Effect of previous botulinum neurotoxin treatment on microvascular decompression for hemifacial spasm.
The objective of this study was to investigate the clinical characteristics, intraoperative findings, complications, and outcomes after the first microvascular decompression (MVD) in patients with and without previous botulinum neurotoxin treatment for hemifacial spasm (HFS). The authors analyzed 246 MVDs performed at the University of Pittsburgh Medical Center between January 1, 2000, and December 31, 2007. One hundred and seventy-six patients with HFS underwent botulinum neurotoxin injection treatment prior to first MVD (Group I), and 70 patients underwent their first MVD without previous botulinum neurotoxin treatment (Group II). Clinical outcome data were obtained immediately after the operation, at discharge, and at follow-up. Follow-up data were collected from 177 patients with a minimum follow-up period of 9 months (mean 54.48 ± 27.84 months). In 246 patients, 89.4% experienced immediate postoperative relief of spasm, 91.1% experienced relief at discharge, and 92.7% experienced relief at follow-up. There was no significant difference in outcomes and complications between Group I and Group II (p > 0.05). Preoperatively, patients in Group I had higher rates of facial weakness, tinnitus, tonus, and platysmal involvement as compared with Group II (p < 0.05). The posterior inferior cerebellar artery and vertebral artery were intraoperatively identified as the offending vessels in cases of vasculature compression in a significantly greater number of patients in Group II compared with Group I (p = 0.008 and p = 0.005, respectively, for each vessel). The lateral spread response (LSR) disappeared in 60.48% of the patients in Group I as compared with 74.19% in Group II (p > 0.05). No significant differences in complications were noted between the 2 groups. Microvascular decompression is an effective and safe procedure for patients with HFS previously treated using botulinum neurotoxin. Intraoperative monitoring with LSR is an effective tool for evaluating adequate decompression.


A new look at the critical community size for childhood infections.
Quasi-stationarity and time to extinction are studied for the classic endemic model. Attention is restricted to the transition region in parameter space where the quasi-stationary distribution is non-normal. A new approximation of the marginal distribution of infected individuals in quasi-stationarity is presented. It leads to a simple explicit expression for an approximation of the critical community size in terms of model parameters.


Recovery from transcription inhibition in irradiated yeast cells.
Repair process operating on radiation damaged DNA may be investigated by studying its functional integrity, e.g. its ability to serve as template for transcription. We measured the synthesis of ribosomal RNA and of the inducible enzyme arginase in yeast cells and followed their recovery after X-ray, alpha-particle and heavy ion exposure. Transcription inhibiting lesions formed upon X-irradiation in yeast cells are repaired during post-exposure incubation ("liquid-holding"). The inactivation curves are strictly exponential immediately after irradiation. After the "liquid holding" treatment the inactivation curves are still exponential but with a progressive decrease of the slopes as a function of incubation time. This indicates that a constant fraction of the lesions is repaired per time interval. But even after long incubation times (24 h) there is still a sizeable unrepaired fraction. Comparing different yeast strains and different irradiation temperatures recovery can also be demonstrated in cells exposed to alpha-particles. In addition, recovery is detected by the arginase assay after irradiation of yeast with very heavy charged particles, e.g. titanium ions.


Twelve-hour fasting compared with expedited oral intake in the initial inpatient management of hyperemesis gravidarum: a randomised trial.
To evaluate fasting for 12 hours compared with expedited oral feeding in hospitalised women with hyperemesis gravidarum (HG). Randomised trial. University Hospital, Malaysia: April 2016-April 2017. One hundred and sixty women hospitalised for HG. Women were randomised upon admission to fasting for 12 hours or expedited oral feeding. Standard HG care was instituted. Primary outcome was satisfaction score with overall treatment at 24 hours (0-10 Visual Numerical Rating Scale VNRS), vomiting episodes within 24 hours and nausea VNRS score at enrolment, and at 8, 16 and 24 hours. Satisfaction score, median (interquartile range) 8 (5-9) versus 8 (7-9) (P = 0.08) and 24-hour vomiting episodes were 1 (0-4) versus 1 (0-5) (P = 0.24) for 12-hour fasting versus expedited feeding, respectively. Repeated measures analysis of variance of nausea scores over 24 hours showed no difference (P = 0.11) between trial arms. Participants randomised to 12-hour fasting compared with expedited feeding were less likely to prefer their feeding regimen in future hospitalisation (41% versus 65%, P = 0.001), to recommend to a friend (65% versus 84%, P = 0.01; RR 0.8, 95% CI 0.6-0.9) and to adhere to protocol (85% versus 95%, P = 0.04; RR 0.9, 95% CI 0.8-1.0). Symptoms profile, ketonuria status at 24 hours and length of hospital stay were not different. Advisory of 12-hour fasting compared with immediate oral feeding resulted in a non-significant difference in satisfaction score but adherence to protocol and fidelity to and recommendation of immediate oral feeding to a friend were lower. The 24-hour nausea scores and vomiting episodes were similar. Women hospitalised for hyperemesis gravidarum could feed as soon, as much and as often as can be tolerated compared with initial fasting.


Prospective study of two retrograde endodontic apical preparations with and without the use of CO2 laser.
This article covers a 4-year study that reports 320 cases in which endodontic surgery was performed for residual apical lesions or lesions that could not be treated in a conventional way. Four groups of 80 teeth each were formed and they were followed up after a 12-month interval. The first group comprised cases treated with a micro bur, retrograde filling and IRM; the second, cases treated at the apical and radicular portions with a CO2 laser; the third, cases in which the retrograde cavity was prepared with an ultrasonic device instead of a micro bur; and the fourth group comprised cases treated in a similar way to the second group, i.e., cases treated at the apical and radicular portions, but with a CO2 laser instead of a micro bur. After 12 months, the results showed a better prognosis with ultrasonic treatment. Regardless of technique, the CO2 laser did not improve the healing process.


Controlling NMDA receptor subunit composition using ectopic retention signals.
Ligand-gated ion channels (LGICs) mediate fast synaptic transmission in the CNS. Typically, these membrane proteins are multimeric complexes associating several homologous subunits around a central pore. Because of the large repertoire of subunits within each family, LGICs exist in vivo as multiple subtypes that differ in subunit composition and functional properties. Establishing the specific properties of individual receptor subtypes remains a major goal in the field of neuroscience and molecular pharmacology. However, isolating specific receptor subtype in recombinant systems can be problematic because of the mixture of receptor populations. This is the case for NMDA receptors (NMDARs), a large family of tetrameric glutamate-gated ion channels that play key roles in brain physiology and pathology. A significant fraction of native NMDARs are triheteromers composed of two GluN1 subunits and two different GluN2 subunits (GluN2A-D). We developed a method based on dual retention signals adapted from G-protein-coupled GABA-B receptors allowing exclusive cell surface expression of triheteromeric rat NMDARs while coexpressed diheteromeric receptors (which contain a single type of GluN2 subunit) are retained intracellularly. Using this approach, we determined the functional properties of GluN1/GluN2A/GluN2B triheteromers, one of the most abundant NMDAR subtypes in the adult forebrain, revealing their unique gating and pharmacological attributes. We envision applicability of the retention signal approach for the study of a variety of heteromeric glutamate-gated ion channel receptors with defined subunit composition.


Reduced responsiveness of [Ca2+]i to adenosine A1- and A2-receptor stimulation in the isoproterenol-stimulated ventricular myocytes of spontaneously hypertensive rats.
To determine the modulatory action of adenosine-receptor stimulation on [Ca2+]i responses to beta-adrenoceptor stimulation in the heart of the spontaneously hypertensive rat (SHR), the electrically induced [Ca2+]i transient in response to isoproterenol (ISO) in single ventricular myocytes pretreated with adenosine agonists in SHRs and its normotensive control Wistar-Kyoto (WKY) rats was measured with a spectrofluorometric method by using fura-2/AM as the calcium indicator. In both types of rat, ISO at 0.001-1 microM augmented the electrically induced [Ca2+]i transient, and the effect was blocked by a beta-adrenoceptor blocker, propranolol. In SHRs that did not exhibit cardiac hypertrophy, the resting level of [Ca2+]i and the amplitude of the electrically induced [Ca2+]i transient were the same as those in WKY rats, whereas the augmentation of the electrically induced [Ca2+]i transient in response to ISO was significantly lower than that in WKY rats. In WKY rats, the effects of ISO on the electrically induced [Ca2+]i transient were inhibited by the adenosine A1-receptor agonist, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA) at 0.01-10 microM. In contrast, the effects of ISO were further enhanced by the adenosine A2-receptor agonist, N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl)]adenosine (DPMA) at 1-10 microM. In SHRs, the inhibitory effect of R-PIA was significantly reduced, whereas the excitatory effect of DPMA was absent. The effects of both adenosine-receptor agonists in both types of rat were abolished by the respective adenosine-receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 3,7-dimethyl-1-propargylxanthine (DMPX). The results indicate that the modulatory actions of adenosine-receptor stimulation on [Ca2+]i response to beta-adrenoceptor stimulation in the hearts of SHRs are reduced, which is independent of cardiac hypertrophy.


The effect of erectile dysfunction on quality of life following treatment for localized prostate cancer.
All forms of prostate cancer therapy carry significant risk of erectile dysfunction, but patients value sexual function so highly that they are often willing to choose a therapy that offers a shorter life expectancy but better potency following treatment. Advances in research methodology now allow reliable collection of meaningful data regarding patients' health-related quality of life, including both objective evaluation of patients' functional status and their perceptions of their own health and its impact on their existence. In the past decade, several validated and reliable questionnaires have been developed that are specifically designed to measure HRQOL in men with prostate cancer. Studies using these instruments have found that function and perceived bother may not be correlated; patients may express satisfaction with their therapy despite loss of sexual function. Erectile aids, including sildenafil, can be helpful for patients following treatment for localized prostate cancer.


