Experience modulates both aromatase activity and the sensitivity of agonistic behaviour to testosterone in black-headed gulls.
In young black-headed gulls (Larus ridibundus), exposure to testosterone increases the sensitivity of agonistic behaviour to a subsequent exposure to this hormone. The aim of this paper is twofold: to analyze whether social experience, gained during testosterone exposure, mediates this increase in hormonal sensitivity (priming), and whether this in turn is mediated by an increase in central aromatase activity. To this end, we performed three experiments. In the first juvenile gulls were exposed to two consecutive treatments with testosterone (T1 and T2), with more than a week interval in between. During T1, half of the birds were housed in social isolation (Iso) and the other half in groups (Soc). All birds were re-housed in a new social situation during the second treatment. The increase in social behaviour during T2 was significantly more rapid in Soc than Iso birds. In experiment 2 we show that 17beta-estradiol treatment facilitates the behaviour measured in experiment 1. In experiment 3 we used a set-up comparable with that of experiment 1, but birds were sacrificed early in the T2 period. Aromatase activity in the preoptic area and the hypothalamus was measured using the tritiated water releasing method. In some parts of the preoptic area and hypothalamus aromatase activity was higher in Soc birds relative to Iso birds. The results indicate that social experience can modulate the increase of social behaviour to testosterone via modulation of aromatase activity and independently of actual hormone levels.


Concomitant and antecedent deep venous thrombosis and cancer survival in male US veterans.
Survival is reportedly worse in patients with cancer concurrently diagnosed with deep venous thrombosis. However, information on specific malignancies is limited. From a cohort study of male US veterans we identified incident cancer cases (n = 412,008) and compared survival patterns among those with versus without a history of deep venous thrombosis. Using Cox proportional hazard models, we estimated hazard ratios (HRs) and 95% confidence intervals as measures of the relative risk of dying. Individuals with (versus without) a concomitant deep venous thrombosis and cancer diagnosis had a higher risk of dying (HR = 1.38; 1.28-1.49). The most prominent excess mortality (HR = 1.29-2.55) was observed among patients diagnosed with deep venous thrombosis at the time of diagnosis of lung, gastric, prostate, bladder, or kidney cancer. Increased risk of dying was also found among cancer patients diagnosed with deep venous thrombosis 1 year (HR = 1.14; 1.07-1.22), 1-5 years (HR = 1.14; 1.10-1.19), and >5 years (HR = 1.27; 1.23-1.31) before cancer; this was true for most cancer sites (HR = 1.17-1.64). In summary, antecedent deep venous thrombosis confers a worse prognosis upon cancer patients. Advanced stage at diagnosis, treatment effects, lifestyle factors, and comorbidity could explain differences by cancer site and time frame between a prior deep venous thrombosis diagnosis and cancer outcome.


Dynamics of globally delay-coupled neurons displaying subthreshold oscillations.
We study an ensemble of neurons that are coupled through their time-delayed collective mean field. The individual neuron is modelled using a Hodgkin-Huxley-type conductance model with parameters chosen such that the uncoupled neuron displays autonomous subthreshold oscillations of the membrane potential. We find that the ensemble generates a rich variety of oscillatory activities that are mainly controlled by two time scales: the natural period of oscillation at the single neuron level and the delay time of the global coupling. When the neuronal oscillations are synchronized, they can be either in-phase or out-of-phase. The phase-shifted activity is interpreted as the result of a phase-flip bifurcation, also occurring in a set of globally delay-coupled limit cycle oscillators. At the bifurcation point, there is a transition from in-phase to out-of-phase (or vice versa) synchronized oscillations, which is accompanied by an abrupt change in the common oscillation frequency. This phase-flip bifurcation was recently investigated in two mutually delay-coupled oscillators and can play a role in the mechanisms by which the neurons switch among different firing patterns.


T1-Weighted Dynamic Contrast-Enhanced MR Perfusion Imaging Characterizes Tumor Response to Radiation Therapy in Chordoma.
Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy. Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists. ROIs were used to calculate vascular permeability and plasma volume and generate dynamic contrast-enhancement curves. Quantitative analysis was performed to determine mean and maximum plasma volume and vascular permeability values, while semiquantitative analysis on averaged concentration curves was used to determine the area under the curve. A Mann-Whitney U test at a significance level of P < .05 was used to assess differences of the above parameters between pre- and postradiation therapy. Plasma volume mean (pretreatment mean = 0.82; posttreatment mean = 0.42), plasma volume maximum (pretreatment mean = 3.56; posttreatment mean = 2.27), and vascular permeability mean (pretreatment mean = 0.046; posttreatment mean = 0.028) in the ROIs significantly decreased after radiation therapy (P < .05); this change thereby demonstrated the potential for assessing tumor response. Area under the curve values also demonstrated significant differences (P < .05). Plasma volume and vascular permeability decreased after radiation therapy, suggesting that these dynamic contrast-enhanced MR perfusion parameters may be useful for monitoring chordoma growth and response to radiation therapy. Additionally, the characteristic dynamic MR signal intensity-time curve of chordoma may provide a radiographic means of distinguishing chordoma from other spinal lesions.


Positive versus negative effects of VEGF165 on Ca2+ signaling and NO production in human endothelial cells.
The role increased vascular endothelial growth factor (VEGF) plays in vascular function during normal vs. preeclamptic pregnancy has been a source of some controversy of late. In this study, we seek to understand how VEGF165 influences vasodilator production via Ca2+ signaling mechanisms in human endothelial cells. We utilize human umbilical vein endothelial cells (HUVEC) as well as intact ex vivo human umbilical vein (HUV Endo) to address direct stimulation of Ca2+ and NO by VEGF165 alone, as well as the effect of VEGF165 on subsequent ATP-stimulated Ca2+ signaling and NO production. We show that VEGF165 stimulates Ca2+ responses in both HUVEC and HUV Endo, which results in a corresponding increase in NO production in HUV Endo. Longer-term VEGF165 pretreatment then inhibits sustained Ca2+ burst responses to ATP in HUVEC and HUV Endo. This is paralleled by a corresponding drop in ATP-stimulated NO production in HUV Endo, likely through inhibition of Cx43 gap-junction function. Thus, although VEGF165 makes a small initial positive impact on vasodilator production via direct stimulation of Ca2+ responses, this is outweighed by the greater subsequent negative impact on Ca2+ bursts and vasodilator production promoted by more potent agonists such as ATP. Overall, elevated levels of VEGF165 associated with preeclampsia could contribute to the endothelial dysfunction by preventing Ca2+ bursts to other agonists including but not limited to ATP. In this manuscript, we show that VEGF levels associated with preeclampsia are a net negative contributor to potential vasodilator production in both a human ex vivo and in vitro endothelial cell model. Therefore, pharmacological targeting of VEGF-stimulated signaling pathways could be a novel treatment modality for preeclampsia-related hypertension.


Switchgrass cultivar/ecotype selection and management for biofuels in the upper southeast USA.
Switchgrass (Panicum virgatum L.), a perennial warm-season grass indigenous to the eastern USA, has potential as a biofuels feedstock. The objective of this study was to investigate the performance of upland and lowland switchgrass cultivars under different environments and management treatments. Four cultivars of switchgrass were evaluated from 2000 to 2001 under two management regimes in plots established in 1992 at eight locations in the upper southeastern USA. Two management treatments included 1) a single annual harvest (in late October to early November) and a single application of 50 kg N/ha/yr and 2) two annual harvests (in midsummer and November) and a split application of 100 kg N/ha/yr. Biomass yields averaged 15 Mg/ha/yr and ranged from 10 to 22 Mg/ha/yr across cultivars, managements, locations, and years. There was no yield advantage in taking two harvests of the lowland cultivars (Alamo and Kanlow). When harvested twice, upland cultivars (Cave-in-Rock and Shelter) provided yields equivalent to the lowland ecotypes. Tiller density was 36% lower in stands cutting only once per year, but the stands appeared vigorous after nine years of such management. Lowland cultivars and a one-cutting management (after the tops have senesced) using low rates of applied N (50 kg/ha) are recommended.


Medical Respite for People Experiencing Homelessness: Financial Impacts with Alternative Levels of Medicaid Coverage.
Medical respite (MR) programs provide medical care, social services, and a safe place to recuperate for people experiencing homelessness after hospital discharge. We examined the financial impact of MR on hospitals and insurers in states with varying Medicaid coverage. Urban case-study hospitals were selected from a state with Medicaid expansion under the Affordable Care Act (Connecticut) and without expansion (Florida). We calculated costs and savings from MR to hospitals and payers from the hospitals' financial data. These hospitals currently incur losses of 26% (Conn.) to 48% (Fla.) on inpatient care costs of patients experiencing homelessness. Medical respite would reduce these losses by reducing the index length of stay by two days, subsequent emergency department visits by 45%, and subsequent inpatient admissions by 35%, offsetting $1.81 in hospital costs for each dollar invested in MR. With appropriate sharing of costs between hospitals and payers, both would save money from MR.


Health of farmed fish: its relation to fish welfare and its utility as welfare indicator.
This brief review focuses on health and biological function as cornerstones of fish welfare. From the function-based point of view, good welfare is reflected in the ability of the animal to cope with infectious and non-infectious stressors, thereby maintaining homeostasis and good health, whereas stressful husbandry conditions and protracted suffering will lead to the loss of the coping ability and, thus, to impaired health. In the first part of the review, the physiological processes through which stressful husbandry conditions modulate health of farmed fish are examined. If fish are subjected to unfavourable husbandry conditions, the resulting disruption of internal homeostasis necessitates energy-demanding physiological adjustments (allostasis/acclimation). The ensuing energy drain leads to trade-offs with other energy-demanding processes such as the functioning of the primary epithelial barriers (gut, skin, gills) and the immune system. Understanding of the relation between husbandry conditions, allostatic responses and fish health provides the basis for the second theme developed in this review, the potential use of biological function and health parameters as operational welfare indicators (OWIs). Advantages of function- and health-related parameters are that they are relatively straightforward to recognize and to measure and are routinely monitored in most aquaculture units, thereby providing feasible tools to assess fish welfare under practical farming conditions. As the efforts to improve fish welfare and environmental sustainability lead to increasingly diverse solutions, in particular integrated production, it is imperative that we have objective OWIs to compare with other production forms, such as high-density aquaculture. However, to receive the necessary acceptance for legislation, more robust scientific backing of the health- and function-related OWIs is urgently needed.


