A possible mechanism for the formation of 14CO2 via 2-methoxyacetic acid in mice exposed to 14C-labeled 2-methoxyethanol.
Small amounts (6-12%) of radioactivity administered by gavage as 14C-labeled 2-methoxyethanol (2-ME) or 2-methoxyacetic acid (2-MAA) to pregnant mice are exhaled as 14CO2 as well as accumulated in tissues that are highly active in the synthesis of macromolecules (Sleet et al., Toxicol. Appl. Pharmacol. 84, 25-35, 1986; Mebus et al., Toxicol. Appl. Pharmacol. 112, 87-94, 1992). In addition, pregnant CD-1 mice similarly administered 13C-labeled 2-ME excrete urinary metabolites that may arise from incorporation of a coenzyme A thioester of 2-MAA into the Krebs cycle, forming methoxycitrate (Sumner et al., Chem. Res. Toxicol. 5, 553-560, 1992). Based on these previously published observations, we propose a mechanism for the further metabolism of methoxycitrate that is consistent with the detection of 14CO2 after administering either [1-14C]2-MAA, [2-14C]2-ME, or [methoxy-14C]2-ME to mice. This postulated pathway may also explain the tissue-specific accumulation of radioactivity arising from [14C]2-ME.


Size-dependent optical behavior of disordered nanostructures on glass substrates.
We demonstrate the distinctive optical properties of disordered nanostructures on glass substrates in accordance with changes in the average size of the nanostructures. Dissimilar sizes of nanostructures were fabricated by using different thicknesses of thermally dewetted Ag nanoparticles as etch masks. Unlike a flat glass substrate, the nanostructured glasses (NSGs) show a changed optical characteristic. By increasing the size of the nanostructures, the wavelength of the peak transmittance of about 99% gradually moved from 730 to 2000 nm. To clearly discern the effect of the different sizes of nanostructures, the normalized angle-dependent transmittance spectra of the NSGs were analyzed. Only if the size becomes relatively larger than the wavelength of the incident light are the transmittance spectra more strongly affected by the incident angle as well as by the relative size, rather than by the Fresnel reflection.


A mathematical model of vowel identification by users of cochlear implants.
A simple mathematical model is presented that predicts vowel identification by cochlear implant users based on these listeners' resolving power for the mean locations of first, second, and/or third formant energies along the implanted electrode array. This psychophysically based model provides hypotheses about the mechanism cochlear implant users employ to encode and process the input auditory signal to extract information relevant for identifying steady-state vowels. Using one free parameter, the model predicts most of the patterns of vowel confusions made by users of different cochlear implant devices and stimulation strategies, and who show widely different levels of speech perception (from near chance to near perfect). Furthermore, the model can predict results from the literature, such as Skinner, et al. [(1995). Ann. Otol. Rhinol. Laryngol. 104, 307-311] frequency mapping study, and the general trend in the vowel results of Zeng and Galvin's [(1999). Ear Hear. 20, 60-74] studies of output electrical dynamic range reduction. The implementation of the model presented here is specific to vowel identification by cochlear implant users, but the framework of the model is more general. Computational models such as the one presented here can be useful for advancing knowledge about speech perception in hearing impaired populations, and for providing a guide for clinical research and clinical practice.


Intracellular Ca transients in rat cardiac myocytes: role of Na-Ca exchange in excitation-contraction coupling.
Membrane current and intracellular Ca concentration ([Ca]i) transients were recorded from isolated rat ventricular myocytes under voltage-clamp control. The cells were dialyzed by the patch pipette solution, which contained the fluorescent Ca indicator indo-1 and 0.5 mM Na. Under these experimental conditions, Ca entry via Na-Ca exchange did not appear to be appreciable even in the absence of extracellular Na. Increasing the duration of voltage-clamp pulses from 5 to 80 ms produced [Ca]i transients of increasing amplitude, while the peak Ca current was not changed. This duration dependence of the [Ca]i transient was most demonstrable at more negative test potentials (e.g., -20 to -30 mV) and was not qualitatively modified by Na-free solutions. This latter result indicates that Ca extrusion by Na-Ca exchange is not responsible for the smaller [Ca]i transients observed when the membrane is repolarized after very brief depolarizations. Although the peak Ca current was not changed by increasing pulse duration, the integrated Ca current was increased. These observations are consistent with a Ca-release mechanism in cardiac excitation-contraction coupling in which 1) the Ca-release process can be modulated by membrane potential or 2) the Ca entering the cell via Ca channels has a preferential access [compared with Ca from the sarcoplasmic reticulum (SR)] to the site(s) that control SR Ca release. The role of Na-Ca exchange in the decline of [Ca]i during relaxation was also explored. Removal of extracellular Na (Nao) resulted in 20% slowing of the decline in [Ca]i during relaxation. From this, we conclude that the Na-Ca exchange competes with SR to remove Ca from the cytoplasm and that under our control conditions the exchanger may account for 20% of this decline. The Nao dependence of relaxation was reduced at more positive membrane potentials and increased by SR Ca loading.


Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR.
Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PKR). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position -88 in the MxA gene promoter in self-limiting HCV infection (OR=0.56; 95% CI: 0.35-0.8; P=0.010) and in nonresponders to therapy (OR=0.49; 95% CI: 0.25-0.95; P=0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR=0.22 95% CI: 0.07-0.67; P=0.002). A polymorphism in the 3'-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR=0.43; 95% CI: 0.21-0.86; P=0.010). A polymorphism at position -168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR=2.75; 95% CI: 1.45-5.24; P=0.002). Further associations were found with a CGG trinucleotide repeat in the 5'UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome.


Mask-based second-generation connectivity and attribute filters.
Connected filters are edge-preserving morphological operators, which rely on a notion of connectivity. This is usually the standard 4 and 8-connectivity, which is often too rigid since it cannot model generalized groupings such as object clusters or partitions. In the set-theoretical framework of connectivity, these groupings are modeled by the more general second-generation connectivity. In this paper, we present both an extension of this theory, and provide an efficient algorithm based on the Max-Tree to compute attribute filters based on these connectivities. We first look into the drawbacks of the existing framework that separates clustering and partitioning and is directly dependent on the properties of a preselected operator. We then propose a new type of second-generation connectivity termed mask-based connectivity which eliminates all previous dependencies and extends the ways the image domain can be connected. A previously developed Dual-Input Max-Tree algorithm for area openings is adapted for the wider class of attribute filters on images characterized by second-generation connectivity. CPU-times for the new algorithm are comparable to the original algorithm, typically deviating less than 10 percent either way.


Effects of a supplemented hypoproteic diet in chronic kidney disease.
We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD). We performed a prospective, open-label, parallel, randomized, controlled trial. The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania. A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups. Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d). Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and "death" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline. In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted. SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD.


Chemotherapy-Induced Nausea and Vomiting: A Narrative Review to Inform Dietetics Practice.
Chemotherapy-induced nausea and vomiting (CINV) are common symptoms experienced by patients with cancer that influence nutrition. They exert a detrimental effect on dietary intake, risk of malnutrition, and quality of life. Whereas CINV are primarily managed with medication, nutrition and dietetics practitioners play an important role in the management of CINV-related complications such as reduced dietary intake. This review discusses the burden of nausea and vomiting that patients with cancer can experience, including the effect on quality of life, nutritional status, and treatment outcomes. Implications for dietetics practice include the need to explore the nature of reported symptoms, identify predisposing risk factors, and to consider the use of a variety of interventions that are individualized to a patient's symptoms. There are little clinical data regarding effective dietetic interventions for nausea and vomiting. In summary, this review discusses dietetics-related issues surrounding CINV, including the pathophysiology, risk factors, prevalence, and both pharmacologic and dietetic treatment options.


Role of human nucleoside transporters in the cellular uptake of two inhibitors of IMP dehydrogenase, tiazofurin and benzamide riboside.
Benzamide riboside (BR) and tiazofurin (TR) are converted to analogs of NAD that inhibit IMP dehydrogenase (IMPDH), resulting in cellular depletion of GTP and dGTP and inhibition of proliferation. The current work was undertaken to identify the human nucleoside transporters involved in cellular uptake of BR and TR and to evaluate their role in cytotoxicity. Transportability was examined in Xenopus laevis oocytes and Saccharomyces cerevisiae that produced individual recombinant human concentrative nucleoside transporter (CNT) and equilibrative nucleoside transporter (ENT) types (hENT1, hENT2, hCNT1, hCNT2, or hCNT3). TR was a better permeant than BR with a rank order of transportability in oocytes of hCNT3 >> hENT1 > hENT2 > hCNT2 >> hCNT1. The concentration dependence of inhibition of [(3)H]uridine transport in S. cerevisiae by TR exhibited lower K(i) values than BR: hCNT3 (5.4 versus 226 microM), hENT2 (16 versus 271 microM), hENT1 (57 versus 168 microM), and hCNT1 (221 versus 220 microM). In cytotoxicity experiments, BR was more cytotoxic than TR to cells that were either nucleoside transport-defective or -competent, and transport-competent cells were more sensitive to both drugs. Exposure to nitrobenzylmercaptopurine ribonucleoside conferred resistance to BR and TR cytotoxicity to hENT1-containing CEM cells, thereby demonstrating the importance of transport capacity for manifestation of cytoxicity. A breast cancer cell line with mutant p53 exhibited 9-fold higher sensitivity to BR than the otherwise similar cell line with wild-type p53, suggesting that cells with mutant p53 may be potential targets for IMPDH inhibitors. Further studies are warranted to determine whether this finding can be generalized to other cell types.