Beta-adrenoceptor-binding studies of the cardioselective beta blockers bisoprolol, H-I 42 BS, and HX-CH 44 BS to heart membranes and intact ventricular myocytes of adult rats: two beta 1-binding sites for bisoprolol.
beta-Adrenoceptor binding of cardioselective drugs to intact ventricular myocytes was performed using [3H]CGP-12177, a hydrophilic non-beta 1/beta 2-selective antagonist radioligand. The beta-adrenoceptor density on the intact cardiomyocytes was about 2 x 10(5) molecules/cell. The beta 1-selective antagonists H-I 42 BS and HX-CH 44 BS competed for [3H]CGP-12177 binding sites on the ventricular myocytes in an essentially monophasic manner with Ki = 72.6 nM and Ki = 76.7 nM, respectively. This is in contrast to the results of binding data from heart membranes, where these beta 1-antagonists bind in a biphasic manner with about 30% of an additional low affinity site, presumably corresponding to the beta 2-adrenoceptor. The beta 1-selective antagonist bisoprolol revealed two binding sites at the heart membranes and at the myocytes as well with Ki(1) = 34.2 and 20.0 nM and Ki(2) = 3,014 and 918 nM, respectively. Our results suggest that viable adult rat ventricular myocytes may contain two beta 1-adrenoceptor binding sites exhibiting different affinities for bisoprolol, whereas beta 2-adrenergic receptors are completely absent.


Lou Gehrig and amyotrophic lateral sclerosis. Is vitamin E to be revisited?
Investigators are beginning to reexamine the use of vitamin E for the treatment of amyotrophic lateral sclerosis. Vitamin E was isolated in the 1920s, and the results of animal studies led rapidly to clinical use. Regrettably, vitamin E did not ameliorate the progression of amyotrophic lateral sclerosis for Lou Gehrig, but more recent advances may identify subpopulations that do respond to vitamin E.


Multicentre evaluation of performance of C-reactive protein analysis over a one-year period.
This communication deals with a longitudinal evaluation of C-reactive protein (CRP) analysis during a one-year period using a single lot of liquid control sera (3 levels) (BIOREF-CRP levels 1, 2 and 3) in different laboratories. A total of 652 sets of data were returned from 20 participating laboratories using 13 different reagent-measuring device combinations. The use of the control materials was defined in a standard operating procedure. Data was returned to the organizers on a monthly basis and questions could be asked or problems presented during the evaluation period. Although the performance of different reagents varied, the control materials were shown to be stable over the whole of the evaluation period when stored at 4-7 degrees C in a refrigerator/cold room. Typical problems were encountered, examples of which are presented here in graphical and tabular form.


[Value of patient health questionnaires (PHQ)-9 and PHQ-2 for screening depression disorders in cardiovascular outpatients].
To analyze the value of 2- and 9-question patient health questionnaires (PHQ-2 and PHQ-9) for screening status of depression in cardiovascular outpatients. From June 2013 to January 2014, a total of 201 outpatients from psycho-cardiological outpatients departments were consecutively enrolled into this study. All patients were asked to complete PHQ-9 and the mental psychological assessment by qualified researchers trained by psychiatry according to the composite international diagnostic interviews (CIDI), 50 cases were retested to assess the retest reliability after one week. The PHQ-2 and PHQ-9 were validated with the CIDI as the reference criteria. According to the CIDI, 42 (21.3%) out of the 201 outpatients were diagnosed as depression. For PHQ-9 scale, a cutoff value of 10 presented satisfactory results with 87.1% sensitivity, 83.5% specificity, 58.7% positive predicting value, 95.6% negative predicting value and the area under the ROC curve (AUC) was 0.877 (SE = 0.032, 95% CI: 0.813-0.938). The Cronbach's alpha coefficients and test-retest reliability of the PHQ-9 were 0.809 and 0.882, respectively. Compared with CIDI, the cutoff value of the PHQ-2 was 3 with 85.7% sensitivity, 69.2% specificity, 57.1% positive predicting value, 93.6% negative predicting value, and the AUC was 0.806 (SE = 0.042, 95% CI: 0.774-0.889). The Cronbach's alpha coefficients and test-retest reliability of the PHQ-2 were 0.785 and 0.813, respectively. The PHQ-2 and PHQ-9 are reliable and efficient instruments for screening and especially excluding depression in cardiovascular outpatients.


Drug resistance in epilepsy: human epilepsy.
The basis of drug resistance in human epilepsy is not understood. Parallels with resistance in cancer suggest that drug resistance proteins may have a role. To examine this possibility, we have studied human brain tissue containing pathologies capable of causing refractory epilepsy. Using immunohistochemistry for P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1), we examined both pathological tissue and control tissue. We demonstrate expression of Pgp and MRP1 in glia from cases of malformation of cortical development studied both before and after the onset of epilepsy, as well as in cases of hippocampal sclerosis and dysembryoplastic neuroepithelial tumours. In one particular type of malformation, we also demonstrate that dysplastic neurons express MRP1. The pattern of immunolabelling suggests overexpression is concentrated particularly around vessels in most of the pathologies. The timing shows that expression may be constitutive in some pathologies. These findings suggest that drug resistance proteins may contribute to drug resistance in refractory epilepsy.


Artificial Metalloenzymes: Recent Developments and Innovations in Bioinorganic Catalysis.
Cellular life is orchestrated by the biochemical components of cells that include nucleic acids, lipids, carbohydrates, proteins, and cofactors such as metabolites and metals, all of which coalesce and function synchronously within the cell. Metalloenzymes allow for such complex chemical processes, as they catalyze a myriad of biochemical reactions both efficiently and selectively, where the metal cofactor provides additional functionality to promote reactivity not readily achieved in their absence. While the past 60 years have yielded considerable insight on how enzymes catalyze these reactions, a need to engineer and develop artificial metalloenzymes has been driven not only by industrial and therapeutic needs, but also by innate human curiosity. The design of miniature enzymes, both rationally and through serendipity, using both organic and inorganic building blocks has been explored by many scientists over the years and significant progress has been made. Herein, recent developments over the past 5 years in areas that have not been recently reviewed are summarized, and prospects for future research in these areas are addressed.


Online measurement of conductivity/permittivity of fluid by a new contactless impedance sensor.
By expanding the contactless conductivity detection (CCD) technique to contactless impedance detection technique, a new contactless impedance sensor is designed to implement the online measurement for both the conductivity of a conductive fluid and the permittivity of a non-conductive fluid. In the new contactless impedance sensor, a new simulated inductor is developed to overcome the unfavorable influences of the coupling capacitances by impedance elimination principle, and the digital phase-sensitive demodulation (DPSD) technique is adopted to realize the impedance measurement. To verify the effectiveness of the new contactless impedance sensor, simulation experiments (using different resistors, capacitors, and their combinations) and practical fluid experiments (using KCl solutions with different concentrations, eight organic solvents, and pure water) are carried out. The experimental results show that the development of the new contactless impedance sensor is successful and the conductivity/permittivity measurement performance of the new sensor is satisfactory. The maximum relative error of conductivity measurement is 3.1% and the maximum relative error of permittivity measurement is 5.5%. Compared with the conventional conductivity/permittivity sensors, the new sensor can implement the contactless online measurement of both the two electrical parameters of fluid. Meanwhile, the new contactless impedance sensor is suitable for industrial applications and has the advantages of simple construction and low cost.


Acquired platelet dysfunction with spontaneous intramuscular hematoma and compartment syndrome in cirrhosis.
Cirrhosis patients are at high risk for bleeding as a result of decreased platelet counts and impaired function, defective production of coagulation factors and abnormalities in clot lysis. The authors report the case of a 58 year-old man with cryptogenic cirrhosis who presented initially with intramuscular hematoma in the thigh which progressed to compartment syndrome. The patient developed disseminated progressive intramuscular hematomas in the muscles of chest, abdomen and finally retroperitoneal hemorrhage secondary to probable accelerated intravascular coagulation and fibrinolysis (AICF) culminating in death. This case highlights many of the common coagulation abnormalities seen in cirrhosis. The authors speculate the sequence of events in our patient at every level of the coagulation cascade which could have lead to this fatal outcome.


Detection of allele-specific methylation through a generalized heterogeneous epigenome model.
High-throughput sequencing has made it possible to sequence DNA methylation of a whole genome at the single-base resolution. A sample, however, may contain a number of distinct methylation patterns. For instance, cells of different types and in different developmental stages may have different methylation patterns. Alleles may be differentially methylated, which may partially explain that the large portions of epigenomes from single cell types are partially methylated, and may have major effects on transcriptional output. Approaches relying on DNA sequence polymorphism to identify individual patterns from a mixture of heterogeneous epigenomes are insufficient as methylcytosines occur at a much higher density than SNPs. We have developed a mixture model-based approach for resolving distinct epigenomes from a heterogeneous sample. In particular, the model is applied to the detection of allele-specific methylation (ASM). The methods are tested on a synthetic methylome and applied to an Arabidopsis single root cell methylome.


Political cycles: Beyond rational expectations.
Existing rational expectations models cannot satisfactorily explain why political budget manipulations systematically raise re-election chances and only occur in "specific contexts". This paper offers a theoretical explanation by including unsophisticated voters into an opportunistic political cycle model; unsophisticated voters are unable to take the optimal behaviour of other agents (fully) into account, but may, nonetheless, vaguely suspect government deception. First, rationally expected manipulations are, on average, fruitless in equilibrium. By including unsophisticated voters we can, however, corroborate empirically found electoral effects of political budget manipulations. Second, unsophisticated voters become anxious and suspicious in an intransparent or uncertain world, but the government tries to "outperform" their scepticism by increasing budget manipulations in order to appear more competent and, ultimately, increase re-election chances. It is, therefore, not surprising that political budget cycles are observed in countries suffering from intransparencies such as developing countries or new democracies. Third and in addition, the model presented here predicts that political opportunism produces, unintentionally, a countercyclical policy effect in election years, thereby, for instance, alleviating the typical problem of policy procyclicality in developing countries. The paper also offers a theoretical explanation for political distortions found in forecasts by US states. Based on overly optimistic revenue forecasts the incumbent state government can conduct expansionary fiscal policies in order to appear more competent prior to an upcoming election. Since the resulting deficit can only be observed afterwards, the government can effectively circumvent a constitutional balanced budget constraint. As a result, there are political forecast and budget cycles in the state. More generally, however, these findings may also apply to European countries where balanced budget constraints are or will be in place (for instance the debt brakes in Switzerland and Germany); similarly, they apply to the supra-national European Fiscal Compact of the European Union.


