Long-term functional dynamics of an aphidophagous coccinellid community remain unchanged despite repeated invasions.
Aphidophagous coccinellids (ladybeetles) are important providers of herbivore suppression ecosystem services. In the last 30 years, the invasion of exotic coccinellid species, coupled with observed declines in native species, has led to considerable interest in the community dynamics and ecosystem function of this guild. Here we examined a 24-year dataset of coccinellid communities in nine habitats in southwestern Michigan for changes in community function in response to invasion. Specifically we analyzed their temporal population dynamics and species diversity, and we modeled the community's potential to suppress pests. Abundance of coccinellids varied widely between 1989 and 2012 and became increasingly exotic-dominated. More than 71% of 57,813 adult coccinellids captured over the 24-year study were exotic species. Shannon diversity increased slightly over time, but herbivore suppression potential of the community remained roughly constant over the course of the study. However, both Shannon diversity and herbivore suppression potential due to native species declined over time in all habitats. The relationship between Shannon diversity and herbivore suppression potential varied with habitat type: a positive relationship in forest and perennial habitats, but was uncorrelated in annual habitats. This trend may have been because annual habitats were dominated by a few, highly voracious exotic species. Our results indicated that although the composition of the coccinellid community in southwestern Michigan has changed dramatically in the past several decades, its function has remained relatively unchanged in both agricultural and natural habitats. While this is encouraging from the perspective of pest management, it should be noted that losses of one of the dominant exotic coccinellids could result in a rapid decline in pest suppression services if the remaining community is unable to respond.


Calibration and validation of the ActiGraph GT3X+ in 2-3 year olds.
To calibrate and validate the ActiGraph GT3X+ to measure sedentary behaviour and physical activity in 2-3 year olds, using 5-s epochs; and to compare the predictive validity of the resulting cut-points with that of NHANES', Trost's, and Pate's 15-s cut-points. Cross-sectional study. Eighteen children (2.86 ± 0.60 years) wore an ActiGraph GT3X+ during video-recorded semi-structured calibration activity sessions. Activity was coded following Children's Activity Rating Scale. Receiver Operating Characteristic analysis was used to derive Axis1 and vector magnitude cut-points for sedentary behaviour and moderate-to-vigorous physical activity at 5-s epochs. Agreement with Children's Activity Rating Scale was assessed with Cohen's kappa, Lin's concordance, and Bland-Altman plots. Predictive validity of all cut-points was assessed in an independent sample of 20 children (2.99 ± 0.48 years) video-recorded during free-play, using the same procedures as the calibration phase. During calibration, vector magnitude cut-points (sedentary behaviour ≤ 96.12 counts; moderate-to-vigorous physical activity ≥ 361.94 counts) showed slightly better classification agreement with Children's Activity Rating Scale than Axis1 cut-points (sedentary behaviour ≤ 5 counts; moderate-to-vigorous physical activity ≥ 165 counts), but the latter showed the lowest bias in estimated sedentary behaviour and moderate-to-vigorous physical activity time. In the validation sample, 5-s Axis1 cut-points showed the best predictive validity and lowest mean differences of all cut-points between predicted and observed sedentary behaviour (-2.31%), light physical activity (-24.40%), and total physical activity time (-0.95%). Moderate-to-vigorous physical activity time was significantly overestimated by all cut-points (128.33-184.17%). Because moderate-to-vigorous physical activity was highly overestimated, using only the 5-s Axis1 sedentary behaviour cut-point to distinguish sedentary behaviour from total physical activity is advised. The high accuracy indicates that these cut-points are useful for epidemiological studies involving the sedentary behaviour and physical activity of 2-3 year olds.


Effect of trichostatin a on viability and microRNA expression in human pancreatic cancer cell line BxPC-3.
To investigate the influence of trichostatin A (TSA) on inhibition of cell proliferation and induction of apoptosis in human pancreatic cancer cells. MTT-based cytotoxicity assay was used to evaluate the cell viability after treatment with TSA. Cell cycle distribution and apoptosis were examined by means of flow cytometry. Expression of microRNA was determined with microRNA array. Expression of miR-200c and miR-21 was detected by Northern blotting. TSA significantly inhibited the proliferation of BxPC-3 human pancreatic cancer cells in a time- and dose-dependent manner. BxPC-3 cells treated with TSA were arrested in G0/G1 phase and were characterized by increased apoptotic rate, accompanied by differential expression of microRNAs. The results suggest that TSA may activate expression of microRNAs that may act as tumor suppressor in human pancreatic cancer cell line BxPC-3.


Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure.
The aim of this 2-year study was to test the hypothesis that folic acid, vitamin B12 and sun exposure could be helpful in treating vitiligo. One hundred patients with vitiligo were treated with oral folic acid and vitamin B12 after being informed that sun exposure might enhance repigmentation. They were requested to keep a record of sun exposure in summer and UVB irradiation in winter. The minimal treatment time suggested was 3-6 months but should be longer if improvement was achieved. Clear repigmentation occurred in 52 patients, including 37 who exposed their skin to summer sun and 6 who used UVB lamps in winter. Repigmentation was most evident on sun-exposed areas, where 38% of the patients had previously noted repigmentation during summer months. Total repigmentation was seen in 6 patients. The spread of vitiligo stopped in 64% of the patients after treatment. Folic acid and vitamin B12 supplementation combined with sun exposure can induce repigmentation better than either the vitamins or sun exposure alone. Treatment should continue as long as the white areas continue to repigment. Further studies are needed to determine ideal minimal dosages of vitamins and UV exposure, as well as treatment time.


Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force.
Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective. To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer. MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011). Randomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms. Investigators abstracted and checked study details and quality using predefined criteria. Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction. Only English-language articles were included. Few studies evaluated newer therapies. Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. Agency for Healthcare Research and Quality.


Small is beautiful, but large is certified: A comparison between fisheries the Marine Stewardship Council (MSC) features in its promotional materials and MSC-certified fisheries.
The Marine Stewardship Council (MSC) sets a standard by which sustainable fisheries can be assessed and eco-certified. It is one of the oldest and most well-known fisheries certifications, and an estimated 15% of global fish catch is MSC-certified. While the MSC is increasingly recognized by decision-makers as an indicator for fishery success, it is also criticized for weak standards and overly-lenient third-party certifiers. This gap between the standard's reputation and its actual implementation could be a result of how the MSC markets and promotes its brand. Here we classify MSC-certified fisheries by gear type (i.e. active vs. passive) as well as by length of the vessels involved (i.e. large scale vs. small scale; with the division between the two occurring at 12 m in overall length). We compared the MSC-certified fisheries (until 31 December 2017) to 399 photographs the MSC used in promotional materials since 2009. Results show that fisheries involving small-scale vessels and passive gears were disproportionately represented in promotional materials: 64% of promotional photographs were of passive gears, although only 40% of MSC-certified fisheries and 17% of the overall catch were caught by passive gears from 2009-2017. Similarly, 49% of the photographs featured small-scale vessels, although just 20% of MSC-certified fisheries and 7% of the overall MSC-certified catch used small-scale vessels from 2009 to 2017. The MSC disproportionately features photographs of small-scale fisheries although the catch it certifies is overwhelmingly from industrial fisheries.


Perceptually-based depth-ordering enhancement for direct volume rendering.
Visualizing complex volume data usually renders selected parts of the volume semitransparently to see inner structures of the volume or provide a context. This presents a challenge for volume rendering methods to produce images with unambiguous depth-ordering perception. Existing methods use visual cues such as halos and shadows to enhance depth perception. Along with other limitations, these methods introduce redundant information and require additional overhead. This paper presents a new approach to enhancing depth-ordering perception of volume rendered images without using additional visual cues. We set up an energy function based on quantitative perception models to measure the quality of the images in terms of the effectiveness of depth-ordering and transparency perception as well as the faithfulness of the information revealed. Guided by the function, we use a conjugate gradient method to iteratively and judiciously enhance the results. Our method can complement existing systems for enhancing volume rendering results. The experimental results demonstrate the usefulness and effectiveness of our approach.


Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10.
Recently, we described the cloning and expression of a human cDNA which is the homologue to P600, a gene transcribed by mouse Th2 clones. Based on its activities on human monocytes and B cells this gene was designated IL-13. In the present study we investigated the effects of IL-13 alone or in combination with IL-4, IFN-gamma, or IL-10 on human monocytes. IL-13 induced significant changes in the phenotype of monocytes. Like IL-4, it enhanced the expression of CD11b, CD11c, CD18, CD29, CD49e (VLA-5), class II MHC, CD13, and CD23, whereas it decreased the expression of CD64, CD32, CD16, and CD14 in a dose-dependent manner. IL-13 induced up-regulation of class II MHC Ag and its down-regulatory effects on CD64, CD32, and CD16 expression were prevented by IL-10. IFN-gamma could also partially prevent the IL-13-induced down-regulation of CD64, but not that of CD32 and CD16. However, IL-13 strongly inhibited spontaneous and IL-10- or IFN-gamma-induced ADCC activity of human monocytes toward anti-D coated Rh+ erythrocytes, indicating that the cytotoxic activity of monocytes was inhibited. Furthermore, IL-13 inhibited production of IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, macrophage inflammatory protein-1 alpha, granulocyte/macrophage-CSF, granulocyte-CSF, IFN-alpha, and TNF alpha by monocytes activated with LPS. In contrast, IL-13 enhanced the production of IL-1 ra by these cells. Similar results on cytokine production were observed or have been obtained with IL-4. Thus IL-13 shares most of its activities on human monocytes with IL-4, but no additive or synergistic effects of IL-4 and IL-13 on human monocytes were observed, suggesting that these cytokines may share common receptor components. Taken together, these results indicate that IL-13 has anti-inflammatory and important immunoregulatory activities.


