quality assurance monitoring is an important response to public demands for accountability in medicine as well as a requirement for institutional accreditation by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO). The author examines the somewhat elusive definition of quality as it is applied to medical care. He reviews the history, terminology, and reasons for quality assurance monitoring and presents the JCAHO-defined concepts of indicators and thresholds. Several common problems associated with the implementation of quality assurance monitoring are discussed along with guidelines for the development of quality assurance indicators in psychiatry.


Proximal and distal honor fit and subjective well-being in the Mediterranean region.
People's psychological tendencies are attuned to their sociocultural context and culture-specific ways of being, feeling, and thinking are believed to assist individuals in successfully navigating their environment. Supporting this idea, a stronger "fit" with one's cultural environment has often been linked to positive psychological outcomes. The current research expands the cultural, conceptual, and methodological space of cultural fit research by exploring the link between well-being and honor, a central driver of social behavior in the Mediterranean region. Drawing on a multi-national sample from eight countries circum-Mediterranean (N = 2257), we examined the relationship between cultural fit in honor and well-being at the distal level (fit with one's perceived society) using response surface analysis (RSA) and at the proximal level (fit with one's university gender group) using profile analysis. We found positive links between fit and well-being in both distal (for some, but not all, honor facets) and proximal fit analyses (across all honor facets). Furthermore, most fit effects in the RSA were complemented with positive level effects of the predictors, with higher average honor levels predicting higher well-being. Our findings highlight the interplay between individual and environmental factors in honor as well as the important role honor plays in well-being in the Mediterranean region.


Coexistence DNA of Borrelia burgdorferi sensu lato and Babesia microti in Ixodes ricinus ticks from north-western Poland.
The tick Ixodes ricinus may carry microorganisms which cause serious human and animal diseases, i.a., the Lyme disease (borreliosis), caused by the spirochaete Borrelia burgdorferi sensu lato and babesiosis, induced by the protozoan Babesia microti. Both microbe species may co-occur in the same and other species of the genus tick and produce a mixed infection in humans and animals. The major objective of the study was to identify DNA of B. burgdorferi and B. microti in the I. ricinus ticks collected in spring and autumn 1999 from 6 sites in north-western Poland. The microbial DNA was identified with polymerase chain reaction (PCR). The marker used to detect the B. burgdorferi s.l. DNA was a fragment of the fla gene encoding the protein flagellin, while the B. microti DNA was detected with a fragment of the gene encoding 16S rRNA. A total of 550, 1,160, and 385 tick adults, nymphs, and larvae, respectively, were examined. Among the 155 (7.4%) B. burgdorferi- infected ticks and the 130 (6.2%) infected with B. microti, mixed infection was detected in 0.6% of individuals. The prevalence of coinfection differed between the tick developmental stages. Coinfection was most prevalent (3.1%) in females, males and nymphs being less affected (0.4 and 0.2%, respectively). No coinfection was revealed in the tick larvae. The study described was the first of its kind to be conducted in the former District of Szczecin. For the phenomenon of microbial co-occurrence and related mixed infections to be properly evaluated, the research will be continued.


Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study.
It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.


Identification and characterization of human surfactant protein A binding protein of Mycoplasma pneumoniae.
Mycoplasma pneumoniae infections represent a major primary cause of human respiratory diseases, exacerbate other respiratory disorders, and are associated with extrapulmonary pathologies. Cytadherence is a critical step in mycoplasma colonization, aided by a network of mycoplasma adhesins and cytadherence accessory proteins which mediate binding to host cell receptors. Furthermore, the respiratory mucosa is enriched with extracellular matrix components, including surfactant proteins, fibronectin, and mucin, which provide additional in vivo targets for mycoplasma parasitism. In this study we describe interactions between M. pneumoniae and human surfactant protein-A (hSP-A). Initially, we found that viable M. pneumoniae cells bound to immobilized hSP-A in a dose- and calcium (Ca(2+))-dependent manner. Mild trypsin treatment of intact mycoplasmas reduced binding markedly (80 to 90%) implicating a surface-associated mycoplasma protein(s). Using hSP-A-coupled Sepharose affinity chromatography and polyacrylamide gel electrophoresis, we identified a 65-kDa hSP-A binding protein of M. pneumoniae. The presence of Ca(2+) enhanced binding of the 65-kDa protein to hSP-A, which was reduced by the divalent cation-chelating agent, EDTA. The 65-kDa hSP-A binding protein of M. pneumoniae was identified by sequence analysis as a novel protein (MPN372) possessing a putative S1-like subunit of pertussis toxin at the amino terminus (amino acids 1 to 226), with the remaining amino acids (227 to 591) exhibiting no homology with other subunits of pertussis toxin, other known toxins, or any reported proteins. Recombinant MPN372 (MPN372) bound to hSP-A in a dose-dependent manner, which was markedly reduced by preincubation with mouse recombinant MPN372 antisera. Also, adherence of viable M. pneumoniae cells to hSP-A was inhibited by recombinant MPN372 antisera, demonstrating that MPN372, a previously designated hypothetical protein, is surface exposed and mediates mycoplasma attachment to hSP-A.