Illness beliefs and treatment beliefs as predictors of short-term and medium-term outcome in chronic back pain.
Patients' illness beliefs were shown to be more relevant than other psychosocial factors of influence for predicting outcome in back pain in primary care. The aim of this study was to determine whether illness beliefs and beliefs about rehabilitation are predictors of functioning, pain intensity, and coping with pain after rehabilitation in a population with longstanding chronic back pain. The study included 110 patients with longstanding chronic back pain in a longitudinal study design with 3 measurement points (before rehabilitation, end of rehabilitation, and 6 months follow-up). Hierarchical multiple regression analyses were conducted to test the relative contribution of illness beliefs and beliefs about rehabilitation to the rehabilitation outcomes while adjusting for baseline values of outcome measures, mental health, sociodemographic, and illness-related variables. Illness beliefs and beliefs about rehabilitation made a significant contribution to the prediction of rehabilitation outcomes. In the short and medium term, incremental variance for coping with pain was as much as 13%, for functioning up to 14%, and for pain intensity between 6% and 9%. Further studies should be conducted as a confirmatory test of our preliminary results and to test the relative relevance of these constructs compared with other yellow flags for chronic patient samples.


Teeth or implants: a 1990s dilemma.
Using endosseous implants to replace missing teeth is a highly predictable process when the precepts defined by Brånemark are followed. The question of whether or not to extract periodontally compromised teeth, however, remains controversial. This article presents a case report illustrating some of the concerns involved when treating a patient with a combination of natural teeth and implants, and proposes several compelling questions regarding the treatment decisions made in this case.


Ion trapping, reduced rotational viscosity, and accelerated electro-optic response characteristics in gold nano-urchin-nematic suspensions.
The free-ion concentration in a nematic liquid crystal (LC) is found to be significantly reduced when gold nano-urchins (AuNUs) of 50-nm diameter are dispersed in the LC in dilute concentrations. The nano-urchins on AuNUs trap a significant amount of mobile ions, reducing the free-ion concentration in the LC media. The reduction of free ions results in a decreased rotational viscosity and accelerated electro-optic response of the LC. The study is carried out with several AuNUs concentrations in the LC, and the experimental results consistently suggest that there exists an optimal concentration of AuNUs, above which they tend to aggregate. At the optimal concentration, the ion trapping is maximum, rotational viscosity is at its lowest, and the electro-optic response is the fastest. Above this optimal AuNUs concentration, the rotational viscosity is found to increase, and consequently, the LC no longer exhibits an accelerated electro-optic response.


A device for dried blood microsampling in quantitative bioanalysis: overcoming the issues associated blood hematocrit.
A cross-laboratory experiment has been performed on a novel dried blood sampler in order to investigate whether it overcomes issues associated with blood volume and hematocrit (HCT) that are observed when taking a subpunch from dried blood spot samples. An average blood volume of 10.6 μl was absorbed by the samplers across the different HCTs investigated (20-65%). No notable change of volume absorbed was noted across the HCT range. Furthermore, the variation in blood sample volumes across six different laboratories was within acceptable limits. The novel volumetric absorptive microsampling device has the potential to deliver the advantages of dried blood spot sampling while overcoming some of the issues associated with the technology.


Arginine 107 of yeast ATP synthase subunit g mediates sensitivity of the mitochondrial permeability transition to phenylglyoxal.
Modification with arginine-specific glyoxals modulates the permeability transition (PT) of rat liver mitochondria, with inhibitory or inducing effects that depend on the net charge of the adduct(s). Here, we show that phenylglyoxal (PGO) affects the PT in a species-specific manner (inhibition in mouse and yeast, induction in human and Drosophila mitochondria). Following the hypotheses (i) that the effects are mediated by conserved arginine(s) and (ii) that the PT is mediated by the F-ATP synthase, we have narrowed the search to 60 arginines. Most of these residues are located in subunits α, β, γ, ϵ, a, and c and were excluded because PGO modification did not significantly affect enzyme catalysis. On the other hand, yeast mitochondria lacking subunit g or bearing a subunit g R107A mutation were totally resistant to PT inhibition by PGO. Thus, the effect of PGO on the PT is specifically mediated by Arg-107, the only subunit g arginine that has been conserved across species. These findings are evidence that the PT is mediated by F-ATP synthase.


Structural Studies of G Protein-Coupled Receptors.
G protein-coupled receptors (GPCRs) constitute the largest and the most physiologically important membrane protein family that recognizes a variety of environmental stimuli, and are drug targets in the treatment of numerous diseases. Recent progress on GPCR structural studies shed light on molecular mechanisms of GPCR ligand recognition, activation and allosteric modulation, as well as structural basis of GPCR dimerization. In this review, we will discuss the structural features of GPCRs and structural insights of different aspects of GPCR biological functions.


On the Importance of Processing Conditions for the Nutritional Characteristics of Homogenized Composite Meals Intended for Infants.
The nutritional quality of infant food is an important consideration in the effort to prevent a further increase in the rate of childhood obesity. We hypothesized that the canning of composite infant meals would lead to elevated contents of carboxymethyl-lysine (CML) and favor high glycemic and insulinemic responses compared with milder heat treatment conditions. We have compared composite infant pasta Bolognese meals that were either conventionally canned (CANPBol), or prepared by microwave cooking (MWPBol). A meal where the pasta and Bolognese sauce were separate during microwave cooking (MWP_CANBol) was also included. The infant meals were tested at breakfast in healthy adults using white wheat bread (WWB) as reference. A standardized lunch meal was served at 240 min and blood was collected from fasting to 360 min after breakfast. The 2-h glucose response (iAUC) was lower following the test meals than with WWB. The insulin response was lower after the MWP_CANBol (-47%, p = 0.0000) but markedly higher after CANPBol (+40%, p = 0.0019), compared with WWB. A combined measure of the glucose and insulin responses (ISIcomposite) revealed that MWP_CANBol resulted in 94% better insulin sensitivity than CANPBol. Additionally, the separate processing of the meal components in MWP_CANBol resulted in 39% lower CML levels than the CANPBol. It was therefore concluded that intake of commercially canned composite infant meals leads to reduced postprandial insulin sensitivity and increased exposure to oxidative stress promoting agents.


Detection of Pathogenic Viruses, Pathogen Indicators, and Fecal-Source Markers within Tanker Water and Their Sources in the Kathmandu Valley, Nepal.
Tanker water is used extensively for drinking as well as domestic purposes in the Kathmandu Valley of Nepal. This study aimed to investigate water quality in terms of microbial contamination and determine sources of fecal pollution within these waters. Thirty-one samples from 17 tanker filling stations (TFSs) and 30 water tanker (WT) samples were collected during the dry and wet seasons of 2016. Escherichia coli was detected in 52% of the 31 TFS samples and even more frequently in WT samples. Of the six pathogenic viruses tested, enteroviruses, noroviruses of genogroup II (NoVs-GII), human adenoviruses (HAdVs), and group A rotaviruses were detected using quantitative PCR (qPCR) at 10, five, four, and two TFSs, respectively, whereas Aichi virus 1 and NoVs-GI were not detected at any sites. Index viruses, such as pepper mild mottle virus and tobacco mosaic virus, were detected using qPCR in 77% and 95% out of 22 samples, respectively, all of which were positive for at least one of the tested pathogenic viruses. At least one of the four human-associated markers tested (i.e., BacHum, HAdVs, and JC and BK polyomaviruses) was detected using qPCR in 39% of TFS samples. Ruminant-associated markers were detected at three stations, and pig- and chicken-associated markers were found at one station each of the suburbs. These findings indicate that water supplied by TFSs is generally of poor quality and should be improved, and proper management of WTs should be implemented.


The relationship between inflammatory markers, leptin and adiponectin in chronic hemodialysis patients.
Chronic inflammation is prevalent in dialysis patients. We investigated the relationship between inflammation and newly identified adipokines: leptin and adiponectin in this population. A total of 129 chronic hemodialysis patients were collected. Serum high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), leptin and adiponectin levels were determined as well as other metabolic variables. Correlation studies and multiple regression analysis were performed among variables. Our results showed that hemodialysis patients had elevated levels of inflammatory markers, leptin and adiponectin. Diabetic subjects had higher serum CRP and lower albumin levels than non-diabetics. Serum CRP levels were positively correlated with IL-6 levels and negatively correlated with albumin levels. Serum leptin levels were directly related to CRP levels while adiponectin levels were inversely related to CRP levels. A significant negative correlation was observed between serum leptin and adiponectin levels. Serum IL-6 levels were the single independent factor affecting CRP levels. Body mass index can predict both serum leptin and adiponectin levels. We conclude that hemodialysis patients are at an increased risk of chronic inflammation and diabetes patients are even more susceptible to this status. Both serum leptin and adiponectin levels are associated with inflammatory markers. As adipose tissue is the major secreting site of these adipokines, our results suggest that adipose tissue plays an important role in the pathogenesis of chronic inflammation in dialysis patients.


BRAF/MEK Inhibitor Therapy: Consensus Statement From the Faculty of the Melanoma Nursing Initiative on Managing Adverse Events and Potential Drug Interactions.
BRAF/MEK inhibitor therapy improves outcomes in BRAF V600E- and V600K-mutated unresectable or metastatic melanoma. However, these regimens are associated with adverse events (AEs) that may lead to unnecessary drug modifications and discontinuations or potentially serious sequelae. In addition, drug-drug interactions (DDIs) may result in AEs or altered therapeutic efficacy. . This article presents consensus statements to guide nurses in the prevention, recognition, and management of AEs and potential DDIs associated with BRAF/MEK inhibitor therapy. . Members of the Melanoma Nurse Initiative reviewed the current literature and clinical experience related to AEs and DDIs associated with BRAF/MEK inhibitor therapy. . The care step pathways provided for select AEs represent a proactive, comprehensive nursing care plan to support optimal patient outcomes. Recommendations are also offered for preventing and managing DDIs.