THE ENDOPLASMIC RETICULUM OF GASTRIC PARIETAL CELLS.
An electron microscopic survey has been made of the gastric parietal or oxyntic cell of the human, cat, beaver, dog, hamster, rat, mouse, and bat, and of the corresponding cell type in two species of frog, two species of toad, and the horned lizard. A feature consistently found in the parietal cells of the mammals or their equivalent in the lower vertebrates is the agranular endoplasmic reticulum, which takes the form of branching and anastomosing small tubules approximately 200 to 500 A in diameter, sometimes expanded into flattened cisternae. In mammalian parietal cells this form of the endoplasmic reticulum is found only in limited amounts, but in the corresponding secretory cells of the amphibia and reptilia the tubular agranular reticulum is abundant. It is believed to comprise a more or less continuous system of channels, but owing to their tortuous course only short profiles are seen in thin sections. Immediately subjacent to the plasmalemma at the free surface, the cytoplasm is relatively free of organelles but is occasionally traversed by the agranular reticulum, which appears to be continuous at some points with the cell surface. The possible participation of the agranular endoplasmic reticulum in hydrochloric acid secretion is discussed.


Population effects of increased climate variation.
Global circulation models predict and numerous observations confirm that anthropogenic climate change has altered high-frequency climate variability. However, it is not yet well understood how changing patterns of environmental variation will affect wildlife population dynamics and other ecological processes. Theory predicts that a population's long-run growth rate is diminished and the chance of population extinction is increased as environmental variation increases. This results from the fact that population growth is a multiplicative process and that long-run population growth rate is the geometric mean of growth rates over time, which is always less than the arithmetic mean. However, when population growth rates for unstructured populations are related nonlinearly to environmental drivers, increasing environmental variation can increase a population's long-run growth rate. This suggests that patterns of environmental variation associated with different aspects of climate change may affect population dynamics in different ways. Specifically, increasing variation in rainfall might result in diminished long-run growth rates for many animal species while increasing variation in temperature might result in increased long-run growth rates. While the effect of rainfall is theoretically well understood and supported by data, the hypothesized effect of temperature is not. Here, I analyse two datasets to study the effect of fluctuating temperatures on growth rates of zooplankton. Results are consistent with the prediction that fluctuating temperatures should increase long-run growth rates and the frequency of extreme demographic events.


Optimal recall length in survey design.
Self-reported data collected via surveys are a key input into a wide range of research conducted by economists. It is well known that such data are subject to measurement error that arises when respondents are asked to recall past utilisation. Survey designers must determine the length of the recall period and face a trade-off as increasing the recall period provides more information, but increases the likelihood of recall error. A statistical framework is used to explore this trade-off. Finally we illustrate how optimal recall periods can be estimated using hospital use data from Sweden's Survey of Living Conditions.


Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lung cancer and mesothelioma.
Immunotherapy has transformed lung cancer care in recent years. In addition to providing durable responses and prolonged survival outcomes for a subset of patients with heavily pretreated non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs)- either as monotherapy or in combination with other ICIs or chemotherapy-have demonstrated benefits in first-line therapy for advanced disease, the neoadjuvant and adjuvant settings, as well as in additional thoracic malignancies such as small-cell lung cancer (SCLC) and mesothelioma. Challenging questions remain, however, on topics including therapy selection, appropriate biomarker-based identification of patients who may derive benefit, the use of immunotherapy in special populations such as people with autoimmune disorders, and toxicity management. Patient and caregiver education and support for quality of life (QOL) is also important to attain maximal benefit with immunotherapy. To provide guidance to the oncology community on these and other important concerns, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). This CPG represents an update to SITC's 2018 publication on immunotherapy for the treatment of NSCLC, and is expanded to include recommendations on SCLC and mesothelioma. The Expert Panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for lung cancer and mesothelioma, including diagnostic testing, treatment planning, immune-related adverse events, and patient QOL considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers using immunotherapy to treat patients with lung cancer or mesothelioma.


beta-Oxidation in human alcoholic and non-alcoholic hepatic steatosis.
1. The CoA and carnitine ester intermediates of mitochondrial beta-oxidation have not previously been quantified in liver disease, although there is some evidence that beta-oxidation is inhibited in alcoholic fatty liver. Mitochondria were isolated from needle liver biopsies from normal subjects, from patients with alcoholic fatty liver and patients with fatty liver of other aetiologies, incubated with 60 mumol/l [U-14C]hexadecanoate and the resultant CoA and carnitine esters were measured. 2. Although there was no significant difference in beta-oxidation flux between the patient groups, there was a significant rise in the proportion of 3-hydroxyacyl-CoA and 2-enoyl-CoA esters in patients with alcoholic fatty liver compared with normal subjects, and in patients with non-alcoholic fatty liver, suggesting an inhibition at the level of 3-hydroxyacyl-CoA dehydrogenase activity. 3. In alcoholic patients this difference could not be accounted for on the basis of the measured activity of short and long-chain 3-hydroxyacyl-CoA dehydrogenases, and it is suggested that either an inhibition of complex I activity or diminished amounts of ubiquinone are likely to be responsible for the observed accumulation of CoA and carnitine esters, which may contribute to the accumulation of triacylglycerols in alcoholic steatosis. In fatty liver of other aetiologies, short- and long-chain 3-hydroxyacyl-CoA dehydrogenase activities were decreased.


Coupling effect of magnetic polariton in perforated metal/dielectric layered metamaterials and its influence on negative refraction transmission.
The optical propagation properties and magnetic polariton behaviors in perforated metal/dielectric layered structures are numerically investigated at near-IR region. A developed three-metal-layer (TML) structure is specially inspected as a simple case. Strong coupling effect of magnetic polariton is discovered in this system, which explains why TML structure reveals better negative-refraction property than the reported double-metal-layer (DML) structure. A clear LC-circuit model is presented to describe the physical mechanism of this coupling effect of magnetic polaritons. Detailed results show that the thickness of metal layer influences the transmission greatly and an optimum value is found.


Comparing evolvabilities: common errors surrounding the calculation and use of coefficients of additive genetic variation.
In 1992, David Houle showed that measures of additive genetic variation standardized by the trait mean, CVA (the coefficient of additive genetic variation) and its square (IA), are suitable measures of evolvability. CVA has been used widely to compare patterns of genetic variation. However, the use of CVAs for comparative purposes relies critically on the correct calculation of this parameter. We reviewed a sample of quantitative genetic studies, focusing on sire models, and found that 45% of studies use incorrect methods for calculating CVA and that practices that render these coefficients meaningless are frequent. This may have important consequences for conclusions drawn from comparative studies. Our results are suggestive of a broader problem because miscalculation of the additive genetic variance from a sire model is prevalent among the studies sampled, implying that other important quantitative genetic parameters might also often be estimated incorrectly. We discuss the most prominent issues affecting the use of CVA and IA, including scale effects, data transformation, and the comparison of traits with different dimensions. Our aim is to increase awareness of the potential mistakes surrounding the calculation and use of evolvabilities, and to compile general guidelines for calculating, reporting, and interpreting these useful measures in future studies.


Evaluating the reliability of equilibrium dissolution assumption from residual gasoline in contact with water saturated sands.
Understanding dissolution dynamics of hazardous compounds from complex gasoline mixtures is a key to long-term predictions of groundwater risks. The aim of this study was to investigate if the local equilibrium assumption for BTEX and TMBs (trimethylbenzenes) dissolution was valid under variable saturation in two dimensional flow conditions and evaluate the impact of local heterogeneities when equilibrium is verified at the scale of investigation. An initial residual gasoline saturation was established over the upper two-thirds of a water saturated sand pack. A constant horizontal pore velocity was maintained and water samples were recovered across 38 sampling ports over 141days. Inside the residual NAPL zone, BTEX and TMBs dissolution curves were in agreement with the TMVOC model based on the local equilibrium assumption. Results compared to previous numerical studies suggest the presence of small scale dissolution fingering created perpendicular to the horizontal dissolution front, mainly triggered by heterogeneities in the medium structure and the local NAPL residual saturation. In the transition zone, TMVOC was able to represent a range of behaviours exhibited by the data, confirming equilibrium or near-equilibrium dissolution at the scale of investigation. The model locally showed discrepancies with the most soluble compounds, i.e. benzene and toluene, due to local heterogeneities exhibiting that at lower scale flow bypassing and channelling may have occurred. In these conditions mass transfer rates were still high enough to fall under the equilibrium assumption in TMVOC at the scale of investigation. Comparisons with other models involving upscaled mass transfer rates demonstrated that such approximations with TMVOC could lead to overestimate BTEX dissolution rates and underestimate the total remediation time.


Judging a book by its cover: the unconscious influence of pupil size on consumer choice.
Past research suggests that men perceive women with large pupils as especially attractive. We employed an innovative methodology to examine whether this effect influences consumer decision-making. A popular psychology book was published with two slightly different front covers. Both covers contained the same photograph of a woman; however, the woman's pupils on one cover were digitally enlarged. Readers indicated whether they were male or female, and whether they possessed the cover with small or large pupils. A significantly greater percentage of men than women had chosen the cover with the large pupils. None of the participants who attempted to guess the nature of the experiment was correct, suggesting that the influence exerted by pupil size was unconscious. These findings provide further support for the notion that people's judgments are unconsciously swayed by pupil size, and demonstrate that this effect operates in a real world setting.


