Inbreeding coefficient estimation with dense SNP data: comparison of strategies and application to HapMap III.
If the parents of an individual are related, it is possible for the individual to have received at 1 locus 2 identical-by-descent alleles that are copies of a single allele carried by the parents' common ancestor. The inbreeding coefficient measures the probability of this event and increases with increasing relatedness between the parents. It is traditionally computed from the observed inbreeding loops in the genealogies and its accuracy thus depends on the depth and reliability of the genealogies. With the availability of genome-wide genetic data, it has become possible to compute a genome-based inbreeding coefficient f, and different methods have been developed to estimate f and identify inbred individuals in a sample from the observed patterns of homozygosity at markers. For this paper, we performed simulations with known genealogies using different SNP panels with different levels of linkage disequilibrium (LD) to compare several estimators of f, including single-point estimates, methods based on the length of runs of homozygosity (ROHs) and different methods that use hidden Markov models (HMMs). We also compared the performances of some of these estimators to identify inbred individuals in a sample using either HMM likelihood ratio tests or an adapted version of the ERSA software. Single-point methods were found to have higher standard deviations than other methods. ROHs gave the best estimates provided the correct length threshold is known. HMMs on sparse data gave equivalent or better results than HMMs modeling LD. Provided LD is correctly accounted for, the inbreeding estimates were very similar using the different SNP panels. The HMM likelihood ratio tests were found to perform better at detecting inbred individuals in a sample than the adapted ERSA. All methods accurately detected inbreeding up to second-cousin offspring. We applied the best method on release 3 of the HapMap phase III project, found up to 4% of inbred individuals, and created HAP1067, an unrelated and outbred dataset of this release. We recommend using HMMs on multiple sparse maps to estimate and detect inbreeding in large samples. If the sample of individuals is too small to estimate allele frequencies, we advise to estimate them on reference panels or to use 1,500-kb ROHs. Finally, we suggest to investigators using HapMap to be careful with inbred individuals, especially in the GIH (Gujarati Indians from Houston in Texas) population.


Interaction effect of green tea consumption and resistance training on office and ambulatory cardiovascular parameters in women with high-normal/stage 1 hypertension.
This study aimed to investigate the chronic effects of green tea (GT) extract and resistance training (RT) on ambulatory and office blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) in a sample of Iranian women with high-normal/stage 1 hypertension. Forty-four middle-aged sedentary women participated in this randomized, double-blind, placebo-controlled study. They were randomly assigned to one of four groups: GT and RT (GR, n = 11), RT (n = 10), GT (n = 10), or control (n = 13). Three weeks of GT consumption were followed by six weeks of the interaction with RT. GR and RT groups performed two circuits of RT at %50 of 1RM two days per week. RT and control groups also received placebo (maltodextrin) with the same timing. The changes of each variable from baseline to post-intervention were compared between the groups using the ANOVA test, and effect size (ES) statistic was also calculated. In comparison with the control group, significant reductions were found for office systolic BP (SBP, 8%, ES = 1.22), and 24 h-SBP (5%, ES = 1.2) in the RT group. However, GR group showed significant decreases in office SBP (10.5%, ES = 1.45), mean BP (8%, ES = 1.11), RPP (13%, ES = 1.47), 24 h-SBP (5%, ES = 1.21), and 24 h-RPP (10%, ES = 1.15). The interaction of regular RT and GT consumption seems to induce more beneficial effects on some important parameters including MBP and RPP when compared to RT or GT alone.


Safety considerations in intravenous infusion devices: the IVAC approach.
The safety-related circuits and characteristics of IVAC Models 260 and 560 are reviewed, with a discussion of how basic safety and reliability philosophies have been incorporated into the design of these instruments. The uses of IV fluid delivery instruments have expanded from traditional fluid replacement to nutritional, electrolyte, and potent cardiovascular drug therapy, creating the need for and forcing the development of safer and more reliable IV instruments. Standards organizations and regulatory agencies, such as AAMI and Germany's TUV, are implementing more exacting standards for new IV instruments. New designs must begin with a basic safety philosophy and then integrate that philosophy into hardware and software. Critical design areas include flow control mechanism, flow detection, microprocessor failsafe, battery operation, user interface, and software tests of the instrument and the microprocessor itself.


Continuous monitoring of electrode-skin impedance mismatch during bioelectric recordings.
In bioelectric recordings, an electrode-skin impedance mismatch leads to a reduced common-mode rejection ratio (CMRR) of the amplifier. For this reason, the impedance of each individual electrode-skin contact is usually measured prior to a recording. The measurement circuit itself degrades the CMRR and is switched off during the bioelectric recording. In this paper, we present a new method that allows to monitor the electrode-skin impedance in a continuous way without reducing the CMRR of the amplifier. The new method is based on an additional common-mode signal that is superimposed on the bioelectric signal.


[Effect of different regimens of chemotherapy and x-ray irradiation on the kinetics of experimental tumor growth].
Studies on the effect of different regimens of chemotherapy and local x-ray irradiation on the kinetics of the growth of Walker carcinosarcoma and Heren carcinoma have demonstrated that in the range of dosage of alkylating action drugs under study and also irradiation, the time of the recurrence onset depends on the therapeutic regimen. In cases when tumor regression is gained, the rate of the regression is not dependent on single doses of the drug or irradiation.


All-metal flexible large-area multiband waveplate.
We propose and demonstrate an all-metal flexible reflective multiband waveplate based on nano-grating structure using high efficient electroplating growing process, which exhibits quarter waveplate at two wavelengths (λ = 465nm and λ = 921nm) and half waveplate at another wavelength (λ = 656nm). Using Finite Difference Time Domain (FDTD) modeling, the phase shift and reflection efficiency are simulated and designed for a variety of geometrical parameters. A fast and cost-effective technique based on conventional interference lithography and nickel electroplating process is demonstrated to fabricate the all-metal, large-area and flexible waveplate. Experimental results show that the fabricated monolithic all-metal nano structure of the proposed device are in high fidelity with the structure on template and the optical performance of the device are in excellent agreement with the theoretical prediction. The proposed structure and the fabrication method suggests an effective way to realize all-metal, ultrathin, self-supporting and flexible devices for various applications in rugged environment such as high temperature or high pressure environment, and also in the fast growing fields of flexible (wearable) optoelectronics, flexible displays and other curved or nonplanar devices.


The effects of 5-HT on articular sensory receptors in normal and arthritic rats.
1. The effects of intra arterial (i.a.) injections of 5-hydroxytryptamine (5-HT, 1-100 micrograms) on the discharge of (a) identified articular high threshold mechanoreceptors and (b) unidentified chemosensitive receptors in the ankle joint have been studied electrophysiologically in anaesthetized normal and arthritic rats. Recordings were made from a fine branch of the medial plantar nerve. 2. 5-HT increased the mechanical responsiveness of high threshold nociceptive mechanoreceptors with C and A delta fibre afferents in both normal and adjuvant-arthritic rats. Receptors in arthritic joints were more sensitive to 5-HT than were those from normal joints. 3. 5-HT produced a complex response from both types of articular receptors following i.a. injection. Two separate components were identified: (a) a fast transient burst of activity was obtained within 10 s of this injection in 66% of units from normal animals and 45% from arthritics, followed by (b) a delayed slow longer-lasting excitation seen in 62% of the units examined from normals and 77% of units from arthritic rats. 4. Increased mechanoreceptor responsiveness produced by 5-HT was reduced or abolished by the 5-HT3 receptor antagonists studied (MDL 72222, ICS 205-930, or GR 38032F, in single doses of 100 micrograms kg-1, i.a.). 5. Fast excitation showed marked tachyphylaxis and was antagonized by MDL 72222, ICS 205-930 or GR 38032F. It was unaffected by ketanserin (100 micrograms kg-1, i.a.). Delayed excitation was reduced or abolished by ketanserin but was unaffected by the 5-HT3-receptor antagonists. 6. Administration of MDL 72222, ICS 205-930 or GR 38032F caused short lasting (< 5 min) reductions in background activity from both types of unit recorded in arthritic rats, as well as in normal rats in which activity had increased following administration of 5-HT. Ketanserin caused similar reductions in background activity in chemosensitive units, but had no effect on mechanoreceptors. 7. At least two types of receptor are involved in the actions of 5-HT on articular sensory receptors with fine afferent fibres. Increased mechano-responsiveness involves a 5-HT3-receptor as does fast excitation. Delayed excitation probably involves a 5-HT2-receptor. Endogenous 5-HT appears not to play a crucial role in sensitization of high threshold mechanoreceptors in this model of chronic inflammation and arthritis, although its local release may potentiate the actions of other inflammatory mediators on sensory receptors in the ankle joint.


Systems theoretic analysis of the central dogma of molecular biology: some recent results.
This paper extends our early study on a mathematical formulation of the central dogma of molecular biology, and focuses discussions on recent insights obtained by employing advanced systems theoretic analysis. The goal of this paper is to mathematically represent and interpret the genetic information flow at the molecular level, and explore the fundamental principle of molecular biology at the system level. Specifically, group theory was employed to interpret concepts and properties of gene mutation, and predict backbone torsion angle along the peptide chain. Finite state machine theory was extensively applied to interpret key concepts and analyze the processes related to DNA hybridization. Using the proposed model, we have transferred the character-based model in molecular biology to a sophisticated mathematical model for calculation and interpretation.