Annexin V binds to the actin-based cytoskeleton at the plasma membrane of activated platelets.
Immunocytochemical studies demonstrate that annexin V relocates to the plasma membranes of intact stimulated blood platelets. Anti-annexin V antibodies label the cytoplasmic side of the substrate-adherent plasma membrane of mechanically unroofed, glass-activated platelets and colocalize with actin. In addition, crosslinking experiments using detergent-solubilized membranes of activated platelets have identified an 85-kDa complex containing annexin V. The 85-kDa complex is also recognized by antibodies against actin, suggesting that annexin V interacts with actin. In addition, annexin V was found to associate with filamentous actin in the presence of millimolar Ca(2+). Annexin V was also shown by immunofluorescence microscopy to be associated with platelet cytoskeletons, colocalizing with actin in the presence of micromolar Ca(2+). These findings provide the first evidence for annexin V binding to the plasma membrane and to the actin-based cytoskeleton in activated platelets and indicate that annexin V may function in both cytoskeletal and membrane domains.


Active wide-field illumination for high-throughput fluorescence lifetime imaging.
Wide-field fluorescence lifetime imaging allows for fast imaging of large sample areas at the cost of low sensitivity to weak fluorescence signals. To overcome this challenge, we developed an active wide-field illumination (AWFI) strategy to optimize the impinging spatial intensity for acquiring optimal fluorescence signals over the whole sample. We demonstrated the ability of AWFI to accurately estimate lifetimes from a multiwell plate sample with concentrations ranging over two orders of magnitude. We further reported its successful application to a quantitative Förster resonance energy transfer lifetime cell-based assay. Overall, this method allows for enhanced accuracy in lifetime-based imaging at high acquisition speed over samples with large fluorescence intensity distributions.


Hepatic artery ligation and cytotoxic infusion in treatment of liver neoplasms.
Since 1970, 38 patients with multiple primary or secondary liver neoplasms have been treated by hepatic artery ligation and distal cytotoxic infusion with fluorouracil. There have been two postoperative deaths. Although liver enzymes (alkaline phosphatase, serum glutamic oxaloacetic transaminase, and lactic dehydrogenase) rise markedly during the first three days, they usually return to preoperative levels within eight days. The median survival time of all patients, including the two postoperative deaths, was 13.3 months. The longest patient survival was 44 months. In the eight patients still living, the median survival time is 17 months, ranging from 11 to 27 months. Substantial palliation can be achieved by hepatic artery ligation and infusion with minimal morbidity and mortality.


Compact passively Q-switched Raman laser at 1176 nm and yellow laser at 588 nm using Nd3+:YAG/Cr4+:YAG composite crystal.
Compact passively Q-switched YVO4 first Stokes Raman laser and its frequency doubling laser were reported by using Nd3+:YAG/Cr4+:YAG composite crystal for what is believed to be the first time. Nanosecond lasers at 1176 and 588 nm were obtained. At the incident pump power of 7.84 W, the average output power at 1176 nm was 423 mW with a pulse width of 1.32 ns and the pulse repetition frequency (PRF) of 13.7 kHz. By applying a KTP crystal, an intracavity second harmonic generation (SHG) laser at 588 nm also was realized. With an incident pump power of 8.95 W, we obtained 105.3 mW average output power of a yellow laser corresponding to the pulse width of 4.95 ns and the PRF of 10.75 kHz. In addition, the composite crystal efficiently compacted the resonant cavity.


Integrating tuberculosis and mental health services: global receptivity of national tuberculosis program directors.
<sec id="st1"> <title>SETTING</title> A global survey of National Tuberculosis Program (NTP) directors. </sec> <sec id="st2"> <title>OBJECTIVES</title> To assess the perceived mental health needs of persons with tuberculosis (TB), current practices, and receptivity to integrating evidence-based mental and substance use treatment into national TB guidelines. </sec> <sec id="st3"> <title>DESIGN</title> Semi-structured survey of NTP directors from 26 countries of all income levels using a standardized questionnaire. </sec> <sec id="st4"> <title>RESULTS</title> Of the 26 countries, 21 were classified as high incidence and/or burden countries for TB, TB and human immunodeficiency virus coinfection, and/or drug-resistant TB. Two NTPs included routine screening for any mental disorder, four assessed alcohol or drug use, and five had standard protocols for the co-management of disorders. If effective and low-cost integrated care models were available, 17 NTP directors felt that it was highly likely, and five somewhat likely, that their NTPs would integrate mental health treatment into national TB guidelines and services. The main perceived barriers to service integration were limited capacity, not recognizing mental health as a problem, insufficient resources, and TB-related social stigma. </sec> <sec id="st5"> <title>CONCLUSIONS</title> NTPs currently do not address mental disorders as part of routine practice. Nevertheless, receptivity is high, which creates a ripe opportunity to integrate the management of TB and mental disorders into the policies and guidelines of NTPs worldwide. </sec>.


Droplets Sliding down a Vertical Surface under Increasing Horizontal Forces.
We have investigated the retention forces of liquid drops on rotating, vertical surfaces. We considered two scenarios: in one, a horizontal, centrifugal force pushes the drop toward the surface (?pushed drop? case), and in the other, a horizontal, centrifugal force pulls the drop away from the surface (?pulled drop? case). Both drops slide down as the centrifugal force increases, although one expects that the pushed drop should remain stuck to the surface. Even more surprising, when the centrifugal force is low, the pushed drop moves faster than the pulled drop, but when the centrifugal force is high, the pushed drop moves much slower than the pulled drop. We explain these results in terms of interfacial modulus between the drop and the surface.


Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies.
Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary levels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.


Adoption of a High-Impact Innovation in a Homogeneous Population.
Adoption of innovations, whether new ideas, technologies, or products, is crucially important to knowledge societies. The landmark studies of adoption dealt with innovations having great societal impact (such as antibiotics or hybrid crops) but where determining the utility of the innovation was straightforward (such as fewer side effects or greater yield). Recent large-scale studies of adoption were conducted within heterogeneous populations and focused on products with little societal impact. Here, we focus on a case with great practical significance: adoption by small groups of highly trained individuals of innovations with large societal impact but for which it is impractical to determine the true utility of the innovation. Specifically, we study experimentally the adoption by critical care physicians of a diagnostic assay that complements current protocols for the diagnosis of life-threatening bacterial infections and for which a physician cannot estimate the true accuracy of the assay based on personal experience. We show through computational modeling of the experiment that infection-spreading models-which have been formalized as generalized contagion processes-are not consistent with the experimental data, while a model inspired by opinion models is able to reproduce the empirical data. Our modeling approach enables us to investigate the efficacy of different intervention schemes on the rate and robustness of innovation adoption in the real world. While our study is focused on critical care physicians, our findings have implications for other settings in education, research, and business, where small groups of highly qualified peers make decisions about the adoption of innovations whose utility is difficult if not impossible to gauge.


The first gene-encoded amphibian neurotoxin.
Many gene-encoded neurotoxins with various functions have been discovered in fish, reptiles, and mammals. A novel 60-residue neurotoxin peptide (anntoxin) that inhibited tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel (VGSC) was purified and characterized from the skin secretions of the tree frog Hyla annectans (Jerdon). This is the first gene-encoded neurotoxin found in amphibians. The IC50 of anntoxin for the TTX-S channel was about 3.4 microM. Anntoxin shares sequence homology with Kunitz-type toxins but contains only two of three highly conserved cysteine bridges, which are typically found in these small, basic neurotoxin modules, i.e. snake dendrotoxins. Anntoxin showed an inhibitory ability against trypsin with an inhibitory constant (Ki) of 0.025 microM. Anntoxin was distributed in skin, brain, stomach, and liver with a concentration of 25, 7, 3, and 2 microg/g wet tissue, respectively. H. annectans lives on trees or other plants for its entire life cycle, and its skin contains the largest amount of anntoxin, which possibly helps defend against various aggressors or predators. A low dose of anntoxin was found to induce lethal toxicity for several potential predators, including the insect, snake, bird, and mouse. The tissue distribution and functional properties of the current toxin may provide insights into the ecological adaptation of tree-living amphibians.