Genetic determinants associated with early age of diagnosis of IBD.
Inflammatory bowel disease (IBD) is typically diagnosed at 20 to 40 years of age. However, very young versus elderly patients with IBD may have different mechanisms of disease that may affect prognosis and care. The purpose of this work was to identify single nucleotide polymorphisms associated with age of onset of Crohn's disease and ulcerative colitis. Patients were genotyped using a custom microarray chip containing 332 IBD-associated single nucleotide polymorphisms. Age at diagnosis as a continuous variable was assessed using linear regression. Patients were then subgrouped by age at diagnosis and compared by the Fisher exact test. Bonferroni correction was used in all of the analyses. This study was conducted at a tertiary academic hospital. Sixty patients with Crohn's disease and 26 with ulcerative colitis were ≤ 16 years old, 259 patients with Crohn's disease and 248 with ulcerative colitis were 17-60 years old, and 10 patients with Crohn's disease and 20 with ulcerative colitis were >60 years old at diagnosis and included in this study. Age at diagnosis and single nucleotide polymorphism correlations were measured in this study. The NOD2 single nucleotide polymorphism rs2076756 was associated with younger age at Crohn's disease diagnosis (p = 0.0002). Patients with the AA/wild-type genotype were diagnosed at 31.9 ± 1.23 years, AG heterozygotes at 25.6 ± 0.99 years, and GG/at-risk allele homozygotes at 22.6 ± 1.32 years. Depending on age categories compared, single nucleotide polymorphisms in POU5F1, TNFSF15, and HLA DRB1*501 were associated with age of Crohn's disease diagnosis. No genetic associations were seen between ulcerative colitis and linear age at diagnosis; however, the G allele of the LAMB1 single nucleotide polymorphism rs886774 was found to be associated with ulcerative colitis diagnosed at ≤ 16 versus >17 years old (p = 0.008). This study was limited to known IBD single nucleotide polymorphisms. This analysis reaffirms the association between NOD2, a molecule of innate immunity, and early Crohn's disease onset. This is the first report of a possible association between early Crohn's disease and the POU5F1, TNFSF15, and HLA DRB1*501 genes. The LAMB1 gene, associated with mucosal basement membrane integrity, was associated with early onset ulcerative colitis and, thus, suggests a fundamentally different mechanism of early disease pathogenesis in ulcerative colitis versus Crohn's disease.


RecA protein stimulates homologous recombination in plants.
A number of RecA-like proteins have been found in eukaryotic organisms. We demonstrate that the prokaryotic recombination protein RecA itself is capable of interacting with genomic homologous DNA in somatic plant cells. Resistance to the DNA crosslinking agent mitomycin C requires homologous recombination as well as excision repair activity. Tobacco protoplasts expressing a nucleus-targeted RecA protein were at least three times as efficient as wild-type cells in repairing mitomycin C-induced damage. Moreover, homologous recombination at a defined locus carrying an endogenous nuclear marker gene was stimulated at least 10-fold in transgenic plant cells expressing nucleus-targeted RecA. The increase in resistance to mitomycin C and the stimulation of intrachromosomal recombination demonstrate that Escherichia coli RecA protein is functional in genomic homologous recombination in plants, especially when targeted to the plant nucleus.


Hyperbolic metamaterials: new physics behind a classical problem.
Hyperbolic materials enable numerous surprising applications that include far-field subwavelength imaging, nanolithography, and emission engineering. The wavevector of a plane wave in these media follows the surface of a hyperboloid in contrast to an ellipsoid for conventional anisotropic dielectric. The consequences of hyperbolic dispersion were first studied in the 50's pertaining to the problems of electromagnetic wave propagation in the Earth's ionosphere and in the stratified artificial materials of transmission lines. Recent years have brought explosive growth in optics and photonics of hyperbolic media based on metamaterials across the optical spectrum. Here we summarize earlier theories in the Clemmow's prescription for transformation of the electromagnetic field in hyperbolic media and provide a review of recent developments in this active research area.


Nonlinear Markov process amplitude EEG model for nonlinear coupling interaction of spontaneous EEG.
To develop an appropriate model for representing spontaneous electroencephalography (EEG) is an important and necessary work in the field of neuroscience. The Markov process amplitude (MPA) EEG model has been proposed in our previous work for representing the features of the EEG in terms of a few parameters. However, being a linear model, the linear MPA EEG model cannot perfectly describe the spontaneous EEG that displays nonlinear phenomena. In this paper, the nonlinear Markov process amplitude (nonlinear MPA) EEG model that includes nonlinear components is introduced. The consistent consideration of the nonlinear features of the EEG investigated by N. Wiener and P. L. Nunez can be seen from the nonlinear MPA EEG model. The similarity in the time domain and the goodness of fitting in the frequency domain with respect to the ongoing EEG are shown. As a result, the EEG power spectrum can be decomposed into the spontaneous components and the nonlinearly coupled components by use of the nonlinear MPA EEG model, which is useful for a better understanding the mechanism of the EEG generation.