Fluid and particle retention in captive okapi (Okapia johnstoni).
Retention time of food in the digestive tract is among the key variables that describe the digestive strategy of a herbivore. Mean retention time (MRT) was measured on 4 captive specimens of the okapi, a strictly browsing ruminant. Retention time was quantified on different diets, using Co-EDTA (fluid phase) and Cr-mordanted fibres (1-2 mm) (particle phase) as pulse-fed markers. Average food intake was 55-65 g DM/(kg BW0.75*d). Fecal excretion of the markers was quantified over 10 days. Different models to calculate retention time and passage rate in the gastrointestinal tract (GIT) and the reticulorumen (RR) were applied. Average MRT(particle)GIT was quantified to be 47+/-8 h and MRT(fluid)GIT 36+/-5 h. Concerning estimation of retention times in the reticulorumen, MRT(particle)RR was quantified to be 27+/-7 h, while MRT(fluid)RR was 17+/-4 h. The quotients MRT(particle)/MRT(fluid) were quantified to be 1.3+/-0.1 for the GIT and 1.6+/-0.2 for the RR. Compared to data established with comparable markers, the okapi has low coefficients of MRT(particle)/MRT(fluid). A less well developed retention mechanism for fibres compared to species like cattle or sheep can be explained by a comparatively high fermentation rate and low digestibility of the natural food of the okapi-browse-in comparison to grass.


Trophic apparatus in cyprinodontiform fishes: functional specializations for picking and scraping behaviors.
Cyprinodontiforms are a diverse and speciose order that includes topminnows, pupfishes, swordtails, mosquitofishes, guppies, and mollies. Sister group to the Beloniformes and Atheriniformes, Cyprinodontiformes contains approximately twice the number of species of these other two orders combined. Recent studies suggest that this group is well suited to capturing prey by "picking" small items from the water surface, water column, and the substrate. Because picking places unusual performance demands on the feeding apparatus, this mode of prey capture may rely upon novel morphological modifications not found in more widespread ram- or suction-based feeding mechanisms. To assess this evolutionary hypothesis, we describe the trophic anatomy of 16 cyprinodontiform species, selected to broadly represent the order as well as capture intrageneric variation. The group appears to have undergone gradual morphological changes to become increasingly specialized for picking and scraping behaviors. We also identify a suite of functional characters related to the acquisition of a novel and previously undescribed mechanism of premaxillary protrusion and retraction, including: modification of the "premaxillomandibular" ligament (which connects each side of the premaxilla to the ipsilateral mandible, or lower jaw), a novel architecture of the ligaments and bony elements that unite the premaxillae, maxillae and palatine bones, and novel insertions of the adductor muscles onto the jaws. These morphological changes to both the upper and lower jaws suggest an evolutionary trend within this group toward increased reliance on picking individual prey from the water column/substrate or for scraping encrusting material from the substrate. We propose that the suite of morphological characters described here enable a functional innovation, "picking," which leads to novel trophic habits.


The role of rat medial frontal cortex in effort-based decision making.
We conducted a series of experiments to elucidate the role of rat medial frontal cortex (MFC) (including prelimbic, infralimbic, and cingulate cortices) in effort-based decision making. Rats were trained on a cost-benefit T-maze task in which they could either choose to climb a barrier to obtain a high reward in one arm (HR arm) or could obtain a small reward in the other with no barrier present (LR arm). Before surgery, all animals were selecting the HR arm on almost every trial. However, after excitotoxic lesions to MFC, the rats shifted to selecting the LR arm on almost every trial. This was not caused by a spatial memory or motor deficit because the same rats returned to selecting the HR arm when the amount of effort needed to be expended to obtain reward in either arm was equalized by putting an identical barrier in the LR arm. Additional experiments demonstrated that the change in effort-based decisions observed in the rats was not caused by a complete insensitivity to reward and effort because they returned to choosing the HR arm if either the cost was reduced (by making the barrier smaller) or the benefit was increased (increasing the food ratio differential). Instead, the MFC lesion shifted the animals' decision criterion, making them more likely to choose the LR arm than the sham-lesioned animals. These results imply that medial frontal cortex is important for allowing the animal to put in more work to obtain greater rewards.


Overexpression of HER-2/neu in uterine serous papillary cancer.
Uterine serous papillary carcinoma (USPC) is a highly aggressive variant of endometrial cancer and histologically similar to high-grade ovarian cancer. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistology in approximately 25% of ovarian cancers. In this study, we have evaluated the expression of HER-2/neu in several fresh, established, paraffin-embedded, fixed USPCs. In addition, we have tested the sensitivity of USPC cells to Herceptin treatment. Ten consecutive USPC specimens were assessed by immunohistochemistry for the intensity of expression of HER-2/neu. In addition, three USPC cell lines were analyzed for expression of HER-2/neu by flow cytometry as well as for sensitivity to Herceptin-mediated, complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), and inhibition of cell proliferation. Eight of 10 (80%) of the USPCs assessed immunohistochemically for the intensity of expression of HER-2/neu stained heavily for HER-2/neu (2+ to 3+). Fresh and established primary USPC cell lines were found to express significantly more HER-2/neu receptor by flow cytometry (on the average, 10-fold greater) when compared with HER-2/neu-positive primary or established breast and ovarian cancer cell lines (P < 0.001). Importantly, although these USPC cell lines were resistant to chemotherapy in vivo and to natural killer- and complement-mediated cytotoxicity in vitro, they were found to be highly sensitive to Herceptin-mediated ADCC. USPC cell proliferation was also inhibited by Herceptin. A significant enhancement of ADCC was demonstrated when effector cells were exposed to low doses of IL-2 in vitro. Physiological concentrations of human serum IgG did not inhibit Herceptin-mediated ADCC against USPC. On the basis of these findings and previous reports showing a positive in vivo correlation between efficacy of Herceptin therapy and the level of HER-2/neu overexpression by tumor cells, we propose that Herceptin might be a novel and attractive therapeutic strategy in patients harboring chemotherapy-resistant, recurrent, or metastatic USPC.


Zinc deficiency leads to lipofuscin accumulation in the retinal pigment epithelium of pigmented rats.
Age-related macular degeneration (AMD) is associated with lipofuscin accumulation whereas the content of melanosomes decreases. Melanosomes are the main storage of zinc in the pigmented tissues. Since the elderly population, as the most affected group for AMD, is prone to zinc deficit, we investigated the chemical and ultrastructural effects of zinc deficiency in pigmented rat eyes after a six-month zinc penury diet. Adult Long Evans (LE) rats were investigated. The control animals were fed with a normal alimentation whereas the zinc-deficiency rats (ZD-LE) were fed with a zinc deficient diet for six months. Quantitative Energy Dispersive X-ray (EDX) microanalysis yielded the zinc mole fractions of melanosomes in the retinal pigment epithelium (RPE). The lateral resolution of the analysis was 100 nm. The zinc mole fractions of melanosomes were significantly smaller in the RPE of ZD-LE rats as compared to the LE control rats. Light, fluorescence and electron microscopy, as well as immunohistochemistry were performed. The numbers of lipofuscin granules in the RPE and of infiltrated cells (Ø>3 µm) found in the choroid were quantified. The number of lipofuscin granules significantly increased in ZD-LE as compared to control rats. Infiltrated cells bigger than 3 µm were only detected in the choroid of ZD-LE animals. Moreover, the thickness of the Bruch's membrane of ZD-LE rats varied between 0.4-3 µm and thin, rangy ED1 positive macrophages were found attached at these sites of Bruch's membrane or even inside it. In pigmented rats, zinc deficiency yielded an accumulation of lipofuscin in the RPE and of large pigmented macrophages in the choroids as well as the appearance of thin, rangy macrophages at Bruch's membrane. Moreover, we showed that a zinc diet reduced the zinc mole fraction of melanosomes in the RPE and modulated the thickness of the Bruch's membrane.


A phase I and pharmacokinetic study of LY231514, the multitargeted antifolate.
LY231514 is a novel antifolate that principally inhibits thymidylate synthase, but with additional folate-dependent enzyme targets. A Phase I study of single-agent LY231514 administered as a daily i.v. infusion over 10 minutes for 5 days, repeated every 3 weeks, was conducted to evaluate the maximum tolerated dose, pharmacokinetic profile, and antitumor activity of the drug using this schedule. Thirty-eight patients with advanced malignancies that were refractory or not amenable to standard therapy were treated with a total of 116 courses of LY231514, escalating treatment doses through 10 dose levels, from 0.2-5.2 mg/m2/day. No objective clinical responses were observed, although minor antitumor activity not fulfilling the response criteria was seen in three patients. A maximum tolerated dose of 4.0 mg/m2/day was determined, with neutropenia as the predominant dose-limiting toxicity. Reversible disturbances of liver biochemistry, fulfilling the protocol definitions of dose-limiting toxicity, were also observed. Other toxicities included diarrhea, mucositis, skin rash, and fatigue. Pharmacokinetic studies were performed at all treatment levels. Analysis showed a linear relation between administered dose and both maximum plasma concentration (Cmax) and area under the plasma concentration/time curve. The drug was cleared with a day 1 total body clearance of 108.9 +/- 38.8 ml/min/m2, with plasma concentrations declining with a mean harmonic terminal half-life of 1.4 +/- 0.98 h. When given by this schedule, LY231514 is tolerable, and Phase II studies are in progress.