Additional palmaroproximal-palmarodistal oblique radiographic projections improve accuracy of detection and characterization of equine flexor cortical lysis.
Radiographic flexor cortical lysis indicates advanced degenerative change and its earlier recognition may improve case outcome. Aims of this prospective, diagnostic accuracy study were to determine effects of radiographic beam angle and observer on accuracy of lesion detection. The sample included 36 limbs from 31 horses. Palmaroproximal-palmarodistal oblique (skyline) radiographs were acquired at standard (n = 38) and more shallow (alternate) angles (n = 58). Images were independently reviewed by four experience levels of five observers each (n = 20) for the presence and severity of flexor cortical lysis. Observers also reported their confidence in these answers. Responses were compared based on seeing a standard skyline or multiple projections. The definitive presence (or absence) and severity of lysis was based upon radiologist consensus agreement. When assessed by observer, the identification of lysis and the assessment of its severity was most similar to that of radiologists when observers of all levels of experience were able to view multiple skyline projections (P = 0.399, P = 0.174). Using multiple views to detect lysis resulted in improved sensitivity (85.3% vs. 97.2%, P < 0.001), decreased specificity (82.8% vs. 74.5%, P = 0.03), and improved interobserver agreement (86.0% vs. 90.2%, P = 0.21). On average, observers of all levels of experience became more confident viewing multiple projections (P < 0.001). Skyline radiographs using a flatter angle of incidence improve radiographic detection and characterization of flexor cortical lysis severity, may allow the beam to be tangential to the more distal portion of the navicular bone, and are recommended when flexor cortical lysis is suspected.


A compact Airy beam light sheet microscope with a tilted cylindrical lens.
Light-sheet imaging is rapidly gaining importance for imaging intact biological specimens. Many of the latest innovations rely on the propagation-invariant Bessel or Airy beams to form an extended light sheet to provide high resolution across a large field of view. Shaping light to realize propagation-invariant beams often relies on complex programming of spatial light modulators or specialized, custom made, optical elements. Here we present a straightforward and low-cost modification to the traditional light-sheet setup, based on the open-access light-sheet microscope OpenSPIM, to achieve Airy light-sheet illumination. This brings wide field single-photon light-sheet imaging to a broader range of endusers. Fluorescent microspheres embedded in agarose and a zebrafish larva were imaged to demonstrate how such a microscope can have a minimal footprint and cost without compromising on imaging quality.


Detection of arterial emboli using Doppler ultrasound in rabbits.
The purpose of this study was to develop an animal model that could be used to test the ability of Doppler ultrasound to detect arterial emboli composed of materials that are often involved in cerebral emboli. Emboli introduced into the rabbit aorta via the left renal artery consisted of clotted whole blood, platelets, atheromatous material, fat, or air. The ultrasound examination was carried out continuously during the studies using a multifrequency transcranial Doppler apparatus with a 2-MHz probe, a sample volume of 15 mm, at a depth of 15 mm. The intensity of the Doppler spectrum was measured and displayed as a 15-shade color scale, each shade representing a 3-dB difference. The diameter of the aorta at the site of the ultrasound examination was similar to the diameter of the middle cerebral artery in humans. All 125 emboli introduced were clearly detected because they caused a Doppler signal at least 15 dB greater than that of the surrounding blood. These results show that the potential for emboli detection using Doppler ultrasound in the clinical situation is now considerable.


Treatment of dural arteriovenous fistula using ethylene vinyl alcohol (onyx) arterial embolization as the primary modality: short-term results.
A dural arteriovenous fistula (DAVF) typically involves meningeal feeding arteries and can cause clinical symptoms ranging from tinnitus to rupture of draining cortical or parenchymal veins. Surgical treatment may be technically demanding. Ethylene vinyl alcohol (Onyx, ev3 Neurovascular) has several properties that make it potentially useful as a primary treatment agent for DAVF. Onyx is expected to be a permanent embolic agent. It should have a decreased risk of catheter retention when compared with other permanent embolic materials. The authors report a series of six patients with symptomatic DAVF who were treated initially with transarterial Onyx embolization and other endovascular techniques. Five patients had complete occlusion of their DAVF noted on the follow-up angiogram obtained between 2 and 4 months. One patient had residual filling via a small arterial branch that was stable on follow-up angiography. None of the patients had worsening of neurological function. One case was complicated by a retained catheter fragment. Transarterial Onyx embolization and other endovascular methods can angiographically obliterate DAVF. In some cases, embolization allowed occlusion of multiple arterial feeding arteries from a single arterial injection. Technically, the embolization was optimized when a microcatheter position immediately adjacent to the point(s) of fistulization was achieved.


[Clinical zoanthropy: a woman with the rare delusion of being an animal].
Clinical zoanthropy, or the conviction of having turned into an animal, is a rare delusion. There are different views about its pathogenesis. This delusion can occur with an underlying psychiatric disorder, but it can also be secondary to structural or functional disorders of the brain. Additional investigations with brain imaging and electroencephalogram are therefore advised. Treatment for the underlying disorder is recommended. In this case report we describe a 54-year-old woman who was briefly convinced she was a chicken, followed by a generalized seizure. We discuss the epidemiology, theories about pathogenesis and treatment advice for clinical zoanthropy. We also discuss the possible relevance of epilepsy to this matter. With this case report, we hope to contribute to documenting this rare, but possibly underreported phenomenon.


Histoplasma capsulatum modulates the acidification of phagolysosomes.
The phagolysosome is perhaps the most effective antimicrobial site within macrophages due both to its acidity and to its variety of hydrolytic enzymes. Few species of pathogens survive and multiply in these vesicles. However, one strategy for microbial survival would be to induce a higher pH within these organelles, thus interfering with the activity of many lysosomal enzymes. Altering the intravesicular milieu might also profoundly influence antigen processing, antimicrobial drug delivery, and drug activity. Here we report the first example of an organism proliferating within phagolysosomes that maintain a relatively neutral pH for a sustained period of time. We inoculated P388D1 macrophages with fluorescein isothiocyanate (FITC)-labeled Histoplasma capsulatum or zymosan. Using the ratio of fluorescence excitations at 495 and 450 nm, we determined that vesicles containing either virulent or avirulent FITC-labeled H. capsulatum yeasts had a pH one to two units higher than vesicles containing either zymosan or methanol-killed H. capsulatum. The difference in pH remained stable for at least 5.5 h postinoculation. Longer-term studies using cells preincubated with acridine orange indicated that phagolysosomes containing live Histoplasma continued to maintain a relatively neutral pH for at least 30 h. Many agents raise the pH of multiple vesicles within the same cell. In contrast, H. capsulatum affects only the phagolysosome in which it is located; during coinoculation of cells with unlabeled Histoplasma and labeled zymosan, organelles containing zymosan still acidified normally. Similarly, unlabeled zymosan had no influence on the elevated pH of vesicles housing labeled Histoplasma. Thus, zymosan and Histoplasma were segregated into separate phagolysosomes that responded independently to their phagocytized contents. This localized effect might reflect an intrinsic difference between phagosomes housing the two particle types, active buffering by the microbe, or altered ion transport across the phagolysosomal membrane such that acidification is inhibited.


Extending human healthspan and longevity: a symposium report.
For many years, it was believed that the aging process was inevitable and that age-related diseases could not be prevented or reversed. The geroscience hypothesis, however, posits that aging is, in fact, malleable and, by targeting the hallmarks of biological aging, it is indeed possible to alleviate age-related diseases and dysfunction and extend longevity. This field of geroscience thus aims to prevent the development of multiple disorders with age, thereby extending healthspan, with the reduction of morbidity toward the end of life. Experts in the field have made remarkable advancements in understanding the mechanisms underlying biological aging and identified ways to target aging pathways using both novel agents and repurposed therapies. While geroscience researchers currently face significant barriers in bringing therapies through clinical development, proof-of-concept studies, as well as early-stage clinical trials, are underway to assess the feasibility of drug evaluation and lay a regulatory foundation for future FDA approvals in the future.


A cytokeratin 8-like protein with plasminogen-binding activity is present on the external surfaces of hepatocytes, HepG2 cells and breast carcinoma cell lines.
Plasminogen binding to cell surfaces may be important for tumor invasion and other processes that involve cellular migration. In this investigation, the principal plasminogen-binding protein was identified in the plasma membrane fraction of rat hepatocytes. The protein had an apparent mass of 59 kDa, was insoluble in a spectrum of detergents, and was identical to cytokeratin 8 (CK 8) as determined by sequence analysis of nine amino acids at the N terminus of two cyanogen bromide fragments. The 59 kDa protein bound CK 8-specific antibody in western blot analyses. These studies demonstrate that CK 8 or a CK 8-like protein binds plasminogen. Given this newly determined and potentially important CK 8 function, immunofluorescence and immunoelectron microscopy studies were performed to determine whether CK 8 may be present on the external surfaces of unpermeabilized, viable hepatocytes. All of the cells in each preparation were immunopositive with two separate CK 8-specific antibodies. A punctate pattern of immunofluorescence was detected on the cell surface with approximately even intensity from cell to cell. By immunoelectron microscopy, CK 8 was preferentially associated with microvilli. In order to determine whether other epithelial cells express cell-surface CK 8, immunofluorescence and immunoelectron microscopy studies were performed with HepG2 hepatocellular carcinoma cells and with BT20 and MCF-7 breast carcinoma cells. The pattern of antigen expression was equivalent with each cell type and comparable to that observed with hepatocytes. These studies support the hypothesis that CK 8 is associated with the external cell surface where it may express important proteinase receptor function.


