The prevalence of beak and feather disease virus infection in wild populations of parrots and cockatoos in New Zealand.
To determine the prevalence of beak and feather disease virus (BFDV) infection in exotic parrots and cockatoos in the wild in New Zealand. Eastern rosellas (Platycercus eximius, n=162) were caught from Te Puke, Wellington and Dunedin, using mistnets, between April 2004 and February 2006, and sulphur crested cockatoos (Cacatua galerita, n=255) were captured for pet-trading from November 2001 to September 2004. Feathers from both species were tested for BFDV, using an established polymerase chain reaction (PCR) test. Post-mortem examinations were conducted on some of the eastern rosellas, and selected tissues from 24 birds positive for BFDV were examined using routine histological methods for the presence of characteristic inclusion bodies. Of the eastern rosellas, 24/162 (14.8%) were positive for BFDV, and the 95% confidence interval (CI) for true prevalence was estimated as 8.6-20.4%, which varied between regions. Eastern rosellas that were positive for BFDV showed no clinical or histological signs of disease or inclusion bodies. Of the sulphur-crested cockatoos, 70/255 (28%) were positive for BFDV, and the 95% CI for true prevalence was calculated as 22-33%. The surprisingly high prevalence of BFDV in wild eastern rosellas and sulphur-crested cockatoos has serious implications for the conservation of native parrots and the export of wild-trapped parrots and cockatoos from New Zealand. Serological studies for BFDV in wild exotic parrots, and molecular studies of virus genotype, are recommended to further characterise the origin and epidemiology of the disease in populations of wild exotic parrots and cockatoos in New Zealand.


Mutual information in coupled multi-shape model for medical image segmentation.
This paper presents extensions which improve the performance of the shape-based deformable active contour model presented earlier in [IEEE Conf. Comput. Vision Pattern Recog. 1 (2001) 463] for medical image segmentation. In contrast to that previous work, the segmentation framework that we present in this paper allows multiple shapes to be segmented simultaneously in a seamless fashion. To achieve this, multiple signed distance functions are employed as the implicit representations of the multiple shape classes within the image. A parametric model for this new representation is derived by applying principal component analysis to the collection of these multiple signed distance functions. By deriving a parametric model in this manner, we obtain a coupling between the multiple shapes within the image and hence effectively capture the co-variations among the different shapes. The parameters of the multi-shape model are then calculated to minimize a single mutual information-based cost criterion for image segmentation. The use of a single cost criterion further enhances the coupling between the multiple shapes as the deformation of any given shape depends, at all times, upon every other shape, regardless of their proximity. We found that this resulting algorithm is able to effectively utilize the co-dependencies among the different shapes to aid in the segmentation process. It is able to capture a wide range of shape variability despite being a parametric shape-model. And finally, the algorithm is robust to large amounts of additive noise. We demonstrate the utility of this segmentation framework by applying it to a medical application: the segmentation of the prostate gland, the rectum, and the internal obturator muscles for MR-guided prostate brachytherapy.


Vertical ionization energies of adenine and 9-methyl adenine.
Vertical ionization energies of 9-H adenine and 9-methyl adenine have been calculated with the following, ab initio, electron propagator methods: the outer valence Green's function (OVGF), partial third-order theory (P3), and the third-order algebraic diagrammatic construction, or ADC(3). Basis set effects have been systematically examined. All methods predict near degeneracy in the pi(2)-n(1) and pi(3)-n(2) pairs of cationic, adenine final states and larger splittings of the corresponding, cationic states of 9-methyl adenine. P3 results for adenine predict the following order of the first six final states: pi(1), n(1), pi(2), n(2), pi(3), n(3). Coupled-cluster calculations on the first three cationic states of adenine confirm these predictions. OVGF and ADC(3) calculations reverse the order of the second and third states and of the fourth and fifth states. All results confirm previous interpretations of experiments in which the second and third spectral bands correspond to the aforementioned pairs of final states and disagree with a recent reassignment based on time-resolved photoelectron spectra. Lower ionization energies and larger splittings in the methylated molecule are interpreted in terms of phase relationships in the Dyson orbitals. ADC(3) results confirm the qualitative validity of the one-electron approximation for the first six final states of both molecules and disclose its inadequacies for higher ionization energies.


Egg of Aedes (Gymnometopa) mediovittatus (Diptera: Culicidae).
The egg of Aedes mediovittatus (Coquillett) is described from scanning electron micrographs. The egg is black, slightly tapered toward the posterior pole, and is approximately 771 microns long and up to 175 microns wide. On the entire egg surface there are about 970 polygonal outer chorionic cells, each bounded by a raised outer chorionic reticulum which forms a wall around each cell. Incorporated into the inner surface of this wall are 13-18 relatively small, poorly defined and variably shaped tubercles. In the center of each cell there is a large, buttonlike, more or less round tubercle with a pitted upper surface. Over most of the egg surface, the walls of this tubercle are connected by spokelike bridges of variable diameter to the cell floor or reticulum wall. The structure of the outer chorionic cells is somewhat modified in areas approaching the anterior and posterior poles.


A prospective investigation of factors that predict desistance from recidivism for adolescents who have sexually offended.
Current approaches to violence risk assessment are focused on the identification of factors that are predictive of future violence rather than factors that predict desistance. This is also true for the popular tools designed to predict adolescent sexual recidivism. Research on strengths-based variables with adolescents who have sexually offended that could serve a protective function is only recently underway. In the current prospective study, scores from clinician-completed assessments using the Estimate of Risk of Adolescent Sexual Offense Recidivism (ERASOR) and the parent-completed form of the Behavioral and Emotional Rating Scale (BERS-2) were evaluated in a sample of 81 adolescent males with at least one sexual offense. As expected, the ERASOR was significantly correlated with sexual recidivism over an average 3.5-year follow-up. In terms of a protective function, the Affective Strength scale of the BERS-2 was significantly negatively correlated with sexual recidivism, although it did not have incremental validity over and above the ERASOR. The BERS-2 School Functioning scale was significantly negatively correlated with nonsexual recidivism. The results are discussed in terms of previous findings and theoretical work on attachment in sexual offending behavior and implications for risk assessment practice.


Annual report of the Australian National Poliovirus Reference Laboratory, 2003.
The Australian National Poliovirus Reference Laboratory was established in late 1994, as part of Australia's commitment to the World Health Organization's (WHO) polio eradication program. The laboratory continues to play a pivotal role in maintaining Australia's polio-free status through surveillance for cases of acute flaccid paralysis (AFP), the main clinical presentation of poliomyelitis, and the testing of specimens from these cases. The annual notification rate for eligible cases of AFP in Australia for 2003 was 0.83 per 100,000 children less than 15 years of age. The annual non-polio AFP rate after classification of cases by the polio expert committee was 0.68 per 100,000, 32 per cent below WHO's annual target. While no polioviruses were isolated from the specimens tested from the 27 cases of AFP in 2003, a novel enterovirus (enterovirus 75) was isolated from one case and enterovirus 71 was isolated from another. During the same period 12 polioviruses, referred from cases other than AFP, tested as Sabin-like by the WHO approved methods of intratypic differentiation. The importation of wild polioviruses from endemic Nigeria into surrounding countries of Africa during 2003, highlights the importance of the continuation of AFP surveillance and high quality laboratory activities throughout the world until global eradication of polio is certified.


Influence of feeding increasing levels of dry corn distillers grains plus solubles in whole corn grain-based finishing diets on total tract digestion, nutrient balance, and excretion in beef steers.
Four crossbred steers (average BW = 478 ± 33 kg) were used in a 4 × 4 Latin square design to determine the effects of dietary concentration of dry corn distillers grains plus solubles (DDGS) in whole corn-based finishing diets on total tract digestion and nutrient balance and excretion. The DDGS were fed at 0% (control), 16.7%, 33.3%, and 50% of dietary DM. All diets contained 10% (DM basis) alfalfa/grass haylage and were formulated to meet or exceed the estimated requirements for CP. Steers were fed the experimental diets ad libitum for a 14-d adaptation period followed by a 5-d period for fecal and urine collection. Increasing concentration of DDGS in diets from 0 to 50% of DM linearly decreased (P < 0.05) total tract DM and starch digestibility (from 77.8 to 72.9%, and 89.2 to 81.5%, respectively). Daily N and P intakes linearly increased (P = 0.06 and P = 0.01, respectively) with increasing DDGS concentration. Fecal and urinary N, P, S, Mg, and K excretion linearly increased (P < 0.05) with increasing DDGS concentration; however, Se and Na excretion did not differ (P > 0.38) among treatments. Retention (g/d; intake minus urinary and fecal excretion) of N did not differ (P > 0.16) among treatments. Retention of P tended (P = 0.07) to linearly increase and retention of S (g/d) linearly increased (P = 0.004), with increasing DDGS concentration. There were no effects (P > 0.16) of dietary treatment on digestion and retention of Se, Mg, K, and Na. Plasma P and S concentrations increased (P = 0.03 and 0.01, respectively) with increasing DDGS concentration. These data indicate that feeding DDGS up to 50% of dietary DM in whole corn grain-based finishing diets does not have a negative effect on nutrient retention but decreases digestibility. Total excretion of N, P, Ca, Mg, S, and K increased as DDGS concentration increased.


A facile method for synthesis of polyaniline nanospheres and effect of doping on their electrical conductivity.
The synthesis of polyaniline (PANI) nanospheres by a simple template-free method has been described. The polymerization of aniline in aqueous medium was accomplished using ammonium persulfate without any protonic acid. The UV-vis spectrum of PANI nanospheres displayed the characteristic absorption peak of π-π* transition of the benzenoid ring at 355 nm. The oxidation state of PANI nanospheres was identified with FT-IR spectroscopy by comparing the two bands at 1582 (ring stretching in quinoid unit) and 1498 cm(-1) (ring stretching in bezenoid unit). The X-ray diffraction patterns demonstrated the low crystalline nature of PANI nanospheres. The morphology of PANI nanospheres was spherical and the mean diameter of nanospheres was found in the range of 3-12 nm. The thermal behavior of PANI nanospheres was studied by thermogravimetric analysis. The effect of doping of HCl and H(2)SO(4) on PANI nanospheres was studied by measuring the current as a function of time of exposure. The high electrical conductivity of 6×10(-2) S cm(-1) was obtained for PANI nanospheres at their optimum doping state by 100 ppm HCl.


