Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates gluco-lipotoxicity-mediated renal disorder in type 2 diabetic db/db mice.
Oligonol is a phenolic product derived from lychee fruit extract containing catechin-type monomers and oligomers of proanthocyanidins, produced by a manufacturing process which converts polyphenol polymers into oligomers. These proanthocyanidins have been reported to exhibit beneficial bioactivities in many studies, and so oligonol, a rich source of polyphenol, is expected to show favorable effects on various chronic diseases. This article summarizes recent work whether oligonol has an ameliorative effect on diabetic indices and renal disorders associated with gluco-lipotoxicity-mediated oxidative stress, inflammation, and apoptosis in db/db mice with diabetes. Oligonol was able to improve diabetic indices, prevent the development of diabetic renal disease, and preserve renal cells and the renal morphological structure via the attenuation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-induced oxidative stress, inhibition of advanced glycation endproduct (AGE) generation, and prevention of apoptosis-induced cell death in db/db mice, being independent of changes in the body weight or serum glucose levels. The present study provides important evidence that oligonol exhibits a pleiotropic effect, representing renoprotective effects against the development of diabetic complications in type 2 diabetic db/db mice.


Simultaneous Multislice Diffusion-Weighted Imaging of the Kidney: A Systematic Analysis of Image Quality.
The aims of this study were to implement a protocol for simultaneous multislice (SMS) accelerated diffusion-weighted imaging (DWI) of the kidneys and to perform a systematic analysis of image quality of the data sets. Ten healthy subjects and 5 patients with renal masses underwent DWI of the kidney in this prospective institutional review board-approved study on a 3 T magnetic resonance scanner. Simultaneous multislice DWI echo-planar sequences (acceleration factors [AFs] 2 and 3) were compared with conventional echo-planar DWI as reference standard for each acquisition scheme. The following 3 acquisition schemes were applied: comparison A, with increased number of acquisitions at constant scan time; comparison B, with reduction of acquisition time; and comparison C, with increased slice resolution (constant acquisition time, increasing number of slices). Interreader reliability was analyzed by calculating the intraclass correlation coefficient (ICC). Qualitative image quality features were evaluated by 2 independent radiologists on a 5-point Likert scale. Quantification accuracy of the apparent diffusion coefficients (ADCs) and signal-to-noise ratios (SNRs) were assessed by region of interest analysis. Furthermore, lesion conspicuity in the 5 patients was assessed using a 5-point Likert scale by 2 independent radiologists. Interreader agreement was substantial with an ICC of 0.68 for the overall image quality and an ICC of 0.73 for the analysis of artifacts. In comparison A, AF2 resulted in increased SNR (P < 0.05) by 21% at stable image quality scores (image quality: P = 0.76, artifacts: P = 0.21). In comparison B, applying AF2, the scan time could be reduced by 46% without significant reduction in qualitative image quality scores (P = 0.059) or SNR (P = 0.126). In comparison C, slice resolution could be improved by 28% using AF2 with stable image quality scores and SNR. In general, AF3 resulted in reduced image quality and SNR. Significantly reduced ADC values were observed for AF3 in comparison C (cortex: P = 0.003; medulla: P = 0.001) compared with the standard echo-planar imaging sequence. The conventional DWI and the SMS DWI with AF2 showed stable lesion conspicuity ([AF1/AF2]: reader 1 [1.8/1.4] and reader 2 [1.8/1.4]). The lesion conspicuity was lower using AF3 (reader 1: 2.2 and reader 2: 1.8). In conclusion, SMS DWI of the kidney is a potential tool to substantially reduce scan time without negative effects on SNR, ADC quantification accuracy, and image quality if an AF2 is used. Although AF3 results in even higher scan time reduction, a negative impact on image quality, SNR, ADC quantification accuracy, and lesion conspicuity must be considered.


Cardiac radiotherapy induces electrical conduction reprogramming in the absence of transmural fibrosis.
Cardiac radiotherapy (RT) may be effective in treating heart failure (HF) patients with refractory ventricular tachycardia (VT). The previously proposed mechanism of radiation-induced fibrosis does not explain the rapidity and magnitude with which VT reduction occurs clinically. Here, we demonstrate in hearts from RT patients that radiation does not achieve transmural fibrosis within the timeframe of VT reduction. Electrophysiologic assessment of irradiated murine hearts reveals a persistent supraphysiologic electrical phenotype, mediated by increases in NaV1.5 and Cx43. By sequencing and transgenic approaches, we identify Notch signaling as a mechanistic contributor to NaV1.5 upregulation after RT. Clinically, RT was associated with increased NaV1.5 expression in 1 of 1 explanted heart. On electrocardiogram (ECG), post-RT QRS durations were shortened in 13 of 19 patients and lengthened in 5 patients. Collectively, this study provides evidence for radiation-induced reprogramming of cardiac conduction as a potential treatment strategy for arrhythmia management in VT patients.


Petri Nets with Fuzzy Logic (PNFL): reverse engineering and parametrization.
The recent DREAM4 blind assessment provided a particularly realistic and challenging setting for network reverse engineering methods. The in silico part of DREAM4 solicited the inference of cycle-rich gene regulatory networks from heterogeneous, noisy expression data including time courses as well as knockout, knockdown and multifactorial perturbations. We inferred and parametrized simulation models based on Petri Nets with Fuzzy Logic (PNFL). This completely automated approach correctly reconstructed networks with cycles as well as oscillating network motifs. PNFL was evaluated as the best performer on DREAM4 in silico networks of size 10 with an area under the precision-recall curve (AUPR) of 81%. Besides topology, we inferred a range of additional mechanistic details with good reliability, e.g. distinguishing activation from inhibition as well as dependent from independent regulation. Our models also performed well on new experimental conditions such as double knockout mutations that were not included in the provided datasets. The inference of biological networks substantially benefits from methods that are expressive enough to deal with diverse datasets in a unified way. At the same time, overly complex approaches could generate multiple different models that explain the data equally well. PNFL appears to strike the balance between expressive power and complexity. This also applies to the intuitive representation of PNFL models combining a straightforward graphical notation with colloquial fuzzy parameters.