Additional surgery for postoperative ischemic symptoms in patients with moyamoya disease: the effectiveness of occipital artery-posterior cerebral artery bypass with an indirect procedure: technical case report.
In patients with moyamoya disease, surgery to revascularize the ischemic brain is a recommended treatment. However, there are a few patients who require additional revascularization surgery because of progression of the disease. Even patients who show no postoperative ischemic symptoms at first may experience late deterioration. We performed additional surgery for such lesions using occipital artery (OA)-posterior cerebral artery (PCA) bypass with indirect revascularization. The efficacy of the procedure is reported. We treated 3 patients with moyamoya disease who showed a transient ischemic attack after revascularization surgery. Three female patients, ranging in age from 6.0 to 35.2 years (mean age, 23.8 years) at the time of surgery, with ischemic symptoms (leg monoparesis in 2, visual impairment in 1) underwent the additional revascularization procedure. Preoperatively, all patients underwent indirect and/or direct revascularization surgery for initial treatment. All patients showed progression of the disease, especially in the PCA. OA-PCA bypass with encephalogaleodurosynangiosis and burr hole surgery were performed for postoperative ischemic symptoms. All patients showed clinical and radiological improvement. The transient ischemic attack was improved in all 3 patients. They did not complain of transient ischemic attack in the recent follow-up period. Follow-up magnetic resonance imaging showed no additional cerebral infarction. Magnetic resonance angiography showed widening of the OA and development of peripheral collateral vessels. Postoperative single-photon emission computed tomographic studies showed marked increase of uptake in both anterior cerebral artery and PCA territories. Cerebral vasodilatory capacity evaluated by an acetazolamide test also showed marked improvement. One patient showed postoperative cerebral edema as a result of focal cerebral hyperperfusion. OA-PCA anastomosis with indirect revascularization was effective for postoperative ischemia that showed symptoms in the anterior cerebral artery and PCA territories as a result of progression of a PCA lesion.


The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety.
There has been increasing interest in the development of effective agents that can be safely used to promote anabolism in the clinical setting for patients with chronic wasting conditions as well as in the prevention and treatment of frailty associated with loss of muscle tissue in aging (sarcopenia). One such agent is the anabolic androgenic steroid (AAS) oxandrolone, which has been used in such clinical situations as HIV-related muscle wasting, severe burn injury, trauma following major surgery, neuromuscular disorders and alcoholic hepatitis for over 30 years. In the US, oxandrolone is the only AAS that is US FDA-approved for restitution of weight loss after severe trauma, major surgery or infections, malnutrition due to alcoholic cirrhosis, and Duchenne's or Becker's muscular dystrophy. Our review of the use of oxandrolone in the treatment of catabolic disorders, HIV and AIDS-related wasting, neuromuscular and other disorders provides strong evidence of its clinical efficacy. Improvements in body composition, muscle strength and function, status of underlying disease or recovery from acute catabolic injury and nutritional status are significant in the vast majority of well designed trials. However, oxandrolone has not yet been studied in sarcopenia.Unlike other orally administered C17alpha-alkylated AASs, the novel chemical configuration of oxandrolone confers a resistance to liver metabolism as well as marked anabolic activity. In addition, oxandrolone appears not to exhibit the serious hepatotoxic effects (jaundice, cholestatic hepatitis, peliosis hepatis, hyperplasias and neoplasms) attributed to the C17alpha-alkylated AASs. Oxandrolone is reported to be generally well tolerated and the most commonly documented adverse effects are transient elevations in transaminase levels and reductions in high density lipoprotein cholesterol level.However, optimal risk:benefit ratios for oxandrolone and other agents in its class will need to be refined before widespread clinical acceptance of AASs as a therapeutic option in sarcopenia and other chronic wasting conditions.


Design considerations for holographic optical interconnects.
The geometrical design characteristics of multiple-image holograms are evaluated. A figure of merit expressing these characteristics as a function of the hologram diameter and the distance between the hologram and the image plane is developed. This value is then used to compare two designs which are capable of forming several hundred interconnections. The results indicate that these connections can be formed between points on the substrate separated by 2-3 cm provided that the holograms are separated from the substrate plane by 0.5-1 cm. Each hologram design is experimentally demonstrated in bleached photographic emulsions.


Learning from single extreme events.
Extreme climatic events (ECEs) have a disproportionate effect on ecosystems. Yet much of what we know about the ecological impact of ECEs is based on observing the effects of single extreme events. We examined what characteristics affect the strength of inference that can be drawn from single-event studies, which broadly fell into three categories: opportunistic observational studies initiated after an ECE, long-term observational studies with data before and after an ECE and experiments. Because extreme events occur rarely, inference from such single-event studies cannot easily be made under the usual statistical paradigm that relies on replication and control. However, single-event studies can yield important information for theory development and can contribute to meta-analyses. Adaptive management approaches can be used to learn from single, or a few, extreme events. We identify a number of factors that can make observations of single events more informative. These include providing robust estimates of the magnitude of ecological responses and some measure of climatic extremeness, collecting ancillary data that can inform on mechanisms, continuing to observe the biological system after the ECE and combining observational data with experiments and models. Well-designed single-event studies are an important contribution to our understanding of biological effects of ECEs.This article is part of the themed issue 'Behavioural, ecological and evolutionary responses to extreme climatic events'.


In vitro digestibility of individual amino acids in rumen-undegraded protein: the modified three-step procedure and the immobilized digestive enzyme assay.
Three soybean meal, 3 SoyPlus (West Central Cooperative, Ralston, IA), 5 distillers dried grains with solubles, and 5 fish meal samples were used to evaluate the modified 3-step in vitro procedure (TSP) and the in vitro immobilized digestive enzyme assay (IDEA; Novus International Inc., St. Louis, MO) for estimating digestibility of AA in rumen-undegraded protein (RUP-AA). In a previous experiment, each sample was ruminally incubated in situ for 16 h, and in vivo digestibility of AA in the intact samples and in the rumen-undegraded residues (RUR) was obtained for all samples using the precision-fed cecectomized rooster assay. For the modified TSP, 5 g of RUR was weighed into polyester bags, which were then heat-sealed and placed into Daisy(II) incubator bottles. Samples were incubated in a pepsin/HCl solution followed by incubation in a pancreatin solution. After this incubation, residues remaining in the bags were analyzed for AA, and digestibility of RUP-AA was calculated based on disappearance from the bags. In vitro RUP-AA digestibility estimates obtained with this procedure were highly correlated to in vivo estimates. Corresponding intact feeds were also analyzed via the pepsin/pancreatin steps of the modified TSP. In vitro estimates of AA digestibility of the feeds were highly correlated to in vivo RUP-AA digestibility, which suggests that the feeds may not need to be ruminally incubated before determining RUP-AA digestibility in vitro. The RUR were also analyzed via the IDEA kits. The IDEA values of the RUR were good predictors of RUP-AA digestibility in soybean meal, SoyPlus, and distillers dried grains with solubles, but the IDEA values were not as good predictors of RUP-AA digestibility in fish meal. However, the IDEA values of intact feed samples were also determined and were highly correlated to in vivo RUP-AA digestibility for all feed types, suggesting that the IDEA value of intact feeds may be a better predictor of RUP-AA digestibility than the IDEA value of the RUR. In conclusion, the modified TSP and IDEA kits are good approaches for estimating RUP-AA digestibility in soybean meal products, distillers dried grains with solubles, and fish meal samples.


Relations between occupational, psychosocial and individual factors and three different categories of back disorder among supermarket workers.
Up-to-date store-wide studies regarding low back pain (LBP) among supermarket/hypermarket workers are lacking. We investigated 12-month store-wide prevalence of different categories of LBP and possible associated biomechanical, individual/psychosocial risk factors across a large supermarket/hypermarket chain. We performed a cross-sectional study of 3,702 subjects working in a group of small/medium-sized supermarkets (n=100) and large hypermarkets (n=7) belonging to a single chain in central-northern Italy applying established ergonomics/job-satisfaction policies. Data regarding the various departments were collected by a medical check-list, physical examination and questionnaire-all conducted by qualified physicians--and were analyzed in relation to a comprehensive biomechanical risk analysis. The overall 12-month prevalence of LBP in our sample (with a 82% response rate) was 34.5% (36.6% for females and 30.7% for males), with few differences being found between supermarkets and hypermarkets. Different types of LBP showed significant associations with stress-related psychosomatic symptoms, but not with job satisfaction (which was high). These encouraging data provide relevant information regarding workers operating in supermarkets/hypermarkets with an active commitment to ergonomic and job-satisfaction policies.


Exercises and Dry Needling for Subacromial Pain Syndrome: A Randomized Parallel-Group Trial.
This randomized clinical trial investigated the effectiveness of exercise versus exercise plus trigger point (TrP) dry needling (TrP-DN) in subacromial pain syndrome. A randomized parallel-group trial, with 1-year follow-up was conducted. Fifty subjects with subacromial pain syndrome were randomly allocated to receive exercise alone or exercise plus TrP-DN. Participants in both groups were asked to perform an exercise program of the rotator cuff muscles twice daily for 5 weeks. Further, patients allocated to the exercise plus TrP-DN group also received dry needling to active TrPs in the muscles reproducing shoulder symptoms during the second and fourth sessions. The primary outcome was pain-related disability assessed using the Disabilities of the Arm, Shoulder, and Hand questionnaire. Secondary outcomes included mean current pain and the worst pain experienced in the shoulder during the previous week. They were assessed at baseline, 1 week, and 3, 6, and 12 months after the end of treatment. Analysis was according to intention to treat with mixed analysis of covariance adjusted for baseline outcomes. At 12 months, 47 patients (94%) completed follow-up. Statistically larger improvements (all, P < .01) in shoulder disability was found for the exercise plus TrP-DN group at all follow-up periods (post: Δ -20.6 [95% confidence interval (CI) -23.8 to -17.4]; 3 months: Δ -23.2 [95% CI -28.3 to -18.1)]; 6 months: Δ -23.6 [95% CI -28.9 to -18.3]; 12 months: Δ -13.9 [95% CI -17.5 to -10.3]). Both groups exhibited similar improvements in shoulder pain outcomes at all follow-up periods. The inclusion of TrP-DN with an exercise program was effective for improving disability in subacromial pain syndrome. No greater improvements in shoulder pain were observed. This study found that the inclusion of 2 sessions of TrP-DN into an exercise program was effective for improving shoulder pain-related disability at short-, medium-, and long-term; however, no greater improvement in shoulder pain was observed.