Expression of long-form N-acetylglucosamine-6-O-sulfotransferase 1 in human high endothelial venules.
Two members of the N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) family, GlcNAc6ST-1 and GlcNAc6ST-2, function in the biosynthesis of 6-sulfo sialyl Lewis X-capped glycoproteins expressed on high endothelial venules (HEVs) in secondary lymphoid organs. Thus, both enzymes play a critical role in L-selectin-expressing lymphocyte homing. Human GlcNAc6ST-1 is encoded by a 1593-bp open reading frame exhibiting two 5' in-frame methionine codons spaced 141 bp apart. Both resemble the consensus sequence for translation initiation. Thus, it has been hypothesized that both long and short forms of GlcNAc6ST-1 may be present, although endogenous expression of either form has not been confirmed in humans. Here, the authors developed an antibody recognizing amino acid residues between the first two human GlcNAc6ST-1 methionines. This antibody specifically recognizes the long form of the enzyme, a finding validated by Western blot analysis and immunofluorescence cytochemistry of HeLa cells misexpressing long and/or short forms of human GlcNAc6ST-1. Using this antibody, the authors carried out immunofluorescence histochemistry of human lymph node tissue sections and found endogenous expression of the long form of the enzyme in human tissue, predominantly in the trans-Golgi network of endothelial cells that form HEVs.


Demography and economics of HIV/AIDS.
The rapid spread of HIV in the 1980s and 1990s in the non-industrialised world is now leading to an AIDS epidemic. This in turn is having a demographic and economic impact on these societies. This article assesses the most recent evidence for these impacts. It concludes that, while there is already a real and measurable impact, there is far worse to come. The demographic consequences will be particularly serious. Economic impact is rather more uncertain, and the article looks at the macro-economic impact as well as that on firms. In addition, it is postulated that economics may not be the most appropriate discipline to assess the true effects of the disease.


Role of nutritional vitamin D in osteoporosis treatment.
Osteoporosis is a systemic skeletal disorder characterized by a decrease in bone mass and microarchitectural deterioration of bone tissue. The World Health Organization has defined osteoporosis as a decrease in bone mass (50%) and bony quality (50%). Vitamin D, a steroid hormone, is crucial for skeletal health and in mineral metabolism. Its direct action on osteoblasts and osteoclasts and interaction with nonskeletal tissues help in maintaining a balance between bone turnover and bone growth. Vitamin D affects the activity of osteoblasts, osteoclasts, and osteocytes, suggesting that it affects bone formation, bone resorption, and bone quality. At physiological concentrations, active vitamin D maintains a normal rate of bone resorption and formation through the RANKL/OPG signal. However, active vitamin D at pharmacological concentration inhibits bone resorption at a higher rate than that of bone formation, which influences the bone quality and quantity. Nutritional vitamin D rather than active vitamin D activates osteoblasts and maintains serum 25(OH)D3 concentration. Despite many unanswered questions, much data support nutritional vitamin D use in osteoporosis patients. This article emphasizes the role of nutritional vitamin D replacement in different turnover status (high or low bone turnover disorders) of osteoporosis together with either anti-resorptive (Bisphosphonate, Denosumab et.) or anabolic (Teriparatide) agents when osteoporosis persists.


Electrophysiological analysis of transmission at the skeletal neuromuscular junction.
The review is divided into two sections. The first deals with methods and problems associated with performing electrophysiological experimentation on the skeletal muscle neuromuscular junction. The second section concentrates on the computer analysis of electrophysiological data. In the first section, the various techniques available for producing skeletal muscle paralysis are described. These include the use of pharmacological manipulations, such as an excess of magnesium ions or a competitive postjunctional nicotinic acetylcholine antagonist, physiological manipulations, such as cutting the muscle fibers, and the muscle fiber sodium channel toxin, mu-conotoxin. Also, in this section, a comparison is made of the use of voltage- and current-recording techniques, including descriptions of, and solutions to, the problems associated with membrane capacitance, nonlinear summation, membrane space constant, and electrical and mechanical interference. In the second section, details are given of the types of computer system commonly used for the analysis of electrophysiological data and also the requirements of the data analysis software. The use of computer algorithms for signal detection, signal evaluation, signal averaging, and curve fitting are qualitatively described, along with some of the problems and pitfalls often associated with these methods.


(No) time for control: Frontal theta dynamics reveal the cost of temporally guided conflict anticipation.
During situations of response conflict, cognitive control is characterized by prefrontal theta-band (3- to 8-Hz) activity. It has been shown that cognitive control can be triggered proactively by contextual cues that predict conflict. Here, we investigated whether a pretrial preparation interval could serve as such a cue. This would show that the temporal contingencies embedded in the task can be used to anticipate upcoming conflict. To this end, we recorded electroencephalography (EEG) from 30 human subjects while they performed a version of a Simon task in which the duration of a fixation cross between trials predicted whether the next trial would contain response conflict. Both their behavior and EEG activity showed a consistent but unexpected pattern of results: The conflict effect (increased reaction times and decreased accuracy on conflict as compared to nonconflict trials) was stronger when conflict was cued, and this was associated with stronger conflict-related midfrontal theta activity and functional connectivity. Interestingly, intervals that predicted conflict did show a pretarget increase in midfrontal theta power. These findings suggest that temporally guided expectations of conflict do heighten conflict anticipation, but also lead to less efficiently applied reactive control. We further explored this post-hoc interpretation by means of three behavioral follow-up experiments, in which we used nontemporal cues, semantically informative cues, and neutral cues. Together, this body of results suggests that the counterintuitive cost of conflict cueing may not be uniquely related to the temporal domain, but may instead be related to the implicitness and validity of the cue.


Cotransmitters in the motor nerves of the guinea pig vas deferens: electrophysiological evidence.
The contractile response of the guinea pig vas deferens to motor nerve stimulation is biphasic. The first phase is antagonized by the specific adenosine triphosphate-receptor antagonist arylazido aminoproprionyl adenosine triphosphate (ANAPP3), and the second by the alpha-receptor antagonist prazosin. The underlying electrical event, the excitatory junction potential, is also blocked by ANAPP3, but not by prazosin.


Two pear glutathione S-transferases genes are regulated during fruit development and involved in response to salicylic acid, auxin, and glucose signaling.
Two genes encoding putative glutathione S-transferase proteins were isolated from pear (Pyrus pyrifolia) and designated PpGST1 and PpGST2. The deduced PpGST1 and PpGST2 proteins contain conserved Glutathione S-transferase N-terminal domain (GST_N) and Glutathione S-transferase, C-terminal domain (GST_C). Using PCR amplification technique, the genomic clones corresponding to PpGST1 and PpGST2 were isolated and shown to contain two introns and a singal intron respectively with typical GT/AG boundaries defining the splice junctions. Phylogenetic analysis clearly demonstrated that PpGST1 belonged to Phi class of GST superfamilies and had high homology with apple MdGST, while PpGST2 was classified into the Tau class of GST superfamilies. The expression of PpGST1 and PpGST2 genes was developmentally regulated in fruit. Further study demonstrated that PpGST1 and PpGST2 expression was remarkably induced by glucose, salicylic acid (SA) and indole-3-aceticacid (IAA) treatments in pear fruit, and in diseased fruit. These data suggested that PpGST1 and PpGST2 might be involved in response to sugar, SA, and IAA signaling during fruit development of pear.


Major faecal microbiota shifts in composition and diversity with age in a geographically restricted cohort of mothers and their children.
Despite the importance, the diversity of the human infant gut microbiota still remains poorly characterized at the regional scale. Here, we investigated the faecal microbiota diversity in a large 16S rRNA gene data set from a healthy cohort of 86 mothers and their children from the Trondheim region in Norway. Samples were collected from mothers during early and late pregnancy, as well as from their children at 3 days, 10 days, 4 months, 1 year and 2 years of age. Using a combination of Sanger sequencing of amplicon mixtures (without cloning), real-time quantitative PCR and deep pyrosequencing, we observed a clear age-related colonization pattern in children that was surprisingly evident between 3- and 10-day samples. In contrast, we did not observe any shifts in microbial composition during pregnancy. We found that alpha-diversity was highest at 2 years and lowest at 4 months, whereas beta-diversity estimates indicated highest interindividual variation in newborns. Variation significantly decreased by the age of 10 days and was observed to be convergent over time; however, there were still major differences between 2 years and adults whom exhibited the lowest interindividual diversity. Taken together, the major age-affiliated population shift within gut microbiota suggests that there are important mechanisms for transmission and persistence of gut bacteria that remain unknown.