Family medicine clerkship curriculum: competencies and resources.
Funded by the Health Resources and Services Administration (HRSA) from 2000-2005, the Family Medicine Curriculum Resource Project (FMCRP) developed a set of resources to improve medical student education. As part of this project, the FMCRP Clerkship Workgroup created and organized resources for developing, teaching, and evaluating a family medicine clerkship. Using the Accreditation Council for Graduate Medical Education competencies as the overarching structure, the organizational scheme incorporated family medicine principles and themes in covering core topics. This curricular resource was designed to be flexible and adaptable to different medical schools and curricular settings.


Sleep posture and unilateral renal stone formation.
Until now, there has been no hypothesis to explain the aetiology of recurrent unilateral urolithiasis in stone formers. Previous studies suggested that sleep posture may lead to alterations of renal haemodynamics. The probable association between sleep posture and unilateral urolithiasis is reported here. In this prospective cohort study, 38 patients with recurrent unilateral renal stones and 42 healthy controls were studied. Background variables were evaluated using a questionnaire. Sleep posture was recorded with a sleep recorder. Unpaired t test, Mann-Whitney test, and chi-squared test were performed as needed and p<0.05 was considered significant. Of 17 patients with right kidney stones, right-side-down sleep posture was seen in 15 (88.2%) and supine/prone in two (11.8%). Of 21 patients with left kidney stone, sleep posture was left-side-down in 13 (61.9%), right-side-down in two (9.5%) and supine/prone in six (28.6%, p=0.0). That is, a significant association was found between lateral sleep posture and ipsilateral kidney stone formation [odds ratio (OR)=21.13 for left-side, 95% confidence interval (CI) 4.16-123.8; and OR=21.14 for right-side, CI 95% 3.6-160.4]. Although the impact of sleep posture in recurrent unilateral stone formation remains unclear, sleep posture may play a causative role in promotion of urolithiasis. Although this observation needs further investigation, further studies should be conducted on the efficacy of appropriate education and learning to increase patients' capability to change routine sleep posture.


Enabling complex nanoscale pattern customization using directed self-assembly.
Block copolymer directed self-assembly is an attractive method to fabricate highly uniform nanoscale features for various technological applications, but the dense periodicity of block copolymer features limits the complexity of the resulting patterns and their potential utility. Therefore, customizability of nanoscale patterns has been a long-standing goal for using directed self-assembly in device fabrication. Here we show that a hybrid organic/inorganic chemical pattern serves as a guiding pattern for self-assembly as well as a self-aligned mask for pattern customization through cotransfer of aligned block copolymer features and an inorganic prepattern. As informed by a phenomenological model, deliberate process engineering is implemented to maintain global alignment of block copolymer features over arbitrarily shaped, 'masking' features incorporated into the chemical patterns. These hybrid chemical patterns with embedded customization information enable deterministic, complex two-dimensional nanoscale pattern customization through directed self-assembly.


Evaluation of prolonged incubation time of 16-20 h with the EUCAST rapid antimicrobial susceptibility disc diffusion testing method.
Antimicrobial resistance rates are continuously increasing, driving the need for rapid antimicrobial susceptibility testing (RAST) results, especially in the treatment of bloodstream infections. The EUCAST RAST method performed directly from positive blood cultures with incubation times from 4 to 8 h was developed in 2018 and is now used in many laboratories. To increase the practicality of the method, an extended incubation time of 16 and 20 h was evaluated in this study. Blood culture bottles were spiked with clinical isolates (n = 325) of the seven most important sepsis pathogens. The EUCAST RAST method was performed, extending the incubation time to 16 and 20 h. Broth microdilution (BMD) was used as a reference, except for screening tests where standard disc diffusion or presence of resistance genes was used. Inhibition zones were possible to read for all species-agent combinations. For 16 and 20 h, the MIC zone diameter correlations were sufficiently similar to allow establishment of common breakpoints for the time interval of 16-20 h. The proportion of isolates in the area of technical uncertainty was, on average, 6% for all species and the number of errors were low, with <1% false-resistant and <0.5% false-susceptible results. This study shows that, for EUCAST RAST, prolonging the recommended incubation to 16-20 h is possible and can be used as a complement when the intended shorter incubation is not possible to achieve. The introduction of the prolonged incubation will increase the usefulness of the EUCAST RAST method in clinical laboratories with limited opening hours.


Complementary roles for CD19 and Bruton's tyrosine kinase in B lymphocyte signal transduction.
CD19 and Bruton's tyrosine kinase (Btk) may function along common signaling pathways in regulating intrinsic and B cell Ag receptor (BCR)-induced signals. To identify physical and functional interactions between CD19 and Btk, a CD19-negative variant of the A20 B cell line was isolated, and CD19-deficient (CD19(-/-)) and CD19-overexpressing mice with the X-linked immunodeficient (Xid; Btk) mutation were generated. In A20 cells, Btk physically associated with CD19 following BCR engagement. CD19 and Btk interactions were not required for initial Btk phosphorylation, but CD19 expression maintained Btk in an activated state following BCR engagement. In primary B cells, CD19 signaling also required downstream Btk function since CD19-induced intracellular Ca(2+) ([Ca(2+)](i)) responses were modest in Xid B cells. In addition, CD19 overexpression did not normalize the Xid phenotype and most phenotypic and functional hallmarks of CD19 overexpression were not evident in these mice. However, CD19 and Btk also regulate independent signaling pathways since their combined loss had additive inhibitory effects on BCR-induced [Ca(2+)](i) responses and CD19 deficiency induced a severe immunodeficiency in Xid mice. Thus, CD19 expression amplifies or prolongs Btk-mediated signaling, rather than serving as a required agent for Btk activation. Consistent with this, phosphatidylinositol 3-monophosphate kinase and Akt activation were normal in CD19(-/-) B cells following IgM engagement, although their kinetics of activation was altered. Thus, these biochemical and compound gene dosage studies indicate that Btk activation and [Ca(2+)](i) responses following BCR engagement are regulated through multiple pathways, including a CD19/Src family kinase-dependent pathway that promotes the longevity of Btk signaling.


[FREE CROIN FLAP FOR REPAIRING DEFECTS OF DONOR AFTER TOE TISSUE TRANSPLANTATION].
To discuss the effectiveness of free croin flap in repairing defects of donor after toe or feetissue flap transplantation. Between March 2010 and May 2015, 23 cases of defects of donor after toe or feet tissue flap transplantation were repaired with free croin flap and followed up for more than 6 months, and the clinical data were retrospectively analyzed. There were 15 males and 8 females, with an age range from 17 to 52 years (mean, 25.6 years). All finger or soft tissue defects were caused by trauma. Defects were repaired in emergency operation with toe or feet tissue flap transplantation in 18 cases, defects were secondarily reconstructed at 3-8 months after injury in 5 cases. The defect area at the feet donor site ranged from 3 cmx3 cm to 10 cmx6 cm, all accompanied with exposure of bone, and tendon. The area of free croin flap was 3.5 cm x 3.5 cm-11.0 cm x 6.5 cm, the vessel of flap was anastomosed with artery and vein of foot. The inguinal donor site was sutured directly. The operation time was 3-9 hours (mean, 4.5 hours); the intraoperative blood loss was 50-300 mL (mean, 120 mL). Vessel crisis occurred in 1 case postoperatively; mild and moderate swelling occurred in 3 cases, with small sporadic blisters formation; free croin flap survived completely in the other cases, and primary healing was obtained at feet wound and inguinal donor sites. Twenty-three cases were followed up 6-24 months (mean, 9 months). The color and texture of the croin flaps were similar to that of the adjacent skin, no obvious scar contracture and pigmentation were observed; the patient could walk with weight loading, the two-point discrimination was 18-35 mm (mean, 26 mm) at 6 months after operation. The color, texture, and shape of reconstructed finger was good; the function of grasping and pinching recovered well; the two-point discrimination was 5.5-11.0 mmfunctional evaluation standard by Chinese Medical Association, the results were excellent in 18 cases and good in 5 cases. Free croin flap can effectively repair skin and soft tissue defects of donor after toe or feet tissue flap transplantation, and good function and appearance of feet can be obtained.


Pharmacokinetics of nitrendipine in the elderly.
The acute and short-term pharmacokinetics of the calcium antagonist nitrendipine were investigated in 18 elderly subjects (9 healthy volunteers and 9 hypertensive patients). The subjects received nitrendipine 10 mg twice daily for 7 days and the pharmacokinetics profiles for days 1 and 7 were compared for evidence of drug accumulation. In the healthy volunteers, neither the area under the curve (AUC) nor Cmax were significantly affected by nitrendipine treatment, although T1/2 was significantly increased on day 7. In the hypertensive patients, AUC was higher on day 7 than day 1, although this was only marginally significant (p = 0.050); Cmax and T1/2 were unchanged. Nitrendipine significantly reduced both systolic and diastolic blood pressure in the hypertensive patients but had no effect on the blood pressure of the healthy normotensive volunteers. Nitrendipine does not appear to accumulate significantly when given twice daily to elderly volunteers and hypertensive patients.


Hypertension and myocarditis in rabbits exposed to hexachlorocyclohexane and endosulfan.
Male albino rabbits were exposed to the organochlorinated pesticides hexachlorocyclohexane (HCH) and endosulfan (2.5 and 5.0 mg/kg, ip) twice a week for 12 mo. The mean body weight of the rabbits at 12 mo was lower than that of the controls. There was rise in blood pressure and heart rate. Electrocardiograms (ECG) in both the exposed groups showed increases in PR, QT and RR intervals. Extensive myocardial damage was recorded with marked degeneration of muscle fibers vacuolization and leucocytic infiltration. Adrenals had thickened capsules and hyperplasia of cortical cells. Both pesticides produced significant increases (p less than 0.001) of 11-hydroxycortisone at all time intervals. Hypertension and myocarditis occurred in rabbits exposed to HCH and endosulfan.