School nurses' view of schoolchildren's health and their attitudes to document it in the school health record--a pilot study.
This study highlights school nurses' view of schoolchildren's health and their attitude to document it in the school health records. A strategic sample of 12 school nurses was interviewed. The interviews were semistructured and analysed with qualitative content analysis. The findings showed that the school nurses' viewed schoolchildren as physical healthy although they called attention to growing problems related to a changed lifestyle. Psychosocial ill-health was however increasing and the most common reason for visiting the school nurse was psychosomatic expressions. According to the nurses' descriptions, health was related to the individual, the school and the family situation. The family situation was mentioned as one of the most important factors of schoolchildren's health. The nurses described no problem to document schoolchildren's physical health. Ethical consideration, tradition, lack of time and the structure of the record were however factors that were said to hinder the documentation of the psychosocial health. In order to promote, protect and recover schoolchildren's health, more research is needed about how beliefs, experience, ethical consideration and resources influence the school nurse's daily work with schoolchildren's health.


Restless legs syndrome in Parkinson's disease: a case-controlled study.
Restless legs syndrome (RLS) is a disorder of motor activity with a circadian pattern, occurring frequently in patients with Parkinson's disease (PD). We sought to estimate the prevalence of RLS in Indian PD patients. One hundred twenty-six consecutive PD patients and 128 healthy age- and sex-matched controls were evaluated using a predesigned questionnaire. RLS was present in 10 of 126 cases of PD (7.9%) and 1 of 128 controls (0.8%, P = 0.01). PD patients with RLS were older than those without RLS (63.70 +/- 7.80 years vs. 57.37 +/- 10.04 years; P = 0.05) and had higher prevalence of depression (40% vs. 10.3%; P = 0.023). No demographic factors or factors related to PD correlated with the presence or severity of RLS. RLS is more common among patients with PD than controls. A greater medical recognition of this disorder is needed in view of available effective treatment.


Comparative study of hematopoietic differentiation between human embryonic stem cell lines.
Directed differentiation of human embryonic stem cells (hESCs) into any desired cell type has been hailed as a therapeutic promise to cure many human diseases. However, substantial roadblocks still exist for in vitro differentiation of hESCs into distinct cell types, including T lymphocytes. Here we examined the hematopoietic differentiation potential of six different hESC lines. We compare their ability to develop into CD34(+) or CD34(+)CD45(+) hematopoietic precursor populations under several differentiation conditions. Comparison of lymphoid potential of hESC derived- and fetal tissue derived-hematopoietic precursors was also made. We found diverse hematopoietic potential between hESC lines depending on the culture or passage conditions. In contrast to fetal-derived hematopoietic precursors, none of the CD34(+) precursors differentiated from hESCs were able to develop further into T cells. These data underscore the difficulties in the current strategy of hESC forward differentiation and highlight distinct differences between CD34(+) hematopoietic precursors generated in vitro versus in vivo.


Three-dimensional structure of (1,4)-beta-D-mannan mannanohydrolase from tomato fruit.
The three-dimensional crystal structure of tomato (Lycopersicon esculentum) beta-mannanase 4a (LeMAN4a) has been determined to 1.5 A resolution. The enzyme adopts the (beta/alpha)(8) fold common to the members of glycohydrolase family GH5. The structure is comparable with those of the homologous Trichoderma reesei and Thermomonospora fusca beta-mannanases: There is a conserved three-stranded beta-sheet located near the N terminus that stacks against the central beta-barrel at the end opposite the active site. Three noncanonical beta-helices surround the active site. Similar helices are found in T. reesei but not T. fusca beta-mannanase. By analogy with other beta-mannanases, the catalytic acid/base residue is E204 and the nucleophile residue is E318. The active site cleft of L. esculentum beta-mannanase most closely resembles that of the T. reesei isozyme. A model of substrate binding in LeMAN4a is proposed in which the mannosyl residue occupying the -1 subsite of the enzyme adopts the (1)S(5) skew-boat conformation.


Potential herd protection against Plasmodium falciparum infections conferred by mass antimalarial drug administrations.
The global malaria burden has decreased over the last decade and many nations are attempting elimination. Asymptomatic malaria infections are not normally diagnosed or treated, posing a major hurdle for elimination efforts. One solution to this problem is mass drug administration (MDA), with success depending on adequate population participation. Here, we present a detailed spatial and temporal analysis of malaria episodes and asymptomatic infections in four villages undergoing MDA in Myanmar. In this study, individuals from neighborhoods with low MDA adherence had 2.85 times the odds of having a malaria episode post-MDA in comparison to those from high adherence neighborhoods, regardless of individual participation, suggesting a herd effect. High mosquito biting rates, living in a house with someone else with malaria, or having an asymptomatic malaria infection were also predictors of clinical episodes. Spatial clustering of non-adherence to MDA, even in villages with high overall participation, may frustrate elimination efforts.


Discovering plant metabolic biomarkers for phenotype prediction using an untargeted approach.
Biomarkers are used to predict phenotypical properties before these features become apparent and, therefore, are valuable tools for both fundamental and applied research. Diagnostic biomarkers have been discovered in medicine many decades ago and are now commonly applied. While this is routine in the field of medicine, it is of surprise that in agriculture this approach has never been investigated. Up to now, the prediction of phenotypes in plants was based on growing plants and assaying the organs of interest in a time intensive process. For the first time, we demonstrate in this study the application of metabolomics to predict agronomic important phenotypes of a crop plant that was grown in different environments. Our procedure consists of established techniques to screen untargeted for a large amount of metabolites in parallel, in combination with machine learning methods. By using this combination of metabolomics and biomathematical tools metabolites were identified that can be used as biomarkers to improve the prediction of traits. The predictive metabolites can be selected and used subsequently to develop fast, targeted and low-cost diagnostic biomarker assays that can be implemented in breeding programs or quality assessment analysis. The identified metabolic biomarkers allow for the prediction of crop product quality. Furthermore, marker-assisted selection can benefit from the discovery of metabolic biomarkers when other molecular markers come to its limitation. The described marker selection method was developed for potato tubers, but is generally applicable to any crop and trait as it functions independently of genomic information.