A prospective short-term study of chronic low back pain patients utilizing novel objective functional measurement.
The present study utilized recently developed diagnostic tests that permit recognition of functional deficits in spine mobility, trunk strength, endurance, coordination, and dynamic lifting capacity. Changes in these tests were compared to changes in psychological functioning (e.g., self-report of pain) as well as to outcome criteria such as return-to-work and resolution of litigation. The study utilized these tests repeatedly during a new treatment approach to feed back objective information of the patient's functional capacity, not amenable to simple visual inspection, to both the patient and the surgeon. The program itself integrated a low back physical rehabilitation program with a multimodal pain management program and was guided by repeated functional capacity measurements. A total of 66 patients were evaluated. Results demonstrated significant improvement in physical function in these patients, which was also accompanied by changes in self-report of pain complaints. Moreover, an 82% return-to-work rate was achieved in this sample which was initially 92% unemployed. These results indicate that the physician dealing with chronic low back dysfunction can employ objective measures of functional capacity as an alternative to the sole reliance on pain patient self-report or structured tests, such as radiographic imaging, which merely document a universal, progressive degenerative process.


Cross-scale interactions and the distribution-abundance relationship.
Positive interspecific relationships between local abundance and extent of regional distribution are among the most ubiquitous patterns in ecology. Although multiple hypotheses have been proposed, the mechanisms underlying distribution-abundance (d-a) relationships remain poorly understood. We examined the intra- and interspecific distribution-abundance relationships for a metacommunity of 13 amphibian species sampled for 15 consecutive years. Mean density of larvae in occupied ponds was positively related to number of ponds occupied by species; employing the fraction of ponds uniquely available to each species this same relationship sharply decelerates. The latter relationship suggested that more abundant species inhabited most available habitats annually, whereas rarer species were dispersal limited. We inferred the mechanisms responsible for this pattern based on the dynamics of one species, Pseudacris triseriata, which transitioned between a rare, narrowly distributed species to a common, widely distributed species and then back again. Both transitions were presaged by marked changes in mean local densities driven by climatic effects on habitat quality. We identified threshold densities separating these population regime shifts that differed with landscape configuration. Our data suggest that these transitions were caused by strong cross-scale interactions between local resource/niche processes and larger scale metapopulation processes. The patterns we observed have relevance for understanding the mechanisms of interspecific d-a relationships and critical thresholds associated with habitat fragmentation.


Biofilms in Periprosthetic Orthopedic Infections Seen through the Eyes of Neutrophils: How Can We Help Neutrophils?
Despite advancements in our knowledge of neutrophil responses to planktonic bacteria during acute inflammation, much remains to be elucidated on how neutrophils deal with bacterial biofilms in implant infections. Further complexity transpires from the emerging findings on the role that biomaterials play in conditioning bacterial adhesion, the variety of biofilm matrices, and the insidious measures that biofilm bacteria devise against neutrophils. Thus, grasping the entirety of neutrophil-biofilm interactions occurring in periprosthetic tissues is a difficult goal. The bactericidal weapons of neutrophils consist of the following: ready-to-use antibacterial proteins and enzymes stored in granules; NADPH oxidase-derived reactive oxygen species (ROS); and net-like structures of DNA, histones, and granule proteins, which neutrophils extrude to extracellularly trap pathogens (the so-called NETs: an allusive acronym for "neutrophil extracellular traps"). Neutrophils are bactericidal (and therefore defensive) cells endowed with a rich offensive armamentarium through which, if frustrated in their attempts to engulf and phagocytose biofilms, they can trigger the destruction of periprosthetic bone. This study speculates on how neutrophils interact with biofilms in the dramatic scenario of implant infections, also considering the implications of this interaction in view of the design of new therapeutic strategies and functionalized biomaterials, to help neutrophils in their arduous task of managing biofilms.


The SAPIEN 3 valve: lights and shadows.
Transcatheter aortic valve implantation (TAVI) has become an accepted alternative treatment option for high-risk or inoperable patients with symptomatic severe aortic stenosis. The future challenge for TAVI devices is to ensure results in terms of safety and efficacy that may justify an eligibility extension for this procedure to patients at intermediate and low risk for surgery. The ideal aortic valve prosthesis should be durable, with optimal hemodynamic performance and able to reduce the current major complications of TAVI procedure, in particular vascular complications (not infrequent with the transfemoral access route), paravalvular leaks, stroke and atrioventricular block requiring a permanent pacemaker. The SAPIEN 3™ (S3) (Edwards Lifesciences, Irvine, CA, USA) is the last Edwards family's transcatheter heart valves and incorporates a number of new and enhanced features intended to reduce the risk of vascular injury and paravalvular regurgitation, and to facilitate rapid and accurate positioning and implantation. The first data on S3 (SAPIEN3 trial) were presented at the EuroPCR 2014 and confirmed the advantage of the S3 compared with the previous Edwards valves (SAPIEN and SAPIEN XT) in terms of prevention of vascular complications and of moderate-severe paravalvular leaks, but showed an increase in the need of a permanent pacemaker post-TAVR. The S3 is certainly a promising evolution of transcatheter valves which may effectively reduce the risk of vascular complications and paravalvular leak. However, the S3 seems to be related to an increased risk of atrioventricular block, even if this complication could be due to the need to implant the valve in a higher position compared to previous models.


The spatial organization of apical junctional complex-associated proteins in feline and human corneal endothelium.
Previous studies suggest that proteins associated with the apical junctional complex (AJC) play essential roles in the development, maintenance and regulation of barrier function in transport epithelium and vascular endothelium. The goal of this study is to identify and determine the spatial organization of several major AJC-associated proteins in normal human and feline corneal endothelium. Fresh corneal tissue was obtained from 4 recipient buttons removed during penetrating keratoplasty (two from keratoconus patients, and two from patients with post-traumatic stromal scarring) as well as from 16 cat eyes. En bloc double- and triple-labeling of corneas was performed using phalloidin, and mouse, rat or rabbit antibodies to ZO-1, occludin, pan-cadherin, alpha-catenin, beta-catenin and plakoglobin (gamma-catenin). The 3-D localization of the proteins was then determined in situ using laser confocal microscopy. Similar staining patterns were obtained for the corneal endothelium of normal cat corneas and fresh human buttons. Apically, f-actin was arranged into dense peripheral bands (DPB) in individual cells that were separated from those in adjacent cells. Diffuse phalloidin staining also extended from the DPB into the cytoplasm apically. Although weaker, phalloidin staining also appeared to be associated with the basolateral cell borders. The adherens junction protein, cadherin, formed a thin pericellular band at the apical cell junctions between the DPB. In addition, cadherin staining also appeared to extend along the basolateral cell borders in a convoluted pattern. Staining for alpha-catenin, beta-catenin and plakoglobin each showed a nearly identical organization as cadherin. ZO-1 formed a single apical band that was localized between the DPB; however, no basolateral ZO-1 staining was detected. Interestingly, the distribution of ZO-1 was discontinuous around the cell, with the largest gaps occurring at the Y-junctions between adjacent endothelial cells. Positive staining for occludin was not detected in either human or feline corneal endothelium. The composition and organization of the AJC of corneal endothelium appears to be different from that of classical transport epithelia; these findings may be related to functional differences between these two cell types.


DeepOrganNet: On-the-Fly Reconstruction and Visualization of 3D / 4D Lung Models from Single-View Projections by Deep Deformation Network.
This paper introduces a deep neural network based method, i.e., DeepOrganNet, to generate and visualize fully high-fidelity 3D / 4D organ geometric models from single-view medical images with complicated background in real time. Traditional 3D / 4D medical image reconstruction requires near hundreds of projections, which cost insufferable computational time and deliver undesirable high imaging / radiation dose to human subjects. Moreover, it always needs further notorious processes to segment or extract the accurate 3D organ models subsequently. The computational time and imaging dose can be reduced by decreasing the number of projections, but the reconstructed image quality is degraded accordingly. To our knowledge, there is no method directly and explicitly reconstructing multiple 3D organ meshes from a single 2D medical grayscale image on the fly. Given single-view 2D medical images, e.g., 3D / 4D-CT projections or X-ray images, our end-to-end DeepOrganNet framework can efficiently and effectively reconstruct 3D / 4D lung models with a variety of geometric shapes by learning the smooth deformation fields from multiple templates based on a trivariate tensor-product deformation technique, leveraging an informative latent descriptor extracted from input 2D images. The proposed method can guarantee to generate high-quality and high-fidelity manifold meshes for 3D / 4D lung models; while, all current deep learning based approaches on the shape reconstruction from a single image cannot. The major contributions of this work are to accurately reconstruct the 3D organ shapes from 2D single-view projection, significantly improve the procedure time to allow on-the-fly visualization, and dramatically reduce the imaging dose for human subjects. Experimental results are evaluated and compared with the traditional reconstruction method and the state-of-the-art in deep learning, by using extensive 3D and 4D examples, including both synthetic phantom and real patient datasets. The efficiency of the proposed method shows that it only needs several milliseconds to generate organ meshes with 10K vertices, which has great potential to be used in real-time image guided radiation therapy (IGRT).


[Immunotherapy with grouped doses].
Once the efficacy and safety of immunotherapy with allergen extracts has been shown, recently it has become evident the need for perfecting those aspects of the treatment that can be improved, such as its dosage form. The conventional dosage of subcutaneous immunotherapy in the phase of dose increase is slow in reaching an efficient level. For this reason other alternative dosages to the conventional one have been tried out, such as grouped dosages, which shorten this period of dose increase. On condition that the safety of the treatment is guaranteed, these doses offer the advantages of reducing the economic cost and the time involved, of reducing the discomfort of the treatment and of improving the patient's adherence to the treatment, and possibly of reaching clinical efficacy more rapidly. Nonetheless, it is not easy to determine the suitable dosage of administration (the shortest and with the least number of adverse reactions) and this article reviews the existing problems when it comes to designing these grouped doses. Finally, we present the results of a comparative study between the conventional dose and a grouped dose, with a double blind design, carried out by us, which shows that the grouped dose is quicker in achieving the desired clinical efficacy, shortens the times of reduction of cutaneous sensitivity to the allergen and of modification of the immunological parameters, all with a low frequency of adverse reactions that is similar to that registered with the conventional dosage.


