Towards understanding assessments of the big five: multitrait-multimethod analyses of convergent and discriminant validity across measurement occasion and type of observer.
Multitrait-multimethod analyses were used to examine the degree of convergent and discriminant validity of the Big Five. Phase 1 examined self-reports of the Big Five across three measurement occasions. Self-reports of the Big Five traits were stable, but were moderately intercorrelated. Phase 2 examined assessments of the Big Five across different types of informants (self, peer, and parent). Assessments converged across types of informants and, importantly, there was no evidence of correlation between the Big Five traits across the perspectives of different types of informants. The present results suggest that the degree of orthogonality of the Big Five traits depends on the source of the data. A single informant produces Big Five traits that are intercorrelated, whereas diverse informants tend to produce a much more orthogonal structure. Discussion focuses on methodological considerations in examining levels of convergent and discriminant validity and the theoretical implications for understanding personality assessments and the relationship between three-and five-factor models of personality.


Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction.
Chemical systems that remain kinetically dormant until activated have numerous applications in materials science. Herein we present a method for the control of gelation that exploits an inbuilt switch: the increase in pH after an induction period in the urease-catalyzed hydrolysis of urea was used to trigger the base-catalyzed Michael addition of a water-soluble trithiol to a polyethylene glycol diacrylate. The time to gelation (minutes to hours) was either preset through the initial concentrations or the reaction was initiated locally by a base, thus resulting in polymerization fronts that converted the mixture from a liquid into a gel (ca. 0.1 mm min(-1)). The rate of hydrolytic degradation of the hydrogel depended on the initial concentrations, thus resulting in a gel lifetime of hours to months. In this way, temporal programming of gelation was possible under mild conditions by using the output of an autocatalytic enzyme reaction to drive both the polymerization and subsequent degradation of a hydrogel.


Hydrogeological study of an anti-tank range.
The Arnhem Anti-Tank Range (Canadian Forces Base [CFB] Valcartier, Canada, in operation since the 1970s) has been characterized, including the drilling, installation, and characterization of 25 wells and a ground-penetrating radar survey. The observed particular features of this site include highly variable flow velocities (from < 3 to 1200 m/yr) and transient flow regime in the regional aquifer below the contaminant source zone of the impact area, sharp flow direction shifts, discontinuous stratigraphy and a local perched aquifer. A transient ground water flow model permitted us to understand how the complex hydrogeological setting shapes contaminant transport in the regional aquifer. The model explains the highly variable energetic material (EM) concentrations measured in the plume with peaks associated to spring and to a lesser extent to fall recharge events. As a conclusion from this work, the authors suggest that the characterization of contaminant sources on slopes should extend over all seasons to be sure to detect potential transient flow conditions and variable contaminant concentrations.


Onycholysis associated with paclitaxel.
Chemotherapeutic agents are known to cause a myriad of cutaneous side effects that the dermatologist is often called upon to identify and treat. The taxoid drug paclitaxel is commonly used in oncology. To date, there have been few adverse dermatologic effects reported secondary to paclitaxel use. This is in contrast to the related drug docetaxel. We report a case in which paclitaxel caused onycholysis and nail loss in a patient being treated for lung cancer. To our knowledge, this finding has not previously been reported in the American dermatologic literature, though it has been reported in association with docetaxel use. It is important for clinicians to recognize that onycholysis can be associated with paclitaxel. Prompt recognition may prevent the unnecessary use of antibiotics or antifungal medications. Discontinuation of paclitaxel chemotherapy generally is not required, and regrowth of nails can be expected following completion of therapy.


Automated fibroglandular tissue segmentation and volumetric density estimation in breast MRI using an atlas-aided fuzzy C-means method.
Breast magnetic resonance imaging (MRI) plays an important role in the clinical management of breast cancer. Studies suggest that the relative amount of fibroglandular (i.e., dense) tissue in the breast as quantified in MR images can be predictive of the risk for developing breast cancer, especially for high-risk women. Automated segmentation of the fibroglandular tissue and volumetric density estimation in breast MRI could therefore be useful for breast cancer risk assessment. In this work the authors develop and validate a fully automated segmentation algorithm, namely, an atlas-aided fuzzy C-means (FCM-Atlas) method, to estimate the volumetric amount of fibroglandular tissue in breast MRI. The FCM-Atlas is a 2D segmentation method working on a slice-by-slice basis. FCM clustering is first applied to the intensity space of each 2D MR slice to produce an initial voxelwise likelihood map of fibroglandular tissue. Then a prior learned fibroglandular tissue likelihood atlas is incorporated to refine the initial FCM likelihood map to achieve enhanced segmentation, from which the absolute volume of the fibroglandular tissue (|FGT|) and the relative amount (i.e., percentage) of the |FGT| relative to the whole breast volume (FGT%) are computed. The authors' method is evaluated by a representative dataset of 60 3D bilateral breast MRI scans (120 breasts) that span the full breast density range of the American College of Radiology Breast Imaging Reporting and Data System. The automated segmentation is compared to manual segmentation obtained by two experienced breast imaging radiologists. Segmentation performance is assessed by linear regression, Pearson's correlation coefficients, Student's paired t-test, and Dice's similarity coefficients (DSC). The inter-reader correlation is 0.97 for FGT% and 0.95 for |FGT|. When compared to the average of the two readers' manual segmentation, the proposed FCM-Atlas method achieves a correlation of r = 0.92 for FGT% and r = 0.93 for |FGT|, and the automated segmentation is not statistically significantly different (p = 0.46 for FGT% and p = 0.55 for |FGT|). The bilateral correlation between left breasts and right breasts for the FGT% is 0.94, 0.92, and 0.95 for reader 1, reader 2, and the FCM-Atlas, respectively; likewise, for the |FGT|, it is 0.92, 0.92, and 0.93, respectively. For the spatial segmentation agreement, the automated algorithm achieves a DSC of 0.69 ± 0.1 when compared to reader 1 and 0.61 ± 0.1 for reader 2, respectively, while the DSC between the two readers' manual segmentation is 0.67 ± 0.15. Additional robustness analysis shows that the segmentation performance of the authors' method is stable both with respect to selecting different cases and to varying the number of cases needed to construct the prior probability atlas. The authors' results also show that the proposed FCM-Atlas method outperforms the commonly used two-cluster FCM-alone method. The authors' method runs at ∼5 min for each 3D bilateral MR scan (56 slices) for computing the FGT% and |FGT|, compared to ∼55 min needed for manual segmentation for the same purpose. The authors' method achieves robust segmentation and can serve as an efficient tool for processing large clinical datasets for quantifying the fibroglandular tissue content in breast MRI. It holds a great potential to support clinical applications in the future including breast cancer risk assessment.


[Increase in colon cancer mortality rates in Chile, during the period 1990-2003].
In Chile, colorectal cancer is the third cause of mortality due to digestive cancer. To assess the evolution of colon cancer mortality rates in the period 1990-2003. Information was obtained from demography and vital statistics yearbooks, published by the Chilean National Statistics Institute. Mortality tendecies and slopes, were calculated using Pearson correlation analysis and linear regression. Proportions were compared using Chi square. There was a significantly rising tendency in mortality for colon cancer in the general population (r= 0.964, p <0.001), in men (r=0.926, p <0.001) and in women (r=0.943, p <0.001). This tendency was not modified if rates were corrected by age. Mortality among women was significantly higher in all study years. The increase in mortality rates in the period was 0.175/100,000 inhabitants per year. The higher mortality rates were observed during 2003, reaching 6.2/100,000 inhabitants. There was a steady increase in colon cancer mortality during the studied period.


Dematiaceous fungi.
Dematiaceous fungi are responsible for a wide variety of infectious syndromes. They are often found in soil and generally distributed worldwide. This suggests that most if not all individuals are exposed to them, presumably from inhalation or trauma. In recent years, these fungi have been increasingly recognised as important pathogens. The spectrum of diseases they are associated with has also broadened and includes superficial and deep local infections, allergic disease, pneumonia, brain abscess and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common aetiological agents. These fungi may have unique pathogenic mechanisms owing to the presence of melanin in their cell walls, which imparts the characteristic dark colour to their spores and hyphae. Diagnosis rests on careful microscopical and pathological examination, as there are no simple laboratory tests to reliably identify these fungi. Therapy depends upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Azoles such as itraconazole and voriconazole have the most consistent in vitro activity, though there is more clinical experience with itraconazole. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.


GNPS-Guided Discovery of Madurastatin Siderophores from the Termite-Associated Actinomadura sp. RB99.
In this study, we analyzed if Actinomadura sp. RB99 produces siderophores that that could be responsible for the antimicrobial activity observed in co-cultivation studies. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and global natural product social molecular networking platform (GNPS) analysis of fungus-bacterium co-cultures resulted in the identification of five madurastatin derivatives (A1, A2, E1, F, and G1), of which were four new derivatives. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, as well as MS/MS data and their absolute structures were elucidated based on Marfey's analysis, DP4+ probability calculation and total synthesis. Structure analysis revealed that madurastatin E1 (2) contained a rare 4-imidazolidinone cyclic moiety and madurastatin A1 (5) was characterized as a Ga3+ -complex. The function of madurastatins as siderophores was evaluated using the fungal pathogen Cryptococcus neoformans as model organism. Based on homology models, we identified the putative NRPS-based gene cluster region of the siderophores in Actinomadura sp. RB99.