A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging.
Although DNA damage is considered a driving force for aging, the nature of the damage that arises endogenously remains unclear. Replicative stress, a source of endogenous DNA damage, is prevented primarily by the ATR kinase. We have developed a mouse model of Seckel syndrome characterized by a severe deficiency in ATR. Seckel mice show high levels of replicative stress during embryogenesis, when proliferation is widespread, but this is reduced to marginal amounts in postnatal life. In spite of this decrease, adult Seckel mice show accelerated aging, which is further aggravated in the absence of p53. Together, these results support a model whereby replicative stress, particularly in utero, contributes to the onset of aging in postnatal life, and this is balanced by the replicative stress-limiting role of the checkpoint proteins ATR and p53.


Development and evaluation of a model-based downscatter compensation method for quantitative I-131 SPECT.
The radionuclide 131I has found widespread use in targeted radionuclide therapy (TRT), partly due to the fact that it emits photons that can be imaged to perform treatment planning or posttherapy dose verification as well as beta rays that are suitable for therapy. In both the treatment planning and dose verification applications, it is necessary to estimate the activity distribution in organs or tumors at several time points. In vivo estimates of the 131I activity distribution at each time point can be obtained from quantitative single-photon emission computed tomography (QSPECT) images and organ activity estimates can be obtained either from QSPECT images or quantification of planar projection data. However, in addition to the photon used for imaging, 131I decay results in emission of a number of other higher-energy photons with significant abundances. These higher-energy photons can scatter in the body, collimator, or detector and be counted in the 364 keV photopeak energy window, resulting in reduced image contrast and degraded quantitative accuracy; these photons are referred to as downscatter. The goal of this study was to develop and evaluate a model-based downscatter compensation method specifically designed for the compensation of high-energy photons emitted by 131I and detected in the imaging energy window. In the evaluation study, we used a Monte Carlo simulation (MCS) code that had previously been validated for other radionuclides. Thus, in preparation for the evaluation study, we first validated the code for 131I imaging simulation by comparison with experimental data. Next, we assessed the accuracy of the downscatter model by comparing downscatter estimates with MCS results. Finally, we combined the downscatter model with iterative reconstruction-based compensation for attenuation (A) and scatter (S) and the full (D) collimator-detector response of the 364 keV photons to form a comprehensive compensation method. We evaluated this combined method in terms of quantitative accuracy using the realistic 3D NCAT phantom and an activity distribution obtained from patient studies. We compared the accuracy of organ activity estimates in images reconstructed with and without addition of downscatter compensation from projections with and without downscatter contamination. We observed that the proposed method provided substantial improvements in accuracy compared to no downscatter compensation and had accuracies comparable to reconstructions from projections without downscatter contamination. The results demonstrate that the proposed model-based downscatter compensation method is effective and may have a role in quantitative 131I imaging.


Overexpression of RAD51 Enables PCR-Based Gene Targeting in Lager Yeast.
Lager beer fermentations rely on specific polyploid hybrids between Saccharomyces cerevisiae and Saccharomyces eubayanus falling into the two groups of S. carlsbergensis/Saaz-type and S. pastorianus/Frohberg-type. These strains provide a terroir to lager beer as they have long traditional associations and local selection histories with specific breweries. Lager yeasts share, based on their common origin, several phenotypes. One of them is low transformability, hampering the gene function analyses required for proof-of-concept strain improvements. PCR-based gene targeting is a standard tool for manipulating S. cerevisiae and other ascomycetes. However, low transformability paired with the low efficiency of homologous recombination practically disable targeted gene function analyses in lager yeast strains. For genetic manipulations in lager yeasts, we employed a yeast transformation protocol based on lithium-acetate/PEG incubation combined with electroporation. We first introduced freely replicating CEN/ARS plasmids carrying ScRAD51 driven by a strong heterologous promoter into lager yeast. RAD51 overexpression in the Weihenstephan 34/70 lager yeast was necessary and sufficient in our hands for gene targeting using short-flanking homology regions of 50 bp added to a selection marker by PCR. We successfully targeted two independent loci, ScADE2/YOR128C and ScHSP104/YLL026W, and confirmed correct integration by diagnostic PCR. With these modifications, genetic alterations of lager yeasts can be achieved efficiently and the RAD51-containing episomal plasmid can be removed after successful strain construction.


Engineering of tissue inhibitor of metalloproteinases mutants as potential therapeutics.
Matrix metalloproteinases (MMPs) play a central role in many biological processes such as development, morphogenesis and wound healing, but their unbalanced activities are implicated in numerous disease processes such as arthritis, cancer metastasis, atherosclerosis, nephritis and fibrosis. One of the key mechanisms to control MMP activities is inhibition by endogenous inhibitors called tissue inhibitors of metalloproteinases (TIMPs). This review highlights the structures and inhibition mechanism of TIMPs, the biological activities of TIMPs, the unique properties of TIMP-3, and the altered specificity towards MMPs achieved by mutagenesis. A potential therapeutic use of TIMP variants is discussed.


Corrugator supercilii muscle terminal nerve ablation using a novel thread technique for the treatment of hyperdynamic vertical glabellar furrows.
A novel percutaneous corrugator supercilii muscle terminal nerve CSMTN ablation technique is proposed for the treatment of hyperdynamic vertical glabellar furrows (HVGF). Two surgical marks are placed on each eyebrow. One is placed at the level of the lateral canthus and the second at the outer border of the limbus. At each of the four marks, the following steps are carried out: (1) a guiding needle is used to punch the frontal skin at 3 mm above the eyebrow (orifice A) and will then travel deeply at the level of the supraperiostium and emerge outside the skin 3 mm below the eyebrow (orifice B) at the palpebral skin; (2) the needle is then reentered exactly at orifice B and will travel underneath the skin at a more superficial level in the subcutaneous layer and then emerge outside exactly at orifice A. Both ends of the thread are gently pulled in a sawing motion with counter tension until no more resistance is felt from the anatomical structures involved, and then the loops of thread are withdrawn from orifice A. Forty-seven subjects underwent bilateral CSMTN ablation. In the first 10 cases, the authors performed only one neurotomy per eye and observed a 50 percent HVGF recurrence rate. Then, the authors chose to perform two neurotomies per side and had a three percent recurrence rate (1/37) with a high degree of patient satisfaction. Major complications such as deforming hematomas, eyelid ptosis, abscess, scar formation or adhesions were not observed during follow up. This novel technique may represent a simple and permanent solution for HVGF.


Colonic inflammation accompanies an increase of β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of high-fat diet-fed mice.
Consumption of an obesigenic/high-fat diet (HFD) is associated with a high colon cancer risk and may alter the gut microbiota. To test the hypothesis that long-term high-fat (HF) feeding accelerates inflammatory process and changes gut microbiome composition, C57BL/6 mice were fed HFD (45% energy) or a low-fat (LF) diet (10% energy) for 36 weeks. At the end of the study, body weights in the HF group were 35% greater than those in the LF group. These changes were associated with dramatic increases in body fat composition, inflammatory cell infiltration, inducible nitric oxide synthase protein concentration and cell proliferation marker (Ki67) in ileum and colon. Similarly, β-catenin expression was increased in colon (but not ileum). Consistent with gut inflammation phenotype, we also found that plasma leptin, interleukin 6 and tumor necrosis factor α concentrations were also elevated in mice fed the HFD, indicative of chronic inflammation. Fecal DNA was extracted and the V1-V3 hypervariable region of the microbial 16S rRNA gene was amplified using primers suitable for 454 pyrosequencing. Compared to the LF group, the HF group had high proportions of bacteria from the family Lachnospiraceae/Streptococcaceae, which is known to be involved in the development of metabolic disorders, diabetes and colon cancer. Taken together, our data demonstrate, for the first time, that long-term HF consumption not only increases inflammatory status but also accompanies an increase of colonic β-catenin signaling and Lachnospiraceae/Streptococcaceae bacteria in the hind gut of C57BL/6 mice.


"What concerns me is..." Expression of emotion by advanced cancer patients during outpatient visits.
Cancer patients have high levels of distress, yet oncologists often do not recognize patients' concerns. We sought to describe how patients with advanced cancer verbally express negative emotion to their oncologists. As part of the Studying Communication in Oncologist-Patient Encounters Trial, we audio-recorded 415 visits that 281 patients with advanced cancer made to their oncologists at three US cancer centers. Using qualitative methodology, we coded for verbal expressions of negative emotion, identified words patients used to express emotion, and categorized emotions by type and content. Patients verbally expressed negative emotion in 17% of the visits. The most commonly used words were: "concern," "scared," "worried," "depressed," and "nervous." Types of emotion expressed were: anxiety (46%), fear (25%), depression (12%), anger (9%), and other (8%). Topics about which emotion was expressed were: symptoms and functional concerns (66%), medical diagnoses and treatments (54%), social issues (14%), and the health care system (9%). Although all patients had terminal cancer, they expressed negative emotion overtly related to death and dying only 2% of the time. Patients infrequently expressed negative emotion to their oncologists. When they did, they typically expressed anxiety and fear, indicating concern about the future. When patients use emotionally expressive words such as those we described, oncologists should respond empathically, allowing patients to express their distress and concerns more fully.


Mobile Phone App for Self-Monitoring of Eating Rhythm: Field Experiment.
Temporal aspects of eating are an integral part of healthy eating, and regular eating has been associated with good diet quality and more successful weight control. Unfortunately, irregular eating is becoming more common. Self-monitoring of behavior has been found to be an efficient behavioral change technique, but the solution should be simple enough to ensure long-lasting adherence. This study aimed to explore the influence of self-monitoring of daily eating pattern with mobile phone app on eating rhythm, eating behavior tendencies, and the underlying motives and attitudes related to eating. A mobile phone app, Button, was developed for effortless self-monitoring of eating rhythm. The feasibility of the app was tested in a 30-day intervention. The participants (N=74) recorded their eating occasions during the intervention by pressing a button in the app widget. The average interval between meals increased (96 [SD 24] min during the first 10 days vs 109.1[SD 36.4] during the last 10 days) and the number of daily eating occasions decreased (4.9 [SD 0.9] during the first 10 days vs 4.4 [SD 0.9] during the last 10 days). The tendencies for cognitive restraint, emotional eating, and uncontrolled eating increased. Eating-related attitudes and motives remained largely unchanged. These results indicate that a simple self-monitoring tool is able to draw a user's attention to eating and is a potential tool to aid people to change their eating rhythm.