A novel biparatopic hybrid antibody-ACE2 fusion that blocks SARS-CoV-2 infection: implications for therapy.
In the absence of a proven effective vaccine preventing infection by SARS-CoV-2, or a proven drug to treat COVID-19, the positive results of passive immune therapy using convalescent serum provide a strong lead. We have developed a new class of tetravalent, biparatopic therapy, 89C8-ACE2. It combines the specificity of a monoclonal antibody (89C8) that recognizes the relatively conserved N-terminal domain of the viral Spike (S) glycoprotein, and the ectodomain of ACE2, which binds to the receptor-binding domain of S. This molecule shows exceptional performance in vitro, inhibiting the interaction of recombinant S1 to ACE2 and transduction of ACE2-overexpressing cells by S-pseudotyped lentivirus with IC50s substantially below 100 pM, and with potency approximately 100-fold greater than ACE2-Fc itself. Moreover, 89C8-ACE2 was able to neutralize authentic viral infection in a standard 96-h co-incubation assay at low nanomolar concentrations, making this class of molecule a promising lead for therapeutic applications.


Layer-Specific Manganese-Enhanced MRI of the Diabetic Rat Retina in Light and Dark Adaptation at 11.7 Tesla.
To employ high-resolution manganese-enhanced MRI (MEMRI) to study abnormal calcium activity in different cell layers in streptozotocin-induced diabetic rat retinas, and to determine whether MEMRI detects changes at earlier time points than previously reported. Sprague-Dawley rats were studied 14 days (n = 8) and 30 days (n = 5) after streptozotocin (STZ) or vehicle (n = 7) injection. Manganese-enhanced MRI at 20 × 20 × 700 μm, in which contrast is based on manganese as a calcium analogue and an MRI contrast agent, was obtained in light and dark adaptation of the retina in the same animals in which one eye was covered and the fellow eye was not. The MEMRI activity encoding of the light and dark adaptation was achieved in awake conditions and imaged under anesthesia. Manganese-enhanced MRI showed three layers, corresponding to the inner retina, outer retina, and the choroid. In normal animals, the outer retina showed higher MEMRI activity in dark compared to light; the inner retina displayed lower activity in dark compared to light; and the choroid showed no difference in activity. Manganese-enhanced MRI activity changed as early as 14 days after hyperglycemia and decreased with duration of hyperglycemia in the outer retina in dark relative to light adaptation. The choroid also had altered MEMRI activity at 14 days, which returned to normal by 30 days. No differences in MEMRI activity were detected in the inner retina. Manganese-enhanced MRI detects progressive reduction in calcium activity with duration of hyperglycemia in the outer retina as early as 14 days after hyperglycemia, earlier than any other time point reported in the literature.


Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.
Theoretical considerations predict that amplification of expressed gene transcripts by reverse transcription-PCR using arbitrarily chosen primers will result in the preferential amplification of the central portion of the transcript. Systematic, high-throughput sequencing of such products would result in an expressed sequence tag (EST) database consisting of central, generally coding regions of expressed genes. Such a database would add significant value to existing public EST databases, which consist mostly of sequences derived from the extremities of cDNAs, and facilitate the construction of contigs of transcript sequences. We tested our predictions, creating a database of 10,000 sequences from human breast tumors. The data confirmed the central distribution of the sequences, the significant normalization of the sequence population, the frequent extension of contigs composed of existing human ESTs, and the identification of a series of potentially important homologues of known genes. This approach should make a significant contribution to the early identification of important human genes, the deciphering of the draft human genome sequence currently being compiled, and the shotgun sequencing of the human transcriptome.


Visual field defects after selective amygdalohippocampectomy and standard temporal lobectomy.
Selective amygdalohippocampectomy (SelAH) is increasingly performed in patients with mesial temporal lobe epilepsy and hippocampal sclerosis. To determine whether visual field defects are less pronounced after SelAH than after standard temporal lobectomy (StTL), we retrospectively analyzed postoperative quantitative visual fields after the 2 procedures. Humphrey visual field analysis was obtained postoperatively in 18 patients who had undergone SelAH and in 33 patients who had undergone StTL. The SelAH was performed via a transcortical approach through the middle temporal gyrus and included the amygdala, 3 cm of the hippocampus, and the parahippocampal gyrus. The visual field pattern deviation was used for analysis. We considered a defect clinically significant if there were 3 contiguous coordinates affected at the 5% level or 2 at the 1% level. All but 2 of 18 patients who had undergone SelAH had homonymous superior quadrantic visual field defects contralateral to the side of the surgery. One patient had no defects by our criteria, and one had a mild defect that reached significance only in the ipsilateral eye. The averaged defect affected mostly coordinates close to the vertical meridian with relative sparing of points close to the horizontal meridian. All but 3 of the 33 patients who had undergone StTL had homonymous superior quadrantic visual field defects. One patient had no defects; 2 had defects that reached significance in only one eye. The averaged defect involved all points in the affected quadrant, but was also greater near the vertical meridian. Of 13 tested visual field coordinates, 4 were significantly less affected by SelAH in the ipsilateral eye and 3 in the contralateral eye. The coordinates close to the horizontal meridian were significantly spared by SelAH. Visual field defects are very common after SelAH but are significantly less pronounced than after StTL. In particular, the visual field close to the horizontal meridian is relatively spared in SelAH.


Creation and bioapplications of porous organic polymer materials.
Enormous effort has been devoted to the synthesis of porous organic polymers (POPs) and their extensive applications in gas adsorption and separation, supercapacitors, optoelectronic devices, chemosensors and catalysis. Owing to their superior characteristics including porous structure, facilely tailored functionalities, low cytotoxicity, desirable biocompatibility and tunable photophysical properties, POPs have attracted unprecedented attention in biomedical and related fields and afforded promising platforms for biomedical applications including nanocarriers, phototherapeutics, biomimetic systems, anti-microbial activity, bioimaging and biosensing. In this review, we will highlight recent research progress of POP-based biomedical platforms, ranging from the elaborate designs and synthetic methodologies to biologically related structure-function correlations.


Human Vγ9Vδ2 T cells specifically recognize and kill acute myeloid leukemic blasts.
Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that Vγ9Vδ2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment.


The spectrum of disease in weakness and wasting of the quadriceps muscles. Case reports.
Three patients who presented with weakness and wasting of the quadriceps muscles ('quadriceps myopathy'), are reported. In each, electrophysiological and biopsy studies revealed completely different pathological processes, including motor unit disease, polymyositis and muscular dystrophy. Double biopsies performed in 2 of the patients showed the disease process to involve upper as well as lower limbs. The diffuse and heterogeneous nature of this form of neuromuscular disease is confirmed.


Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes. Heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters.
Mechanisms causing cellular insulin resistance in gestational diabetes mellitus are not known. We, therefore, studied isolated omental adipocytes obtained during elective cesarean sections in nondiabetic (control) and GDM gravidas. Cellular insulin resistance was attributed to impaired stimulation of glucose transport; compared with control subjects, basal and maximally insulin-stimulated transport rates (per surface area) were reduced 38 and 60% in GDM patients, respectively. To determine underlying mechanisms, we assessed the number, subcellular distribution, and translocation of GLUT4, the predominant insulin-responsive glucose transporter isoform. The cellular content of GLUT4 was decreased by 44% in GDM patients as assessed by immunoblot analysis of total postnuclear membranes. However, GDM patients segregated into two subgroups; half expected profound (76%) cellular depletion of GLUT4 and half had GLUT4 levels in the normal range. Cellular GLUT4 was negatively correlated with adipocyte size in the control subjects and GDM patients with normal GLUT4 (r = 0.60), but fell way below this continuum in GDM patients with low GLUT4, indicating that heterogeneity was not caused by differences in obesity. All GDM. distribution. In basal cells, increased amounts of GLUT4 were detected in membranes fractionating with (such that the plasma membrane GLUT4 level in GDM (such that the plasma membrane GLUT4 level in GDM patients was equal to that observed in insulin-stimulated cells from control subjects). Furthermore, insulin stimulation induced translocation of GLUT4 from low-density microsomes to plasma membranes in control subjects but did not alter subcellular distribution in GDM patients. In other experiments, cellular content of GLUT1 was normal in GDM patients, and GLUT1 did not undergo insulin-mediated recruitment to plasma membranes in either control subjects or GDM patients. A faint signal was detected for GLUT3 only in low-density microsomes and only with one of two different antibodies. In GDM, we conclude that insulin resistance in adipocytes involves impaired stimulation of glucose transport and arises from a heterogeneity of defects intrinsic to the glucose transport effector system. GLUT4 content in adipocytes is profoundly depleted in approximately 50% of GDM patients, whereas all patients are found to exhibit a novel abnormality in GLUT4 subcellular distribution. This latter defect is characterized by accumulation of GLUT4 in membranes cofractionating with plasma membranes and high-density microsomes in basal cells and absence of translocation in response to insulin. The data suggest that abnormalities in cellular traffic or targeting relegate GLUT4 to a membrane compartment from which insulin cannot recruit transporters to the cell surface and have important implications regarding skeletal muscle insulin resistance in GDM and NIDDM.


