Aging of CKN: modulus versus conductivity analysis.
It was recently reported that the electrical modulus peaks narrows upon annealing of the ionic system CKN [Paluch et al., Phys. Rev. Lett. 110, 015702 (2013)], which was interpreted as providing evidence of dynamic heterogeneity of this glass. The present analysis of the same data in terms of the ac conductivity shows no shape changes, however. We discuss the relation between both findings and show further that the ac conductivity conforms to the prediction of the random barrier model at all times during the annealing.


Automated Echocardiographic Detection of Severe Coronary Artery Disease Using Artificial Intelligence.
The purpose of this study was to establish whether an artificially intelligent (AI) system can be developed to automate stress echocardiography analysis and support clinician interpretation. Coronary artery disease is the leading global cause of mortality and morbidity and stress echocardiography remains one of the most commonly used diagnostic imaging tests. An automated image processing pipeline was developed to extract novel geometric and kinematic features from stress echocardiograms collected as part of a large, United Kingdom-based prospective, multicenter, multivendor study. An ensemble machine learning classifier was trained, using the extracted features, to identify patients with severe coronary artery disease on invasive coronary angiography. The model was tested in an independent U.S. How availability of an AI classification might impact clinical interpretation of stress echocardiograms was evaluated in a randomized crossover reader study. Acceptable classification accuracy for identification of patients with severe coronary artery disease in the training data set was achieved on cross-fold validation based on 31 unique geometric and kinematic features, with a specificity of 92.7% and a sensitivity of 84.4%. This accuracy was maintained in the independent validation data set. The use of the AI classification tool by clinicians increased inter-reader agreement and confidence as well as sensitivity for detection of disease by 10% to achieve an area under the receiver-operating characteristic curve of 0.93. Automated analysis of stress echocardiograms is possible using AI and provision of automated classifications to clinicians when reading stress echocardiograms could improve accuracy, inter-reader agreement, and reader confidence.


Genotyping pooled DNA on microarrays: a systematic genome screen of thousands of SNPs in large samples to detect QTLs for complex traits.
Large samples and systematic screens of thousands of DNA markers are needed to detect quantitative trait loci (QTLs) of small effect size. One approach to conduct systematic genome scans for association is to use microarrays which, although expensive and non-reusable, simultaneously genotype thousands of single-nucleotide polymorphisms (SNPs). This brief report provides proof of principle that groups of pooled DNA (for example cases and controls) can be genotyped reliably on a microarray. DNA was pooled for 105 Caucasian males and genotyped three times on microarrays for more than 10,000 SNPs (Affymetrix GeneChip Mapping 10K Array Xba 131). The average correlation was 0.973 between the allele frequency estimates for the three microarrays using the same DNA pool. The correlation was 0.923 between the average of the three microarray estimates using pooled DNA and individual genotyping estimates for a Caucasian population as provided by Affymetrix (NetAffx). Thus, genotyping pooled DNA on microarrays can provide a systematic and powerful approach for identifying QTL associations for complex traits including behavioral dimensions and disorders.


An intersectional analysis of long COVID prevalence.
Long COVID symptoms - which include brain fog, depression, and fatigue - are mild at best and debilitating at worst. Some U.S. health surveys have found that women, lower income individuals, and those with less education are overrepresented among adults with long COVID, but these studies do not address intersectionality. To fill this gap, we conduct an intersectional analysis of the prevalence and outcomes of long COVID in the U.S. We posit that disparities in long COVID have less to do with the virus itself and more to do with social determinants of health, especially those associated with occupational segregation and the gendered division of household work. We use 10 rounds of Household Pulse Survey (HPS) data collected between June 2022 and March 2023 to perform an intersectional analysis using a battery of descriptive statistics that evaluate (1) the prevalence of long COVID and (2) the interference of long COVID symptoms with day-to-day activities. We also use the HPS data to estimate a set of multivariate logistic regressions that relate the odds of having long COVID and activity limitations due to long COVID to a set of individual characteristics as well as intersections by sex, race/ethnicity, education, and sexual orientation and gender identity. Findings indicate that women, some people of color, sexual and gender minorities, and people without college degrees are more likely to have long COVID and to have activity limitations from long COVID. Women have considerably higher odds of developing long COVID compared to men, a disparity exacerbated by having less education. Intersectional analysis by gender, race, ethnicity, and education reveals a striking step-like pattern: college-educated men have the lowest prevalence of long COVID while women without college educations have the highest prevalence. Daily activity limitations are more evenly distributed across demographics, but a different step-like pattern is present: fewer women with degrees have activity limitations while limitations are more widespread among men without degrees. Regression results confirm the negative association of long COVID with being a woman, less educated, Hispanic, and a sexual and gender minority, while results for the intersectional effects are more nuanced. Results point to systematic disparities in health, highlighting the urgent need for policies that increase access to quality healthcare, strengthen the social safety net, and reduce economic precarity.


Ordinal regression by a generalized force-based model.
This paper introduces a new instance-based algorithm for multiclass classification problems where the classes have a natural order. The proposed algorithm extends the state-of-the-art gravitational models by generalizing the scaling behavior of the class-pattern interaction force. Like the other gravitational models, the proposed algorithm classifies new patterns by comparing the magnitude of the force that each class exerts on a given pattern. To address ordinal problems, the algorithm assumes that, given a pattern, the forces associated to each class follow a unimodal distribution. For this reason, a weight matrix that allows to modify the metric in the attributes space and a vector of parameters that allows to modify the force law for each class have been introduced in the model definition. Furthermore, a probabilistic formulation of the error function allows the estimation of the model parameters using global and local optimization procedures toward minimization of the errors and penalization of the non unimodal outputs. One of the strengths of the model is its competitive grade of interpretability which is a requisite in most of real applications. The proposed algorithm is compared to other well-known ordinal regression algorithms on discretized regression datasets and real ordinal regression datasets. Experimental results demonstrate that the proposed algorithm can achieve competitive generalization performance and it is validated using nonparametric statistical tests.


Association of Psychopharmacological Medication Preference with Autistic Traits and Emotion Regulation in ADHD.
This study intends to evaluate the relationship between medication switching and autistic traits, emotion dysregulation, and methylphenidate side effects in children with attention deficit hyperactivity disorder (ADHD). Children with ADHD, ages 9-18, treated with methylphenidate (MTP) (n = 23), and switched to atomoxetine (ATX) (n = 20) were included. All participants were interviewed with K-SADS-PL to confirm ADHD diagnosis and exclude comorbid psychiatric disorders. The participants then completed Difficulty in Emotion Regulation Scale (DERS) and Autism-Spectrum Quotient (AQ) and their parents completed Autism Spectrum Screening Questionnaire (ASSQ) and Barkley Stimulant Side Effect Rating Scale(BSSERS). The MTP group scored higher than the ATX group in ASSQ, AQ, and the lack of emotional clarity subscale of DERS, while the ATX group had higher scores in the emotional non-acceptance subscale of DERS. No differences were found between the MTP and ATX groups in methylphenidate side-effect severity. Multiple regression analyses revealed that non-acceptance of emotions predicted the switch to ATX while lack of emotional clarity predicted the maintenance of MTP therapy, rather than autistic traits. This study highlights emotion regulation difficulties and how different emotional profiles may influence medication selection in children with ADHD.


Effects of different visual stimuli on postures and knee moments during sidestepping.
Evasive sidestepping during sports commonly results in noncontact anterior cruciate ligament injuries. Sidestepping in response to different simple visual stimuli has been studied previously but never investigated using quasi-game-realistic visual conditions. We compared the biomechanics of high-level and low-level soccer players when sidestepping in response to projected, three-dimensional defender(s) and the traditionally used planned and unplanned arrow stimuli. A three-dimensional motion analysis system captured the trunk and lower limb kinematics and ground reaction forces of 15 high-level and 15 low-level soccer players sidestepping in response to a one-defender scenario (1DS), two-defender scenario (2DS), arrow-planned condition (AP), and arrow-unplanned condition (AUNP). The temporal constraints imposed by the stimuli conditions resulted in increasing difficulty from AP, 1DS, 2DS, to AUNP. Selected joint kinematics and three-dimensional knee moments during the weight-acceptance phase of sidestepping were analyzed. Hip external rotation at initial foot contact was smaller when participants sidestepped in response to the projected defenders versus arrow conditions. Hip abduction was smallest in the AP, moderate in the defender scenarios, and largest in the AUNP. Peak knee valgus moments were 25% larger in the defender scenarios and 70% larger in the AUNP compared with the AP. High-level players exhibited decreased hip abduction and knee valgus moments in the 2DS compared with the low-level players. Compared with the arrow conditions, sidestepping in response to the defender(s) resulted in different postures and knee moments, which further differentiated between high-level and low-level players in the complex 2DS. These findings highlight the effects of stimuli realism and complexity on the visual-perceptual-motor skill of sidestepping, which has implications for anterior cruciate ligament injury prevention.


Interactive effects of global change factors on soil respiration and its components: a meta-analysis.
As the second largest carbon (C) flux between the atmosphere and terrestrial ecosystems, soil respiration (Rs) plays vital roles in regulating atmospheric CO2 concentration ([CO2 ]) and climatic dynamics in the earth system. Although numerous manipulative studies and a few meta-analyses have been conducted to determine the responses of Rs and its two components [i.e., autotrophic (Ra) and heterotrophic (Rh) respiration] to single global change factors, the interactive effects of the multiple factors are still unclear. In this study, we performed a meta-analysis of 150 multiple-factor (≥2) studies to examine the main and interactive effects of global change factors on Rs and its two components. Our results showed that elevated [CO2 ] (E), nitrogen addition (N), irrigation (I), and warming (W) induced significant increases in Rs by 28.6%, 8.8%, 9.7%, and 7.1%, respectively. The combined effects of the multiple factors, EN, EW, DE, IE, IN, IW, IEW, and DEW, were also significantly positive on Rs to a greater extent than those of the single-factor ones. For all the individual studies, the additive interactions were predominant on Rs (90.6%) and its components (≈70.0%) relative to synergistic and antagonistic ones. However, the different combinations of global change factors (e.g., EN, NW, EW, IW) indicated that the three types of interactions were all important, with two combinations for synergistic effects, two for antagonistic, and five for additive when at least eight independent experiments were considered. In addition, the interactions of elevated [CO2 ] and warming had opposite effects on Ra and Rh, suggesting that different processes may influence their responses to the multifactor interactions. Our study highlights the crucial importance of the interactive effects among the multiple factors on Rs and its components, which could inform regional and global models to assess the climate-biosphere feedbacks and improve predictions of the future states of the ecological and climate systems.