Two clinical phenotypes in polycythemia vera.
Polycythemia vera is the ultimate phenotypic consequence of the V617F mutation in Janus kinase 2 (encoded by JAK2), but the extent to which this mutation influences the behavior of the involved CD34+ hematopoietic stem cells is unknown. We analyzed gene expression in CD34+ peripheral-blood cells from 19 patients with polycythemia vera, using oligonucleotide microarray technology after correcting for potential confounding by sex, since the phenotypic features of the disease differ between men and women. Men with polycythemia vera had twice as many up-regulated or down-regulated genes as women with polycythemia vera, in a comparison of gene expression in the patients and in healthy persons of the same sex, but there were 102 genes with differential regulation that was concordant in men and women. When these genes were used for class discovery by means of unsupervised hierarchical clustering, the 19 patients could be divided into two groups that did not differ significantly with respect to age, neutrophil JAK2 V617F allele burden, white-cell count, platelet count, or clonal dominance. However, they did differ significantly with respect to disease duration; hemoglobin level; frequency of thromboembolic events, palpable splenomegaly, and splenectomy; chemotherapy exposure; leukemic transformation; and survival. The unsupervised clustering was confirmed by a supervised approach with the use of a top-scoring-pair classifier that segregated the 19 patients into the same two phenotypic groups with 100% accuracy. Removing sex as a potential confounder, we identified an accurate molecular method for classifying patients with polycythemia vera according to disease behavior, independently of their JAK2 V617F allele burden, and identified previously unrecognized molecular pathways in polycythemia vera outside the canonical JAK2 pathway that may be amenable to targeted therapy. (Funded by the Department of Defense and the National Institutes of Health.).


Atopic disorders and depression: findings from a large, population-based study.
Atopy, a common disorder characterized by a sensitivity to allergic reactions, affects a large proportion of the adult population and, as with depression, is associated with immune-inflammatory pathway changes. We sought to determine the role of atopic disorders in depression using data from a randomly-selected, population-based study of men and women. Cross-sectional data derived from the Geelong Osteoporosis Study for 942 males and 1085 females were analyzed. Depression [major depressive disorder (MDD), minor depression and dysthymia] was assessed using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition. Data on medical conditions, including atopic disorders (asthma, hay fever and eczema), smoking status, alcohol consumption, socioeconomic status, and physical activity were documented by self-report. Logistic regression modeling was used to explore the associations between atopic disorders and depression. Atopic disorders were associated with a 59% increased likelihood of depression [gender and smoking-adjusted odds ratio (OR) 1:50, 95% CI 1.20-1.97]. Sub-group analyses revealed a similar pattern for those with MDD [gender and smoking-adjusted OR 1:54, 95% CI 1.22-1.94]. These associations were independent of socio-demographic characteristics, clinical and lifestyle factors. Reliance on self-report for allergic symptoms and cross-sectional nature of study. This population-based study provides evidence of the potential contribution of allergic disorders to depression. Further research is required to elucidate the direction of this association and to further explicate its underlying physiology, including immune-inflammation markers.


Transforming growth factor β signaling controls activities of human intestinal CD8(+)T suppressor cells.
In healthy individuals, interactions between intestinal epithelial cells and lamina propria lymphocytes give rise to a population of CD8(+) T cells with suppressor functions (Ts cells). Disruption of Ts cell activities can lead to mucosal inflammation. We investigated what factors were required for expansion of the Ts cell population or loss of their activity in patients with Crohn's disease (CD). We developed a method to generate Ts cell lines from freshly isolated lamina propria lymphocytes from patients with ulcerative colitis (UC), patients with CD, or healthy individuals (controls). Cells were stimulated with a monoclonal antibody against CD3, interleukin (IL)-7, and IL-15. After 14 days in culture, CD8(+)T cells were purified and cultured with IL-7 and IL-15. The resulting Ts cells were analyzed for suppressor activity, expression of surface markers, and cytokine secretion profiles. RNA was isolated from the 3 groups of Ts cells and used in microarray analyses. Ts cells from patients with UC and controls suppressed proliferation of CD4(+) T cells; the suppression required cell contact. In contrast, Ts cells from patients with CD had a reduced capacity to suppress CD4(+) T-cell proliferation. The difference in suppressive ability was not associated with surface or intracytoplasmic markers or secretion of cytokines. Microarray analysis identified changes in expression of genes regulated by transforming growth factor (TGF)-β that were associated with the suppressive abilities of Ts cells. We found that TGF-β or supernatants from Ts cells of patients with CD reduced the suppressor activity of control Ts cells. Ts cells isolated from patients with CD have a reduced ability to suppress proliferation of CD4(+)T cells compared with control Ts cells. TGF-β signaling reduces the suppressor activity of Ts cells.


Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease.
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that, in most cases, involves homozygous deletion of the SMN1 gene. This causes a deficiency in survival motor neuron (SMN) protein, which plays a critical role in motor neuron development. SMA has a range of phenotype expression resulting in variable age of symptom onset, maximum motor strength achieved, and survival. Without intervention, infants with a more severe form of the disease (type 1 SMA) die before 2 years of age. Although it is rare, SMA is the most common fatal inherited disease of infancy, and until recently, treatment was primarily supportive. In 2016, a new agent, nusinersen, was approved by the FDA. Other treatments are in development, including a gene therapy, AVXS-101. These treatments are not only improving the lives of patients with SMA and their families, they are changing the disease phenotype. They have the greatest benefit when given early in the disease course. To discuss current knowledge about SMA, provide clinical evidence for available and emerging treatment options, and present approaches for adding new therapies to hospital/health system formularies to ensure timely access to newly approved therapies for SMA. Advances in clinical care have significantly extended the lives of individuals with SMA, and research into the genetic mechanisms leading to disease have revealed strategies for intervention that target the underlying cause of SMA. Nusinersen is now on the market, and other treatment options, such as AVXS-101, may soon be approved. This article provides an overview of SMA and the genetic mechanisms leading to SMN deficiency, then describes how new and emerging treatments work to overcome this deficiency and prevent associated nerve damage and disability. In addition, we discuss steps for incorporating AVXS-101 into hospital/health system formularies, along with barriers and concerns that may delay access, based in part on lessons learned with nusinersen.


Batrachotoxin-modified sodium channels in planar lipid bilayers. Characterization of saxitoxin- and tetrodotoxin-induced channel closures.
The guanidinium toxin-induced inhibition of the current through voltage-dependent sodium channels was examined for batrachotoxin-modified channels incorporated into planar lipid bilayers that carry no net charge. To ascertain whether a net negative charge exists in the vicinity of the toxin-binding site, we studied the channel closures induced by tetrodotoxin (TTX) and saxitoxin (STX) over a wide range of [Na+]. These toxins carry charges of +1 and +2, respectively. The frequency and duration of the toxin-induced closures are voltage dependent. The voltage dependence was similar for STX and TTX, independent of [Na+], which indicates that the binding site is located superficially at the extracellular surface of the sodium channel. The toxin dissociation constant, KD, and the rate constant for the toxin-induced closures, kc, varied as a function of [Na+]. The Na+ dependence was larger for STX than for TTX. Similarly, the addition of tetraethylammonium (TEA+) or Zn++ increased KD and decreased kc more for STX than for TTX. These differential effects are interpreted to arise from changes in the electrostatic potential near the toxin-binding site. The charges giving rise to this potential must reside on the channel since the bilayers had no net charge. The Na+ dependence of the ratios KDSTX/KDTTX and kcSTX/kcTTX was used to estimate an apparent charge density near the toxin-binding site of about -0.33 e X nm-2. Zn++ causes a voltage-dependent block of the single-channel current, as if Zn++ bound at a site within the permeation path, thereby blocking Na+ movement. There was no measurable interaction between Zn++ at its blocking site and STX or TTX at their binding site, which suggests that the toxin-binding site is separate from the channel entrance. The separation between the toxin-binding site and the Zn++ blocking site was estimated to be at least 1.5 nm. A model for toxin-induced channel closures is proposed, based on conformational changes in the channel subsequent to toxin binding.


Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets.
Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes, including in vitro bioequivalence performance. Five generic products (T1, T2, T3, T4, and T5) containing combination of amoxicillin trihydrate and potassium clavulanate as 1 g strength present in immediate release tablets were compared to the reference listed drug product Augmentin® (R) for weight variation, friability, resistance to crushing, and chemical content of amoxicillin. Difference (ƒ1) and similarity (ƒ2) factors were calculated to assess in vitro bioequivalence requirements. The tablets from different products have shown compliance with the pharmacopeial requirements of the performed tests. The measured resistance to crushing of tablets did not influence the dissolution time. Three generic products released more than 85% of amoxicillin by the first 15 min as did the reference product and were considered as bioequivalent products. T1 and T4 had ƒ1 values of 16.5% and 25.4% respectively and their ƒ2 values were 44.5 and 34.6 respectively, indicating failure to meet in vitro bioequivalence requirements. Tablet formulations can play an important role in achieving bioequivalence. Independent investigations such as this study serve as an important tool to reveal possible inferior or noncompliant products that may find their way to the market.


[An epidemic of asthma caused by soybean in L'Hospitalet de Llobregat (Barcelona)].
Twenty-six epidemics of asthma occurred in Barcelona between 1981 and 1987 in relation to inhalation of soy dust from grain silo unloading in the harbor. No further epidemics occurred after filters were installed, until a 1994 outbreak of asthma due to soy was detected in L'Hospitalet de Llobregat, a city on the outskirts of Barcelona. We describe 9 patients who presented with acute asthma attacks of sudden onset within a time span of 135 minutes. Counts of total IgE and IgE specific to soy extract were analyzed in all patients. Skin prick tests confirmed exposure to soy in all cases. Atmospheric levels of alcoholic fractions of soy particles (beta-sitosterol and stigmasterol) registered in L'Hospitalet de Llobregat were higher than those detected in Barcelona. We confirmed that soy had been unloaded in the harbor the same day, and that climatic conditions favored the movement of air from the port toward the city of L'Hospitalet. We postulate the need to periodically review preventive measures given the potential severity of the such epidemics.