Between Lake Baikal and the Baltic Sea: genomic history of the gateway to Europe.
The history of human populations occupying the plains and mountain ridges separating Europe from Asia has been eventful, as these natural obstacles were crossed westward by multiple waves of Turkic and Uralic-speaking migrants as well as eastward by Europeans. Unfortunately, the material records of history of this region are not dense enough to reconstruct details of population history. These considerations stimulate growing interest to obtain a genetic picture of the demographic history of migrations and admixture in Northern Eurasia. We genotyped and analyzed 1076 individuals from 30 populations with geographical coverage spanning from Baltic Sea to Baikal Lake. Our dense sampling allowed us to describe in detail the population structure, provide insight into genomic history of numerous European and Asian populations, and significantly increase quantity of genetic data available for modern populations in region of North Eurasia. Our study doubles the amount of genome-wide profiles available for this region. We detected unusually high amount of shared identical-by-descent (IBD) genomic segments between several Siberian populations, such as Khanty and Ket, providing evidence of genetic relatedness across vast geographic distances and between speakers of different language families. Additionally, we observed excessive IBD sharing between Khanty and Bashkir, a group of Turkic speakers from Southern Urals region. While adding some weight to the "Finno-Ugric" origin of Bashkir, our studies highlighted that the Bashkir genepool lacks the main "core", being a multi-layered amalgamation of Turkic, Ugric, Finnish and Indo-European contributions, which points at intricacy of genetic interface between Turkic and Uralic populations. Comparison of the genetic structure of Siberian ethnicities and the geography of the region they inhabit point at existence of the "Great Siberian Vortex" directing genetic exchanges in populations across the Siberian part of Asia. Slavic speakers of Eastern Europe are, in general, very similar in their genetic composition. Ukrainians, Belarusians and Russians have almost identical proportions of Caucasus and Northern European components and have virtually no Asian influence. We capitalized on wide geographic span of our sampling to address intriguing question about the place of origin of Russian Starovers, an enigmatic Eastern Orthodox Old Believers religious group relocated to Siberia in seventeenth century. A comparative reAdmix analysis, complemented by IBD sharing, placed their roots in the region of the Northern European Plain, occupied by North Russians and Finno-Ugric Komi and Karelian people. Russians from Novosibirsk and Russian Starover exhibit ancestral proportions close to that of European Eastern Slavs, however, they also include between five to 10 % of Central Siberian ancestry, not present at this level in their European counterparts. Our project has patched the hole in the genetic map of Eurasia: we demonstrated complexity of genetic structure of Northern Eurasians, existence of East-West and North-South genetic gradients, and assessed different inputs of ancient populations into modern populations.


Hyperthermia aggravates and hypothermia ameliorates epileptic brain damage.
The influence of hyperthermia and hypothermia on epileptic brain damage was studied in rats, in which status epilepticus was induced by flurothyl. Histopathological changes were examined by light microscopy after 1 or 7 days of recovery. Two series of animals were studied. In the first, short periods of seizures (20 and 25 min) were employed to examine whether moderate hyperthermia (39.5 degrees C) would aggravate epileptic brain damage, and a longer period (45 min) was used to investigate whether moderate hypothermia (32.5 degrees C) would ameliorate the damage. The second series investigated whether brief periods of status epilepticus (10 min) would cause brain damage if hyperthermia were high or excessive. For this series, animals with body temperatures of 37.0, 39.0, and 41.0 degrees C were studied. Data from normothermic animals (37.5 degrees C) confirmed previously described neuronal damage. Although hyperthermic animals failed to show increased damage in the CA1 sector, or in the hilar region of the dentate gyrus, they showed enhanced damage in the neocortex and globus pallidus (GP). In substantia nigra pars reticulata (SNPR) four out of five hyperthermic animals had bilateral infarcts after 20 min of status epilepticus, whereas no normothermic animal showed such damage. Hypothermia seemed to ameliorate epileptic brain damage in the neocortex (n.s.) and GP (P < 0.05) following status epilepticus for 45 min. Three out of seven hypothermic animals had mild SNPR involvement compared to severe infarction of the nucleus in five out of six normothermic animals (P < 0.05). Thus, hyperthermia aggravated and hypothermia ameliorated epileptic brain damage both in regions showing selective neuronal necrosis (neocortex) and in regions developing pan-necrosis (GP and SNPR). The second series displayed an unexpected result of excessive hyperthermia. Animals subjected to only 10 min of status epilepticus at a temperature of 41 degrees C showed not only neocortical lesions, but also moderate to extensive damage to the hippocampus (CA1, subiculum, and dentate gyrus). It is concluded that at high body and brain temperature, brief periods of status epilepticus can yield extensive brain damage, primarily affecting the hippocampus.


Influence of H. pylori infection on meal-stimulated gastric acid secretion and gastroesophageal acid reflux.
Gastric acid secretion, gastrin release, gastric emptying, and gastroesophageal acid reflux were measured in asymptomatic individuals before and after elimination of Helicobacter pylori gastritis. After basal gastric acid secretion and serum gastrin concentrations were measured, meal-stimulated gastric acid secretion and gastrin release were assessed during in vivo intragastric titration to pH 3. Experiments were repeated 4 wk after treatment with lansoprazole, amoxicillin, and clarithromycin. Esophageal pH was also monitored for 24 h before and after therapy. Basal gastric acidity increased approximately 20 mmol/l in subjects whose infection was eradicated (P < 0.05) but not in those with persistent infection. Basal and meal-stimulated gastric acid secretion did not change after H. pylori eradication, despite a 41% reduction in meal-stimulated gastrin release (P < 0.05). Gastroesophageal acid reflux increased two- to threefold after successful treatment (P < 0. 05) but did not change in subjects with persistent infection. Thus elimination of H. pylori gastritis increases gastric acidity, probably by reducing nonparietal alkaline secretion, and this may facilitate gastroesophageal acid reflux.


Myeloperoxidase activity and its corresponding mRNA expression as well as gene polymorphism in the population living in the coal-burning endemic fluorosis area in Guizhou of China.
The myeloperoxidase (MPO) activity and its corresponding mRNA expression as well as gene polymorphism were investigated in the population who live in the endemic fluorosis area. In the study, 150 people were selected from the coal-burning endemic fluorosis area and 150 normal persons from the non-fluorosis area in Guizhou province of China. The blood samples were collected from these people. The activity of MPO in the plasma was determined by spectrophotometer; the expression of MPO mRNA was measured by employing real-time polymerase chain reaction; DNAs were extracted from the leucocytes in blood and five SNP genotypes of MPO promoter gene detected by a multiplex genotyping method, adapter-ligation-mediated allele-specific amplification. The results showed that the MPO activity and its corresponding mRNA in blood were significantly increased in the population living in the area of fluorosis. The different genotype frequencies of MPO, including -1228G/A, -585T/C, -463G/A, and -163C/T, and the three haplotypes with higher frequencies, including -163C-463G-585T-1228G-1276T, -163C-463G-585T-1228G-1276C, and -163C-463G-585T-1228A-1276T, were significantly associated with fluorosis. The results indicated that the elevated activity of MPO induced by endemic fluorosis may be connected in mechanism to the stimulated expression of MPO mRNA and the changed gene polymorphism.


Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder.
It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[β -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.


Evaluation of an emergency contraception introduction project in Kenya.
The Consortium for Emergency Contraception introduced Postinor-2, a progestin-only EC product, into Kenya as part of its work to expand access to EC in developing countries. Introduction activities included registering Postinor-2, training providers, and developing provider and client materials. We surveyed family planning clients and providers to assess the impact of these activities. Knowledge of EC among clients and providers improved between the baseline and evaluation surveys. More women and providers had heard of EC and more providers were distributing it. Support for access to EC in Kenya also improved. The results indicate, though, that further information is needed. Only one-fifth of women at the evaluation had heard of EC and almost half of the women expressed concerns about EC at baseline and evaluation. More research and experience using novel ways of informing women about EC in Africa is needed, and information needs to address women's concerns.


Foreskin Morbidity in Uncircumcised Males.
As a consequence of the discussion on whether the health benefits of newborn male circumcision outweigh the risks and the discrepancies in reported figures of complications, we evaluated the incidence and morbidity of foreskin surgery due to medical indications in boys from the Capital Region of Denmark in 2014. Medical records from all boys operated on the foreskin due to medical reasons in the Capital Region in 2014 were reviewed. Patients with hypospadias, ritual circumcision, and redo-surgery because of complications to nontherapeutic circumcision were excluded. A total of 181 patients were included. The cumulative risk of undergoing foreskin operation before 18 years of age was 1.7%. Forty patients had histologic verified balanitis xerotica obliterans (BXO) corresponding to a total risk of 0.37% of developing BXO. Mean age at surgery was 10.1 years (range 1-17). Phimosis was the most frequently reported indication (95.0%). The remaining 5.0% underwent surgery because of frenulum breve causing problems during erection. Before surgery, 27.1% had foreskin-related voiding problems and 17.1% had at least 1 episode of balanitis. Circumcision was initially performed in 44 cases. The remaining 137 patients had a foreskin-preserving operation performed. Nine boys had secondary circumcision after initially having foreskin-preserving operation. Fifty patients initially had preputial histology performed. BXO was verified in 37 patients. Of the 9 patients with redo-surgery due to recurrent phimosis, a further 3 had histologically verified BXO. Childhood foreskin-related problems in a region with no tradition of newborn male circumcision should not be neglected.


Structural Biology of RNA Polymerase II Transcription: 20 Years On.
Gene transcription by RNA polymerase II (Pol II) is the first step in the expression of the eukaryotic genome and a focal point for cellular regulation during development, differentiation, and responses to the environment. Two decades after the determination of the structure of Pol II, the mechanisms of transcription have been elucidated with studies of Pol II complexes with nucleic acids and associated proteins. Here we provide an overview of the nearly 200 available Pol II complex structures and summarize how these structures have elucidated promoter-dependent transcription initiation, promoter-proximal pausing and release of Pol II into active elongation, and the mechanisms that Pol II uses to navigate obstacles such as nucleosomes and DNA lesions. We predict that future studies will focus on how Pol II transcription is interconnected with chromatin transitions, RNA processing, and DNA repair.