Impaired Antibody Response Following the Second Dose of the BNT162b2 Vaccine in Patients With Myeloproliferative Neoplasms Receiving Ruxolitinib.
Data on the effect of ruxolitinib on antibody response to severe acute respiratory coronavirus 2 (SARS-CoV-2) vaccination in patients with myeloproliferative neoplasms (MPN) is lacking. We prospectively evaluated anti-spike-receptor binding domain antibody (anti-S Ab) levels after the second dose of the BNT162b2 (Pfizer-BioNTech) vaccine in MPN patients. A total of 74 patients with MPN and 81 healthy controls who were vaccinated were enrolled in the study. Of the MPN patients, 27% received ruxolitinib at the time of vaccination. Notably, MPN patients receiving ruxolitinib had a 30-fold lower median anti-S Ab level than those not receiving ruxolitinib (p < 0.001). Further, the anti-S Ab levels in MPN patients not receiving ruxolitinib were significantly lower than those in healthy controls (p < 0.001). Regarding a clinical protective titre that has been shown to correlate with preventing symptomatic infection, only 10% of the MPN patients receiving ruxolitinib had the protective value. Univariate analysis revealed that ruxolitinib, myelofibrosis, and longer time from diagnosis to vaccination had a significantly negative impact on achieving the protective value (p = 0.001, 0.021, and 0.019, respectively). In subgroup analysis, lower numbers of CD3+ and CD4+ lymphocytes were significantly correlated with a lower probability of obtaining the protective value (p = 0.011 and 0.001, respectively). In conclusion, our results highlight ruxolitinib-induced impaired vaccine response and the necessity of booster immunisation in MPN patients. Moreover, T-cell mediated immunity may have an important role in the SARS-CoV-2 vaccine response in patients with MPN, though further studies are warranted.


Structural analysis of the interaction of the pyrimidine tract-binding protein with the internal ribosomal entry site of encephalomyocarditis virus and foot-and-mouth disease virus RNAs.
Initiation of translation of a subset of eukaryotic mRNAs results from internal ribosomal entry. This process is exemplified by encephalomyocarditis virus (EMCV), which contains an internal ribosomal entry site (IRES) within its 5' nontranslated region that is approximately 450-nt long and consists of a series of stem-loops designated H-L. We have previously identified a cellular 58-kDa polypeptide that binds specifically to this IRES and that is implicated in its function as the pyrimidine tract-binding protein PTB. We have now mapped PTB binding sites directly on the IRES elements of EMCV and the related foot-and-mouth disease virus (FMDV) using structure-specific enzymatic probes and base-specific chemical probes. PTB bound to six sites on the EMCV IRES: site 1 (UCUU401) is upstream of domain H, site 2 is the basal helix of domain H (nt 407-410 and 440-443), site 3 (UCUUU423) is the apical loop of domain H, site 4 is the apical helix and adjacent internal bulged loop of domain K, site 5 (CUUUA750) is the apical loop of domain K, and site 6 (CCUUU815) is downstream of domain L. PTB bound to sites on the FMDV IRES that correspond precisely to EMCV sites 3, 5, and 6. These sites have the consensus sequence CUUU and form two groups that are located near to the 5' and 3' borders of these IRES elements. Their position, and the effects of mutation of them on IRES function are consistent with PTB's role in IRES-mediated initiation being to bind to multiple sites in the IRES, thereby stabilizing a specific active conformation.


HIV Diagnosis and the Clinical Course of COVID-19 Among Patients Seeking Care Within the New York City Public Hospital System During the Initial Pandemic Peak.
Reports conflict on how HIV infection influences the clinical course of COVID-19. The New York City (NYC) public hospital system provides care for over 14,000 people with HIV, was central in responding to the COVID-19 pandemic, and is therefore in a unique position to evaluate the intersection of these concurrent infections. Retrospective chart review of patients presenting to NYC Health and Hospitals (NYC H+H) diagnosed with COVID-19 infection from March 1, 2020, through April 28, 2020, compared people living with HIV (PLWH) and a propensity-matched (PM) control group of patients without HIV to evaluate associations between HIV status and COVID-19 outcomes. Two hundred thirty-four PLWH presented for COVID-19 testing and 110 (47%) were diagnosed with COVID-19. Among 17,413 patients with COVID-19 and without HIV, 1:n nearest neighbor propensity score matching identified 194 patients matched on age, sex, race, and any comorbidity. In the sample with COVID-19 (N = 304), PLWH (9.1%) had lower rates of mortality than controls [19.1%; PM odds ratio (PM-OR): 0.41, 95% confidence interval (CI): 0.19-0.86]. Among hospitalized COVID-19 patients (N = 179), HIV infection was associated with lower rates of mechanical ventilation (PM-OR: 0.31, 95% CI: 0.11-0.84) and mortality (PM-OR: 0.40, 95% CI: 0. 17-0.95). In the extended pandemic period through April 2021, aggregate data by HIV status suggested elevated hospitalization and mortality rates in PLWH versus people without HIV. These results suggest that the direct biological impacts of the HIV virus do not negatively influence COVID-19-related outcomes when controlling for comorbidity and demographic variables.


[The value of mammary thermography. A report on 655 cases (author's transl)].
A total of 655 patients were investigated by both mammography and contact thermography, and 63 cancers of the breast were detected. Thermography was slightly more sensitive (0.82) than mammography (0.75). They were of equal specificity (0.96 and 0.97). A critical analysis of the experimental conditions, however, leads the authors to propose thermography as the essential investigation completing clinical examination and mammography. It may also have a certain prognostic value, but this remains to be demonstrated.


Ankyrin-G directly binds to kinesin-1 to transport voltage-gated Na+ channels into axons.
Action potentials (APs) propagating along axons require the activation of voltage-gated Na(+) (Nav) channels. How Nav channels are transported into axons is unknown. We show that KIF5/kinesin-1 directly binds to ankyrin-G (AnkG) to transport Nav channels into axons. KIF5 and Nav1.2 channels bind to multiple sites in the AnkG N-terminal domain that contains 24 ankyrin repeats. Disrupting AnkG-KIF5 binding with small interfering RNA or dominant-negative constructs markedly reduced Nav channel levels at the axon initial segment (AIS) and along entire axons, thereby decreasing AP firing. Live-cell imaging showed that fluorescently tagged AnkG or Nav1.2 cotransported with KIF5 along axons. Deleting AnkG in vivo or virus-mediated expression of a dominant-negative KIF5 construct specifically decreased the axonal level of Nav, but not Kv1.2, channels in mouse cerebellum. These results indicate that AnkG functions as an adaptor to link Nav channels to KIF5 during axonal transport before anchoring them to the AIS and nodes of Ranvier.


Clinical and cost effectiveness of a cleanser protectant lotion for treatment of perineal skin breakdown in low-risk patients with incontinence.
Perineal dermatitis due to urinary and/or fecal incontinence is a common problem. A multicenter, open label, phase II product evaluation was conducted to determine the effectiveness of a new cleanser protectant lotion in reducing perineal erythema and pain in patients at low-risk for perineal dermatitis and to compare the cost of this product to standard protocols of care. Nineteen elderly patients (14 male, 5 female, mean age 73.1 years) participated in the study. Average baseline scores for erythema and pain were 2.3 (+/- 0.5) and 1.5 (+/- 1.0), respectively (scale 0 to 4). After 7 days, both scores were significantly lower (mean scores 0.6 +/- 0.8 and 0.3 +/- 0.8, respectively; P < 0.01). Based on an average of 2.6 perineal episodes per day, the one-step product evaluated would cost $136 per patient/year less than standard protocols of care while reducing caregiver time (average 23 seconds per episode of care). Optimal perineal care may reduce the incidence of complications; studies to ascertain the safety and effectiveness of commonly used products and procedures are needed.


Multiprocessor pyramid architectures for bottom-up image analysis.
This paper describes three hierarchical organizations of small processors for bottom-up image analysis:pyramids, interleaved pyramids, and pyramid trees. Progressively lower levels in the hierarchies process image windows of decreasing size. Bottom-up analysis is made feasible by transmitting up the levels quadrant borders and border-related information that captures quadrant interaction of interest for a given computation. The operation of the pyramid is illustrated by examples of standard algorithms for interior-based computations (e.g., area) and border-based computations of local properties (e.g., perimeter). A connected component counting algorithm is outlined that illustrates the role of border-related information in representing quadrant interaction. Interleaved pyramids are obtained by sharing processors among several pyramids. They increase processor utilization and throughput rate at the cost of increased hardware. Trees of shallow interleaved pyramids, calld pyramid trees, are introduced to reduce the hardware requirements of large interleaved pyramids at the expense of increased processing time, without sacrificing processor utilization. The three organizations are compared with respect to several performance measures.


Acute disseminated encephalomyelitis in children. A descriptive study in Tehran, Iran.
To determine the frequency, etiology (viral infection or vaccination), presenting signs and symptoms, response to therapy, complication and course of acute disseminated encephalomyelitis (ADEM) in our hospitals. A 2-year retrospective, descriptive, chart review of children with final diagnosis of ADEM in 2 hospitals (Hazrat Rasool and Mofid in Tehran, Iran during 2000-2002) were carried out. The diagnosis is based upon clinical presentation, physical examination and ruling out of other disease (imaging, laboratories and so forth) of expert pediatric neurologists. Acute disseminated encephalomyelitis was documented in all cases by characteristics MRI changes included inflammation and demyelination in subcortical or periventricular regions. Acute disseminated encephalomyelitis were diagnosed in 15 patients. More than half of patients were between 9-14 years old. It was rare in 1-5 years old children. It had an abrupt onset, preceding infection/vaccination with no gender differences. Approximately 46.4% of cases had a recent upper respiratory tract illness. Varicella zoster virus infection, urinary tract infection, and mycoplasma pneumoniae were observed. Presentation signs included ataxia, decreased consciousness, fever plus nausea/vomiting, cranial nerve involvement, dysarthric speech, convulsion, hemiparesis, paresthesia, meningismus, and headache. We identified inflammation and demyelination in subcortical than periventricular lesions by magnetic resonance imaging. Prognosis was excellent with low mortality rate (6.6%). Acute disseminated encephalomyelitis is common in our children, possibly because of the high prevalence of causative infections. Due to advances in control of traditional exanthematous diseases such as measle, rubella and so forth, most cases of ADEM in this study followed non-specific upper respiratory infections. Differentiation of ADEM from a single episode of multiple sclerosis is difficult. Diagnosis of multiple sclerosis should be carried out if new symptoms and signs or imaging abnormalities appear, more than 3 months after the onset of clinical symptoms in ADEM cases.


