Social inclusion and the Fatosphere: the role of an online weblogging community in fostering social inclusion.
Overweight and obesity are one of the most salient issues within society today, and the stigmatisation of overweight individuals is prevalent and widespread. Utilising interviews with 44 individuals who blog within an online fat acceptance community known as the Fatosphere, participants' perceptions of inclusion and exclusion were examined within their offline and online environments. Additionally, the effect this had on their offline lives was examined. Participants described a profound sense of exclusion within their offline lives through three agencies: the medicalisation of 'fatness', the weight loss industry and the media, which echoed descriptions of moral judgement. Furthermore, a sense of inclusion was described within the Fatosphere through the protection and support that they found within this 'safe space'. The effects of the Fatosphere influenced their lives in both negative and positive ways, allowing them to better deal with stigma and discrimination, but sometimes effecting their offline relationships in a negative manner. The Fatosphere provides a unique opportunity for corpulent individuals to engage in a community that is removed from the prominent weight-related discourse within modern society.


DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY (DPD) IN GI MALIGNANCIES: EXPERIENCE OF 4-YEARS.
OBJECTIVES: 5-Fluorouracil (5-FU) is an integral part of treatment of GI malignancies. While normal DPD enzyme activity is rate limiting in 5-FU catabolism, its deficiency could increase concentrations of bioavailable 5-FU anabolic products leading to 5-FU related toxicity syndrome. METHODOLOGY: Twenty-three patients were tested for DPD deficiency after excessive toxicities from 5-FU and/or capecitabine. DPD activity was evaluated by Peripheral Blood Mononuclear Cell (PBMC) radioassay, genotyping of DPYD gene by Denaturing High Performance Liquid Chromatography (DHPLC), or 2-(13)C uracil breath test (UraBT). RESULTS: Of 23 patients with excessive toxicities from 5-FU and/or capecitabine, 7 (30%) were DPD deficient with a median age of 66 years, M:F ratio = 1.3:1 and ethnicities included Caucasian (71%), African-American (14%) and South-Asian (14%). DPD activity ranged from 0.064 - 0.18nmol/min/mg. Three patients were treated with bolus 5-FU/LV, two with capecitabine, and two with high dose bolus 5-FU with 2', 3', 5'-tri-O-acetyluridine. Toxicities included mucositis (71%), diarrhea (43%), skin rash (43%), memory loss/altered mental status (43%), cytopenias (43%), nausea (29%), hypotension (14%), respiratory distress (14%) and acute renal failure (14%) Re-challenge with capecitabine in one patient after the Mayo regimen caused grade 3 hand-foot syndrome. Genotypic analysis of the DPYD gene in one patient with severe leucopenia demonstrated a heterozygous mutation (IVS14+1 G>A, DPYD). The UraBT in two patients of 112.8; PDR of 49.4%) and borderline normal values revealed 1 to be DPD-deficient (DOB(50) of 130.9; PDR of 52.5%) in a second patient. There were 2 toxicity-related deaths among (DOB(50) DPD-deficient patients (28%). CONCLUSIONS: DPD deficiency was observed in several ethnicities. Akin to 5-FU, capecitabine can also lead to severe toxicities in DPD-deficient patients. Screening patients for DPD deficiency prior to administration of 5-FU or capecitabine using UraBT could potentially lower risk of toxicity. Future studies should validate this technique.


Disease-specific mortality may underestimate the total effect of prostate cancer screening.
To study the difference between the disease-specific and excess mortality rate in the European Randomized Study of Screening for Prostate Cancer section Rotterdam. A total of 42,376 men were randomized to systematic screening or usual care. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC) patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a possible diagnosis with PC. The disease-specific mortality rate was based on the number of men who died from PC. The excess mortality rate based on the arm-specific excess number of deaths and the disease-specific mortality rate were compared between the two study arms. The overall mortality rate was not significantly different between the intervention and the control arms of the study: RR 1.02 (95% CI 0.98-1.07). The disease-specific mortality rate was 0.42 men per 1000 person-years in the intervention and 0.48 men per 1000 person-years in the control arm: RR 0.86 (95% CI 0.64-1.17). The excess mortality rate was 0.40 per 1000 person-years in the intervention arm and 0.61 men per 1000 person-years in the control arm, and the RR for excess mortality was 0.66 (95% CI 0.39-1.13). In contrast to the disease-specific mortality rates an increased difference in the excess mortality rates was observed between the two arms. This observation may be due to a systematic underestimation of the disease-specific deaths, and/or an additional disease-related mortality that is measured by an excess mortality analysis but not by a disease-specific mortality.


A mobile one-lead ECG device incorporated in a symptom-driven remote arrhythmia monitoring program. The first 5,982 Hartwacht ECGs.
In recent years many mobile devices able to record health-related data in ambulatory patients have emerged. However, well-organised programs to incorporate these devices are sparse. Hartwacht Arrhythmia (HA) is such a program, focusing on remote arrhythmia detection using the AliveCor Kardia Mobile (KM) and its algorithm. The aim of this study was to assess the benefit of the KM device and its algorithm in detecting cardiac arrhythmias in a real-world cohort of ambulatory patients. All KM ECGs recorded in the HA program between January 2017 and March 2018 were included. Classification by the KM algorithm was compared with that of the Hartwacht team led by a cardiologist. Statistical analyses were performed with respect to detection of sinus rhythm (SR), atrial fibrillation (AF) and other arrhythmias. 5,982 KM ECGs were received from 233 patients (mean age 58 years, 52% male). The KM algorithm categorised 59% as SR, 22% as possible AF, 17% as unclassified and 2% as unreadable. According to the Hartwacht team, 498 (8%) ECGs were uninterpretable. Negative predictive value for detection of AF was 98%. However, positive predictive value as well as detection of other arrhythmias was poor. In 81% of the unclassified ECGs, the Hartwacht team was able to provide a diagnosis. This study reports on the first symptom-driven remote arrhythmia monitoring program in the Netherlands. Less than 10% of the ECGs were uninterpretable. However, the current performance of the KM algorithm makes the device inadequate as a stand-alone application, supporting the need for manual ECG analysis in HA and similar programs.


Size distribution of linear and helical polymers in actin solution analyzed by photon counting histogram.
Actin is a ubiquitous protein that is a major component of the cytoskeleton, playing an important role in muscle contraction and cell motility. At steady state, actin monomers and filaments (F-actin) coexist, and actin subunits continuously attach and detach at the filament ends. However, the size distribution of actin oligomers in F-actin solution has never been clarified. In this study, we investigated the size distribution of actin oligomers using photon-counting histograms. For this purpose, actin was labeled with a fluorescent dye, and the emitted photons were detected by confocal optics (the detection volume was of femtoliter (fL) order). Photon-counting histograms were analyzed to obtain the number distribution of actin oligomers in the detection area from their brightness, assuming that the brightness of an oligomer was proportional to the number of protomers. We found that the major populations at physiological ionic strength were 1-5mers. For data analysis, we successfully applied the theory of linear and helical aggregations of macromolecules. The model postulates three states of actin, i.e., monomers, linear polymers, and helical polymers. Here we obtained three parameters: the equilibrium constants for polymerization of linear polymers, K(l)=(5.2 +/- 1.1) x 10(6) M(-1), and helical polymers, K(h)=(1.6 +/- 0.5) x 10(7) M(-1); and the ratio of helical to linear trimers, gamma = (3.6 +/- 2.3) x 10(-2). The excess free energy of transforming a linear trimer to a helical trimer, which is assumed to be a nucleus for helical polymers, was calculated to be 2.0 kcal/mol. These analyses demonstrate that the oligomeric phase at steady state is predominantly composed of linear 1-5mers, and the transition from linear to helical polymers occurs on the level of 5-7mers.


Nuclear gene sequences provide evidence for the monophyly of australidelphian marsupials.
Relationships among the seven extant orders of marsupials remain poorly understood. Most classifications recognize a fundamental split between Ameridelphia, which contains the American orders Didelphimorphia and Paucituberculata, and Australidelphia, which contains four Australasian orders (Dasyuromorphia, Diprotodontia, Notoryctemorphia, and Peramelina) and the South American order Microbiotheria, represented by Dromiciops gliroides. Ameridelphia and Australidelphia are each supported by key morphological characters with dichotomous character states. To date, molecular studies indexing all marsupial orders have reported inconclusive results. However, several studies have suggested that Dromiciops is nested within Australidelphia. This result has important implications for understanding the biogeographic history of living marsupials. To address questions in higher-level marsupial systematics, we sequenced portions of five nuclear genes (Apolipoprotein B gene; Breast and Ovarian cancer susceptibility gene 1; Recombination activating gene 1; Interphotoreceptor retinoid binding protein gene; and von Willebrand factor gene) for representatives of all orders of marsupials, as well as placental outgroups. The resulting 6.4kb concatenation was analyzed using maximum parsimony, distance methods, maximum likelihood, and Bayesian methods. tests were used to examine a priori hypotheses. All analyses provided robust support for the monophyly of Australidelphia (bootstrap support=99-100%; posterior probability=1.00). Ameridelphia received much lower support, although this clade was not rejected in statistical tests. Within Diprotodontia, both Vombatiformes and Phalangeriformes were supported at the 100% bootstrap level and with posterior probabilities of 1.00.