Naming outcomes of anterior temporal lobectomy in epilepsy patients: a systematic review of the literature.
Anterior temporal lobectomy (ATL) is the standard surgical treatment for medically intractable temporal lobe epilepsy (TLE). While seizure outcome is favorable, cognitive outcomes are a concern, particularly in respect of memory and naming. A systematic review of the literature on the naming outcomes of ATL is presented in this article. Searches were conducted on PubMed and PsycInfo, yielding a total of 93 articles, 21 of which met inclusion criteria. Declines in visual naming are common following ATL in the dominant hemisphere, and particularly, for naming living stimuli or famous faces. The Boston Naming Test (BNT) declines by a mean of 5.8 points, exceeding the Reliable Change Index (RCI). There are no reports of deficits in auditory naming following ATL, despite the fact that auditory naming has shown to be a more sensitive measure of dysnomia than the BNT in TLE patients. The absence of structural hippocampal pathology and late-onset epilepsy are the strongest predictors of naming decline. Recommendations are made for further study.


Socio-economic variations in the mental health treatment gap for people with anxiety, mood, and substance use disorders: results from the WHO World Mental Health (WMH) surveys.
The treatment gap between the number of people with mental disorders and the number treated represents a major public health challenge. We examine this gap by socio-economic status (SES; indicated by family income and respondent education) and service sector in a cross-national analysis of community epidemiological survey data. Data come from 16 753 respondents with 12-month DSM-IV disorders from community surveys in 25 countries in the WHO World Mental Health Survey Initiative. DSM-IV anxiety, mood, or substance disorders and treatment of these disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI). Only 13.7% of 12-month DSM-IV/CIDI cases in lower-middle-income countries, 22.0% in upper-middle-income countries, and 36.8% in high-income countries received treatment. Highest-SES respondents were somewhat more likely to receive treatment, but this was true mostly for specialty mental health treatment, where the association was positive with education (highest treatment among respondents with the highest education and a weak association of education with treatment among other respondents) but non-monotonic with income (somewhat lower treatment rates among middle-income respondents and equivalent among those with high and low incomes). The modest, but nonetheless stronger, an association of education than income with treatment raises questions about a financial barriers interpretation of the inverse association of SES with treatment, although future within-country analyses that consider contextual factors might document other important specifications. While beyond the scope of this report, such an expanded analysis could have important implications for designing interventions aimed at increasing mental disorder treatment among socio-economically disadvantaged people.


IGF-I is distinctly located in the bony fish pituitary as revealed for Oreochromis niloticus, the Nile tilapia, using real-time RT-PCR, in situ hybridisation and immunohistochemistry.
In bony fish, IGF-I released from the liver under the control of pituitary GH is the main endocrine regulator of growth, maintenance and development, and the amount of circulating IGF-I regulates synthesis and release of GH. In mammals and amphibia, evidence indicates that anterior pituitary endocrine cells also contain IGF-I. However, only preliminary and conflicting data exist on IGF-I gene expression in bony fish pituitary. Thus, we investigated the presence of IGF-I in the tilapia (Oreochromis niloticus) pituitary by quantitative real-time RT-PCR, in situ hybridisation and immunohistochemistry. The absolute amount of IGF-I mRNA in the whole pituitary (7.4+/-3.3 x 10(-3)pg/microg total RNA) was 1000-times lower than in liver (7.5+/-3.1 pg/microg total RNA). IGF-I peptide occurred in both neuro- and adenohypophysis but IGF-I gene expression was mainly restricted to the adenohypophysis. In the neurohypophysis, only few cells, probably pituicytes, contained IGF-I mRNA whereas IGF-I peptide was found also in numerous axons in the pars nervosa. In the adenohypophysis, both IGF-I mRNA and peptide were present in the majority of ACTH cells in all individuals investigated. In alpha-MSH cells, only IGF-I mRNA but no IGF-I peptide was detected likely suggesting an immediate release of IGF-I after synthesis. IGF-I mRNA and peptide were further observed in GH cells but their presence showed pronounced inter-individual differences likely due to the physiological, e.g., nutritional, status of the individual. IGF-I released from the GH cells may serve as auto/paracrine mediator of a negative feedback mechanism in addition to liver-derived endocrine IGF-I. Generally, the constitutive synthesis of IGF-I in ACTH cells and the varying content in GH and alpha-MSH cells suggest particular roles for IGF-I. Local IGF-I may regulate synthesis and release of pituitary hormones in an autocrine and/or paracrine manner as well as prevent apoptosis and stimulate proliferation of endocrine cells.


Cone-beam CT dose and imaging performance evaluation with a modular, multipurpose phantom.
A modular phantom for dosimetry and imaging performance evaluation in cone-beam computed tomography (CBCT) is reported, providing a tool for quantitative technical assessment that can be adapted to a broad variety of CBCT imaging configurations and clinical applications. The phantom presents a set of modules that can be ordered in various configurations suitable to a particular CBCT system. Modules include slabs containing a uniform medium, low-contrast inserts, line-spread features, and disk features suitable to measurement of image uniformity, noise, noise-power spectrum (NPS), contrast, contrast-to-noise ratio (CNR), Hounsfield (HU) accuracy, linearity, spatial resolution modulation transfer function (MTF), and magnitude of cone-beam artifact. Automated software recognizes the phantom configuration in DICOM images and provides structured reporting of such test measures. In any modular configuration, the phantom permits measurement of air kerma in central and peripheral locations with an air ionization chamber (e.g., Farmer chamber). The utility and adaptability of the phantom were demonstrated across a spectrum of CBCT systems, including scanners for orthopaedic imaging (Carestream OnSight 3D, Rochester NY), breast imaging (Doheny prototype, UC Davis), image-guided surgery (IGS, Medtronic O-arm, Littleton MA), angiography (Siemens Artis Zeego, Forcheim Germany), and image-guided radiation therapy (IGRT, Elekta Synergy XVI, Stockholm Sweden). The phantom provided a consistent platform for quantitative assessment of dose and imaging performance compatible with a broad spectrum of CBCT systems. The purpose of the survey was not to obtain head-to-head performance comparison of systems designed for such distinct clinical applications. Rather, the survey demonstrated the suitability of the phantom to a broad spectrum of systems in a manner that provides characterization pertinent to disparate applications and imaging tasks. For example: the orthopaedic CBCT system (pertinent clinical tasks relating to high-resolution bone imaging) was shown to achieve MTF consistent with imaging of high-contrast trabecular bone structures (i.e., the MTF reduced to 10% at spatial frequency, f 10 = 1.2 mm-1 ); the breast system (even higher-resolution imaging of microcalcifications) exhibited f 10 = 2.2 mm-1 ; the IGS system (tasks including both bone and soft-tissue contrast resolution) provided f 10 = 0.9 mm-1 and soft-tissue CNR = 1.64; the angiography system (soft-tissue body interventions) demonstrated CNR = 1.2 in soft tissues approximating liver lesions; and the IGRT system (pertinent tasks emphasizing HU linearity and image uniformity) showed linear response with HU values ( R 2 = 1), with a cupping artifact ( t cup = 5.8%) due to x-ray scatter. The phantom provides an adaptable, quantitative basis for CBCT dosimetry and imaging performance evaluation suitable to a broad variety of CBCT systems. The dosimetry and image quality metrics are consistent with up-to-date methods for rigorous, quantitative, physics testing and should be suitable to emerging standards for CBCT quality assurance.


A chicken middle-repetitive DNA sequence which shares homology with mammalian ubiquitous repeats.
We have identified and sequenced two members of a chicken middle repetitive DNA sequence family. By reassociation kinetics, members of this family (termed CRl) are estimated to be present in 1500-7000 copies per chicken haploid genome. The first family member sequenced (CRlUla) is located approximately 2 kb upstream from the previously cloned chicken Ul RNA gene. The second CRl sequence (CRl)Va) is located approximately 12 kb downstream from the 3' end of the chicken ovalbumin gene. The region of homology between these two sequences extends over a region of approximately 160 base pairs. In each case, the 160 base pair region is flanked by imperfect, but homologous, short direct repeats 10-15 base pairs in length. When the CRl sequences are compared with mammalian ubiquitous interspersed repetitive DNA sequences (human Alu and Mouse Bl families), several regions of extensive homology are evident. In addition, the short nucleotide sequence CAGCCTGG which is completely conserved in ubiquitous repetitive sequence families from several mammalian species is also conserved at a homologous position in the chicken sequences. These data imply that at least certain aspects of the sequence and structure of these interspersed repeats must predate the avian-mammalian divergence. It seems that the CRl family may possibly represent an avian counterpart of the mammalian ubiquitous repeats.


Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark.
The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate. To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort. This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020. Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi. The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort. Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort. In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.