Biological effects of combustion-derived particles from different biomass sources on human bronchial epithelial cells.
Combustion-derived particles (CDPs), in particular from traffic, are regarded as a central contributor for adverse health effects linked to air pollution. Recently, also biomass burning has been recognized as an important source for CDPs. Here, the effects of CDPs (PM10) originating from burning of pellet, charcoal and wood on key processes associated to lung carcinogenesis were explored. Human bronchial epithelial cells (HBEC3-KT) were exposed to 2.5 μg/cm2 of CDPs for 24 h and biological effects were examined in terms of cytotoxicity, inflammation, epithelial to mesenchymal transition (EMT)-related effects, DNA damage and genotoxicity. Reduced cell migration, inflammation and modulation of various PM-associated genes were observed mainly after exposure to wood and pellet. In contrast, only particles from pellet burning induced alteration in cell proliferation and DNA damage, which resulted in cell cycle alterations. Charcoal instead, appeared in general less effective in inducing pro-carcinogenic effects. These results illustrate differences in the toxicological profile due to the CDPs source. The different chemical compounds adsorbed on CDPs seemed to be central for particle properties, leading to an activation of various cellular signaling pathways involved in early steps of cancer progression.


Warming magnifies predation and reduces prey coexistence in a model litter arthropod system.
Climate warming can destabilize interactions between competitors as smaller organisms gain advantages in warmer environments. Whether and how warming-induced effects on competitive interactions are modified by predation remains unknown. We hypothesized that predation will offset the competitive advantage of smaller prey species in warmer environments because of their greater vulnerability to predation. To test this, we assembled a litter arthropod community with two Collembola species (Folsomia candida and Proisotoma minuta) of different body sizes across a temperature gradient (three thermal environments) and in the presence and absence of predatory mites. Predatory mites reduced Collembola coexistence with increasing temperatures. Contradicting our hypothesis, the larger prey species always outperformed the smaller prey species in warmer environments with predators. Larger prey probably benefited as they expressed a greater trait (body length) plasticity to warming. Warming can thus magnify predation effects and reduce the probability of prey coexistence.


The rationale for requesting a second consecutive sperm ejaculate for assisted reproductive technology.
We assessed the value of requesting a second semen sample provided within 1 hour of the first in cases of unacceptable ejaculate quality (compared to previous occasions) or very poor semen characteristics. The study population consisted of 109 males with severe oligo-terato-astenospermic (OTA) syndrome in an assisted reproduction program. Semen volume, sperm count and sperm motility were recorded in the first and second samples with a Makler Counting Chamber before sperm processing, and total motile sperm in the ejaculate was calculated. Differences in sperm parameters between the consecutive samples were determined by paired-sample t test. In 36 cases (33%) the second sample was found to be superior in quality to the first and was therefore used for the fertilization process. Of the 12/109 cases in which the first ejaculate demonstrated no motile sperm, five (41%) had detectable motile sperm in the second (total 0.1 x 10(6), 0.2 x 10(6), 0.3 x 10(6), 8.4 x 10(6) and 20.8 x 10(6)). We conclude that a request for second ejaculate immediately after the first in males with poor semen quality or no detectable motile sperm can yield a better sample in a significant percentage of cases. Using this method, clinicians can avoid the utilization of elaborate sperm processing techniques and the need for unnecessary micromanipulative fertilization.


Blood pressure and other metabolic syndrome factors and risk of brain tumour in the large population-based Me-Can cohort study.
Brain tumour has few established determinants. We assessed to which extent risk of brain tumour was related to metabolic syndrome factors in adults. In the Me-Can project, 580 000 individuals from Sweden, Austria, and Norway were followed for a median of 10 years after baseline measurement. Data on brain tumours were obtained from national cancer registries. The factors of metabolic syndrome (BMI, SBP and DBP, and blood levels of glucose, cholesterol, and triglycerides), separately and combined, were analysed in quintiles and for transformed z-scores (mean transformed to 0 and standard deviation to 1). Cox proportional hazards multivariate regression models were used, with corrections for measurement error. During follow-up, 1312 primary brain tumours were diagnosed, predominantly meningioma (n = 348) and high-grade glioma (n = 436). For meningioma, the hazard ratio was increased for z-scores of SBP [hazard ratio = 1.27 per unit standard deviation, 95% confidence interval (CI) 1.03-1.57], of DBP (hazard ratio = 1.29, 95% CI 1.04-1.58), and of the combined metabolic syndrome score (hazard ratio = 1.31, 95% CI 1.11-1.54). An increased risk of high-grade glioma was found for DBP (hazard ratio = 1.23, 95% CI 1.01-1.50) and triglycerides (hazard ratio = 1.35, 95% CI 1.05-1.72). For both meningioma and high-grade glioma, the risk was more than double in the fifth quintiles of DBP compared to the lowest quintile. For meningioma this risk was even larger for SBP. Increased blood pressure was associated with risk of brain tumours, especially of meningiomas.


Steroid regulation of human placental integrins: suppression of alpha2 integrin expression in cytotrophoblasts by glucocorticoids.
Maintenance of uterine-placental attachment during human pregnancy may depend at least partly on adhesive interactions between cytotrophoblasts and their extracellular matrix (ECM). Such interactions are often mediated by integrins, signal-transducing heterodimeric transmembrane glycoproteins. We previously showed that glucocorticoid (GC) suppressed the expression of collagen and laminin in human placenta; here we show that GC also modulates the expression by human cytotrophoblasts of the integrin subunits alpha2 and beta1, components of a known receptor for these ECM ligands. Cytotrophoblasts were isolated from human term placentas, cultured up to 4 days in the presence of 0-1000 nM dexamethasone (DEX), and assayed for 1) integrin messenger RNA (mRNA) levels by Northern hybridization, 2) integrin subunit synthesis after [35S]methionine labeling, or 3) cell surface integrin levels after 125I labeling by lactoperoxidase. In four independent experiments, 100 nM DEX reduced mRNA levels for integrin alpha2 to 6+/-1% of the control value. This effect was similar between 1-4 days of treatment and was dose dependent between 1-1000 nM DEX. Cortisol treatment (100 nM) inhibited levels of integrin alpha2 mRNA, but 100 nM testosterone, estradiol, and progesterone were less effective, suggesting that this response was specific to GC. In immunoprecipitation studies, treatment of cytotrophoblasts with 100 nM DEX for 2 days reduced the rates of synthesis of the alpha2 integrin subunit as well as its expression on the cell surface to 1-10% of control levels. DEX effects on the beta1 integrin subunit were less dramatic. DEX reduced beta1 mRNA levels to only 69+/-8% of control levels, a smaller reduction compared with effects on alpha2 integrin mRNA. DEX inhibited beta1 protein synthesis and cell surface expression to 60-70% of control levels. In all experiments, DEX had no effect on total protein synthesis. Thus, our results demonstrate that GC treatment specifically and markedly down-regulates expression of alpha2 integrin subunit by human cytotrophoblasts. This finding is consistent with the concept that uterine-placental adherence across gestation may be regulated by coordinate effects on ECM ligands and cellular adhesion receptors.


BNCT of 3 cases of spontaneous head and neck cancer in feline patients.
Having demonstrated BPA-BNCT induced control of experimental squamous cell carcinomas (SCC) of the hamster cheek pouch mucosa with no damage to normal tissue we explored the feasibility and safety of treating spontaneous head and neck tumors, with particular focus on SCC, of terminal feline patients with low dose BPA-BNCT employing the thermal beam of the RA-1 Reactor within a preclinical context. The biodistribution studies showed that, in all three cases evaluated, BPA delivered absolute boron values to tumor in the range that proved therapeutically useful in the experimental model of SCC. BPA-BNCT studies showed no radiotoxic effects, partial tumor control in terms of impaired growth and partial necrosis, an improvement in clinical condition and prolonged survival beyond the terminal condition of the feline patients at the time of recruitment.


Signal pathway of hippocampal apoptosis and cognitive impairment of mice caused by cerium chloride.
Experimental studies have demonstrated that lanthanides could impair cognitive functions of children and animals, but very little is known about the hippocampal apoptosis and its molecular mechanism. The study investigated the signal pathway of hippocampal apoptosis induced by intragastric administration of CeCl(3) for 60 consecutive days. It showed that cerium had been significantly accumulated in the mouse hippocampus, and CeCl(3) caused hippocampal apoptosis and impairment of spatial recognition memory of mice. CeCl(3) effectively activated caspase-3 and -9, inhibited Bcl-2, and increased the levels of Bax and cytochrome c, promoted accumulation of reactive oxygen species in the mouse hippocampus. It implied that CeCl(3)-induced apoptosis in the mouse hippocampus could be triggered via mitochondrion-mediated pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers.


E2F1 represses beta-catenin/TCF activity by direct up-regulation of Siah1.
Transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Its activity is strictly controlled by the pRB/E2F pathway. In the majority of cancer cells, however, this pathway is frequently found deregulated, and the underlying mechanism involving transcriptional control by E2F1 has not yet been fully elucidated. Here we report the identification of two putative E2F1-binding sites located upstream from Siah1 transcription start site (+1). Chromatin immunoprecipitation assay reveals that transcription factor E2F1 is capable of binding to the putative sites, and luciferase reporter assay shows that E2F1 can activate transcription from the Siah1 promoter. Ectopic expression of E2F1 elevates the Siah1 level, hence suppressing the beta-catenin/TCF activity. Consistently, knock-down of endogenous E2F1 by a shRNA strategy results in reduced expression of Siah1. Moreover, repression of beta-catenin/TCF activity by E2F1 can be attenuated by shRNA-based repression of endogenous Siah1, implying that Siah1 is a bona fide E2F1 target gene, which at least partly, mediates the suppression of beta-catenin/TCF signalling pathway.