Refinement of the critical genomic region for hypoglycaemia in the Chromosome 9p deletion syndrome.
Background: Large contiguous gene deletions at the distal end of the short arm of chromosome 9 result in the complex multi-organ condition chromosome 9p deletion syndrome. A range of clinical features can result from these deletions with the most common being facial dysmorphisms and neurological impairment. Congenital hyperinsulinism is a rarely reported feature of the syndrome with the genetic mechanism for the dysregulated insulin secretion being unknown. Methods: We studied the clinical and genetic characteristics of 12 individuals with chromosome 9p deletions who had a history of neonatal hypoglycaemia. Using off-target reads generated from targeted next-generation sequencing of the genes known to cause hyperinsulinaemic hypoglycaemia (n=9), or microarray analysis (n=3), we mapped the minimal shared deleted region on chromosome 9 in this cohort. Targeted sequencing was performed in three patients to search for a recessive mutation unmasked by the deletion. Results: In 10/12 patients with hypoglycaemia, hyperinsulinism was confirmed biochemically. A range of extra-pancreatic features were also reported in these patients consistent with the diagnosis of the Chromosome 9p deletion syndrome. The minimal deleted region was mapped to 7.2 Mb, encompassing 38 protein-coding genes. In silico analysis of these genes highlighted SMARCA2 and RFX3 as potential candidates for the hypoglycaemia. Targeted sequencing performed on three of the patients did not identify a second disease-causing variant within the minimal deleted region. Conclusions: This study identifies 9p deletions as an important cause of hyperinsulinaemic hypoglycaemia and increases the number of cases reported with 9p deletions and hypoglycaemia to 15 making this a more common feature of the syndrome than previously appreciated. Whilst the precise genetic mechanism of the dysregulated insulin secretion could not be determined in these patients, mapping the deletion breakpoints highlighted potential candidate genes for hypoglycaemia within the deleted region.


Carcinoembryonic antigen-related cell adhesion molecule 1: a link between insulin and lipid metabolism.
Liver-specific inactivation of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) by a dominant-negative transgene (l-SACC1 mice) impaired insulin clearance, caused insulin resistance, and increased hepatic lipogenesis. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we characterized the metabolic phenotype of mice with null mutation of the Ceacam1 gene (Cc1(-/-)). Mice were originally generated on a mixed C57BL/6x129sv genetic background and then backcrossed 12 times onto the C57BL/6 background. More than 70 male mice of each of the Cc1(-/-) and wild-type Cc1(+/+) groups were subjected to metabolic analyses, including insulin tolerance, hyperinsulinemic-euglycemic clamp studies, insulin secretion in response to glucose, and determination of fasting serum insulin, C-peptide, triglyceride, and free fatty acid levels. Like l-SACC1, Cc1(-/-) mice exhibited impairment of insulin clearance and hyperinsulinemia, which caused insulin resistance beginning at 2 months of age, when the mutation was maintained on a mixed C57BL/6x129sv background, but not until 5-6 months of age on a homogeneous inbred C57BL/6 genetic background. Hyperinsulinemic-euglycemic clamp studies revealed that the inbred Cc1(-/-) mice developed insulin resistance primarily in liver. Despite substantial expression of CEACAM1 in pancreatic beta-cells, insulin secretion in response to glucose in vivo and in isolated islets was normal in Cc1(-/-) mice (inbred and outbred strains). Intact insulin secretion in response to glucose and impairment of insulin clearance in l-SACC1 and Cc1(-/-) mice suggest that the principal role of CEACAM1 in insulin action is to mediate insulin clearance in liver.


The rhodanese RhdA helps Azotobacter vinelandii in maintaining cellular redox balance.
The tandem domain rhodanese-homology protein RhdA of Azotobacter vinelandii shows an active-site loop structure that confers structural peculiarity in the environment of its catalytic cysteine residue. The in vivo effects of the lack of RhdA were investigated using an A. vinelandii mutant strain (MV474) in which the rhdA gene was disrupted by deletion. Here, by combining analytical measurements and transcript profiles, we show that deletion of the rhdA gene generates an oxidative stress condition to which A. vinelandii responds by activating defensive mechanisms. In conditions of growth in the presence of the superoxide generator phenazine methosulfate, a stressor-dependent induction of rhdA gene expression was observed, thus highlighting that RhdA is important for A. vinelandii to sustain oxidative stress. The potential of RhdA to buffer general levels of oxidants in A. vinelandii cells via redox reactions involving its cysteine thiol is discussed.