'We are suffering. Nothing is changing.' Black mother's experiences, communication, and support in the neonatal intensive care unit in the United States: A Qualitative Study.
Black mothers experience markedly disproportionate maternal morbidity and mortality in the United States, with racism often cited as the root cause manifesting through several pathways. The study examined Black mothers' perceived provider communication, support needs, and overall experiences in the neonatal intensive care unit (NICU). This study used grounded theory embedded in the Black feminist theoretical (BFT) framework to generate new ideas grounded in the data. Data was collected through semi-structured interviews using videoconferencing, with questions related to the mother's overall NICU experiences, communication within the NICU, and perceived support needs. Data were analyzed using thematic analysis. Twelve mothers participated in the study; most were married (n = 10), had a cesarean birth, had a previous pregnancy complication (e.g., diabetes, hypertension), had attained a graduate degree or more (n = 9), earned an annual household income of $75,000 or more, and were between 35-44 years of age (n = 7). Three broad domains with several accompanying themes and sub-themes were identified, explicating the mother's experiences in the NICU. Specifically, factors influencing NICU hospitalization for mothers included maternal care/nursing experiences, interactions in the NICU, and the perceived support need that might attenuate negative care and birthing experiences. . The study adds to the growing literature championing Black maternal health equity and multilevel quality improvement strategies to foster equitable maternal health. Our study reinforces the need for racially congruent interventions and policy reformations to protect Black birthing people regardless of socioeconomic factors and social class using life course, holistic approaches, and intersectionality mindset. Importantly, using the BFT, this study calls for culturally sensitive research to capture the nuances associated with the multiplicity of experiences of Black people.


Inhibitory learning of phototaxis by honeybees in a passive-avoidance task.
Honeybees are a standard model for the study of appetitive learning and memory. Yet, fewer attempts have been performed to characterize aversive learning and memory in this insect and uncover its molecular underpinnings. Here, we took advantage of the positive phototactic behavior of bees kept away from the hive in a dark environment and established a passive-avoidance task in which they had to suppress positive phototaxis. Bees placed in a two-compartment box learned to inhibit spontaneous attraction to a compartment illuminated with blue light by associating and entering into that chamber with shock delivery. Inhibitory learning resulted in an avoidance memory that could be retrieved 24 h after training and that was specific to the punished blue light. The memory was mainly operant but involved a Pavlovian component linking the blue light and the shock. Coupling conditioning with transcriptional analyses in key areas of the brain showed that inhibitory learning of phototaxis leads to an up-regulation of the dopaminergic receptor gene Amdop1 in the calyces of the mushroom bodies, consistently with the role of dopamine signaling in different forms of aversive learning in insects. Our results thus introduce new perspectives for uncovering further cellular and molecular underpinnings of aversive learning and memory in bees. Overall, they represent an important step toward comparative learning studies between the appetitive and the aversive frameworks.


Multivariate analysis of toxicological and environmental properties of soil nematicides.
In intensive agriculture, the use of pesticides and soil fumigants is necessary to produce economically viable crops worldwide. However, this practice may involve undesirable effects on human health and the environment. In 1995, methyl bromide was restricted by the Montreal Protocol because of possible ozone depletion. The objective of this study was to compare intrinsic environmental and toxicological properties of 11 active substances with nematicidal properties, some of them recognized as methyl bromide alternatives. Four groups of active substances were discriminated by a series of principal component analyses (PCAs): (a) high toxicity to non-target fauna, humans and animals and medium persistence in the environment (cadusafos, ethoprophos and fenamiphos); (b) high toxicity to humans, animals and non-target fauna and high persistence (carbofuran and fosthiazate); (c) low toxicity to non-target fauna, humans and animals and low persistence (carbosulfan, benfuracarb and oxamyl); (d) low toxicity to humans, animals and non-target fauna and medium persistence in the environment (1,3-dichloropropene, chloropicrin and methyl bromide). Evaluating the multiple aspects of toxicological and environmental properties of active substances through PCA is proposed as a helpful tool for initially comparing the complex toxicological behaviour of active substances as plant protection products.


Antibiotic resistance and putative virulence factors of Serratia marcescens with respect to O and K serotypes.
Serratia marcescens serotypes O6:K14, O8:K14 and O28:K28 are common in the natural environment, but rare in hospitals. Serotypes O14:K14 and O27:K14 predominate among clinical strains, but not in the environment, suggesting that the latter serotypes may be more suited for survival in the clinical setting. Consequently, 469 epidemiologically distinct strains of S. marcescens were tested for various putative virulence factors and analysed for associations with serotype. The factors positively associated with serotype O14:K14 were agglutination of five different species of red blood cells and expression of type 1 fimbriae. These were found in 63% and 53% of O14:K14 strains, respectively, compared with 7% and 12% of the three 'environmental serotypes'. Almost a quarter of the collection expressed the mannose-resistant haemagglutinin indicative of type 3 fimbriae, but this was not associated with any serotype. The production of DNAase, haemolysin, lipase, lecithinase, proteases and siderophores was almost universal and showed no serotype correlations. Almost half of the strains (46%) were resistant to serum and serotypes O27:K14 and O6:K14 were strongly associated with this characteristic. Serotype O27:K14 was also associated with higher proportions of antibiotic-resistant strains than other serotypes, but the same was not true of serotype O14:K14. All three 'environmental serotypes' were associated with low frequencies of antibiotic resistance; <12% were resistant to gentamicin, carbenicillin or piperacillin, or any combination of these three, compared with 20-25% of O14:K14 strains and >42-51% of O27:K14 strains. Pigment production was strongly associated with serotype. None of the O14:K14 or O27:K14 strains produced prodigiosin, but frequencies for the three 'environmental serotypes' ranged from 31% of O28:K28 strains to 85% of O6:K14 strains. The results of this study suggest that the adherence capability of S. marcescens strains may play a role in the colonisation of hospital patients, while the production of prodigiosin is a marker of environmental origin.


Vascular endothelial growth factors and angiogenesis.
VEGF was discovered in 1989. Research -conducted over the past 10 years has -demonstrated that VEGF is a major regulator of angiogenesis and vasculogenesis. This paper reviews the molecular data on the multiple forms of VEGF, their signalling and accessory receptors. Five genes encoding VEGF-like proteins have been identified; the different isoforms of each VEGF molecule are generated by alternative splicing mechanisms. The different VEGF's recognize signalling tyrosine kinase receptors (Flt-1, Flk-1 and Flt-4) and accessory receptors. VEGF expression is stimulated by hypoxia-dependent and -independent mechanisms. Hypoxic responses are mediated by specific transcription factors that are expressed in a tissue dependent fashion and that are developmentally regulated. VEGF is thought to play a role in tumor angiogenesis and may contribute to cardioprotection in ischemic heart -diseases. Its role in pulmonary hypertension induced by chronic hypoxia is discussed. This review also stresses the difficulty of applying results from in vitro -studies to in vivo situations.


Interference with brachyury function inhibits convergent extension, causes apoptosis, and reveals separate requirements in the FGF and activin signalling pathways.
Brachyury plays a key role in mesoderm formation during vertebrate development. Absence of the gene results in loss of posterior mesoderm and failure of the notochord to differentiate, while misexpression of Brachyury in the prospective ectoderm of Xenopus results in ectopic mesoderm formation. Brachyury is therefore both necessary and sufficient for posterior mesoderm formation. Here we present a detailed cellular and molecular analysis of the consequences of inhibiting Brachyury function during Xenopus development. Our results show that Brachyury is required for the convergent extension movements of gastrulation, for mesoderm differentiation in response to FGF, and for the survival of posterior mesodermal cells in both Xenopus and mouse.


Characterization of Water Solubility in n-Octacosane Using Raman Spectroscopy.
In this study, we demonstrate the ability of polarization-difference Raman spectroscopy (PDRS) to detect dissolved free water molecules in a n-octacosane (n-C28H58) liquid-rich phase, and thus to determine its solubility, at temperatures and pressures relevant to the Fischer-Tropsch synthesis. Our results for the pure alkane reveal thermal decomposition above a temperature of 500 K as well as an increase of gauche conformers of the alkane chains with an increase in temperature. For binary homogeneous mixtures, raw spectra obtained from two different polarization scattering geometries did not show a relevant signal in the OH stretching frequency range. In contrast, isotropic spectra obtained from the PDRS technique reveal a narrow and tiny peak associated with the dangling OH bonds. Over the complete range of temperatures and pressures, no signature of hydrogen-bonded water molecules was observed in the isotropic Raman scattering intensities. A thorough investigation covering a large range of temperatures and pressures using PDRS signals showed that the higher the fraction of gauche conformers of hydrocarbon, the higher the solubility of water. The proportion of gauche and trans conformers was found to be water-concentration-independent, and the intensity of the OH-dangling peak increased linearly with increasing the vapor partial pressure of water. Therefore, we established a relation between a relevant intensity ratio and the concentration of water obtained from SAFT calculations. Contrary to the results from relevant literature, the calibration factor was found to be temperature-independent between 424 and 572 K. The isotropic Raman scattering intensities are corrected in order to provide a better representation of the vibrational density of states. The influence of correction of the isotropic scattering intensities on the solubility measurements as well as on the analysis of the molecular arrangement is discussed.


Multiplexing enhancement for the detection of multiple pathogen DNA.
Various methods for the detection of pathogens have been researched and developed. However, most of detection methods are cost-ineffective and laborious. To minimize costs and labor, multi-detection of pathogen have been widely used. In this paper, we propose a novel multi-detection method, which can enhance multi-detection capability using fluorescent dye labeled DNA nanostructures that is named DNA nanobarcodes. By using three fluorescence colors, multi-detection capability is significantly increased because of the increased combination of three colors. Moreover, our approach uses a relatively simple DNA nanostructure to precisely control the fluorescence intensity ratio. Therefore, high multi-detection ability is achieved without constructing a complicated DNA nanostructure probe. Our novel detection method can overcome the obstacles of conventional methods and enhance multi-detection capability effectively. By using our new system, we were able to successfully detect nine different DNA pathogens simultaneously. Our system can easily increase the multiplexibility by using more fluosrescent colors on DNA nanobarcode.


Expression of melanoma-associated antigens in rapidly dividing human melanocytes in culture.
Conditions were established to induce rapid clonal growth of melanocytes from newborn foreskin. Surface antigen expression was analyzed using monoclonal antibodies derived by immunization of mice with melanoma cell, melanocyte, and placental membrane preparations. Unlike resting melanocytes in normal skin, cultured melanocytes expressed most major melanoma-associated antigens tested, e.g., nerve growth factor receptor, proteoglycan, transferrin-related Mr 97,000 protein antigen, Mr 120,000 protein, and gangliosides 9-O-acetyl GD3 and GD3. HLA-DR antigen and ganglioside GD2 were expressed at very low levels or not expressed. After several subpassages, most melanocyte cultures, including clones and melanocytes, initially sorted by rosetting with monoclonal antibody to nerve growth factor receptor, lost their characteristic bipolar morphology and expression of nerve growth factor receptor and Mr 97,000 antigen but continued to express high molecular weight proteins such as proteoglycan, Mr 130,000/105,000 and 120,000 antigen. The few melanocyte cultures that did maintain their characteristic bipolar to spindle morphology continued to express all melanoma-associated antigens and even began to express HLA-DR antigens. Melanocytes cultured in the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate also maintained their bipolar morphology, were often pigmented, and continued to express melanoma-associated antigens for several passages; they did not express HLA-DR antigen. Our studies indicate that rapidly proliferating melanocytes in culture undergo antigenic changes associated with malignancy.