Mechanisms of contour perception in monkey visual cortex. I. Lines of pattern discontinuity.
We have studied the mechanism of contour perception by recording from neurons in the visual cortex of alert rhesus monkeys. In order to assess the relationship between neural signals and perception, we compared the responses to edges and lines with the responses to patterns in which human observers perceive a contour where no line or edge is given (anomalous contour), such as the border between gratings of thin lines offset by half a cycle. With only one exception out of 60, orientation-selective neurons in area V1 did not signal the anomalous contour. Many neurons failed to respond to this stimulus at all, others responded according to the orientation of the grating lines. In area V2, 45 of 103 neurons (44%) signaled the orientation of the anomalous contour. Sixteen did so without signaling the orientation of the inducing lines. Some responded better to anomalous contours than to the optimum bars or edges. Preferred orientations and widths of tuning for anomalous contour and bar or edge were found to be highly correlated, but not identical, in each neuron. Similar to perception, the neuronal responses depended on a minimum number of lines inducing the contour, but not so much on line spacing, and tended to be weaker when the lines were oblique rather than orthogonal to the border. With oblique lines, the orientations signaled were biased towards the orientation orthogonal to the lines, as in the Zöllner illusion. We conclude that contours may be defined first at the level of V2. While the unresponsiveness of neurons in V1 to this type of anomalous contour is in agreement with linear filter predictions, the responses of V2 neurons need to be explained. We assume that they sum the signals of 2 parallel paths, one that defines edges and lines and another that defines anomalous contours by pooling signals from end-stopped receptive fields oriented mainly orthogonal to the contour.


The impact of in-work tax credit for families on self-rated health in adults: a cohort study of 6900 New Zealanders.
In-work tax credit (IWTC) for families, a welfare-to-work policy intervention, may impact health status by improving income and employment. Most studies estimate that IWTCs in the USA and the UK have no effect on self-rated health (SRH) and several other health outcomes, but these estimates may be biased by confounding. The current study estimates the impact of one such IWTC intervention (called In-Work Tax Credit) on SRH in adults in New Zealand, controlling more fully for confounding. We used data from seven waves (2002-2009) of the Survey of Family, Income and Employment, restricted to a balanced panel of adults in families. The exposures, eligibility for IWTC and the amount of IWTC a family was eligible for, were derived for each wave by applying government eligibility and entitlement criteria. The outcome, SRH, was collected annually. We used fixed effects regression analyses to eliminate time-invariant confounding and adjusted for measured time-varying confounders. Becoming eligible for IWTC was associated with no detectable change in SRH over the past year (β=0.001, 95% CI -0.022 to 0.023). A $1000 increase in the IWTC amount a family was eligible for increased SRH by 0.003 units (95% CI -0.005 to 0.011). This study found that becoming eligible for IWTC or a substantial increase in the IWTC amount was not associated with any detectable difference in SRH over the short term. Future research should investigate the impact of IWTC on health over the longer term.


A comprehensive catalog of predicted functional upstream open reading frames in humans.
Upstream open reading frames (uORFs) latent in mRNA transcripts are thought to modify translation of coding sequences by altering ribosome activity. Not all uORFs are thought to be active in such a process. To estimate the impact of uORFs on the regulation of translation in humans, we first circumscribed the universe of all possible uORFs based on coding gene sequence motifs and identified 1.3 million unique uORFs. To determine which of these are likely to be biologically relevant, we built a simple Bayesian classifier using 89 attributes of uORFs labeled as active in ribosome profiling experiments. This allowed us to extrapolate to a comprehensive catalog of likely functional uORFs. We validated our predictions using in vivo protein levels and ribosome occupancy from 46 individuals. This is a substantially larger catalog of functional uORFs than has previously been reported. Our ranked list of likely active uORFs allows researchers to test their hypotheses regarding the role of uORFs in health and disease. We demonstrate several examples of biological interest through the application of our catalog to somatic mutations in cancer and disease-associated germline variants in humans.


Role of 3 Tesla MR Neurography and CT-guided Injections for Pudendal Neuralgia: Analysis of Pain Response.
Magnetic resonance neurography (MRN) has an increasing role in the diagnosis and management of pudendal neuralgia, a neurogenic cause of chronic pelvic pain. The objective of this research was to determine the role of MRN in predicting improved pain outcomes following computed tomography (CT)-guided perineural injections in patients with pudendal neuralgia. This study used a retrospective cross-sectional study design. The research was conducted at a large academic hospital. Patients: Ninety-one patients (139 injections) who received MRN and CT-guided pudendal blocks were analyzed. A 3Tesla (T) scanner was used to evaluate the lumbosacral plexus for pudendal neuropathy. Prior to receiving a CT-guided pudendal perineural injection, patients were given pain logs and asked to record pain on a visual analog scale. MRN findings for pudendal neuropathy were compared to the results of the CT-guided pudendal nerve blocks. Injection pain responses were categorized into 3 groups - positive block, possible positive block, and negative block.Statistical Tests: A chi-square test was used to test any association, and a Cochran-Armitage trend test was used to test any trend. Significance level was set at .05. All analyses were done in SAS Version 9.4 (SAS Institute, Inc., Cary, NC). Ninety-one patients (139 injections) who received MRN were analyzed. Of these 139 injections, 41 were considered positive (29.5%), 52 of 139 were possible positives (37.4%), and 46 of 139 were negative blocks (33.1%). Of the patients who had a positive pudendal block, no significant difference was found between the MRN result and the pudendal perineural injection response (P = .57). Women had better overall response to pudendal blocks, but this response was not associated with MRN findings (P = .34). However, positive MRN results were associated with better pain response in men (P = .005). Patients who reported bowel dysfunction also had a better response to pudendal perineural injection (P = .02). Some limitations include subjectivity of pain reporting, reporting consistency, absence of a control group, and the retrospective nature of the chart review. Pudendal perineural injections improve pain in patients with pudendal neuralgia and positive MRN results are associated with better response in men. MRI, MRN, CT injection, pudendal neuralgia, pudendal nerve, pelvic pain, chronic pelvic pain, pudendal neuropathy.


Metallome evolution in ageing C. elegans and a copper stable isotope perspective.
Ageing is accompanied by important chemical deregulations resulting in bodily metal imbalances. The way and extent to which these deregulations are associated with ageing processes are however poorly understood and their use as potential biomarkers of ageing has not been investigated. In this study, we report whole-body elementary concentrations and copper and zinc isotopic compositions of Caenorhabditis elegans in ageing wild type (i.e.'normal'-lived) and mutant (i.e. short and long-lived) strains. We show that the strains are characterized by different levels of mutation-related variations such as in phosphorus and magnesium as well as in zinc isotopic composition. During ageing, strains are affected by elemental age-related variations, such as an increase in calcium and iron concentrations and a decrease in the copper isotopic composition and concentration for long-lived mutants. The deregulated metabolism of copper seems to be connected to ageing probably in association with the production of reactive oxygen species. We emphasize that the copper stable isotope composition could serve as a biomarker of normal or accelerated ageing in the future.


Physical aggression is associated with heightened social reflection impulsivity.
Physical aggression harms individuals, disrupts social functioning across multiple forms of psychopathology, and leads to destruction within communities. Physical aggression is associated with aberrations in the interpretation of ambiguous information. However, the specific cognitive mechanisms supporting this link remain elusive. One potentially relevant cognitive mechanism is reflection impulsivity, the amount of information gathered during decision-making. Reflection impulsivity characterizes how individuals resolve ambiguity in the process of forming judgments when multiple interpretations of a stimulus are possible. In a sample of 98 incarcerated men, we examined reflection impulsivity using a novel social information sampling task. The primary aim of the study was to investigate the relationship between physical aggression and social reflection impulsivity. Additionally, we assessed the frequency of different social judgments (hostile vs. benign), the extent to which reflection impulsivity varied in the context of these different social judgments, and subjective certainty about social judgments. Finally, we investigated whether social reflection impulsivity moderated the relationship between physical aggressiveness and violent crime. Results indicated that more physically aggressive individuals displayed heightened social reflection impulsivity, which was amplified in the context of hostile judgments. Moreover, more physically aggressive individuals were more certain about their hostile judgments and more certain when judgments were made with unconstrained access to behavioral information. Finally, impulsive hostile judgments in physically aggressive individuals related to a more extensive history of assault charges. These findings suggest that physically aggressive individuals exhibit deficits in information gathering, leading to ill-informed and inflexible social judgments. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


A Hypoxia-Inducible HIF1-GAL3ST1-Sulfatide Axis Enhances ccRCC Immune Evasion via Increased Tumor Cell-Platelet Binding.
Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer and the major cause of mortality for individuals with von Hippel-Lindau (VHL) disease. ccRCC is characterized most frequently by inactivation of VHL tumor suppressor protein that mediates degradation of the alpha subunit of the hypoxia-inducible factor (HIF) transcription factor family. HIF has been implicated in disease progression and the aim of this study was to identify novel HIF target genes that may contribute to ccRCC. We show that GAL3ST1, an enzyme that catalyzes the sulfonation of the plasma membrane sulfolipid sulfatide, is among the top 50 upregulated genes in ccRCC tissue relative to matched normal tissue. Increased expression of GAL3ST1 in primary ccRCC correlates with decreased survival. We show that GAL3ST1 is a HIF target gene whose expression is induced upon VHL loss leading to the accumulation of its enzymatic product sulfatide. Notably, platelets bind more efficiently to renal cancer cells with high GAL3ST1-sulfatide expression than to GAL3ST1-sulfatide-negative counterparts, which protects ccRCC cells against natural killer cell-mediated cytotoxicity. These results suggest that GAL3ST1 is a HIF-responsive gene that may contribute to ccRCC development via promoting cancer cell evasion of immune surveillance. IMPLICATIONS: Cancer development is in part dependent on evasion of immune response. We identify a HIF target gene product GAL3ST1 that may play a role in this critical process.