What determines successful implementation of inpatient information technology systems?
To identify the factors and strategies that were associated with successful implementation of hospital-based information technology (IT) systems in US Department of Veterans Affairs (VA) hospitals, and how these might apply to other hospitals. Qualitative analysis of 118 interviews conducted at 7 VA hospitals. The study focused on the inpatient setting, where nurses are the main patient-care providers; thus, the research emphasized the impact of Computerized Patient Record System and Bar Code Medication Administration on nurses. Hospitals were selected to represent a range of IT implementation dates, facility sizes, and geography. The subjects included nurses, pharmacists, physicians, IT staff, and managers. Interviews were guided by a semi-structured interview protocol, and a thematic analysis was conducted, with initial codes drawn from the content of the interview guides. Additional themes were proposed as the coding was conducted. Five broad themes arose as factors which affected the process and success of implementation: (1) organizational stability and implementation team leadership, (2) implementation timelines, (3) equipment availability and reliability, (4) staff training, and (5) changes in work flow Overall IT implementation success in the VA depended on: (1) whether there was support for change from both leaders and staff, (2) development of a gradual and flexible implementation approach, (3) allocation of adequate resources for equipment and infrastructure, hands-on support, and deployment of additional staff, and (4) how the implementation team planned for setbacks, and continued the process to achieve success. Problems that developed in the early stages of implementation tended to become persistent, and poor implementation can lead to patient harm.


Spatial properties of fundus reflectance and red-green relative spectral sensitivity.
We investigated the spatial characteristics of the diffuse light in the eye at two different wavelengths and the extent to which this may affect red-green relative spectral sensitivity. The fundus reflectance of six subjects was measured for different field sizes ranging from a 0.18° to 7.28° radius and for two different wavelengths, 560 and 650 nm. The experimental setup consisted of having an instrument project uniform disks on the fundus and recording their retinal images after a double pass through the eye. Additionally, the relative spectral sensitivity for the same wavelengths was measured using heterochromatic flicker photometry for a stimulus of a 0.4° radius with and without the presence of a synchronously flickering concentric annulus. We concluded that although light backscattered from the fundus contributes to vision, the effect is not strong and can only be observed under appropriate laboratory conditions. This suggests that diffuse light from deeper fundus layers is unlikely to have a practical relevance to vision.


Myofibrillogenesis in living cells microinjected with fluorescently labeled alpha-actinin.
Fluorescently labeled alpha-actinin, isolated from chicken gizzards, breast muscle, or calf brains, was microinjected into cultured embryonic myotubes and cardiac myocytes where it was incorporated into the Z-bands of myofibrils. The localization in injected, living cells was confirmed by reacting permeabilized myotubes and cardiac myocytes with fluorescent alpha-actinin. Both living and permeabilized cells incorporated the alpha-actinin regardless of whether the alpha-actinin was isolated from nonmuscle, skeletal, or smooth muscle, or whether it was labeled with different fluorescent dyes. The living muscle cells could beat up to 5 d after injection. Rest-length sarcomeres in beating myotubes and cardiac myocytes were approximately 1.9-2.4 microns long, as measured by the separation of fluorescent bands of alpha-actinin. There were areas in nearly all beating cells, however, where narrow bands of alpha-actinin, spaced 0.3-1.5 micron apart, were arranged in linear arrays giving the appearance of minisarcomeres. In myotubes, alpha-actinin was found exclusively in these closely spaced arrays for the first 2-3 d in culture. When the myotubes became contraction-competent, at approximately day 4 to day 5 in culture, alpha-actinin was localized in Z-bands of fully formed sarcomeres, as well as in minisarcomeres. Video recordings of injected, spontaneously beating myotubes showed contracting myofibrils with 2.3 microns sarcomeres adjacent to noncontracting fibers with finely spaced periodicities of alpha-actinin. Time sequences of the same living myotube over a 24-h period revealed that the spacings between the minisarcomeres increased from 0.9-1.3 to 1.6-2.3 microns. Embryonic cardiac myocytes usually contained contractile networks of fully formed sarcomeres together with noncontractile minisarcomeres in peripheral areas of the cytoplasm. In some cells, individual myofibrils with 1.9-2.3 microns sarcomeres were connected in series with minisarcomeres. Double labeling of cardiac myocytes and myotubes with alpha-actinin and a monoclonal antibody directed against adult chicken skeletal myosin showed that all fibers that contained alpha-actinin also contained skeletal muscle myosin. This was true whether alpha-actinin was present in Z-bands of fully formed sarcomeres or present in the closely spaced beads of minisarcomeres. We propose that the closely spaced beads containing alpha-actinin are nascent Z-bands that grow apart and associate laterally with neighboring arrays containing alpha-actinin to form sarcomeres during myofibrillogenesis.


The Escherichia coli Serogroup O1 and O2 Lipopolysaccharides Are Encoded by Multiple O-antigen Gene Clusters.
Escherichia coli strains belonging to serogroups O1 and O2 are frequently associated with human infections, especially extra-intestinal infections such as bloodstream infections or urinary tract infections. These strains can be associated with a large array of flagellar antigens. Because of their frequency and clinical importance, a reliable detection of E. coli O1 and O2 strains and also the frequently associated K1 capsule is important for diagnosis and source attribution of E. coli infections in humans and animals. By sequencing the O-antigen clusters of various O1 and O2 strains we showed that the serogroups O1 and O2 are encoded by different sets of O-antigen encoding genes and identified potentially new O-groups. We developed qPCR-assays to detect the various O1 and O2 variants and the K1-encoding gene. These qPCR assays proved to be 100% sensitive and 100% specific and could be valuable tools for the investigations of zoonotic and food-borne infection of humans with O1 and O2 extra-intestinal (ExPEC) or Shiga toxin-producing E. coli (STEC) strains.