RNA-binding protein HuR is required for stabilization of SLC11A1 mRNA and SLC11A1 protein expression.
The solute carrier family 11 member 1 (SLC11A1, formerly NRAMP1) gene is associated with infectious and autoimmune diseases and plays an important role in macrophage activation. Human SLC11A1 mRNA contains an AU-rich element (ARE) within the 3' untranslated region; however, its role in the regulation of SLC11A1 gene expression has not been elucidated. Here we analyze the expression of SLC11A1 in human monocytes and HL-60 cells and then use HL-60 cells as a model to determine whether RNA-binding protein HuR is associated with the ARE and involved in SLC11A1 mRNA turnover. Our results demonstrate a binding of HuR to the SLC11A1 ARE in phorbol myristate acetate (PMA)-differentiated cells dramatically increased compared to that in undifferentiated cells. Interestingly, PMA-induced accumulation of cytoplasmic HuR occurs in parallel with an increase in the binding of HuR to SLC11A1 ARE and with an increase in the SLC11A1 mRNA level. This suggests that HuR's cytoplasmic localization plays an important role in the regulation of SLC11A1 expression. We also observe that down-regulation of HuR expression by RNA interference (RNAi) results in a decrease in SLC11A1 expression which can be restored by the addition of recombinant HuR protein to the RNAi-treated cells. Finally, we show that HuR overexpression in HL-60 cells significantly increases the SLC11A1 mRNA stability. Taken together, our data demonstrate that HuR is a key mediator of posttranscriptional regulation and expression of the SLC11A1 gene.


Clinical features and correlates of outcomes for high-risk, marginalized mothers and newborn infants engaged with a specialist perinatal and family drug health service.
Background. There is a paucity of research in Australia on the characteristics of women in treatment for illicit substance use in pregnancy and the health outcomes of their neonates. Aims. To determine the clinical features and outcomes of high-risk, marginalized women seeking treatment for illicit substance use in pregnancy and their neonates. Methods. 139 women with a history of substance abuse/dependence engaged with a perinatal drug health service in Sydney, Australia. Maternal (demographic, drug use, psychological, physical, obstetric, and antenatal care) and neonatal characteristics (delivery, early health outcomes) were examined. Results. Compared to national figures, pregnant women attending a specialist perinatal and family drug health service were more likely to report being Australian born, Aboriginal or Torres Strait Islander, younger, unemployed, and multiparous. Opiates were the primary drug of concern (81.3%). Pregnancy complications were common (61.9%). Neonates were more likely to be preterm, have low birth weight, and be admitted to special care nursery. NAS was the most prevalent birth complication (69.8%) and almost half required pharmacotherapy. Conclusion. Mother-infant dyads affected by substance use in pregnancy are at significant risk. There is a need to review clinical models of care and examine the longer-term impacts on infant development.


Unplanned quitting in a triethnic sample of U.S. smokers.
Smokers who report quitting without prior planning have been shown to report longer abstinence compared with those who planned. Little is known about unplanned quitting (UQ) among U.S. smokers, minorities, or nondaily and light smokers. Using an online panel, we recruited equal numbers of Black, White, and Latino nondaily, light daily, and moderate/heavy daily smokers. Of the 1,127 who reported a past-year quit attempt, we queried whether it was planned and the maximum number of days abstinent. Overall, 38% reported that their last quit attempt was unplanned. The impact of planned versus unplanned quitting interacted with smoking level and race. Among White moderate/heavy smokers, mean days abstinent was 99 for those who reported an unplanned quit attempt compared with 60 days for those who reported a planned attempt (p = .02). Among Black moderate/heavy smokers, the mean days abstinent was higher among those whose last attempt was planned, 92 days, compared with 56 days among those whose last attempt was unplanned (p = .09). The pattern among Latinos resembled Whites but was not significant. Results remained after adjusting for confounds such as age, gender, education, income, time to first cigarette, and menthol use. There were no significant differences in abstinence by quit type for light or nondaily smokers. Future studies are needed to elucidate why UQ appears to have differential effectiveness across racial/ethnic groups and different levels of cigarette use. Research examining the impact of UQ on long-term quitting, which is not addressed here, is needed.