Staphylococcus aureus at a maternity ward. I. Colonization of mothers and neonates and survival of various S. aureus types in colonized individuals.
Colonization by Staphylococcus aureus, characterized by phage type or production of enterotoxins and toxic-shock-syndrome-toxin, was followed in 50 mothers and their babies. Types or groups of staphylococci predominating during the particular period at the maternity department were evaluated according to survival rates in the colonized subjects. S. aureus frequently colonized nipples at the start of lactation and was found regularly on umbilical stump and in eye and mouth corners of the babies. During the second stage of the study phage untypable staphylococci producing enterotoxin C (NT/C) strongly predominated. These microorganisms colonized in the greatest extent both mothers and neonates. The majority of NT/C complex originated probably from one or two clones characterized, among others, by high biological activity.


Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae.
The aim of the present study was to assess the inotropic effects of vasoactive intestinal peptide (VIP) on isolated myocardial trabeculae from the right atrium and the left ventricle of human hearts. Furthermore, using reverse transcriptase-PCR, we wanted to determine the presence of mRNAs encoding the three cloned human VIP receptors, VPAC(1), VPAC(2) and PAC(1). The trabeculae were paced at 1.0 Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. VIP had a potent positive inotropic effect in some of the atrial and ventricular trabeculae tested. This effect was almost completely blocked by the VIP-receptor antagonist VIP-(6-28). mRNAs encoding the human VPAC(1), VPAC(2) and PAC(1) receptors were detected in human myocardial trabeculae from both the right atrium and the left ventricle. In conclusion, VIP has a direct positive inotropic effect in both the atria and the ventricles of the human heart. The presence of mRNAs for the VPAC(1), VPAC(2) and PAC(1) receptors suggest that VIP may mediate its effect via these receptors.


Relinquishing in-home dementia care: difficulties and perceived helpfulness during the nursing home transition.
Institutionalization of an elderly relative suffering from dementia is a key transition in the caregiving career. This study determines factors that predict the problems and help dementia caregivers perceive while institutionalizing an elderly relative. By using a sample of 185 dementia caregivers interviewed before and after institutionalization, the authors conducted a multivariate regression to identify relevant predictors of search difficulties, professional help, and family help during the nursing home transition. The personal and social resources of caregivers prior to placement (e.g., mastery, family conflict, socioemotional support, duration of care, education, and physical health) were reliable predictors of search difficulties and perceived helpfulness. Such findings will prove useful to long-term care practitioners who wish to facilitate the institutionalization process for caregiving families.


A N-heterocyclic carbene derived highly regioselective ambident C-C-S and C-C-N 1,3-dipolar system.
N-Heterocyclic carbene derived 2-phenylthiocarbamoyl benzimidazolium and imidazolinium inner salts are a unique ambident C-C-S and C-C-N 1,3-dipolar system able to undergo highly efficient and regioselective cycloaddition with dimethyl acetylenedicarboxylate and ethyl propiolate to furnish, respectively, spiro[imidazole-2,3'-thiophene] and spiro[imidazole-2,3'-pyrrole] derivatives in good to excellent yields.


Discordant e antigen, DNA polymerase activity, and Dane particle responses in two patients representing an index case-contact case pair with hepatitis B virus infection.
Discordant results for e antigen, DNA polymerase activity, and Dane particle frequency were noted in the sera of two patients representing an index case-contact case pair with chronic aggressive hepatitis B. The lack of correlation between presence of e antigen and the infecting viral strain, as well as the strong relationship of e antigen to persistent and significant viremia, emphasize the role of the host's immune response in the expression of this antigen.


Ligand-induced endocytosis of the pattern recognition receptor FLS2 in Arabidopsis.
Pattern-recognition receptors (PRRs) trigger innate immune responses in animals and plants. One such PRR is the flagellin receptor FLS2 in Arabidopsis. Here, we demonstrate that a functional fusion of FLS2 to the green fluorescent protein (GFP) resides in cell membranes of most tissues. Stimulation with the flagellin epitope flg22 induces its transfer into intracellular mobile vesicles, followed by degradation. FLS2 internalization depends on cytoskeleton and proteasome functions, and receptor activation. A variant FLS2 mutated in Thr 867, a potential phosphorylation site, binds flg22 normally, but is impaired in flg22 responses and FLS2 endocytosis. We propose that plant cells regulate pathogen-associated molecular pattern (PAMP)-mediated PRR activities by subcellular compartmentalization.


Programmed cell death of developing mammalian neurons after genetic deletion of caspases.
An analysis of programmed cell death of several populations of developing postmitotic neurons after genetic deletion of two key members of the caspase family of pro-apoptotic proteases, caspase-3 and caspase-9, indicates that normal neuronal loss occurs. Although the amount of cell death is not altered, the death process may be delayed, and the cells appear to use a nonapoptotic pathway of degeneration. The neuronal populations examined include spinal interneurons and motor, sensory, and autonomic neurons. When examined at both the light and electron microscopic levels, the caspase-deficient neurons exhibit a nonapoptotic morphology in which nuclear changes such as chromatin condensation are absent or reduced; in addition, this morphology is characterized by extensive cytoplasmic vacuolization that is rarely observed in degenerating control neurons. There is also reduced terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling in dying caspase-deficient neurons. Despite the altered morphology and apparent temporal delay in cell death, the number of neurons that are ultimately lost is indistinguishable from that seen in control animals. In contrast to the striking perturbations in the morphology of the forebrain of caspase-deficient embryos, the spinal cord and brainstem appear normal. These results are consistent with the growing idea that the involvement of specific caspases and the occurrence of caspase-independent programmed cell death may be dependent on brain region, cell type, age, and species or may be the result of specific perturbations or pathology.


Securinine, a myeloid differentiation agent with therapeutic potential for AML.
As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potential of avoiding the significant side effects that occur with the traditional AML therapeutics. We identified a natural compound securinine, as a leukemia differentiation-inducing agent. Securinine is a plant-derived alkaloid that has previously been used clinically as a therapeutic for primarily neurological related diseases. Securinine induces monocytic differentiation of a wide range of myeloid leukemia cell lines as well as primary leukemic patient samples. Securinine's clinical potential for AML can be seen from its ability to induce significant growth arrest in cell lines and patient samples as well as its activity in significantly impairing the growth of AML tumors in nude mice. In addition, securinine can synergize with currently employed agents such as ATRA and decitabine to induce differentiation. This study has revealed securinine induces differentiation through the activation of DNA damage signaling. Securinine is a promising new monocytic differentiation inducing agent for AML that has seen previous clinical use for non-related disorders.


microRNA-1225 inhibit apoptosis of pancreatic cancer cells via targeting JAK1.
The microRNA miRNA-1225-5p (miR-1225) is known as an essential modulator of the development of multiple cancers and other biological reactions. However, the understanding of its contribution to pancreatic cancer (PC) is insufficient. The effects of miR-1225 on PC cell survival and tumorigenesis in vivo as well as on the modulation of cell apoptosis were investigated. The expression of miR-1225 was upregulated in 20 human LC samples from acute myeloid leukemia patients with adverse prognosis and poor responses to therapy as well as in several human PC cell lines, as compared to that in healthy tissues, normal tissues, and normal pancreatic cells. In contrast, Janus kinase 1 (JAK1) expression was downregulated in human-derived PC samples and PC cell lines. EdU staining demonstrated that the aberrant expression of miR-1225 impaired the proliferation and survival of these two PC cell lines. The depletion of miR-1225 expression increased the apoptosis of both PANC-1 and AsPC-1 cells, as revealed by the TdT-mediated dUTP nick end labeling (TUNEL) staining and flow cytometry results. The results of dual-luciferase reporter assay indicated that miR-1225 targeted the 3'-untranslated region of JAK1 for silencing. Silencing of JAK1 expression counteracted the suppressive influence of miR-1225 depletion in PC cells. Thus, these results offer an insight into the biological and molecular mechanisms underlying the development of PC and provide potential strategies for PC treatment.


Mining in Twitter for adverse events from malaria drugs: the case of doxycycline.
During the post-marketing period, when medicines are used by large population contingents and for longer periods, unexpected adverse events (AE) can occur, potentially altering the drug's risk-benefit ratio enough to demand regulatory action. AE are health problems that can occur during treatment with a pharmaceutical product, which in the drug's post-marketing period can require a significant increase in health care and result in unnecessary and often fatal harm to patients. Therefore, a key objective for the health system is to identify AE as soon as possible in the post-marketing period. Some countries have pharmacovigilance systems responsible for collecting voluntary reports of post-marketing AE, but studies have shown that social networks can be used to obtain more and faster reports. The current project's main objective is to build a totally automated system using Twitter as a source to detect both new and previously known AE and conduct the statistical analysis of the resulting data. A system was thus built to collect, process, analyze, and assess tweets in search of AE, comparing them to U.S. Food and Drug Administration (FDA) data and the reference standard. The results allowed detecting new and existing AE related to the drug doxycycline, showing that Twitter can be useful in pharmacovigilance when employed jointly with other data sources.


Benefits of blinded continuous glucose monitoring during a randomized clinical trial.
Real-time, personal continuous glucose monitoring (CGM) is a validated technology that can help patients improve glycemic control. Blinded CGM is a promising technology for obtaining retrospective data in clinical research where the quantity and quality of blood glucose information is important. This study was designed to investigate the use of novel procedures to enhance data capture from blinded CGM. Following a 4-week run-in, 46 patients with type 1 diabetes were randomized to one of two prandial insulins for a 12-week treatment period, after which they were crossed over to the alternate treatment for 12 weeks. Continuous glucose monitoring was implemented at the end of run-in (practice only) and during the last 2 weeks of each treatment period. Eighty percent of 288 possible daily glucose values were required for at least three days. Continuous glucose monitoring was extended for an additional week if these criteria were not met, and patients were allowed to insert sensors at home when necessary. Continuous glucose monitoring results were compared to reference eight-point self-monitoring of blood glucose (SMBG). Higher than expected sensor failure rate was approximately 25%. During run-in, 12 of 45 attempted profiles failed adequacy criteria. However, treatment periods had only 1 of 82 attempted profiles considered inadequate (6 cases required an additional week of CGM). Using SMBG as reference, 93.7% of 777 CGM values were in Clarke error grid zones A+B. With appropriate training, adequate practice, and opportunity to repeat blinded CGM as needed, nearly 100% of attempted profiles can be obtained successfully.