The effect of parathyroidectomy on bone mineral density in primary hyperparathyroidism
This study aimed to investigate the change in bone mineral density (BMD) before and 1 year after parathyroidectomy in patients with primary hyperparathyroidism (PHPT). The clinical and biochemical parameters and DEXA screening of patients with symptomatic PHPT (n = 28) and asymptomatic PHPT (n = 63) were investigated before and 1 year after parathyroidectomy. Patients with symptomatic PHPT had a higher prevalence of nephrolithiasis (18.2% vs. 4.6%, P = 0.032) when compared to the prevalence in patients with asymptomatic PHPT. The prevalence of osteoporosis in the lumbar spine (63.0% vs. 37.5%, P = 0.026) and femoral neck (40.7% vs. 20.6%, P = 0.048) was higher in symptomatic PHPT when compared to the prevalence in asymptomatic PHPT. After parathyroidectomy, the decreases in the prevalence of osteoporosis in the lumbar spine (25.8% vs. 9.4%, P = 0.014), femoral neck (22.1% vs. 8.2%, P =0.009), and total hip (22.4% vs. 5.3%, P = 0.007) were higher in symptomatic PHPT compared to the asymptomatic PHPT group. A higher BMD gain (g/cm2) was seen in the lumbar spine (10.83% vs. 4.65%, P=0.016) and femoral neck (12.61% vs. 4.37%, P=0.005) in symptomatic PHPT compared to the asymptomatic PHPT group. Parathyroidectomy provided more BMD gain in the lumbar spine and femoral neck in patients with symptomatic PHPT when compared to patients with asymptomatic PHPT 1 year after parathyroidectomy.


Transcriptome and epigenome landscape of human cortical development modeled in organoids.
Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.


Preparation of plasma membrane from isolated neurons.
A bulk fraction enriched with respect to neuronal cell bodies was used as starting material for the isolation of neuronal plasma membrane The cells were gently homogenized in isotonic sucrose and a crude membrane containing fraction sedimented at 3000 g. Subsequently, the membrane fraction was purified on a discontinuous sucrose density gradient between 35% and 25 5% sucrose (w/w). Enzymatic analyses showed a 4-5-fold enrichment in plasma membrane markers, and a 10-15% contamination of mitochondrial and microsomal material. Electron micrographs of the membrane fraction confirmed the enzymatic data Fragmented membranes were found, mainly in vesicular form No ribosomes, but a few mitochondria and some multilamellar membranes were seen


EagleView: a genome assembly viewer for next-generation sequencing technologies.
The emergence of high-throughput next-generation sequencing technologies (e.g., 454 Life Sciences [Roche], Illumina sequencing [formerly Solexa sequencing]) has dramatically sped up whole-genome de novo sequencing and resequencing. While the low cost of these sequencing technologies provides an unparalleled opportunity for genome-wide polymorphism discovery, the analysis of the new data types and huge data volume poses formidable informatics challenges for base calling, read alignment and genome assembly, polymorphism detection, as well as data visualization. We introduce a new data integration and visualization tool EagleView to facilitate data analyses, visual validation, and hypothesis generation. EagleView can handle a large genome assembly of millions of reads. It supports a compact assembly view, multiple navigation modes, and a pinpoint view of technology-specific trace information. Moreover, EagleView supports viewing coassembly of mixed-type reads from different technologies and supports integrating genome feature annotations into genome assemblies. EagleView has been used in our own lab and by over 100 research labs worldwide for next-generation sequence analyses. The EagleView software is freely available for not-for-profit use at http://bioinformatics.bc.edu/marthlab/EagleView.


Structural insight for chain selection and stagger control in collagen.
Collagen plays a fundamental role in all known metazoans. In collagens three polypeptides form a unique triple-helical structure with a one-residue stagger to fit every third glycine residue in the inner core without disturbing the poly-proline type II helical conformation of each chain. There are homo- and hetero-trimeric types of collagen consisting of one, two or three distinct chains. Thus there must be mechanisms that control composition and stagger during collagen folding. Here, we uncover the structural basis for both chain selection and stagger formation of a collagen molecule. Three distinct chains (α1, α2 and α3) of the non-collagenous domain 2 (NC2) of type IX collagen are assembled to guide triple-helical sequences in the leading, middle and trailing positions. This unique domain opens the door for generating any fragment of collagen in its native composition and stagger.


Molecular variants of the sodium/hydrogen exchanger type 3 gene and essential hypertension.
The objectives of this study were to identify polymorphic variants within the gene coding for the sodium/hydrogen exchanger type 3 (NHE3) and to examine their relationship with hypertension and biochemical indices of sodium balance. Case-control comparisons on a total of 691 subjects of which 399 (68% with essential hypertension) were of African or Afro-Caribbean origin (blacks) and 292 (50% with essential hypertension) were of Caucasian origin (whites). Eight exons of the C terminus of the NHE3 gene were screened systematically. A total of six variants were identified: (G1579A, G1709A, G1867A, C1945T, A2041G and C2405T). Further analyses in relation to essential hypertension and phenotypic characteristics were confined to the more frequent A2041G and the C2405T polymorphisms. The genotype frequencies of the A2041G polymorphism were significantly different between the whites and blacks, with the A allele being more frequent in the white population (0.43 for the whites and 0.14 for the blacks, respectively; P < 0.001). In contrast, there was no significant difference in the C2405T polymorphism between whites and blacks (C allele frequency: 0.86 for the whites and 0.88 for the blacks, respectively). In both the white and the black groups, there were no significant associations between these variants and essential hypertension (P > 0.05) or with serum electrolytes, creatinine or plasma renin activity (PRA) (ANOVA P > 0.05). These results suggest a high degree of structural conservation of the NHE3 gene; however, the lack of association between these polymorphisms and blood pressure status does not necessarily eliminate the participation of this important sodium/hydrogen exchanger in the pathophysiology of essential hypertension, as we cannot exclude the existence of functionally important genetic variants in other sequences within the NEH3 gene.


Beyond Acetylcholinesterase Inhibitors: Novel Cholinergic Treatments for Alzheimer's Disease.
The major components of the cholinergic receptor system of the human brain include projections from the basal forebrain nuclei, and utilize the two types of receptors that they synapse on, nicotinic and muscarinic acetylcholine receptors. With the widespread cortical and subcortical projections of the basal forebrain, activity of these two receptor systems provide modulation of neurotransmitter activity underlying normal cognitive processes, such as attention, episodic memory, and working memory. Alzheimer's disease (AD) targets and damages cholinergic neurons in the basal forebrain, and as these projections are lost, cognitive performance progressively declines. Currently, the most widely prescribed treatment for AD is acetylcholinesterase inhibitor medications, which work by partially blocking the degradation of acetylcholine in the synapse and enabling more of the neurotransmitter to reach and activate cholinergic receptors. However since these medications have limited effectiveness, alternate treatments that focus on augmenting the activity of the receptors themselves, independent of acetylcholinesterase inhibition, are being explored. This review will discuss: 1) the role of the cholinergic system in modulating cognition, 2) novel cholinergic treatment strategies for AD-related cognitive decline, in particular treatments intended to increase cholinergic system activity by selectively targeting muscarinic and nicotinic acetylcholinergic receptors to improve cognitive performance, 3) risks, and additional considerations for cholinergic cognitive treatments for AD.


Narrow-front loop migration in a population of the common cuckoo Cuculus canorus, as revealed by satellite telemetry.
Narrow migration corridors known in diurnal, social migrants such as raptors, storks and geese are thought to be caused by topographical leading line effects in combination with learning detailed routes across generations. Here, we document narrow-front migration in a nocturnal, solitary migrant, the common cuckoo Cuculus canorus, using satellite telemetry. We tracked the migration of adult cuckoos from the breeding grounds in southern Scandinavia (n = 8), to wintering sites in south-western Central Africa (n = 6) and back to the breeding grounds (n = 3). Migration patterns were very complex; in addition to the breeding and wintering sites, six different stopover sites were identified during the 16,000 km annual route that formed a large-scale clockwise loop. Despite this complexity, individuals showed surprisingly similar migration patterns, with very little variation between routes. We compared observed tracks with simulated routes based on vector orientation (with and without effects of barriers on orientation and survival). Observed distances between routes were often significantly smaller than expected if the routes were established on the basis of an innate vector orientation programme. Average distance between individuals in eastern Sahel after having migrated more than 5,000 km for example, was merely 164 km. This implies that more sophisticated inherent guiding mechanisms, possibly involving elements of intermediate goal area navigation or more elaborate external cues, are necessary to explain the complex narrow-front migration pattern observed for the cuckoos in this study.