Development of algorithms to estimate EQ-5D and derive health utilities from WHOQOL-HIV Bref: a mapping study.
This study aimed to develop and evaluate different families of applicable models available for utility mapping between World Health Organization Quality of Life for HIV-abbreviated version (WHOQOL-HIV Bref) and EQ-5D-3L and to propose an optimised algorithm to estimate health utilities of people living with HIV. Estimation dataset was collected between July 2014 and September 2016 in a cross-sectional study including 1526 people living with HIV/Aids (PLWH) under care at the Instituto Nacional de Infectologia Evandro Chagas-FIOCRUZ, in Brazil. Data of WHOQOL-HIV Bref and EQ-5D-3L questionnaires were collected. Fisher's exact tests were used for testing WHOQOL-HIV Bref response frequencies among groups of responses to each of the five EQ-5D-3L domains. Multiple correspondence analyses (MCA) were used to inspect the relationships between both instrument responses. Different families of applicable models available for utility mapping between WHOQOL-HIV Bref and EQ-5D-3L were adjusted for the prediction of disutility. Candidate models' performances using mean absolute error (MAE), mean squared error (MSE), and root mean squared error (RMSE) were similarly good, which was evidenced by the overlapping of its 95% confidence intervals of the mean tenfold cross-validation or estimated generalisation errors. However, the Hurdle Logistic-Log-Normal model was better on average according to generalisation errors both in the prediction of Brazilian utility values (MAE = 0.1037, MSE = 0.0178, and RMSE = 0.1332) and for those of the UK (MAE = 0.1476, MSE = 0.0443, and RMSE = 0.2099). Mapping EQ-5D-3L responses or deriving health utilities directly from WHOQOL-HIV Bref responses can be a valid alternative for settings with no preference-based health utility data.


[Navigation surgery for pancreatic disease using multislice computed tomography].
In navigation surgery, preoperatively acquired image data are used so that surgical instruments can be guided inside the body while their location is displayed on a computer monitor. It is used in cranial nerve and spinal surgery. In the field of abdominal surgery, however, surgical manipulations in the target area cause major changes in the displayed images compared with those obtained preoperatively, and therefore, with the exception of certain organs, navigation surgery is difficult to apply. In general, this type of surgery aims to use intraoperative image information to improve surgical precision, carry out the preoperative plan accurately, and avoid dangerous areas. Three-dimensional images of the vascular architecture obtained with multislice computed tomography (MS-CT) make it possible to visualize arteries, the portal vein, bile duct, and even the pancreatic duct from any angle, which cannot be done with conventional angiography. Accurate positional relationships in the affected region can be determined preoperatively by manipulating multiplanar reconstruction images at a work station. MS-CT is extremely useful in navigation for safe performance of all types of pancreatectomy.


Myocardial and forearm blood flow reserve in mild-moderate essential hypertensive patients.
Structural readaptation of systemic resistance-sized arterioles in response to an elevated blood pressure reduces the forearm vasodilator reserve in patients with essential hypertension. The development of a similar process at the coronary microvascular level has frequently been hypothesized, but little information about coronary remodeling during the uncomplicated stage of hypertension has been obtained, and the relationship with concomitant changes in forearm blood flow reserve is not known. To assess the minimal myocardial resistance and its relationship with the minimal forearm resistance in a group of male patients with mild-to-moderate uncomplicated hypertension and carefully matched controls. The minimal myocardial resistance (Rmin(myocardia), the mean arterial pressure: hyperemic myocardial flow ratio after administration of 0.84 mg/kg dipyridamole, measured by using positron emission tomography and [3N]-ammonia), minimal forearm vascular resistance (Rmin(forearm), a hemodynamic index of arteriolar structure derived from the mean blood pressure and maximal postischemic forearm blood flow by venous plethysmography), echocardiographic cardiac mass and wall thickness were measured in 25 male patients with mild-to-moderate uncomplicated essential hypertension, most of whom had previously been treated, and in seven sex- and age-matched normotensive controls. Rmin(myocardial) (and hyperemia: baseline myocardial flow ratios) did not differ significantly between the two groups, whereas Rmin(forearm) was significantly higher in hypertensives. There was no significant intra-individual correlation between the two parameters. The left ventricular mass index was greater in patients and was related previously to Rmin(forearm) but not to Rmin(myocardial) for the overall sample. In a subgroup analysis, Rmin(forearm) values were 2SD above control values in nine patients and within the normal range in the remaining 16. The myocardial reserve was very similar in the two subgroups. The myocardial vasodilator reserve appeared to be preserved in these mild-to-moderate uncomplicated hypertensive patients, whereas the forearm vasodilator capacity was reduced, suggesting that the hypertensive readaptation process was not distributed homogeneously over the two vascular beds.


A high-gain, compact, nonimaging concentrator: RXI.
The design procedure of a new nonimaging concentrator (called an RXI) is explained. Rays that impinge on the concentrator aperture, within the acceptance angle, are directed to the receiver by means of one refraction, one reflection, and one total internal reflection. The concentrator can be made as a single dielectric piece (in which the receiver is immersed) whose aspect ratio (thickness/aperture diameter) is close to 1/3. Ray-tracing analysis of a rotational symmetric RXI shows total transmissions of greater than 94.5% (no absorption or reflection losses are considered) when the acceptance angle of the incoming rays is small (<3°) and when the receiver area is the smallest possible (maximal concentration.).


Eligibility of real-life patients with COPD for inclusion in RCTs: a commentary.
Randomized clinical trials (RCTs) are performed to provide evidence to support treatment decisions. Based on the nature of those studies and the need to avoid confounding factors, it has been argued that the population selected in RCTs only partially represents the real-life population. This assumption casts doubts on the applicability of the results provided by RCTs in the management of individuals with an established diagnosis of COPD, and advocates the need for complementary studies with a pragmatic design. Herein, we comment on the recent article published by Halpin and colleagues on the Journal [Halpin et al, Respir Res 17:120, 2016], in which higher rates of inclusions in RCTs for COPD are found compared to previous observations. By analyzing the design of the studies and the end results, we conclude that the accumulating evidence contribute to shed lights on how representative is the outpatient population of real life settings.