The sub-cellular localisation of the potato (Solanum tuberosum L.) carotenoid biosynthetic enzymes, CrtRb2 and PSY2.
Carotenoids are isoprenoids with important biological roles both for plants and animals. The yellow flesh colour of potato (Solanum tuberosum L.) tubers is a quality trait dependent on the types and levels of carotenoids that accumulate. The carotenoid biosynthetic pathway is well characterised, facilitating the successful engineering of carotenoid content in numerous crops including potato. However, a clear understanding concerning the factors regulating carotenoid accumulation and localisation in plant storage organs, such as tubers, is lacking. In the present study, the localisation of key carotenoid biosynthetic enzymes was investigated, as one of the unexplored factors that could influence the accumulation of carotenoids in potato tubers. Stable transgenic potato plants were generated by over-expressing β-CAROTENE HYDROXYLASE 2 (CrtRb2) and PHYTOENE SYNTHASE 2 (PSY2) genes, fused to red fluorescent protein (RFP). Gene expression and carotenoid levels were both significantly increased, confirming functionality of the fluorescently tagged proteins. Confocal microscopy studies revealed different sub-organellar localisations of CrtRb2-RFP and PSY2-RFP within amyloplasts. CrtRb2 was detected in small vesicular structures, inside amyloplasts, whereas PSY2 was localised in the stroma of amyloplasts. We conclude that it is important to consider the location of biosynthetic enzymes when engineering the carotenoid metabolic pathway in storage organs such as tubers.


Formulations for intermittent release of parathyroid hormone (1-34) and local enhancement of osteoblast activities.
The objective of these studies was to develop simple, implantable devices that intermittently release PTH(1-34) and thus could be used for locally stimulating bone formation. The formulations were based on the association polymer system of cellulose acetate phthalate and Pluronic F-127. Release profiles for intermittent devices showed five discrete peaks, whereas sustained devices exhibited zero-order kinetics. Osteoblastic activity was greater for cells intermittently treated with PTH(1-34) compared to sustained exposure. These controlled release devices delivering PTH(1-34) in an intermittent manner may be useful for affecting osteoblast activities in a localized area.


Interference with Sin3 function induces epigenetic reprogramming and differentiation in breast cancer cells.
Sin3A/B is a master transcriptional scaffold and corepressor that plays an essential role in the regulation of gene transcription and maintenance of chromatin structure, and its inappropriate recruitment has been associated with aberrant gene silencing in cancer. Sin3A/B are highly related, large, multidomian proteins that interact with a wide variety of transcription factors and corepressor components, and we examined whether disruption of the function of a specific domain could lead to epigenetic reprogramming and derepression of specific subsets of genes. To this end, we selected the Sin3A/B-paired amphipathic alpha-helices (PAH2) domain based on its established role in mediating the effects of a relatively small number of transcription factors containing a PAH2-binding motif known as the Sin3 interaction domain (SID). Here, we show that in both human and mouse breast cancer cells, the targeted disruption of Sin3 function by introduction of a SID decoy that interferes with PAH2 binding to SID-containing partner proteins reverted the silencing of genes involved in cell growth and differentiation. In particular, the SID decoy led to epigenetic reprogramming and reexpression of the important breast cancer-associated silenced genes encoding E-cadherin, estrogen receptor alpha, and retinoic acid receptor beta and impaired tumor growth in vivo. Interestingly, the SID decoy was effective in the triple-negative M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cell line, restoring sensitivity to 17beta-estradiol, tamoxifen, and retinoids. Therefore, the development of small molecules that can block interactions between PAH2 and SID-containing proteins offers a targeted epigenetic approach for treating this type of breast cancer that may also have wider therapeutic implications.


Revisiting van der Waals Radii: From Comprehensive Structural Analysis to Knowledge-Based Classification of Interatomic Contacts.
The front cover artwork is provided by the TheoMAT group of ITMO University (Russia) and the Inorganic Systems Engineering Group of Delft University of Technology (The Netherlands). The image illustrates how one can find the most probable interatomic distance and determine the van der Waals parameters for interatomic interaction from extended and diverse structural datasets. The new approach for background elimination and analysis of extended bulk structural datasets is reported in our paper. Read the full text of the Article at 10.1002/cphc.201901083.


[Application of a physiologic stability index at a pediatric intensive care unit].
This study was conducted to evaluate usefulness of the physiologic stability index (PSI) in a pediatric intensive care Unit (PICU) of a University based hospital at Santiago, Chile. Subjects include all patients (n = 152) consecutively admitted to our PICU between april 1987 and august 1988. The PSI system was applied during the first four days from admission. The age of the patients ranged from 10 days to 15 years. Scores obtained from survivors and non survivors were compared using an analysis of variance. For maximum PSI, survivors had significantly lower scores (9.39 points) that non survivors (21.71 points). Multiple logistic regression was used to display associations between mean obtained scores and probability of death and a curve was plotted which is similar to that obtained in previous experiences from other countries.


Full field-of-view virtual reality goggles for mice.
Visual virtual reality (VR) systems for head-fixed mice offer advantages over real-world studies for investigating the neural circuitry underlying behavior. However, current VR approaches do not fully cover the visual field of view of mice, do not stereoscopically illuminate the binocular zone, and leave the lab frame visible. To overcome these limitations, we developed iMRSIV (Miniature Rodent Stereo Illumination VR)-VR goggles for mice. Our system is compact, separately illuminates each eye for stereo vision, and provides each eye with an ∼180° field of view, thus excluding the lab frame while accommodating saccades. Mice using iMRSIV while navigating engaged in virtual behaviors more quickly than in a current monitor-based system and displayed freezing and fleeing reactions to overhead looming stimulation. Using iMRSIV with two-photon functional imaging, we found large populations of hippocampal place cells during virtual navigation, global remapping during environment changes, and unique responses of place cell ensembles to overhead looming stimulation.


Genome of a low-salinity ammonia-oxidizing archaeon determined by single-cell and metagenomic analysis.
Ammonia-oxidizing archaea (AOA) are thought to be among the most abundant microorganisms on Earth and may significantly impact the global nitrogen and carbon cycles. We sequenced the genome of AOA in an enrichment culture from low-salinity sediments in San Francisco Bay using single-cell and metagenomic genome sequence data. Five single cells were isolated inside an integrated microfluidic device using laser tweezers, the cells' genomic DNA was amplified by multiple displacement amplification (MDA) in 50 nL volumes and then sequenced by high-throughput DNA pyrosequencing. This microscopy-based approach to single-cell genomics minimizes contamination and allows correlation of high-resolution cell images with genomic sequences. Statistical properties of coverage across the five single cells, in combination with the contrasting properties of the metagenomic dataset allowed the assembly of a high-quality draft genome. The genome of this AOA, which we designate Candidatus Nitrosoarchaeum limnia SFB1, is ∼1.77 Mb with >2100 genes and a G+C content of 32%. Across the entire genome, the average nucleotide identity to Nitrosopumilus maritimus, the only AOA in pure culture, is ∼70%, suggesting this AOA represents a new genus of Crenarchaeota. Phylogenetically, the 16S rRNA and ammonia monooxygenase subunit A (amoA) genes of this AOA are most closely related to sequences reported from a wide variety of freshwater ecosystems. Like N. maritimus, the low-salinity AOA genome appears to have an ammonia oxidation pathway distinct from ammonia oxidizing bacteria (AOB). In contrast to other described AOA, these low-salinity AOA appear to be motile, based on the presence of numerous motility- and chemotaxis-associated genes in the genome. This genome data will be used to inform targeted physiological and metabolic studies of this novel group of AOA, which may ultimately advance our understanding of AOA metabolism and their impacts on the global carbon and nitrogen cycles.


Oscillatory activity in neocortical networks during tactile discrimination near the limit of spatial acuity.
Oscillatory interactions within functionally specialized but distributed brain regions are believed to be central to perceptual and cognitive functions. Here, using human scalp electroencephalography (EEG) recordings combined with source reconstruction techniques, we study how oscillatory activity functionally organizes different neocortical regions during a tactile discrimination task near the limit of spatial acuity. While undergoing EEG recordings, blindfolded participants felt a linear three-dot array presented electromechanically, under computer control, and reported whether the central dot was offset to the left or right. The average brain response differed significantly for trials with correct and incorrect perceptual responses in the timeframe approximately between 130 and 175ms. During trials with correct responses, source-level peak activity appeared in the left primary somatosensory cortex (SI) at around 45ms, in the right lateral occipital complex (LOC) at 130ms, in the right posterior intraparietal sulcus (pIPS) at 160ms, and finally in the left dorsolateral prefrontal cortex (dlPFC) at 175ms. Spectral interdependency analysis of activity in these nodes showed two distinct distributed networks, a dominantly feedforward network in the beta band (12-30Hz) that included all four nodes and a recurrent network in the gamma band (30-100Hz) that linked SI, pIPS and dlPFC. Measures of network activity in both bands were correlated with the accuracy of task performance. These findings suggest that beta and gamma band oscillatory networks coordinate activity between neocortical regions mediating sensory and cognitive processing to arrive at tactile perceptual decisions.