Earlier maturation of pregnant black and white adolescents.
A survey was made of the menarcheal age and anthropometry of 1,844 lower income, nulliparous female patients receiving prenatal care. No differences were observed between black and white patients in height and maximum pregnant weight. A significantly earlier mean menarcheal age was observed in adolescents (12 to 16 years) compared with adults (17 to 31 years). Younger adolescents (12 to 14 years) of both races were taller and heavier (prepregnancy) than National Center for Health Statistics standards and had a significantly greater weight-for-height. Menarcheal age and body habitus were consistent with other reports that younger pregnant adolescents tend to be earlier maturers than older pregnant adolescents and adults. Compared with their age-group cohorts (13 to 31 years) in the two-decades-old Collaborative Perinatal Study of the National Institute of Neurological Communicative Disorders and Stroke, these female patients were larger and had greater pregnancy weight gains. These anthropometric findings may reflect the two decades of improvements in social assistance and prenatal care for lower income women.


Reduced alpha 1-adrenergic receptor-mediated inositide hydrolysis in cardiac atria of senescent rats.
We investigated the effect of age on epinephrine stimulation of phosphoinositide hydrolysis in atrial slices prepared from F-344 female rats. Three age groups were chosen for study: young adults (aged 6 months), mature adults (aged 15 months), and senescent animals (aged 25 months). Tissue slices were labeled with [3H]myoinositol and epinephrine-stimulated hydrolysis measured in the presence of LiCl. Epinephrine caused a dose-dependent increase in phosphoinositide hydrolysis in each age group. This increase was blocked by prazosin, suggesting that alpha 1-adrenergic receptors are involved. In animals aged 6 months, epinephrine caused a maximal increase in hydrolysis of 2.8-fold over basal. The maximal response was reduced at 15 months (2.52-fold increase, p less than 0.05) and at 25 months (2.02-fold increase, p less than 0.01). The potency for epinephrine stimulation of phosphoinositide hydrolysis was unchanged with age. The data indicate that alpha 1-mediated phosphoinositide hydrolysis in atria is reduced with age.


Slide-Ring Materials Using Cyclodextrin.
We have recently synthesized slide-ring materials using cyclodextrin by cross-linking polyrotaxanes, a typical supramolecule. The slide-ring materials have polymer chains with bulky end groups topologically interlocked by figure-of-eight shaped junctions. This indicates that the cross-links can pass through the polymer chains similar to pulleys to relax the tension of the backbone polymer chains. The slide-ring materials also differ from conventional polymers in that the entropy of rings affects the elasticity. As a result, the slide-ring materials show quite small Young's modulus not proportional to the cross-linking density. This concept can be applied to a wide variety of polymeric materials as well as gels. In particular, the slide-ring materials show remarkable scratch-proof properties for coating materials for automobiles, cell phones, mobile computers, and so on. Further current applications include vibration-proof insulation materials for sound speakers, highly abrasive polishing media, dielectric actuators, and so on.


A case of peripheral primitive neuroectodermal tumor of the ovary.
Peripheral primitive neuroectodermal tumor (PNET) belongs to the PNET/Ewing's sarcoma family. PNET is a small round cell tumor of putative neuroectoderm origin and is the second most common sarcoma among children and young adults. It may occur anywhere in the body and within any age group; however, it is most likely to occur in the bone and soft tissues. There have been a small number of case reports of PNET arising in the ovary. We presented a case of PNET arising in the right ovary of an 18-year-old woman. The tumor was metastased to the lymph nodes of the pelvis and para-aorta at surgical staging. We had persecuted Taxol/carboplatin chemotherapy, pelvic cavity radiotherapy, and Vincristine/Actinomycin, Cyclophosphamide/Doxorubicin (VACA). She died after 10 months due to septic shock.


Heart rate increases in liraglutide treated chronic heart failure patients: association with clinical parameters and adverse events.
Background. Liraglutide, a glucagon-like peptide-1 agonist, is used for treatment of type 2 diabetes and has beneficial cardiovascular properties. However, treatment increases heart rate (HR) and possibly the risk of cardiovascular events in chronic heart failure (CHF) patients. We investigated potential associations between HR changes and clinical, laboratory and echocardiographic parameters and clinical events in liraglutide treated CHF patients. Methods. This was a sub-study of the LIVE study. CHF patients (N = 241) with a left ventricular ejection fraction ≤45% were randomised to 1.8 mg liraglutide daily or placebo for 24 weeks. Electrocardiograms (N = 117) and readouts from cardiac implanted electronic devices (N = 20) were analysed for HR and arrhythmias. Results. In patients with sinus rhythm (SR), liraglutide increased HR by 8 ± 9 bpm (pulse measurements), 9 ± 9 bpm (ECG measurements) and 9 ± 6 bpm (device readouts) versus placebo (all p<.005). Increases in HR correlated with liraglutide dose (p=.01). HR remained unchanged in patients without SR. Serious cardiac adverse events were not associated with HR changes. Conclusions. During 6 months of treatment, HR increased substantially in CHF patients with SR treated with liraglutide but was not associated with adverse events. The long-term clinical significance of increased HR in liraglutide treated CHF patients needs to be determined.


Testing the triple network model of psychopathology in a transdiagnostic neurodevelopmental cohort.
The triple network model of psychopathology posits that altered connectivity between the Salience (SN), Central Executive (CEN), and Default Mode Networks (DMN) may underlie neurodevelopmental conditions. However, this has yet to be tested in a transdiagnostic sample of young people. We investigated this in 175 children (60 girls) that represent a heterogeneous population who are experiencing neurodevelopmental difficulties in cognition and behavior, and 60 comparison children (33 girls). Hyperactivity/impulsivity and inattention were assessed by parent-report. Resting-state functional Magnetic Resonance Imaging data were acquired and functional connectivity was calculated between independent network components and regions of interest. We then examined whether connectivity between the SN, CEN and DMN was dimensionally related to hyperactivity/impulsivity and inattention, whilst controlling for age, gender, and motion. Hyperactivity/impulsivity was associated with increased functional connectivity between the SN, CEN, and DMN in at-risk children, whereas it was associated with decreased functional connectivity between the CEN and DMN in comparison children. These effects replicated in an adult parcellation of brain function and when using increasingly stringent exclusion criteria for in-scanner motion. Triple network connectivity characterizes transdiagnostic neurodevelopmental difficulties with hyperactivity/impulsivity. We suggest that this may arise from delayed network segregation, difficulties sustaining CEN activity to regulate behavior, and/or a heightened developmental mismatch between neural systems implicated in cognitive control relative to those implicated in reward/affect processing.


A novel RARα/CAR-mediated mechanism for regulation of human organic solute transporter-β gene expression.
The organic solute transporter-α/β (OSTα/β) is a heteromeric transporter that is essential for bile acid and sterol disposition and for the enterohepatic circulation. To better understand the mechanism underlying OST gene regulation, the effects of retinoic acid (RA) on OSTα/β gene expression were investigated. The results show a dose-dependent induction of OSTβ but not OSTα expression in both Huh7 and HepG2 cells by RA treatment. A novel functional RA receptor response element (RARE; so-called DR5) in the promoter of OSTβ gene was identified. The interaction of RARα/RXRα with the RARE was verified by electrophoretic mobility shift and chromatin immunoprecipitation assays and its functional importance by hOSTβ promoter activation in luciferase reporter assays. The studies demonstrated that the RARE is also a constitutive androstane receptor (CAR) binding site for OSTβ gene regulation. These results suggest that OSTβ is a target of both FXR-mediated (by binding to IR-1 element) and RARα- and CAR-mediated (by binding to DR5 element) gene regulation pathways. In summary, this study has uncovered a novel RARE (DR5) element in the promoter of OSTβ that binds RARα or CAR heterodimerized with RXRα and appears to function synergistically with the IR-1 element to provide maximal induction of OSTβ in response to RA. These findings demonstrate a role for RARα and CAR in controlling OSTβ expression levels.


In vivo and in vitro rearing of entomopathogenic nematodes (Steinernematidae and Heterorhabditidae).
Entomopathogenic nematodes (EPN) (Steinernematidae and Heterorhabditidae) have a mutualistic partnership with Gram-negative Gamma-Proteobacteria in the family Enterobacteriaceae. Xenorhabdus bacteria are associated with steinernematids nematodes while Photorhabdus are symbionts of heterorhabditids. Together nematodes and bacteria form a potent insecticidal complex that kills a wide range of insect species in an intimate and specific partnership. Herein, we demonstrate in vivo and in vitro techniques commonly used in the rearing of these nematodes under laboratory conditions. Furthermore, these techniques represent key steps for the successful establishment of EPN cultures and also form the basis for other bioassays that utilize these organisms for research. The production of aposymbiotic (symbiont-free) nematodes is often critical for an in-depth and multifaceted approach to the study of symbiosis. This protocol does not require the addition of antibiotics and can be accomplished in a short amount of time with standard laboratory equipment. Nematodes produced in this manner are relatively robust, although their survivorship in storage may vary depending on the species used. The techniques detailed in this presentation correspond to those described by various authors and refined by P. Stock's Laboratory, University of Arizona (Tucson, AZ, USA). These techniques are distinct from the body of techniques that are used in the mass production of these organisms for pest management purposes.