Common Components of Efficacious In-Home End-of-Life Care Programs: A Review of Systematic Reviews.
Multiple randomized controlled trials on in-home end-of-life (EOL) programs, often with multifaceted and varying components, have shown benefits and reduced costs. The objective of this review was to determine which components of these programs are most commonly associated with better outcomes than usual care. MEDLINE, CINAHL, and the Cochrane Library databases were searched from 2003 to 2014 for reviews of studies of in-home programs treating individuals with advanced illness. Original quantitative studies were included from these reviews, and the details of every program that had a significant positive effect on any outcome measured were extracted. Nineteen reviews met the inclusion criteria, from which 40 relevant studies were identified. Thirty unique components emerged from the content analysis of the program descriptions. On average, each program contained 11 components; the six most common were linkage with acute care, multidisciplinary nature, EOL expertise and training, holistic care, pain and symptom management, and professional psychosocial support. Linkage, around-the-clock availability, and customized care planning were most common to the nine interventions for which a significant cost reduction was reported. Efficacious in-home EOL programs comprised multiple components. Knowledge of these features can help inform the design of this care in local contexts that will more likely improve outcomes for individuals in an effective and cost-efficient manner.


Dioxin-like exposures and effects on estrogenic and androgenic exposures and micronuclei frequency in mother-newborn pairs.
In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)(R) bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX(R)-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased dioxin-like activity in the perfused placenta tissue after ex vivo TCDD perfusions (from 17 to 280pg CALUX(R)-TEQ/g plasma lipids) suggest that accumulation in the placenta prevents immediate transplacental transfer of TCDD. Androgenic activity were also similar in the paired mother-newborns (0.10 versus 0.18ng CALUX(R)-AEQ/mL plasma), whereas cord blood plasma estrogenic activity was higher than maternal levels (22.6 versus 18.5ng CALUX(R)-EEQ/mL plasma). In cord blood plasma androgenic activity was strongly positively associated with maternal levels (Rs=0.8, P<0.001) whereas dioxin-like and estrogenic activities were modestly associated with maternal levels (Rs</=0.4, P<0.001). The micronuclei frequency, an indicator of genetic instability was significantly associated with dioxin-like activity in cord blood, independently of other recorded factors (Rs=0.4, P<0.003). This study demonstrated interactions in vivo between dioxin-like, estrogenic and androgenic exposures during fetal development of humans.


Healthcare Disparities Identified Between Hmong and Other Asian Origin Groups Living with Chronic Hepatitis B Infection in Sacramento County 2014-2017.
Chronic hepatitis B (CHB) disproportionately affects non-US born Asians. The Hmong have been shown to have the highest rates of CHB and mortality from liver cancer compared to other Asian groups. From September 2014 to September 2017, testing for CHB within Sacramento County was conducted through community-based testing events and an electronic health record alert that identified Asian patients by surname. Demographic and laboratory data were collected for analysis and patients were followed through the study period to assess linkage to care and treatment to compare differences between Asian origin groups. Of 4350 patients tested for CHB, 318 (7.3%) were HBsAg positive, including 90 Chinese, 47 Hmong, and 101 Vietnamese. Hmong were more likely to have Medicaid insurance compared to other Asian origin groups (15%, p < 0.001). Hmong had significantly lower rates of hepatitis B DNA testing (p < 0.001), referral to hepatology (p < 0.001), attendance of first (p < 0.001) and second medical visit (p = 0.0003), and lower rates of antiviral treatment compared to other Asian origin groups. Hmong also had the highest proportion of non-English speakers (p < 0.001). Hmong patients in the Sacramento CHB testing and linkage to care program experience socioeconomic disadvantages compared to Vietnamese and Chinese patients. These factors may contribute to decreased linkage of care and decreased anti-viral treatment rates for CHB.


Inhibition of formation of cyclic AMP and cyclic GMP by vasopressin in smooth-muscle cells is insensitive to pertussis toxin.
Pretreatment of A-10 cells with pertussis toxin had no effect on [arginine]vasopressin-mediated inhibition of cyclic nucleotide accumulation. Pretreatment of the cells with the same concentration of pertussis toxin produced 90-95% inhibition of [32P]ADP ribosylation in membranes, suggesting that these cells possess pertussis-toxin substrate and that the toxin enters the cells to reach its site of action. The functional integrity of the pertussis-toxin substrate in these cells is confirmed by the observation that in these cell membranes increasing concentrations of GTP inhibited basal, forskolin- and NaF-stimulated adenylate cyclase activities, and this inhibition was abolished when the cells were pretreated with pertussis toxin. In addition, thrombin-mediated inhibition of isoprenaline-stimulated cyclic AMP accumulation was also inhibited by pertussis-toxin pretreatment of the cells. These data suggest that, unlike thrombin, [arginine]vasopressin-induced inhibitory effects on cyclic nucleotide accumulation in smooth-muscle cells are not mediated by pertussis-toxin substrate.