Advection of Karenia brevis blooms from the Florida Panhandle towards Mississippi coastal waters.
Harmful Algal Blooms (HABs) of Karenia brevis have been documented along coastal waters of every state bordering the Gulf of Mexico (GoM). Some Gulf Coast locations, such as Florida and Texas, suffer from recurrent intense and spatially large blooms, while others such as Mississippi seem to rarely observe them. The main objective of this work is to understand the dynamics that led to the K. brevis bloom in Mississippi coastal waters in fall 2015. Blooms of K. brevis from the Florida Panhandle region are often advected westward towards the Mississippi-Alabama coast; however there is interannual variability in their presence and intensity in Mississippi coastal waters. The 2015 K. brevis bloom was compared to the 2007 Florida Panhandle K. brevis bloom, which showed a westward advection pattern, but did not intensify along the Mississippi coast. Cell counts and flow cytometry were obtained from the Mississippi Department of Marine Resources, Alabama Department of Public Health, Florida Fish and Wildlife Conservation Commission and The University of Southern Mississippi. Ocean color satellite imagery from the Moderate Resolution Imaging Spectroradiometer onboard the Aqua satellite was used to detect and delineate the blooms in 2007 and 2015. Two different regional applications of NCOM-Navy Coastal Ocean Model (1-km resolution NCOM-GoM/Gulf of Mexico and 6-km resolution NCOM-IASNFS/Intra Americas Sea Nowcast Forecast System) were used to understand the circulation and transport pathways. A Lagrangian particle tracking software was used to track the passive movement of particles released at different locations for both bloom events. Ancillary data (e.g., nutrients, wind, salinity, river discharge) from local buoys, monitoring stations and coincident oceanographic cruises were also included in the analysis. The blooms of K. brevis reached the Mississippi coast both years; however, the bloom in 2007 lasted only a few days and there is no evidence that it entered the Mississippi Sound. Two major differences were observed between both years. First, circulation patterns in 2015 resulting from an intense westward-northwestward that persisted until December allowed for continuous advection, whereas this pattern was not evident in 2007. Second, local river discharge was elevated throughout late fall 2015 while 2007 was below the average. Thus, elevated discharge may have provided sufficient nutrients for bloom intensification. These results illustrate the complex, but important interactions in coastal zones. Further, they emphasize the importance in establishing comprehensive HAB monitoring programs, which facilitate our understanding of nutrient and phytoplankton dynamics, and stress the importance for multi-agency cooperation across state boundaries.


Disruption of reconsolidation erases a fear memory trace in the human amygdala.
Memories become labile when recalled. In humans and rodents alike, reactivated fear memories can be attenuated by disrupting reconsolidation with extinction training. Using functional brain imaging, we found that, after a conditioned fear memory was formed, reactivation and reconsolidation left a memory trace in the basolateral amygdala that predicted subsequent fear expression and was tightly coupled to activity in the fear circuit of the brain. In contrast, reactivation followed by disrupted reconsolidation suppressed fear, abolished the memory trace, and attenuated fear-circuit connectivity. Thus, as previously demonstrated in rodents, fear memory suppression resulting from behavioral disruption of reconsolidation is amygdala-dependent also in humans, which supports an evolutionarily conserved memory-update mechanism.


The unique contribution of behavioral scientists to medical education: the top ten competencies.
Understandably, the focus of most physicians is primarily on the biomedical-What is this disease or injury? Behavioral scientists from various disciplines in medical education generally have a broader approach-Who is this person with these symptoms and what is their story? Since behavioral scientists are often alone among U. S. residency faculty, physicians may fail to recognize the value of their approach to medical resident training. This review identifies and describes the top areas of expertise that behavioral scientists bring to medical education and how their training prepares them to think differently than other medical educators. In the course of identifying each competency, this review will emphasize the ways in which their skills and techniques are the origin of subtle impact in their teaching encounters, explore ways of targeting that impact, and discuss examples of this impact.


Use of T4 DNA polymerase replacement synthesis for specific labeling of plasmid-cloned inserts.
A strategy employing T4 DNA polymerase replacement synthesis is described whereby only the insert portion of recombinant plasmids are radioisotopically labeled. Prior purification of the inserted DNA is not required. The recombinant plasmid is first digested with one or more restriction endonucleases selected to cleave the vector segment into fragments at least 30% shorter than the insert DNA segment. This mixture of fragments is then digested by the T4 DNA polymerase-associated 3' exonuclease in the absence of deoxynucleoside triphosphates (dNTPs) for a length of time which allows complete degradation of all fragments shorter than the insert. The remaining insert DNA, which is now partially single-stranded, is then resynthesized by addition of dNTPs, one or more of which is labeled. The resulting DNA is full length, double-stranded, and unnicked. The strategy is widely applicable, and reliably and reproducibly yields DNA of high specific activity. We have used this method to label more than 15 cloned inserts ranging in size from 3.2 to 25 kilobases.


HIV tropism and decreased risk of breast cancer.
During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection. We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer. Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.


Stanniocalcin 1 is a luminal epithelial marker for implantation in pigs regulated by progesterone and estradiol.
Stanniocalcin 1 (STC1) is a glycoprotein that decreases calcium and increases phosphate in cells/tissues. This investigation examined endocrine regulation of STC1 in endometria of pigs during the estrous cycle and pregnancy. STC1 mRNA was present exclusively in luminal epithelium (LE) between d 12 and 15 of the estrous cycle, increased between d 12 and d 20, and was not detectable by d 30 of pregnancy. STC1 protein was also detected in uterine flushings. To determine effects of estrogen and progesterone, pigs were ovariectomized and treated with these hormones alone or together. Progesterone, but not estrogen, induced STC1 in LE. Cotreatment with progesterone and estrogen further stimulated STC1 over progesterone alone. To determine effects of pseudopregnancy, nonpregnant gilts were given daily injections of estradiol benzoate from d 11 to d 14. STC1 was not expressed in LE on d 90 of pseudopregnancy, suggesting that the estradiol given to induce pseudopregnancy and/or long-term exposure to progesterone are required for down-regulation of STC1. To determine effects of long-term progesterone, without effects of estradiol, pigs were ovariectomized on d 12, given daily injections of progesterone through d 39, and hysterectomized on d 40 after estrus. STC1 was expressed in LE of progesterone-treated pigs, suggesting that estrogen is involved in down-regulation of STC1. We conclude that STC1 is induced in LE by progesterone and further stimulated by estrogen, and its down-regulation in LE by d 25 likely requires exposure of the progestinized uterus to estrogen. The temporal and cell type-specific expression of STC1 makes this gene a unique marker for implantation in pigs.


Cognitive Impairment After Ischemic and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association/American Stroke Association.
Cognitive impairment is a common consequence of stroke and has direct implications for poststroke functioning and quality of life, including the ability to maintain a job, live independently, sustain interpersonal relationships, and drive a vehicle. In this scientific statement, we critically appraise the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) and provide a framework for clinical care while highlighting gaps that merit further study. We performed a scoping literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, clinical guidelines, review articles, and editorials on the incidence and prevalence, natural history, diagnosis, and management of PSCI. Scoping reviews determine the scope of a body of literature on a given topic to indicate the volume of literature and the studies currently available and provide an overview of its focus. PSCI is common after stroke, especially in the first year, and ranges from mild to severe. Although cognitive impairment is reversible in some cases early after stroke, up to one-third of individuals with stroke develop dementia within 5 years. The pathophysiology is not yet fully elucidated but is likely attributable to an acute stroke precipitating a series of pathological events, often in the setting of preexisting microvascular and neurodegenerative changes. Screening for associated comorbidities and interdisciplinary management are integral components of the care of individuals with PSCI. There is a need for prospective studies evaluating the individual trajectory of PSCI and the role of the acute vascular event in the predisposition for Alzheimer disease and related dementias, as well as high-quality, randomized clinical trials focused on PSCI management.


Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects.
The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients. Since in vitro replication of HIV is increased with oxidative stress, this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation, a measure of oxidative stress, and viral load in humans. A randomized placebo-controlled, double-blind study. Forty-nine HIV-positive patients were randomized to receive supplements of both DL-alpha-tocopherol acetate (800 IU daily) and vitamin C (1000 mg daily), or matched placebo, for 3 months. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. New or recurrent infections for the 6-month period after study entry were also recorded. The vitamin group (n = 26) had an increase in plasma concentrations of alpha-tocopherol (P < 0.0005) and vitamin C (P < 0.005) and a reduction in lipid peroxidation measured by breath pentane (P < 0.025), plasma lipid peroxides (P < 0.01) and malondialdehyde (P < 0.0005) when compared with controls (n = 23). There was also a trend towards a reduction in viral load (mean +/- SD changes over 3 months, -0.45 +/- 0.39 versus +0.50 +/- 0.40 log10 copies/ml; P = 0.1; 95% confidence interval, -0.21 to -2.14). The number of infections reported was nine in the vitamin group and seven in the placebo group. Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.


Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.
The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected.


A nanostructured Fabry-Perot interferometer.
A polymer-based micromachined Fabry-Perot interferometer (µFPI) with embedded nanostructures in its cavity, called nanostructured-FPI, is reported. The nanostructures inside the cavity are a layer of Au-coated nanopores. As a refractive-index sensitive optical sensor, it offers the following advantages over a traditional µFPI for label-free biosensing applications, including increased sensing surface area, extended penetration depth of the excitation light and amplified optical transducing signals. For a nanostructured-FPI with nanopore size of 50 nm in diameter and the gap size of FPI cavity of 50 µm, measurements find that it has ~20 times improvement in free spectral range (FSR), ~2 times improvement in finesse and ~4 times improvement in contrast of optical transducing signals over a traditional µFPI even without any device performance optimization. Several chemicals have also been evaluated using this device. Fourier transform has been performed on the measured optical signals to facilitate the analysis of the transducing signals.


From cosmology to cold atoms: observation of Sakharov oscillations in a quenched atomic superfluid.
Predicting the dynamics of many-body systems far from equilibrium is a challenging theoretical problem. A long-predicted phenomenon in hydrodynamic nonequilibrium systems is the occurrence of Sakharov oscillations, which manifest in the anisotropy of the cosmic microwave background and the large-scale correlations of galaxies. Here, we report the observation of Sakharov oscillations in the density fluctuations of a quenched atomic superfluid through a systematic study in both space and time domains and with tunable interaction strengths. Our work suggests a different approach to the study of nonequilibrium dynamics of quantum many-body systems and the exploration of their analogs in cosmology and astrophysics.


Structure and dissociation characteristics of metal chloride anion clusters containing redox-active metal ions studied by laser desorption and electrospray ionization mass spectrometry and ab initio calculations.
Copper chloride anion clusters with both copper oxidation states can be made by laser desorption of CuCl(2) crystals. We have used this method to study the dissociation characteristics of such cluster ions. The stability and the structure of the observed complexes were probed by ab initio calculations. These calculations show that many of these complexes are bridged structures. Thus, for the Cu(2)Cl(4) dimer anion, formally [ClCu-Cl-CuCl(2)](-) , with putative mixed copper oxidation states, the two copper ions become equivalent through bridging. Such bridging does not occur when redox inactive metal ions are present as in [ClCu-Cl-CaCl(2)](-) . By observing the dissociation characteristics of a variety of metal chloride cluster anions produced from binary mixtures, the following Cl(-) affinity order is obtained: FeCl(3) > CuCl > CaCl(2) > FeCl(2) > AgCl ≈ CuCl(2) ≈ ZnCl(2) > LiCl. Ab initio calculations on the Cl(-) affinity of selected chlorides confirm this order as do Cl(-) affinity estimates from the experimentally known vertical electron detachment energies of the superhalogens CaCl(3)(-) and LiCl(2)(-) . An equimolar mixture of CuCl(2) and FeCl(3) produces an intense cluster ion, which, from (65)Cu labeling experiments, is best described as FeCl(4)(-)···Cu(+)···(-)Cl(4) Fe, a Cu(+) bound superhalogen FeCl(4)(-) dimer. The Cu(+) ion can be replaced by the redox inactive alkali cations and by Ag(+) but these metal ion bound FeCl(4)(-) dimers show an entirely different fragmentation behavior which is attributed to the absence of bridging. Electrospray ionization (ESI) of CuCl(2) produces an extended series of (CuCl(2))(n) Cl(-) anions (n = 1-11) and so in ESI very limited reduction of Cu(2+) takes place. The (CuCl(2))(n) Cl(-) anions show an abundant dissociation via loss of neutral Cu(2)Cl(4) which according to our ab initio calculations is 9 kcal/mol more stable than two CuCl(2).


Myelinating satellite oligodendrocytes are integrated in a glial syncytium constraining neuronal high-frequency activity.
Satellite oligodendrocytes (s-OLs) are closely apposed to the soma of neocortical layer 5 pyramidal neurons but their properties and functional roles remain unresolved. Here we show that s-OLs form compact myelin and action potentials of the host neuron evoke precisely timed Ba(2+)-sensitive K(+) inward rectifying (Kir) currents in the s-OL. Unexpectedly, the glial K(+) inward current does not require oligodendrocytic Kir4.1. Action potential-evoked Kir currents are in part mediated by gap-junction coupling with neighbouring OLs and astrocytes that form a syncytium around the pyramidal cell body. Computational modelling predicts that glial Kir constrains the perisomatic [K(+)]o increase most importantly during high-frequency action potentials. Consistent with these predictions neurons with s-OLs showed a reduced probability for action potential burst firing during [K(+)]o elevations. These data suggest that s-OLs are integrated into a glial syncytium for the millisecond rapid K(+) uptake limiting activity-dependent [K(+)]o increase in the perisomatic neuron domain.


Free-breathing motion compensation using template matching: a technique allowing for tracer kinetic modeling of liver metastases.
Modeling tracer kinetics from dynamic magnetic resonance imaging (dMRI) to understand microvascular characteristics typically requires acquisitions longer than 1 breath-hold. This has limited the application of dMRI in assessment of the upper abdomen. Here we present a template-based motion correction strategy for dMRI of liver metastases based on the correlation coefficient (CC), originally developed for tracking coronary arteries. This postprocessing method allows patient free breathing during sagittal dMRI acquisition and allows a more precise parametric mapping using tracer kinetic models. In a study of 6 subjects, a 64 x 64 template was accurately tracked retrospectively with mean CC = 0.72 +/- 0.07. Mean superior-inferior displacement tracked was 1.82 +/- 1.20 pixels, whereas mean anterior-posterior displacement was 7.72 +/- 4.58 pixels. Application of the CC method significantly improved the global fit (chi2) of a tracer kinetic model throughout tumor regions. Therefore, use of the CC postprocessing method for dMRI scans can improve the precision of dMRI tracer kinetic models.


Sinus headache: a neurology, otolaryngology, allergy, and primary care consensus on diagnosis and treatment.
Sinus headache is a widely accepted clinical diagnosis, although many medical specialists consider it an uncommon cause of recurrent headaches. The inappropriate diagnosis of sinus headache can lead to unnecessary diagnostic studies, surgical interventions, and medical treatments. Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to define conditions that lead to headaches of rhinogenic origin but have done so from different perspectives and in isolation of each other. An interdisciplinary ad hoc committee convened to discuss the role of sinus disease as a cause of headache and to review recent epidemiological studies that suggest sinus headache (headache of rhinogenic origin) and migraine are frequently confused with one another. This committee reviewed available scientific evidence from multiple disciplines and concluded that considerable research and clinical study are required to further understand and delineate the role of nasal pathology and autonomic activation in migraine and headaches of rhinogenic origin. However, this group agreed that greater diagnostic and therapeutic attention needs to be given to patients with sinus headaches.


Kinetics of zinc and cadmium release in freshly contaminated soils.
The kinetics of metal release from the solid phase to solution was measured on two sets of 14 freshly contaminated soils with diverse properties. From measurements of metal concentrations in extracted soil pore water, the amount accumulated from the soil by diffusive gradients in thin-film (DGT) devices, and the distribution coefficient for labile metal, Kdl, estimated by isotopic exchange, we calculated the response time, Tc, of the soil-solution system to the removal of metal by DGT and the rate constant for release from the solid phase, k(-1). Resupply was so fast for Zn that Tc (and k(-1)) could be measured only in three of the soils, with either a silty or a sandy loam texture and low to intermediate pH (4.84-5.66). In only six clay soils was resupply of Cd too fast to measure. The generally slower release rates of Cd compared to Zn may reflect the 100-fold lower concentration of Cd, which allowed a greater proportion of it to occupy stronger binding sites with slower release rates. The rate constants derived indicate that supply from the solid phase to solution will not limit uptake of Cd or Zn by plants in clay soils, but it could be a factor in sandy or silty soils with a low pH. These findings suggest that risk assessment of clay soils could be undertaken using measurements of metals in soil solution. However, devices such as DGT, which respond to the kinetics of supply, are necessary to assess available metal in low pH, sandy, and silty soils.