Suicide prevention evaluation in a Western Athabaskan American Indian Tribe--New Mexico, 1988-1997.
Since 1979, suicide and homicide have alternated as the second and third leading causes of death among young American Indians and Alaska Natives (AI/ANs). From 1979 through 1992, suicide rates for AI/ANs in all age groups were approximately 1.5 times the rates for the overall U.S. population. During 1991-1993, suicide rates for AI/ANs aged 15-24 and 25-34 years were 31.7 and 26.6 per 100,000 population, respectively; males aged 15-34 years accounted for 64% of all AI/AN suicides. In the overall U.S. population during 1991-1993, the rates for persons in these same age groups were 13.0 and 14.5, respectively. Since 1980, suicide has been either the second or third leading cause of death for persons aged 15-24 years in the overall U.S. population. Although knowledge about suicide among AI/ANs has increased, information about the efficacy of suicide prevention and intervention programs in general, and specifically in AI/AN communities, is scarce. In January 1990, following concern raised by tribal officials in 1988 about suicide among youth, a Western Athabaskan tribe in rural New Mexico implemented a suicide prevention and intervention program that targeted tribal members aged 15-19 years. This report summarizes the results of the program through 1997 and indicates that rates of suicide and attempted suicide among this target population decreased substantially after the program was implemented.


Drosophila Nod protein binds preferentially to the plus ends of microtubules and promotes microtubule polymerization in vitro.
Nod, a nonmotile kinesin-like protein, plays a critical role in segregating achiasmate chromosomes during female meiosis. In addition to localizing to oocyte chromosomes, we show that functional full-length Nod-GFP (Nod(FL)-GFP) localizes to the posterior pole of the oocyte at stages 9-10A, as does kinesin heavy chain (KHC), a plus end-directed motor. This posterior localization is abolished in grk mutants that no longer maintain the microtubule (MT) gradient in the oocyte. To test the hypothesis that Nod binds to the plus ends of MTs, we expressed and purified both full-length Nod (Nod(FL)) and a truncated form of Nod containing only the motor-like domain (Nod318) from Escherichia coli and assessed their interactions with MTs in vitro. Both Nod(FL) and Nod318 demonstrate preferential binding to the ends of the MTs, displaying a strong preference for binding to the plus ends. When Nod318-GFP:MT collision complexes were trapped by glutaraldehyde fixation, the preference for binding to plus ends versus minus ends was 17:1. Nod(FL) and Nod318 also promote MT polymerization in vitro in a time-dependent manner. The observation that Nod is preferentially localized to the plus ends of MTs and stimulates MT polymerization suggests a mechanism for its function.


Solid-state circular dichroism and hydrogen bonding, part 2: the case of hypothemycin re-investigated.
The impact of crystalline forces on the solid-state circular dichroism (CD) spectrum of hypothemycin (), a biologically active molecule extracted from natural sources, has been analyzed by means of time-dependent density functional theory CD calculations. Input structures were extracted from the X-ray geometry of and consisted in the isolated molecule, its cluster with five water molecules, and 20 different dimers (plus water molecules) representative of all the closest neighbors found in the crystal. The effects of solid-state intermolecular hydrogen bonds and through-space exciton couplings in determining the solid-state CD spectrum of hypothemycin were evaluated and compared.


Dual effects of tetracaine on spontaneous calcium release in rat ventricular myocytes.
1. Confocal microfluorometry was used to study the effects of tetracaine on spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) in isolated rat ventricular myocytes. 2. At low concentrations (0.25-1.25 mM), tetracaine caused an initial inhibition of spontaneous release events (Ca2+ sparks) and Ca2+ waves, which was followed by a gradual increase in Ca2+ release activity. The frequency and magnitude of sparks were first decreased and then increased with respect to control levels. At high concentrations (> 1.25 mM), tetracaine abolished all forms of spontaneous release. 3. Exposure of the myocytes to tetracaine resulted in a gradual increase in the SR Ca2+ load as indexed by changes in the magnitude of caffeine-induced Ca2+ transients. 4. In cardiac SR Ca(2+)-release channels incorporated into lipid bilayers, tetracaine (> 0.25 mM) induced a steady inhibition of channel activity. Addition of millimolar Ca2+ to the luminal side of the channel caused an increase in channel open probability under control conditions as well as in the presence of various concentrations of tetracaine. 5. We conclude that the primary effect of tetracaine on SR Ca(2+)-release channels is inhibition of channel activity both in vitro and in situ. The ability of tetracaine to reduce spark magnitude suggests that these events are not due to activation of single channels or non-reducible clusters of channels and, therefore, supports the multichannel origin of sparks. We propose that the paradoxical late potentiation of release by submaximal concentrations of tetracaine is caused by a gradual increase in SR Ca2+ load and subsequent activation of the Ca(2+)-release channels by Ca2+ inside the SR.


Effect of anaesthesia on insulin-induced hypoglycemia in rabbits.
The aim of this study was to determine how anaesthetized rabbits survive much longer than awake rabbits after receiving an insulin overdose. Insulin appeared to act in both groups of rabbits because there was a prompt fall in circulating glucose, free fatty acids, and beta-hydroxybutyrate concentrations. Carbohydrate appeared to be the principal energy source for anaesthetized rabbits because their respiratory quotient approached unity. Although the fall in glycemia was similar in both groups of rabbits, the circulating lactate concentration rose only in the anaesthetized group. This rise in lactate in the initial 60 min after insulin was given could account for most of the fall in glycemia if the source of lactate was the glucose pool. The decline in hepatic glycogen was close to 100 mumol/g liver; this would account for about one-third of the total energy turnover and close to one-half of the measured glucose appearance in these anaesthetized rabbits. As judged from the rate of oxygen consumption, muscle glycogen seemed to supply two-thirds of the fuel to be oxidized in these rabbits. However, only one-third of the lactate released from muscle was first converted to glucose and the remainder was oxidized directly to CO2. Although insulin provided the metabolic setting for a rapid rate of glucose oxidation, this rate appeared to be diminished when the overall rate of oxygen consumption was lower during anaesthesia.


Effects and Progress of Photo-Crosslinking Hydrogels in Wound Healing Improvement.
Wound healing is a dynamic physiological process, including three stages: inflammation, tissue formation, and remodeling. The quality of wound healing is affected by many topical and systemic factors, while any small factor may affect the process. Therefore, improving the quality of wound healing is a complex and arduous challenge. Photo-crosslinking reaction using visible light irradiation is a novel method for hydrogel preparation. Photo-crosslinking hydrogels can be controlled in time and space, and are not interfered by temperature conditions, which have been widely used in the fields of medicine and engineering. This review aims to summarize the application of photo-crosslinking hydrogels in improving the quality of wound healing, mainly including the material design, application mechanism, and effect of photo-crosslinking hydrogels applied in wound healing, followed by the applicable animal models for experimental research. Finally, this review analyzes the clinical application prospects of photo-crosslinking hydrogels in the field of wound healing.


Biophysical insights into how surfaces, including lipid membranes, modulate protein aggregation related to neurodegeneration.
There are a vast number of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), associated with the rearrangement of specific proteins to non-native conformations that promotes aggregation and deposition within tissues and/or cellular compartments. These diseases are commonly classified as protein-misfolding or amyloid diseases. The interaction of these proteins with liquid/surface interfaces is a fundamental phenomenon with potential implications for protein-misfolding diseases. Kinetic and thermodynamic studies indicate that significant conformational changes can be induced in proteins encountering surfaces, which can play a critical role in nucleating aggregate formation or stabilizing specific aggregation states. Surfaces of particular interest in neurodegenerative diseases are cellular and subcellular membranes that are predominately comprised of lipid components. The two-dimensional liquid environments provided by lipid bilayers can profoundly alter protein structure and dynamics by both specific and non-specific interactions. Importantly for misfolding diseases, these bilayer properties can not only modulate protein conformation, but also exert influence on aggregation state. A detailed understanding of the influence of (sub)cellular surfaces in driving protein aggregation and/or stabilizing specific aggregate forms could provide new insights into toxic mechanisms associated with these diseases. Here, we review the influence of surfaces in driving and stabilizing protein aggregation with a specific emphasis on lipid membranes.


Comparison between AER and behavioral thresholds in normally and abnormally hearing chinchillas.
The present study compared the auditory evoked response (AER) and behavioral thresholds from the chinchilla before and after acoustic overstimulation. Bipolar electrodes were chronically implanted in the inferior colliculus of seven monauralized behaviorally conditioned animals (shock-avoidance). AER to 20-msec and behavioral thresholds to 20- and 500-msec tone bursts were determined for a range of frequencies before and after a 4-hour exposure to a 2000 Hz, 120dB SPL pure tone for six of the animals. One animal served as control and received no exposure. Results revealed a relatively close correspondence between AER and behavioral thresholds both before and after noise exposure in the same animal. Postexposure AER and behavioral thresholds displayed mild to moderate losses in sensitivity in the 1 to 4 kHz range. These findings justify further development of this particular AER as an indicator of hearing sensitivity in the chinchilla.


Therapeutic potential of mesenchymal stem cells for diabetes.
Mesenchymal stem cells (MSCs) are self-renewing multipotent cells that have the capacity to secrete multiple biologic factors that can restore and repair injured tissues. Preclinical and clinical evidence have substantiated the therapeutic benefit of MSCs in various medical conditions. Currently, MSCs are the most commonly used cell-based therapy in clinical trials because of their regenerative effects, ease of isolation and low immunogenicity. Experimental and clinical studies have provided promising results using MSCs to treat diabetes. This review will summarize the role of MSCs on tissue repair, provide emerging strategies to improve MSC function and describe how these processes translate to clinical treatments for diabetes.


The aspHS gene as a new target for detecting Aspergillus fumigatus during infections by quantitative real-time PCR.
Invasive aspergillosis (IA) is a serious nosocomial infection caused by Aspergillus spp. which has a high mortality rate due to the fact, among other factors, that it is difficult to diagnose. Within the Aspergillus genus, A. fumigatus is the main species causing IA. We propose a virulence factor, the aspHS gene, as a novel target for the specific detection of A. fumigatus by quantitative real-time PCR (qPCR). This target gene encodes a haemolysin, which is overexpressed in vivo during infection. We have designed specific primers and hydrolysis (Taqman) probes for the detection of this target and a chimeric internal amplification control (IC), designed to detect false negative results due to PCR inhibition. This qPCR assay was tested with DNA extracted from a wide collection of microorganisms, tissues from infected mice, and human bronchoalveolar lavage (BAL) samples. Results showed that it, together with the DNA extraction method, could detect A. fumigatus with high specificity. Furthermore, it can distinguish between germinated (first step to the development of infection) and non-germinated conidia (not detected). Our data indicate that these techniques could be sufficiently sensitive and rapid to help clinicians establish an earlier diagnosis, but the presence of PCR inhibitors in clinical samples such as BAL fluids needs to be addressed.