Microbiologic determinants of exacerbation in chronic obstructive pulmonary disease.
The culture of bronchial secretions from the lower airway has been reported to be positive for potentially pathogenic microorganisms (PPMs) in patients with stable chronic obstructive pulmonary disease (COPD), but the determinants and effects of this bacterial load in the airway are not established. To determine the bronchial microbial pattern in COPD and its relationship with exacerbation, we pooled analysis of crude data from studies that used protected specimen brush sampling, with age, sex, smoking, lung function, and microbiologic features of the lower airway as independent variables and exacerbation as the outcome, using logistic regression modeling. Of 337 study participants, 70 were healthy, 181 had stable COPD, and 86 had exacerbated COPD. Differences in the microbial characteristics in the participating laboratories were not statistically significant. A cutoff point of 10(2) colony-forming units (CFU) per milliliter or greater for the identification of abnormal positive culture results for PPMs was defined using the 95th percentile in the pooled analysis of healthy individuals. Bronchial colonization of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, chi(2) test), with a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher microbial loads were associated with exacerbation and showed a statistically significant dose-response relationship after adjustment for covariates (odds ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a statistically significant risk factor after adjustment for microbial load (odds ratio, 11.12; 95% confidence interval, 1.17-105.82). One quarter of the patients with COPD are colonized by PPMs during their stable periods. Exacerbation is associated with the overgrowth of PPMs and with the appearance of P aeruginosa in the lower airway, which is associated with exacerbation symptoms independent of load.


Health-related quality of life measures for physically active elderly in community exercise programs in catalonia: comparative analysis with sedentary people.
Objective. To evaluate Health-Related Quality of Life (HRQoL), medication used, and Stock of Health Capital (SHC) in physically active elderly participants in Community Exercise Programs (CEPs) compared to a sedentary group. Methods. EuroQol standardized instrument was completed by physically active elderly (n = 2,185) who participated in CEPs. Common items were compared to HRQoL data of 1,874 sedentary elderly people, taken from the Catalan Health Survey 2006 (CHS'06). Visual Analogue Scale (VAS) outcomes and medication used were assessed through parametric statistics. Dimensions of health conditions were compared, between sedentary people and physically active elderly participants in CEPs. SHC results were obtained combining the EuroQol scores and Life Expectancy (LE) values. An economic value of €34,858.70 was assigned to these years of LE. Results. Physically active subjects had better HRQoL values (75.36 in males and 70.71 in females) than CHS'06 sedentary subjects (58.35 in males and 50.59 in females). Medication used was different between physically active subjects (1.89 in males and 2.87 in females) and CHS'06 sedentary subjects (4.34 in males and 4.21 in females). SHC data for physically active elderly (€465,988.31/QALY in males and €522,550.31/QALY in females) were higher than for CHS'06 sedentary subjects (€363,689.33/QALY in males and €346,615.91/QALY in females).


Gender differences in oral health status and behavior of Greek dental students: A meta-analysis of 1981, 2000, and 2010 data.
The aim of this study was to investigate the oral health status and behavior of Greek dental students over time, and to meta-analyze these findings to test the widely documented hypothesis that women have better oral health behavior, oral hygiene, and periodontal status but higher dental caries rates than men. A total sample of 385 students was examined using identical indices to assess oral health and behavioral data initially in 1981 while the years 2000 and 2010 were selected due to significant changes that took place in the dental curriculum in the 1990s and 2000s. Data by gender concerning the outcome variables recorded in every one of the three surveys were analyzed using Mantel-Haenszel and continuous outcomes methods. A significant improvement in the oral health status and behavior of students was observed over time. The meta-analysis of data by gender showed that females brushed their teeth significantly more often than males [summary odds ratio (OR): 1.95 and 95% confidence interval (CI): 1.08-3.54]. Males and females were found to have a similar risk of developing dental caries. The hypothesis that young women have better oral hygiene habits compared to men was confirmed. However, the hypothesis that women have better oral hygiene and periodontal status but exhibit higher dental caries experience than men was not supported by the findings of the study.


Surgically mismanaged ptosis associated with double elevator palsy.
The primary goal in mismanaged as well as untreated cases of combined double elevator muscle palsy and ptosis is alleviation of the paretic ocular motor imbalance to correct pseudoptosis, followed, if necessary, by levator resection to correct any residual true ptosis component. The great hypotropia often found in double elevator muscle palsy should be corrected, preferably by a muscle transposition procedure combined, in certain cases, with inferior rectus muscle recession if the inferior rectus muscle has contracted. Only in young patients can these two surgical procedures be safely combined, particularly if it is desirable to decrease the number of general anesthetics that the patient must take. Only after proper management of the paretic strabismus should the levator be resected, because, in certain cases, extraocular muscle surgery will completely abolish the upper lid ptosis.


Hypoxia inhibits human recombinant large conductance, Ca(2+)-activated K(+) (maxi-K) channels by a mechanism which is membrane delimited and Ca(2+) sensitive.
Large conductance, Ca(2+)-activated K(+) (maxi-K ) channel activity was recorded in excised, inside-out patches from HEK 293 cells stably co-expressing the alpha- and beta-subunits of human brain maxi-K channels. At +50 mV, and in the presence of 300 nM Ca2+i, single channel activity was acutely and reversibly suppressed upon reducing P(O(2)) from 150 to > 40 mmHg by over 30 %. The hypoxia-evoked reduction in current was due predominantly to suppression in NP(o), although a minor component was attributable to reduced unitary conductance of 8-12 %. Hypoxia caused an approximate doubling of the time constant for activation but was without effect on deactivation. At lower levels of Ca2+i(30 and 100 nM), hypoxic inhibition did not reach significance. In contrast, 300 nM and 1 microM Ca2+i both sustained significant hypoxic suppression of activity over the entire activating voltage range. At these two Ca2+i levels, hypoxia evoked a positive shift in the activating voltage (by approximately 10 mV at 300 nM and approximately 25 mV at 1 microM). At saturating [Ca(2+)](i) (100 microM), hypoxic inhibition was absent. Distinguishing between hypoxia-evoked changes in voltage- and/or Ca2+i-sensitivity was achieved by evoking maximal channel activity using high depolarising potentials (up to +200 mV) in the presence of 300 nM or 100 microM Ca2+i or in its virtual absence (> 1 nM). Under these experimental conditions, hypoxia caused significant channel inhibition only in the presence of 300 nM Ca2+i. Thus, since regulation was observed in excised patches, maxi-K channel inhibition by hypoxia does not require soluble intracellular components and, mechanistically, is voltage independent and Ca2+i sensitive.


Visualization of the Breakdown of the Axonal Transport Machinery: a Comparative Ultrastructural and Immunohistochemical Approach.
Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins and organelles are as well subjected to axonal transport deficits in demyelinated tissues is not known. The aim of this study was to correlate ultrastructural morphology with the immunohistochemical appearance of acute axonal injury in a model of toxin-induced oligodendrocyte degeneration. C57BL/6J mice were intoxicated with 0.25% cuprizone to induce demyelination. The corpus callosum was investigated by serial block-face scanning electron microscopy (i.e., 3D EM), immunohistochemistry, and immunofluorescence microscopy. Brain tissues of progressive MS patients were included to test the relevance of our findings in mice for MS. Volumes of axonal swellings, determined by 3D EM, were comparable to volumes of axonal spheroids, determined by anti-APP immunofluorescence stains. Axonal swellings were present at myelinated and non-myelinated axonal internodes. Densities of amyloid precursor protein (APP)+ spheroids were highest during active demyelination. Besides APP, vesicular glutamate transporter 1 and mitochondrial proteins accumulated at sites of axonal spheroids. Such accumulations were found as well in lesions of progressive MS patients. In this correlative ultrastructural-immunohistochemical study, we provide strong evidence that breakdown of the axonal transport machinery results in focal accumulations of mitochondria and different synaptic proteins. We provide new marker proteins to visualize acute axonal injury, which helps to further understand the complex nature of axonal damage in progressive MS.


Students' reflections on shadowing interprofessional teamwork: a Norwegian case study.
This article reports the students' reflections on interprofessional teamwork during brief exposures to real-life experiences in hospitals or home-based rehabilitation service. Each of the 10 interprofessional groups, comprising three students, followed a rehabilitation team for a day. The composition of each student group correlated with the rehabilitation team. Data were collected from interviews with the student groups and subjected to a thematic analysis. The following four main themes were identified for which the students seemed to affect collaboration: sharing knowledge; team setting and position within the organisation; patient centred focus; and challenges in crossing professional borders when performing tasks. Each of these themes is presented and discussed in relation to the educational literature. In conclusion, the data suggest that a well organized, one-day observation-based learning experience helped to motivate students and helped to enable them to relate theory and practice.


Neuropathological findings in autism.
Autism is currently viewed as a largely genetically determined neurodevelopmental disorder, although its underlying biological causes remain to be established. In this review, we examine the available neuropathological literature on autism and discuss the findings that have emerged. Classic neuropathological observations are rather consistent with respect to the limbic system (nine of 14 studied cases showed increased cell packing density and smaller neuronal size), the cerebellum (21 of 29 studied cases showed a decreased number of Purkinje cells, and in all of five cases that were examined for age-related morphological alterations, these changes were found in cerebellar nuclei and inferior olive) and the cerebral cortex (>50% of the studied cases showed features of cortical dysgenesis). However, all reported studies had to contend with the problem of small sample sizes, the use of quantification techniques not free of bias and assumptions, and high percentages of autistic subjects with comorbid mental retardation (at least 70%) or epilepsy (at least 40%). Furthermore, data from the limbic system and on age-related changes lack replication by independent groups. It is anticipated that future neuropathological studies hold great promise, especially as new techniques such as design-based stereology and gene expression are increasingly implemented and combined, larger samples are analysed, and younger subjects free of comorbidities are investigated.


Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques.
Recently, we and others have shown that natural killer (NK) cells exhibit memory-like recall responses against cytomegalovirus (CMV) and human immunodeficiency/virus simian immunodeficiency virus (HIV/SIV) infections. Although the mechanism(s) have not been fully delineated, several groups have shown that the activating receptor NKG2C is elevated on NK cells in the context of rhesus CMV (rhCMV) or human CMV (hCMV) infections. CD94, which heterodimerizes with NKG2C is also linked to adaptive NK cell responses. Because nonhuman primates (NHP) play a crucial role in modeling HIV (SIV) infections, it is crucial to be able to assess and characterize the NKG2 family in NHP. Unfortunately, it is not possible to detect CD94 using commercially available antibodies in NHP. Our work, a first for NHP, has focused on developing RNA flow cytometry using mRNA transcripts as proxies distinguishing NKG2C from NKG2A. We have expanded the application of this technology and here we show the first characterization of CD94+ (KLRD1+) NK cells in NHP using multiparametric RNA flow cytometry. Peripheral blood mononuclear cells from naive and matched acutely (n = 4) or chronically (n = 12) SIV-infected rhesus macaques were analyzed by flow cytometry using commercially available antibodies, determining expression of transcripts for NKG2A, NKG2C, and CD94 (KLRC1, KLRC2, and KLRD1, respectively) on NK cells using RNA flow cytometry. Our data show that KLRC1+/- KLRC2+ KLRD1+ NK cells decrease following chronic, but not acute, infection with SIV. This approach will allow us to investigate the kinetics of infection and NK memory formation and will further improve our understanding of basic NK cell biology, especially in the context of SIV infection.IMPORTANCE Nonhuman primates play a crucial role in approximating human biology and many diseases that are difficult, if not impossible, to achieve in other animal models, notably HIV. Current advances in adaptive NK cell research positions us to address fundamental deficiencies in our fight against infection and disease at the earliest moments after infection or substantially earlier in disease progression. We show here that we can identify specific NK cell subpopulations that are modulated following chronic, but not acute, SIV infection. The ability to identify these subsets more precisely will inform therapeutic and vaccine strategies targeting an optimized NK cell response.


[Hospital admission of subjects with chronic obstructive bronchopulmonary disease (COPD) and air pollution in the city of Parma (Italy). A preliminary analysis].
A study was conducted in subjects admitted to hospital for chronic obstructive bronchopulmonary disease (COPD) in the city of Parma (Italy). The aim was to evaluate changes in patients' percent vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), as a function of changing degrees of atmospheric pollution as measured by PM10, NO2 and O3 concentrations in the outside air. Study results revealed an association between PM10 concentrations and hospital admissions for COPD. Statistically significant differences were found between PM10 concentrations measured three-four days before admission and in days not followed by admission to hospital. Regression analysis between PM10 concentrations at 24, 48, 72, and 96 hours before admission and respiratory function showed a significant association between FVC% and FEV1% and PM10 concentrations at 96 hours. The relative risk was calculated to be 1.016 (95% confidence intervals: 1.001-1.032), which corresponds to a 1.6% increased risk of admission to hospital for COPD for each unit increase in PM10 concentration in the outside air.


The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA: implications for chemosensitivity and resistance.
Recent evidence suggests that patients with advanced microsatellite unstable (MSI) colorectal cancers lack a survival benefit with 5-fluorouracil (5-FU)-based chemotherapy. Additionally, tumor cells with MSI (caused by defective DNA mismatch repair) are more resistant to 5-FU in culture compared with microsatellite stable cells, despite similar amounts of 5-FU incorporation into the cell's DNA. We examined whether the component of the DNA mismatch repair (MMR) system that normally recognizes single base pair mismatches could specifically recognize 5-FU incorporated into DNA as a potential mechanism for chemosensitivity. We synthesized oligonucleotides with and without incorporated 5-FU and created oligonucleotides with a single base pair mismatch (as a positive control) to perform electromobility gel shift assays (EMSA) with a purified, baculovirus-synthesized hMutS alpha MMR complex. We also utilized surface plasmon resonance to measure relative binding differences between the oligonucleotides and hMutS alpha in real time. Using EMSA, we demonstrate that hMutS alpha recognizes and binds 5-FU-modified DNA. The reaction is specific as added ATP dissociates the hMutS alpha complex from the 5-FU-modified strand. Using surface plasmon resonance, we demonstrate greater binding between hMutS alpha and 5-FU-modified DNA compared with complementary DNA or DNA containing a C/T mismatch. The MMR complex hMutS alpha specifically recognizes and binds to 5-FU-modified DNA. Because MMR components are required for the induction of apoptosis by many DNA-damaging agents, the chemosensitivity of 5-FU for patients with advanced colorectal cancer may be in part due to recognition of 5-FU incorporated into tumor DNA by the MMR proteins.


Coverage evaluation surveys following soil-transmitted helminthiasis and schistosomiasis mass drug administration in Wolaita Zone of Ethiopia-The Geshiyaro project.
The Geshiyaro project aims to break transmission of soil-transmitted helminths and schistosomiasis in the Wolaita Zone of Ethiopia through a combination of two interventions: behavior change communication (BCC) for increased water, sanitation and hygiene (WaSH) infrastructure use alongside preventive chemotherapy (PC) using albendazole (ALB) and praziquantel (PZQ), targeted to reach 90% treatment coverage. Coverage evaluation surveys (CES) were conducted post-treatment, and the resultant survey coverage was compared to reported administrative coverage. This provided a secondary confirmation of the Geshiyaro project coverages, and is used to monitor the success of each Mass Drug Administration (MDA) round. A community-based cross-sectional study was conducted in 13 woredas (districts) of the Wolaita Zone. All eligible individuals from the selected households were invited for an interview. The study design, sample size, analysis and report writing were conducted according to the World Health Organization (WHO) CES guidelines for PC. The study interviewed a total of 3,568 households and 18,875 individuals across 13 woredas in the Wolaita Zone. Overall, the survey coverage across all studied woredas was 81.5% (95% CI; 80.9-82.0%) for both ALB and PZQ. Reported administrative coverage across all studied woredas was higher than survey coverage, 92.7% and 91.2% for ALB and PZQ, respectively. A significant portion of individuals (17.6%) were not offered PC. The predominant reason for not achieving the target coverage of 90% was beneficiary absenteeism during MDA (6.6% ALB, 6.8% PZQ), followed by drug distributors failing to reach all households (4.7% ALB, 4.8% PZQ), and beneficiaries not informed of the program (1.3% ALB, 1.7% PZQ). Programmatic actions will need to be taken during the next MDA campaign to achieve the targeted Geshiyaro project coverage threshold across data collection and program engagement. Adequate training and supervision on recording and reporting administrative coverage should be provided, alongside improved social mobilization of treated communities to increase participation, and strengthened institutional partnerships and communication.


Neurosurgery Resident Attrition Rates Defy Trends and Decrease During COVID-19 Pandemic.
We sought to determine the effects of the coronavirus disease 2019 (COVID-19) pandemic on U.S. neurosurgery resident attrition. We report the changes in resident attrition due to transfers, withdrawal, or dismissal from program training during the COVID-19 pandemic. Neurosurgery resident attrition data reported by the American Council of Graduate Medical Education for the academic year starting in July 2007 to the academic year ending in June 2022 were collected, and the rate of attrition was calculated. Individual postgraduate year program transfer rates were also calculated for the previous 7 consecutive academic years. The attrition rates for the academic years before the pandemic were compared with those during the pandemic. A total of 465 residents did not graduate from neurosurgical training during the past 15 academic years, of which 3 years were at least partially during the COVID-19 pandemic, resulting in a mean attrition rate of 2.5%. The attrition rates during the pandemic were lower than those before the pandemic (1.7% vs. 2.7%; P < 0.001), driven largely by a nearly twofold decrease in the withdrawal rate (0.67% vs. 1.2%; P = 0.003). Bivariate regression between the withdrawal and attrition rates showed a statistically significant correlation (r = 0.809; P < 0.001; r2 = 0.654). The first full year of the COVID-19 pandemic saw the most dramatic changes, with a z score for attrition of -1.9. Linear regression of the effect of training during the COVID-19 pandemic on attrition revealed a statistically significant difference (r = 0.563; P = 0.029; r2 = 0.317). The rate of withdrawal was most affected by training during the pandemic (r = 0.594; P = 0.010; r2 = 0.353). A statistically significant decline occurred in the rate of neurosurgery resident attrition during the COVID-19 pandemic that was most notable during the first full academic year (2020-2021). These findings were largely driven by a decrease in residents withdrawing from training programs. This contrasts with the overall trend toward resignation among healthcare workers during the pandemic. It is unclear what enduring ramifications this will have on neurosurgery residencies moving forward and whether we will see higher attrition rates as we transition toward a new normal. Future studies should examine trends in the attrition rates after the COVID-19 pandemic and determine the long-term effects of decreased attrition rates of residents during the pandemic.


Inhaled sevoflurane produces better delayed myocardial protection at 48 versus 24 hours after exposure.
Ischemia preconditioning produces a delayed window of cardioprotection against subsequent ischemia and reperfusion injury. Contradictory results have been reported regarding the ability of inhaled anesthetics to produce similar effects. Our investigation was designed to test whether inhaled sevoflurane is capable of producing a delayed window of anesthetic preconditioning and to compare the differences at 24 and 48 h after exposure. Male Fischer-344 rats, 2-4 mo old, were exposed to sevoflurane (2.5% for 60 min). Twenty-four or 48 h after exposure, the hearts were isolated and perfused for 30 min (equilibration) followed by 25 min of ischemia and then 60 min of reperfusion. Control hearts received no treatment before ischemia. Left ventricular (LV) function, creatine kinase (CK), and infarct size (IS) were measured. Nuclear magnetic resonance was used to measure Na+(i), [Ca2+]i, and pH(i). There was improved LV function and significant reduction in IS and CK and in both the 24- and 48-h delayed groups compared with the controls. There was also a significant recovery of LV function and reduction in IS and CK in the 48-h group when compared with the 24-h group. There was significant adenosine triphosphate preservation in both the 24- and 48-h groups, as well as a significant reduction in acidosis, [Ca2+]I, and Na+(i) in response to ischemia in both the groups versus the control. Sevoflurane is capable of producing a delayed window of preconditioning, and it takes more than 24 h to produce maximal protective effects.