The molecular neurobiology of the sleep-deprived, fuzzy brain.
Sleep deprivation is well established to cause diminution of cognitive function, including disruption of both minute-to-minute working memory and decrements in the stabilization of long-term memories. Moreover, "replay" during sleep of episodes and sequences of events that were experienced during wakefulness has been implicated in consolidation of long-term memories. However, the molecular mechanisms underlying the role of sleep in memory function are just starting to be defined. In this issue of Science Signaling, Tudor et al identify one molecular component underlying the effects of sleep on memory function: dynamic experience-dependent regulation of protein synthesis in the hippocampus.


Observations on the pathological spectrum and clinical course of microsporidiosis in men infected with the human immunodeficiency virus: follow-up study.
The purposes of this research were to determine whether microsporidian infection is accompanied by structural alterations of the duodenal mucosa and to characterize the clinical and morphological evolution of intestinal microsporidiosis. In a previous systematic electron microscopic evaluation of mucosal biopsy specimens from patients with human immunodeficiency virus infection, we detected Enterocytozoon bieneusi in the duodenal tissue of 31 men. This report concerns a follow-up study of these 31 men, who underwent repeated clinical and laboratory evaluations, including repeated duodenal biopsies. Eighteen men had chronic diarrhea at enrollment and 13 had no diarrhea. The CD4+ cell counts (per mm3) ranged from 10 to 660 and were normal for three men. E. bieneusi infection was accompanied by a wide spectrum of histopathology of duodenal tissue; over a mean follow-up of 15 months, no consistent change in duodenal mucosal morphology was observed, and diarrhea did not invariably develop. These observations indicate that diarrhea and severe villus injury do not invariably accompany infection. Further studies are needed to determine the relationship between E. bieneusi infection and clinical illness.


Alcohol consumption and dementia risk: a dose-response meta-analysis of prospective studies.
It is widely believed that light-to-moderate alcohol intake may protect against dementia while excessive drinking may instead increase the risk. Nonetheless, these findings need cautious interpretations due to varying methodologies and lack of standard definition, which hindered our transferring into preventative practice. The objective of this study is to investigate the potential dose-response association between alcohol consumption and risk of dementia. A systematic search was conducted in electronic databases to identify relevant studies. Risk estimates were combined using a random-effect model. Eleven studies with 73,330 participants and 4586 cases for all-cause dementia (ACD), five studies with 52,715 participants and 1267 cases for Alzheimer's dementia (AD) and four studies with 49,535 participants and 542 cases for vascular dementia were included. We observed a nonlinear association between alcohol consumption and ACD risk (p nonlinearity < 0.05). The alcohol dose associated with lower risk of dementia was confined to at most 12.5 g/day, with the risk hitting bottom (RR ≈ 0.9) at roughly 6 g/day. Of note, the ACD risk seemed to be elevated (≈10%) when the dose surpasses certain levels: 23 drinks/week or 38 g/day. For the alcohol type, recommendation for wine is prioritized. The subgroup analysis further indicated that the effect of alcohol may be greater in younger adults (<60 years old) with regard to fighting against dementia. Modest alcohol consumption (≤12.5 g/day) is associated with a reduced risk of dementia with 6 g/day of alcohol conferring a lower risk than other levels while excessive drinking (≥38 g/day) may instead elevate the risk.


Effects of xylitol on blood glucose, glucose tolerance, serum insulin and lipid profile in a type 2 diabetes model of rats.
The present study was conducted to examine the antidiabetic effects of xylitol in a type 2 diabetes rat model. Six-week-old male Sprague-Dawley rats were randomly divided into 3 groups: normal control (NC), diabetic control (DBC) and xylitol (XYL). Diabetes was induced only in the DBC and XYL animal groups by feeding them a 10% fructose solution for 2 weeks followed by an injection (i.p.) of streptozotocin (40 mg/kg body weight). One week after the streptozotocin injection, the animals with a nonfasting blood glucose level of >300 mg/dl were considered to be diabetic. The XYL group was fed further with a 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 5 weeks of intervention, food and fluid intake, body weight, blood glucose, serum fructosamine and most of the serum lipids were significantly decreased, and serum insulin concentration and glucose tolerance ability was significantly increased in the XYL group compared to the DBC group. Liver weight, liver glycogen and serum triglycerides were not influenced by feeding with xylitol. The data of this study suggest that xylitol can be used not only as a sugar substitute but also as a supplement to antidiabetic food and other food products.


Success Rate and Utility of Ultrasound-guided Synovial Biopsies in Clinical Practice.
The utility of synovial biopsy in increasing our understanding of the pathogenesis of inflammatory arthropathies, as well as in evaluating treatments, is well established. Ultrasound (US) allows synovial assessment and therefore assists in biopsying synovial tissue in a safe and well-tolerated manner. This study's objectives were to (1) determine the rate of success in retrieving synovial tissue using US guidance, (2) describe the indications for US-guided synovial biopsies in the clinical setting, (3) determine how frequently the synovial biopsy can lead to a clear diagnosis, and (4) assess the quality of the synovial tissue obtained using this technique. Synovial biopsies of small and large joints were performed under US guidance between February 2007 and December 2014 using a semiautomatic core biopsy needle. The biopsy procedure was considered successful if synovial tissue was found at histological examination. Seventy-four patients with undifferentiated arthritis underwent 76 synovial biopsies. The success rate in retrieving synovial tissue was 81.6% (62/76). One patient taking acetyl salicylic acid at 75 mg at the time of the biopsy presented with hemarthrosis 48 h after the procedure, which resolved following simple arthrocentesis. A definitive diagnosis was achieved in 16% of the patients where synovial tissue was sampled successfully. US-guided synovial biopsies in clinical practice can be performed safely on patients with undifferentiated arthritis and with heterogeneous presentations. The rate of success in acquiring synovial tissue is high. The procedure usually retrieves quality tissue and leads to a definite diagnosis in a significant minority of patients.


Coexisting Crohn's Disease and Takayasu's Arteritis in Two Patients Treated with Anti-TNF-α Therapies.
Crohn's disease (CD) and Takayasu's arteritis (TA) are inflammatory granulomatous autoimmune disorders. Simultaneous occurrence of CD and TA in the same individual is rare. We report two cases treated with biologic agents. Case 1: A 16-year-old male presented with abdominal pain, nausea, vomiting. CT angiogram showed thickening of the terminal ileum, wall thickening and narrowing of multiple large and medium arteries including aorta and left common carotid. Colonoscopy with biopsy of the stenotic ileocecal valve confirmed CD. Resected carotid artery pathology was consistent with TA. Treatment was initially begun with prednisone, then methotrexate was started followed by infliximab. Due to side effects, methotrexate was switched to azathioprine. He remained asymptomatic. Case 2: A 38-year-old male with well-characterized Crohn's ileocolitis for 15 years, who had been treated with prednisone, mesalamine, sulfasalazine, and azathioprine presented with chest, upper back and abdominal pain. CT angiogram showed vasculitis of large and medium arteries, with stenosis of the right renal artery, and wall thickening of the sigmoid colon. He was diagnosed with TA. He underwent treatment with infliximab and adalumimab on different occasions, which were later discontinued due to fever, bacteremia and complications from sepsis. He remained on prednisone and azathioprine. In these two patients with both CD and TA the diagnoses were confirmed by imaging and pathologic findings. Both patients developed vascular complications. Tumor necrosis factor inhibitor therapy was effective in one patient but discontinued in the other due to infection. Further research into the association of CD and TA may provide clues to their etiologies and guide effective interventions.


Impact of chronic heart failure on elderly persons' daily life: a validation study.
Knowledge about how elderly persons perceive the impact of chronic heart failure (CHF) on daily life is important when planning nursing care. For this purpose, disease specific instruments are needed. However, few instruments have been developed or tested specifically on elderly persons. To validate a Swedish version of the Minnesota Living with Heart Failure Questionnaire (LHFQ) on elderly persons with CHF, and use it to describe the impact of CHF on daily life in the same population. The sample comprised of 357 persons, aged between 65 and 99, diagnosed with CHF. A questionnaire including background data, the LHFQ and the SF-12 was used. A factor analysis resulted in four dimensions: physical, emotional, treatment and pleasure. LHFQ showed convergent validity and ability to discriminate between known groups. Cronbach's alpha for the total scale was 0.94. Impairments in the physical dimension were most common, especially fatigue (88%) and shortness of breath (87%). The LHFQ showed satisfying psychometric properties in an elderly Swedish population with CHF and can, with minor alterations, be recommended for research and clinical use. The impact of chronic heart failure on daily life was mostly physical, but other impairments were also common.