Trabecular damage due to blunt anterior segment injury and its relationship to traumatic glaucoma.
Gonioscopy, performed within 48 hours of traumatic hyphema, revealed not only angle recession but also a high incidence of damage to the trabecular meshwork and the Schlemm canal. These trabecular lesions tend to scar and become much more difficult to recognize over the ensuing weeks. Large tears into the ciliary body (angle recession) also had a tendency to "close." Using a specially calibrated BB gun hyphema was induced in rhesus monkeys. Trabecular tears were recognized by gonioscopic and histologic examination. Impaired outflow facility developed between 10 and 30 days after injury in the one surviving animal studied to date. In patients developing open-angle glaucoma years after trauma, evidence of past trabecular injury was seen by gonioscopy in addition to the obvious ciliary body tears (angle recession). The "normal" fellow eye had early glaucoma, ocular hypertension, or "high normal" intraocular pressure. The evidence presented supports the hypothesis that traumatic glaucoma is the result of trabecular meshwork injury from the original trauma and the rapid scarring that results, in combination with an underlying predisposition for the development of primary open-angle glaucoma and the passage of time.


[Cognitive structure and risk of myocardial infarct].
In a psychophysiological experiment with 18 patients with cardiovascular disorders but without infarction we proved the influence of habituallized cognitive structures on reactivity under mental load. We used the concepts of different causal attribution (Explanatory style: Peterson and Seligman) and psychic regulation of activity and action (Activity style: Günther). It can be shown that patients with pessimistic explanatory style as well as with diffuse psychic activity control show coronary-prone reaction patterns under load (indicators: cortisol and triglycerids in serum).


Endoscopic ultrasound in the diagnosis and management of carcinoma pancreas.
Endoscopic ultrasound (EUS) has become an important component in the diagnosis and treatment of carcinoma pancreas. With the advent of advanced imaging techniques and tissue acquisition methods the role of EUS is becoming increasingly important. Small pancreatic tumors can be reliably diagnosed with EUS. EUS guided fine needle aspiration establishes diagnosis in some cases. EUS plays an important role in staging of carcinoma pancreas and in some important therapeutic methods that include celiac plexus neurolysis, EUS guided biliary drainage and drug delivery. In this review we attempt to review the role of EUS in diagnosis and management of carcinoma pancreas.


Supraglottic contributions to pitch raising. Videoendoscopic study with spectroanalysis.
Several questions pertaining to pitch raising recur frequently. Does the larynx rise with the production of higher frequencies? What happens to the pharyngeal walls between the soft palate and the larynx when the fundamental frequency is raised? How does the soft palate participate in pitch raising? To answer these questions, the present study was undertaken with the recently described simultaneous velolaryngeal endoscopy technique. Nine professional singers were asked to find the limits of their vocal range in any of six voice qualities: speech, falsetto, cry/sob, twang, belting, and opera. Simultaneous activities of the larynx, the pharyngeal walls, and the soft palate were submitted to videoendoscopy with synchronous voice recording and studied with spectroanalysis of discrete segments of the total phonation range. Our dual endoscopic study showed that 1) the larynx rose in all subjects with the production of higher frequencies, 2) with the highest fundamental frequency, the lateral pharyngeal walls significantly contracted toward the midline in an "upside-down V shape," creating a very narrow pharyngeal tube, and 3) the soft palate lifted and the velopharyngeal port narrowed considerably with higher frequencies.


Effects of a computerized working memory training program on working memory, attention, and academics in adolescents with severe LD and comorbid ADHD: a randomized controlled trial.
Youths with coexisting learning disabilities (LD) and attention deficit hyperactivity disorder (ADHD) are at risk for poor academic and social outcomes. The underlying cognitive deficits, such as poor working memory (WM), are not well targeted by current treatments for either LD or ADHD. Emerging evidence suggests that WM might be improved by intensive and adaptive computerized training, but it remains unclear whether this intervention would be effective for adolescents with severe LD and comorbid ADHD. A total of sixty 12- to 17-year olds with LD/ADHD (52 male, 8 female, IQ > 80) were randomized to one of two computerized intervention programs: working memory training (Cogmed RM) or math training (Academy of Math) and evaluated before and 3 weeks after completion. The criterion measures of WM included auditory-verbal and visual-spatial tasks. Near and far transfer measures included indices of cognitive and behavioral attention and academic achievement. Adolescents in the WM training group showed greater improvements in a subset of WM criterion measures compared with those in the math-training group, but no training effects were observed on the near or far measures. Those who showed the most improvement on the WM training tasks at school were rated as less inattentive/hyperactive at home by parents. Results suggest that WM training may enhance some aspects of WM in youths with LD/ADHD, but further development of the training program is required to promote transfer effects to other domains of function.


[Distribution of alpha1-antitrypsin phenotypes in Icelanders.].
Although the Z and S alleles causing alpha1-arantitrypsin deficiency are present at a high frequency in Northern Europeans, alpha1-arantitrypsin deficiency has never been identified in an Icelandic patient. In this study the frequency of the major alpha1-antitrypsin phenotypes M, F, S and Z, was determined in 511 unrelated Icelandic individuals by isoelectric focusing in polyacrylamide gel slabs. The frequencies of the alleles in this population were: M = 0.946; F = 0.006; S = 0.037; and Z = 0.011. The results demonstrate the presence of alpha1-arantitrypsin deficiency alleles in the Icelandic population at somewhat lower allele frequency than is found in the other Nordic populations.


Dissection of RNA-mediated ryegrass mosaic virus resistance in fertile transgenic perennial ryegrass (Lolium perenne L.).
Ryegrass mosaic virus (RgMV) frequently reduces yield and persistence of perennial ryegrass. We introduced an untranslatable RgMV coat protein (RgMV-CP) gene into perennial ryegrass using particle bombardment to explore the potential of RNA-mediated virus resistance. Nine months after inoculation with the RgMV-Bulgaria strain, the most resistant transgenic line showed no immuno-detectable RgMV-CP in all replications of the primary transformant and a sexual progeny. A significant influence of the transgenic line, virus strain and the period after inoculation on the RgMV level was observed. Typical examples of recovery resistance from initially susceptible plants were not identified. Molecular analysis revealed RgMV resistance operates by targeted RNA degradation resulting in post-transcriptional transgene silencing (PTGS) along with inhibition of virus RNA replication and was not associated with a threshold of transgene expression. Suppression of PTGS by RgMV differed significantly in two progenies with identical RgMV-CP transgene integration and a similar RgMV-CP transgene methylation pattern, suggesting the presence of quantitative components controlling the stability of PTGS in perennial ryegrass. This study extends RNA-mediated virus resistance, post transcriptional gene silencing and crop improvement by genetic engineering to an agronomically important perennial monocot.


Practical application of bioinformatics by the multidisciplinary VIZIER consortium.
This review focuses on bioinformatics technologies employed by the EU-sponsored multidisciplinary VIZIER consortium (Comparative Structural Genomics of Viral Enzymes Involved in Replication, FP6 PROJECT: 2004-511960, active from 1 November 2004 to 30 April 2009), to achieve its goals. From the management of the information flow of the project, to bioinformatics-mediated selection of RNA viruses and prediction of protein targets, to the analysis of 3D protein structures and antiviral compounds, these technologies provided a communication framework and integrated solutions for steady and timely advancement of the project. RNA viruses form a large class of major pathogens that affect humans and domestic animals. Such RNA viruses as HIV, Influenza virus and Hepatitis C virus are of prime medical concern today, but the identities of viruses that will threaten human population tomorrow are far from certain. To contain outbreaks of common or newly emerging infections, prototype drugs against viruses representing the Virus Universe must be developed. This concept was championed by the VIZIER project which brought together experts in diverse fields to produce a concerted and sustained effort for identifying and validating targets for antivirus therapy in dozens of RNA virus lineages.


Use of in vivo real-time optical imaging for esophageal neoplasia.
Esophageal adenocarcinoma carries a poor prognosis, as it typically presents at a late stage. Thus, a major research priority is the development of novel diagnostic-imaging strategies that can detect neoplastic lesions earlier and more accurately than current techniques. Advances in optical imaging allow clinicians to obtain real-time histopathologic information with instant visualization of cellular architecture and the potential to identify neoplastic tissue. The various endoscopic imaging modalities for esophageal neoplasia can be grouped into 2 major categories: (1) wide-field imaging, a comparatively lower-resolution view for imaging larger surface areas, and (2) high-resolution imaging, which allows individual cells to be visualized. This review will provide an overview of the various forms of real-time optical imaging in the diagnosis and management of Barrett's esophagus and esophageal adenocarcinoma.


Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau.
Alzheimer's disease (AD) is a neurodegenerative disease with a high incidence rate. The main pathological features of AD are β-amyloid plaques (APs), which are formed by β-amyloid protein (Aβ) deposition, and neurofibrillary tangles (NFTs), which are formed by the excessive phosphorylation of the tau protein. Although a series of studies have shown that the accumulation of metal ions, including calcium ions (Ca2+), can promote the formation of APs and NFTs, there is no systematic review of the mechanisms by which Ca2+ affects the development and progression of AD. In view of this, the current review summarizes the mechanisms by which Ca2+ is transported into and out of cells and organelles, such as the cell, endoplasmic reticulum, mitochondrial and lysosomal membranes to affect the balance of intracellular Ca2+ levels. In addition, dyshomeostasis of Ca2+ plays an important role in modulating the pathogenesis of AD by influencing the production and aggregation of Aβ peptides and tau protein phosphorylation and the ways that disrupting the metabolic balance of Ca2+ can affect the learning ability and memory of people with AD. In addition, the effects of these mechanisms on the synaptic plasticity are also discussed. Finally, the molecular network through which Ca2+ regulates the pathogenesis of AD is introduced, providing a theoretical basis for improving the clinical treatment of AD.