Identifying the links between consumer food waste, nutrition, and environmental sustainability: a narrative review.
Emerging research demonstrates unexpected relationships between food waste, nutrition, and environmental sustainability that should be considered when developing waste reduction strategies. In this narrative review, we synthesize these linkages and the evidence related to drivers of food waste and reduction strategies at the consumer level in the United States. Higher diet quality is associated with greater food waste, which results in significant quantities of wasted resources (e.g., energy, fertilizer) and greenhouse gas emissions. Food waste also represents waste of micronutrients that could otherwise theoretically fill nutritional gaps for millions of people. To make progress on these multiple fronts simultaneously, nutrition professionals must expand beyond their traditional purview, into more interdisciplinary arenas that make connections with food waste and environmental sustainability.


Genotyping of Listeria monocytogenes isolates by high-resolution melting curve (HRM) analysis of tandem repeat locus.
Listeria monocytogenes is responsible for causing listeriosis, a type of food poisoning with high mortality. This bacterium is mainly transmitted to humans through the consumption of contaminated foods. Detection of L. monocytogenes through molecular methods is crucial for food safety and clinical diagnosis. Present techniques are characterized by low discrimination power and high cost, as well as being time-consuming and taking several days to give the final result. In our study, MLVA-HRM (Multiple-Locus Variable-number tandem repeats Analysis ‒ High-Resolution Melting) was investigated as an alternative method for a fast and precise method for the genotyping of L. monocytogenes isolates. Forty-eight isolates of L. monocytogenes obtained from the microbial bank of Department of Microbiology, Iran University of Medical Sciences, were typed by MLVA-HRM analysis using five Variable Numbers of Tandem Repeat (VNTR) loci. A total of 43 different types were obtained. This research demonstrated the usefulness of the MLVA-HRMA method and its ability to discriminate L. monocytogenes isolates. Since this method is easier and more efficient than existing methods, it can be widely used in food processing plants and diagnostic laboratories as a fast and accurate method.


Effects of acute and chronic treatment with the sodium hydrogen exchanger 1 (NHE-1) inhibitor cariporide on myocardial infarct mass in rabbits with hypercholesterolaemia.
We investigated the cardioprotective effect of acute and chronic sodium hydrogen exchanger 1 (NHE-1) inhibition with cariporide under pathological conditions in rabbits fed an atherogenic diet (0.25% cholesterol, 3% coconut oil), an experimental model of atherosclerosis. New Zealand White rabbits were fed over 4 weeks with normal diet or with atherogenic diet and randomized in 3 subgroups (n=7 in each group); placebo, acute cariporide (0.3 mg/kg, 10 min. before occlusion of left anterior descending coronary artery and chronic cariporide (4 weeks 0.1% in chow). In the final infarction experiments the animals were subjected to 30 min. of myocardial ischaemia by occlusion of a branch of the left anterior descending coronary artery followed by 2 hr of reperfusion. Infarct mass was evaluated by triphenyl-tetrazolium chloride staining and the infarct size expressed as a percentage of area at risk. Besides the assessment of aortic endothelium-dependent function aortic and cardiac vessels were inspected for atherosclerotic lesions. In cholesterol-fed rabbits, the infarct size was significantly increased when compared with normal diet animals (63+/-3% versus 41+/-3%). Acute cariporide treatment reduced the infarct size in normal diet rabbits to 14%+/-3% (66% decrease, P<0.05) as well as in atherogenic diet rabbits to 22+/-3% (65% decrease, P<0.05). Chronic treatment with cariporide also reduced the infarct size significantly: normal diet 19+/-2% (53% decrease, P<0.05), atherogenic diet 32+/-3% (49% decrease, P<0.05). Total cholesterol serum levels in rabbits with atherogenic diet were significantly higher (15.3+/-2.7 mmol/l) than those on a standard diet (0.65+/-0.08 mmol/l). Chronic cariporide treatment significantly attenuated the increase of serum cholesterol (7.9+/-1.9 mmol/l) and improved the lipoprotein pattern. Although the aortas and heart vessels of hypercholesterolaemic animals were without any histological evidence of atherosclerosis they developed endothelial dysfunction (reduced endothelium-dependent relaxation by ACh), which was prevented by chronic cariporide treatment. Acute and chronic treatment with the NHE-1 inhibitor cariporide significantly reduced infarct mass. This effect was associated with improved endothelial function.


Induction of resident memory T cells enhances the efficacy of cancer vaccine.
Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.


Controlled Polymerization of Norbornene Cycloparaphenylenes Expands Carbon Nanomaterials Design Space.
Carbon-based materials-such as graphene nanoribbons, fullerenes, and carbon nanotubes-elicit significant excitement due to their wide-ranging properties and many possible applications. However, the lack of methods for precise synthesis, functionalization, and assembly of complex carbon materials has hindered efforts to define structure-property relationships and develop new carbon materials with unique properties. To overcome this challenge, we employed a combination of bottom-up organic synthesis and controlled polymer synthesis. We designed norbornene-functionalized cycloparaphenylenes (CPPs), a family of macrocycles that map onto armchair carbon nanotubes of varying diameters. Through ring-opening metathesis polymerization, we accessed homopolymers as well as block and statistical copolymers constructed from "carbon nanohoops" with a high degree of structural control. These soluble, sp2-carbon-dense polymers exhibit tunable fluorescence emission and supramolecular responses based on composition and sequence. This work represents an important advance toward bridging the gap between small molecules and functional carbon-based materials.


Weakened portfolio effects constrain management effectiveness for population aggregates.
Population diversity can reduce temporal variability in aggregate population abundances in a process known as the portfolio effect. Portfolio effects may weaken, however, due to greater synchrony among component populations. While weakened portfolio effects have been previously documented, the consequences of reduced stability on meeting conservation goals for population aggregates that are harvested (e.g., stock aggregates in fisheries) are rarely quantified. Here, we demonstrate how changes in variability within components, synchrony among components, and population productivity interact to influence the probability of achieving an array of management objectives for Fraser River sockeye salmon: a stock aggregate of high economic, ecological, and cultural value. We first present evidence that component variability and synchrony have increased over the last two decades, consistent with a weakening portfolio effect. We then parameterize a stochastic, closed-loop model that simulates the population dynamics of each stock, the fishery that harvests the stock aggregate, and the management framework used to establish mixed-stock exploitation rates. We find that while median aggregate abundance and catch through time were relatively insensitive to greater aggregate variability, catch stability and performance metrics associated with achieving management targets generally declined as component variability and synchrony increased. A notable exception we observed is that harvest control means that scale exploitation rates based on aggregate abundance may be more effective as synchrony increases. Reductions in productivity led to broad declines in performance, but also moderated the impacts of component variability and synchrony on the proportion of component stocks above management targets and catch stability. Our results suggest that even precautionary management strategies that account for declines in productivity may underestimate risk, particularly to socioeconomic objectives, if they fail to consider changes in aggregate variability. Adequately incorporating changes in portfolio effect strength may be particularly relevant when developing recovery strategies that are robust to climate change, which is likely to increase synchrony and component variability.


Tolmetin sodium-loaded thermosensitive mucoadhesive liquid suppositories for rectal delivery; strategy to overcome oral delivery drawbacks.
Tolmetin sodium (TS) is a nonsteroidal anti-inflammatory drug (NSAID) indicated for treatment of musculoskeletal issues. As other NSAID, TS displays a marked side effects on the gastro-intestinal (GI) tract after oral administration. Traditional solid suppositories can cause pain and discomfort for patients, may reach the end of the colon; consequently, the drug can undergo the first-pass effect. TS liquid suppository (TS-LS) was developed to enhance patient compliance and rectal mucosal safety in high-risk patients receiving highly NSAID therapy. This work was conducted to optimize and evaluate Poloxamer P407/P188-based thermoresponsive TS-LS by using mucoadhesive polymers such as methylcellulose (MC). TS-LS was prepared by cold method and characterized their in vitro physicochemical properties as gelation temperature (GT), gel strength, bioadhesive properties, and in vitro release. The safety of the prepared suppository on rectum, stomach, and liver was evaluated histologically. Pharmacokinetic analyses were performed to compare rectal TS-LS to orally Rhumtol® capsules. The results showed that the optimized TS-LS; composed of P407/P188/MC (21/9/0.5% w/w) displayed gelation at rectum temperature ∼32.90 °C, gel strength of 21.35 s and rectal retention force at the administration site of 24.25 × 102 dyne/cm2. Moreover, TS-LS did not cause any morphological damage to the rectal tissues. Pharmacokinetic parameters of optimized TS-LS formulation revealed 4.6 fold increase in bioavailability as compared to Rhumtol® capsules. Taken together, the results demonstrated that liquid suppository is a potential and physically safe rectal delivery carrier for improvement rectal bioavailability and in vivo safety of TS.


Leg structure explains host site preference in bat flies (Diptera: Streblidae) parasitizing neotropical bats (Chiroptera: Phyllostomidae).
Bat flies (Streblidae) are diverse, obligate blood-feeding insects and probably the most conspicuous ectoparasites of bats. They show preferences for specific body regions on their host bat, which are reflected in behavioural characteristics. In this study, we corroborate the categorization of bat flies into three ecomorphological groups, focusing only on differences in hind leg morphology. As no detailed phylogeny of bat flies is available, it remains uncertain whether these morphological differences reflect the evolutionary history of bat flies or show convergent adaptations for the host habitat type. We show that the division of the host bat into three distinct habitats contributes to the avoidance of interspecific competition of bat fly species. Finally, we found evidence for density-dependent competition between species belonging to the same ecomorphological group.