Co-occurrence of conduct disorder and depression in a clinic-based sample of boys with ADHD.
Children with attention-deficit/hyperactivity disorder (ADHD) are at risk for the development of comorbid conduct disorder (CD) and depression. The current study examined potential psychosocial risk factors for CD and depression in a clinic-based sample of 203 boys (aged 6-10 years) with ADHD. The boys and their mothers participated in an evaluation that involved assessments of cognitive, behavioral, academic, and family functioning. Potential predictors of CD and depression involved four domains: parenting behaviors, family environment, academic/cognitive functioning, and peer relations. ADHD groups were defined using mother- and teacher-report of DSM-IV symptoms. Mother-ratings of DSM-IV symptoms were obtained for a subsample of 91 boys approximately 5 years after the initial assessment. For both mother- and teacher-defined ADHD groups, social problems were related to depression symptoms; hostile, inconsistent, and detached parenting behaviors were related to CD symptoms; and family environment characterized by low cohesion, high conflict, and low marital satisfaction was related to CD and depression symptoms. For the teacher-defined ADHD group, parenting variables also predicted depression symptoms. Academic and cognitive variables did not predict CD or depression symptoms when parenting, family, and peer relationship variables were taken into account. Depression prospectively predicted CD, but not the reverse, and parental hostile control and familial conflict prospectively predicted CD for the teacher-defined ADHD group only. Source-specificity is a useful consideration when describing the relation of parenting and home environment with CD and depression symptoms in boys with ADHD. Intervention efforts that address these parenting, family, and peer relationship variables may aid in preventing the development of comorbid conditions.


The impact of 'best-practice' patient care in fibromyalgia on practice economics.
The office time required for primary care physicians (PCPs) to diagnose, treat and manage fibromyalgia (FM) patients can be extensive. The study objective was to determine if PCPs can positively impact practice economics by requiring fewer patient visits and less office time, while still achieving an acceptable quality of life, as reported by the physician. Survey of PCPs who diagnose, manage and treat FM patients. Surveys were administered to US private practice PCPs, obtaining information on the number of office visits, and time spent with FM patients. PCPs were allotted into two groups: FM-efficient (FME; n = 40) and FM usual care (FMUC; n = 54), based on their reported ability to achieve an acceptable quality of life for ≥50% of their FM patients in less than four office visits post FM diagnosis. An economic model estimated the monetary value of each PCP cohorts' time spent with a newly diagnosed FM patient over a 2-year timeframe. Significant office time cost differences across 2 years exist between FME PCPs and FMUC PCPs ($840 vs. $1117, P < 0.05). FME PCPs had a significantly lower cost of scheduled time to confirm diagnosis ($243 vs. $339, P < 0.05) and time to find right treatment ($264 vs. $365, P < 0.05) than FMUC PCPs. Both groups incurred costs related to excess visit time, but it was less for FME PCPs ($119, 29 minutes) than FMUC PCPs ($182, 44 minutes, P < 0.01), driven by quicker diagnosis confirmation (P < 0.01) and treatment initiation (P < 0.01). Research suggests that efficient FM care delivery during diagnosis and treatment can be associated with improved practice economics.


[Elevated levels of leptin and LDL-cholesterol in patients with well controlled congenital adrenal hyperplasia].
The objective of this study was to evaluate patients with classic CAH before and after treatment with glucocorticoids/mineralocorticoid and compare the metabolic profile of the well controlled (WC) and poorly controlled (PC) group. We selected newly diagnosed patients and patients monitored for CAH, classical form, regularly using or not glucocorticoids/mineralocorticoid in the Genetics Service Hupes-UFBA, seen from March/2004 to May/2006. All patients underwent detailed clinical evaluation and laboratory tests (glucose, sodium and potassium; total cholesterol, HDL, LDL, triglycerides and uric acid; leptin, 17-hydroxyprogesterone, total testosterone, C peptide, and insulin). Patients with normal androgens were classified as well controlled (WC), and those with high levels of androgens either using or not glucocorticoids/mineralocorticoids were classified as poorly controlled (PC). We studied 41 patients with CAH: 11 in the WC group and 30 in PC group. Leptin and LDL cholesterol levels were higher in WC than in the PC group (p < 0.05). Uric acid values were lower in WC compared with the PC group (p < 0.05). Adequate control of CAH with steroids seems safe, as it is associated with only mild changes in lipid profile and leptin values. No other metabolic abnormality was associated with glucocorticoid use. The reason for lower uric acid levels found in WC CAH patients is unknown and should be further studied.


Impact of on-site cardiac interventional facilities on management and outcome of patients with acute coronary syndromes.
To investigate the impact of on-site cardiac interventional facilities on the management and outcome of patients with versus those without ST elevation acute coronary syndromes (ACS) in the Canadian-American Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb population. Data from 4605 patients were analyzed in relation to the admitting hospital's capability to perform coronary procedures (noninvasive, angiography-capable and interventional hospitals). Differences in medication use, revascularization rate and patient outcome were determined. Whereas medication use during hospitalization and at discharge differed between non-ST elevation ACS patients treated in the three groups, these were generally more comparable among ST elevation ACS patients. In both ST segment cohorts, patients treated in interventional hospitals underwent coronary procedures more often (angiography rate greater than 70% versus 40% for noninvasive hospitals) and sooner (median two to three days versus four days in noninvasive hospitals) than those treated in other hospitals. Recurrent ischemia was significantly less common in non-ST elevation ACS patients treated in interventional hospitals (32% versus 36% in angiography-capable and 40% in noninvasive hospitals, P<0.001) and tended to be less common among ST elevation ACS patients treated in interventional hospitals. Patients treated in interventional hospitals tended to have lower mortality in the non-ST elevation ACS cohort but significantly fewer died in the ST elevation ACS during hospitalization and at 30 days, six months and one year (8.8% versus 11% in angiography-capable and 15% in noninvasive hospitals, P=0.015). These differences in mortality persisted after adjustment for key baseline covariates. Separate analysis of Canadian and American patients revealed similar mortality patterns, as to the total population, in both ST segment cohorts. Presence of an on-site cardiac interventional facility favourably affected the management and outcome of ACS patients in both non-ST and ST elevation cohorts.


Risk factors for developing postthymectomy myasthenia gravis in thymoma patients.
Thymoma patients with no prior history of myasthenia gravis (MG) occasionally have MG after thymectomy. This study aimed to identify risk factors for developing postthymectomy MG. We retrospectively reviewed the characteristics and clinical outcomes of thymoma patients without preoperative MG who underwent a thymectomy at our institute. Of the 229 thymoma patients who underwent surgery from 1991 to 2011, 123 had no history of MG. The serum of all patients was analyzed for acetylcholine receptor antibodies (AchR-Ab), and 33 patients had detectable levels (greater than 0.2 nmol/L). Ten seropositive patients had MG develop postoperatively within 3 to 2,859 days, whereas 90 seronegative patients did not. Univariate analysis showed that a positive result for serum AchR-Ab (p < 0.001), type B1/B2/B3 thymoma histology (p = 0.025), and incomplete resection (p = 0.008) were risk factors for the development of MG. In patients with post-thymectomy MG, the AchR-Ab levels at the onset of MG were significantly higher than the preoperative levels (p = 0.036). The analysis of the 33 antibody-positive patients showed a significant correlation between antibody levels and the onset of disease (p = 0.003). The analysis of 12 patients with incomplete resection revealed that perioperative chemotherapy or radiotherapy reduced the risk of development of MG (p = 0.009). A positive result for serum AchR-Ab, type B1/B2/B3 thymoma histology, and incomplete resection were considered risk factors for the development of postthymectomy MG. Preoperative levels of serum AchR-Ab should be examined in all thymoma patients. Perioperative chemotherapy or radiotherapy for the patients with incomplete resection might reduce the risk of MG development.


Outstanding micro-endemism in New Caledonia: More than one out of ten animal species have a very restricted distribution range.
New Caledonia is a biodiversity hotspot, with an extremely high number of endemic species with narrow distribution ranges that are at high risk of extinction due to open-cast nickel mining, invasive species and seasonal man-induced fires. Mentions of micro-endemism permeate the literature on the biota of this archipelago. However, so far there has been no research comparing distribution range in different animal groups. The aim of this study is to examine the implication of different sampling effort variables in order to distinguish micro-endemicity from data deficiency, and evaluate the distribution range, frequency, and extent to which micro-endemism is common to several groups of organisms. We compiled a dataset derived from publications in Zoologia Neocaledonica, comprising 1,149 species, of which 86% are endemic to New Caledonia. We found that the sampling effort variables that were best correlated with distribution range were the number of sampling dates and the number of collectors per species. The median value of sampling dates was used to establish a cut-off point for defining adequately sampled species. We showed that, although only 52% of species were sampled adequately enough to determine their distribution range, the number of species with a very narrow distribution range was still high. Among endemics from New Caledonia, 12% (116 species) have ranges ≤5.2km2 and 3.9% (38 species) have ranges between 23 and 100 km2. Surprisingly, a similar trend was observed in non-endemic species: 22% occurred in areas ≤ 5.2 km2, and 8% in areas 23-100 km2, suggesting that environmental dissimilarity may play an important role in the distribution of these species. Micro-endemic species were predominant in 18 out of 20 orders. These results will contribute to a re-assessment of the IUCN red list of species in this archipelago, indicating that at least 116 species are probably critically endangered.


Prediction of novel miRNAs and associated target genes in Glycine max.
Small non-coding RNAs (21 to 24 nucleotides) regulate a number of developmental processes in plants and animals by silencing genes using multiple mechanisms. Among these, the most conserved classes are microRNAs (miRNAs) and small interfering RNAs (siRNAs), both of which are produced by RNase III-like enzymes called Dicers. Many plant miRNAs play critical roles in nutrient homeostasis, developmental processes, abiotic stress and pathogen responses. Currently, only 70 miRNA have been identified in soybean. We utilized Illumina's SBS sequencing technology to generate high-quality small RNA (sRNA) data from four soybean (Glycine max) tissues, including root, seed, flower, and nodules, to expand the collection of currently known soybean miRNAs. We developed a bioinformatics pipeline using in-house scripts and publicly available structure prediction tools to differentiate the authentic mature miRNA sequences from other sRNAs and short RNA fragments represented in the public sequencing data. The combined sequencing and bioinformatics analyses identified 129 miRNAs based on hairpin secondary structure features in the predicted precursors. Out of these, 42 miRNAs matched known miRNAs in soybean or other species, while 87 novel miRNAs were identified. We also predicted the putative target genes of all identified miRNAs with computational methods and verified the predicted cleavage sites in vivo for a subset of these targets using the 5' RACE method. Finally, we also studied the relationship between the abundance of miRNA and that of the respective target genes by comparison to Solexa cDNA sequencing data. Our study significantly increased the number of miRNAs known to be expressed in soybean. The bioinformatics analysis provided insight on regulation patterns between the miRNAs and their predicted target genes expression. We also deposited the data in a soybean genome browser based on the UCSC Genome Browser architecture. Using the browser, we annotated the soybean data with miRNA sequences from four tissues and cDNA sequencing data. Overlaying these two datasets in the browser allows researchers to analyze the miRNA expression levels relative to that of the associated target genes. The browser can be accessed at http://digbio.missouri.edu/soybean_mirna/.