Chronic progressive neurological involvement in Borrelia burgdorferi infection.
Five patients with chronic meningitis were hospitalized several times for progressive neurological symptoms. The clinical manifestations included cranial neuritis, radiculoneuritis, myelitis and encephalitis. In two cases cerebral infarction occurred. The course was commonly characterized by a tendency to deteriorate. From the clinical point of view, it was repeatedly difficult to exclude multiple sclerosis or tuberculous meningitis. Finally, specific antibodies against Borrelia burgdorferi were detected by indirect immunofluorescence assay. The diagnosis of a borreliosis was not considered initially because there was no history of tick-bite or erythema chronicum migrans, and the neurological involvement of the central nervous system seemed unusual. The latency between the first symptoms and diagnosis varied from 3 months to 5 years. After a parenteral, high-dose therapy with penicillin, there was a significant improvement in all patients. In two cases, there was evidence of intrathecally produced antibodies to myelin basic protein.


Familial CLL: genes and environment.
Families with multiple individuals affected with chronic lymphocytic leukemia (CLL) and other related B-cell tumors have been described in the literature. Familial CLL does not appear to differ from sporadic CLL in terms of prognostic markers and clinical outcome. While some environmental factors (such as farming-related exposures and occupational chemicals) may increase risk of CLL, results of epidemiologic studies have been generally inconsistent. Rates of CLL in the population show significant international variation, with the highest rates in the U.S. and Europe and the lowest rates in Asia. Migrants from Asia to the U.S. also have low rates of CLL, which supports a greater role for genetic compared with environmental risk factors. Large, population-based case-control and cohort studies have also shown significant familial aggregation of CLL and related conditions including non-Hodgkin and Hodgkin lymphoma. Monoclonal B-cell lymphocytosis also aggregates in families with CLL. However, the clinical implication of familial aggregation is minimal given the overall rarity of CLL. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for loci that contribute to susceptibility, but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated immune function and other genes, but more studies are needed to verify these findings. The ability to conduct large-scale genomic studies will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate etiologic pathways.


Investigating concordance in diabetes diagnosis between primary care charts (electronic medical records) and health administrative data: a retrospective cohort study.
Electronic medical records contain valuable clinical information not readily available elsewhere. Accordingly, they hold important potential for contributing to and enhancing chronic disease registries with the goal of improving chronic disease management; however a standard for diagnoses of conditions such as diabetes remains to be developed. The purpose of this study was to establish a validated electronic medical record definition for diabetes. We constructed a retrospective cohort using health administrative data from the Institute for Clinical Evaluative Sciences Ontario Diabetes Database linked with electronic medical records from the Deliver Primary Healthcare Information Project using data from 1 April 2006-31 March 2008 (N = 19,443). We systematically examined eight definitions for diabetes diagnosis, both established and proposed. The definition that identified the highest number of patients with diabetes (N = 2,180) while limiting to those with the highest probability of having diabetes was: individuals with ≥2 abnormal plasma glucose tests, or diabetes on the problem list, or insulin prescription, or ≥2 oral anti-diabetic agents, or HbA1c ≥6.5%. Compared to the Ontario Diabetes Database, this definition identified 13% more patients while maintaining good sensitivity (75%) and specificity (98%). This study establishes the feasibility of developing an electronic medical record standard definition of diabetes and validates an algorithm for use in this context. While the algorithm may need to be tailored to fit available data in different electronic medical records, it contributes to the establishment of validated disease registries with the goal of enhancing research, and enabling quality improvement in clinical care and patient self-management.


Self-reported Health is Related to Body Height and Waist Circumference in Rural Indigenous and Urbanised Latin-American Populations.
Body height is a life-history component. It involves important costs for its expression and maintenance, which may originate trade-offs on other costly components such as reproduction or immunity. Although previous evidence has supported the idea that human height could be a sexually selected trait, the explanatory mechanisms that underlie this selection are poorly understood. Despite extensive studies on the association between height and attractiveness, the role of immunity in linking this relation is scarcely studied, particularly in non-Western populations. Here, we tested whether human height is related to health measured by self-perception, and relevant nutritional and health anthropometric indicators in three Latin-American populations that widely differ in socioeconomic and ecological conditions: two urbanised populations from Bogota (Colombia) and Mexico City (Mexico), and one isolated indigenous population (Me'Phaa, Mexico). Results showed that self-reported health is best predicted by an interaction between height and waist circumference: the presumed benefits of being taller are waist-dependent, and affect taller people more than shorter individuals. If health and genetic quality cues play an important role in human mate-choice, and height and waist interact to signal health, its evolutionary consequences, including cognitive and behavioural effects, should be addressed in future research.


Assessing completeness of perinatal hepatitis B virus infection reporting through comparison of immunization program and surveillance data--United States.
In the United States, an estimated 24,000 women with hepatitis B virus (HBV) infection give birth each year. To prevent mother-to-child HBV transmission, the Advisory Committee on Immunization Practices (ACIP) recommends administering postexposure prophylaxis of hepatitis B vaccine (HepB) and hepatitis B immune globulin (HBIG) to infants born to HBV-infected women within 12 hours of delivery, followed by completion of the HepB series. In 1990, CDC established a national Perinatal Hepatitis B Prevention Program (PHBPP) to support federal immunization program grantees in performing this ACIP-recommended case management of infants born to HBV-infected women. Perinatal HBV infections currently are reported by state and local health departments to CDC through two parallel processes: by immunization programs as part of federal program grant reporting requirements and by communicable disease surveillance units as part of the National Notifiable Diseases Surveillance System (NNDSS). A review of perinatal HBV infection reporting for infants born in 2005 identified 68 cases reported by immunization programs and 47 cases reported by communicable disease surveillance units, resulting in a total of 73 unique cases, 42 (58%) of which were reported by both systems. Following investigation, data reconciliation, and additional NNDSS reporting, 78 unique cases were identified, 63 (84%) of which were reported by both systems. Improved information-sharing between immunization programs and communicable disease surveillance units of health departments is essential to ensure more complete identification, case management, and quantification of perinatal HBV infections. Accuracy and completeness of perinatal HBV infection reporting can help ensure and measure progress toward elimination of HBV transmission in the United States.


Edge-on adsorption of multi-chain functional alkanes stabilizes noncovalent monolayers on MoS2.
Modified long-chain alkanes are often used to functionalize graphene and MoS2 noncovalently, with the goal of controlling the substrate electronic structure or interactions with the environment. Alkyl chain adsorption enthalpy is lower on MoS2 than on graphite; the decreased molecule-substrate interaction strength suggests utility for monolayer structures that increase stability through other means. Previously, we have found that diyne phospholipid monolayers on HOPG are more stable toward solution processing than monolayers of single-chain amphiphiles. Here, we show that this is also true for assembly on MoS2, but that the additional stability appears to arise from edge-on adsorption, producing monolayers in which alkyl chains form two stacked layers on the substrate.


Induction of antibody response to Chlamydia trachomatis in the genital tract by oral immunization.
Groups of BALB/c mice were orally immunized with Chlamydia trachomatis serovar L2/434/Bu in order to characterize the nature and kinetics of the chlamydial antibody response in the cervix and other mucosal sites. These animals were subsequently challenged intravaginally to determine whether oral immunization offers protection against chlamydial antigen shedding in the genital tract. Following oral immunization, immunoglobulin A antibody activity was detected in the genital tract as well as other mucosal sites. Subsequent intravaginal challenges exhibited booster effects on preexisting antibody activity in the genital tract. Significant protection against challenge infection in the genital tract was observed by oral immunization. This was indicated by the absence of any chlamydial antigen shedding in cervical secretions. On the other hand, passively administered chlamydial-specific serum immunoglobulin G antibody did not significantly influence the course of cervical shedding of the organism and did not confer any protection against a subsequent intravaginal challenge. It is concluded that prior oral immunization can induce a secretory antibody response in the genital tract and provide protection against subsequent infection.


Calcium-dependent prolonged effects on melanophores of [4-norleucine, 7-D-phenylalanine]-alpha-melanotropin.
A single injection of the melanotropin analog [4-norleucine, 7-D-phenylalanine]-alpha-melanotropin into frogs (Rana pipiens) caused near maximum darkening of the skins of the frogs for at least 6 weeks. Injections of the natural hormone alpha-melanotropin or of the analog [Nle4]-alpha-melanotropin also caused darkening, but this effect lasted only a few days. Morphological examination of the skins of frogs injected with [Nle4, D-Phe7]-alpha-melanotropin revealed that both dermal and epidermal melanophores were dispersed during the entire 6-week period. In vitro [Nle4, D-Phe7]-alpha-melanotropin also causes prolonged darkening of the skin of the lizard Anolis carolinensis. In the absence of the melanotropin, skins previously darkened with the analog could be lightened by removal of calcium from the incubation medium but could then be redarkened by adding calcium. The cycle could be repeated indefinitely without addition of melanotropin. These results demonstrate the role of calcium in receptor signal transduction and the prolonged biological effects of [Nle4, D-Phe7]-alpha-melanotropin long after its removal from the assay medium.