[Infiltration of India ink from subarachnoid space to nasal mucosa along olfactory nerves in rabbits].
The mode of the transportation of India ink to the nasal cavity was studied when it was given to the subarachnoid space chiefly through facial nerve sheath and partly by cisterna magna injection. From subarachnoid space India ink infiltrated through perineurium, epineurium and perineural space of the fila olfactoria and of olfactory nerve fibers to lamina propria of the olfactory mucosa and spread also to the respiratory mucosa. It was further taken into lymphatic vessels and accumulated in bilateral cervical lymph nodes. In normal rabbits, India ink didn't penetrate the basement membrane into the epithelial layer at all, but in rabbits with chronic rhinitis showing edema, degeneration and destruction of mucosa, India ink was found to pass easily through the basement membrane into the epithelial layer and further to leak into the nasal cavity in all cases. It was a new finding that in cases with rhinitis large particles like India ink could infiltrate from the subarachnoid space to the nasal cavity passing through the nasal mucosa, and was considered to be a possible cause of idiopathic cerebrospinal fluid rhinorrhea.


Does Vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes?
Despite recent reports linking vitamin D deficiency with increased risk of diabetes mellitus and complications, there is limited data on patients with diabetic peripheral neuropathy. We aimed to evaluate the incidence and associations of vitamin D deficiency in 210 patients with Type 2 diabetes with and without diabetic peripheral neuropathy. Renal, liver, lipid profile and HbA(1c) were measured. Vitamin D status was determined by measuring 25-dihydroxyvitamin D. Presence or absence of coronary heart disease was determined and early-morning urine microalbumin:creatinine ratio was measured. All patients were assessed clinically using neuropathy symptom score, neuropathy disability score and nerve conduction study. Eighty-seven patients had diabetic peripheral neuropathy and these patients had significantly longer duration of diabetes and higher HbA(1c). Age, gender, incidence of retinopathy and coronary heart disease were not significantly different from those without neuropathy. Mean (SD) vitamin D was significantly lower in those with neuropathy [36.9 (39.9) nmol/l] compared with those without [58.32 (58.9) nmol/l] and 81.5% of patients with neuropathy had vitamin D deficiency compared with 60.4% of those without. Vitamin D showed significant (P < 0.05) correlations with total cholesterol, LDL-cholesterol and urine microalbumin:creatinine ratio. Binary logistic regression analysis showed that diabetic peripheral neuropathy was significantly associated with vitamin D deficiency (odds ratio = 3.47; 95% CI = 1.04-11.56, P = 0.043) after inclusion of potential confounders such as duration of diabetes, HbA(1c) and LDL-cholesterol. Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy, and further studies are required to confirm if Vitamin D supplementation could prevent or delay the onset.


[Cardiac conduction abnormalities after neoadjuvant chemotherapy with doxorubicin and docetaxel for primary breast carcinoma: a case report].
A 65-year-old woman with primary breast carcinoma (T 3 N 0 M 0) received neoadjuvant chemotherapy consisting of 4 cycles of 50 mg.m-2 doxorubicin (ADM) and 60 mg.m-2 docetaxel (TXT). The patient received 50 mg.m-2 ADM and 60 mg.m-2 TXT intravenously on day 1 of each cycle every three weeks. The patient underwent transthoracic echocardiography and electrocardiography (ECG) before surgery and these results were normal. ECG showed bigeminy, trigeminy after intubation and incomplete AV block (Mobitz type II) during and after surgery. The patient recovered from these arrhythmias on the first postoperative day. Our data indicate one possibility that the management of anesthetic condition might easily induce the cardiac conduction abnormalities of this patient using ADM as neoadjuvant chemotherapy.


Dental implants--isn't it about time?
Long-term studies indicate that dental implants are the most successful restorations fabricated and placed by dentists; however, only 30 percent of the dentists in this country restore implants on a regular basis. This article provides a six-step process for adding implant restoration to the regular services general practitioners provide for patients.


Franckeite as a naturally occurring van der Waals heterostructure.
The fabrication of van der Waals heterostructures, artificial materials assembled by individual stacking of 2D layers, is among the most promising directions in 2D materials research. Until now, the most widespread approach to stack 2D layers relies on deterministic placement methods, which are cumbersome and tend to suffer from poor control over the lattice orientations and the presence of unwanted interlayer adsorbates. Here, we present a different approach to fabricate ultrathin heterostructures by exfoliation of bulk franckeite which is a naturally occurring and air stable van der Waals heterostructure (composed of alternating SnS2-like and PbS-like layers stacked on top of each other). Presenting both an attractive narrow bandgap (<0.7 eV) and p-type doping, we find that the material can be exfoliated both mechanically and chemically down to few-layer thicknesses. We present extensive theoretical and experimental characterizations of the material's electronic properties and crystal structure, and explore applications for near-infrared photodetectors.


Do Primary Care Physicians Contribute to the Immunization Status of Their Adult Patients? A Story of Patients' Overconfidence Coupled With Physicians' Passivity.
Context: Immunization coverage counts among the priorities of public health services. To identify factors that motivate or fail to motivate patients to update their vaccination status would help to design future strategies and awareness campaigns. Objective: Our aim was to assess the impact of primary care physicians on the immunization status of their adult patients, and to explore possible explanations. Methods: We invited students and collaborators of Geneva University to bring their paper vaccination records to receive an assessment of their immunization status and personalized vaccination recommendations. Participants completed a first questionnaire at the recruitment phase, and a second 2-3 months later. We assessed their immunization status with the viavac algorithms based on the Swiss national immunization plan. Results: Having a primary care physician did not correlate with better immunization status: only 22.5% patients who reported having a physician and 20% who reported having no physician were up-to-date (n = 432; p > 0.5). A linear regression indicates that the frequency of medical consultations did not affect patients' immunization status either. Even the participants who recently showed their vaccination record to their primary care physician did not have a better vaccination status. We explored possible explanatory factors and found evidence for the patients' overconfidence about their own immunization status: 71.2% of the participants who predicted that they were up-to-date were wrong about their actual status, and 2-3 months after having received their immunization assessment, 52.8% of the participants who "remembered" having received the assessment that they were up-to-date were wrong: they had in fact received the opposite information that they were not up-to-date. This substantial proportion of wrong beliefs suggests that adult patients are unworried and overconfident about their own immunization status, which is likely to induce a passive resistance toward vaccination updating. Conclusions: This study indicates that the vaccination coverage and beliefs of adults about their immunization status is suboptimal, and that primary care physicians need further support to improve their health-protection mandate through routine immunization check-ups. We highlight that the current covid vaccination campaigns offer a rare opportunity to update patients' immunization status and urge physicians to do so.


Sulfonamide allergies and outcomes related to use of potentially cross-reactive drugs in hospitalized patients.
To characterize patient-reported sulfonamide allergies, assess the influence of these allergies on drug prescribing practices, and determine the frequency and nature of adverse reactions in patients with sulfonamide allergies who receive potentially cross-reactive drugs. Prospective observational study. Tertiary care hospital. Ninety-four hospitalized adult patients with reported sulfonamide allergies. Patients were followed during their hospital stay to document prescribing of and adverse reactions to sulfonamide antibiotics and sulfonamide nonantibiotics. Allergy characteristics and prescribing of sulfonamide-containing drugs were analyzed with descriptive statistics. Trimethoprim-sulfamethoxazole (TMP-SMX) allergy was reported by 42 patients (45%), whereas 42 patients (45%) did not recall the drug to which they were allergic. Fifty-nine patients (63%) reported the allergy's physical manifestation as rash, 13 (14%) anaphylaxis, and 2 (2)% Stevens-Johnson's syndrome. Median time since last reported allergic reaction to a sulfonamide-containing agent was 20 years. Forty patients (43%) had been taking a sulfonamide nonantibiotic as an outpatient for an average of 6.2 years; 24 (60%) of those patients took furosemide. Sixteen (40%) of the patients receiving sulfonamide nonantibiotics reported an allergy to TMP-SMX. Nine patients (10%) with no past sulfonamide nonantibiotic use received a sulfonamide nonantibiotic as an inpatient, with furosemide most commonly prescribed. No adverse events were reported before admission or observed during the inpatient stay (range 2-23 days). Inpatient and outpatient use of potentially cross-reactive drugs was observed in 52% of patients, although numerous patients were unable to give an accurate allergy history. No adverse effects were reported or documented with outpatient or inpatient sulfonamide nonantibiotic use, even among patients with histories of life-threatening reactions to sulfonamides.


Synthetic aperture rainbow refractometry.
This work proposed a synthetic aperture rainbow refractometry (SARR) by synthesizing rainbow signals of the same droplet with dual-wavelength laser beams, in order to increase the aperture of rainbow refractometry. In this way, the SARR can apply to long distance and small droplets measurement. An achromatic imaging system, which simultaneously records while separating the two rainbow signals in two channels of a color image, is elaborately designed. A data processing algorithm is developed to retrieve the optimal droplet refractive index and size. Numerical simulations of different droplet sizes from 10 μm to 200 μm certify the viability of the SARR. Proof-of-concept experiments of micron-sized ethanol droplets are performed with 1650 mm measurement distance. Results show that the SARR can accurately measure droplet refractive index and size with uncertainties of 2.3 × 10-4 and 2μm, respectively. The feasibility and accuracy of the proposed SARR are successfully demonstrated, paving the way for rainbow refractometry applied to large-scale industrial applications.