Different behavioural responses to anthropogenic noise by two closely related passerine birds.
Anthropogenic noise, now common to many landscapes, can impair acoustic communication for many species, yet some birds compensate for masking by noise by altering their songs. The phylogenetic distribution of these noise-dependent signal adjustments is uncertain, and it is not known whether closely related species respond similarly to noise. Here, we investigated the influence of noise on habitat occupancy rates and vocal frequency in two congeneric vireos with similar song features. Noise exposure did not influence occupancy rates for either species, yet song features of both changed, albeit in different ways. With increases in noise levels, plumbeous vireos (Vireo plumbeus) sang shorter songs with higher minimum frequencies. By contrast, grey vireos (Vireo vicinior) sang longer songs with higher maximum frequencies. These findings support the notion that vocal plasticity may help some species occupy noisy areas, but because there were no commonalities among the signal changes exhibited by these closely related birds, it may be difficult to predict how diverse species may modify their signals in an increasingly noisy world.


[Functional morphology of the cricopharyngeal muscle].
In the cricopharyngeal part of the inferior constrictor in the human and canine pharynx, there is a group of odd muscle fibers (transversal portion), which contracts at every phase of sigh. Registration of mechanical and electrical activity of the transversal portion of the canine cricopharyngeal muscle in chronic experiments demonstrates an important role of this structure to prevent from getting an excessive amount of air into the digestive tract at a sigh.


Simultaneous chirality sensing of multiple amines by (19)F NMR.
The rapid detection and differentiation of chiral compounds is important to synthetic, medicinal, and biological chemistry. Palladium complexes with chiral pincer ligands are demonstrated to have utility in determining the chirality of various amines. The binding of enantiomeric amines induces distinct (19)F NMR shifts of the fluorine atoms appended on the ligand that defines a chiral environment around palladium. It is further demonstrated that this method has the ability to evaluate the enantiomeric composition and discriminate between enantiomers with chiral centers several carbons away from the binding site. The wide detection window provided by optimized chiral chemosensors allows the simultaneous identification of as many as 12 chiral amines. The extraordinary discriminating ability of this method is demonstrated by the resolution of chiral aliphatic amines that are difficult to separate using chiral chromatography.


Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.
Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.


Survival of severe congenital diaphragmatic hernia has morbid consequences.
Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes. At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression. Infants with TO were significantly more premature at birth (control vs TO, 37.4 +/- 1.0 vs 31.1 +/- 1.7 weeks; P < .01). Growth failure ( z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0). In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.


Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review.
This paper reviews data on the prognosis of gastrointestinal stromal tumors (GISTs). These tumors are specific KIT-expressing and KIT-signaling-driven mesenchymal tumors, many of which have KIT-activating mutations. GISTs occur in the entire gastrointestinal (GI) tract and may also arise from the omentum, mesenteries, and retroperitoneum. They range from small benign tumors to sarcomas at all sites of occurrence. A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Understanding the natural history of GIST before introduction of STI-571 will help assess the impact and position of this new treatment. The frequency of benign versus malignant GISTs varies between sites. Benign GISTs outnumber malignant GISTs in the stomach, whereas malignant GISTs are more common in the intestines. Tumors that have metastasized at presentation have a very poor prognosis. Traditionally, the 3 key prognostic factors have been mitotic rate, tumor size, and site. Tumors that are small (< or =2 cm) and show mitotic activity not exceeding 5 mitoses per 50 high-power fields (HPFs) have an excellent prognosis, probably independent of site, although this has not been shown specifically for all sites. In the stomach, most epithelioid GISTs are benign, provided that mitotic counts do not exceed 5/50 HPFs. However, a small proportion of tumors apparently lacking mitotic activity do metastasize. Tumors with a mitotic rate >5/50 HPFs usually have a malignant behavior. The Ki67 index may help identify tumors with malignant potential, but large site-specific series are not yet available. Genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential.


Stream networks and long-term surface uplift in the new madrid seismic zone.
Stream networks are sensitive to low rates of surface uplift and can be used to decipher the history of large earthquakes even where faults do not rupture the surface, as in intraplate seismic zones. Statistical analysis of alluvial network data from topographic maps in the New Madrid seismic zone, in the central United States, shows that stream-segment gradients deviate the most from an estimated natural stream profile where surface uplift is greatest. Evidence of cumulative deformation distilled from stream network patterns represents at least several meters of differential surface uplift during Holocene time, which suggests that more than one cycle of surface deformation occurred.


In situ synthesis of thin zeolitic-imidazolate framework ZIF-8 membranes exhibiting exceptionally high propylene/propane separation.
Metal-organic frameworks (MOFs) are a class of hybrid porous crystalline materials comprising of metal centers coordinated to organic linkers. Owing to their well-defined pores and cavities in the scale of molecules combined with abundant surface chemistry, MOFs offer unprecedented opportunities for a wide range of applications including membrane-based gas separations. It is not straightforward (often requiring multiple steps) to prepare membranes of MOFs due to the fact that the heterogeneous nucleation and growth of MOF crystals on porous supports are not generally favored. Furthermore, the performance of polycrystalline MOF membranes strongly depends on the membrane microstructure, in particular, the grain boundary structure. Here we report a simple one step in situ method based on a counter-diffusion concept to prepare well-intergrown ZIF-8 membranes with significantly enhanced microstructure, resulting in exceptionally high separation performance toward propylene over propane.