Effects of autoclaving and high pressure on allergenicity of hazelnut proteins.
Hazelnut is reported as a causative agent of allergic reactions. However it is also an edible nut with health benefits. The allergenic characteristics of hazelnut-samples after autoclaving (AC) and high-pressure (HHP) processing have been studied and are also presented here. Previous studies demonstrated that AC treatments were responsible for structural transformation of protein structure motifs. Thus, structural analyses of allergen proteins from hazelnut were carried out to observe what is occurring in relation to the specific-IgE recognition of the related allergenic proteins. The aims of this work are to evaluate the effect of AC and HHP processing on hazelnut in vitro allergenicity using human-sera and to analyse the complexity of hazelnut allergen-protein structures. Hazelnut-samples were subjected to AC and HHP processing. The specific IgE- reactivity was studied in 15 allergic clinic-patients via western blotting analyses. A series of homology-based-bioinformatics 3D-models (Cora 1, Cora 8, Cora 9 and Cora 11) were generated for the antigens included in the study to analyse the co mplexity of their protein structure. This study is supported by the Declaration of Helsinki and subsequent ethical guidelines. A severe reduction in vitro in allergenicity to hazelnut after AC processing was observed in the allergic clinic-patients studied. The specific-IgE binding of some of the described immunoreactive hazelnut protein-bands: Cora 1 ~18KDa, Cora 8 ~9KDa, Cora 9 ~35-40KDa and Cora 11 ~47-48 KDa decreases. Furthermore a relevant glycosylation was assigned and visualized via structural analysis of proteins (3D-modelling) for the first time in the protein-allergen Cora 11 showing a new role which could open a new door for allergenicity-unravellings. Hazelnut allergenicity-studies in vivo via Prick-Prick and other means using AC processing are crucial to verify the data we observed via in vitro analyses. Glycosylation studies provided us with clues to elucidate, in the near future, mechanisms of the structures that contribute to hazelnut allergenicity, which thus, in turn, help alleviate food allergens.


Cleavage stage mitochondrial DNA is correlated with preimplantation human embryo development and ploidy status.
To evaluate whether the mitoscore of cleavage stage embryos might correlate with developmental kinetics and the ploidy status. This retrospective single-center study involved all cycles between April 2016 and April 2018 in which preimplantation genetic testing for aneuploidy (PGT-A) on day 3 was performed. The mitochondrial DNA (mtDNA) content and embryo ploidy were determined on 375 single blastomere biopsies by next generation sequencing (NGS). After intracytoplasmic sperm injection, a time-lapse imaging system (embryoscope) was used to follow the development. The median mtDNA content of cleavage stage embryos (49.4) was used to stratify the embryos into two groups to compare embryo development and ploidy status: low mitoscore group (≤ 49.4) and high mitoscore group (> 49.4). The total number of euploid embryos was equal between both mitoscore groups (32.1% versus 33.5%; p = 0.854). However, embryos in the low mitoscore group had a significantly higher cell number on day 3 (8.13 ± 1.59 versus 7.62 ± 1.5; p = 0.0013) and showed a significantly faster development up until the 8-cell stage. Mitoscore was not different between euploid and aneuploid embryos, with the same blastomere number at the time of biopsy. Furthermore, absence of cavitation within 118 h after insemination was correlated with higher mitoscore values (60.22 ± 42.23 versus 50.97 ± 13.37; p = 0.006) and a lower chance of being euploid (17.1% versus 47.4%; p = 0.001). mtDNA content of cleavage stage embryos correlates with time-lapse parameters. Early blastulation is correlated with a lower mtDNA content and a higher chance of euploidy.


Smoking status in Iranian male adolescents: a cross-sectional study and a meta-analysis.
The present study aimed to estimate the prevalence of smoking status and its associated factors in Iranian adolescents and a meta-analysis of recent cross-sectional studies in order to estimate the corresponding prevalence for all Iranian adolescents. In a cross-sectional study, 1064 male high school students in Zanjan city (northwest of Iran) were recruited. A self-administered questionnaire was used for smoking status and associated factors. Through the meta-analysis, all relevant published studies were reviewed. Almost one-third of adolescents (34.2%, n=354) have experienced smoking either experimentally (23.4%, n=242), or regularly (10.8%, n=112). Multivariate analysis showed that older age (OR=1.20; 95% CI: 1.05-1.37), risky behaviors (OR=1.83; 1.25-2.68), Tramadol medication (OR=2.19; 1.54-3.11), low self-esteem (OR=1.07; 1.03-1.11), positive attitude toward smoking (OR=1.15; 1.09-1.21), positive thinking about smoking (OR=1.07; 1.01-1.14) and having smoker friends (OR=1.94; 1.36-2.77) were significantly associated with cigarette smoking in adolescents. Meta-analysis results showed that 7% of Iranian adolescents are regular smokers and 27% are experimenters. Increasing prevalence of smoking in Iranian adolescents is a major concern for public health. Controlling risky behaviors and increasing health education are recommended.


Brain endothelial miR-146a negatively modulates T-cell adhesion through repressing multiple targets to inhibit NF-κB activation.
Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development of neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) has emerged as an anti-inflammatory molecule by inhibiting NF-κB activity in various cell types, but its effect in BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a was upregulated in microvessels of MS-active lesions and the spinal cord of mice with experimental autoimmune encephalomyelitis. In vitro, TNFα and IFNγ treatment of human cerebral microvascular endothelial cells (hCMEC/D3) led to upregulation of miR-146a. Brain endothelial overexpression of miR-146a diminished, whereas knockdown of miR-146a augmented cytokine-stimulated adhesion of T cells to hCMEC/D3 cells, nuclear translocation of NF-κB, and expression of adhesion molecules in hCMEC/D3 cells. Furthermore, brain endothelial miR-146a modulates NF-κB activity upon cytokine activation through targeting two novel signaling transducers, RhoA and nuclear factor of activated T cells 5, as well as molecules previously identified, IL-1 receptor-associated kinase 1, and TNF receptor-associated factor 6. We propose brain endothelial miR-146a as an endogenous NF-κB inhibitor in BECs associated with decreased leukocyte adhesion during neuroinflammation.


Care Burden and Mental Ill Health in Spouses of People With Parkinson Disease Dementia and Lewy Body Dementia.
To explore and compare levels of mental health, care burden, and relationship satisfaction among caregiving spouses of people with mild cognitive impairment or dementia in Parkinson disease (PD-MCI or PDD) or dementia with Lewy bodies (DLB). Spouses (n = 136) completed measures of mood, stress, resilience, general health, quality of life, care burden, and relationship satisfaction, as well as sociodemographic factors. Additionally, data on motor and neuropsychiatric symptom severity of people with PD-MCI, PDD, or DLB were obtained in a subsample. Most spouses were married women (>85%) who provided a median of 4 years of care and 84 hours of weekly care. Among these, relationship dissatisfaction, stress, anxiety, care burden, and feelings of resentment were common. Spouses of people with PDD and DLB had significantly higher rates of burden, resentment, and depression compared to spouses of people with PD-MCI. Furthermore, unique group differences emerged whereby spouses of people with PDD had significantly longer duration of care provision, higher stress, more relationship dissatisfaction, and fewer positive interactions, compared to PD-MCI group, whereas anxiety and lower levels of mental health were prominent in spouses of people with DLB, compared to PD-MCI group. Despite this, the majority of spouses reported good quality of life, resilience, and satisfaction with the caring role. Both PDD and DLB significantly contribute to poorer mental health and higher levels of care burden in spouses. Clinicians should actively screen the risk of burden, stress, depression, and anxiety among caregiving spouses of people with these conditions.


[High levels of high-sensitivity C-reactive protein and impaired autonomic activity in smokers].
We investigated the relationship between high sensitivity C-reactive protein (hs-CRP) activity and autonomic nervous activity using heart rate variability in smokers. The study consisted of 136 healthy subjects, including 66 smokers (35 women, 31 men; mean age 36 years) and 70 nonsmokers (43 women, 27 men; mean age 34 years). Serum samples were collected from all the subjects. Three-channel, 24-hr Holter monitoring was performed to derive the mean heart rate, standard deviation of normal NN intervals (SDNN), standard deviation of 5-minute mean NN intervals (SDANN), root mean square differences of successive NN intervals (RMSSD), high- (HF) and low- (LF) frequency power components, and the LF/HF ratio. In smokers, the mean duration of smoking was 13.6+/-8.2 years (range 3 to 45 years), and the mean number of cigarettes consumed per day was 16.3+/-7.1 (range 5 to 40). Smokers exhibited significantly higher mean heart rate, hs-CRP and fibrinogen levels, mean platelet volume, white blood cell count, LF, and LF/HF ratio, with significantly lower SDNN, SDANN, RMSSD, and HF values. In smokers, hs-CRP was correlated with the number of cigarettes consumed per day, duration of smoking, fibrinogen level, mean platelet volume, white blood cell count, LF, and LF/HF ratio, and inversely correlated with HF, SDNN, and SDANN. Even smoking a single cigarette resulted in an acute, 0.07-fold increase in the hs-CRP level (p<0.0001). In linear regression analysis, both the number of cigarettes consumed per day (beta=0.52, p=0.011) and duration of smoking (beta=0.073, p<0.0001) had an independent effect on the hs-CRP level. Smoking both impairs the sympathovagal balance and increases the hs-CRP activity in otherwise healthy smokers, the combination of which would probably contribute to a higher rate of cardiovascular events.


The secondary buckling transition: wrinkling of buckled spherical shells.
We theoretically explain the complete sequence of shapes of deflated spherical shells. Decreasing the volume, the shell remains spherical initially, then undergoes the classical buckling instability, where an axisymmetric dimple appears, and, finally, loses its axisymmetry by wrinkles developing in the vicinity of the dimple edge in a secondary buckling transition. We describe the first axisymmetric buckling transition by numerical integration of the complete set of shape equations and an approximate analytic model due to Pogorelov. In the buckled shape, both approaches exhibit a locally compressive hoop stress in a region where experiments and simulations show the development of polygonal wrinkles, along the dimple edge. In a simplified model based on the stability equations of shallow shells, a critical value for the compressive hoop stress is derived, for which the compressed circumferential fibres will buckle out of their circular shape in order to release the compression. By applying this wrinkling criterion to the solutions of the axisymmetric models, we can calculate the critical volume for the secondary buckling transition. Using the Pogorelov approach, we also obtain an analytical expression for the critical volume at the secondary buckling transition: The critical volume difference scales linearly with the bending stiffness, whereas the critical volume reduction at the classical axisymmetric buckling transition scales with the square root of the bending stiffness. These results are confirmed by another stability analysis in the framework of Donnel, Mushtari and Vlasov (DMV) shell theory, and by numerical simulations available in the literature.