Targeting host DEAD-box RNA helicase DDX3X for treating viral infections.
DDX3X or DDX3, a member of the DEAD (asp, glu, ala, asp) box RNA helicase family of proteins, is a multifunctional protein, which is usurped by several viruses and is vital to their production. To date, 18 species of virus from 12 genera have been demonstrated to be dependent on DDX3 for virulence. In addition, DDX3 has been shown to function within 7 of 10 subcellular regions that are involved in the metabolism of viruses. As such, due to its direct interaction with viral components across most or all stages of viral life cycles, DDX3 can be considered an excellent host target for pan-antiviral drug therapy and has been reported to be a possible broad-spectrum antiviral target. Along these lines, it has been demonstrated that treatment of virally infected cells with small molecule inhibitors of DDX3 blunts virion productions. On the other hand, DDX3 bolsters an innate immune response and viruses have evolved capacities to sequester or block DDX3, which dampens an innate immune response. Thus, enhancing DDX3 production or co-targeting direct viral products that interfere with DDX3's modulation of innate immunity would also diminish virion production. Here we review the evidence that supports the hypothesis that modulating DDX3's agonistic and antagonistic functions during viral infections could have an important impact on safely and efficiently subduing a broad-spectrum of viral infections.


Heterogeneity in chronic myeloid leukaemia dynamics during imatinib treatment: role of immune responses.
Previous studies have shown that during imatinib therapy, the decline of chronic myeloid leukaemia BCR-ABL transcript numbers involves a fast phase followed by a slow phase in averaged datasets. Drug resistance leads to regrowth. In this paper, variation of treatment responses between patients is examined. A significant positive correlation is found between slopes of the fast and the slow phase of decline. A significant negative correlation is found between slopes of the slow phase of decline and the regrowth phase. No correlation is found between slopes of the fast phase of decline and the regrowth phase. A mathematical model that is successfully fitted to diverse clinical profiles explains these correlations by invoking the immune response as a key determinant of tumour decline during treatment. Boosting immunity during drug therapy could enhance the response to treatment in patients.


Levodopa-dyskinesia incidence by age of Parkinson's disease onset.
We assessed the 5-year risk of levodopa-induced dyskinesias by age of Parkinson's disease (PD) onset in a population-based cohort. The medical records linkage system of the Rochester Epidemiology project was used to identify residents of Olmsted County, Minnesota, with incident PD for the period 1976 through 1990. In this population-based study, the 5-year dyskinesia incidence declined with age. With PD onset after 70 years of age, the incidence was 16%. With onset from 40 to 59 years of age, the incidence was higher at 50%. These incidence data may overestimate the functional importance, because patients with minimal or reversible dyskinesias were counted.


Theoretical study on the isomeric structures and the stability of silylenoid (Tsi)Cl2SiLi (Tsi = C(SiMe3)3).
The structures and isomerization of silylenoid (Tsi)Cl(2)SiLi (Tsi = C(SiMe(3))(3)) were studied by density functional theory (DFT) at the B3LYP/6-31G(d) level. Four equilibrium structures and three isomeric transition states were located. The three-membered ring and p-complex structures, 1 and 2, are the two most stable forms. Two other local minima, the sigma-complex 3 and tetrahedron structure 4, should rearrange to 1 with very low barriers, and then to the most stable isomer 2. To exploit further the stability of silylenoid (Tsi)Cl(2)SiLi, the insertion reactions of 2 and silylene (Tsi)ClSi into the HF molecule have been investigated at the B3LYP/6-31G(d) level, respectively. The results show that the insertion of 2 into HF is very similar to that of (Tsi)ClSi into HF, but the latter is more favorable. To probe the influence of the substituent Tsi on the stability of silylenoid (Tsi)Cl(2)SiLi, the isomers and insertion reaction of silylenoid CH(3)Cl(2)SiLi were investigated in a similar way of those with (Tsi)Cl(2)SiLi. The results indicate that silylenoid containing very bulky group Tsi exhibits unusual stability because of the severe steric hindrance produced by Tsi at the center to which it is attached.


Modeling Individual Patient Count/Rate Data over Time with Applications to Cancer Pain Flares and Cancer Pain Medication Usage.
The purpose of this article is to investigate approaches for modeling individual patient count/rate data over time accounting for temporal correlation and non-constant dispersions while requiring reasonable amounts of time to search over alternative models for those data. This research addresses formulations for two approaches for extending generalized estimating equations (GEE) modeling. These approaches use a likelihood-like function based on the multivariate normal density. The first approach augments standard GEE equations to include equations for estimation of dispersion parameters. The second approach is based on estimating equations determined by partial derivatives of the likelihood-like function with respect to all model parameters and so extends linear mixed modeling. Three correlation structures are considered including independent, exchangeable, and spatial autoregressive of order 1 correlations. The likelihood-like function is used to formulate a likelihood-like cross-validation (LCV) score for use in evaluating models. Example analyses are presented using these two modeling approaches applied to three data sets of counts/rates over time for individual cancer patients including pain flares per day, as needed pain medications taken per day, and around the clock pain medications taken per day per dose. Means and dispersions are modeled as possibly nonlinear functions of time using adaptive regression modeling methods to search through alternative models compared using LCV scores. The results of these analyses demonstrate that extended linear mixed modeling is preferable for modeling individual patient count/rate data over time, because in example analyses, it either generates better LCV scores or more parsimonious models and requires substantially less time.


Suspended Metasurface for Broadband High-Efficiency Vortex Beam Generation.
Electromagnetic (EM) waves carrying orbital angular momentum (OAM) exhibit phase vortex and amplitude singularity. Broadband OAM generation with high efficiency is highly desired with suggested applications such as broadband imaging and communications. In this paper, suspended metasurface structure achieving low-Q factor is proposed to realize broadband phase control and excellent reflection efficiency. Broadband vortex beam generation with OAM order of 1 and 2 are realized using the proposed suspended structure. Furthermore, by analyzing different metasurface aperture phase distribution schemes, the efficiency of the OAM generator is maximally achieved. The designs are validated by simulation and measurement. The proposed OAM generators work across 4-10 GHz with efficiency higher than 82%. This design provides a route to broadband metasurface realization and high efficiency OAM generation.


On the Mechanism of Connecting Deltahedral Zintl Clusters via Conjugated Buta-1,3-dien-1,4-diyl Functionalities: Synthesis and Structure of [Ge9 -CH=CH-CH=CH-Ge9 ]6.
We report on the synthesis and structure, as well as on the mechanism of formation of the [Ge9 -CH=CH-CH=CH-Ge9 ]6- unit. As shown by in situ NMR spectroscopy (1 H, COSY, HSQC, HMBC), both (1Z,3Z)- and (1E,3Z)-[Ge9 -CH=CH-CH=CH-Ge9 ]6- are formed during the reaction of a mixture of 1,4-bis(trimethylsilyl)butadiyne and A4 Ge9 (A=K, Rb) with ethylenediamine. However, upon layering of the obtained solution with 222-crypt/toluene (222-crypt=4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo-[8.8.8]hexacosan) only the (1Z,3Z)-isomer crystallizes as {[A(222-crypt)]6 [(1Z,3Z)-(Ge9 -CH=CH-CH=CH-Ge9 )]}(tol)2 (en)2 (A=K, Rb) salts. Single crystals of these salts were characterized by X-ray structure analysis and Raman spectroscopy, indicating the presence of three superimposed conformers of (1Z,3Z)-[Ge9 -CH=CH-CH=CH-Ge9 ]6- , which show different orientations of the cluster units with respect to the planar (1Z,3Z)-buta-1,3-dien-1,4-diyl linker unit.


[Detection and significance of IL-6 and TNF-α in patients with Graves disease and periodontitis].
To investigate the expression of IL-6 and TNF-α in gingival crevicular fluid (GCF) and serum of patients with Graves' disease(GD) and periodontitis (CP), and to analyze the correlation between Graves' disease and periodontitis. One hundred and twenty subjects were selected and divided into 4 groups: 30 healthy participants as the control group, 30 patients with CP, 30 patients with GD, and 30 patients with GD and CP. The serum and GCF level of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA), and clinical periodontal parameters including probing depth (PD), clinical attachment level (CAL) and sulcus bleeding indexes (SBI) were examined. The date was analyzed with SPSS19.0 software package. The concentration of IL-6 and TNF-α in serum and GCF of patients with GD+CP group was significantly higher than that in CP group and GD group (P<0.05). The level of IL-6 and TNF-α in serum and GCF of patients in GD+CP group and GD group was positively correlated with FT3 and FT4 (P<0.05), and the correlation between GD+CP group was significantly higher than that in GD group. The level of IL-6 and TNF-α in GD+CP group were significantly higher than those in CP group and GD group, indicating that there is an interaction between periodontitis and Graves' disease in immune mechanism.


Identification of substrates of the Mycobacterium tuberculosis proteasome.
The putative proteasome-associated proteins Mpa (Mycobaterium proteasomal ATPase) and PafA (proteasome accessory factor A) of the human pathogen Mycobacterium tuberculosis (Mtb) are essential for virulence and resistance to nitric oxide. However, a direct link between the proteasome protease and Mpa or PafA has never been demonstrated. Furthermore, protein degradation by bacterial proteasomes in vitro has not been accomplished, possibly due to the failure to find natural degradation substrates or other necessary proteasome co-factors. In this work, we identify the first bacterial proteasome substrates, malonyl Co-A acyl carrier protein transacylase and ketopantoate hydroxymethyltransferase, enzymes that are required for the biosynthesis of fatty acids and polyketides that are essential for the pathogenesis of Mtb. Maintenance of the physiological levels of these enzymes required Mpa and PafA in addition to proteasome protease activity. Mpa levels were also regulated in a proteasome-dependent manner. Finally, we found that a conserved tyrosine of Mpa was essential for function. Thus, these results suggest that Mpa, PafA, and the Mtb proteasome degrade bacterial proteins that are important for virulence in mice.


Interactions of liposomes with human erythrocyte ghosts.
Interactions between human erythrocyte ghosts and small unilamellar vesicles consisting of various lipids and containing high intravesicular concentrations of calcein were studied. The entrapped marker leaked out under the influence of erythrocyte ghost in dependence on ghost and vesicle concentration, phospholipid composition as well as cholesterol content of the liposomes. Small unilamellar vesicles composed of sphingomyelin/cholesterol mixtures at a molar ratio of 1:1 are less permeable than those prepared from other phospholipids in the presence of erythrocyte ghosts. The amount of ghost associated liposomal lipid was measured by addition of cholesteryl [14C]oleate. It was shown to be minimal compared to the transfer of [14C]cholesterol between liposomes and ghosts. The half-time of the transfer process was also increased by incorporation of sphingomyelin into the liposomes, the retarding effect being apparent at levels of 5 mol% sphingomyelin.