Evaluation of degenerative diseases of the lumbar spine with reformatted and 3-dimensional computed tomography images.
To evaluate the identification of degenerative lesions of the lumbar spine with multiplanar reformatted images and 3-dimensional computed tomography (3DCT). Fifty-three patients with degenerative spinal disease findings on lumbar CT scanning were reviewed in this retrospective study at the Department of Radiology, Medical Faculty, Sutcu Imam University, Kahramanmaras, Turkey between January 2006 to January 2009. Two-dimensional multiplanar reformatted and 3DCT images were obtained. First, the axial CT images, and then 2-dimensional multiplanar reformatted images (2DMPR) were evaluated. The findings seen on reformatted CT images that were not visualized, or visualized only in retrospect on axial images were recorded. Finally, the 3D images were evaluated by the same team. The results were again recorded in the same manner. When 53 patients were taken into account, the 2DMPR provided better visualization of lateral neural foraminal stenosis in 62%, bulging of the disc in 32%, degenerative retrolisthesis in 15%, and spondylolysis in 15% as compared to axial images. The 3DCT images clearly revealed the presence of lateral neural foraminal stenosis in 41%, degenerative retrolisthesis in 13%, lateral spondylolisthesis in 15% as compared to axial and 2DMPR. The 2DMPR and 3DCT images provide significant anatomic and diagnostic information not readily derived from axial CT. It is useful in detecting degenerative conditions of the spine and associated complications.


When Listening Is Better Than Reading: Performance Gains on Cardiac Auscultation Test Questions.
In 2007, the United States Medical Licensing Examination embedded multimedia simulations of heart sounds into multiple-choice questions. This study investigated changes in item difficulty as determined by examinee performance over time. The data reflect outcomes obtained following initial use of multimedia items from 2007 through 2012, after which an interface change occurred. A total of 233,157 examinees responded to 1,306 cardiology test items over the six-year period; 138 items included multimedia simulations of heart sounds, while 1,168 text-based items without multimedia served as controls. The authors compared changes in difficulty of multimedia items over time with changes in difficulty of text-based cardiology items over time. Further, they compared changes in item difficulty for both groups of items between graduates of Liaison Committee on Medical Education (LCME)-accredited and non-LCME-accredited (i.e., international) medical schools. Examinee performance on cardiology test items with multimedia heart sounds improved by 12.4% over the six-year period, while performance on text-based cardiology items improved by approximately 1.4%. These results were similar for graduates of LCME-accredited and non-LCME-accredited medical schools. Examinees' ability to interpret auscultation findings in test items that include multimedia presentations increased from 2007 to 2012.


Comprehensive molecular phylogenetic analysis and evolution of the genus Phyllactinia (Ascomycota: Erysiphales) and its allied genera.
Phyllactinia is a unique genus within the Erysiphales (Ascomycota) having a partly endo-parasitic nature of the mycelium within the host plant tissues. We constructed phylogenetic trees for the genus Phyllactinia and its allied genera based on a total of 120 nucleotide sequences of the 28S rDNA and ITS regions to discuss their phylogenetic relationships with special references to host plants, biogeography, evolutionary dating, and taxonomy. The analysis of the Erysiphales confirmed the monophyly of the endo-parasitic genera, i.e. Leveillula, Phyllactinia, and Pleochaeta. Phyllactinia specimens used in this study were divided into six distinctive groups and three subgroups. Interestingly, Leveillula, an obligately endo-parasitic genus of the Erysiphales, grouped together with Phyllactinia, although this was not significantly supported by the Kishino-Hasegawa and Shimodaira-Hasegawa tests. This suggests that the evolution within this group of fungi occurred from partial endo-parasitism to obligate endo-parasitism. The host range of Phyllactinia is mostly confined to woody plants, especially deciduous trees. Betulaceae, Fagaceae, Ulmaceae, Moraceae, and Rosaceae may have close connections to the divergence of the groups and subgroups of Phyllactinia concerned. Most of these plant families are known as major members of the boreotropical flora of the Tertiary, which suggests an early Tertiary origin of this genus. A comparison of the phylogenies of hosts and parasites revealed that host range expansion at higher taxonomic levels (higher than family level) is independent of the phylogeny of plants. Conversely, host range expansions in lower taxonomic levels (infrafamilial or infrageneric) tend to occur within a single family or genus. An estimation of the evolutionary timing using a molecular clock approach suggested that Phyllactinia split from Pleochaeta about 60 M years ago (Ma) in the early Tertiary and divergence of the six major clades of Phyllactinia occurred between 5 and 40 Ma during the Oligocene and Miocene. Divergence within the major clades and within Leveillula occurred maybe from more than 5 Ma onwards during the Pliocene and Quaternary. This is the first comprehensive phylogenetic study of Phyllactinia and other endo-parasitic genera of the Erysiphales.