[Functional di-domain of neuronal growth inhibitory factor].
Neuronal growth inhibitory factor (GIF), known also as metallothionein-III (MT-III), was the first validated to be capable of inhibiting growth of neuronal cells in nervous system, its beta-domain being functional. GIF functional di-domain (GIFbeta- beta) was constructed to study the structure and function of GIF. N terminal beta-domain and C terminal beta-domain cDNAs were amplified by PCR, inserted into vector pGEX-4T-1 and expressed in Escherichia coli, as carboxyl terminal extension of glutathione-S-transferase (GST), by IPTG induction. After digestion by thrombin, the fusion protein was isolated by passing through a glutathione-Sepharose 4B affinity chromatography column and was purified by gel fit ration on Sephacryl-S100. About 60 mg protein per liter of bacterial cell culture was achieved. The results of SDS-PAGE, amino acid composition, molecular mass, the ratio of metal/protein and sulfhydryl group/protein showed that the purified protein was the GIFbeta- beta. Circular dichroism (CD) spectroscopy show GIFbeta- beta has characteristic metal-sulfhydryl clusters of metallothionein family. Inhibitory activities detected by the MTT reduction assay are: GIF > GIFbeta-beta > GIF beta-domain.


[Overweight and obesity].
Being over-weight and obesity are conditions which are becoming ever more common and this trend presents a series of social and psychological problems, apart from the well known health risks such as hypertension, heart disease, type 2 diabetes, orthopaedic problems, cancers of the endometrium and breast etc. The prevention and control of excess weight and obesity is largely based on adopting a healthy lifestyle and above all on diet and exercise. These ideas are also included in the Health Plan for 2002-2004, and are among the ten most important strategic objectives for promoting healthy living, disease prevention and informing the public on health matters.


False positive GI bleed on Tc-99m RBC scintigraphy due to ileal varices.
Tc-99m labeled RBC scintigraphy is commonly employed in the evaluation of acute gastrointestinal bleeding. On Tc-99m RBC studies gastrointestinal bleeding is seen as an initial focus of increased radiotracer activity that on subsequent images increases in intensity and changes position in a pattern that conforms to segments of bowel. We report a case of a patient with multiple episodes of hematochezia that presented with lower gastrointestinal hemorrhage. A Tc-99m labeled RBC scan was performed and the findings suggested a GI bleed. However, subsequent angiography revealed prominent ileal varices simulating an acute bleed. Although most varices fill promptly and should not be misinterpreted as a focus of hemorrhage, slow filling varices can simulate an acute bleed and lead to a false positive interpretation.


Clinical considerations in transitioning patients with epilepsy from clonazepam to clobazam: a case series.
In treating refractory epilepsy, many clinicians are interested in methods used to transition patients receiving clonazepam to clobazam to maintain or increase seizure control, improve tolerability of patients' overall drug therapy regimens, and to enhance quality of life for patients and their families. However, no published guidelines assist clinicians in successfully accomplishing this change safely. The following three case reports provide insight into the transition from clonazepam to clobazam. First, an 8-year-old Caucasian boy with cryptogenic Lennox-Gastaut syndrome beginning at 3.5 years of age, who was experiencing multiple daily generalized tonic-clonic, absence, myoclonic, and tonic seizures at presentation. Second, a 25-year-old, left-handed, White Hispanic man with moderate mental retardation and medically refractory seizures that he began experiencing at 1 year of age, secondary to tuberous sclerosis. When first presented to an epilepsy center, he had been receiving levetiracetam, valproate, and clonazepam, but reported having ongoing and frequent seizures. Third, a 69-year-old Korean woman who had been healthy until she had a stroke in 2009 with subsequent right hemiparesis; as a result, she became less physically and socially active, and had her first convulsive seizure approximately 4 months after the stroke. From these cases, we observe that a rough estimate of final clobazam dosage for each mg of clonazepam under substitution is likely to be at least 10-fold, probably closer to 15-fold for many patients, and as high as 20-fold for a few. Consideration and discussion of the pharmacokinetic, pharmacologic, and clinical properties of 1,4- and 1,5-benzodiazepine action provide a rationale on why and how these transitions were successful.


Regression calibration in failure time regression.
In this paper we study a regression calibration method for failure time regression analysis when data on some covariates are missing or mismeasured. The method estimates the missing data based on the data structure estimated from a validation data set, a random subsample of the study cohort in which covariates are always observed. Ordinary Cox (1972; Journal of the Royal Statistical Society, Series B 34, 187-220) regression is then applied to estimate the regression coefficients, using the observed covariates in the validation data set and the estimated covariates in the nonvalidation data set. The method can be easily implemented. We present the asymptotic theory of the proposed estimator. Finite sample performance is examined and compared with an estimated partial likelihood estimator and other related methods via simulation studies, where the proposed method performs well even though it is technically inconsistent. Finally, we illustrate the method with a mouse leukemia data set.


Floral vibrations by buzz-pollinating bees achieve higher frequency, velocity and acceleration than flight and defence vibrations.
Vibrations play an important role in insect behaviour. In bees, vibrations are used in a variety of contexts including communication, as a warning signal to deter predators and during pollen foraging. However, little is known about how the biomechanical properties of bee vibrations vary across multiple behaviours within a species. In this study, we compared the properties of vibrations produced by Bombus terrestris audax (Hymenoptera: Apidae) workers in three contexts: during flight, during defensive buzzing, and in floral vibrations produced during pollen foraging on two buzz-pollinated plants (Solanum, Solanaceae). Using laser vibrometry, we were able to obtain contactless measures of both the frequency and amplitude of the thoracic vibrations of bees across the three behaviours. Despite all three types of vibrations being produced by the same power flight muscles, we found clear differences in the mechanical properties of the vibrations produced in different contexts. Both floral and defensive buzzes had higher frequency and amplitude velocity, acceleration and displacement than the vibrations produced during flight. Floral vibrations had the highest frequency, amplitude velocity and acceleration of all the behaviours studied. Vibration amplitude, and in particular acceleration, of floral vibrations has been suggested as the key property for removing pollen from buzz-pollinated anthers. By increasing frequency and amplitude velocity and acceleration of their vibrations during vibratory pollen collection, foraging bees may be able to maximise pollen removal from flowers, although their foraging decisions are likely to be influenced by the presumably high cost of producing floral vibrations.


Dimerization in a half-filled one-dimensional extended hubbard model.
We use a density-matrix renormalization group method to study quantitatively the phase diagram of a one-dimensional extended Hubbard model at half filling by investigating the correlation functions and structure factors. We confirmed the existence of a novel narrow region with long-range bond-order-wave order that was highly controversial recently between the charge-density-wave phase and Mott insulator phase. We determined accurately the position of the bicritical point U(b) approximately 7.2t, V(b) approximately 3.746t, which is quite different from previous studies.


Disulfide bond configuration of human cytomegalovirus glycoprotein B.
Glycoprotein B (gB) is the most highly conserved of the envelope glycoproteins of human herpesviruses. The gB protein of human cytomegalovirus (CMV) serves multiple roles in the life cycle of the virus. To investigate structural properties of gB that give rise to its function, we sought to determine the disulfide bond arrangement of gB. To this end, a recombinant form of gB (gB-S) comprising the entire ectodomain of the glycoprotein (amino acids 1 to 750) was constructed and expressed in insect cells. Proteolytic fragmentation and mass spectrometry were performed using purified gB-S, and the five disulfide bonds that link 10 of the 11 highly conserved cysteine residues of gB were mapped. These bonds are C94-C550, C111-C506, C246-C250, C344-C391, and C573-C610. This configuration closely parallels the disulfide bond configuration of herpes simplex type 2 (HSV-2) gB (N. Norais, D. Tang, S. Kaur, S. H. Chamberlain, F. R. Masiarz, R. L. Burke, and F. Markus, J. Virol. 70:7379-7387, 1996). However, despite the high degree of conservation of cysteine residues between CMV gB and HSV-2 gB, the disulfide bond arrangements of the two homologs are not identical. We detected a disulfide bond between the conserved cysteine residue 246 and the nonconserved cysteine residue 250 of CMV gB. We hypothesize that this disulfide bond stabilizes a tight loop in the amino-terminal fragment of CMV gB that does not exist in HSV-2 gB. We predicted that the cysteine residue not found in a disulfide bond of CMV gB, cysteine residue 185, would play a role in dimerization, but a cysteine substitution mutant in cysteine residue 185 showed no apparent defect in the ability to form dimers. These results indicate that gB oligomerization involves additional interactions other than a single disulfide bond. This work represents the second reported disulfide bond structure for a herpesvirus gB homolog, and the discovery that the two structures are not identical underscores the importance of empirically determining structures even for highly conserved proteins.


Genetic and environmental influences on antisocial behavior: a meta-analysis of twin and adoption studies.
A meta-analysis of 51 twin and adoption studies was conducted to estimate the magnitude of genetic and environmental influences on antisocial behavior. The best fitting model included moderate proportions of variance due to additive genetic influences (.32), nonadditive genetic influences (.09), shared environmental influences (.16), and nonshared environmental influences (.43). The magnitude of familial influences (i.e., both genetic and shared environmental influences) was lower in parent-offspring adoption studies than in both twin studies and sibling adoption studies. Operationalization, assessment method, zygosity determination method, and age were significant moderators of the magnitude of genetic and environmental influences on antisocial behavior, but there were no significant differences in the magnitude of genetic and environmental influences for males and females.


Use of crystal methamphetamine among male adolescents in Cape Town, South Africa: Caregivers' experiences.
Against the background that crystal methamphetamine (colloquially known as "tik") is extensively used by the emerging working class Coloured youth in Cape Town, South Africa, this exploratory qualitative study was conducted to explore the experience of mothers whose children use methamphetamine. The researchers conducted one-to-one semi-structured in-depth interviews with sixteen (16) purposively selected caregivers (mothers) whose sons use methamphetamine. Interviews were recorded and simultaneously translated and transcribed. Thematic analysis was used to identify themes related to the experiences of caregivers of youth with methamphetamine problems. Findings showed that youth misbehaviour provided a context that led to feelings of shame and embarrassment. Participants also experienced personal challenges which included emotional problems, fear and self-blame. Participants also expressed family disruptions and financial drain as adverse experiences as a results of their sons' misbehaviour. The study results highlight the psychosocial challenges for caregivers of children who use methamphetamine. These findings underscore the need for effort to be directed at the development of formal support interventions for mothers of youth who are troubled with addiction.