Excellent response to pasireotide therapy in an aggressive and dopamine-resistant prolactinoma.
Prolactinomas are the most commonly encountered pituitary adenomas in the clinical setting. While most can be controlled by dopamine agonists, a subset of prolactinomas are dopamine-resistant and very aggressive. In such tumors, the treatment of choice is neurosurgery and radiotherapy, with or without temozolomide. Here, we report a patient with an highly aggressive, dopamine-resistant prolactinoma, who only achieved biochemical and tumor control during pasireotide long-acting release (PAS-LAR) therapy, a second-generation somatostatin receptor ligand (SRL). Interestingly, cystic degeneration, tumor cell necrosis or both was observed after PAS-LAR administration suggesting an antitumor effect. This case shows that PAS-LAR therapy holds clinical potential in selective aggressive, dopamine-resistant prolactinomas that express somatostatin (SST) receptor subtype 5 and appears to be a potential new treatment option before starting temozolomide. In addition, PAS-LAR therapy may induce cystic degeneration, tumor cell necrosis or both in prolactinomas.


Blocking PAR2 Alleviates Bladder Pain and Hyperactivity via TRPA1 Signal.
Bladder disorders associated with interstitial cystitis are frequently characterized by increased contractility and pain. The goals of this study were to examine 1) the effects of blocking proteinase-activated receptor-2 (PAR2) on the exaggerated bladder activity and pain evoked by cystitis and 2) the underlying mechanisms responsible for the role of PAR2 in regulating cystic sensory activity. The protein expression of PAR2 was amplified in rats with cystitis by inducing it with systemic administration of cyclophosphamide (CYP) as compared with control rats. Blocking PAR2 by intrathecal infusion of PAR2 antagonist FSLLRY-NH2 attenuated bladder hyperactivity and pain. In addition, blocking PAR2 attenuated the transient receptor potential A1 (TRPA1) signal pathway, whereas inhibition of the TRPA1 decreased bladder hyperactivity and pain. The data revealed specific signaling pathways leading to CYP-induced bladder hyperactivity and pain, including the activation of PAR2 and TRPA1. Inhibition of these pathways alleviates cystic pain. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of overactive bladder and pain often observed in cystitis.


Cold atmospheric plasma induces silver nanoparticle uptake, oxidative dissolution and enhanced cytotoxicity in glioblastoma multiforme cells.
Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50-60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in U373MG cells was >100-fold greater when treated with both CAP and PVA-AgNP compared with either therapy alone (IC50 of 4.30 μg/mL with PVA-AgNP alone compared with 0.07 μg/mL after 25s CAP and 0.01 μg/mL 40s CAP). Combined cytotoxicity was ROS-dependent and was prevented using N-Acetyl Cysteine. A novel darkfield spectral imaging method investigated and quantified AgNP uptake in cells determining significantly enhanced uptake, aggregation and subcellular accumulation following CAP treatment, which was confirmed and quantified using atomic absorption spectroscopy. The results indicate that CAP decreases nanoparticle size, decreases surface charge distribution of AgNP and induces uptake, aggregation and enhanced cytotoxicity in vitro.


Electromagnetic interference from left ventricular assist device in patients with transvenous implantable cardioverter-defibrillator.
Many advanced heart failure patients have both a left ventricular assist device (LVAD) and an implantable cardioverter-defibrillator (ICD). This study examines incidence, clinical impact, and management of LVAD-related EMI. We performed a three-center retrospective analysis of transvenous ICD implanted patients with LVAD implanted between January 1, 2005 and December 31, 2020. The primary outcome was EMI after LVAD implantation, categorized as LVAD-related noise or telemetry interference. The rate of LVAD-related EMI among the 737 patients (mean age 58.6 ± 12.8 years) studied was 5.0%. Telemetry interference (1.5%) compromised ICD interrogation in all patients. This was resolved successfully with use of a metal shield, encased wand, radiofrequency tower, different ICD programmer or by increasing distance between ICD programmer and LVAD (n = 6). ICD replacement was required to reestablish successful communication in three patients. LVAD-related noise (3.5%) led to oversensing (n = 4), inappropriate mode switches (n = 4), noise reversion (n = 3), inhibition of pacing (n = 2), inappropriate detection as atrial fibrillation (AF) (n = 2) and inappropriate detection as ventricular tachycardia (VT) and/or ventricular fibrillation (VF) (n = 2). This noise interference persisted (n = 3), resolved spontaneously (n = 16), resolved with programming change (n = 6) or required lead revision (n = 1). EMI from LVAD impacts ICD function, although, the incidence rate is low. Physicians implanting both, LVAD in patients with ICD (more common) or ICD in patients with LVAD, should be aware of possible interferences. Telemetry failure not resolved by metal shielding was overcome by ICD generator replacement to a different manufacturer. In most cases, LVAD-related noise resolves spontaneously.


Role of N6-methyladenosine methylation in glioma: recent insights and future directions.
Glioma is the most pervasive intracranial tumor in the central nervous system (CNS), with glioblastoma (GBM) being the most malignant type having a highly heterogeneous cancer cell population. There is a significantly high mortality rate in GBM patients. Molecular biomarkers related to GBM malignancy may have prognostic values in predicting survival outcomes and therapeutic responses, especially in patients with high-grade gliomas. In particular, N6-methyladenine (m6A) mRNA modification is the most abundant form of post-transcriptional RNA modification in mammals and is involved in regulating mRNA translation and degradation. Cumulative findings indicate that m6A methylation plays a crucial part in neurogenesis and glioma pathogenesis. In this review, we summarize recent advances regarding the functional significance of m6A modification and its regulatory factors in glioma occurrence and progression. Significant advancement of m6A methylation-associated regulators as potential therapeutic targets is also discussed.


Characterization of bovine Sarcocystis species by analysis of their 18S ribosomal DNA sequences.
Two Sarcocystis hirsuta isolates from 2 cattle (Bos taurus), 2 Sarcocystis hominis-like isolates from 2 cattle, 1 each Sarcocystis hominis-like isolate from a zoo-born dwarf zebu (B. taurus) and from a zoo-born bison (Bison bison), and 1 each Sarcocystis cruzi isolate from the dwarf zebu and the bison have been characterized by comparing the directly sequenced polymerase chain reaction products of their 18S rRNA genes. Sequences of 2 different isolates from the same species always showed a very high, nearly complete identity to each other both within all or only the conserved overlapping nucleotides. Thus, the 18S rDNA sequences of both S. hirsuta isolates proved to belong to a single species. The same is true for all 3 S. cruzi sequences. The 4 S. hominis-like isolates could not be placed within a single species using these criteria. They formed 2 separate groups (1 cattle isolate and the bison isolate, and the other cattle isolate and the dwarf zebu isolate). The results suggest that zoo-born large mammals do serve as intermediate hosts for Sarcocystis species known from indigenous herbivores, and that there might be another species found in cattle that is morphologically very similar to S. hominis.


Cryptococcus neoformans promotes its transmigration into the central nervous system by inducing molecular and cellular changes in brain endothelial cells.
Cryptococcus spp. cause fungal meningitis, a life-threatening infection that occurs predominately in immunocompromised individuals. In order for Cryptococcus neoformans to invade the central nervous system (CNS), it must first penetrate the brain endothelium, also known as the blood-brain barrier (BBB). Despite the importance of the interrelation between C. neoformans and the brain endothelium in establishing CNS infection, very little is known about this microenvironment. Here we sought to resolve the cellular and molecular basis that defines the fungal-BBB interface during cryptococcal attachment to, and internalization by, the human brain endothelium. In order to accomplish this by a systems-wide approach, the proteomic profile of human brain endothelial cells challenged with C. neoformans was resolved using a label-free differential quantitative mass spectrometry method known as spectral counting (SC). Here, we demonstrate that as brain endothelial cells associate with, and internalize, cryptococci, they upregulate the expression of several proteins involved with cytoskeleton, metabolism, signaling, and inflammation, suggesting that they are actively signaling and undergoing cytoskeleton remodeling via annexin A2, S100A10, transgelin, and myosin. Transmission electronic microscopy (TEM) analysis demonstrates dramatic structural changes in nuclei, mitochondria, the endoplasmic reticulum (ER), and the plasma membrane that are indicative of cell stress and cell damage. The translocation of HMGB1, a marker of cell injury, the downregulation of proteins that function in transcription, energy production, protein processing, and the upregulation of cyclophilin A further support the notion that C. neoformans elicits changes in brain endothelial cells that facilitate the migration of cryptococci across the BBB and ultimately induce endothelial cell necrosis.


Natriuretic effect of acute nifedipine administration is not mediated by the renal kallikrein-kinin system.
Despite their vasodilating action, calcium antagonists increase renal sodium excretion. To ascertain whether renal kallikrein plays a role in the renal effects of calcium antagonists, nifedipine (N) (10 mg orally) or placebo (P) was given to 17 male patients with mild to moderate essential hypertension during a 6-h infusion of either saline (S) or aprotinin (A) (2 X 10(6) KIU in 200 ml of saline). Blood pressure (BP) and heart rate (HR) were measured every 10 min, and blood samples were taken at -10, 0, 30, 60, 120, 240, 360 min for plasma renin activity (PRA), creatinine, and osmolarity determinations. Urinary kallikrein, aldosterone, creatinine, and electrolytes were measured in 6-h urine collections. The acute administration of N induced a significant systolic BP (SBP) and diastolic (DBP) fall and a transient PRA increase that peaked at 30 min and were not modified by A infusion. Urinary volume (+47%), Na+ (+54%) and Cl- (+58%) excretion were significantly enhanced by N. There were less pronounced and statistically not significant increases in urinary excretion of Ca2+ (+38%) and K+ (+29%). Infusion of A did not interfere with the natriuretic effect of N. Our data do not support the hypothesis that the kallikrein-kinin system plays an important role in mediating the renal effects of nifedipine in humans.


Impact of XPM and FWM on the digital implementation of impairment compensation for WDM transmission using backward propagation.
The impact of cross-phase modulation (XPM) and four-wave mixing (FWM) on electronic impairment compensation via backward propagation is analyzed. XPM and XPM+FWM compensation are compared by solving, respectively, the backward coupled Nonlinear Schrödinger Equation (NLSE) system and the total-field NLSE. The DSP implementations as well as the computational requirements are evaluated for each post-compensation system. A 12 x 100 Gb/s 16-QAM transmission system has been used to evaluate the efficiency of both approaches. The results show that XPM post-compensation removes most of the relevant source of nonlinear distortion. While DSP implementation of the total-field NLSE can ultimately lead to more precise compensation, DSP implementation sing the coupled NLSE system can maintain high accuracy with better computation efficiency and low system latency.