Epidemiologic risk factors for esophageal cancer development.
In retrospective studies of esophageal cancer (EC), cigarettes and hookah smoking, nass use (a chewing tobacco product), opium consumption, hot tea drinking, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett's esophagus is clearly recognized as a risk factor for EC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we review the epidemiologic studies that have investigated the epidemiologic patterns and causes of EC.


A reaffirmed philosophy and practice of occupational therapy for the 1980s.
This paper culled from the occupational therapy literature of the 1978-1983 period statements in support of our philosophical base, in opposition to our treatment modalities, and in examination of the cause and course of our internal professional debate. The futurist literature projecting external trends in economic and sociocultural areas, including medicine and health, was also sampled for evidence that might either sustain or further challenge traditional theory and practice. The conclusion drawn was that our heritage of belief in and use of occupation as both the central organizing theme and mode of professional practice is better suited to future intervention strategies than are borrowed, nontraditional treatment media. Four recommendations for actualizing a more unified theory and practice are proposed.


Intraoperative radiotherapy (IORT) as boost in breast cancer.
The term IORT (intraoperative radiotherapy) is currently used for various techniques that show huge differences in dose delivery and coverage of the tissue at risk. The largest evidence for boost IORT preceding whole breast irradiation (WBI) originates from intraoperative electron treatments (IOERT) with single doses around 10 Gy. At median follow-up periods at 6 years, outstandingly low local recurrence rates of less than 1% are observed. Higher local relapse rates were described for G3 tumors and triple negative breast cancers as well as for IORT following primary systemic treatment for locally advanced tumors. Even there, long term (>5y) local tumor control rates mostly beyond 95% were maintained. Compared to other boost methods, an intraoperative treatment has evident advantages in terms of precision (by avoiding a "spatial and/or temporal miss"), cosmetic outcome and patient comfort. Direct visualisation of a tumor bed during surgery guarantees for an accurate dose delivery, which has additionally gained importance in times of primary reconstruction techniques after lumpectomy, since IORT is performed before breast tissue including parts of the tumor bed is mobilized for plastic purposes. As a consequence of direct tissue exposure without distension by hematoma/seroma, IORT allows for small treatment volumes and complete skin sparing, both having a positive effect on late tissue tolerance and, hence, cosmetic appearance. Boost IORT marginally prolongs the surgical procedure, while significantly shortening postoperative radiotherapy. Its combination with external beam radiotherapy to the whole breast (WBI) is currently tested in two multicentric prospective trials: as kV-IORT in the multicentric TARGIT-B (oost) study, and as IOERT in the HIOB trial (3 weeks hypofractionated WBI preceded by IORT electron boost).


Lung Cancer Assistant: a hybrid clinical decision support application for lung cancer care.
Multidisciplinary team (MDT) meetings are becoming the model of care for cancer patients worldwide. While MDTs have improved the quality of cancer care, the meetings impose substantial time pressure on the members, who generally attend several such MDTs. We describe Lung Cancer Assistant (LCA), a clinical decision support (CDS) prototype designed to assist the experts in the treatment selection decisions in the lung cancer MDTs. A novel feature of LCA is its ability to provide rule-based and probabilistic decision support within a single platform. The guideline-based CDS is based on clinical guideline rules, while the probabilistic CDS is based on a Bayesian network trained on the English Lung Cancer Audit Database (LUCADA). We assess rule-based and probabilistic recommendations based on their concordances with the treatments recorded in LUCADA. Our results reveal that the guideline rule-based recommendations perform well in simulating the recorded treatments with exact and partial concordance rates of 0.57 and 0.79, respectively. On the other hand, the exact and partial concordance rates achieved with probabilistic results are relatively poorer with 0.27 and 0.76. However, probabilistic decision support fulfils a complementary role in providing accurate survival estimations. Compared to recorded treatments, both CDS approaches promote higher resection rates and multimodality treatments.


Clinical and bacteriological characteristics of infective endocarditis in the elderly.
To determine the clinical and bacteriological features of infective endocarditis in the elderly. Prospective case series. A university hospital that is both a referral and a primary care centre. 114 consecutive patients treated for infective endocarditis from November 1990 to December 1993: 25 were > 70 years of age (group 1) and 89 were < 70 years old (group 2). Location of infective endocarditis, clinical signs, and symptoms were similar in the two groups, except for a lower occurrence of embolic episodes in the elderly (group 1:8%, group 2: 28%; P < 0.04). A higher rate of infective endocarditis on intracardiac prosthetic devices was noted in group 1 (group 1: 52%, group 2: 25%; P < 0.05). The distribution of causative micro-organisms showed a higher proportion of bacteria from the gastrointestinal tract in the elderly (group D streptococci and enterococci: 48% in group 1 v 20% in group 2) and the presumed portal of entry was more often digestive (group 1: 50%, group 2: 17%; P = 0.01). Elderly patients were less often operated on (group 1: 24%, group 2: 43%; P = 0.07) and their mortality rate was higher (group 1: 28%, group 2: 13%; P = 0.08). Infective endocarditis in patients over 70 often occurs in those with intracardiac prosthetic devices and is more often due to bacteria from the gastrointestinal tract. Its prognosis appears to be worse than in younger subjects.


Correlation between clinical features and magnetic resonance imaging findings in lumbar disc prolapse.
Lumbar disc prolapse is one of the common causes of low back pain seen in the working population. There are contradictorty reports regarding the clinical significance of various magnetic resonance imaging (MRI) findings observed in these patients. The study was conducted to correlate the abnormalities observed on MRI and clinical features of lumbar disc prolapse. 119 clinically diagnosed patients with lumbar disc prolapse were included in the study. Clinical evaluation included pain distribution, neurological symptoms and signs. MR evaluation included grades of disc degeneration, type of herniation, neural foramen compromise, nerve root compression, and miscellaneous findings. These MRI findings were tested for inter- and intraobserver variability. The MRI findings were then correlated with clinical symptoms and the level of disc prolapse as well as neurological signs and symptoms. Statistical analysis included the Kappa coefficient, Odd's ratio, and logistic regression analysis. There were no significant inter- or intraobserver variations for most of MRI findings (Kappa value more than 0.5) except for type of disc herniation which showed a interobserver variation of 0.46 (Kappa value). The clinical level of pain distribution correlated well with the MRI level (Kappa 0.8), but not all disc bulges produced symptoms. Central bulges and disc protrusions with thecal sac compression were mostly asymptomatic, while centrolateral protrusions and extrusions with neural foramen compromise correlated well with the dermatomal distribution of pain. Root compression observed in MRI did not produce neurological symptoms or deficits in all patients but when deficits were present, they correlated well with the presence of root compression in MRI. Multiple level disc herniations with foramen compromise were strongly associated with the presence of neurological signs. The presence of centrolateral protrusion or extrusion with gross foramen compromise correlates with clinical signs and symptoms very well, while central bulges and disc protrusions correlate poorly with clinical signs and symptoms. The presence of neural foramen compromise is more important in determining the clinical signs and symptoms while type of disc herniation (bulge, protrusion, or extrusion) correlates poorly with clinical signs and symptoms.


Quasi-2D Cu2 S crystals on graphene: in-situ growth and ab-initio calculations.
Two-dimensional crystals of beta-copper sulfide are synthesized in an in-situ electron microscopy experiment. Copper crystals are deposited on an amorphous carbon film containing sulfur. The carbon film graphitizes upon heating and electron irradiation and allows the reaction of Cu and S towards two-dimensional Cu(2) S crystals. These are energetically favourable and bonded via van der Waals interactions to the graphitic substrate.


Environmentally co-occurring mercury resistance plasmids are genetically and phenotypically diverse and confer variable context-dependent fitness effects.
Plasmids are important mobile elements that can facilitate genetic exchange and local adaptation within microbial communities. We compared the sequences of four co-occurring pQBR family environmental mercury resistance plasmids and measured their effects on competitive fitness of a Pseudomonas fluorescens SBW25 host, which was isolated at the same field site. Fitness effects of carriage differed between plasmids and were strongly context dependent, varying with medium, plasmid status of competitor and levels of environmental mercury. The plasmids also varied widely in their rates of conjugation and segregational loss. We found that few of the plasmid-borne accessory genes could be ascribed functions, although we identified a putative chemotaxis operon, a type IV pilus-encoding cluster and a region encoding putative arylsulfatase enzymes, which were conserved across geographically distant isolates. One plasmid, pQBR55, conferred the ability to catabolize sucrose. Transposons, including the mercury resistance Tn5042, appeared to have been acquired by different pQBR plasmids by recombination, indicating an important role for horizontal gene transfer in the recent evolution of pQBR plasmids. Our findings demonstrate extensive genetic and phenotypic diversity among co-occurring members of a plasmid community and suggest a role for environmental heterogeneity in the maintenance of plasmid diversity.