Is it really myositis? A consideration of the differential diagnosis.
The idiopathic inflammatory myopathies are an important and treatable group of disorders. However, the potential toxicity associated with the immune therapeutic regimens used to treat these disorders may be significant; therefore, accurate diagnosis before such treatment is essential. The differential diagnosis is potentially large. Accurate diagnosis usually depends on a combination of careful clinical assessment in conjunction with detailed laboratory investigations. Muscle biopsy remains essential in achieving an accurate diagnosis that will then guide treatment. This review describes the diagnostic approach used. There has been debate over the requirements for an accurate diagnosis of inflammatory myopathy (i.e., polymyositis and dermatomyositis). It is increasingly recognized that there can be clinical and muscle histopathologic overlap between the features of inflammatory myopathies and those of other muscle disorders, in particular, the genetic muscular dystrophies. Pathologic findings of inflammation and major histocompatibility complex upregulation, although typical of inflammatory myopathies, have been shown to occur in some muscular dystrophies, complicating the diagnostic process. Inclusion body myositis is much less responsive to immunotherapy and is now recognized as the most common acquired muscle disease in those older than 50 years of age. It is likely that genetic muscular dystrophies and inclusion body myositis account for some cases of apparently "treatment-resistant" myositis. A thorough clinical assessment, including a detailed family history, complemented by electromyography and creatine kinase measurements, should be undertaken in any patient with presumed idiopathic inflammatory myopathy. In addition, a muscle biopsy remains essential in all cases. A precise tissue diagnosis confirming features of an active inflammatory process should be achieved before immunosuppressive treatment is commenced. An increasing array of immunocytochemical and histioenzymatic stains now allows a full analysis and will help to confirm or exclude virtually all the differential diagnostic possibilities considered in this review. Electron microscopy may also be valuable in selected cases. Close collaboration between clinicians and muscle pathologists is essential in allowing the most accurate interpretation of myopathologic findings in the clinical context.


Distribution of zeranol in bovine tissues determined by selected ion monitoring capillary gas chromatography/mass spectrometry.
Bovine tissues, including liver, muscle, kidney, bile, serum, and urine, have been quantified by selected ion monitoring capillary gas chromatography/mass spectrometry to establish the distribution of the anabolic drug, zeranol, and its metabolites, taleranol and zearalanone, after administration of zeranol to 9 bovine animals. The method used to isolate, confirm, and quantify zeranol is undergoing validation by the United States Department of Agriculture, Food Safety Inspection Service (FSIS). Application of this method demonstrates utility in determining residue levels of zeranol in a variety of tissues with levels ranging over 4 orders of magnitude (i.e., 100 parts per trillion (ppt) to 1 part per million (ppm]. The analyte levels determined in this study complement previously reported pharmacokinetic data on the distribution of zeranol in addition to providing more specific information for taleranol and zearalanone. In this quantitative study it is shown that the liver is the main organ of deposition for zeranol, taleranol, and zearalanone, that taleranol is the main metabolite in the bovine, and that zeranol is efficiently eliminated.


A prototypic small molecule database for bronchoalveolar lavage-based metabolomics.
The analysis of bronchoalveolar lavage fluid (BALF) using mass spectrometry-based metabolomics can provide insight into lung diseases, such as asthma. However, the important step of compound identification is hindered by the lack of a small molecule database that is specific for BALF. Here we describe prototypic, small molecule databases derived from human BALF samples (n=117). Human BALF was extracted into lipid and aqueous fractions and analyzed using liquid chromatography mass spectrometry. Following filtering to reduce contaminants and artifacts, the resulting BALF databases (BALF-DBs) contain 11,736 lipid and 658 aqueous compounds. Over 10% of these were found in 100% of samples. Testing the BALF-DBs using nested test sets produced a 99% match rate for lipids and 47% match rate for aqueous molecules. Searching an independent dataset resulted in 45% matching to the lipid BALF-DB compared to<25% when general databases are searched. The BALF-DBs are available for download from MetaboLights. Overall, the BALF-DBs can reduce false positives and improve confidence in compound identification compared to when general databases are used.


Ability of monophosphoryl lipid A to augment the antibody response of young mice.
Treatment with nontoxic monophosphoryl lipid A increased the magnitude of the immunoglobulin M (IgM) antibody response to type III pneumococcal polysaccharide in young (2- to 4-week-old) mice. This was accompanied by the appearance of significant numbers of IgG1- and IgG3- secreting antibody-forming cells in 4-week-old mice. These findings indicate that monophosphoryl lipid A can be used as an adjuvant to improve the immunogenicity of poorly immunogenic antigens in young, immunologically immature animals.


Robotic Biofeedback for Post-Stroke Gait Rehabilitation: A Scoping Review.
This review aims to recommend directions for future research on robotic biofeedback towards prompt post-stroke gait rehabilitation by investigating the technical and clinical specifications of biofeedback systems (BSs), including the complementary use with assistive devices and/or physiotherapist-oriented cues. A literature search was conducted from January 2019 to September 2022 on Cochrane, Embase, PubMed, PEDro, Scopus, and Web of Science databases. Data regarding technical (sensors, biofeedback parameters, actuators, control strategies, assistive devices, physiotherapist-oriented cues) and clinical (participants' characteristics, protocols, outcome measures, BSs' effects) specifications of BSs were extracted from the relevant studies. A total of 31 studies were reviewed, which included 660 stroke survivors. Most studies reported visual biofeedback driven according to the comparison between real-time kinetic or spatiotemporal data from wearable sensors and a threshold. Most studies achieved statistically significant improvements on sensor-based and clinical outcomes between at least two evaluation time points. Future research should study the effectiveness of using multiple wearable sensors and actuators to provide personalized biofeedback to users with multiple sensorimotor deficits. There is space to explore BSs complementing different assistive devices and physiotherapist-oriented cues according to their needs. There is a lack of randomized-controlled studies to explore post-stroke stage, mental and sensory effects of BSs.


Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis.
Despite continuous medical advances, atherosclerosis remains the prime cause of mortality worldwide. Emerging findings on brown and beige adipocytes highlighted that these fat cells share the specific ability of non-shivering thermogenesis due to the expression of uncoupling protein 1. Brown fat is established during embryogenesis, and beige cells emerge from white adipose tissue exposed to specific stimuli like cold exposure into a process called browning. The consecutive energy expenditure of both thermogenic adipose tissues has shown therapeutic potential in metabolic disorders like obesity and diabetes. The latest data suggest promising effects on atherosclerosis development as well. Upon cold exposure, mice and humans have a physiological increase in brown adipose tissue activation and browning of white adipocytes is promoted. The use of drugs like β3-adrenergic agonists in murine models induces similar effects. With respect to atheroprotection, thermogenic adipose tissue activation has beneficial outcomes in mice by decreasing plasma triglycerides, total cholesterol and low-density lipoproteins, by increasing high-density lipoproteins, and by inducing secretion of atheroprotective adipokines. Atheroprotective effects involve an unaffected hepatic clearance. Latest clinical data tend to find thinner atherosclerotic lesions in patients with higher brown adipose tissue activity. Strategies for preserving healthy arteries are a major concern for public health.


Streptavidin-biotin binding in the presence of a polymer spacer. A theoretical description.
The binding of streptavidin to biotin located at the terminal ends of poly(ethylene oxide) tethered to a planar surface is studied using molecular theory. The theoretical model is applied to mimic experiments (Langmuir 2008, 24, 2472) performed using drop-shape analysis to study receptor-ligand binding at the oil/water interface. Our theoretical predictions show very good agreements with the experimental results. Furthermore, the theory enables us to study the thermodynamic and structural behavior of the PEO-biotin + streptavidin layer. The interfacial structure, shown by the volume fraction profiles of bound proteins and polymers, indicates that the proteins form a thick layer supported by stretched polymers, where the thickness of the layer is greater than the height of the protein. When the polymer spacer is composed of PEO (3000), a thick layer with multilayers of proteins is formed, supported by the stretched polymer chains. It was found that thick multilayers of proteins are formed when long spacers are present or at very high protein surface coverages on short spacers. This shows that the flexibility of the polymer spacer plays an important role in determining the structure of the bound proteins due to their ability to accommodate highly distorted conformations to optimize binding and protein interactions. Protein domains are predicted when the amount of bound proteins is small due to the existence of streptavidin-streptavidin attractive interactions. As the number of proteins is increased, the competition between attractive interactions and steric repulsions determines the stability and structure of the bound layer. The theory predicts that the competition between these two forces leads to a phase separation at higher protein concentrations. The point where this transition happens depends on both spacer length and protein surface coverage and is an important consideration for practical applications of these and other similar systems. If the goal is to maximize protein binding, it is favorable to be above the layer transition, as multiple layers can accommodate greater bound protein densities. On the other hand, if the goal is to use these bound proteins as a linker group to build more complex structures, such as when avidin or streptavidin serves as a linker between two biotinylated polymers or proteins, the optimum is to be below the layer transition such that all bound linker proteins are available for further binding.


Clinical and Translational Significance of Basophils in Patients with Cancer.
Despite comprising a very small proportion of circulating blood leukocytes, basophils are potent immune effector cells. The high-affinity receptor for IgE (FcɛRI) is expressed on the basophil cell surface and powerful inflammatory mediators such as histamine, granzyme B, and cytokines are stored in dense cytoplasmic granules, ready to be secreted in response to a range of immune stimuli. Basophils play key roles in eliciting potent effector functions in allergic diseases and type 1 hypersensitivity. Beyond allergies, basophils can be recruited to tissues in chronic and autoimmune inflammation, and in response to parasitic, bacterial, and viral infections. While their activation states and functions can be influenced by Th2-biased inflammatory signals, which are also known features of several tumor types, basophils have received little attention in cancer. Here, we discuss the presence and functional significance of basophils in the circulation of cancer patients and in the tumor microenvironment (TME). Interrogating publicly available datasets, we conduct gene expression analyses to explore basophil signatures and associations with clinical outcomes in several cancers. Furthermore, we assess how basophils can be harnessed to predict hypersensitivity to cancer treatments and to monitor the desensitization of patients to oncology drugs, using assays such as the basophil activation test (BAT).