Noninvasive monitoring of intraocular pharmacokinetics of daunorubicin using fluorophotometry.
Daunorubicin is a cytotoxic drug, which, in nontoxic doses, is effective in preventing cellular proliferation in experimental vitreoretinopathy. We studied dose and clearance of daunorubicin in various ocular tissues using fluorophotometry techniques. In vitro tests: The emission of fluorescence from the daunorubicin solution having a concentration range of 0.1 to 10 micrograms/mL in phosphate buffer was measured using an excitation wavelength range of 489 +/- 10 nm. The emission of fluorescence was measured at 514 nm; the linearity of the response was determined using linear regression analysis. There is a fluorescence peak of daunorubicin at 485 nm. The validity and reproducibility of the method were examined. In vivo tests: The rabbits were randomized into three groups and daunorubicin concentrations of 4, 6, or 8 micrograms/mL were injected into the vitreous. Fluorophotometry scanning from the retina to the anterior chamber was performed with a commercially available fluorophotometer at various times up to 48 hours after injection to quantify fluorescence emission of daunorubicin. The standard curve of fluorescence versus concentration of daunorubicin was linear in the range of 0.1 to 8 micrograms/mL. It was sensitive up to 0.1 microgram. The daunorubicin time concentration profile showed a dose response relationship over the 48-hour period studied. The half-life of daunorubicin in the vitreous was about 5 hours. We performed fluorophotometry using a fluorophotometer whose exciter emits light at 489 nm, which is very close to an absorption peak of daunorubicin. These two values are close enough to obviate the need for modifying the commercial fluorophotometer. Therefore the concentration of daunorubicin in the vitreous cavity can be measured noninvasively.


Hypothyroidism after craniospinal irradiation with proton or photon therapy in patients with medulloblastoma.
Craniospinal irradiation (CSI) often results in endocrine deficiencies in children with medulloblastoma due to irradiation of the hypothalamic-pituitary axis (HPA) or the thyroid gland. CSI with Proton radiation therapy (PRT) has the potential to decrease the risk of hypothyroidism by reduction in radiation dose to these organs. This study compares the risk for hypothyroidism in patients with medulloblastoma treated with Photon radiation therapy (XRT) or PRT. The records of patients with medulloblastoma diagnosed at a single institution between 1997 and 2014 who received CSI were, retrospectively, reviewed. Ninety-five patients (54 XRT and 41 PRT) who had baseline and yearly follow-up thyroid studies were included. We used interval censored Cox regression to calculate hazard ratios of developing any, primary, and central hypothyroidism. With a median time to last thyroid studies post radiation of 3.8 years in PRT and 9.6 years in XRT, 33/95 (34.7%) patients developed hypothyroidism (median time to hypothyroidism: 2.6 years). Hypothyroidism developed in 25/54 (46.3%) who received XRT vs. 8/41 (19%) in the PRT group (HR =1.85, p = .14). Primary hypothyroidism developed in 15/95 (15.8%) patients: 12/54 (22.2%) after XRT and 3/41 (7.3%) after PRT (HR =2.1, p = .27). Central hypothyroidism developed in 17/95 (18.0%) patients: 13/54 (24.0%) after XRT and 4/41 (9.8%) after PRT (HR =2.16, p = .18). The use of PRT in patients with medulloblastoma was associated with numerically lower but not significantly lower risk of hypothyroidism. Further studies including larger numbers and longer follow up must be performed to assess whether lower radiation doses achieved with PRT show statistically significant differences.


Reproductive Characteristics and Pregnancy Outcomes in Hidden Celiac Disease Autoimmunity.
Untreated symptomatic celiac disease (CD) adversely affects female reproduction; however, the effect of hidden CD autoimmunity is uncertain. We identified women who were not previously diagnosed with CD and tested positive for tissue transglutaminase and endomysial antibodies between 2006 and 2011 in a community-based retrospective cohort study. We evaluated (i) the rate of adverse pregnancy outcomes and medical complications of pregnancy in successful singleton deliveries and (ii) reproductive characteristics in seropositive women without a clinical diagnosis of CD and age-matched seronegative women. Among 17,888 women whose serum samples were tested for CD autoimmunity, 215 seropositive and 415 seronegative women were included. We reviewed 231 and 509 live singleton deliveries of 117 seropositive and 250 seronegative mothers, respectively. Menarche and menopausal age, gravidity, parity, and age at first child were similar in seropositive and seronegative women. CD seropositivity was not associated with an increased risk of maternal pregnancy complications. Maternal seropositivity was associated with small for gestational age in boys (OR 3.77, 95% CI: 1.47-9.71; P = 0.006), but not in girls (OR 0.57, 95% CI: 0.15-2.17; P = 0.41). CD serum positivity was not associated with prematurity, small for gestational age (birth weight <10th percentile), or 5-minute Apgar score of less than 7. Although underpowered, the present study did not show any difference in reproductive characteristics or rates of adverse pregnancy outcomes in women with and without CD autoimmunity, except for birth weight in male offspring. Larger studies are needed to determine the effects of CD autoimmunity on female reproduction.


Semantic ambiguity within and across languages: an integrative review.
Semantic ambiguity often occurs within a language (e.g., the word "organ" in English means both a body part and a musical instrument), but it can also cross a language boundary, such that a given word form is shared in two languages, but its meanings are different (e.g., the word "angel" means "sting" in Dutch). Bilingual individuals are therefore faced not only with ambiguity in each of their languages, but also with ambiguity across languages. The current review focuses on studies that explored such cross-language ambiguity and examines how the results from these studies can be integrated with what we have learned about within-language ambiguity resolution. In particular, this review examines how interactions of frequency and context manifest themselves in ambiguity that crosses a language boundary and call for the inclusion of language context as a contributing factor. An extension of the monolingual reordered access model (Duffy, Morris, & Rayner, 1988) is outlined to discuss the interactions between these factors. Furthermore, the effects of the similarity between the two meanings, task differences, and individual differences are explored. This review highlights the need for studies that test within- and cross-language ambiguity in the same individuals before strong conclusions can be made about the nature of interactions between frequency, semantic context, and language context.


Multiple outbreaks of puffer fish intoxication in Bangladesh, 2008.
During April and June 2008, we investigated three outbreaks of marine puffer fish intoxication in three districts of Bangladesh (Narshingdi, Natore, and Dhaka). We also explored trade of marine puffer fish in Cox's Bazaar, a coastal area of the country. We identified 95 people who had consumed puffer fish; 63 (66%) developed toxicity characterized by tingling sensation in the body, perioral numbness, dizziness, and weakness, 14 of them died. All three outbreaks were caused by consumption of large (0.2-1.5 kg) marine puffer fish, sold in communities where people were unfamiliar with the marine variety of the fish and its toxicity. Coastal fishermen reported that some local businessmen distributed the fresh fish to non-coastal parts of the country, where people were unfamiliar with the larger variety, to make a quick profit. Lack of knowledge about marine puffer toxicity contributed to the outbreaks. Health communication campaigns will enhance people's knowledge and may prevent future outbreaks.


Walnuts change lipoprotein composition suppressing TNFα-stimulated cytokine production by diabetic adipocyte.
Walnut consumption can provide both vascular and metabolic health benefits, and walnut-induced changes in lipoprotein particle chemical payloads may be responsible for these health benefits. To explore this possibility with a focus on metabolic health, this study investigated the impact of walnut consumption on lipoprotein lipid composition and changes in LDL anti-inflammatory properties, as reported by inflamed adipocyte. Hypercholesterolemic, postmenopausal females were treated with 40 g/day (i.e., 1.6 servings/day; n=15) of walnuts for 4 weeks. Fatty acids and their oxygenated metabolites, i.e., oxylipins, were quantified in isolated lipoproteins. Human primary adipocytes were exposed to LDL and TNFα-stimulated adipokine production was measured. Walnut treatment elevated α-linolenic acid and its epoxides in all lipoproteins and depleted mid-chain alcohols in VLDL and LDL, but not HDL. Walnuts also reduced TNFα-induced diabetic adipocyte production of IL-6 (-48%, P=.0006) and IL-8 (-30%, P=.01), changes inversely correlated with levels of α-linolenic acid-derived epoxides but not α-linolenic acid itself. In conclusion, modest walnut consumption can alter lipoprotein lipid profiles and enhance their ability to inhibit TNFα-dependent pro-inflammatory responses in human diabetic primary adipocytes. Moreover, this study suggests the oxylipins, rather than the parent fatty acids, mediate LDL action of adipocytes.


Palbociclib-induced severe hepatitis: A case study and literature review.
Palbociclib is a selective and reversible CDK4/6 inhibitor approved for patients presenting with HR+ HER2- locally advanced or metastatic breast cancer. Its adverse effect (AE) is mainly reported on the occurrence of leukopenia and fatigue. Even though palbociclib has an extensive hepatic metabolism, there are rare reports about significant liver toxicity. We present the case of a 61-year-old female with metastatic breast cancer treated with palbociclib and an aromatase inhibitor (letrozole). The patient developed a rare AE of severe acute drug-induced hepatitis but improved dramatically after stopping the palbociclib and receiving treatment with N-acetylcysteine (NAC). The treatment with NAC may be a proof of concept for the mechanism of palbociclib liver injury.