The traumatized eye.
Injuries to the eye, both contusional and perforating, have a considerable visual morbidity not the least of which is a cosmetically unacceptable eye. Meticulous primary surgical repair and judicious secondary reconstruction of the eye may not only preserve visual functions but substantially improve the patient's appearance. Most cosmetic problems follow perforating eye injuries and include corneal leucomata, iris and pupillary abnormalities, cataract, phthisis bulbi and enucleation. Oculo-motor abnormalities, particularly divergent squint, are common where substantial loss of vision has occurred in one or both eyes. In the series reported 215 eyes were enucleated secondary to ocular trauma over a 10 year period (2,162 injured eyes), the vast majority following perforating injury. The risk of sympathetic ophthalmia was the reason for enucleation in 50.7 per cent of cases although sympathetic ophthalmia was identified in only two instances. Cosmetic defects secondary to contusional injuries are uncommon and mostly due to iris abnormalities and cataract.


Prenatal infection and schizophrenia: a review of epidemiologic and translational studies.
An emerging literature from epidemiologic, clinical, and preclinical investigations has provided evidence that gestational exposure to infection contributes to the etiology of schizophrenia. In recent years, these studies have moved from ecologic designs, which ascertain infection based on epidemics in populations, to investigations that have capitalized on reliable biomarkers in individual pregnancies. These studies have documented specific candidate infections that appear to be associated with an elevated risk of schizophrenia. Animal models of maternal immune activation inspired by this work have revealed intriguing findings indicating behavioral, neurochemical, and neurophysiologic abnormalities consistent with observations in schizophrenia. In parallel studies in humans and animals, investigators are working to uncover the cellular and molecular mechanisms by which in utero exposure to infection contributes to schizophrenia risk. In this review, the authors discuss and critically evaluate the epidemiologic literature on in utero exposure to infection and schizophrenia, summarize emerging animal models of maternal immune activation, and discuss putative unique and common mechanisms by which in utero exposure to infection alters neurodevelopment, potentially increasing susceptibility to schizophrenia. The promise of this work for facilitating the identification of susceptibility loci in genetic studies of schizophrenia is illustrated by examples of interaction between in utero exposure to infection and genetic variants. The authors then elaborate on possible implications of this work, including the use of preventive measures for reducing the incidence of schizophrenia. Finally, they discuss new approaches aimed at addressing current challenges in this area of research.


Effects of litter removal on plant species diversity: a case study in tropical Eucalyptus forest ecosystems in South China.
The removal of litterfall in the Eucalyptus plantations in South China affected the plant biodiversity in these ecosystems was found based on the field observation and lab analysis. The protection times of species diversity of three Eucalyptus communities were different (Community I with no protection, Community II with 7-year-protection, Community III with 35-year-protection). The total numbers of species in these communities (from Community I to II to III) are 1, 6, and 17 respectively. The results showed that the protection of litterfall from being taken out of the ecosystem is important and can increase plant species diversity. This study combined biomass data, the chemical and physical properties of the soil, and the diversity of microbes in the communities. It is concluded that the mechanism of the effects of litter removal on biodiversity includes three factors: removing the suitable habitat of microbe and animal, decreasing the soil nutrient, and changing the special habitat for the germination and growth of invading plants. These results should have important implications for managing these Eucalyptus forest ecosystems in South China.


Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis.
Cell surface oligosaccharides can be engineered to display unusual functional groups for the selective chemical remodeling of cell surfaces. An unnatural derivative of N-acetyl-mannosamine, which has a ketone group, was converted to the corresponding sialic acid and incorporated into cell surface oligosaccharides metabolically, resulting in the cell surface display of ketone groups. The ketone group on the cell surface can then be covalently ligated under physiological conditions with molecules carrying a complementary reactive functional group such as the hydrazide. Cell surface reactions of this kind should prove useful in the introduction of new recognition epitopes, such as peptides, oligosaccharides, or small organic molecules, onto cell surfaces and in the subsequent modulation of cell-cell or cell-small molecule binding events. The versatility of this technology was demonstrated by an example of selective drug delivery. Cells were decorated with biotin through selective conjugation to ketone groups, and selectively killed in the presence of a ricin A chain-avidin conjugate.


[Use of centimetric range microwave therapy in multimodality treatment of patients with destructive pulmonary tuberculosis].
Centimeter microwave therapy (CMWT) was employed in the multimodality treatment of 50 patients with destructive pulmonary tuberculosis. Its results were compared with a matched control group comprising 43 patients. CMWT increased the rate of decay cavity closure, improved bronchial patency and prevented its deterioration. This was followed by improved lipid peroxidation, antioxidative activity, and an immunological responsiveness of the body.