The omics strategy: the use of systems vaccinology to characterize immune responses to childhood immunization.
Vaccines have had a transformative impact on child health. Despite this impact, the immunological processes involved in protective responses are not entirely understood and vaccine development has been largely empirical. Recent technological advances offer the opportunity to reveal the immunology underlying vaccine response at an unprecedented resolution. These data could revolutionize the way vaccines are developed and tested and further augment their role in securing the health of children around the world. Systems level information and tools are now being deployed by vaccinologists at all stages of the vaccine development pathway; however, this review will specifically describe some of the key findings that have be gleaned from multi-omics datasets collected in the context of childhood immunization. Despite the success of vaccines, there remains hard-to-target pathogens, refractory to current vaccination strategies. Moreover, zoonotic diseases with pandemic potential are a threat to global health, as recently illustrated by COVID-19. Systems vaccinology holds a great deal of promise in revealing a greater understanding of vaccine responses and consequently modernizing vaccinology. However, there is a need for future studies - particularly in vulnerable populations that are targets for vaccination programmes - if this potential is to be fulfilled.


Purinergic receptors in the rat lens: activation of P2X receptors following hyperosmotic stress.
A range of P2Y and P2X receptors is expressed in the rat lens. Because most P2X receptors are located in the cytoplasm, the authors sought to determine whether P2X receptors are functionally active. Rat lenses were cultured under either isotonic or hypertonic conditions in the presence of P2 receptor agonists or antagonists. Lenses were fixed and cryosectioned, cell membranes were labeled, and confocal microscopy was used to determine whether the different reagents affected cell morphology. Application of the P2 receptor inhibitor PPADS to lenses cultured under isotonic conditions induced extracellular space dilations between fiber cells in a distinct zone in the outer cortex. This damage was not caused by the inhibition of P2X(1) or P2Y(1) because more selective antagonists for P2X(1) (MRS2159) and P2Y(1) (MRS2179) either did not cause any damage or induced extracellular dilations located between superficial fiber cells at the lens modiolus, respectively. Although the P2 agonists ATPgammaS and ADPbetaS both induced a distinctive disruption to cell morphology in the same localized zone as PPADS, the P2X-specific agonist alpha,beta-methyl-ATP induced no change to cell morphology. However, under hypertonic conditions that cause the insertion of P2X(1,4) into the membranes, alpha,beta-methyl-ATP induced a localized zone of damage that was associated with changes in actin distribution. The results show that P2X receptors may play a minimal role in mediating ion fluxes in the rat lens under steady state conditions. In contrast, hypertonic cell shrinkage activates previously inactive P2X receptors in the lens, suggesting P2X receptors may play a role in the lens in response to osmotic stress.


Progesterone receptor membrane component-1 regulates hepcidin biosynthesis.
Iron homeostasis is tightly regulated by the membrane iron exporter ferroportin and its regulatory peptide hormone hepcidin. The hepcidin/ferroportin axis is considered a promising therapeutic target for the treatment of diseases of iron overload or deficiency. Here, we conducted a chemical screen in zebrafish to identify small molecules that decrease ferroportin protein levels. The chemical screen led to the identification of 3 steroid molecules, epitiostanol, progesterone, and mifepristone, which decrease ferroportin levels by increasing the biosynthesis of hepcidin. These hepcidin-inducing steroids (HISs) did not activate known hepcidin-inducing pathways, including the BMP and JAK/STAT3 pathways. Progesterone receptor membrane component-1 (PGRMC1) was required for HIS-dependent increases in hepcidin biosynthesis, as PGRMC1 depletion in cultured hepatoma cells and zebrafish blocked the ability of HISs to increase hepcidin mRNA levels. Neutralizing antibodies directed against PGRMC1 attenuated the ability of HISs to induce hepcidin gene expression. Inhibiting the kinases of the SRC family, which are downstream of PGRMC1, blocked the ability of HISs to increase hepcidin mRNA levels. Furthermore, HIS treatment increased hepcidin biosynthesis in mice and humans. Together, these data indicate that PGRMC1 regulates hepcidin gene expression through an evolutionarily conserved mechanism. These studies have identified drug candidates and potential therapeutic targets for the treatment of diseases of abnormal iron metabolism.


Outcomes of extremely preterm infants following severe intracranial hemorrhage.
Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH. Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI). Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI. Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.


Deep brain stimulation reduces neuronal entropy in the MPTP-primate model of Parkinson's disease.
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n > or = 18 and P < or = 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n > or = 24 and P < or = 10(-4) in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit.


Opto-VLSI-based tunable single-mode fiber laser.
A new tunable fiber ring laser structure employing an Opto-VLSI processor and an erbium-doped fiber amplifier (EDFA) is reported. The Opto-VLSI processor is able to dynamically select and couple a waveband from the gain spectrum of the EDFA into a fiber ring, leading to a narrow-linewidth high-quality tunable laser output. Experimental results demonstrate a tunable fiber laser of linewidth 0.05 nm and centre wavelength tuned over the C-band with a 0.05 nm step. The measured side mode suppression ratio (SMSR) is greater than 35 dB and the laser output power uniformity is better than 0.25 dB. The laser output is very stable at room temperature.


Guiding BMP adoption to improve water quality in various estuarine ecosystems in Western Australia.
The Australian Government's Coastal Catchment Initiative (CCI) seeks to achieve targeted reductions in nutrient pollution to key coastal water quality hotspots, reducing algal blooms and fish kills. Under the CCI a Water Quality Improvement Plan (WQIP) is being prepared for targeted estuaries (Swan-Canning, near Perth, and the Vasse-Geographe, 140 km south of Perth) to address nutrient pollution issues. A range of projects are developing, testing and implementing agricultural Best Management Practices (BMPs) to reduce excessive loads of nutrients reaching the receiving waters. This work builds on progress-to-date achieved in a similar project in the Peel-Harvey Catchment (70 km south of Perth). It deals with the necessary steps of identifying the applicability of BMPs for nutrient attenuation, developing and promoting BMPs in the context of nutrient use and attenuation on farm and through catchments and estimating the degree to which BMP implementation can protect receiving waters. With a range of BMPs available with varying costs and effectiveness, a Decision Support System (DSS) to guide development of the WQIP and implementation of BMPs to protect receiving waters, is under development. As new information becomes available the DSS will be updated to ensure relevance and accuracy for decision-making and planning purposes. The DSS, calibrated for application in the catchments, will play a critical role in adaptive implementation of the WQIP by assessing the effect of land use change and management interventions on pollutant load generation and by providing a tool to guide priority setting and investment planning to achieve agreed WQIP load targets.


Monomer abundance distribution patterns as a universal biosignature: examples from terrestrial and digital life.
Organisms leave a distinctive chemical signature in their environment because they synthesize those molecules that maximize their fitness. As a result, the relative concentrations of related chemical monomers in life-bearing environmental samples reflect, in part, those compounds' adaptive utility. In contrast, rates of molecular synthesis in a lifeless environment are dictated by reaction kinetics and thermodynamics, so concentrations of related monomers in abiotic samples tend to exhibit specific patterns dominated by small, easily formed, low-formation-energy molecules. We contend that this distinction can serve as a universal biosignature: the measurement of chemical concentration ratios that belie formation kinetics or equilibrium thermodynamics indicates the likely presence of life. We explore the features of this biosignature as observed in amino acids and carboxylic acids, using published data from numerous studies of terrestrial sediments, abiotic (spark, UV, and high-energy proton) synthesis experiments, and meteorite bodies. We then compare these data to the results of experimental studies of an evolving digital life system. We observe the robust and repeatable evolution of an analogous biosignature in a digital lifeform, suggesting that evolutionary selection necessarily constrains organism composition and that the monomer abundance biosignature phenomenon is universal to evolved biosystems.


ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part I - Assessment and Management of Various Cardiovascular Risk Factors.
Cardiovascular disease contributes significantly to the adverse clinical outcomes of peritoneal dialysis (PD) patients. Numerous cardiovascular risk factors play important roles in the development of various cardiovascular complications. Of these, loss of residual renal function is regarded as one of the key cardiovascular risk factors and is associated with an increased mortality and cardiovascular death. It is also recognized that PD solutions may incur significant adverse metabolic effects in PD patients. The International Society for Peritoneal Dialysis (ISPD) commissioned a global workgroup in 2012 to formulate a series of recommendations regarding lifestyle modification, assessment and management of various cardiovascular risk factors, as well as management of the various cardiovascular complications including coronary artery disease, heart failure, arrhythmia (specifically atrial fibrillation), cerebrovascular disease, peripheral arterial disease and sudden cardiac death, to be published in 2 guideline documents. This publication forms the first part of the guideline documents and includes recommendations on assessment and management of various cardiovascular risk factors. The documents are intended to serve as a global clinical practice guideline for clinicians who look after PD patients. The ISPD workgroup also identifies areas where evidence is lacking and further research is needed.


The attracting power of the gaze of politicians is modulated by the personality and ideological attitude of their voters: a functional magnetic resonance imaging study.
Observing someone rapidly moving their eyes induces reflexive shifts of overt and covert attention in the onlooker. Previous studies have shown that this process can be modulated by the onlooker's personality, as well as by the social features of the person depicted in the cued face. Here, we investigated whether an individual's preference for social dominance orientation, in-group perceived similarity (PS), and political affiliation of the cued-face modulated neural activity within specific nodes of the social attention network. During functional magnetic resonance imaging, participants were requested to perform a gaze-following task to investigate whether the directional gaze of various Italian political personages might influence the oculomotor behaviour of in-group or out-group voters. After scanning, we acquired measures of PS in personality traits with each political personage and preference for social dominance orientation. Behavioural data showed that higher gaze interference for in-group than out-group political personages was predicted by a higher preference for social hierarchy. Higher blood oxygenation level-dependent activity in incongruent vs. congruent conditions was found in areas associated with orienting to socially salient events and monitoring response conflict, namely the left frontal eye field, right supramarginal gyrus, mid-cingulate cortex and left anterior insula. Interestingly, higher ratings of PS with the in-group and less preference for social hierarchy predicted increased activity in the left frontal eye field during distracting gaze movements of in-group as compared with out-group political personages. Our results suggest that neural activity in the social orienting circuit is modulated by higher-order social dimensions, such as in-group PS and individual differences in ideological attitudes.


Acculturation-based family conflict: A validation of Asian American Family Conflict Scale among Chinese Americans.
Acculturation-based family conflicts can influence parent-child relationships and children's development among immigrant families. The Asian American Family Conflict Scale (AAFCS) was developed to measure conflicting practices and values between parents and children in the context of acculturation. Given that considerable cultural and institutional changes have taken place in original countries for the Chinese immigrant population, it is important to investigate whether the factor structure of the AAFCS is appropriate for measuring the attitudes and practices of acculturation among the current Chinese immigrant population. A sample of Chinese American immigrant parents (n = 269) from the Survey of Asian American Families was employed to conduct exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The principal-axis factoring method of EFA was used to determine the factor structure of the AAFCS, followed by the weighted least squares means and variance estimation in CFA to assess the fitness of the measurement model. A nine-item one-factor model (without the first item regarding decision making) was suggested by EFA with all factor loadings greater than .45. CFA results indicated a good fit of the nine-item one-factor model: χ2 (27, 296) = 40.24, p < .05, root-mean-square error of approximation = .04, 90% CI [.00, .07], comparative fit index = .99, Tucker-Lewis index = .99. The validation of the AAFCS is useful for practitioners and researchers to better assess the outcomes of acculturation conflicts among Chinese immigrants who are adjusting to living in the United States. This study can inform social work practitioners in regards to cultural sensitivity and cultural competency when working with Chinese immigrants and their U.S.-born children.


Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise.
Catecholamines can offset the negative effect of acidosis and raised extracellular K+ concentration in the isolated rabbit heart when these factors are changed with similar kinetics and concentrations as those observed in exercise. This effect appears to be mediated by changes in Ca2+ handling in the heart. To test the role of Ca2+ in vivo, we studied the interactive effects of infusions of KCl, lactic acid, norepinephrine (NE), and CaCl2 on cardiovascular performance in the anesthetized rabbit. After propranolol, CaCl2 was given during acidosis and hyperkalemia. Acidosis (arterial pH 7.17 +/- 0.3) markedly reduced cardiac performance, and its effects were exacerbated by hyperkalemia (7.3 +/- 0.4 mM). NE reversed the cardiac response to combined acidosis and hyperkalemia. After propranolol, arterial pH and arterial K+ concentration changed more rapidly with acidosis and hyperkalemia, combined with a faster fall in cardiac performance, but CaCl2 offset these negative hemodynamic effects. The rises in plasma Ca2+, NE, and sympathetic activity during exercise may therefore interact to ameliorate the harmful effects of acidosis and hyperkalemia.


Repair of critical size defects in the rat cranium using ceramic-reinforced PLA scaffolds obtained by supercritical gas foaming.
Bioresorbable scaffolds made of poly(L-lactic acid) (PLA) obtained by supercritical gas foaming were recently described as suitable for tissue engineering, portraying biocompatibility with primary osteoblasts in vitro and interesting mechanical properties when reinforced with ceramics. The behavior of such constructs remained to be evaluated in vivo and therefore the present study was undertaken to compare different PLA/ceramic composite scaffolds obtained by supercritical gas foaming in a critical size defect craniotomy model in Sprague-Dawley rats. The host-tissue reaction to the implants was evaluated semiquantitatively and similar tendencies were noted for all graft substitutes: initially highly reactive but decreasing with time implanted. Complete bone-bridging was observed 18 weeks after implantation with PLA/ 5 wt % beta-TCP (PLA/TCP) and PLA/5 wt % HA (PLA/HA) scaffolds as assessed by histology and radiography. We show here for the first time that this solvent-free technique provides a promising approach in tissue engineering demonstrating both the biocompatibility and osteoconductivity of the processed structures in vivo.


Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC.
Endothelial dysfunction precedes pathogenesis of vascular complications in diabetes. In recent years, the mechanisms of endothelial dysfunction were investigated to outline strategies for its treatment. However, the therapies for dysfunctional endothelium resulted in multiple clinical trial failures and remain elusive. There is a need for defining hyperglycemia-induced endothelial dysfunction with both generic and specific dysfunctional changes in endothelial cells (EC) using a systems approach. In this study, we investigated hyperglycemia-induced endothelial dysfunction in HUVEC and HMVEC. We investigated hyperglycemia-induced functional changes (superoxide (O₂⁻), and hydrogen peroxide (H₂O₂) production and mitochondrial membrane polarization) and gene expression fingerprints of related enzymes (nitric oxide synthase, NAD(P)H oxidase, and reactive oxygen species (ROS) neutralizing enzymes) in both ECs. Gene expression of NOS2, NOS3, NOX4, CYBA, UCP1, CAT, TXNRD1, TXNRD2, GPX1, NOX1, SOD1, SOD2, PRDX1, 18s, and RPLP0 were measured using real-time PCR. O₂⁻ production was measured with dihydroethidium (DHE) fluorescence measurement. H2O2 production was measured using Amplex Red assay. Mitochondrial membrane polarization was measured using JC-10 based fluorescence measurement. We showed that the O₂⁻ levels increased similarly in both ECs with hyperglycemia. However, these endothelial cells showed significantly different underlying gene expression profile, H₂O₂ production and mitochondrial membrane polarization. In HUVEC, hyperglycemia increased H₂O₂ production, and hyperpolarized mitochondrial membrane. ROS neutralizing enzymes SOD2 and CAT gene expression were downregulated. In contrast, there was an upregulation of nitric oxide synthase and NAD(P)H oxidase and a depolarization of mitochondrial membrane in HMVEC. In addition, ROS neutralizing enzymes SOD1, GPX1, TXNRD1 and TXNRD2 gene expression were significantly upregulated in high glucose treated HMVEC. Our findings highlighted a unique framework for hyperglycemia-induced endothelial dysfunction. We showed that multiple pathways are differentially affected in these endothelial cells in hyperglycemia. High occurrences of gene expression changes in HMVEC in this study supports the hypothesis that microvasculature precedes macrovasculature in epigenetic regulation forming vascular metabolic memory. Identifying genomic phenotype and corresponding functional changes in hyperglycemic endothelial dysfunction will provide a suitable systems biology approach for understanding underlying mechanisms and possible effective therapeutic intervention.


LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner.
Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that has been implicated in the progression of breast, pancreatic and colorectal cancer (CRC). To determine mechanisms underlying growth promotion by LRH-1 in CRC, we undertook global expression profiling following siRNA-mediated LRH-1 knockdown in HCT116 cells, which require LRH-1 for growth and in HT29 cells, in which LRH-1 does not regulate growth. Interestingly, expression of the cell cycle inhibitor p21 (CDKN1A) was regulated by LRH-1 in HCT116 cells. p21 regulation was not observed in HT29 cells, where p53 is mutated. p53 dependence for the regulation of p21 by LRH-1 was confirmed by p53 knockdown with siRNA, while LRH-1-regulation of p21 was not evident in HCT116 cells where p53 had been deleted. We demonstrate that LRH-1-mediated p21 regulation in HCT116 cells does not involve altered p53 protein or phosphorylation, and we show that LRH-1 inhibits p53 recruitment to the p21 promoter, likely through a mechanism involving chromatin remodelling. Our study suggests an important role for LRH-1 in the growth of CRC cells that retain wild-type p53.