Investigation of an Outbreak of Hepatitis A in a Coastal Area, Kerala, Southern India.
An outbreak investigation was initiated following an unusual occurrence of hepatitis A reported among people residing in the coastal belt of Vadi to Vedikunnu area, Kollam district, Kerala, southern India. The time frame of disease occurrence, pattern of its distribution, and the incubation period of hepatitis A infection indicated the probability of occurrence of the outbreak as a result of pipe line water contamination due to mixing of sewage from a canal. The results add evidence to the epidemiology of hepatitis A in the state and warrant the establishment of an efficient water quality surveillance system.


[Exploring the therapeutic mechanism of Longqi Fang for diabetic kidney disease based on network pharmacology and verification in rats].
To study the therapeutic mechanism of Longqi Fang (LQF) for diabetic kidney disease (DKD) based on GEO database and network pharmacology. LQF and DKD targets were obtained using the databases including GEO, TCMSP, CNKI, ChemDraw, and SwissTarget Prediction, and LQF-DKD intersection targets were obtained with VENNY. String was used for protein-protein interaction (PPI) analysis, and R package for KEGG and GO enrichment analysis. Cytoscape 3.7.2 software Network graphs were constructed. The results of network pharmacology analysis were verified in SD rat models of DKD by daily treatment of the rats with LQF at low (1 g/kg), medium (2 g/kg), and high (2 g/kg) doses, and kidney pathology was observed with HE staining and the changes in renal function were assessed. Western blotting was used to detect the expression levels of NF-κB and p-NF-κB proteins. We identified 760 main targets of LQF, and obtained 1026 differential genes using GEO database and 61 LQF-DKD intersection targets using Venny database. The core targets obtained through PPI network analysis included Myc, EGF, CASP3, VEGFA, CCL2, SPP1, VCAM1 and ICAM1. Go analysis showed that LQF affects mainly nuclear receptor activity and ligand activated transcription factor activity. KEGG analysis showed that LQF affects inflammatory signaling pathways by interfering with NF-κB, TNF, and PI3K-AKT. In rat models of DKD, treatment with LQF resulted in significant improvements of the renal functions (P < 0.05) and glomerular and tubular structure and arrangement in a dose-dependent manner. Western blotting results showed that LQF dose-dependently downregulated NF-κB and p-NF-κB expressions in the rat models. The therapeutic mechanism of LQF for DKD involves multiple components, targets and signal pathways that mediate an inhibitory effect on NF-κB signaling pathway to protect the renal function.


Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice.
Reactive oxygen species, endothelial dysfunction, inflammation, and mitogen-activated protein kinases have important roles in the pathogenesis of ischemia/reperfusion kidney injury. Stanniocalcin-1 (STC1) suppresses superoxide generation in many systems through the induction of mitochondrial uncoupling proteins and blocks the cytokine-induced rise in endothelial permeability. Here we tested whether transgenic overexpression of STC1 protects from bilateral ischemia/reperfusion kidney injury. This injury in wild-type mice caused a halving of the creatinine clearance; severe tubular vacuolization and cast formation; increased infiltration of macrophages and T cells; higher vascular permeability; greater production of superoxide and hydrogen peroxide; and higher ratio of activated extracellular regulated kinase/activated Jun-N-terminal kinase and p38, all compared to sham-treated controls. Mice transgenic for human STC1 expression, however, had resistance to equivalent ischemia/reperfusion injury indicated as no significant change from controls in any of these parameters. Tubular epithelial cells in transgenic mice expressed higher mitochondrial uncoupling protein 2 and lower superoxide generation. Pre-treatment of transgenic mice with paraquat, a generator of reactive oxygen species, before injury restored the susceptibility to ischemia/reperfusion kidney injury, suggesting that STC1 protects by an anti-oxidant mechanism. Thus, STC1 may be a therapeutic target for ischemia/reperfusion kidney injury.


Recurrent Network Dynamics; a Link between Form and Motion.
To discriminate visual features such as corners and contours, the brain must be sensitive to spatial correlations between multiple points in an image. Consistent with this, macaque V2 neurons respond selectively to patterns with well-defined multipoint correlations. Here, we show that a standard feedforward model (a cascade of linear-non-linear filters) does not capture this multipoint selectivity. As an alternative, we developed an artificial neural network model with two hierarchical stages of processing and locally recurrent connectivity. This model faithfully reproduced neurons' selectivity for multipoint correlations. By probing the model, we gained novel insights into early form processing. First, the diverse selectivity for multipoint correlations and complex response dynamics of the hidden units in the model were surprisingly similar to those observed in V1 and V2. This suggests that both transient and sustained response dynamics may be a vital part of form computations. Second, the model self-organized units with speed and direction selectivity that was correlated with selectivity for multipoint correlations. In other words, the model units that detected multipoint spatial correlations also detected space-time correlations. This leads to the novel hypothesis that higher-order spatial correlations could be computed by the rapid, sequential assessment and comparison of multiple low-order correlations within the receptive field. This computation links spatial and temporal processing and leads to the testable prediction that the analysis of complex form and motion are closely intertwined in early visual cortex.


Cognitive decline and cardiometabolic risk among Hispanic and non-Hispanic white adults in the San Luis Valley Health and Aging Study.
Cardiometabolic risk factors, including hypertension, dyslipidemia, central obesity, insulin resistance and diabetes are linked to cognitive impairment. The Hispanic population appears to be differentially affected by both cardiometabolic risk factors and cognitive impairment. We sought to determine whether ethnic differences in cognitive impairment in long-resident southwestern US elders was explained by the presence of cardiometabolic risk factors, and to explore patterns of cognitive decline over time. We performed a secondary analysis of data collected on 378 Hispanic and 409 non-Hispanic white adult participants in a longitudinal study of community-dwelling elderly in southern Colorado. Measures of cardiometabolic risk included waist circumference, blood pressure, diagnosis of diabetes, and random blood glucose. Cognitive measures included the Mini-Mental State Exam (MMSE) and the behavioral dyscontrol scale (a measure of executive cognitive function), at baseline and after an average of 22 months. Subjects were also administered the Center for Epidemiologic Studies Depression Scale, and the Coronary Artery Risk Development in Young Adults 1-Year Activity Recall. At baseline, Hispanic elders had a greater number of cardiometabolic risk factors and lower MMSE and behavioral dyscontrol scale scores than non-Hispanic whites. Hispanic ethnicity was associated with a greater likelihood of decline in general cognitive function, but not executive cognitive function, after adjusting for age and education. This differential decline was not explained by either individual or total number of baseline cardiometabolic risk factors, depression, or physical activity. A borderline increased risk of decline in general cognitive function was seen in sedentary individuals (P = 0.05).


New methodology for facilitating food wastage quantification. Identifying gaps and data inconsistencies.
The Food and Agriculture Organization of the United Nations estimated that about 1.3 billion tons of food produced for human consumption was lost or wasted globally. Thus, the reduction of the current food loss and waste along the agrifood chain is becoming a priority, both for optimization of resources and reduction waste generation costs. For this purpose, the first step is to quantify the food wastage generation to be able to identify corrective measures. However, in spite of the considerable efforts already undertaken to establish common methodologies to measure the food wastage at different geographical scales, there are still some gaps and inconsistencies. In this regard, the information gathering is labour-intensive because of the different actors involved. The creation of new methodologies and tools capable of automatically identifying these agents would be of great value so as to subsequently apply the more appropriates quantification methodologies. This work aims at providing a new methodology to facilitate this process thanks to the previous identification and classification of the potential food wastage generators. As a result, it provides baseline information for one of the earliest steps of the food wastage quantification process, which is the establishment of the scope of the food wastage inventory. The baseline data needed is taken from the Statistical classification of economic activities in the European Community (NACE), particularly from the most disaggregated level called "classes". This information has been combined with data from the trading income tax at municipal scale thanks to the use of Geographic Information Systems (GIS) and the common codes for NACE classes, generating a visual tool for the localization of points with potential of food-wastage generation and their weight of each economic activity over the agrifood chain. The proposed methodology has been implemented for the real case of the municipality of Zamudio (Spain) and it has allowed the identification of the different entities linked with economic activities that are potential generators of food wastage, the weight of each activity over the entire agrifood chain, and the geographical location of these entities in the territory. Furthermore, this methodology was used to compare the nature and number of these activities in another municipality (Karrantza, Spain) and it has also been applied to the entire region of the Basque Country (Spain).


Limited adoption of current guidelines for clinical breast examination by primary care physician educators.
In 2004, the CDC and the American Cancer Society (ACS) published performance guidelines recommending a validated method of clinical breast exams (CBE) using the vertical strips method (VSM) along with other key exam components. We examined the use of the VSM by academic medicine physicians and identified predictor variables for its adoption. Clinician educators in the Society of General Internal Medicine (SGIM) and physicians in the Society of Teachers of Family Medicine (STFM) were administered web-based surveys on CBE practices in 2009. A total of 1,772 (42%) physicians responded. Only 40% of respondents reported using the VSM, compared with 53% using the circular search method. Variables and their odds ratios (ORs) associated with an increase adoption of the VSM were having a primary teaching hospital affiliation (OR 1.4 [1.1, 1.9]), having taken a course on breast health or breast cancer in the past 5 years (OR 1.5 [1.1, 2.0]), and having completed residency in the past 5 years (OR 2.3 [1.6, 3.4]) and/or 10-15 years (OR 1.6 [1.2, 2.2]) compared to more than 15 years. The extent of teaching responsibilities was not associated with adoption of the VSM. A majority of physician responders highly involved in education of students and residents continue to practice methods of CBE that do not reflect the current guidelines. Faculty development and training on updated CBE practices may accelerate adoption of guideline-recommended care.