Prenatal ethanol (EtOH) exposure alters the sensitivity of the adult dentate gyrus to acute EtOH exposure.
Prenatal ethanol (EtOH) exposure results in a spectrum of structural, cognitive, and behavioral abnormalities, collectively termed "fetal alcohol spectrum disorders" (FASDs). The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of EtOH. Prenatal EtOH exposure can lead to long-lasting impairments in the ability to process spatial information, as well as produce long-lasting deficits in the ability of animals to exhibit long-term potentiation (LTP), a biological model of learning and memory processing. These deficits also have the ability to facilitate EtOH and/or other drug abuse later in life. This study sought to determine prenatal EtOH exposure altered the effects of acute EtOH application on synaptic plasticity. Prenatal EtOH exposure was modeled using a liquid diet where dams were given 1 of 3 diets: (i) a liquid diet containing EtOH (35.5% EtOH-derived calories), (ii) a liquid diet, isocaloric to the EtOH diet, but with maltose-dextrin substituting for the EtOH-derived calories, and (iii) an ad libitum diet of standard rat chow. Extracellular recordings from transverse brain slices (350 μm) prepared from 50- to 70-day-old rats, following prenatal EtOH exposure (gestational day 1 to 21). LTP was examined in the dentate gyrus following acute EtOH exposure (0, 20, or 50 mM) in these slices. Prenatal EtOH exposure attenuated LTP in the adult dentate gyrus. In control offspring, acute application of EtOH in adulthood attenuated (20 mM) or blocked (50 mM) LTP. Conversely, the effect of acute EtOH application on LTP was not as pronounced in prenatal EtOH offspring. Prenatal EtOH exposure alters the sensitivity of the adult dentate gyrus to acute EtOH application producing a long-lasting tolerance to the inhibitory effects of EtOH. This decreased sensitivity may provide a mechanism promoting the formation of drug-associated memories and help explain the increased likelihood of developing an alcohol dependency often observed in individuals with FASDs.


HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor.
The molecular chaperone heat shock protein 90 (Hsp90) and its accessory cochaperones function by facilitating the structural maturation and complex assembly of client proteins, including steroid hormone receptors and selected kinases. By promoting the activity and stability of these signaling proteins, Hsp90 has emerged as a critical modulator in cell signaling. Here, we present evidence that Hsp90 chaperone activity is regulated by reversible acetylation and controlled by the deacetylase HDAC6. We show that HDAC6 functions as an Hsp90 deacetylase. Inactivation of HDAC6 leads to Hsp90 hyperacetylation, its dissociation from an essential cochaperone, p23, and a loss of chaperone activity. In HDAC6-deficient cells, Hsp90-dependent maturation of the glucocorticoid receptor (GR) is compromised, resulting in GR defective in ligand binding, nuclear translocation, and transcriptional activation. Our results identify Hsp90 as a target of HDAC6 and suggest reversible acetylation as a unique mechanism that regulates Hsp90 chaperone complex activity.


Choosing a lung isolation device for thoracic surgery: a randomized trial of three bronchial blockers versus double-lumen tubes.
There is no consensus on the best technique for lung isolation for thoracic surgery. In this study, we compared the clinical performance of three bronchial blockers (BBs) available in North America with left-sided double-lumen tubes (DLTs) for lung isolation in patients undergoing left-sided thoracic surgery. One hundred four patients undergoing left-sided thoracotomy or video-assisted thoracoscopic surgery were randomly assigned to one of the four lung isolation groups (n = 26/group). Lung isolation was with an Arndt wire-guided BB (Cook Critical Care, Bloomington, IN), a Cohen Flexi-tip BB (Cook Critical Care) or a Fuji Uni-blocker (Fuji Systems, Tokyo) or with a left-sided DLT (Mallinckrodt Medical, Cornamadde, Athlone, Westmeath, Ireland). Anesthetic management and lung isolation were performed according to a standardized protocol. Each group was randomly subdivided into two subgroups (n = 13/subgroup): immediate suction (at the time of insertion of the lung isolation device) (Subgroup I) or delayed suction (20 min after insertion of the lung separation device) (Subgroup D) according to when suction was applied to the BB suction channel or the bronchial lumen of the DLT. Using a verbal analog scale, lung collapse was assessed by the surgeons, who were blinded to the lung isolation technique. There was no difference among the lung isolation devices in lung collapse scores at 0 (P = 0.66), 10 (P = 0.78), or 20 min (P = 0.51) after pleural opening. The time to initial lung isolation was less for DLTs (93 +/- 62 s) than BBs (203 +/- 132) (P = 0.0001). There were no differences among the BBs in the time to lung isolation (P = 0.78). There were significantly more repositions after initial placement of the lung isolation device with BBs (35 incidents) than with DLTs (two incidents) (P = 0.009). The Arndt BB required repositioning more frequently (16 incidents) than the Cohen BB (8) or the Fuji BB (11) (P = 0.032). The three BBs provided equivalent surgical exposure to left-sided DLTs during left-sided open or video-assisted thoracoscopic surgery thoracic procedures. BBs required longer to position and required intraoperative repositioning more often. The Arndt BB needed to be repositioned more often than the other BBs.


Estimation of thermal coefficients of magneto-optical media.
Previously we described a method for estimating the thermal conductivity of magneto-optic recording media. The method relies on identifying the laser power that brings the maximum temperature of the TbFeCo layer to as high as the Curie temperature. We extensively use a similar method to estimate the heat capacity of a dielectric layer, a TbFeCo layer, and an aluminum alloy layer of magneto-optic recording media. Measurements are conducted on static disks with a beam of light focused on a TbFeCo layer. The method has the advantage of thermal diffusion depending on a multilayer structure and irradiation time.


A reproductive threat-based model of evolved sex differences in jealousy.
Although heterosexual women and men consistently demonstrate sex differences in jealousy, these differences disappear among lesbians and gay men as well as among heterosexual women and men contemplating same-sex infidelities (infidelities in which the partner and rival are the same sex). Synthesizing these past findings, the present paper offers a reproductive threat-based model of evolved sex differences in jealousy that predicts that the sexes will differ only when the jealous perceivers' reproductive outcomes are differentially at risk. This model is supported by data from a web-based study in which lesbians, gay men, bisexual women and men, and heterosexual women and men responded to a hypothetical infidelity scenario with the sex of the rival randomly determined. After reading the scenario, participants indicated which type of infidelity (sexual versus emotional) would cause greater distress. Consistent with predictions, heterosexual women and men showed a sex difference when contemplating opposite-sex infidelities but not when contemplating same-sex infidelities, whereas lesbians and gay men showed no sex difference regardless of whether the infidelity was opposite-sex or same-sex.


Managing recent-onset diabetes: choosing durable, well-tolerated therapies and understanding the role of incretin-based therapies.
Management of recent-onset diabetes offers osteopathic physicians the opportunity to work with patients to set treatment goals and expectations for this progressive yet manageable disease, as well as intervene early to reduce the risk of diabetes-related complications. Starting effective therapy early--and intensifying therapy appropriately--to achieve and maintain glycemic goals has been shown to reduce microvascular risks and produce legacy effects that may have macrovascular benefits. Metformin remains a cornerstone of therapy for those patients who can tolerate it. Early combination therapy that is well tolerated reduces risks of hypoglycemia or unwanted weight gain, improves patient adherence, and addresses the multifactoral pathophysiology of even recent-onset diabetes. Incretin-based therapies have been shown to be effective across the spectrum of type 2 diabetes mellitus, including recent-onset diabetes. The present article reviews the use of incretin-based therapies early in the disease process of type 2 diabetes mellitus.


Thirty-sixth Lauriston S. Taylor Lecture on radiation protection and measurements--from the field to the laboratory and back: the what ifs, wows, and who cares of radiation biology.
My scientific journey started at the University of Utah chasing fallout. It was on everything, in everything, and was distributed throughout the ecosystem. This resulted in radiation doses to humans and caused me great concern. From this concern I asked the question, "Are there health effects from these radiation doses and levels of radioactive contamination?" I have invested my scientific career trying to address this basic question. While conducting research, I got acquainted with many of the What ifs of radiation biology. The major What if in my research was, "What if we have underestimated the radiation risk for internally-deposited radioactive material?" While conducting research to address this important question, many other What ifs came up related to dose, dose rate, and dose distribution. I also encountered a large number of Wows. One of the first was when I went from conducting environmental fallout studies to research in a controlled laboratory. The activity in fallout was expressed as pCi L⁻¹, whereas it was necessary to inject laboratory animals with μCi g⁻¹ body weight to induce measurable biological changes, chromosome aberrations, and cancer. Wow! That is seven to nine orders of magnitude above the activity levels found in the environment. Other Wows have made it necessary for the field of radiation biology to make important paradigm shifts. For example, one shift involved changing from "hit theory" to total tissue responses as the result of bystander effects. Finally, Who cares? While working at U.S. Department of Energy headquarters and serving on many scientific committees, I found that science does not drive regulatory and funding decisions. Public perception and politics seem to be major driving forces. If scientific data suggested that risk had been underestimated, everyone cared. When science suggested that risk had been overestimated, no one cared. This result-dependent Who cares? was demonstrated as we tried to generate interactions by holding meetings with individuals involved in basic low-dose research, regulators, and the news media. As the scientists presented their "exciting data" that suggested that risk was overestimated, many of the regulators simply said, "We cannot use such data." The newspaper people said, "It is not possible to get such information by my editors." In spite of these difficulties, research results from basic science must be made available and considered by members of the public as well as by those that make regulatory recommendations. Public outreach of the data is critical and must continue to be a future focus to address properly the question of, "Who cares?" My journey in science, like many of yours, has been a mixture of chasing money, beatings, and the joys of unique and interesting research results. Perhaps through our experiences, we can improve research environments, funding, and use of the valuable information that is generated. Scientists that study at all levels of biological organization, from the environment to the laboratory and human epidemiology, must share expertise and data to address the What Ifs, Wows, and Who Cares of radiation biology.