Genetic and non-genetic factors affecting the expression of COVID-19-relevant genes in the large airway epithelium.
The large airway epithelial barrier provides one of the first lines of defense against respiratory viruses, including SARS-CoV-2 that causes COVID-19. Substantial inter-individual variability in individual disease courses is hypothesized to be partially mediated by the differential regulation of the genes that interact with the SARS-CoV-2 virus or are involved in the subsequent host response. Here, we comprehensively investigated non-genetic and genetic factors influencing COVID-19-relevant bronchial epithelial gene expression. We analyzed RNA-sequencing data from bronchial epithelial brushings obtained from uninfected individuals. We related ACE2 gene expression to host and environmental factors in the SPIROMICS cohort of smokers with and without chronic obstructive pulmonary disease (COPD) and replicated these associations in two asthma cohorts, SARP and MAST. To identify airway biology beyond ACE2 binding that may contribute to increased susceptibility, we used gene set enrichment analyses to determine if gene expression changes indicative of a suppressed airway immune response observed early in SARS-CoV-2 infection are also observed in association with host factors. To identify host genetic variants affecting COVID-19 susceptibility in SPIROMICS, we performed expression quantitative trait (eQTL) mapping and investigated the phenotypic associations of the eQTL variants. We found that ACE2 expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-binding ACE2 isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.


Herbicide resistance in transgenic plants expressing a bacterial detoxification gene.
The herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) is a photosynthetic (photosystem II) inhibitor in plants. A gene, bxn, encoding a specific nitrilase that converts bromoxynil to its primary metabolite 3,5-dibromo-4-hydroxybenzoic acid, was cloned from the natural soil bacterium Klebsiella ozaenae. For expression in plants, the bxn gene was placed under control of a light-regulated tissue-specific promoter, the ribulose bisphosphate carboxylase small subunit. Transfer of this chimeric gene and expression of a bromoxynil-specific nitrilase in leaves of transgenic tobacco plants conferred resistance to high levels of a commercial formulation of bromoxynil. The results presented indicate a successful approach to obtain herbicide resistance by introducing a novel catabolic detoxification gene in plants.


MECHANISMS IN ENDOCRINOLOGY: Endocannabinoids and metabolism: past, present and future.
The endocannabinoid system (ECS), including cannabinoid type 1 and type 2 receptors (CB1R and CB2R), endogenous ligands called endocannabinoids and their related enzymatic machinery, is known to have a role in the regulation of energy balance. Past information generated on the ECS, mainly focused on the involvement of this system in the central nervous system regulation of food intake, while at the same time clinical studies pointed out the therapeutic efficacy of brain penetrant CB1R antagonists like rimonabant for obesity and metabolic disorders. Rimonabant was removed from the market in 2009 and its obituary written due to its psychiatric side effects. However, in the meanwhile a number of investigations had started to highlight the roles of the peripheral ECS in the regulation of metabolism, bringing up new hope that the ECS might still represent target for treatment. Accordingly, peripherally restricted CB1R antagonists or inverse agonists have shown to effectively reduce body weight, adiposity, insulin resistance and dyslipidemia in obese animal models. Very recent investigations have further expanded the possible toolbox for the modulation of the ECS, by demonstrating the existence of endogenous allosteric inhibitors of CB1R, the characterization of the structure of the human CB1R, and the likely involvement of CB2R in metabolic disorders. Here we give an overview of these findings, discussing what the future may hold in the context of strategies targeting the ECS in metabolic disease.


Barriers and Enablers to the Implementation of School Wellness Policies: An Economic Perspective.
Local wellness policies (LWPs) are mandated among school systems to enhance nutrition/physical activity opportunities in schools. Prior research notes disparities in LWP implementation. This study uses mixed methods to examine barriers/enablers to LWP implementation, comparing responses by student body income. Schools ( n = 744, 24 systems) completed an LWP implementation barriers/enablers survey. Semistructured interviews ( n = 20 random subsample) described barriers/enablers. Responses were compared by majority of lower (≥50% free/reduced-price meals; lower income [LI]) versus higher income (HI) student body. In surveys, LI and HI schools identified common barriers (parents/families, federal/state regulations, students, time, funding) and enablers (school system, teachers, food service, physical education curriculum/resources, and staff). Interviews further elucidated how staffing and funding served as enablers for all schools, and provide context for how and why barriers differed by income: time, food service (HI schools), and parents/families (LI schools). Findings support commonalities in barriers and enablers among all schools, suggesting that regardless of economic context, schools would benefit from additional supports, such as physical education and nutrition education resources integrated into existing curricula, additional funding, and personnel time dedicated to wellness programming. LI schools may benefit from additional funding to support parent and community involvement.


Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated Caspase pathways.
Fluoride is an environmental toxicant and induces dental fluorosis and oxidative stress. Lycopene (LYC) is an effective antioxidant that is reported to attenuate fluoride toxicity. To determine the effects of LYC on sodium fluoride (NaF) -induced teeth and ameloblasts toxicity, rats were treated with NaF (10 mg/kg) and/or LYC (10 mg/kg) by orally administration for 5 weeks; ameloblasts were treated with NaF (5 mM) and/or LYC (2 μM) for 6 h. We found that the concentrations of fluoride, malondialdehyde (MDA) and reactive oxygen species (ROS), gene expressions and activities of Caspase-9 and Caspase-3, and the gene expressions of Bax were significantly decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX), the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated rats group; concentrations of MDA and ROS, gene expressions and activities of Caspase-9 and Caspase-3, and the gene expression of Bax, and ameloblasts apoptosis rate were significantly decreased, while the activities of SOD and GPX, the gene expression of Bcl-2 were significantly increased in the LYC + NaF-treated ameloblasts group. These results suggest that LYC significantly combated NaF-induced ameloblasts apoptosis and dental fluorosis by attenuation oxidative stress and down-regulation Caspase pathway.