Disruption of hypoxia inducible factor-2α in neutrophils decreases colitis-associated colon cancer.
Neutrophils are abundant immune cells in the colon tumor microenvironment. Studies have shown that neutrophils are recruited into hypoxic foci in colon cancer. However, the impact of hypoxia signaling on neutrophil function and its involvement in colon tumorigenesis remain unclear. To address this, we generated mice with a deletion of hypoxia (HIF)-1α or HIF-2α in neutrophils driven by the MRP8Cre (HIF-1αΔNeu) or (HIF-2αΔNeu) and littermate controls. In an azoxymethane (AOM)/dextran sulfate sodium (DSS) model of colon cancer, the disruption of neutrophils-HIF-1α did not result in any significant changes in body weight, colon length, tumor size, proliferation, or burden. However, the disruption of HIF-2α in neutrophils led to a slight increase in body weight, a significant decrease in the number of tumors, and a reduction in tumor size and volume compared to their littermate controls. Histological analysis of colon tissue from mice with HIF-2α-deficient neutrophils revealed notable reductions in proliferation as compared to control mice. Additionally, we observed reduced levels of pro-inflammatory cytokines, such as TNF-α and IL-1β, in neutrophil-specific HIF-2α deficient mice in both the tumor tissue as well as the neutrophils. Importantly, it is worth noting that the reduced tumorigenesis associated with HIF-2α deficiency in neutrophils was not evident in already established syngeneic tumors or a DSS-induced inflammation model, indicating a potential role of HIF-2α specifically in colon tumorigenesis. In conclusion, we found that the loss of neutrophil-specific HIF-2α slows colon tumor growth and progression by reducing the levels of inflammatory mediators.


Interconnected Porous Monolith Prepared via UiO-66 Stabilized Pickering High Internal Phase Emulsion Template.
High internal phase emulsion (HIPE) templating offers an efficient approach to prepare 3D hierarchical porous metal-organic framework (MOF)-based monoliths. However, conventional poly-Pickering HIPEs synthesized from MOF-stabilized HIPEs have low permeability due to closed-cell structures, thus limiting their applications. Herein, interconnected porous MOF monoliths, prepared by adding a small amount of polyvinyl alcohol (PVA) as co-stabilizer into UiO-66 stabilized Pickering HIPE templates are reported. The morphology of the porous monoliths was studied by scanning electron microscopy (SEM). The pore size could be well controlled by varying the PVA concentration. A unique morphology, formed by an ice template, was clearly seen on the cell wall. The pores were thus interconnected. The mass transfer performance of the monoliths having different cell structures was investigated by CO2 adsorption. The interconnected porous structure significantly accelerated the CO2 adsorption process, as well as enhancing the saturated adsorption capacity.


Be Careful with an IV Line.
Obtaining an intravenous (IV) access is a simple procedure which can be done in almost any hospital setting. One of the most dreaded complications of this procedure is an inadvertent intra-arterial cannulation. This can result in an accidental injection of medications intra-arterially, which can potentially lead to life altering consequences. In the hope that these types of events can be prevented, we are presenting a case of a 57-year-old male who underwent bougie dilatation for an oesophageal stricture and was accidentally given medication for pain management intra-arterially through an improperly placed IV line, which resulted in ischaemia, gangrene and subsequent loss of the hand. Those who try to obtain an IV access should always be on the lookout for possible clues that can prevent an inadvertent IA injection, especially if cannulation is in an area where an artery is in close proximity to a vein; these clues include but are not limited to the following: a bright-red flash of blood in the cannula, pulsatile movement of blood in the IV line, and intense pain or burning at the site of injection. These signs, as well as educating the patient on early symptoms of ischaemia, may allow early action to be taken, to prevent irreparable damage. We always have to be careful when we insert an I.V line.


GATA2 deficiency and human hematopoietic development modeled using induced pluripotent stem cells.
GATA2 deficiency is an inherited or sporadic genetic disorder characterized by distinct cellular deficiency, bone marrow failure, various infections, lymphedema, pulmonary alveolar proteinosis, and predisposition to myeloid malignancies resulting from heterozygous loss-of-function mutations in the GATA2 gene. How heterozygous GATA2 mutations affect human hematopoietic development or cause characteristic cellular deficiency and eventual hypoplastic myelodysplastic syndrome or leukemia is not fully understood. We used induced pluripotent stem cells (iPSCs) to study hematopoietic development in the setting of GATA2 deficiency. We performed hematopoietic differentiation using iPSC derived from patients with GATA2 deficiency and examined their ability to commit to mesoderm, hemogenic endothelial precursors (HEPs), hematopoietic stem progenitor cells, and natural killer (NK) cells. Patient-derived iPSC, either derived from fibroblasts/marrow stromal cells or peripheral blood mononuclear cells, did not show significant defects in committing to mesoderm, HEP, hematopoietic stem progenitor, or NK cells. However, HEP derived from GATA2-mutant iPSC showed impaired maturation toward hematopoietic lineages. Hematopoietic differentiation was nearly abolished from homozygous GATA2 knockout (KO) iPSC lines and markedly reduced in heterozygous KO lines compared with isogenic controls. On the other hand, correction of the mutated GATA2 allele in patient-specific iPSC did not alter hematopoietic development consistently in our model. GATA2 deficiency usually manifests within the first decade of life. Newborn and infant hematopoiesis appears to be grossly intact; therefore, our iPSC model indeed may resemble the disease phenotype, suggesting that other genetic, epigenetic, or environmental factors may contribute to bone marrow failure in these patients following birth. However, heterogeneity of PSC-based models and limitations of in vitro differentiation protocol may limit the possibility to detect subtle cellular phenotypes.


Actions of ethanol on voltage-sensitive sodium channels: effects on neurotoxin binding.
Exposure of rat forebrain synaptosomes (P2) to ethanol in vitro reduced the specific binding of [3H]batrachotoxinin A 20-alpha-benzoate ([3H]BTX-B) to voltage-sensitive sodium channels. This effect of ethanol was concentration-dependent and was affected by the membrane potential. Under depolarizing conditions ethanol was significantly more potent at inhibiting [3H]BTX-B binding. Scatchard analysis of [3H]BTX-B binding revealed that ethanol increased the equilibrium binding constant without affecting the apparent maximum number of binding sites. The rate of formation of the [3H]BTX-B/receptor complex was unchanged in the presence of ethanol whereas the rate of dissociation was accelerated by ethanol. These findings are consistent with an indirect allosteric mechanism for inhibition of [3H]BTX-B binding. The binding of [3H]saxitoxin was unaffected by ethanol suggesting that the specific receptor sites in the channel display differential sensitivity to the inhibitory effect of ethanol. These data, in conjunction with ion flux measurements, provide further evidence that ethanol can affect the voltage-sensitive sodium channels in neuronal membranes.


Effects of Temperature and Wildflower Strips on Survival and Macronutrient Stores of the Alfalfa Leafcutting Bee (Hymenoptera: Megachilidae) Under Extended Cold Storage.
Megachile rotundata (F.) is an important pollinator of alfalfa in the United States. Enhancing landscapes with wildflowers is a primary strategy for conserving pollinators and may improve the sustainability of M. rotundata. Changing cold storage temperatures from a traditionally static thermal regime (STR) to a fluctuating thermal regime (FTR) improves overwintering success and extends M. rotundata's shelf life and pollination window. Whether floral resources enhance overwintering survival and/or interact with a thermal regime are unknown. We tested the combined effects of enhancing alfalfa fields with wildflowers and thermal regime on survival and macronutrient stores under extended cold storage (i.e., beyond one season). Megachile rotundata adults were released in alfalfa plots with and without wildflower strips. Completed nests were harvested in September and stored in STR. After a year, cells were randomly assigned to remain in STR for 6 months or in FTR for a year of extended cold storage; emergence rates were observed monthly. Macronutrient levels of emerged females were assessed. FTR improved M. rotundata survival but there was no measurable effect of wildflower strips on overwintering success or nutrient stores. Timing of nest establishment emerged as a key factor: offspring produced late in the season had lower winter survival and dry body mass. Sugars and glycogen stores increased under FTR but not STR. Trehalose levels were similar across treatments. Total lipid stores depleted faster under FTR. While wildflowers did not improve M. rotundata survival, our findings provide mechanistic insight into benefits and potential costs of FTR for this important pollinator.


Allergens from Fusarium solani identified by immunoblotting in asthma patients In Iran.
We extracted Fusarium solani antigens to evaluate specific anti-F. solani IgE in fifty-one patients with asthma (33 men and 18 women) and in 22 non-atopic healthy subjects (15 men and 7 women). F. solani strains were cultured in Sabouraud glucose agar and subjected to cell disruption using the freeze-and-thaw method. The obtained cytoplasmic extracts were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Sensitisation to F. solani antigens has been evaluated in asthmatic patients using the immunoblotting assay. The SDS-PAGE identified 29 protein bands in the cytoplasmic extracts of F. solani isolates, with molecular weights ranging from 24 kDa to 112 kDa. Immunoblotting detected specific anti-F. solani IgE antibody in all asthma patients, but not in the control group. The predominant reactive allergens in patients corresponded to the bands with molecular weights of 24 kDa, 58.5 kDa, 64.5 kDa, 69 kDa, 72 kDa, and 97 kDa. Our results suggest that various allergenic components of F. solani may produce symptoms of asthma in susceptible individuals and they call for further research.