Kindlin-1 protects cells from oxidative damage through activation of ERK signalling.
Kindlin-1 is a FERM domain containing adaptor protein that is found predominantly at cell-extracellular matrix adhesions where it binds to β-integrin subunits and is required for integrin activation. Loss of function mutations in the FERMT1 gene which encodes Kindlin-1 leads to the development of Kindler Syndrome (KS) an autosomal recessive skin disorder characterized by skin blistering, photosensitivity, and predisposition to aggressive squamous cell carcinoma (SCC). Here we show that loss of Kindlin-1 sensitizes both SCC cells and keratinocytes to oxidative stress: Kindlin-1 deficient cells have higher levels of reactive oxygen species, decreased viability and increased DNA damage after treatment with either hydrogen peroxide (H2O2) or irradiation with UVA. We show that Kindlin-1 is required to fully activate ERK signalling after oxidative damage, and that activation of ERK protects cells from DNA damage following oxidative stress: inhibition of ERK activation sensitizes Kindlin-1 expressing cells, but not Kindlin-1 deficient cells to oxidative stress. Finally we demonstrate that the Kindlin-1 dependent activation of ERK and protection from DNA damage following oxidative stress depends on the ability of Kindlin-1 to bind integrins. Thus loss of Kindlin-1 leads to an imbalance in the cellular oxidative state, which renders Kindlin-1 deficient cells more prone to the effects of ROS generated in response to oxidative stress. We propose that Kindlin-1 dependent activation of ERK signalling is a key molecular mechanism that renders KS keratinocytes more sensitive to oxidative damage and contributes to the increased photosensitivity in KS patients.


Unravelling the effect of New Year's Eve celebrations on SARS-CoV-2 transmission.
Public holidays have been associated with SARS-CoV-2 incidence surges, although a firm link remains to be established. This association is sometimes attributed to events where transmissions occur at a disproportionately high rate, known as superspreading events. Here, we describe a sudden surge in new cases with the Omicron BA.1 strain amongst higher education students in Belgium. Contact tracers classed most of these cases as likely or possibly infected on New Year's Eve, indicating a direct trigger by New Year celebrations. Using a combination of contact tracing and phylogenetic data, we show the limited role of superspreading events in this surge. Finally, the numerous simultaneous transmissions allowed a unique opportunity to determine the distribution of incubation periods of the Omicron strain. Overall, our results indicate that, even under social restrictions, a surge in transmissibility of SARS-CoV-2 can occur when holiday celebrations result in small social gatherings attended simultaneously and communitywide.


In-depth review of symptoms, triggers, and treatment of temporal migraine headaches (Site II).
This study was designed to report the details of the technique and assess the efficacy of surgical deactivation of temporal-triggered migraine headaches. It also examined the effect of surgical deactivation of temporal-triggered migraine headaches on migraine triggers and associated symptoms besides the pain. The authors analyzed the charts of 246 patients receiving surgery for temporal-triggered migraine headaches by a single surgeon (B.G.) over a 10-year period, who were followed for at least 1 year. Median regression adjusted for age, sex, and follow-up time was used to determine postoperative reduction in temporal-specific migraine headache index, which is the product of frequency, severity, and duration. The association between individual symptom or trigger resolution and index value reduction was studied by logistic regression. Details of the surgical treatment are discussed. Eighty-five percent of patients reported a successful surgery (≥50 percent improvement of headache index) at least 12 months after surgery (mean follow-up, 3 years). Fifty-five percent reported complete elimination of temporal migraine headache. Symptoms resolving with successful site II surgery included nausea, photophobia, phonophobia, difficulty concentrating, vomiting, blurry vision, and eyelid ptosis (p < 0.05). Triggers resolving included letdown after stress, air travel, missed meals, bright lights, loud noises, fatigue, weather change, and certain smells (p < 0.05). Surgical deactivation of temporal-triggered migraine headaches is effective regardless of age, sex, or follow-up time. Successful site II surgery is associated with changes in specific symptoms and triggers. This information can assist in trigger avoidance and contribute to constellations used for temporal-triggered migraine headaches trigger-site identification. Therapeutic, IV.


Spatiotemporal Dynamics of Vibrio spp. within the Sydney Harbour Estuary.
Vibrio are a genus of marine bacteria that have substantial environmental and human health importance, and there is evidence that their impact may be increasing as a consequence of changing environmental conditions. We investigated the abundance and composition of the Vibrio community within the Sydney Harbour estuary, one of the most densely populated coastal areas in Australia, and a region currently experiencing rapidly changing environmental conditions. Using quantitative PCR (qPCR) and Vibrio-specific 16S rRNA amplicon sequencing approaches we observed significant spatial and seasonal variation in the abundance and composition of the Vibrio community. Total Vibrio spp. abundance, derived from qPCR analysis, was higher during the late summer than winter and within locations with mid-range salinity (5-26 ppt). In addition we targeted three clinically important pathogens: Vibrio cholerae, V. Vulnificus, and V. parahaemolyticus. While toxigenic strains of V. cholerae were not detected in any samples, non-toxigenic strains were detected in 71% of samples, spanning a salinity range of 0-37 ppt and were observed during both late summer and winter. In contrast, pathogenic V. vulnificus was only detected in 14% of samples, with its occurrence restricted to the late summer and a salinity range of 5-26 ppt. V. parahaemolyticus was not observed at any site or time point. A Vibrio-specific 16S rRNA amplicon sequencing approach revealed clear shifts in Vibrio community composition across sites and between seasons, with several Vibrio operational taxonomic units (OTUs) displaying marked spatial patterns and seasonal trends. Shifts in the composition of the Vibrio community between seasons were primarily driven by changes in temperature, salinity and NO2, while a range of factors including pH, salinity, dissolved oxygen (DO) and NOx (Nitrogen Oxides) explained the observed spatial variation. Our evidence for the presence of a spatiotemporally dynamic Vibrio community within Sydney Harbour is notable given the high levels of human use of this waterway, and the significant increases in seawater temperature predicted for this region.


Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.
This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians. The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. The target audience for this guideline includes all clinicians. The target patient population includes men and women with low bone density and osteoporosis. ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence). ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence). ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence). ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence). ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence). ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence).


Alcohol consumption and physical health-related quality of life in older women using the transformation of SF-36 to account for death.
Moderate alcohol consumption has been associated with health benefits in several studies, but few studies investigating such association for elders have been done. So, we explored the relationship between alcohol intake and changes in physical health-related quality of life (HRQoL). As analyses of longitudinal HRQoL data excluding diseased participants produced overestimated results, we compared the methods with and without incorporating death and estimated valid physical HRQoL and its decline over time. Study subjects were women from the Australian Longitudinal Study on Women's Health, ages 70-75 years at Survey 1 in 1996 (n = 12,432), and were followed-up at 3 yearly intervals for 6 years. Alcohol consumption was divided into seven categories to identify harmful alcohol levels for older women. We measured Physical Component Score (PCS) of Medical Outcomes Study Short-Form (SF-36), and applied the transformed PCS incorporating death as a valid score to estimate HRQoL changes for each alcohol group with adjustment for potential confounders. Significant declines of values were observed and the values of 'non-drinker' and 'rare drinker' were lower than the other groups during 6 years in both PCS and the transformed PCS. Analysis of the PCS showed significant Alcohol x Time interaction effects for non-drinker and rare drinker groups, as the scores were overestimated towards higher values at Survey 2 due to loss to follow-up of women who died. In the transformed PCS, these interaction effects diminished, and a clearer dose-response relationship between alcohol and physical HRQoL was observed at the third survey. We examined the influence of deaths on the study conclusions with using PCS and its transformed value which included deaths. Being a nondrinker of alcohol was associated with greater risk of mortality and poorer physical HRQoL. Moderate alcohol consumption was not harmful, and may carry some health benefits for older women.


Structural insights into enzymatic degradation of oxidized polyvinyl alcohol.
The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our environment. Yet PVA can be assimilated by microbes in two steps: oxidation and cleavage. Here we report novel α/β-hydrolase structures of oxidized PVA hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3 and Pseudomonas sp. VM15C, including complexes with substrate analogues, acetylacetone and caprylate. The active site is covered by a lid-like β-ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the CC bond of β-diketone, although it has a catalytic triad similar to that of most α/β-hydrolases. Analysis of the crystal structures suggests a double-oxyanion-hole mechanism, previously only found in thiolase cleaving β-ketoacyl-CoA. Three mutations in the lid region showed enhanced activity, with potential in industrial applications.


Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter.
Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R(2) = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence.


Short term and dosage influences of palm based medium- and long-chain triacylglycerols on body fat and blood parameters in C57BL/6J mice.
Structured lipid medium- and long-chain triacylglycerols (MLCT) are claimed to be able to manage obesity. The present study investigated the body fat influence of enzymatically interesterifed palm-based medium- and long-chain triacylglycerols (P-MLCT) on diet-induced obesity (DIO) C57BL/6J mice compared with commercial MLCT oil (C-MLCT) and a control, which was the non enzymatically modified palm kernel and palm oil blend (PKO-PO blend). It also investigated the low fat and high fat effects of P-MLCT. DIO C57BL/6J mice were fed ad libitum with low fat (7%) and high fat (30%) experimental diets for 8 weeks before being sacrificed to obtain blood serum for analysis. From the results, there is a trend that P-MLCT fed mice were found to have the lowest body weight, body weight gain, total fat pad accumulation (perirenal, retroperitoneal, epididymal and mesenteric), total triglyceride levels and efficiency in controlling blood glucose level, compared with C-MLCT and the PKO-PO blend in both low fat and high fat diets. Nevertheless, the PKO-PO blend and P-MLCT caused significantly (P < 0.05) higher total cholesterol levels compared to C-MLCT. P-MLCT present in low fat and high fat dosage were shown to be able to suppress body fat accumulation. This effect is more prominent with the low fat dosage.


Multiple chemical sensitivity and workplace discrimination: the national EEOC ADA research project.
Information from the Integrated Mission System of the United States Equal Employment Opportunity Commission (EEOC) was used to investigate the employment discrimination experiences of Americans with multiple chemical sensitivity (MCS) in comparison to Americans in a general disability group with allergies, asthma, HIV, gastrointestinal impairment, cumulative trauma disorder and tuberculosis. Specifically, the researchers examined demographic characteristics of the charging parties; the industry designation, location, and size of employers against whom allegations were filed; the nature of discrimination (i.e., type of adverse action) alleged to occur; and the legal outcomes or resolutions of these allegations. Findings indicate that persons with MCS were, on average, older than the comparison group and comparatively overrepresented by Caucasians and women. People with MCS were proportionally more likely than the comparison group to allege discrimination related to reasonable accommodations. People with MCS were proportionally more likely than the comparison group to file allegations against employers in the manufacturing and public administration industries, employers with 201-500 workers, and employers in the Western Census region. People with MCS were proportionally more likely than the comparison group to receive non-merit resolutions as a result of the EEOC's Americans with Disabilities Act Title I investigatory process. Implications for policy and advocacy are addressed.


Factors associated with birth outcomes from cryopreserved blastocysts: experience from 4,597 autologous transfers of 7,597 cryopreserved blastocysts.
To evaluate factors associated with cryopreserved blastocyst transfer birth outcomes, including age, expansion time, cryopreservation protocol, cryodamage, and number of embryos transferred. Retrospective cohort study. Private infertility practice. Cryopreserved blastocyst transfer patients from January 2003 to April 2012. None. Birth per transfer and children per embryo. Overall live birth per transfer was 32%, with 17% twin births and 0.3% triplets. Live birth per transfer was significantly higher for vitrification compared with slow-freeze (day 5 cryopreservation: 47% vs. 35%; day 6 cryopreservation: 46% vs. 24%), as was live born children per transferred embryo (39% vs. 29% for day 5; 36% vs. 18% for day 6). Birth rates declined only slightly with increasing age at cryopreservation through 37 years, followed by an increasingly rapid decline in success with increasing age thereafter. Live birth rates declined rapidly (49%-18% for vitrification and 37%-10% for slow-freeze) as the percentage of intact cells after cryopreservation decreased from 95%-100% to 70%-79%, with almost no births when the percentage of intact cells was <70%. Increasing numbers of embryos per transfer were associated with significant increase in live birth per transfer but significant decrease in children per transferred embryo. Birth rates were much lower for blastocysts with delayed expansion on day 7 (10% per transfer). Birth outcomes from cryopreserved blastocyst transfer are influenced by age, timing of expansion, cryopreservation protocol, visible cryodamage, and the number of embryos transferred. Vitrification substantially improves outcomes versus slow freezing.


Differential changes in long-interval intracortical inhibition and silent period duration during fatiguing hand exercise.
During fatiguing exercise corticomotor excitability increases as force declines, which may serve to increase motor output to the exercising muscle, but paradoxically at the same time there is an increase in silent period (SP) duration which is thought to represent a build-up of intracortical inhibition. Paired-pulse TMS at long interstimulus intervals can also be used to derive an index of long-interval cortical inhibition (LICI), however this has not yet been investigated in fatigue. Our aim was to measure LICI during and after a fatiguing exercise and determine if the changes in the index of LICI parallel the changes in SP duration. To do this, we used single and paired-pulse TMS to measure motor evoked potential (MEP) amplitude, LICI and SP duration during, and for 10 min after, a 10-min intermittent maximal fatiguing exercise of the index finger, designed to fatigue the first dorsal interosseous (FDI) muscle (force after 10-min of exercise 64 +/- 7% of baseline, P < 0.05). Single-pulse MEP amplitude and SP duration were increased during fatiguing exercise (minute 10; 179 +/- 24% and 128 +/- 9% of baseline, respectively, P < 0.05), in contrast the measure of LICI was reduced compared to baseline (minute 10; 0.45 +/- 0.17 vs. baseline; 0.70 +/- 0.10, P < 0.05). These results suggest that SP duration and LICI may reflect processes occurring in different neuronal populations. The increased SP duration may correspond to processes of central fatigue in centres 'upstream' of primary motor cortex (M1), whereas the decrease in LICI, together with increased MEP amplitude, are consistent with an increase in M1 output during fatigue that may serve to compensate for reduced central drive.


Integration and dissociation of limb elements in flying vertebrates: a comparison of pterosaurs, birds and bats.
Flapping flight has evolved independently in three vertebrate clades: pterosaurs, birds and bats. Each clade has a unique flight mechanism involving different elements of the forelimb. Here, patterns of limb integration are examined using partial correlation analysis within species and matrix correlation analysis across species to test whether the evolution of flapping flight has involved developmental dissociation of the serial homologues in the fore- and hind limb in each clade. Our sample included seven species of birds, six species of bats, and three species of pterosaurs for which sufficient sample sizes were available. Our results showed that, in contrast to results previously reported for quadrupedal mammals, none of the three clades demonstrated significant integration between serial homologues in the fore- and hind limb. Unexpectedly, there were few consistent patterns of within-forelimb correlations across each clade, suggesting that wing integration is not strongly constrained by functional relationships. However, there was significant integration within the hind limbs of pterosaurs and birds, but not bats, possibly reflecting the differing functions of hind limbs (e.g. upright support vs. suspension) in these clades.


A toxicological and dermatological assessment of macrocyclic lactone and lactide derivatives when used as fragrance ingredients.
The Macrocyclic Lactone and Lactide derivative (ML) group of fragrance ingredients was critically evaluated for safety following a complete literature search. For high end users, calculated maximum dermal exposures vary from 0.47% to 11.15%; systemic exposures vary from 0.0008 to 0.25mg/kg/day. The MLs had low acute toxicity and no significant toxicity in repeat dose oral or dermal toxicity studies. Effects on blood biochemistry were reversible after 2 weeks of no treatment. No mutagenic or genotoxic activity in bacteria and mammalian cell line assays was observed. Reproductive and developmental toxicity was not observed. Human dermatological studies show MLs are generally not irritating after one application. Minor irritation was observed in a few individuals following multiple applications. At rates consistent with reported levels for current human exposure, no phototoxicity or photosensitization was observed. In animal studies, the MLs are not sensitizers at lower exposures from consumer products. Eleven ML materials were evaluated for human sensitization. Of these, only ethylene brassylate showed evidence of sensitization in 2/27 studies (sensitization frequency 4/2059 total). Based on these findings, the Panel is of the opinion that there are no safety concerns for the MLs at reported levels of use and exposure as fragrance ingredients.