Rethinking Heart Failure.
An increasing body of clinical observations and experimental evidence suggests that cardiac dysfunction results from autonomic dysregulation of the contractile output of the heart. Excessive activation of the sympathetic nervous system and a decrease in parasympathetic tone are associated with increased mortality. Elevated levels of circulating catecholamines closely correlate with the severity and poor prognosis in heart failure. Sympathetic over-stimulation causes increased levels of catecholamines, which induce excessive aerobic metabolism leading to excessive cardiac oxygen consumption. Resulting impaired mitochondrial function causes acidosis, which results in reduction in blood flow by impairment of contractility. To the extent that the excessive aerobic metabolism resulting from adrenergic stimulation comes to a halt the energy deficit has to be compensated for by anaerobic metabolism. Glucose and glycogen become the essential nutrients. Beta-adrenergic blockade is used successfully to decrease hyperadrenergic drive. Neurohumoral antagonists block adrenergic over-stimulation but do not provide the heart with fuel for compensatory anaerobic metabolism. The endogenous hormone ouabain reduces catecholamine levels in healthy volunteers, promotes the secretion of insulin, induces release of acetylcholine from synaptosomes and potentiates the stimulation of glucose metabolism by insulin and acetylcholine. Ouabain stimulates glycogen synthesis and increases lactate utilisation by the myocardium. Decades of clinical experience with ouabain confirm the cardioprotective effects of this endogenous hormone. The so far neglected sympatholytic and vagotonic effects of ouabain on myocardial metabolism clearly make a clinical re-evaluation of this endogenous hormone necessary. Clinical studies with ouabain that correspond to current standards are warranted.


Sternal insufficiency fracture related to steroid-induced osteoporosis: A case report.
Osteoporosis often results in fractures, deformity and disability. A rare but potentially challenging complication of osteoporosis is a sternal insufficiency fracture. This case report details a steroid-induced osteoporotic male who suffered a sternal insufficiency fracture after minimal trauma. Prompt diagnosis and appropriate management resulted in favourable outcome for the fracture, though a sequalae involving a myocardial infarction ensued with his osteoporosis and complex health history. The purpose of this case report is to heighten awareness around distinct characteristics of sternal fractures in osteoporotic patients. Discussion focuses on the incidence, mechanism, associated factors and diagnostic challenge of sternal insufficiency fractures. This case report highlights the role primary contact practitioners can play in recognition and management of sternal insufficiency fractures related to osteoporosis.


[Proctectomy with external sphincter elements' preservation in surgery of low-ampullary rectal cancer].
Operational technique for the rectum tumors, localized at the level of dentate line, developed in the State center of coloproctology, allows preservation of external anal sphincter elements and thus, partial preservation of defecation control. Technique is described and proved, preliminary treatment results of 42 patients are analysed. The operation is oncologically effective (local recurrence rate 4,8%). Preservation of external sphincter elements has a high functional value in complex with "neorectum" and "neosphincter". A majority of operated patients can keep the stool, 80% of able-bodied patients continued their professional activities.


Left Ventricular Fibrosis and CMR Tissue Characterization of Papillary Muscles in Mitral Valve Prolapse Patients.
Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies. MVP patients with indication for surgery due to severe mitral regurgitation (n=19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings. MVP patients (54±10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096±78ms vs 994±54ms and 33.9±5.6% vs 25.9±3.1%, respectively, p<0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE+ in LV and PM was identified in 5 (26.3%) patients, while DB-LGE+ was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE+ in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs 36.8%, p=0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p=0.029). CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.


Landing the executive job: how to prepare for employment in the '90s.
The 1990s have been an era of transition for much of the American workforce as companies change with the times. Executives in home care have been dealing with change as well. The authors polled executives and executive recruiters to discover their secrets for success in today's job market.


Histologic changes in the mouse testis after bilateral vasectomy.
To study the effect of vasectomy on histological appearance of the testis. Parkes strain mice were used as the animal model; they were bilaterally vasectomized (Vx) or sham-operated (So) and killed at intervals of 4, 6, 9, and 12 months after the operation. Testes were excised from 5 Vx and 5 So mice at each interval and processed for histological examination. Testes of So mice showed normal histological features. By contrast, marked alterations were observed in the seminiferous tubules in testes of Vx mice, except in those killed 4 months after the operation. The seminiferous epithelium in the tubules was only 2-3 layers thick and showed much depletion of germ cells; in severe cases, the epithelium consisted of only a thin layer of Sertoli cells, spermatogonia and a few spermatocytes. Exfoliation of germ cells, occurrence of multinucleated giant cells and vacuolated appearance of the epithelium were of common features in the tubules. Furthermore, lumen of the rete testis in Vx mice was greatly dilated and showed accumulation of spermatozoa with immature germ cells; in mice vasectomized for 6-12 months, several macrophages ingesting spermatozoa were often observed in the lumen of the rete testis. Spermatic granuloma was also sometimes noticed in corpus or in cauda regions of the epididymis in mice vasectomized for 6-12 months. We suggest that consequences of vasectomy should be thoroughly understood in order to make this method rather more popular as a reversible method of male contraception.


Purification and partial characterization of a pyruvate oxidoreductase from the photosynthetic bacterium Rhodospirillum rubrum grown under nitrogen-fixing conditions.
A pyruvate oxidoreductase with the capacity to support pyruvate-dependent nitrogenase activity in vitro has been purified from the photosynthetic bacterium Rhodospirillum rubrum. The enzyme requires CoA for activity and is irreversibly inactivated by oxygen. The molecular properties and Km values for the substrates have been studied. In supporting nitrogenase activity addition of ferredoxin is required. Overall the enzyme is similar to the nif-specific pyruvate: flavodoxin oxidoreductase purified from Klebsiella pneumoniae.


Essential structural and functional features of small heat shock proteins in molecular chaperoning process.
Small heat shock proteins are ubiquitously found in all three domains of life, although they are the most poorly conserved family of molecular chaperones. Their involvement in anti-stress mechanisms of the cells have been clearly demonstrated by induction of their expression in response to various environmental and pathological stresses. Small heat shock proteins comprise the most effective chaperone family concerning their unusual capacity of substrate binding. It is well documented that small heat shock proteins associate with unfolding substrate proteins and form large oligomeric complexes to prevent their aggregation and accumulation, that otherwise would impair the normal cell functions. The substrates captured by small heat shock proteins are further refolded to their native state by ATP depended chaperones. During heat stress, the induced expression and activation of the small heat shock proteins, might reflect that this mechanism of protein quality control contributes to acquired thermotolerance in hyperthermophilic archaea, as well.


Is the Mitochondrial Membrane Potential (∆Ψ) Correctly Assessed? Intracellular and Intramitochondrial Modifications of the ∆Ψ Probe, Rhodamine 123.
The mitochondrial membrane potential (∆Ψ) is the driving force providing the electrical component of the total transmembrane potential of hydrogen ions generated by proton pumps, which is utilized by the ATP synthase. The role of ∆Ψ is not limited to its role in bioenergetics since it takes part in other important intracellular processes, which leads to the mandatory requirement of the homeostasis of ∆Ψ. Conventionally, ∆Ψ in living cells is estimated by the fluorescence of probes such as rhodamine 123, tetramethylrodamine, etc. However, when assessing the fluorescence, the possibility of the intracellular/intramitochondrial modification of the rhodamine molecule is not taken into account. Such changes were revealed in this work, in which a comparison of normal (astrocytic) and tumor (glioma) cells was conducted. Fluorescent microscopy, flow cytometry, and mass spectrometry revealed significant modifications of rhodamine molecules developing over time, which were prevented by amiodarone apparently due to blocking the release of xenobiotics from the cell and their transformation with the participation of cytochrome P450. Obviously, an important role in these processes is played by the increased retention of rhodamines in tumor cells. Our data require careful evaluation of mitochondrial ∆Ψ potential based on the assessment of the fluorescence of the mitochondrial probe.


Pregnancy-related mortality in southern Nepal between 2001 and 2006: independent estimates from a prospective, population-based cohort and a direct sisterhood survey.
Demographic household surveys in Nepal between 1996 and 2006 indicate potentially large decreases in the pregnancy-related mortality ratio and raise hopes that Nepal may be on track to meet Millennium Development Goal 5. Between 2002 and 2006, 23,478 pregnant women in Sarlahi District, Nepal, were followed through pregnancy to 42 days postpartum. The pregnancy-related mortality ratio (PRMR) was estimated directly, comparing deaths among women during pregnancy or within 42 days of pregnancy termination to livebirths. In a separate household survey, 13,319 married females reported on the pregnancy history of 28,829 sisters, allowing for a concurrent comparison of estimation methodologies. In the prospective study, there were 121 pregnancy-related deaths and 23,662 livebirths (PRMR = 511, 95% confidence interval: 425, 611). In the household survey, participants reported 396 deaths among sisters, 87 (22.0%) of which were pregnancy related, and 116,491 person-years of exposure (PRMR = 529, 95% confidence interval: 419, 638). Two independent estimates collected with different methods in the same geographic area over similar time periods resulted in similarly high estimates of mortality that are approximately twice the current national estimate. Access to life-saving maternal health interventions remains low in rural Nepal, and continued efforts are necessary to ensure equitable and country-wide progress toward Millennium Development Goal 5.


Development and validation of a high-performance liquid chromatography-mass spectrometry assay for determination of amphetamine, methamphetamine, and methylenedioxy derivatives in meconium.
A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of amphetamine, methamphetamine, and methylendioxy derivatives in meconium, using 3,4-methylendioxypropylamphetamine as internal standard. The analytes were initially extracted from the matrix by 17 mM methanolic HCl. Subsequently, a solid-phase extraction with Bondelut Certify columns was applied. Chromatography was performed on a C(18) reversed-phase column using a linear gradient of 10 mM ammonium bicarbonate, pH 9.0-methanol as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with an atmospheric pressure ionization-electrospray interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay. Mean recoveries ranged between 61.1 and 87.2% for different analytes. The quantification limits were 0.005 microg/g meconium for amphetamine, methamphetamine, and 4-hydroxy-3-methoxymethamphetamine and 0.004 microg/g meconium for 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine. The method was applied to analysis of meconium in newborns to assess eventual fetal exposure to amphetamine derivatives.