Preparation of diastereomerically pure dilignol model compounds.
A gram-scale synthetic access to diastereomerically pure dilignol β-O-4 type model compounds, which represent valuable candidates for studies of lignin cleavage and valorization, is described. Following a straightforward procedure both diastereoisomers of 1,3-dilignols can be prepared. In the key-step, tert-butyl aryloxy esters are used as enolate precursors for additions on aldehydes. After separation, the resulting erythro and threo β-hydroxy esters are independently reduced to afford the target compounds in high yields.


Intestinal blood flow and oxygen consumption: responses to hemorrhage in the developing piglet.
Age-related differences in the intestinal hemodynamic and oxygenation responses to arterial hemorrhage were studied in anesthetized and ventilated 1-d, 3-d, 1-wk, and 2-wk-old piglets. Steady-state values of superior mesenteric blood flow, venous pressure, and arteriovenous oxygen difference were obtained before and after 5 and 10 mL/kg arterial hemorrhage. With 5 mL/kg hemorrhage, intestinal blood flow fell significantly below baseline values, but oxygen extraction increased to maintain oxygen uptake at control levels in all age groups. In contrast to 2-wk-old piglets, the intestine of 1-d, 3-d, and 1-wk-old animals could not compensate for the greater reduction in blood flow produced by 10 mL/kg hemorrhage, resulting in a significant reduction in oxygen uptake. Thus, the intestine of developing piglets up to 1 wk of age appears to be at greater risk for tissue hypoxia induced by arterial hemorrhage than that of older animals.


Wearable Sensors for Learning Enhancement in Higher Education.
Wearable sensors have traditionally been used to measure and monitor vital human signs for well-being and healthcare applications. However, there is a growing interest in using and deploying these technologies to facilitate teaching and learning, particularly in a higher education environment. The aim of this paper is therefore to systematically review the range of wearable devices that have been used for enhancing the teaching and delivery of engineering curricula in higher education. Moreover, we compare the advantages and disadvantages of these devices according to the location in which they are worn on the human body. According to our survey, wearable devices for enhanced learning have mainly been worn on the head (e.g., eyeglasses), wrist (e.g., watches) and chest (e.g., electrocardiogram patch). In fact, among those locations, head-worn devices enable better student engagement with the learning materials, improved student attention as well as higher spatial and visual awareness. We identify the research questions and discuss the research inclusion and exclusion criteria to present the challenges faced by researchers in implementing learning technologies for enhanced engineering education. Furthermore, we provide recommendations on using wearable devices to improve the teaching and learning of engineering courses in higher education.


L-arginine and free radical scavengers increase cerebral blood flow and brain tissue nitric oxide concentrations after controlled cortical impact injury in rats.
To examine the mechanism of the increase in cerebral blood flow induced by L-arginine administration after traumatic brain injury, the cerebral hemodynamic effects of L-arginine, D-arginine, and the free radical scavengers superoxide dismutase (SOD) and catalase were compared in the controlled cortical impact injury model in rats. Animals were anesthetized with isoflurane. Measured parameters included mean blood pressure, intracranial pressure, cerebral blood flow using laser Doppler flowmetry (LDF) and brain tissue nitric oxide (NO) concentrations using an NO electrode. L-arginine, but not D-arginine, administration resulted in a significant increase in tissue NO concentrations and an improvement in LDF at the impact site, compared to control animals given saline. Administration of SOD alone and in combination with catalase resulted in a significant increase in brain tissue NO concentrations. However, LDF was consistently improved only when both SOD and catalase were given. These studies support the theory that L-arginine administration improves post-traumatic cerebral blood flow by increasing NO production. Free radical production after trauma may also contribute to the reduction in CBF by inactivating NO.


Conformational stability, structural parameters and vibrational assignment from variable temperature infrared spectra of krypton solutions and ab initio calculations of ethylisothiocyanate.
Variable temperature (-105 to -150 degrees C) studies of the infrared spectra (3500-400 cm(-1)) of ethylisothiocyanate, CH(3)CH(2)NCS, dissolved in liquid krypton have been recorded. Additionally the infrared spectra of the gas and solid have been re-investigated. These spectroscopic data indicate a single conformer in all physical states with a large number of molecules in the gas phase at ambient temperature in excited states of the CN torsional mode which has a very low barrier to conformational interchange. To aid in the analyses of the vibrational and rotational spectra, ab initio calculations have been carried out by the perturbation method to the second order (MP2) with valence and core electron correlation using a variety of basis sets up to 6-311+G(2df,2pd). With the smaller basis sets up to 6-311+G(d,p) and cc-PVDZ, the cis conformer is indicated as a transition state with all larger basis sets the cis conformer is the only stable form. The predicted energy difference from these calculations between the cis form and the higher energy trans conformer is about 125 cm(-1) which represents essentially the barrier to internal rotation of the NCS group (rotation around NC axis). Density functional theory calculation by the B3LYP method with the same basis sets predicts this barrier to be about 25 cm(-1). By utilizing the previously reported microwave rotational constants with the structural parameters predicted by the ab initio MP2(full)/6-311+G(d,p) calculations, adjusted r(0) structural parameters have been obtained for the cis form. The determined heavy atom parameters are: r(NC)=1.196(5), r(CS)=1.579(5), r(CN)=1.439(5), r(CC)=1.519(5)A for the distances and angles of angleCCN=112.1(5), angleCNC=146.2(5), angleNCS=174.0(5) degrees . The centrifugal distortion constants, dipole moments, conformational stability, vibrational frequencies, infrared intensities and Raman activities have been predicted from ab initio calculations and compared to experimental quantities when available. These results are compared to the corresponding quantities of some similar molecules.


Perceptual load as a major determinant of the locus of selection in visual attention.
In this paper, we propose that the debate concerning the locus of attentional selection can be resolved by specifying the conditions under which early selection is possible. In the first part, we present a theoretical discussion that integrates aspects from structural and capacity approaches to attention and suggest that perceptual load is a major factor in determining the locus of selection. In the second part, we present a literature review that examines the conditions influencing the processing of irrelevant information. This review supports the conclusion that a clear physical distinction between relevant and irrelevant information is not sufficient to prevent irrelevant processing; early selection also requires that the perceptual load of the task be sufficiently high to exceed the upper limit of available attentional resources.


First Report of Leaf Spot Caused by Alternaria tenuissima on Panicle Hydrangea (Hydrangea paniculata) in China.
Panicle hydrangea (Hydrangea paniculata), belonging to the Saxifragaceae family (Wu et al. 2001), is an ornamental flowering plant which is native to China and Japan. In July 2021, brown leaf spots (diameter ranged from 3 to 5 mm) were observed on panicle hydrangea plants in a 0.1 ha field of Northeast Agriculture University (126.72°E, 45.74°N), Heilongjiang Province. The incidence was approximately 30%. Small circular or irregular brown spots initially appeared on the older leaves, and these lesions gradually expanded with time. In some serious cases, lesions joint together and caused leaf wilting. To identify the causal agent, ten symptomatic leaves from different panicle hydrangea plants were collected, and surface sterilized with 70% ethanol for 30 s, followed by 0.5% NaClO treatment for 4 min, and then rinsed with sterile water three times. Tissues between healthy and necrotic area were cut into 5×5 mm pieces after air drying on sterile filter paper. The pieces were placed on potato dextrose agar (PDA) amended with streptomycin sulfate (50 mg/liter) and incubated at 25°C for 5 days. Fifteen pure isolates were obtained using the hyphal tip technique and cultured on PDA for 7 days at 25°C for morphological and molecular identification. Colonies of all isolates were dark olivaceous with white margin. Conidiophores were septate, singly arising, and light brown, with a size range of 10.2-60.1 × 1.4-5.6 µm (n=50). Conidia were obclavate to obpyriform, brown to dark brown, and in a size range of 15.0-25.2 × 5.1-15.3 µm (n=50). To further identify these isolates, four different genomic DNA regions including ribosomal DNA internal transcribed spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNA polymerase II second largest subunit (rpb2), and histone 3 (HIS3) were amplified and sequenced with primers ITS1/ITS4 (White et al. 1990), gpd1/gpd2 (Berbee et al. 1999), RPB2-5F2/RPB2-7R (Sung et al. 2007), and H3-1a/H3-1b (Xu et al. 2022) for three representative isolates (DXQ2-2, DXQ2-3, and DXQ2-4), respectively. The sequences of ITS, GADPH, rpb2, and HIS3 for these three isolates were identical and only sequences of DXQ2-2 were deposited in GenBank (GenBank accession nos. OL305828, OL333601, OL333602, and OL436242). These sequences showed 100%, 100%, 100%, and 99.61% identity with A. tenuissima BJ-CX-1 (GenBank accession nos. MK683974, MK683784, MK684069, and MK683879), respectively. Based on morphological features and DNA sequences analyses, these isolates were identified as Alternaria tenuissima (Simmons 2007). To fulfill Koch's postulates, ten healthy and surface disinfected leaves of one panicle hydrangea plant grown in pot were sprayed with a conidial suspension (1×106 conidia/mL) of isolate DXQ2-2. Meanwhile, ten surface disinfected leaves of another panicle hydrangea plant grown in pot sprayed with sterilize water served as the control. All plants were maintained in a greenhouse at 25℃ and 70% relative humidity. Five days after inoculation, leaves inoculated with conidial suspension showed leaf spot symptoms that were similar to those observed in the field, whereas no symptom was observed on the control leaves. The experiment was conducted twice. The Alternaria tenuissima isolate was successfully re-isolated from the symptomatic leaves and confirmed based on above morphological and molecular methods. To our knowledge, this is the first report of leaf spot on panicle hydrangea caused by A. tenuissima. Leaf spot has a negative effect on the aesthetic value of panicle hydrangea, so further investigation and management is needed to control this disease.