The domestication syndrome in vegetatively propagated field crops.
Vegetatively propagated crops are globally significant in terms of current agricultural production, as well as for understanding the long-term history of early agriculture and plant domestication. Today, significant field crops include sugarcane (Saccharum officinarum), potato (Solanum tuberosum), manioc (Manihot esculenta), bananas and plantains (Musa cvs), sweet potato (Ipomoea batatas), yams (Dioscorea spp.) and taro (Colocasia esculenta). In comparison with sexually reproduced crops, especially cereals and legumes, the domestication syndrome in vegetatively propagated field crops is poorly defined. Here, a range of phenotypic traits potentially comprising a syndrome associated with early domestication of vegetatively propagated field crops is proposed, including: mode of reproduction, yield of edible portion, ease of harvesting, defensive adaptations, timing of production and plant architecture. The archaeobotanical visibility of these syndrome traits is considered with a view to the reconstruction of the geographical and historical pathways of domestication for vegetatively propagated field crops in the past. Although convergent phenotypic traits are identified, none of them are ubiquitous and some are divergent. In contrast to cereals and legumes, several traits seem to represent varying degrees of plastic response to growth environment and practices of cultivation, as opposed to solely morphogenetic 'fixation'.


Identification of P1 gene domain containing epitope(s) mediating Mycoplasma pneumoniae cytoadherence.
A genomic library of Mycoplasma pneumoniae was constructed by cloning sheared genomic DNA into the expression vector lambda gt11. Recombinant clones were screened using anti-M. pneumoniae mAbs reactive with adhesin P1 epitopes that mediate cytadherence. 10 clones with different size inserts were isolated. These clones possessed P1 sequences localized to the COOH terminus of the P1 gene. All clones produced fusion proteins that reacted with acute and convalescent sera of patients infected with M. pneumoniae. Interestingly, one clone, P1-7, contained an epitope that was confined to a region of 13 amino acids present in the M. pneumoniae genome as a single copy. The identification of this cytadherence-related epitope permits the production of a synthetic peptide that can be used as a rational vaccine candidate and serodiagnostic probe.


Indications for ureteropyeloscopy based on radiographic findings and urine cytology in detection of upper urinary tract carcinoma.
To verify the indication of diagnostic ureteropyeloscopy based on clinical features for upper urinary tract urothelial cancer with over 100 patients and over a 10-year series. From January 1997 to December 2008, consecutive 129 units in 124 patients underwent ureteropyeloscopy to obtain a definitive diagnosis of upper urinary tract cancer or to rule out a malignancy. Patients were divided into four subgroups based on voided urine cytology and preoperative radiographic findings: group A (n = 8), positive urine cytology and positive radiographic findings; group B (n = 4), positive cytology and negative radiographic findings; group C (n = 55), negative cytology and positive radiographic findings and group D (n = 62), gross hematuria originating from the upper urinary tract with negative cytology and negative radiographic findings. Ureteropyeloscopic findings were compared with radiographic and cytological results. Adverse effects were also investigated. In group A, all patients had confirmed cancer. In group B, one revealed small cancer and the remaining three confirmed carcinoma in situ by biopsy with ureteropyeloscopy. In groups C and D, 33 patients (60%) and four (6.5%) revealed cancer. Seventy-eight patients out of 80 (97.5%) in groups C and D were confirmed to have benign disease. No patient was found with malignancy during follow up after negative finding of ureteropyeloscopy. Ureteropyeloscopy can help in detecting upper urinary tract cancer or to rule out malignancy for patients with negative voiding cytology. However, ureteropyeloscopy is redundant for patients with positive radiographic findings and positive voiding cytology.


Toxicity of leachate from weathering plastics: An exploratory screening study with Nitocra spinipes.
Between 60% and 80% of all marine litter is plastic. Leachate from plastics has previously been shown to cause acute toxicity in the freshwater species Daphnia magna. Here, we present an initial screening of the marine environmental hazard properties of leachates from weathering plastics to the marine harpacticoid copepod [Crustacea] Nitocra spinipes. Twenty-one plastic products made of different polymeric materials were leached and irradiated with artificial sunlight. Eight of the twenty-one plastics (38%) produced leachates that caused acute toxicity. Differences in toxicity were seen for different plastic products, and depending on the duration of irradiation. There was no consistent trend in how toxicity of leachate from plastics changed as a function of irradiation time. Leachate from four plastics became significantly more toxic after irradiation, two became significantly less toxic and two did not change significantly. Analysis of leachates from polyvinyl chloride (PVC) by liquid chromatography coupled to a full-scan high-resolution mass spectrometer showed that the leachates were a mixture of substances, but did not show evidence of degradation of the polymer backbone. This screening study demonstrates that leachates from different plastics differ in toxicity to N. spinipes and that the toxicity varies under simulated weathering.


Carbon exchange responses of a mesic grassland to an extreme gradient of precipitation.
Growing evidence indicates that ecosystem processes may be differentially sensitive to dry versus wet years, and that current understanding of how precipitation affects ecosystem processes may not be predictive of responses to extremes. In an experiment within a mesic grassland, we addressed this uncertainty by assessing responses of two key carbon exchange processes-aboveground net primary production (ANPP) and soil respiration (Rs)-to an extensive gradient of growing season precipitation. This gradient comprised 11 levels that specifically included extreme values in precipitation; defined as the 1st, 5th, 95th, and 99th percentiles of the 112-year climate record. Across treatments, our experimental precipitation gradient linearly increased soil moisture availability in the rooting zone (upper 20 cm). Relative to ANPP under nominal precipitation amounts (defined as between the 15th and 85th percentiles), the magnitude of ANPP responses were greatest to extreme increases in precipitation, with an underlying linear response to both precipitation and soil moisture gradients. By contrast, Rs exhibited marginally greater responses to dry versus wet extremes, with a saturating relationship best explaining responses of Rs to both precipitation and soil moisture. Our findings indicate a linear relationship between ANPP and precipitation after incorporating responses to precipitation extremes in the ANPP-precipitation relationship, yet in contrast saturating responses of Rs. As a result, current linear ANPP-precipitation relationships (up to ~ 1000 mm) within mesic grasslands appear to hold as appropriate benchmarks for ecosystems models, yet such models should incorporate nonlinearities in responses of Rs amid increased frequencies and magnitudes of precipitation extremes.


Technological Innovations in Disease Management: Text Mining US Patent Data From 1995 to 2017.
Patents are important intellectual property protecting technological innovations that inspire efficient research and development in biomedicine. The number of awarded patents serves as an important indicator of economic growth and technological innovation. Researchers have mined patents to characterize the focuses and trends of technological innovations in many fields. To expand patent mining to biomedicine and facilitate future resource allocation in biomedical research for the United States, we analyzed US patent documents to determine the focuses and trends of protected technological innovations across the entire disease landscape. We analyzed more than 5 million US patent documents between 1995 and 2017, using summary statistics and dynamic topic modeling. More specifically, we investigated the disease coverage and latent topics in patent documents over time. We also incorporated the patent data into the calculation of our recently developed Research Opportunity Index (ROI) and Public Health Index (PHI), to recalibrate the resource allocation in biomedical research. Our analysis showed that protected technological innovations have been primarily focused on socioeconomically critical diseases such as "other cancers" (malignant neoplasm of head, face, neck, abdomen, pelvis, or limb; disseminated malignant neoplasm; Merkel cell carcinoma; and malignant neoplasm, malignant carcinoid tumors, neuroendocrine tumor, and carcinoma in situ of an unspecified site), diabetes mellitus, and obesity. The United States has significantly improved resource allocation to biomedical research and development over the past 17 years, as illustrated by the decreasing PHI. Diseases with positive ROI, such as ankle and foot fracture, indicate potential research opportunities for the future. Development of novel chemical or biological drugs and electrical devices for diagnosis and disease management is the dominating topic in patented inventions. This multifaceted analysis of patent documents provides a deep understanding of the focuses and trends of technological innovations in disease management in patents. Our findings offer insights into future research and innovation opportunities and provide actionable information to facilitate policy makers, payers, and investors to make better evidence-based decisions regarding resource allocation in biomedicine.


Acute lymphoblastic leukemia with an unusual t(8;14)(q11.2;q32): a Pediatric Oncology Group Study.
We present the clinicopathologic findings and survival data on 10 patients with acute lymphoblastic leukemia (ALL) and a rare t(8;14)(q11.2;q32). There were five male and five female patients, nine Caucasians and one Black, aged 4-17 (median 10.9) years. Three had Down syndrome. Eight (80%) patients had a white blood cell (WBC) count <50 x 109/l at presentation. No patient had central nervous system involvement or a mediastinal mass. Two patients had concurrent splenomegaly and hepatomegaly. Adenopathy was absent in four, minimal in three, moderate in one and prominent in two patients. All eight cases where immunophenotyping was performed by flow cytometry showed a B-precursor phenotype with expression of CD10 (CALLA). Only one case exhibited t(8;14)(q11.2;q32) as the sole karyotypic abnormality. Three patients were classified as standard-risk and seven high-risk by NCI (National Cancer Institute) consensus risk group categories. All patients achieved complete remission and seven patients were in complete continuous remission (CCR) after chemotherapy designed for B-precursor ALL. Three patients relapsed after 23.5, 31.3 and 32.1 months of EFS; the first patient also had t(9;22)(q34;q11), the second had a WBC count of 126 x 109/l at presentation while the third patient had no high risk features except for age 10 years. Thus, from our data, the t(8;14)(q11.2;q32) does not appear to confer an increased risk of relapse. Further observations are needed to confirm this conclusion.