Teaching the RAPID approach at the start of emergency medicine clerkship: an evaluation.
The RAPID approach (Resuscitation, Analgesia and assessment, Patient needs, Interventions, Disposition) was developed as an approach to managing emergency department patients. It is a mental checklist to help trainees provide comprehensive care, addressing issues in priority. Its impact on trainee performance has not been assessed. Forty-two clerkship students were enrolled, with 21 students in each group. They received or did not receive the teaching intervention on an alternate basis. Students were assessed through daily encounter cards, a case presentation, a self-assessment form, a prerotation case (case E), and a six-case short-answer exit examination (cases A to F) with case E repeated. Case E was designed specifically to assess students' ability to provide comprehensive care. Fourteen students participated in focus groups. Students in the intervention group had significantly higher exit examination case E scores (11.67 of 14 v. 10.26 of 14, p = 0.008) and improvement in their case E scores from pre- to postrotation (1.82 v. 0.26, p = 0.006). There were no significant differences in the other outcome measures. Intervention group students made positive comments around analgesia, addressing nonmedical needs and counseling on health promotion during focus groups. Students exposed to the RAPID approach at the start of their emergency medicine rotation performed better on the one component of the written examination for which it was designed to improve performance. Students found it to be a useful mental checklist for comprehensive care, possibly addressing the hidden curriculum. Emergency medicine educators should consider further study and careful implementation of the RAPID approach.


ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons.
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by motor neuron cell death. However, not all motor neurons are equally susceptible. Most of what we know about the surviving motor neurons comes from gene expression profiling; less is known about their functional traits. We found that resistant motor neurons cultured from SOD1 ALS mouse models have enhanced axonal outgrowth and dendritic branching. They also have an increase in the number and size of actin-based structures like growth cones and filopodia. These phenotypes occur in cells cultured from presymptomatic mice and mutant SOD1 models that do not develop ALS but not in embryonic motor neurons. Enhanced outgrowth and upregulation of filopodia can be induced in wild-type adult cells by expressing mutant SOD1. These results demonstrate that mutant SOD1 can enhance the regenerative capability of ALS-resistant motor neurons. Capitalizing on this mechanism could lead to new therapeutic strategies.


Lack of CD34 positive stromal cells within angiomyomas (vascular leiomyomas).
To investigate the role of CD34 positive stromal cells in the morphogenesis and tumour growth regulation of angiomyomas (vascular leiomyomas). Histochemical analysis using monoclonal antibodies to CD34 and CD31 was performed in 10 angiomyomas and their adjacent soft tissue. CD34 positive stromal cells were not seen within the tumour tissue; the thick walled vessels within the tumours lacked CD34 positive stromal cells. In contrast, bundles of CD34 positive stromal cells were detected at the tumour border of all of the angiomyomas and in the adventitial tissue of the surrounding normal vessels. The lack of CD34 positive stromal cells within an angiomyoma is associated with the characteristic morphology of an angiomyoma.


Cryoballoon versus radiofrequency catheter ablation for paroxysmal atrial fibrillation.
Catheter ablation is an established treatment for atrial fibrillation (AF). Cryoballoon ablation (CBA) has emerged as an alternative to radiofrequency ablation (RFA). However, there are few data comparing these modalities for treatment of paroxysmal AF (pAF) in the U.S. The purpose of this study was to compare procedural times, safety, and efficacy of CBA against RFA. A single-center prospective cohort study evaluated patients who underwent catheter ablation for pAF using CBA or RFA between January 1, 2010 and October 31, 2013. Patients with prior ablation and those without rhythm follow-up for at least 3 months were excluded. The primary end point was freedom from AF, atrial flutter, and atrial tachycardia (FFAF) >30 seconds after a 3-month blanking period without requirement for antiarrhythmic drugs. We also compared rates of successful pulmonary vein isolation (PVI), fluoroscopy and procedure times, and major complication rates. A total of 201 patients were included (CBA = 101, RFA = 100). The rate of successful PVI was 99.3% in CBA versus 97.4% in RFA (P = 0.08). Procedure times were shorter with CBA (192.9 ± 44.0 minutes vs 283.7 ± 78.0 minutes, P < 0.001) as well as total fluoroscopy times (46.0 ± 22.4 minutes vs 73.0 ± 30.1 minutes, P < 0.001). Overall complication rates were equivalent; however, fewer cardiac perforations occurred with CBA (0% vs 4%, P = 0.042). The 1-year FFAF rates were 60.3% for CBA and 61.1% for RFA (log rank P = 0.93). CBA was associated with equivalent 1-year FFAF rate as RFA for pAF. Procedure and fluoroscopy times were shorter for CBA and fewer cardiac perforations occurred.


Incidence and severity of chronic pain after caesarean section: A systematic review with meta-analysis.
The frequency of caesarean section has increased dramatically in recent decades. Despite this, robust data regarding the consequences of caesarean section in terms of developing chronic postsurgical pain (CPSP) are still lacking. This systematic review analysed the incidence and severity of CPSP in women 3 to less than 6, 6 to less than 12, and at least 12 months after caesarean section. Systematic review of prospective and retrospective observational studies and randomised controlled trials with meta-analysis. We searched MEDLINE to May 2015. We included all studies investigating the incidence and/or severity of CPSP at least 3 months after caesarean section. The primary outcome was chronic postsurgical wound pain (CPSP 'wound'). Secondary outcomes were persistent pain in the back area, pelvic region or reported as residual pain, and severity of 'birth-related' chronic pain. Meta-analysis using the random-effects model based on 15 studies (n = 4475) reporting CPSP 'wound' at 3 to less than 6 months after caesarean section revealed an incidence of 15.4% [95% confidence interval (CI): 9.9 to 20.9%]. For 6 to less than 12 and at least 12 months after caesarean section, the incidence of CPSP 'wound' was estimated at 11.5% (95% CI: 8.1 to 15.0%, n = 3345) and 11.2% (95% CI: 7.4 to 15.0%, n = 3451), respectively. Meta-regression analysis using the publication year as predictor revealed stable CPSP 'wound' incidences at each postoperative time slot from 2002 to the present. Of those patients who reported chronic pain, 9.6% (95% CI: 0.0 to 21.0%) had severe pain, 23.5% (95% CI: 10.0 to 37.0%) had moderate pain and 49.2% (95% CI: 18.9 to 79.4%) had mild pain at 6 months. Major limitations are high statistical heterogeneity of the meta-analyses and inconsistencies in reporting severity of chronic 'birth-related' pain. This meta-analysis finds a clinically relevant incidence of CPSP 'wound' after caesarean section ranging from 15% at 3 months to 11% at 12 months or longer that has been largely stable in recent years.


Effect of high-sugar grasses on methane emissions simulated using a dynamic model.
High-sugar grass varieties have received considerable attention for their potential ability to decrease N excretion in cattle. However, feeding high-sugar grasses alters the pattern of rumen fermentation, and no in vivo studies to date have examined this strategy with respect to another environmental pollutant: methane (CH(4)). Modeling allows us to examine potential outcomes of feeding strategies under controlled conditions, and can provide a useful framework for the development of future experiments. The purpose of the present study was to use a modeling approach to evaluate the effect of high-sugar grasses on simulated CH(4) emissions in dairy cattle. An extant dynamic, mechanistic model of enteric fermentation and intestinal digestion was used for this evaluation. A simulation database was constructed and analysis of model behavior was undertaken to simulate the effect of (1) level of water-soluble carbohydrate (WSC) increase in dietary dry matter, (2) change in crude protein (CP) and neutral detergent fiber (NDF) content of the plant with an increased WSC content, (3) level of N fertilization, and (4) presence or absence of grain feeding. Simulated CH(4) emissions tended to increase with increased WSC content when CH(4) was expressed as megajoules per day or percent of gross energy intake, but when CH(4) was expressed in terms of grams per kilogram of milk, results were much more variable due to the potential increase in milk yield. As a result, under certain conditions, CH(4) (g/kg of milk) decreased. The largest increases in CH(4) emissions (MJ/d or % gross energy intake) were generally seen when WSC increased at the expense of CP in the diet and this can largely be explained by the representation in the model of the type of volatile fatty acid produced. Effects were lower when WSC increased at the expense of NDF, and intermediary when WSC increased at the expense of a mixture of CP and NDF. When WSC increased at the expense of NDF, simulated milk yield increased and, therefore, CH(4) (g/kg of milk) tended to decrease. Diminished increases of CH(4) (% gross energy intake or g/kg of milk) were simulated when DMI was increased with elevated WSC content. Simulation results suggest that high WSC grass, as a strategy to mitigate N emission, may increase CH(4) emissions, but that results depend on the grass composition, DMI, and the units chosen to express CH(4). Overall, this project demonstrates the usefulness of modeling for hypothesis testing in the absence of observed experimental results.


Science, research and social change in Indigenous health--evolving ways of knowing.
History tells us of the overwhelming destructive influence of exotic culture, politics and knowledge forms upon the worldview and wellbeing of Indigenous Australians. The power of dominant culture to oppress, control and dominate traditional Indigenous ways of knowing and being has been identified as a being a crucial influence on the health status, future hopes and aspirations of Indigenous Australians. Fundamental to this assertion is that the alienating effect of the belief in and application of the scientific method in relation to learning and knowing is a phenomenon that is incompatible with the law and cultural ways of traditional Indigenous people. The establishment of the Centre of Clinical Research Excellence (CCRE) is predicated upon and responds to a deep need in our community today to synthesise the ideological and epistemological premises of an increasing range of cultures and world views. It recognises that clinical research, for example, is important to the health of Aboriginal and Torres Strait Islander peoples, but also that the way such research is designed and carried out is also crucial to its potential to effect change in and improve the state of Indigenous health in Australia. This paper examines knowledge principles and processes associated with research in Indigenous communities, explores emerging research trends in science and proposes an epistemological framework for synthesis of traditional approaches with those of the scientific paradigm.


Exploring preferences of at-risk individuals for preventive treatments for rheumatoid arthritis.
Some immunomodulatory drugs have been shown to delay the onset of, or lower the risk of developing, rheumatoid arthritis (RA), if given to individuals at risk. Several trials are ongoing in this area; however, little evidence is currently available about the views of those at risk of RA regarding preventive treatment. Three focus groups and three interviews explored factors that are relevant to first degree relatives (FDRs) of RA patients and members of the general public when considering taking preventive treatment for RA. The semi-structured qualitative interview prompts explored participant responses to hypothetical attributes of preventive RA medicines. Transcripts of focus group/interview proceedings were inductively coded and analysed using a framework approach. Twenty-one individuals (five FDRs, 16 members of the general public) took part in the study. Ten broad themes were identified describing factors that participants felt would influence their decisions about whether to take preventive treatment if they were at increased risk of RA. These related either directly to features of the specific treatment or to other factors, including personal characteristics, attitude towards taking medication, and an individual's actual risk of developing RA. This research highlights the importance of non-treatment factors in the decision-making process around preventive treatments, and will inform recruitment to clinical trials as well as information to support shared decision making by those considering preventive treatment. Studies of treatment preferences in individuals with a confirmed high risk of RA would further inform clinical trial design.