The Neuromuscular Response to Spinal Manipulation in the Presence of Pain.
The purpose of this study was to evaluate differences in muscle activity in participants with and without low back pain during a side-lying lumbar diversified spinal manipulation. Surface and indwelling electromyography at eight muscle locations were recorded during lumbar side-lying manipulations in 20 asymptomatic participants and 20 participants with low back pain. The number of muscle responses and muscle activity onset delays in relation to the manipulation impulse were compared in the 2 pain groups using mixed linear regressions. Effect sizes for all comparisons were calculated using Cohen's d. Muscle responses occurred in 61.6% ± 23.6% of the EMG locations in the asymptomatic group and 52.8% ± 26.3% of the symptomatic group. The difference was not statistically significant but there was a small effect of pain (d = 0.350). Muscle activity onset delays were longer for the symptomatic group at every EMG location except the right side indwelling L5 electrode, and a small effect of pain was present at the left L2, quadratus lumborum and trapezius surface electrodes (d = 0.311, 0.278, and 0.265) respectively. The indwelling electrodes demonstrated greater muscle responses (P ≤ .01) and shorter muscle activity onset delays (P < .01) than the surface electrodes. The results revealed trends that indicate participants with low back pain have less muscle responses, and when muscle responses are present they occur with longer onset delays following the onset of a manipulation impulse.


At seeming safe concentrations, synergistic effects of PM2.5 and formaldehyde co-exposure induces Alzheimer-like changes in mouse brain.
Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Air pollution is a multi-pollutants co-exposure system, which may affect brain. The indoor environment is where exposure to both air particulate matter (<2.5 μm in diameter) (PM2.5) and formaldehyde (FA) can occur simultaneously. Whether exposure to such a multi-pollutant (PM2.5 plus FA) mixture contributes to the development of AD, and whether there is a difference between exposure to PM2.5 or FA alone needs to be investigated. To determine the objective, C57BL/6J mice were exposed daily to PM2.5 (0.193 mg/Kg/day), FA (0.155 mg/Kg/day) or multi-pullutants (0.193 mg/Kg/day PM2.5 plus 0.155 mg/Kg/day FA) for one week. AD-like changes and upstream events were investigated after exposure. The results showed that exposure to PM2.5 or FA alone in this study had little or no adverse effects on the mouse brain. However, some AD-like pathologies were detected after multi-pullutants co-exposure. This work suggested PM2.5 plus FA co-exposure has more potential to induce AD-like pathologies than exposure alone. Oxidative stress and inflammation may be involved into the toxic mechanisms. Synergistic effects of co-exposure may induce the hygienic or safety standards of each pollutant not safe.


Arterial input function and gray matter cerebral blood volume measurements in children.
To investigate how arterial input functions (AIFs) vary with age in children and compare the use of individual and population AIFs for calculating gray matter CBV values. Quantitative measures of cerebral blood volume (CBV) using dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) require measurement of an AIF. AIFs are affected by numerous factors including patient age. Few data presenting AIFs in the pediatric population exists. Twenty-two previously treated pediatric brain tumor patients (mean age, 6.3 years; range, 2.0-15.3 years) underwent DSC-MRI scans on a 3T MRI scanner over 36 visits. AIFs were measured in the middle cerebral artery. A functional form of an adult population AIF was fitted to each AIF to obtain parameters reflecting AIF shape. The relationship between parameters and age was assessed. Correlations between gray matter CBV values calculated using the resulting population and individual patient AIFs were explored. There was a large variation in individual patient AIFs but correlations between AIF shape and age were observed. The center (r = 0.596, P < 0.001) and width of the first-pass peak (r = 0.441, P = 0.007) were found to correlate significantly with age. Intrapatient coefficients of variation were significantly lower than interpatient values for all parameters (P < 0.001). Differences in CBV values calculated with an overall population and age-specific population AIF compared to those calculated with individual AIFs were 31.3% and 31.0%, respectively. Parameters describing AIF shape correlate with patient age in line with expected changes in cardiac output. In pediatric DSC-MRI studies individual patient AIFs are recommended.


Sinonasal mycosis following transfrontal craniotomy in three dogs.
Three dogs were presented for investigation of chronic nasal discharge and epistaxis 141, 250, and 357 days after undergoing transfrontal craniotomy to treat an intracranial meningioma (2 dogs) or a meningoencephalocele (1 dog). CT findings were consistent with destructive rhinitis and frontal sinusitis in all 3 dogs, with results of histologic examination and fungal culture of samples obtained during frontal sinusotomy confirming mycotic infection. Frontal sinusotomy revealed fungal plaques covering a combination of bone and residual surgical tissue adhesive at the site of the previous craniotomy in all 3 dogs. Aspergillus spp were identified in all 3 dogs, and Chrysosporium sp was also identified in 1 dog. Surgical curettage was followed by antifungal treatment (topical clotrimazole in 2 dogs and oral itraconazole for 3 months in 1 dog). Nasal discharge improved in the short-term but recurred in all dogs 99, 118, and 110 days after frontal sinusotomy. One dog received no further treatment, 1 dog received an additional 8.5 months of oral itraconazole treatment, and 1 dog underwent 2 additional surgical debridement procedures. At last follow-up, 2 dogs were alive 311 and 481 days after frontal sinusotomy; the third dog was euthanized because of status epilepticus 223 days after frontal sinusotomy. Sinonasal mycosis should be considered as a potential complication in dogs developing persistent mucopurulent nasal discharge, intermittent epistaxis, and intermittent sneezing following transfrontal craniotomy. The pathophysiology may be multifactorial, and potential risk factors, including use of surgical tissue adhesive in the frontal sinus, require further investigation.


Pulmonary embolism due to the right atrial myxoma.
A 47-year-old man was admitted to the hospital with a pleuritic pain, dyspnea, nonproductive cough and low-grade fever. An ECG documented a sinus tachycardia with S1Q3T3 pattern and incomplete right bundle branch block, and lung scintigraphy showed multiple perfusion defects. The initial diagnosis was pulmonary embolism. Echocardiography, undertaken before application of the anticoagulant therapy because of hematological disturbances reflecting possible coagulopathy (elevated erythrocyte sedimentation rate, increased leukocyte count, decreased platelet count), revealed a large mobile tumor in the right atrium. Tumor was surgically removed, and histological findings was supported a diagnosis of the cardiac myxoma. The right cardiac myxoma should be considered in the differential diagnosis of pulmonary embolism, particularly in cases presented in conjunction with constitutional symptoms and/or hematological disturbances. In these patients echocardiography should be undertaken early to exclude the rare but treatable diseases of the right heart.


Environmental consequences of invasive species: greenhouse gas emissions of insecticide use and the role of biological control in reducing emissions.
Greenhouse gas emissions associated with pesticide applications against invasive species constitute an environmental cost of species invasions that has remained largely unrecognized. Here we calculate greenhouse gas emissions associated with the invasion of an agricultural pest from Asia to North America. The soybean aphid, Aphis glycines, was first discovered in North America in 2000, and has led to a substantial increase in insecticide use in soybeans. We estimate that the manufacture, transport, and application of insecticides against soybean aphid results in approximately 10.6 kg of carbon dioxide (CO2) equivalent greenhouse gasses being emitted per hectare of soybeans treated. Given the acreage sprayed, this has led to annual emissions of between 6 and 40 million kg of CO2 equivalent greenhouse gasses in the United States since the invasion of soybean aphid, depending on pest population size. Emissions would be higher were it not for the development of a threshold aphid density below which farmers are advised not to spray. Without a threshold, farmers tend to spray preemptively and the threshold allows farmers to take advantage of naturally occurring biological control of the soybean aphid, which can be substantial. We find that adoption of the soybean aphid economic threshold can lead to emission reductions of approximately 300 million kg of CO2 equivalent greenhouse gases per year in the United States. Previous studies have documented that biological control agents such as lady beetles are capable of suppressing aphid densities below this threshold in over half of the soybean acreage in the U.S. Given the acreages involved this suggests that biological control results in annual emission reductions of over 200 million kg of CO2 equivalents. These analyses show how interactions between invasive species and organisms that suppress them can interact to affect greenhouse gas emissions.


The role of peroxisome proliferator-activated receptors in the development and physiology of gametes and preimplantation embryos.
In several species, a family of nuclear receptors, the peroxisome proliferator-activated receptors (PPARs) composed of three isotypes, is expressed in somatic cells and germ cells of the ovary as well as the testis. Invalidation of these receptors in mice or stimulation of these receptors in vivo or in vitro showed that each receptor has physiological roles in the gamete maturation or the embryo development. In addition, synthetic PPAR gamma ligands are recently used to induce ovulation in women with polycystic ovary disease. These results reveal the positive actions of PPAR in reproduction. On the other hand, xenobiotics molecules (in herbicides, plasticizers, or components of personal care products), capable of activating PPAR, may disrupt normal PPAR functions in the ovary or the testis and have consequences on the quality of the gametes and the embryos. Despite the recent data obtained on the biological actions of PPARs in reproduction, relatively little is known about PPARs in gametes and embryos. This review summarizes the current knowledge on the expression and the function of PPARs as well as their partners, retinoid X receptors (RXRs), in germ cells and preimplantation embryos. The effects of natural and synthetic PPAR ligands will also be discussed from the perspectives of reproductive toxicology and assisted reproductive technology.