Orientational Epitaxy of van der Waals Molecular Heterostructures.
The shape of individual building blocks is an important parameter in bottom-up self-assembly of nanostructured materials. A simple shape change from sphere to spheroid can significantly affect the assembly process due to the modification to the orientational degrees of freedom. When a layer of spheres is placed upon a layer of spheroids, the strain at the interface can be minimized by the spheroid taking a special orientation. C70 fullerenes represent the smallest spheroids, and their interaction with a sphere-like C60 is investigated. We find that the orientation of the C70 within a close-packed C70 layer can be steered by contacting a layer of C60. This orientational steering phenomenon is potentially useful for epitaxial growth of multilayer van der Waals molecular heterostructures.


Functional Analysis of the Transmembrane and Cytoplasmic Domains of Pcdh15a in Zebrafish Hair Cells.
Protocadherin 15 (PCDH15) is required for mechanotransduction in sensory hair cells as a component of the tip link. Isoforms of PCDH15 differ in their cytoplasmic domains (CD1, CD2, and CD3), but share the extracellular and transmembrane (TMD) domains, as well as an intracellular domain known as the common region (CR). In heterologous expression systems, both the TMD and CR of PCDH15 have been shown to interact with members of the mechanotransduction complex. The in vivo significance of these protein-protein interaction domains of PCDH15 in hair cells has not been determined. Here, we examined the localization and function of the two isoforms of zebrafish Pcdh15a (CD1 and CD3) in pcdh15a-null mutants by assessing Pcdh15a transgene-mediated rescue of auditory/vestibular behavior and hair cell morphology and activity. We found that either isoform alone was able to rescue the Pcdh15a-null phenotype and that the CD1- or CD3-specific regions were dispensable for hair bundle integrity and labeling of hair cells with FM4-64, which was used as a proxy for mechanotransduction. When either the CR or TMD domain was deleted, the mutated proteins localized to the stereocilial tips, but were unable to rescue FM4-64 labeling. Disrupting both domains led to a complete failure of Pcdh15a to localize to the hair bundle. Our findings demonstrate that the TMD and cytoplasmic CR domains are required for the in vivo function of Pcdh15a in zebrafish hair cells.SIGNIFICANCE STATEMENT Tip links transmit force to mechanotransduction channels at the tip of hair bundles in sensory hair cells. One component of tip links is Protocadherin 15 (PCDH15). Here, we demonstrate that, when transgenically expressed, either zebrafish Pcdh15a-cytodomain 1 (CD1) or Pcdh15a-CD3 can rescue the phenotype of a pcdh15a-null mutant. Even when lacking the specific regions for CD1 or CD3, truncated Pcdh15a that contains the so-called common region (CR) at the cytoplasmic/membrane interface still has the ability to rescue similar to full-length Pcdh15a. In contrast, Pcdh15a lacking the entire cytoplasmic domain is not functional. These results demonstrate that the CR plays a key role in the mechanotransduction complex in hair cells.


A rotary molecular motor that can work at near 100% efficiency.
A single molecule of F1-ATPase is by itself a rotary motor in which a central gamma-subunit rotates against a surrounding cylinder made of alpha3beta3-subunits. Driven by the three betas that sequentially hydrolyse ATP, the motor rotates in discrete 120 degree steps, as demonstrated in video images of the movement of an actin filament bound, as a marker, to the central gamma-subunit. Over a broad range of load (hydrodynamic friction against the rotating actin filament) and speed, the F1 motor produces a constant torque of ca. 40 pN nm. The work done in a 120 degree step, or the work per ATP molecule, is thus ca. 80 pN nm. In cells, the free energy of ATP hydrolysis is ca. 90 pN nm per ATP molecule, suggesting that the F1 motor can work at near 100% efficiency. We confirmed in vitro that F1 indeed does ca. 80 pN nm of work under the condition where the free energy per ATP is 90 pN nm. The high efficiency may be related to the fully reversible nature of the F1 motor: the ATP synthase, of which F1 is a part, is considered to synthesize ATP from ADP and phosphate by reverse rotation of the F1 motor. Possible mechanisms of F1 rotation are discussed.


Thickness of posterior palatal masticatory mucosa: the use of computerized tomography.
Periodontal plastic surgery is used to fulfill the esthetic and functional demands of patients. The palatal masticatory mucosa is the main donor site for connective tissue, and the thickness of the graft tissue obtained is an important factor for the success of this technique. The aim of this study was to measure the thickness of masticatory mucosa in the posterior palatal area using computerized tomography (CT). The thickness measurements were performed on the images of 100 adult subjects who underwent CT on the maxilla for implant surgery. Twenty-four standard measurement points were defined in the hard palate according to the gingival margin and the middle palatal suture. The radiographic measurements were used after calibration. The data were analyzed to determine the differences in the mucosal thickness according to gender, age, tooth position, and depth of the palatal vault. The overall mean thickness of the palatal masticatory mucosa was 3.83 +/- 0.58 mm (range: 2.29 to 6.25 mm). Females had significantly thinner mean masticatory mucosa (3.66 +/- 0.52 mm) than males (3.95 +/- 0.60 mm) (P <0.0001). The thickness of the palatal masticatory mucosa increased with age. The mean thickness according to tooth site was 3.46 mm (maxillary canine), 3.66 mm (first premolar), 3.81 mm (second premolar), 3.13 mm (first molar), 3.31 mm (the base of the interproximal papilla of the first and second molars), and 3.39 mm (second molar). There was an overall increase in the thickness of the palatal masticatory mucosa as the distance from the gingival margin to the middle palatine suture increased, with the exception of the Ca-d (a point at 12 mm from the gingival margin of the canine) region. There was no significant difference in the thickness of the palatal masticatory mucosa between the groups with high or low palatal vaults. The palatal masticatory mucosa thickness increased from the canine to premolar region but decreased at the first molar region and increased again in the second molar region, with the thinnest area at the first molar region and the thickest at the second premolar region. The canine to premolar region seems to be the most appropriate donor site that contains a uniformly thick mucosa. CT can be considered an alternative method for the measurement of palatal soft tissue thickness.