Nutrition Care of Critically Ill Patients with Leukemia: A Retrospective Study.
Adults with acute leukemia (AL) are at high risk of malnutrition due to their disease and treatment side effects and may be admitted to the intensive care unit (ICU), further increasing the risk of malnutrition. Although ICU care includes some form of nutrition, patients typically receive less than prescribed energy and protein. Our objective was to characterize the nutrition care for critically ill patients with AL. We completed a retrospective review of adults with AL admitted to the Medical/Surgical ICU >24 hours. Descriptive statistics were performed on collected data including: demographics, APACHE II and Nutric scores, nutrition therapy, reasons for withholding nutrition, and mortality status at discharge. Data were collected on 154 AL patients with an average APACHE II score of 27 and Nutric score of 5.96. ICU mortality was 36%. Enteral nutrition (EN) was most commonly prescribed. Patients on EN received 55% of energy and 51% of protein prescribed. EN was commonly withheld for airway management and gastrointestinal impairment. Patients with AL received low amounts of energy and protein in the ICU and had a high Nutric score. Strategies and barriers to improve protein intake in this population are identified.


Managing invasive species in the presence of endogenous technological change with uncertainty.
This research incorporates the development and adoption of an induced technology under uncertainty into a conceptual dynamic model to more broadly examine efficient policies for mitigating invasive species infestations. We find that under optimal policy, marginal costs of adopting conventional control measures are equal to the sum of the marginal benefits from development and adoption of new technology, as well as the use of conventional control measures. This result implies that a resource allocation designed for controlling invasive species is not adequate when an induced technology is not considered. Our results also reveal that the shadow values associated with the probabilities of developing and then adopting an induced technology increase as the shadow values associated with the stock of an invasive species population increase.


Trend in light-induced excited-state spin trapping in Fe(II)-based spin crossover systems.
A computational study of the light-induced excited spin-state trapping (LIESST) in a number of Fe(II) spin crossover complexes, coordinated by monodentate, bidentate and multidentate ligands is carried out, with the goal to uncover the trend in the low temperature relaxation rate. A nine order of magnitude change in low temperature relaxation rate is observed among the complexes. The trend is rationalized in terms of the change in metal-ligand covalency, numerically estimated by the crystal orbital Hamiltonian population, thus influencing the back donation or delocalization of the electrons from the low-lying Fe(II)-centered molecular orbital to the empty low-lying ligand-centered π* antibonding molecular orbitals.


Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase.
Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 22.214.171.124) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris-HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl2 and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 A resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 A and four molecules in the asymmetric unit.


Angiomatous meningioma associated with rapidly aggravated peritumoral leptomeningitis: A case report.
A special type of meningioma is known to have infiltrated inflammatory cells within the tumor, associated with peritumoral inflammation. However, there have been no reports of meningioma with inflammatory response only around the tumor, without inflammatory cells within the tumor itself. A 70-year-old woman presented with transient right hemiparesis due to an extra-axial tumor on the left frontal convexity. The tumor appeared hypointense on T1-weighted magnetic resonance images and hyperintense on T2-weighted images without peritumoral edema, and was homogenously enhanced associated with the peritumoral leptomeningeal enhancement. Cerebrospinal fluid examination showed an increase in the number of inflammatory cells with a predominance of mononuclear cells. During the following 1 month, the tumor size was unchanged, but the peritumoral leptomeningeal enhancement was remarkably enlarged with uncontrolled focal seizures. The tumor was subtotally removed and semisolid substances in the subarachnoid space were biopsied. Pathological examination with immunostaining revealed angiomatous meningioma: the tumor had no inflammatory cell infiltration within it, but was associated with the infiltration of immunoglobulin G4-negative lymphocytes into the border zone between the tumor and the dura mater, as well as numerous neutrophils and fibrinous exudates in the peritumoral subarachnoid space. The tumor removal rapidly improved the leptomeningeal enhancement and inflammatory reactions. The authors reported the first case of angiomatous meningioma associated with massive peritumoral inflammation without inflammatory infiltrates within the tumor itself.


Implantation and pregnancy rates from vitrified embryos.
The main objective of this study was to evaluate the effectiveness of vitrification technique through embryo viability, embryo implantation rate and clinical pregnancy in patients undergoing controlled ovarian stimulation. Viable embryos of patients deriving from in vitro fertilization were vitrified using the protocol of Irvine Scientific by closed system. 28 cycles of freezing and thawing of embryos were evaluated during the periods from January 2010 to December 2012 in the Clinical Reproduction, Presidente Prudente - SP. Total of 176 embryos was frozen. The average number of frozen/thawed embryos per patient was 5, totaling 140 thawed embryos. These thawed embryos, 78,6% (110/140) displayed viable morphologically (at least 50% from intact blastomeres) and 75% (105/140) of thawed embryos were transferred. In 28 cycles in which there was transference, an average of 3.75 embryos were transferred per patient, from which resulted in 17 biochemical pregnancies and of these 8 pregnancies reached term (28,6%) and embryonic implantation rate was 20%. It can be concluded that the method of embryos vitrification is an effective technique, with high survival rate, allowing the storage of surplus embryos with satisfactory pregnancy rates in thawing cycles.


Modulation of the attentional span by foveal and parafoveal task load: An ERP study using attentional probes.
Due to capacity limitation, visual attention must be focused to a limited region of the visual field. Nevertheless, it is assumed that the size of that region may vary with task demands. We aimed to obtain direct evidence for the modulation of visuospatial attention as a function of foveal and parafoveal task load. Participants were required to fixate the center word of word triplets. In separate task blocks, either just the fixated word or both the fixated and the parafoveal word to the right should be semantically classified. The spatiotemporal distribution of attention was assessed with task-irrelevant probes flashed briefly at center or parafoveal positions, during or in between word presentation trials. The N1 component of the ERP elicited by intertrial probes at possible target positions increased with task demands within a block. These results suggest the recruitment of additional attentional resources rather than a redistribution of a fixed resource pool, which persists across trials.


A Pak- and Pix-dependent branch of the SDF-1alpha signalling pathway mediates T cell chemotaxis across restrictive barriers.
Pak (p21-activated kinase) serine/threonine kinases have been shown to mediate directional sensing of chemokine gradients. We hypothesized that Pak may also mediate chemokine-induced shape changes, to facilitate leucocyte chemotaxis through restrictive barriers, such as the extracellular matrix. A potent inhibitor, Pak(i), was characterized and used to probe the role of Pak-family kinases in SDF-1alpha (stromal-cell derived factor-1alpha/CXCL12)-induced chemotaxis in a T cell model. Pak(i) potently inhibited SDF-1alpha-induced Pak activation by a bivalent mechanism, as indicated by its complete inactivation upon point mutation of two binding sites, but partial inactivation upon mutation of either site alone. Importantly, Pak(i) was not toxic to cells over the time frame of our experiments, since it did not substantially affect cell surface expression of CXCR4 (CXC chemokine receptor 4) or integrins, cell cycle progression, or a number of ligand-induced responses. Pak(i) produced dose-dependent inhibition of SDF-1alpha-induced migration through rigid filters bearing small pores; but unexpectedly, did not substantially affect the magnitude or kinetics of chemotaxis through filters bearing larger pores. SDF-1alpha-induced Pak activation was partly dependent on PIX (Pak-interactive exchange factor); correspondingly, an allele of beta-PIX that cannot bind Pak inhibited SDF-1alpha-induced chemotaxis through small, but not large pores. By contrast, other key players in chemotaxis: G(i), PI3K (phosphoinositide 3-kinase), and the Rho-family G-proteins, Rac and Cdc42 (cell division cycle 42), were required for SDF-1alpha-induced migration regardless of the barrier pore-size. These studies have revealed a distinct branch of the SDF-1alpha signalling pathway, in which the Rac/Cdc42 effector, Pak, and its partner, PIX, specifically regulate the cellular events required for chemokine-induced migration through restrictive barriers.


Deciphering the role of microRNAs in mustard gas-induced toxicity.
Mustard gas (sulfur mustard, SM), a highly vesicating chemical warfare agent, was first deployed in warfare in 1917 and recently during the Iraq-Iran war (1980s) and Syrian conflicts (2000s); however, the threat of exposure from stockpiles and old artillery shells still looms large. Whereas research has been long ongoing on SM-induced toxicity, delineating the precise molecular pathways is still an ongoing area of investigation; thus, it is important to attempt novel approaches to decipher these mechanisms and develop a detailed network of pathways associated with SM-induced toxicity. One such avenue is exploring the role of microRNAs (miRNAs) in SM-induced toxicity. Recent research on the regulatory role of miRNAs provides important results to fill in the gaps in SM toxicity-associated mechanisms. In addition, differentially expressed miRNAs can also be used as diagnostic markers to determine the extent of toxicity in exposed individuals. Thus, in our review, we have summarized the studies conducted so far in cellular and animal models, including human subjects, on the expression profiles and roles of miRNAs in SM- and/or SM analog-induced toxicity. Further detailed research in this area will guide us in devising preventive strategies, diagnostic tools, and therapeutic interventions against SM-induced toxicity.


Critical role of Interleukin 21 and T follicular helper cells in hypertension and vascular dysfunction.
T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. T follicular helper (Tfh) cells that produce interleukin 21 (IL21) promote germinal center (GC) B cell responses leading to immunoglobulin (Ig) production. Here we investigate the role of IL21 and Tfh cells in hypertension. In response to angiotensin (Ang) II-induced hypertension, T cell IL21 production is increased, and Il21-/- mice develop blunted hypertension, attenuated vascular end-organ damage, and decreased interleukin 17A (IL17A) and interferon gamma production. Tfh-like cells and GC B cells accumulate in the aorta and plasma IgG1 is increased in hypertensive WT but not Il21-/-mice. Furthermore, Tfh cell deficient mice develop blunted hypertension and vascular hypertrophy in response to Ang II infusion. Importantly, IL21 neutralization reduces blood pressure (BP) and reverses endothelial dysfunction and vascular inflammation. Moreover, recombinant IL21 impairs endothelium-dependent relaxation ex vivo and decreases nitric oxide production from cultured endothelial cells. Finally, we show in humans that peripheral blood T cell production of IL21 correlates with systolic BP and IL17A production. These data suggest that IL21 may be a novel therapeutic target for the treatment of hypertension and its micro- and macrovascular complications.