Water-column stratification governs the community structure of subtropical marine picophytoplankton.
The increase in the areal extent of the subtropical gyres over the past decade has been attributed to a global tendency towards increased water-column stratification. Here, we examine how vertical stratification governs the community structure of the picophytoplankton that dominate these vast marine ecosystems. We analysed phytoplankton community composition in the three Southern Subtropical basins of the Pacific, Indian and Atlantic Oceans using a variety of methods and show that the distributions of picocyanobacteria and photosynthetic picoeukaryotes (PPEs) are strongly correlated with depth and strength of vertical mixing: the changes in community structure occur at various taxonomic levels. In well-mixed waters, PPEs, in particular haptophytes, dominate, whereas in strongly stratified waters, picocyanobacteria of the genus Prochlorococcus are prevalent, regardless of whether the relative contributions to total biomass are assessed in terms of pigment or of carbon. This ecological diochotomy within the picophytoplankton supports the hypothesis that genomic streamlining provides a selective advantage for Prochlorococcus in highly stable, oligotrophic systems, but may restrict their ability to dominate in regions subject to dynamic mixing.


Tetanus-diphtheria-acellular pertussis vaccination of adults in the USA.
Pertussis is an important cause of morbidity and mortality, and its incidence has been increasing in adolescents and adults over the past two decades. Waning immunity in adolescents and adults may be partially responsible. Adults can suffer significant illness from pertussis and its complications, such as pneumonia, rib fractures and syncope. Moreover, adults serve as a source of disease for infants, who are more vulnerable to severe complications and even death. The economic burden of pertussis is substantial, in terms of both medical and nonmedical costs. Fortunately, the burden of pertussis disease can now be safely and effectively reduced by vaccinating adults with tetanus-diphtheria-acellular pertussis (Tdap) vaccine. Further research is needed to elucidate the role of vaccination in pregnant women and those over 65 years of age, and also to determine whether further booster doses of Tdap are needed.


Hereditary hemochromatosis: diagnosis and treatment in primary care.
Hereditary hemochromatosis (HHC) is one of the most common inherited disorders in the Caucasian population. Diagnosis usually made after an elevation in ferritin and serum transferrin saturation is noted, often accompanied by asymptomatic hepatomegaly. Diagnosis is confirmed by genetic testing or liver biopsy. Damage to organs is due to excessive intestinal iron, which is transported to and then deposited in the liver parenchyma, and the heart, skin, and endocrine organs, causing skin pigmentation, development of cirrhosis and hepatic carcinoma, diabetes and endocrine failure, and heart failure. Bony changes can be manifested by arthritis, often in non-weight-bearing joints. The treatment of HHC is phlebotomy, which depletes iron stores. When diagnosis is made before organ damage occurs, treatment can prevent manifestations of the disease. Skin pigmentation and some cardiac damage may reverse on depletion of iron stores, but liver and endocrine damage is rarely reversible. Arthropathy is also not reversible, and often continues to progress even with effective treatment. When hemochromatosis is diagnosed, all first degree relatives of the patient should undergo genetic testing. With early detection and treatment this can be a manageable chronic disease. If undetected, it is potentially fatal.


Review: nanocomposites in food packaging.
The development of nanocomposites is a new strategy to improve physical properties of polymers, including mechanical strength, thermal stability, and gas barrier properties. The most promising nanoscale size fillers are montmorillonite and kaolinite clays. Graphite nanoplates are currently under study. In food packaging, a major emphasis is on the development of high barrier properties against the migration of oxygen, carbon dioxide, flavor compounds, and water vapor. Decreasing water vapor permeability is a critical issue in the development of biopolymers as sustainable packaging materials. The nanoscale plate morphology of clays and other fillers promotes the development of gas barrier properties. Several examples are cited. Challenges remain in increasing the compatibility between clays and polymers and reaching complete dispersion of nanoplates. Nanocomposites may advance the utilization of biopolymers in food packaging.


Adsorption states and mobility of trimethylacetic acid molecules on reduced TiO(2)(110) surface.
Combined scanning tunneling microscopy (STM), X-rays photoelectron spectroscopy (XPS) and density functional theory (DFT) studies have probed the bonding configurations and mobility of trimethylacetic acid (TMAA) molecules on the TiO(2)(110) surface at RT. Upon TMAA dissociation through deprotonation, two distinctly different types of stable chemisorption configurations of the carboxylate group (TMA) have been identified according to their position and appearance in STM images. In configuration A, two carboxylate O atoms bond to two Ti(4+) cations, while in configuration B one O atom fills the bridging oxygen vacancy (V(O)) with the other O bounded at an adjacent regular Ti(4+) site. Calculated adsorption energies for the configurations A and B are comparable at 1.28 and 1.36 eV, respectively. DFT results also show that TMA may rotate at RT about its O atom that filled the V(O) (in configuration B), with a rotation barrier of approximately 0.65 eV. Both the observation of the constant initial sticking coefficient and preference for TMAA molecules to dissociate at selective sites indicate that TMAA adsorption is mediated by a mobile precursor state. Several possible molecular (physisorbed) states of TMAA have indeed been identified by DFT, all being highly mobile at RT. In contrast, the TMA diffusion in the chemisorbed (dissociative) state is a very slow with a calculated barrier of 1.09 eV for diffusion along the Ti row.


Effect of Insoluble Surfactants on Drainage and Rupture of a Film between Drops Interacting under a Constant Force.
The deformation, drainage, and rupture of an axisymmetrical film between colliding drops in the presence of insoluble surfactants under the influence of van der Waals forces is studied numerically at small capillary and Reynolds numbers and small surfactant concentrations. Constant-force collisions of Newtonian drops in another Newtonian fluid are considered. The mathematical model is based on the lubrication equations in the gap between drops and the creeping flow approximation of Navier-Stokes equations in the drops, coupled with velocity and stress boundary conditions at the interfaces. A nonuniform surfactant concentration on the interfaces, governed by a convection-diffusion equation, leads to a gradient of the interfacial tension which in turn leads to additional tangential stress on the interfaces (Marangoni effects). The mathematical problem is solved by a finite-difference method on a nonuniform mesh at the interfaces and a boundary-integral method in the drops. The whole range of the dispersed to continuous-phase viscosity ratios is investigated for a range of values of the dimensionless surfactant concentration, Peclét number, and dimensionless Hamaker constant (covering both "nose" and "rim" rupture). In the limit of the large Peclét number and the small dimensionless Hamaker constant (characteristic of drops in the millimeter size range) a fair approximation to the results is provided by a simple expression for the critical surfactant concentration, drainage being virtually uninfluenced by the surfactant for concentrations below the critical surfactant concentration and corresponding to that for immobile interfaces for concentrations above it. Copyright 2000 Academic Press.


Longitudinal validity of using digital hand photographs for assessing hand osteoarthritis progression over 7 years in community-dwelling older adults with hand pain.
To determine the longitudinal construct validity of assessing hand OA progression on digital photographs over 7 years compared with progression determined from radiographs, clinical features and change in symptoms. Participants were community-dwelling older adults (≥50 years) in North Staffordshire, UK. Standardized digital hand photographs were taken at baseline and 7 years, and hand joints graded for OA severity using an established photographic atlas. Radiographic hand OA was assessed using the Kellgren and Lawrence grading system. Hand examination determined the presence of nodes, bony enlargement and deformity. Symptoms were reported in self-complete questionnaires. Radiographic and clinical progression and change in symptoms were compared to photographic progression. Differences were examined using analysis of covariance and Chi-Square tests. Of 253 individuals (61% women, mean age 63 years) the proportion with photographic progression at the joint and joint group-level was higher in individuals with radiographic or clinical progression compared to those without, although differences were not statistically significant. At the person-level, those with moderate photographic progression over 7 years had significantly higher summed radiographic and clinical scores (adjusted for baseline scores) compared to those with no or mild photographic progression. Similar findings were observed for change in symptoms, although differences were small and not statistically significant. Assessing hand OA on photographs shows modest longitudinal construct validity over 7 years compared with change in radiographic and clinical hand OA at the person-level. Using photographs to assess overall long-term change in a person with hand OA may be a reasonable alternative when hand examinations and radiographs are not feasible.


A novel pyrroline-5-carboxylic acid and acetoacetic acid adduct in hyperprolinaemia type II.
From investigations of a child with hyperprolinaemia type II, we demonstrated in vitro that pyridoxal phosphate forms a novel adduct with a proline metabolite, pyrroline-5-carboxylic acid, through Claisen condensation. Studies indicated that this was a previously unsuspected generic reaction of aldehydes and some ketones. We have subsequently found the acetoacetic acid adduct in both plasma and urine from the affected child. Mixtures of acetoacetic acid and pyrroline-5-carboxylic acid were co-incubated at pH 7.4 and 37 degrees C, dried, or extracted and dried, derivatised and analysed by gas chromatography/mass spectrometry (GC/MS). Urine and plasma from the child were analysed. Fourteen new peaks were found in derivatised pyrroline-5-carboxylic acid/acetoacetic acid co-incubates. From accurate molecular mass data, the four largest peaks were probably diastereoisomers of tri-trimethylsilyl (tri-TMS) derivatives of alcohol adducts formed by Claisen condensation. Eight other peaks were mono- and di-trimethylsilyl derivatives of the adduct and a decarboxylated product. The adduct was demonstrated unequivocally in the child's acute urine and traces in plasma. Pyrroline-5-carboxylic acid forms an adduct with acetoacetic acid, which was present in urine of a sick child with hyperprolinaemia type II. Evidence suggests it formed in vivo. The biological significance of this novel reaction of aldehydes and ketones merits investigation.


Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition.
Nutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone of energy balance. Here, we aimed to identify a physiological signal that arises from excess caloric intake and negatively controls hypothalamic leptin action. We found that deficiency of the gastric inhibitory polypeptide receptor (Gipr) for the gut-derived incretin hormone GIP protected against diet-induced neural leptin resistance. Furthermore, a centrally administered antibody that neutralizes GIPR had remarkable antiobesity effects in diet-induced obese mice, including reduced body weight and adiposity, and a decreased hypothalamic level of SOCS3, an inhibitor of leptin actions. In contrast, centrally administered GIP diminished hypothalamic sensitivity to leptin and increased hypothalamic levels of Socs3. Finally, we show that GIP increased the active form of the small GTPase Rap1 in the brain and that its activation was required for the central actions of GIP. Altogether, our results identify GIPR/Rap1 signaling in the brain as a molecular pathway linking overnutrition to the control of neural leptin actions.


Small cell carcinoma of the urinary bladder. The Mayo Clinic experience.
Small cell carcinoma (SCC) of the urinary bladder accounts for 0.35-0.70% of all bladder tumors. There is no standard approach to the management of SCC of the urinary bladder. The authors performed a retrospective study at Mayo Clinic (Rochester, MN) to characterize the clinical and pathologic features of patients with SCC of the urinary bladder diagnosed between 1975 and 2003 with emphasis on management. Forty-four patients were identified who had primary bladder SCC, 61.4% of whom had pure SCC. The male:female ratio was 3:1, the mean age was 66.9 years, and the mean follow-up was 3.2 years. Twelve patients (27.3%) had Stage II disease, 13 patients (29.6%) had Stage III disease, and 19 patients (43.2%) had Stage IV disease. The overall median survival was 1.7 years. The 5-year survival rates for patients with Stage II, III, and IV disease were 63.6%, 15.4%, and 10.5%, respectively. Six of eight patients with Stage II bladder SCC achieved a cure with radical cystectomy. Five patients with Stage IV disease had obvious metastases and received chemotherapy. Fourteen patients underwent radical cystectomy and were diagnosed later with locally advanced disease (T4b) or lymph node metastasis (N1-N3; Stage IV disease). Only 2 of 19 patients with Stage IV disease who received adjuvant chemotherapy were alive at 5 years. Patients with bladder SCC should undergo radical cystectomy except when metastatic disease is present (M1), in which case, systemic chemotherapy is indicated. Adjuvant treatment is not indicated for patients with Stage II disease after radical cystectomy but should be considered for patients with Stage III and IV disease. Chemotherapy should be a platinum-based regimen.


Assessment of radiogenic cancer initiation frequency per clonogenic rat mammary cell in vivo.
Radiogenic initiation of mammary cancer is here shown to be a common cellular event. With the aid of a rat mammary clonogen transplant system designed to maximize progression of initiated cells to overt neoplasia, the estimated absolute cancer risk per surviving 7 Gy-irradiated mammary clonogen was [4.1 +/- 1.2 (SE)] X 10(-3), that is (5.8 +/- 1.7) X 10(-4) initiated cells per clonogen-Gy. To maximize neoplastic progression, all clonogen graft recipient rats were glucocorticoid deficient (adrenalectomized with minimal mineralocorticoid replacement) and hyperprolactinemic (implanted intrasplenically with pituitary tissue and an estrone capsule). Each rat was grafted with 4 X 10(6) "morphologically intact" monodispersed mammary cells in the interscapular white fat pad. Group A received cells which had been irradiated 1 day earlier with 7 Gy 137Cs gamma-rays. Groups B and C received unirradiated mammary cells. On day 35 after transplantation, the graft sites of group B were locally exposed to 7 Gy 140 kVp X-rays. Kaplan-Meier estimates (11) of the survivor functions were used to calculate the final tumor incidences corrected for intercurrent animal loss. Estimated mammary carcinoma frequencies so calculated were 65 tumors/131 graft sites in group A, 93/119 in group B, and 13/129 in group C. The relative cancer risks per rat due to the radiation exposure of the grafted cells were 5.0 for group A and 7.8 for group B. These data on neoplasia incidence in grafted mammary clonogens and data on autologous neoplasia in the host rat mammary glands were subjected to statistical analysis. The results indicate that both neoplasm frequency and latency are in large part dependent on initiation target cell number. The high frequency of radiogenic initiation per mammary clonogen observed in this study is in accord with findings with a similar thyroid clonogen transplant system.


Emission of oxygenated polycyclic aromatic hydrocarbons from indoor solid fuel combustion.
Indoor solid fuel combustion is a dominant source of polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (OPAHs) and the latter are believed to be more toxic than the former. However, there is limited quantitative information on the emissions of OPAHs from solid fuel combustion. In this study, emission factors of OPAHs (EF(OPAH)) for nine commonly used crop residues and five coals burnt in typical residential stoves widely used in rural China were measured under simulated kitchen conditions. The total EF(OPAH) ranged from 2.8 ± 0.2 to 8.1 ± 2.2 mg/kg for tested crop residues and from 0.043 to 71 mg/kg for various coals and 9-fluorenone was the most abundant specie. The EF(OPAH) for indoor crop residue burning were 1-2 orders of magnitude higher than those from open burning, and they were affected by fuel properties and combustion conditions, like moisture and combustion efficiency. For both crop residues and coals, significantly positive correlations were found between EFs for the individual OPAHs and the parent PAHs. An oxygenation rate, R(o), was defined as the ratio of the EFs between the oxygenated and parent PAH species to describe the formation potential of OPAHs. For the studied OPAH/PAH pairs, mean R(o) values were 0.16-0.89 for crop residues and 0.03-0.25 for coals. R(o) for crop residues burned in the cooking stove were much higher than those for open burning and much lower than those in ambient air, indicating the influence of secondary formation of OPAH and loss of PAHs. In comparison with parent PAHs, OPAHs showed a higher tendency to be associated with particulate matter (PM), especially fine PM, and the dominate size ranges were 0.7-2.1 μm for crop residues and high caking coals and <0.7 μm for the tested low caking briquettes.


Point mutations associated with Leber hereditary optic neuropathy in a Latvian population.
To study mutations associated with Leber hereditary optic neuropathy (LHON) in patients suspected of having this mitochondrial disorder in a Latvian population. Additional aims were to determine the heteroplasmy status of all non-synonymous polymorphisms identified in the current study and to identify the mitochondrial haplogroups of the studied participants because these factors may contribute to the manifestation of LHON. Twelve patients, including patients in two families, were enrolled in the current study. LHON was suspected based on the findings of ophthalmologic examinations. In clinically affected individuals, the presence of all previously reported LHON-associated mutations was assessed with sequencing analysis. Additionally, the SURVEYOR endonuclease assay was used to detect heteroplasmy. The mitochondrial haplogroups were identified with restriction analysis and the sequencing of hypervariable segment 1. In one family (mother and son), there was one primary LHON-associated mutation, G11778A. In addition, one rare previously reported LHON-associated polymorphism, A13637G, was detected in two unrelated patients. A non-synonymous polymorphism at T6253C was found in one individual. This mutation was reported in the background of the 3460 mutation among LHON patients in a Chinese population. No non-synonymous point mutations in mitochondrial DNA were found in five of the study participants. Molecular analysis of 12 patients with suspected LHON confirmed the diagnosis in four patients and allowed the use of appropriate prophylactic measures and treatment. Further investigations and additional studies of different populations are necessary to confirm the role of the non-synonymous polymorphisms A13637G and T6253C in the manifestation of LHON and the associations of these polymorphisms with mitochondrial haplogroups and heteroplasmy.


Comparison of susceptibility of cystic-fibrosis-related and non-cystic-fibrosis-related Pseudomonas aeruginosa to chlorine-based disinfecting solutions: implications for infection prevention and ward disinfection.
Multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from cystic fibrosis (CF) sputum was shown to be more tolerant to the most commonly used chlorine-based disinfecting agent in the UK, with approximately 7 out of 10 isolates surviving a residual free chlorine (RFC) concentration of 500 p.p.m., when compared with antibiotic-sensitive invasive P. aeruginosa from a non-CF blood culture source, where 8 out of 10 isolates were killed at a RFC concentration of 100 p.p.m. All CF isolates were killed at 1000 p.p.m. chlorine. Additional studies were performed to examine factors that influenced the concentration of RFC from chlorine-based (sodium dichloroisocyanurate) disinfecting agents in contact with CF sputum and their components (bacterial cells, glycocalyx) to assess the reduction of the bactericidal activity of such disinfecting agents. Pseudomonas glycocalyx had a greater inhibitory effect of chlorine deactivation than bacterial cells. Calibration curves demonstrated the relative deactivating capacity on RFC from clinical soils, in the order pus>CF sputum>wound discharge fluid/synovial fluid>ascites fluid>bile, where quantitatively each 1 % (w/v) CF sputum reduced the RFC by 43 p.p.m. Sublethal stressing of P. aeruginosa with chlorine resulted in lowered susceptibility to colistin (P = 0.0326) but not to meropenem, tobramycin or ciprofloxacin. In conclusion, heavy contamination of healthcare fomites with CF sputum containing MDR P. aeruginosa may result in exhaustion of RFC, and this, combined with an increased resistance to chlorine with such strains, may lead to their survival and increased antibiotic resistance in such environments. CF infection prevention strategies in such scenarios should therefore target interventions with increased concentrations of chlorine to ensure the eradication of MDR P. aeruginosa from the CF healthcare environment.