Gastrogastric reflexes regulating gastric tone and their relationship to perception.
Our aim was to investigate in humans the gastrogastric reflexes that regulate gastric tone and their relationship to perception. In nine healthy subjects, liquid distension (in 100-ml steps), warm stimuli (in 3 degrees C increments), and cold stimuli (in 6 degrees C decrements) were randomly applied in the stomach for 3 min at 8-min intervals. Gastric tone was measured as isobaric volume changes of air by a barostat, and perception was scored by a graded (0-6) questionnaire. Liquid accommodation produced an additional expansion of isobaric air maintained by the barostat (51 +/- 13 ml with 100 ml of liquid filling, P < 0.05), but this effect became inconsistent with further filling. An accommodation-like reflex was best evidenced by warm stimulation below the discomfort threshold (58 +/- 13 ml relaxation at 47 +/- 1 degrees C, P < 0.05). By contrast, cooling below discomfort induced a reflex contraction (-62 +/- 22 ml change at 18 +/- 2 degrees C, P < 0.05). In conclusion, gastric tone, i.e., accommodation and contraction, is modulated by a net of reflexes that arise from the proper wall of the stomach below the discomfort threshold.


Chemical diversity in molecular orbital energy predictions with kernel ridge regression.
Instant machine learning predictions of molecular properties are desirable for materials design, but the predictive power of the methodology is mainly tested on well-known benchmark datasets. Here, we investigate the performance of machine learning with kernel ridge regression (KRR) for the prediction of molecular orbital energies on three large datasets: the standard QM9 small organic molecules set, amino acid and dipeptide conformers, and organic crystal-forming molecules extracted from the Cambridge Structural Database. We focus on the prediction of highest occupied molecular orbital (HOMO) energies, computed at the density-functional level of theory. Two different representations that encode the molecular structure are compared: the Coulomb matrix (CM) and the many-body tensor representation (MBTR). We find that KRR performance depends significantly on the chemistry of the underlying dataset and that the MBTR is superior to the CM, predicting HOMO energies with a mean absolute error as low as 0.09 eV. To demonstrate the power of our machine learning method, we apply our model to structures of 10k previously unseen molecules. We gain instant energy predictions that allow us to identify interesting molecules for future applications.


Olfaction and the homing ability of pigeons raised in a tropical area in Brazil.
Several workers have investigated the effect of anosmia on pigeon navigation in different geographical locations because it has been suggested that homing behavior is based on different cues, such as olfactory cues, the Earth's magnetic field or infrasound, and that in the absence of one cue another would be used. In this situation, no cue is universally indispensable, including olfactory ones. In order to extend such observations to a novel biome, we observed the behaviour of 192 young inexperienced birds raised in southeastern Brazil, a tropical area where olfactory tests had never been run before. The birds were released from eight symmetrically distributed sites 17 to 44 km from the loft. Half of these birds (experimentals) had been made temporarily anosmic by washing their olfactory mucosae with 4% solution of ZnSO4 the day before release, while controls were treated with Ringer solution. The results of release tests showed that anosmia totally impaired the navigational performance of experimental birds, which were unable to home from sites at relatively short distances from home (34-44 km) and whose pooled initial bearings produced a (negative) homeward component not significantly different from 0. Homing performance of controls was significantly better, and their pooled vanishing bearings had a significant homeward component, in spite of much scatter in individual releases. We conclude that pigeon homing in the study area depends on olfactory information, even though local environmental conditions in the interior of the State of Sao Paulo, as in several other parts of the world, do not appear to be as favorable as Italy for the development of efficient olfactory navigation.


C. R. Henderson: farm boy, athlete, and scientist.
Charles R. Henderson was proud to be a product of a farm in Page County, Iowa. He was a one man track team in Coin, Iowa, and a brilliant student. He became a world class competitor in track at Iowa State College and, at the same time, compiled a top academic record. His early experiences set the stage for the exceptional contributions of his animal breeding career, which did not begin until he was nearly 40 yr of age, but which spanned 40 yr when he was the acknowledged leader in development of statistical methodology applied to animal breeding. His career goals were to find the best possible ways to analyze data and to provide the best genetic evaluations to the livestock industry. If the best could not be done because of computational limitations, then he would pragmatically work to find the best way that was possible. Only his interest in Cornell hockey overshadowed his enjoyment in listening to classical music. He was an avid sports fan, especially for the St. Louis Cardinals or any midwestern team against the New York Yankees. Midwestern trips during the weeks when the Drake Relays were held were as often as possible. Henderson's acknowledged scientific hero was Jay L. Lush, with whom he studied during his Ph.D. program at Iowa State College and with whom he shared similar talents and the intuition that made both of them leaders in the field of animal breeding.


The cause of death in patients with glioblastoma is multifactorial: clinical factors and autopsy findings in 117 cases of supratentorial glioblastoma in adults.
To delineate the causes of death (COD) in adults with supratentorial glioblastoma multiforme (GM) we reviewed 117 consecutive cases examined at autopsy over a nineteen year period at the University of Washington. Twenty cases (17%) had expired unexpectedly without ante mortem diagnosis, 5 patients (4%) had been diagnosed as having lower grade astrocytomas prior to death. Other than the 20 patients without ante mortem diagnosis, all patients had a surgical procedure for treatment and/or diagnosis (biopsy 10%, craniotomy 90%). Postsurgical therapy varied, but there was no significant difference in median length of survival among the different treatment groups. Factors considered as potential COD were: herniation (axial, transtentorial, subfalcine, tonsillar), surgical complications (death within thirty days of surgery secondary to cerebral hemorrhage and/or edema), severe systemic illness, brainstem invasion by tumor, and neutron-induced cerebral injury (cerebral and brainstem gliosis were evident in these cases). A potential COD could be identified in 93% of patients. Patients with no ante mortem diagnosis were likely to have herniated (p = 0.01), whereas patients who underwent neutron irradiation were unlikely to have herniated (p = 0.001). No other variables were statistically significant predictors of herniation, including multifocal tumors (20 patients), and brainstem invasion by tumor (18 patients). No patients died as a result of treatment except those who underwent neutron radiotherapy and those who died postoperatively. Although significant mass effect, as evidenced by herniation, was apparent in 61% of patients, most of these patients had an additional identifiable COD. We conclude that the COD in patients with GM varies and is multifactorial.


[Morphofunctional distinctions of young rovers with high level of blood (arterial) pressure].
We've studied morphofunctional peculiarities of 47 young sportsmen-rovers. 25.6% of the young sportsmen suffered from the 1st degree arterial hypertension and 8.5% had high--normal blood pressure. Profound clinical and dynamic checkup proved that in the group of rovers with high blood pressure the indices of arterial blood pressure compared to those of the group of sportsmen having normal blood pressure there is certain enlargement of ventriculus sinister cordis myocardium mass and deterioration of functional reserve.


Adolescent pregnant women's health practices and their impact on maternal, fetal and neonatal outcomes: a mixed method study protocol.
Considering that individuals' health practices can affect the health of both mothers and babies, this study is designed to: (a) assess adolescent pregnant women's health practices and their relationship with maternal, fetal, and neonatal outcomes; (b) explore the perception of adolescent pregnant women about their own health practices; and (c) recommend some strategies to improve adolescent pregnant women's health practices during pregnancy. This mixed-method study with the sequential explanatory design has two phases. The first phase (quantitative phase) is a prospective study to assess the adolescent pregnant women's health practices and its relationship with maternal, fetal, and neonatal outcomes who live in Tehran, the capital city of Iran. A cluster sampling method will be used to select 316 adolescent pregnant women who visit health centers in Tehran. The second phase is a qualitative study designed to explore the adolescent pregnant women's perception of important aspects and factors of health practices that can affect their health outcomes. In this phase, purposive sampling and in-depth individual interviews will be conducted for data collection. The conventional content analysis approach will be employed for data analysis. In addition to literature review and nominal group technique, the findings of the qualitative and quantitative phases, will be used to recommend some strategies to support adolescent pregnant women to improve their health practices during pregnancy. This is the first study looking into health practices in adolescent pregnant women which will be performed via a mixed-method approach, aiming to develop health practices improvement strategies. It is worth noting that there is no strategic guideline in Iran's health system for improvement of health practices of adolescents. Therefore, it is hoped that the strategy proposed in the current study can enhance health practices of adolescents during pregnancy and ultimately improve their pregnancy and childbirth outcomes. IR.TBZMED.REC.1397.670.


Incidence of non-Hodgkin's lymphoma in Sweden, Denmark, and Finland from 1960 through 2003: an epidemic that was.
Reports during the early 1990s indicated non-Hodgkin's lymphoma (NHL) as one of the most rapidly increasing malignancies. More recent trends remain poorly characterized, as do the underlying reasons for NHL time trends, in particular, the effect of changes in classification and registration of lymphoproliferative malignancies. Insights into the descriptive epidemiology of NHL may shed light upon its elusive etiology. We used data from the Swedish, Danish, and Finnish national cancer registers to assess the incidences of NHL and other lymphoproliferative malignancies between 1960 and 2004. Using Poisson regression, we estimated the annual rate of change in NHL incidence per decade by sex, age, and country. In Sweden, Denmark, and Finland, the NHL incidence increased in both genders and all age categories by about 4% every year up until the early 1990s. Thereafter, the incidence increased at a slower rate (ages 60-79 years), stabilized (ages 50-59 and > or =80 years), and decreased (ages 0-49 years), respectively, similarly for males and females in the three countries. Time trends of NHL were not reciprocated and explained by trends for other lymphoproliferative malignancies nor explained by trends in NHL as secondary primaries or NHL diagnosed postmortem. The epidemic increase of NHL has recently subsided. Changes in the classification of lymphoproliferative malignancies, or occurrence of NHL as second primaries, only offer a marginal explanation.