Off-the-shelf bone marrow-derived mesenchymal stem cell treatment for acute graft-versus-host disease: real-world evidence.
Temcell is a cryopreserved, human bone marrow-derived mesenchymal stem cell (MSC) product approved for the treatment of patients of all ages with acute graft-versus-host disease (GVHD). Initial experience with Temcell in a real-world setting from a cellular therapy registry in Japan is presented. A total of 381 consecutive patients were enrolled since its approval in 2016. The median cell number infused was 2.00 × 106/kg. The most common number of infusions was 8 in 100 patients. Of the 306 evaluable patients, the overall response rate (ORR) on day 28 after the start of MSC therapy was 56%. Of the 151 evaluable patients who received it as second-line therapy following first-line steroid therapy for classic acute GVHD, the ORR was 61%. Liver involvement of GVHD and ≥14 days from first-line steroid therapy to second-line MSC therapy was associated with a lower ORR. Day 28 ORR, patient age, GVHD grade, GVHD organ involvement, and a number of GVHD therapies before MSC therapy were associated with nonrelapse mortality. Overall survival at 6 months in 381 patients was 40%. This study suggests that Temcell is one of the treatment options for steroid-refractory acute GVHD until a new treatment with survival benefit is developed.


Mitochondrial DNA Release Is Induced by Apoptotic Stress and Drives the SASP.
Minority mitochondrial outer membrane permeabilization (miMOMP) during senescence drives the SASP.


Delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: proposal of an evidence-based combined clinical and imaging reference standard.
Aneurysmal subarachnoid hemorrhage is associated with high morbidity and mortality, with delayed neurologic deficits from delayed cerebral ischemia contributing to a large portion of the adverse outcomes in this patient population. There is currently no consensus reference standard for establishing the diagnosis of delayed cerebral ischemia either in the research or clinical settings, ultimately limiting strategies for preventing delayed infarction and permanent neurologic deficits. There are currently both clinical and imaging-based criteria for the diagnosis of delayed neurologic deficits and vasospasm, respectively, however, neither clinical nor angiographic assessment alone has been shown to identify patients who develop adverse outcomes from delayed infarction. Thus, the purpose of this work is to propose a 3-tiered combined imaging and clinical reference standard based on evidence from the literature to standardize the diagnosis of delayed cerebral ischemia, both to allow consistency across research studies and to ultimately improve outcomes in the clinical setting.


Taxonomic redescription and biological notes on Diaugia angusta (Diptera, Tachinidae): parasitoid of the palm boring weevils Metamasius ensirostris and M. hemipterus (Coleoptera, Dryophthoridae).
Diaugia angusta Perty, 1833 is a Neotropical species of Tachinidae (Diptera) reported here as a parasitoid of Metamasius ensirostris (Germar, 1824) and Metamasius hemipterus (Linnaeus, 1758) (Coleoptera: Dryophthoridae) in Brazil. Several species of Dryophthoridae and Curculionidae cause damage to bromeliad and palm species, and most are regarded as pests. In the present study, the male and female of Diaugia angusta are morphologically characterized and illustrated to provide a means for the identification of this parasitoid. Data obtained from preliminary field research show that natural parasitism of Metamasius pupae by Diaugia angusta varies by year but can reach nearly 30%. A network of parasitoid-host interactions among tachinid parasitoids and coleopteran hosts reported as bromeliad and palm pests (Dryophthoridae and Curculionidae) in the Americas indicates that the species of the tribe Dexiinisensu lato (including Diaugia angusta) might be promising as biological control agents of these pests.


Effects of intra-set rest on the ability to repeat work at maximal isometric strength.
The aim of this paper was to analyze how the rest between interval repetitions in intra-set training (at maximal isometric loads) could affect the ability to repeat maximal contractions in subjects with different levels of performance and different experience in strength development work. Twenty subjects were divided randomly into two different groups depending on their sport characteristics: ten subjects were trained in strength development work (Group Strenght--23.1±4.6 years; 172.0±5.3 cm; 79.9±12.1 kg; 2175.6±490.8 N; 46.9±4.9 mL/kg.min), and ten subjects were trained in endurance work (Group Endurance--21.3±4.5 years; 172.4±4.1 cm; 60.0±4.6 kg; 815.5±206.5 N; 67.4±4.9 mL/kg.min). To assess the ability to repeat maximal efforts, 20 repetitions of 5 seconds were performed in a half-squat position, with 1 minute of rest between repetitions. For both groups, four different phases were observed in the Interval Maximal Force test during the 20-repetition assessment: potentiation, maintenance, moderate loss, and significant loss. For the GE, the loss in maximum strength capacity began in the fourth repetition (GS4th: 3.4%, ns, Effect Size: 0.09 vs. GE3th: 1.6%; ns; ES: 0.06) and reached a statistically significant value in the twelfth repetition (GS12th: 12.7%, P=0.03, ES: 0.35 vs. GE7th: 12.5%; P=0.01; ES: 0.49). The number of repetitions at which the strength began to decrease depended on the subject's sport characteristic and performance level. This study shows how an appropriate intra-set rest inclusion can significantly increase the work performed in every set without changing the muscle contraction characteristics, thus delaying muscle fatigue and maintaining the desired training objective.


The Autism-Spectrum Quotient (AQ)--adolescent version.
The Autism Spectrum Quotient (AQ) quantifies autistic traits in adults. This paper adapted the AQ for children (age 9.8-15.4 years). Three groups of participants were assessed: Group 1: n=52 adolescents with Asperger Syndrome (AS) or high-functioning autism (HFA); Group 2: n=79 adolescents with classic autism; and Group 3, n=50 controls. The adolescents with AS/HFA did not differ significantly from the adolescents with autism but both clinical groups scored higher than controls. Approximately 90% of the adolescents with AS/HFA and autism scored 30+, vs. none of the controls. Among the controls, boys scored higher than girls. The AQ can rapidly quantify where an adolescent is situated on the continuum from autism to normality.


[Genotoxicity evaluation of nanoparticles].
There are considered the results of studies of genotoxicity of nanoparticles with an emphasis on studies in vivo. Oxidative stress was determined as a general mechanism genotoxicity of nanoparticles defined. There are reported the practical considerations relating to the genotoxic assessment of nanoparticles. In particular there was pointed out the priority of research in vivo, there was indicated to a possible dependence of the manifestation of effects as well on the properties of nanoparticles, as the timing of exposure, dose, route of administration, the peculiarities of the sample preparation. There was noted the desirability of the usage of positive controls in experiments. As tasks requiring solutions, there were separated the assessment of the ability of nanoparticles to the induction of gene mutations and evaluation of their genotoxic effects in embryonic and germ cells. There was given a conclusion on the general state of the problem and there were identified the priorities of research in genotoxicology of nanoparticles.


Renal tubular acidosis in renal transplantation recipients.
We aimed to investigate the prevalence, type, and possible risk factors of renal tubular acidosis (RTA) in Turkish patients with renal transplantation. The study included 66 adult renal transplantation recipients. We recorded the parameters of venous blood gas analysis including serum pH value, serum bicarbonate (HCO(3)) concentration, presence of metabolic acidosis, which was defined as low HCO(3) (<22 mEq/L), and serum pH value (<7.35) together, and base excess and urine pH at the last follow-up. Creatinine clearance was determined from 24-hour collected urine samples. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap. Mean age of 66 patients was 37.0 +/- 10.4 years; 48 of 66 patients were male. RTA was found in 14 (21.2%) patients. Considering for differential diagnosis of RTA, 4 patients had type 2 RTA and 10 had type 1 RTA. On the contrary, type 4 RTA was observed in no patients. Creatinine clearance was meaningfully lower in acidosis group than in those of the nonacidosis group (55.16 +/- 23.27 vs. 71.06 +/- 28.14 mL/min; p = 0.028). HCO(3) was correlated with hemoglobin level (r = 0.423, p = 0.001) and creatinine clearance (r = 0.262, p = 0.034). It was inversely correlated with cyclosporine A (CsA) level (r = -0.499, p = 0.035). RTA is a common complication after kidney transplantation. It is related with low creatinine clearance, low hemoglobin level, and high CsA level. Particularly, the value of creatinine clearance is lower and the possibility of RTA is higher.


Reverse Genetics Systems for the De Novo Rescue of Diverse Members of Paramyxoviridae.
Paramyxoviruses place significant burdens on both human and wildlife health; while some paramyxoviruses are established within human populations, others circulate within diverse animal reservoirs. Concerningly, bat-borne paramyxoviruses have spilled over into humans with increasing frequency in recent years, resulting in severe disease. The risk of future zoonotic outbreaks, as well as the persistence of paramyxoviruses that currently circulate within humans, highlights the need for efficient tools through which to interrogate paramyxovirus biology. Reverse genetics systems provide scientists with the ability to rescue paramyxoviruses de novo, offering versatile tools for implementation in both research and public health settings. Reverse genetics systems have greatly improved over the past 30 years, with several key innovations optimizing the success of paramyxovirus rescue. Here, we describe the significance of such advances and provide a generally applicable guide for the development and use of reverse genetics systems for the rescue of diverse members of Paramyxoviridae.


Charge transport within a three-dimensional DNA nanostructure framework.
Three-dimensional (3D) DNA nanostructures have shown great promise for various applications including molecular sensing and therapeutics. Here we report kinetic studies of DNA-mediated charge transport (CT) within a 3D DNA nanostructure framework. A tetrahedral DNA nanostructure was used to investigate the through-duplex and through-space CT of small redox molecules (methylene blue (MB) and ferrocene (Fc)) that were bound to specific positions above the surface of the gold electrode. CT rate measurements provide unambiguous evidence that the intercalative MB probe undergoes efficient mediated CT over longer distances along the duplex, whereas the nonintercalative Fc probe tunnels electrons through the space. This study sheds new light on DNA-based molecular electronics and on designing high-performance biosensor devices.