Polymorphisms and expressions of ADSL, MC4R and CAPN1 genes and their effects on economic traits in Egyptian chicken breeds.
In recent years, strategic plans for poultry production have emphasized quantitative traits, particularly body weight and carcass traits (meat yield), in response to overpopulation challenges. Candidate genes such as adenylosuccinate lyase (ADSL), melanocortin-4-receptor (MC4R), and calpain 1 (CAPN1) have played vital roles in this context due to their associations with muscle growth and body composition. This study aims to investigate the influence of polymorphisms and gene expressions of the aforementioned genes on body weight (BW), growth rate (GR), breast weight (BrW), and thigh weight (TW) across four distinct chicken breeds: Fayoumi, Matrouh, Mamourah, and Leghorn. The use of PCR-SSCP analysis revealed genetic polymorphisms through the identification of various patterns (genotypes) within the three examined genes. The ADSL, MC4R, and CAPN1 genes exhibited five, three, and two different genotypes, respectively. These polymorphisms displayed promising connections with enhancing economically significant production traits, particularly BW, BrW and TW. Furthermore, gene expression analyses were conducted on breast and thigh tissues obtained from the chicken breeds at 60 days of age, where ADSL and MC4R exhibited a noteworthy up-regulation in Fayoumi and Matrouh breeds, and down-regulation in Mamourah and Leghorn. In contrast, CAPN1 expression decreased across most breeds with a slight increase noted in Fayoumi breed. In conclusion, this investigation underscores the substantial impact of ADSL, MC4R, and CAPN1 genes on economically important production traits within Egyptian domestic chicken breeds. Consequently, these genes emerge as significant molecular markers, holding potential utility in avian selection and breeding programs aimed at enhancing productive performance.


Potential of MR spectroscopy for assessment of glioma grading.
Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids. In this review, we describe potential of MRS for grading of gliomas. Low-grade gliomas are generally characterized by a relatively high concentration of N-acetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies. Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade.


Climate change as a threat multiplier to environmental reproductive justice.
Legacies of racial capitalism and colonialism drive present day racial disparities in perinatal health outcomes. Climate change amplifies existing social inequalities associated with environmental exposures and reproductive health, of which BIPOC (Black, Indigenous, and people of color) communities bear a disproportionate burden. Through case studies, this article summarizes three examples of climate justice issues with reproductive healthcare outcomes: traffic related air pollution exposure, chemical exposures in personal care products and plastics, and natural disaster frequency. We advocate for incorporation of climate justice and environmental health impact into medical school curriculum, increased prenatal screening for environmental toxins, and physician engagement with local environmental issues.


Autoradiographic determination of dexamethasone binding sites along the rabbit nephron.
Specific binding sites of tritiated dexamethasone ([3H]dex) along the tubule of rabbit kidney were investigated using an autoradiographic method (dry film) on isolated tubular segments. After in vitro incubation of kidney pyramids with [3H]dex (0.15-53 nM) in the presence or absence of an excess (X200) of unlabeled dexamethasone, tubular segments were microdissected and processed for autoradiography. A quantitative analysis of specific labeling over cytoplasm and nuclei was performed. Specific nuclear binding was observed in all tubular segments beyond the pars recta. This binding was dose dependent and reached much higher values than those reported for aldosterone. In the proximal tubule, the specific labeling was also high but remained mostly cytoplasmic. The meaning of these drastically different intracellular localizations is still open to interpretation. Autoradiography was performed after in vivo injection of [3H]dex and [3H]aldosterone. The results were not different from those described here for dexamethasone and from those previously reported for aldosterone after in vitro incubation. We conclude that specific nuclear binding sites for dexamethasone range over the nephron except for proximal tubule, with no great difference among segments, in contrast to specific sites for aldosterone, which are restricted to distal and cortical collecting tubules. The exact significance of the proximal cytoplasmic specific binding of [3H]dex remains to be determined.


Histopathology slides from medical research to medical practice in interwar Strasbourg.
Histopathologists have been interested in cancer since the beginning of cellular theory. Rudolf Virchow and Julius Cohnheim defined cancer as a disease due to specific changes in tissues; cancer was thus considered a "pathologist's disease." Virchow emphasized the principles of biopsy and its value in the diagnosis of malignant tumours, but he himself did not promote it as an instrument for diagnosis. In the nineteenth century, in fact, cancer was a pathologists' disease in research only, not in diagnosis. By the mid-twentieth century, pathologists figured in medical practice as mediators between alternative therapeutic solutions. Histopathology entered a new arena, medical practice. In this paper, the process through which microscope slides moved from histopathology research to medical practice will be explored in detail with the aim of understanding how medical research integrates routine medical practices. The quasi-inherent character of scientific knowledge as relevant to medical practice is not taken for granted here. Through a study of medical school laboratory records from the interwar period in Strasbourg, I argue that pathologists could direct patients to specific forms of therapy on the basis of microscopic slides of cancer cells because they had defined (and re-defined) cancers by contributing to establishing radiation therapy practices.


Total Synthesis of the Proposed Structure of Neaumycin B.
The total synthesis of the proposed structure of anti-glioblastoma natural product neaumycin B was achieved in 22 steps (longest linear sequence). The synthesis features HCl-mediated [6,6]-spiroketalization, a combination of Krische iridium-catalyzed crotylation, Marshall palladium-catalyzed propargylation, Fürstner nickel-catalyzed regio- and enantioselective vicinal monoprotected diol formation, Brown crotylation and asymmetric halide-aldehyde cycloaddition, so as to establish the challenging contiguous stereocenters.


Comparing the tolerability and effectiveness of two treatment regimens in a smoking clinic.
This study compares the effectiveness and tolerability of bupropion versus bupropion plus nicotine patch for smoking cessation in a routine clinical setting. Patients at the Sepulveda Veterans Health Administration Smoking Cessation Clinic completed a baseline survey and received counseling over 2 months, along with bupropion or bupropion plus nicotine patch. Of the 227 patients randomized to treatment, 112 (49%) received bupropion only and 115 (51%) received the combination therapy. At least one side effect was noted in 55% of bupropion patients and 70% of combination therapy patients; treatment regimens were changed in 7% and 14%, respectively. Abstinence rates at 2 months were 26% for the bupropion group and 37% for the combination therapy group (p = 0.1), and at 6 months were 42% versus 35%, respectively (p = 0.4). Although 6-month abstinence rates were derived from patient self-report and should be interpreted with caution, these results suggest that most patients referred to the clinic are able to take these medications. There was no difference in the rate of switching treatments, or in long-term abstinence rates.


HER2Δ16 Engages ENPP1 to Promote an Immune-Cold Microenvironment in Breast Cancer.
The tumor-immune microenvironment (TIME) is a critical determinant of therapeutic response. However, the mechanisms regulating its modulation are not fully understood. HER2Δ16, an oncogenic splice variant of the HER2, has been implicated in breast cancer and other tumor types as a driver of tumorigenesis and metastasis. Nevertheless, the underlying mechanisms of HER2Δ16-mediated oncogenicity remain poorly understood. Here, we show that HER2∆16 expression is not exclusive to the clinically HER2+ subtype and associates with a poor clinical outcome in breast cancer. To understand how HER2 variants modulated the tumor microenvironment, we generated transgenic mouse models expressing either proto-oncogenic HER2 or HER2Δ16 in the mammary epithelium. We found that HER2∆16 tumors were immune cold, characterized by low immune infiltrate and an altered cytokine profile. Using an epithelial cell surface proteomic approach, we identified ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) as a functional regulator of the immune cold microenvironment. We generated a knock-in model of HER2Δ16 under the endogenous promoter to understand the role of Enpp1 in aggressive HER2+ breast cancer. Knockdown of Enpp1 in HER2Δ16-derived tumor cells resulted in decreased tumor growth, which correlated with increased T-cell infiltration. These findings suggest that HER2Δ16-dependent Enpp1 activation associates with aggressive HER2+ breast cancer through its immune modulatory function. Our study provides a better understanding of the mechanisms underlying HER2Δ16-mediated oncogenicity and highlights ENPP1 as a potential therapeutic target in aggressive HER2+ breast cancer.


Zinc in Cancer Therapy Revisited.
Zinc is a trace element, which is abundant in nature. It is also an essential and important micronutrient found in many foods. It has a role in multiple bodily processes including wound healing and boosting of the immune system. This review shows evidence of zinc deficiency in cancer patients of all types, a deficiency that correlates with disease severity and negatively correlates with survival rates. Lower zinc levels led to more severe and advanced disease symptoms and to lower survival rates. Zinc is a nanoparticle and acts as a photosensitizer in photodynamic therapy in various combinations with other substances. It also shows incredible cytotxicity and tumor suppressive ability in studies conducted both in vitro and in vivo as well as in studies conducted in humans. This result is shown in all types of cancer tested. Zinc shows incredible toxicity toward cancer cells without showing any side effects toward healthy cells. It is recommended that zinc be added to cancer treatment regimens to alleviate zinc deficiency in cancer patients and perhaps to treat cancer as a whole.


Lateral photovoltaic effect in flexible free-standing reduced graphene oxide film for self-powered position-sensitive detection.
Lightweight, simple and flexible self-powered photodetectors are urgently required for the development and application of advanced optical systems for the future of wearable electronic technology. Here, using a low-temperature reduction process, we report a chemical approach for producing freestanding monolithic reduced graphene oxide papers with different gradients of the carbon/oxygen concentration ratio. We also demonstrate a novel type of freestanding monolithic reduced graphene oxide self-powered photodetector based on a symmetrical metal-semiconductor-metal structure. Upon illumination by a 633-nm continuous wave laser, the lateral photovoltage is observed to vary linfearly with the laser position between two electrodes on the reduced graphene oxide surface. This result may suggest that the lateral photovoltaic effect in the reduced graphene oxide film originates from the built-in electric field by the combination of both the photothermal electric effect and the gradient of the oxygen-to-carbon composition. These results represent substantial progress toward novel, chemically synthesized graphene-based photosensors and suggest one-step integration of graphene-based optoelectronics in the future.


Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation.
The hepatic response to systemic injury is characterized by a co-ordinated increase in the expression of several, functionally essential plasma proteins. The factors responsible for initial hepatic stimulation have been identified and include the cytokines IL-1 (interleukin-1), tumor necrosis factor alpha (TNF alpha), IL-6 (interleukin-6), hepatocyte-stimulating factor-III (HSF-III) as well as corticosteroids. The absolute level of expression of the regulated proteins appears to be modulated by the pre-existing hepatic hormonal environment and changes to that environment that occur during acute phase reactions. The specific effects of glucocorticoids, IL-1 and activation of protein kinase C are addressed in this study. In order to predict the phenotype of liver response in acute phase, the hepatic activities of all inflammatory cytokines present must be established. Moreover, it must be recognized that the hepatic environment itself can modulate the anabolic response of the liver to these cytokines. The same considerations are needed when determining the changes seen during the progression to chronic inflammation.


Characteristics of a hepatitis C patient cohort at a specialized tertiary care facility: Identifying criteria to improve the allocation of public health resources.
Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clínicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.


Gemcitabine and vinorelbine combination in platinum-sensitive recurrent ovarian cancer.
Most patients with ovarian cancer are candidates for second-line or salvage treatments often for prolonged periods. Patients with platinum-sensitive disease can benefit from a platinum retreatment with a likelihood of response dependents on the treatment-free interval. Alternative agents and combination chemotherapy are potential therapeutic approaches. At our institution, we carried out a phase II trial to evaluate feasibility, efficacy, and toxicity of gemcitabine and vinorelbine combination in recurrent ovarian carcinoma. The aim of the present study was to evaluate the role of this combination in patients with platinum-sensitive disease. Patients with platinum-sensitive disease recurring after 1 or more lines of platinum-based chemotherapy were included. Vinorelbine at 25 mg/m followed by gemcitabine at 1000 mg/m was administered intravenously on days 1 and 8 every 3 weeks. Response Evaluation Criteria in Solid Tumors and cancer antigen 125 test (CA-125 Kinetics [Rustin criteria]) were adopted to classify responses. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria. Thirty-nine patients were eligible. Platinum-free interval (PFI) was 6 to 12 months in 13 patients (33.3%; PFI 6-12) and more than 12 months in 26 patients (66.7%; PFI > 12). The overall response rate was 48.7%, with 6 complete responses. Median response duration was 38 weeks. The response rate was 23% in PFI 6-12 and 62% in PFI >12. The most frequently observed toxicity was hematological, with 23% of the patients having grade 3 or 4 neutropenia. Gemcitabine and vinorelbine combination is effective and well tolerated in recurrent platinum-sensitive ovarian cancer. It may represent an option in the management of these patients because the chronic nature of the disease.


Global QCD Analysis of Pion Parton Distributions with Threshold Resummation.
We perform the first global QCD analysis of pion valence, sea quark, and gluon distributions within a Bayesian Monte Carlo framework with threshold resummation on Drell-Yan cross sections at next-to-leading log accuracy. Exploring various treatments of resummation, we find that the large-x asymptotics of the valence quark distribution ∼(1-x)^{β_{v}} can differ significantly, with β_{v} ranging from ≈1 to >2.5 at the input scale. Regardless of the specific implementation, however, the resummation induced redistribution of the momentum between valence quarks and gluons boosts the total momentum carried by gluons to ≈40%, increasing the gluon contribution to the pion mass to ≈40 MeV.


Behavioral and immunohistochemical characterization of rapid reconditioning following extinction of contextual fear.
A fundamental property of extinction is that the behavior that is suppressed during extinction can be unmasked through a number of postextinction procedures. Of the commonly studied unmasking procedures (spontaneous recovery, reinstatement, contextual renewal, and rapid reacquisition), rapid reacquisition is the only approach that allows a direct comparison between the impact of a conditioning trial before or after extinction. Thus, it provides an opportunity to evaluate the ways in which extinction changes a subsequent learning experience. In five experiments, we investigate the behavioral and neurobiological mechanisms of postextinction reconditioning. We show that rapid reconditioning of unsignaled contextual fear after extinction in male Long-Evans rats is associative and not affected by the number or duration of extinction sessions that we examined. We then evaluate c-Fos expression and histone acetylation (H4K8) in the hippocampus, amygdala, prefrontal cortex, and bed nucleus of the stria terminalis. We find that in general, initial conditioning has a stronger impact on c-Fos expression and acetylation than does reconditioning after extinction. We discuss implications of these results for theories of extinction and the neurobiology of conditioning and extinction.


[A new simplified method for implanting temporary epicardial electrodes].
The authors present a new simplified method for implanting temporary epicardial electrodes, which can be carried out extemporaneously during operation from a standard electrode. The modified electrode showed an improvement over the standard electrode in the myocardial thresholds with respect to milliamperage as well as voltage at both atrial and ventricular levels (p less than 0.05 for atrial and P less than 0.005 for ventricular). On the 7th day after placement the modified electrode appears to be more reliable than the standard electrode and demonstrates less degeneration of its threshold and current characteristics (P less than 0.05).


New genotypes of Liao ning virus (LNV) in Australia exhibit an insect-specific phenotype.
Liao ning virus (LNV) was first isolated in 1996 from mosquitoes in China, and has been shown to replicate in selected mammalian cell lines and to cause lethal haemorrhagic disease in experimentally infected mice. The first detection of LNV in Australia was by deep sequencing of mosquito homogenates. We subsequently isolated LNV from mosquitoes of four genera (Culex, Anopheles, Mansonia and Aedes) in New South Wales, Northern Territory, Queensland and Western Australia; the earliest of these Australian isolates were obtained from mosquitoes collected in 1988, predating the first Chinese isolates. Genetic analysis revealed that the Australian LNV isolates formed two new genotypes: one including isolates from eastern and northern Australia, and the second comprising isolates from the south-western corner of the continent. In contrast to findings reported for the Chinese LNV isolates, the Australian LNV isolates did not replicate in vertebrate cells in vitro or in vivo, or produce signs of disease in wild-type or immunodeficient mice. A panel of human and animal sera collected from regions where the virus was found in high prevalence also showed no evidence of LNV-specific antibodies. Furthermore, high rates of virus detection in progeny reared from infected adult female mosquitoes, coupled with visualization of the virus within the ovarian follicles by immunohistochemistry, suggest that LNV is transmitted transovarially. Thus, despite relatively minor genomic differences between Chinese and Australian LNV strains, the latter display a characteristic insect-specific phenotype.


Indwelling cephalic or saphenous vein catheter use for regional limb perfusion in 44 horses with synovial injury involving the distal aspect of the limb.
To describe indwelling cephalic or saphenous vein catheter use for intravenous regional limb perfusion (ID-IV-RLP) to treat horses with synovial injury (contamination/infection) of the distal aspect of the limb. Retrospective case series. Horses (n = 44; 45 limbs) treated with proximal ID-IV-RLP. Horses had ID-IV-RLP using a cephalic (21 limbs) or saphenous (24 limbs) vein. Amikacin was the most frequently used antibiotic. Number of perfusions ranged from 3 to 21 (median 7). A cast was applied to 14 injured limbs (1 tube cast, 1 full-limb cast, 2 foot casts, and 10 half-limb casts). Synovial sepsis of the distal portion of 87% of limbs (39) resolved, and 61% of horses returned to soundness. Catheter-related complications occurred in 27% of the limbs but were not significantly associated with outcome. Presence of osteomyelitis was significantly associated with a poor outcome. ID-IV-RLP using the cephalic or saphenous vein is an alternative to traditional RLP. An indwelling catheter provided prolonged venous access and facilitated successive perfusions.


Learned phase coded aperture for the benefit of depth of field extension.
Modern consumer electronics market dictates the need for small-scale and high-performance cameras. Such designs involve trade-offs between various system parameters. In such trade-offs, Depth Of Field (DOF) is a significant issue very often. We propose a computational imaging-based technique to overcome DOF limitations. Our approach is based on the synergy between a simple phase aperture coding element and a convolutional neural network (CNN). The phase element, designed for DOF extension using color diversity in the imaging system response, causes chromatic variations by creating a different defocus blur for each color channel of the image. The phase-mask is designed such that the CNN model is able to restore from the coded image an all-in-focus image easily. This is achieved by using a joint end-to-end training of both the phase element and the CNN parameters using backpropagation. The proposed approach provides superior performance to other methods in simulations as well as in real-world scenes.


Adenosine potentiates human lung mast cell tissue plasminogen activator activity.
We investigated whether adenosine, a potent contributor to the regulation of pulmonary function, can modulate human lung mast cell (HLMC) fibrinolytic activity. Tissue plasminogen activator (tPA) activity and tPA transcript expression levels from a human mast cell line (HMC-1) and HLMC were monitored following adenosine application. Adenosine potentiated mast cell tPA activity and tPA gene expression in a dose-dependent manner. Adenosine effects were abolished in the presence of adenosine deaminase. HMC-1 cells and HLMC predominantly expressed adenosine A(2A) and A(2B) receptor transcripts (A(2B) ≈ A(2A) > A(3) >> A(1)). Pharmacological and signaling studies suggest that the A(2A) receptor is the major subtype accounting for adenosine-induced mast cell tPA activity. Finally, the supernatant from HMC-1 cells and HLMC treated with adenosine (for 24 h) significantly increased fibrin clot lysis, whereas ZM241385, an A(2A) receptor antagonist, abolished this effect. To our knowledge, this study provides the first data to demonstrate the potentiating effect of adenosine on mast cell tPA activity and fibrin clot lysis.


Topical antibiotics and minor skin trauma.
Recent double-blind controlled studies show that the application of a neomycin-bacitracin-polymyxin preparation reduces the incidence of staphylococcal and streptococcal infection of minor skin trauma. Allergic sensitization to neomycin is rare. Systemic side effects occur only with improper massive exposure. Resistant strains have appeared only in "closed populations." It is concluded that topical antibiotic combinations are safe and effective.