Modeling of human factor Va inactivation by activated protein C.
Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (F)Xa and its cofactor FVa) plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC), an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and "protection" of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative analysis of in vitro experiments and mathematical constructs we are able to produce a final validated model that includes 24 chemical reactions and interactions with 14 unique rate constants which describe the flux in concentrations of 24 species. This study highlights the complexity of the inactivation process and provides a module of equations describing the Protein C pathway that can be integrated into existing comprehensive mathematical models describing tissue factor initiated coagulation.


Is blue dye still required during sentinel lymph node biopsy for breast cancer?
In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates. Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique. A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% (n = 158/160), with blue dye alone 92.5% (n = 148/160) and with radioisotope alone 97.5% (n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients. The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation.


Role of heme oxygenase-1 in cardiovascular function.
Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Due to the properties of inducible HO (HO-1) and its products, we hypothesized that HO-1 would play an important role in the regulation of cardiovascular function. In this article we will review the role of HO-1 in cardiovascular function, and highlight our previous studies using gene deletion and gene overexpression transgenic approaches in mice. These studies will include the investigation of HO-1 in the setting of hypertension (renovascular), atherosclerosis and vascular injury (vein graft stenosis), hypotension (endotoxemia), and ischemia/reperfusion injury (heart). In a chronic renovascular hypertension model, blood pressure elevation, cardiac hypertrophy, acute renal failure, and acute mortality induced by one kidney-one clip surgery are more severe in HO-1 null mice. Moreover, absence of HO-1 leads to accelerated atherosclerotic lesion formation and vein graft disease. In addition, HO-1 null mice with endotoxemia have earlier resolution of hypotension, yet the mortality and the incidence of end organ damage are higher in the absence of HO-1. In contrast, mice with cardiac-specific overexpression of HO-1 have an improvement in cardiac function, smaller myocardial infarcts, and reduced inflammatory and oxidative damage after coronary artery ligation and reperfusion. Taken together, these studies suggest that an absence of HO-1 has detrimental consequences, while overexpression of HO-1 plays a protective role in ischemia/reperfusion injury.


Training of Attentional Filtering, but Not of Memory Storage, Enhances Working Memory Efficiency by Strengthening the Neuronal Gatekeeper Network.
Memory training (MT) in older adults with memory deficits often leads to frustration and, therefore, is usually not recommended. Here, we pursued an alternative approach and looked for transfer effects of 1-week attentional filter training (FT) on working memory performance and its neuronal correlates in young healthy humans. The FT effects were compared with pure MT, which lacked the necessity to filter out irrelevant information. Before and after training, all participants performed an fMRI experiment that included a combined task in which stimuli had to be both filtered based on color and stored in memory. We found that training induced processing changes by biasing either filtering or storage. FT induced larger transfer effects on the untrained cognitive function than MT. FT increased neuronal activity in frontal parts of the neuronal gatekeeper network, which is proposed to hinder irrelevant information from being unnecessarily stored in memory. MT decreased neuronal activity in the BG part of the gatekeeper network but enhanced activity in the parietal storage node. We take these findings as evidence that FT renders working memory more efficient by strengthening the BG-prefrontal gatekeeper network. MT, on the other hand, simply stimulates storage of any kind of information. These findings illustrate a tight connection between working memory and attention, and they may open up new avenues for ameliorating memory deficits in patients with cognitive impairments.


Long bone articular and diaphyseal structure in Old World monkeys and apes. II: Estimation of body mass.
Body mass estimation equations are generated from long bone cross-sectional diaphyseal and articular surface dimensions in 176 individuals and 12 species of hominoids and cercopithecoids. A series of comparisons is carried out to determine the best body mass predictors for each of several taxonomic/locomotor groupings. Articular breadths are better predictors than articular surface areas, while cross-sectional shaft strengths are better predictors than shaft external breadths. Percent standard errors of estimate (%SEEs) and percent prediction errors for most of the better predictors range between 10-20%. Confidence intervals of equations using sex/species means are fairly representative of those calculated using individual data, except for sex/species means equations with very low %SEEs (under about 10%), where confidence intervals (CIs) based on individuals are likely to be larger. Given individual variability, or biological "error," this may represent a lower limit of precision in estimating individual body masses. In general, it is much more preferable to determine at least broad locomotor affinities, and thus appropriate modern reference groups, before applying body mass estimation equations. However, some structural dimensions are less sensitive to locomotor distinctions than others; for example, proximal tibial articular M-L breadth is apparently "locomotor blind" regarding body mass estimation within the present study sample. In other cases where locomotor affiliation is uncertain, mean estimates from different reference groups can be used, while for some dimensions no estimation should be attempted. The techniques are illustrated by estimating the body masses of four fossil anthropoid specimens of Proconsul nyanzae, Proconsul heseloni, Morotopithecus bishopi, and Theropithecus oswaldi.


ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression.
Dynamic regulation of diverse nuclear processes is intimately linked to covalent modifications of chromatin. Much attention has focused on methylation at lysine 4 of histone H3 (H3K4), owing to its association with euchromatic genomic regions. H3K4 can be mono-, di- or tri-methylated. Trimethylated H3K4 (H3K4me3) is preferentially detected at active genes, and is proposed to promote gene expression through recognition by transcription-activating effector molecules. Here we identify a novel class of methylated H3K4 effector domains--the PHD domains of the ING (for inhibitor of growth) family of tumour suppressor proteins. The ING PHD domains are specific and highly robust binding modules for H3K4me3 and H3K4me2. ING2, a native subunit of a repressive mSin3a-HDAC1 histone deacetylase complex, binds with high affinity to the trimethylated species. In response to DNA damage, recognition of H3K4me3 by the ING2 PHD domain stabilizes the mSin3a-HDAC1 complex at the promoters of proliferation genes. This pathway constitutes a new mechanism by which H3K4me3 functions in active gene repression. Furthermore, ING2 modulates cellular responses to genotoxic insults, and these functions are critically dependent on ING2 interaction with H3K4me3. Together, our findings establish a pivotal role for trimethylation of H3K4 in gene repression and, potentially, tumour suppressor mechanisms.


Maternal use of folic acid supplements during pregnancy and four-year-old neurodevelopment in a population-based birth cohort.
The use of folic acid supplements during very early pregnancy is recommended in order to reduce the incidence of neural tube defects. Little is known about the possible benefits of folic acid on child neurodevelopment. A total of 420 children (87% of those eligible) from a birth cohort had complete data for final analyses at age 4 years. Information about folic acid and other over-the-counter dietary supplements was obtained prospectively using interviewer-administered questionnaires at the end of the first trimester of pregnancy. Psychological outcomes were assessed by two psychologists and teachers 4 years later. Low maternal socio-economic status, smoking, high parity and short duration of breast feeding were associated with lower prevalence of folic acid supplement use. Verbal (b = 3.98, SE = 1.69), motor (b = 4.54, SE = 1.66) and verbal-executive function (b = 3.97, SE = 1.68) scores, social competence (b = 3.97, SE = 1.61) and inattention symptom [OR = 0.46; 95% CI 0.22, 0.95] scores were associated with reported folic acid use. Reported folic acid supplement use during pregnancy was associated with improved neurodevelopment in children after adjusting for a number of sociodemographic and behavioural factors.


Patients' experiences of person-centred integrated heart failure care and palliative care at home: an interview study.
Patients with severe heart failure (HF) suffer from a high symptom burden and high mortality. European and Swedish guidelines for HF care recommend palliative care for these patients. Different models for integrated palliative care and HF care have been described in the literature. No studies were found that qualitatively evaluated these models. The purpose of this study is to describe patients' experiences of a new model of person-centred integrated HF and palliative care at home. Interviews were conducted with 12 patients with severe HF (New York Heart Association class IIIâ€"IV) and included in the research project of Palliative advanced home caRE and heart FailurE caRe (PREFER). Qualitative content analysis was used for data analysis. Two themes and a total of five categories were identified. The first theme was feeling secure and safe through receiving care at home with the categories: having access to readily available care at home, being followed up continuously and having trust in the team members' ability to help. The second theme was being acknowledged as both a person and a patient, with the following two categories: being met as a person, participating in decisions about one's care and receiving help for symptoms of both HF and comorbidities. CONCLUSIONS: Person-centred integrated HF and palliative care provides a secure environment and holistic care for patients with severe HF. This approach is a way to improve the care management in this population. NCT01304381; Results.


Search for neutral supersymmetric Higgs bosons in pp collisions at sqrt[s] = 1.8TeV.
We present the results of a search for neutral Higgs bosons produced in association with b quarks in pp-->bb(phi)-->bbb final states with 91+/-7 pb(-1) of pp collisions at sqrt[s] = 1.8 TeV recorded by the Collider Detector at Fermilab. We find no evidence of such a signal and the data are interpreted in the context of the neutral Higgs sector of the minimal supersymmetric extension of the standard model. With basic parameter choices for the supersymmetric scale and the stop-quark mixing, we derive 95% C.L. lower mass limits for neutral Higgs bosons for tan(beta) values in excess of 35.