Evolutionary pathways of N2 neuraminidases of swine and human influenza A viruses: origin of the neuraminidase genes of two reassortants (H1N2) isolated from pigs.
The complete nucleotide sequences of the neuraminidase (NA) genes of two reassortant (H1N2) and two H3N2 influenza A viruses isolated from pigs were determined and phylogenetic relationships between these and previously reported N2 NA genes were investigated. On the basis of pairwise nucleotide sequence identity, the NA genes of two reassortants, A/sw/Kanagawa/2/78 and A/sw/Ehime/1/80, were most closely related to those of human influenza A virus strains isolated in 1972 and the earliest available swine H3N2 influenza A viruses, respectively. Phylogenetic trees showed that the NA genes can be segregated into three groups, including lineages for (i) swine strains, (ii) the earliest human strain and (iii) recent human strains. The evolutionary tree for the 11 nucleotide and amino acid sequences suggested that the NAs of A/sw/HK/4/76 and A/sw/Kanagawa/2/78 belong to the lineage for recent human viruses. In contrast, the NA genes of the A/sw/HK/3/76 and H1N2 reassortant A/sw/Ehime/1/80 viruses were found to be of a swine lineage. The swine virus NA genes were further characterized by the cocirculation of two distinct lineages. Although the rates of synonymous (silent) substitutions for the swine and human viruses were nearly identical (0.00946 to 0.00884 per site per year), the rate of non-synonymous (amino acid changing) substitutions for swine virus NA genes was about 60% of that for the human virus.


Zinc in gut-brain interaction in autism and neurological disorders.
A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.


An Insight into Surface Topographical Parameters and Bacterial Adhesion: A Case Study of Listeria monocytogenes Scott A Attachment on 304 Stainless Steel.
Bacterial attachment on surfaces is an important biological and industrial concern. Many parameters affect cell attachment behavior, including surface roughness and other topographical features. An understanding of these relationships is critical in the light of recent outbreaks caused by foodborne bacteria. Postharvest packing lines have been identified as a potential source of cross-contamination with pathogens, which can cause subsequent foodborne illness. The objective of this article is to evaluate the influence of surface topographical features on bacterial attachment at various processing temperatures to determine the extent of bacterial colonization. Type 304 stainless steel surfaces and pathogenic Listeria monocytogenes Scott A were used for a detailed investigation. Two commonly used surface types, extruded and ground, were evaluated to determine differences in bacterial attachment on the same type of material. Fifteen surface topography parameters at three processing temperatures were studied to evaluate possible correlations with microbial attachment on these surfaces. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, and confocal microscopy were used for both qualitative and quantitative analyses of surfaces. An analysis of variance and multivariate regression analysis were used to predict the attachment behavior of L. monocytogenes Scott A on stainless steel surfaces. Surface isotropy, average surface roughness, surface spacing, and processing temperatures were strongly correlated with bacterial attachment on 304 stainless steel material.


Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses.
To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses. 6 adult horses. Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week intervals; PO and IV administrations of dexamethasone were accompanied by IV or PO sham treatments, respectively. Plasma dexamethasone and serum cortisol concentrations were assessed at predetermined intervals. Maximum plasma dexamethasone concentration after PO administration of powdered dexamethasone in unfed horses was significantly higher than the maximum plasma concentration after PO administration of dexamethasone solution in unfed or fed horses. Mean bioavailability of dexamethasone ranged from 28% to 66% but was not significantly different among horses receiving either formulation PO in the unfed or fed state. After dexamethasone treatment PO or IV, serum cortisol concentrations were significantly less than baseline at 1 to 72 hours in unfed horses and at 2 to 48 hours in fed horses. PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of suppression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours.


Distance education methods are useful for delivering education to palliative caregivers: A single-arm trial of an education package (PalliativE Caregivers Education Package).
Face-to-face/group education for palliative caregivers is successful, but relies on caregivers travelling, being absent from the patient, and rigid timings. This presents inequities for those in rural locations. To design and test an innovative distance-learning educational package (PrECEPt: PalliativE Caregivers Education Package). Single-arm mixed-method feasibility proof-of-concept trial (ACTRN12616000601437). The primary outcome was carer self-efficacy, with secondary outcomes focused on caregiver preparedness and carer tasks/needs. Analysis focused on three outcome measures (taken at baseline and 6 weeks) and feasibility/acceptability qualitative data. A single specialist palliative care service. Eligible informal caregivers were those of patients registered with the outpatient or community service, where the patient had a prognosis of ⩾12 weeks, supporting someone with nutrition/hydration and/or pain management needs, proficient in English and no major mental health diagnosis. Two modules were developed and tested (nutrition/hydration and pain management) with 18 caregivers. The materials did not have a statistically significant impact on carer self-efficacy. However, statistically significant improvements were observed on the two subsidiary measures of (1) caregiving tasks, consequences and needs ( p = 0.03, confidence interval: 0.72, 9.4) and (2) caregiver preparedness ( p = 0.001, confidence interval: -1.22, -0.46). The study determined that distance learning is acceptable and feasible for both caregivers and healthcare professionals. Distance education improves caregiver preparedness and is a feasible and acceptable approach. A two-arm trial would determine whether the materials benefitted caregivers and patients compared to a control group not receiving the materials. Additional modules could be fruitfully developed and offered.


Differences between generalized q-sampling imaging and diffusion tensor imaging in the preoperative visualization of the nerve fiber tracts within peritumoral edema in brain.
Diffusion tensor imaging (DTI) tractography enables the in vivo visualization of white matter tracts inside normal brain tissue, which provides the neurosurgeon important information to plan tumor resections. However, DTI is associated with restrictions in the resolution of crossing fibers in the vicinity of the tumor or in edema. We find that generalized q-sampling imaging (GQI) can overcome these difficulties and is advantageous over DTI for the tractography of the fiber bundle in peritumoral edema. To demonstrate the differences between GQI and DTI in the preoperative mapping of fiber tractography in peritumoral edema of cerebral tumors, and discuss the clinical application of GQI in neurosurgical planning. Five patients with brain tumors underwent 3-T magnetic resonance imaging scans, and the data were reconstructed by DTI and GQI. We adjusted the parameters and compared the differences between DTI and GQI in visualizing the fiber tracts in the peritumoral edema of cerebral tumors. GQI and DTI showed substantial differences in displaying the nerve fibers in the edema surrounding the tumor. The GQI tractography method could fully display existing intact fibers in the edema, whereas the fiber tracts in edema displayed by DTI tractography were incomplete, missing, or ruptured. GQI can visualize the tracts in the peritumoral edema of cerebral tumors better than DTI. Although GQI has many limitations, its future in the preoperative guidance of brain tumor lesions is promising.