Multispectral Optoacoustic Tomography (MSOT) of Human Breast Cancer.
Purpose: In a pilot study, we introduce fast handheld multispectral optoacoustic tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and noncancerous breast tissue.Experimental Design: We imaged 10 female patients ages 48-81 years with malignant nonspecific breast cancer or invasive lobular carcinoma. Three healthy volunteers ages 31-36 years were also imaged. Fast-MSOT was based on unique single-frame-per-pulse (SFPP) image acquisition employed to improve the accuracy of spectral differentiation over using a small number of wavelengths. Breast tissue was illuminated at the 700-970 nm spectral range over 0.56 seconds total scan time. MSOT data were guided by ultrasonography and X-ray mammography or MRI.Results: The extended spectral range allowed the computation of oxygenated hemoglobin (HBO2), deoxygenated hemoglobin (HB), total blood volume (TBV), lipid, and water contributions, allowing first insights into in vivo high-resolution breast tissue MSOT cancer patterns. TBV and Hb/HBO2 images resolved marked differences between cancer and control tissue, manifested as a vessel-rich tumor periphery with highly heterogeneous spatial appearance compared with healthy tissue. We observe significant TBV variations between different tumors and between tumors over healthy tissues. Water and fat lipid layers appear disrupted in cancer versus healthy tissue; however, offer weaker contrast compared with TBV images.Conclusions: In contrast to optical methods, MSOT resolves physiologic cancer features with high resolution and revealed patterns not offered by other radiologic modalities. The new features relate to personalized and precision medicine potential. Clin Cancer Res; 23(22); 6912-22. ©2017 AACR.


Changes in Quality of Life Associated with Complications of Diabetes: Results from the ADVANCE Study.
To measure the impact of complications on summary measures of health-related quality of life among people with type 2 diabetes. Patients participating in the Action in Diabetes and Vascular Disease:Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial were administered a health-related quality-of-life questionnaire, the three-level EuroQol five-dimensional questionnaire (EQ-5D-3L), on four occasions over a 5-year period. We used two-way fixed-effects longitudinal regression models to investigate the impact of incident diabetes complications (stroke, heart failure, myocardial infarction, ischemic heart disease, renal failure, blindness, and amputation) on EQ-5D-3L utility score (where 1 = perfect health), while controlling for characteristics of individuals that do not vary over time. The effect of having any one of the seven complications was to reduce the EQ-5D-3L utility score by 0.054 (95% confidence interval 0.044-0.064), and this was not significantly affected by baseline age, sex, economic region, or the value set used to derive utilities. The complication with the largest disutility was amputation (0.122), followed by stroke (0.099), blindness (0.083), renal failure (0.049), heart failure (0.045), and myocardial infarction (0.026). Ischemic heart disease did not significantly reduce the utility score. Quality of life also declined with elapsed time-by an average of 0.006 per year, in addition to the effect of complications. Common complications significantly reduce health-related quality of life. Utility scores derived from the EQ-5D-3L provide a potential measure that can be used to summarize patient-reported outcomes and inform health economic models. Prevention of complications is critical to reduce the progressive burden of declining quality of life for people with diabetes.


The mycosporine-like amino acids porphyra-334 and shinorine are antioxidants and direct antagonists of Keap1-Nrf2 binding.
Mycosporine-like amino acids (MAAs) are UVR-absorbing metabolites typically produced by cyanobacteria and marine algae, but their properties are not limited to direct sun screening protection. Herein, we examine the antioxidant activities of porphyra-334 and shinorine and demonstrate that these MAAs are prospective activators of the cytoprotective Keap1-Nrf2 pathway. The ability of porphyra-334 and shinorine to bind with Keap1 was determined using fluorescence polarization (FP) and thermal shift assays to detect Keap1 receptor antagonism. Concomitantly, the ability of porphyra-334 and shinorine to dissociate Nrf2 from Keap1 was confirmed also by measurement of increased mRNA expression of Nrf2 targeted genes encoding oxidative stress defense proteins in primary skin fibroblasts prior and post UVR exposure. Surprisingly, enhanced transcriptional regulation was only promoted by MAAs in cells after exposure to UVR-induced oxidative stress. Furthermore, the in-vitro antioxidant activities of porphyra-334 and shinorine determined by the DPPH free-radical quenching assay were low in comparison to ascorbic acid. However, their antioxidant capacity determined by the ORAC assay to quench free radicals via hydrogen atom transfer is substantial. Hence, the dual nature of MAAs to provide antioxidant protection may offer a prospective chemotherapeutic strategy to prevent or retard the progression of multiple degenerative disorders of ageing.


Fourier transform infrared spectra of cells on glass coverslips. A further step in spectral pathology.
Over the last few years, great effort has been placed on developing Fourier Transform Infrared (FTIR) microspectroscopy as a tool to help in the histopathological diagnosis of cancer. The ever increasing workload in pathology departments is calling for a technique that could identify the presence of cancer cells in cytology and tissue samples in an objective, fast and automated way. However, pathologists use glass slides which absorb infrared (IR) radiation thus removing important mid-IR spectral data in the fingerprint region (proteins, DNA, RNA; 1800 cm-1 to 900 cm-1). To this purpose, we hypothesised whether using thinner glass slides, i.e., glass coverslips, would allow us to obtain spectral data not only from the lipid region (3100 cm-1 to 2700 cm-1) but also from the fingerprint region. To this purpose, we studied peripheral blood mononuclear cells (PBMC), a leukaemia cell line (K562) and a lung cancer cell line (CALU-1). Cells were placed on DAKO coverslips and their FTIR spectra obtained at MIRAS beamline, Alba synchrotron light source (Barcelona, Catalonia). The data presented here not only shows for the first time that it is possible to obtain spectral data from most of the amide I region (1800 cm-1 to 1570 cm-1) of cells placed on glass coverslips but more important, principal component analysis was able to separate between the three types of cells for both the lipid and the amide I regions. The methodology here described is a further step in the application of FTIR microspectroscopy in histopathology departments.


Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time.
Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment. One hundred seven patients with confirmed early LD and 26 healthy controls were evaluated using standardized instruments for pain, fatigue, depressive symptoms, functional impact, and cognitive functioning. Prior to antibiotic treatment, patients experience notable symptoms of fatigue and pain statistically higher than controls. After treatment, there are no group differences, suggesting that symptoms resolve and that there are no residual cognitive impairments at the level of group analysis. However, using subgroup analyses, some individuals experience persistent symptoms that lead to functional decline and these individuals can be identified immediately post-completion of standard antibiotic treatment using well-validated symptom measures. Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up.


Environmental risk analysis of hazardous material rail transportation.
An important aspect of railroad environmental risk management involves tank car transportation of hazardous materials. This paper describes a quantitative, environmental risk analysis of rail transportation of a group of light, non-aqueous-phase liquid (LNAPL) chemicals commonly transported by rail in North America. The Hazardous Materials Transportation Environmental Consequence Model (HMTECM) was used in conjunction with a geographic information system (GIS) analysis of environmental characteristics to develop probabilistic estimates of exposure to different spill scenarios along the North American rail network. The risk analysis incorporated the estimated clean-up cost developed using the HMTECM, route-specific probability distributions of soil type and depth to groundwater, annual traffic volume, railcar accident rate, and tank car safety features, to estimate the nationwide annual risk of transporting each product. The annual risk per car-mile (car-km) and per ton-mile (ton-km) was also calculated to enable comparison between chemicals and to provide information on the risk cost associated with shipments of these products. The analysis and the methodology provide a quantitative approach that will enable more effective management of the environmental risk of transporting hazardous materials.


Interleukin-13 selectively suppresses the growth of human macrophage progenitors at the late stage.
Interleukin-13 (IL-13) is a pleiotropic cytokine that inhibits the production of inflammatory cytokines of monocytes. We investigated the effects of IL-13 on the clonal growth of human hematopoietic progenitors. IL-13 alone did not support any colony formation. IL-13 markedly suppressed macrophage colonies that were formed in the presence of IL-3 and erythropoietin, granulocyte-macrophage colony-stimulating factor, or macrophage colony-stimulating factor. Macrophage colony cells showed dendritic cell-line morphology and cellular aggregates. IL-13 did not affect granulocyte colony and erythroid burst formation. Delayed addition of IL-13 and replating onto the culture dishes with IL-13 showed that macrophage colony formation was suppressed during days 8 and 14 of culture. These results indicate that IL-13 affects the growth of the late stage of committed macrophage progenitors. Single-cell culture of isolated CD34+CD33+ cells with IL-13 confirmed that macrophage colony formation was significantly suppressed. These results show that IL-13 directly suppresses the proliferation of differentiating macrophages. In addition, these suppressive effects of IL-13 were synergistic with IL-4. Furthermore, in the liquid culture of bone marrow cells in the presence of IL-13, the number of CD14 (monocyte-macrophage antigen)-positive cells decreased and CD18 (LFA-1 beta)-positive cells increased. It is concluded that IL-13 affects the growth of the late stage of macrophage precursors as well as mature monocytes. Induction of differentiation of human monocytes may be correlated with the suppression of their progenitors.


Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.
A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic. Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline. A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups. A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).


Do spike insoles enhance postural stability and plantar-surface cutaneous sensitivity in the elderly?
Balance problems are often related to a loss of plantar-sensitivity in elderly people. The purpose of this study was to explore the contribution of plantar cutaneous inputs induced by a spike support surface to the control of stance. Nineteen elderly (mean age 69.0 years, range 62-80) and 19 young adults (mean age 25.9 years, range 21-32) were instructed to stand (standing session) or to walk (walking session) for 5 min with sandals equipped with spike insoles (spike condition). Both sessions also involved a no spike condition in which participants stood or walked for 5 min without these insoles (no spike condition). In all conditions, postural responses were assessed during unperturbed stance and were performed (1) immediately after putting the spike or the no spike insoles, and (2) 5 min after standing or walking with them. Sway parameters, such as centre of foot pressure mean location, surface area, mean speed, root mean square and median frequency on the antero-posterior and medio-lateral axes, were calculated. As postural performances are often related to plantar-surface sensitivity, cutaneous sensitivity threshold was also evaluated with Semmes-Weinstein monofilaments. Although no immediate effect of the spike insoles was found, results indicated that standing or walking for 5 min with sandals equipped with spike insoles led to a significant improvement of quiet standing in the elderly. Balance improvement was also observed in young adults. The results provided evidence that wearing sandals with spike insoles can contribute, at least temporarily, to the improvement of unperturbed stance in elderly people with relatively intact plantar cutaneous sensation. Further research is needed to assess the effects of longer and discontinuous stimulations with spike insoles on postural control.


Acquired prosopagnosia with spared within-class object recognition but impaired recognition of degraded basic-level objects.
We present a new case of acquired prosopagnosia resulting from extensive lesions predominantly in the right occipitotemporal cortex. Functional brain imaging revealed atypical activation of all core face areas in the right hemisphere, with reduced signal difference between faces and objects compared to controls. In contrast, Herschel's lateral occipital complex showed normal activation to objects. Behaviourally, Herschel is severely impaired with the recognition of familiar faces, discrimination between unfamiliar identities, and the perception of facial expression and gender. Notably, his visual recognition deficits are largely restricted to faces, suggesting that the damaged mechanisms are face-specific. He showed normal recognition memory for a wide variety of object classes in several paradigms, normal ability to discriminate between highly similar items within a novel object category, and intact ability to name basic objects (except four-legged animals). Furthermore, Herschel displayed a normal face composite effect and typical global advantage and global interference effects in the Navon task, suggesting spared integration of both face and nonface information. Nevertheless, he failed visual closure tests requiring recognition of basic objects from degraded images. This abnormality in basic object recognition is at odds with his spared within-class recognition and presents a challenge to hierarchical models of object perception.


Antibodies to avian influenza viruses in Canada geese (Branta canadensis): a potential surveillance tool?
Traditionally, the epidemiology of avian influenza viruses (AIVs) in wild birds has been defined by detection of virus or viral RNA through virus isolation or reverse-transcription polymerase chain reaction. Our goals were to estimate AIV antibody prevalence in Canada geese (Branta canadensis) and measure effects of age and location on these estimates. We collected 3,205 samples from nine states during June and July 2008 and 2009: Georgia, Massachusetts, Minnesota, Mississippi, New Jersey, North Carolina, Pennsylvania, Washington, and West Virginia. Serum samples were tested for AIV antibodies with the use of a commercial blocking enzyme-linked immunosorbent assay. Overall, 483 (15%) Canada geese had detectable antibodies to AIV. Significantly higher prevalences were detected in geese collected from northeastern and upper midwestern states compared with southeastern states. This trend is consistent with results from virus isolation studies reporting AIV prevalence in North American dabbling ducks. Within Pennsylvania, significantly higher antibody prevalences were detected in goose flocks sampled in urban locations compared to flocks sampled in rural areas. Antibody prevalence was significantly higher in after-hatch-year geese compared to hatch-year geese. No significant differences in prevalence were detected from 10 locations sampled during both years. Results indicate that Canada geese are frequently exposed to AIVs and, with resident populations, may potentially be useful as sentinels to confirm regional AIV transmission within wild bird populations.


3D movies and risk of seizures in patients with photosensitive epilepsy.
3D television (TV) and cinema have experienced a recent surge in popularity aided in part by the success of films such as "Toy Story 3" and "Avatar". In parallel with this trend there have been increasing concerns about the safety of 3D TV and cinema for patients with photosensitive epilepsy. General practitioners, paediatricians and neurologists are being consulted about their opinions on the risk of triggering a seizure. Photosensitive epilepsy occurs in 1 in 4000 of the population but the incidence is higher in people aged 7-19 years. We found little evidence in the literature and confusing advice on various websites. We discuss this evidence in an attempt to clarify the advice that health professionals should be giving on this issue. We conclude that 3D cinema and television are only unlikely to trigger seizures in patients with non-photosensitive epilepsy. In young people with photosensitive epilepsy the risk of triggering a seizure is not greater with 3D TV or cinema than with conventional television, and we suggest means by which this risk can be minimised. We suggest removing 3D glasses when watching conventional TV to prevent the eyes from picking up flicker. Unfortunately there is currently insufficient evidence to draw more formal conclusions and clinical trials would be of great benefit.


Diet inequality prevails among consumers interested and knowledgeable in nutrition.
Previous studies have demonstrated a correlation between diet cost and adherence to nutritional recommendations among consumers in general. This has adverse effects on diet and health inequality. It could be hypothesized that consumers knowledgeable in nutrition escape this correlation. Investigate whether the previously observed relationship between diet cost and nutritional quality prevails among consumers with an above-average interest in and knowledge of nutrition. Full open diet registrations of 330 students taking a basic university-level course in nutrition over a total of 780 days. The consumers with the highest daily average diet cost differ from the lowest cost quartile: The diets had higher micronutrient density, more fruits and vegetables, and lower energy density. The highest cost daily diet quartile had a significantly higher energy adjusted intake of the micronutrients that were on average consumed below the recommendation (vitamin D, folate, and iron for women). On the other hand, alcohol intake was significantly higher among the high diet cost group. The highest diet cost respondents consumed more fish, meat, coffee, and spreads, whereas the lowest diet cost respondents had a higher consumption of cereals, bread, jam, sausage, and milk. Dietary differences prevail even in the above-average interested and knowledgeable group. The respondents did not use their higher level of knowledge to break this commonly observed relationship. This suggests that an increased minimum level of knowledge in nutrition may not by itself eliminate dietary inequality.


Spatial Neglect Predicts Upper Limb Use in the Activities of Daily Living.
Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL. Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment. Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later. This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients.


Bamboo leaf extract improves spatial learning ability in a rat model with senile dementia.
Senile dementia (SD) is a syndrome characterized by progressive neurological deterioration. Treatment for the disease is still under investigation. Bamboo leaf extract (B-extract) has been known for its biological efficacy in anti-oxidant and anti-cancer activities. However, study on B-extract for its protection against dementia is very limited. The effect of B-extract on a rat model with SD was examined. B-extract improved spatial learning ability of the dementia rats. The hippocampus of dementia model rats showed reduced levels of acetylcholine (ACh), epinephrine (E), norepinephrine (NE), and dopamine (DA), and increased activities of acetylcholine esterase (AChE) and monoamine oxidase (MAO). Treatment with B-extract 20 mg/(kg·d) for 7 weeks significantly inhibited the enzyme activity compared with untreated dementia rats, and raised the levels of ACh, E, and DA in the hippocampus. In addition, treatment with B-extract elevated the level of γ-aminobutyric acid (GABA), but reduced the level of glutamate (Glu) in the brain. These data suggest that B-extract might be a potential drug in treating impairment of spatial memory in dementia rats by regulating the central neurotransmitter function.


Story recall and narrative coherence of high-functioning children with autism spectrum disorders.
Previous research has found few quantitative differences between children with high-functioning autism spectrum disorders (ASDs) and well-matched controls in the length, complexity, and structure of their narratives. Researchers have noted, however, that narratives of children with ASDs have an unusual and idiosyncratic nature. This study provides an analysis of narratives in 17 children with high-functioning ASDs and 17 typically developing children matched on age, gender, language abilities, and cognitive abilities. We examined story recall and narrative coherence. The study revealed no group differences in story length or syntactic complexity. Children with ASDs also did not differ from controls in their use of the gist of a story to aid recall, or in their sensitivity to the importance of story events. Children with ASDs did, however, produce narratives that were significantly less coherent than the narratives of controls. Children with ASDs appeared less likely to use the gist of the story to organize their narratives coherently. These findings are discussed with regard to their relationship to other cognitive and linguistic difficulties of children with ASDs.