Short- and long-latency interhemispheric inhibitions are additive in human motor cortex.
Transcranial magnetic stimulation (TMS) of the human primary motor cortex (M1) at suprathreshold strength results in inhibition of M1 in the opposite hemisphere, a process termed interhemispheric inhibition (IHI). Two phases of IHI, termed short-latency interhemispheric inhibition (SIHI) and long-latency interhemispheric inhibition (LIHI), involving separate neural circuits, have been identified. In this study we evaluated how these two inhibitory processes interact with each other. We studied 10 healthy right-handed subjects. A test stimulus (TS) was delivered to the left M1, and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) muscle. Contralateral conditioning stimuli (CCS) were applied to the right M1 either 10 ms or 50 ms prior to the TS, inducing SIHI and LIHI, respectively, in the left M1. The effects of SIHI and LIHI alone, and SIHI and LIHI delivered together, were compared. The TS was adjusted to produce 1-mV or 0.5-mV MEPs when applied alone or after CCS. SIHI and LIHI were found to be additive when delivered together, irrespective of the strength of the TS. The interactions were affected neither by varying the strength of the conditioning stimulus producing SIHI nor by altering the current direction of the TS. Small or opposing interactions, however, may not have been detected. These results support previous findings suggesting that SIHI and LIHI act through different neural circuits. Such inhibitory processes may be used individually or additively during motor tasks and should be studied as separate processes in functional studies.


Two homologous EF-G proteins from Pseudomonas aeruginosa exhibit distinct functions.
Genes encoding two proteins corresponding to elongation factor G (EF-G) were cloned from Pseudomonas aeruginosa. The proteins encoded by these genes are both members of the EFG I subfamily. The gene encoding one of the forms of EF-G is located in the str operon and the resulting protein is referred to as EF-G1A while the gene encoding the other form of EF-G is located in another part of the genome and the resulting protein is referred to as EF-G1B. These proteins were expressed and purified to 98% homogeneity. Sequence analysis indicated the two proteins are 90/84% similar/identical. In other organisms containing multiple forms of EF-G a lower degree of similarity is seen. When assayed in a poly(U)-directed poly-phenylalanine translation system, EF-G1B was 75-fold more active than EF-G1A. EF-G1A pre-incubate with ribosomes in the presence of the ribosome recycling factor (RRF) decreased polymerization of poly-phenylalanine upon addition of EF-G1B in poly(U)-directed translation suggesting a role for EF-G1A in uncoupling of the ribosome into its constituent subunits. Both forms of P. aeruginosa EF-G were active in ribosome dependent GTPase activity. The kinetic parameters (K M) for the interaction of EF-G1A and EF-G1B with GTP were 85 and 70 μM, respectively. However, EF-G1B exhibited a 5-fold greater turnover number (observed k cat) for the hydrolysis of GTP than EF-G1A; 0.2 s(-1) vs. 0.04 s(-1). These values resulted in specificity constants (k cat (obs)/K M) for EF-G1A and EF-G1B of 0.5 x 10(3) s(-1) M(-1) and 3.0 x 10(3) s(-1) M(-1), respectively. The antibiotic fusidic acid (FA) completely inhibited poly(U)-dependent protein synthesis containing P. aeruginosa EF-G1B, but the same protein synthesis system containing EF-G1A was not affected. Likewise, the activity of EF-G1B in ribosome dependent GTPase assays was completely inhibited by FA, while the activity of EF-G1A was not affected.


Monocytes activate natural killer cells via inflammasome-induced interleukin 18 in response to hepatitis C virus replication.
Production of interferon (IFN)-γ by natural killer (NK) cells is attenuated during chronic infection with hepatitis C virus (HCV). We investigated whether this is due to intrinsic or extrinsic mechanisms of NK cells. Peripheral blood mononuclear cells (PBMCs) were collected from patients with chronic HCV infection or uninfected blood donors (controls); NK cells and monocytes were isolated or eliminated. We cultured hepatoma cells that express luciferase-tagged subgenomic HCV replicons (Huh7/HCV replicon cells) or their HCV-negative counterparts (Huh7) with NK cells in the presence or absence of other populations of PBMCs. Antiviral activity, cytotoxicity, and cytokine production were assessed. NK cells produced greater amounts of IFN-γ when PBMC were cocultured with Huh7/HCV replicon cells than with Huh7 cells; NK cells and PBMCs from controls suppressed HCV replication to a greater extent than those from patients with chronic HCV infection. This antiviral effect was predominantly mediated by tumor necrosis factor (TNF)-α and IFN-γ. The antiviral activity of NK cells and their production of IFN-γ were reduced when they were used in coculture alone (rather than with PBMC), or after depletion of CD14(+) monocytes, after knockdown of the inflammasome in monocytes, or after neutralization of interleukin-18, which is regulated by the inflammasome. These findings indicate a role for monocytes in NK cell activation. Compared with control monocytes, monocytes from patients with chronic HCV infection had reduced TNF-α-mediated (direct) and reduced NK cell-mediated (indirect) antiviral effects. Control monocytes increased the antiviral effects of NK cells from patients with chronic HCV infection and their production of IFN-γ. Monocytes sense cells that contain replicating HCV and respond by producing interleukin-18 via the inflammasome and by activating NK cells. Patients with chronic HCV infection have reduced monocyte function, attenuating NK cell IFN-γ-mediated responses.


Theory of input spike auto- and cross-correlations and their effect on the response of spiking neurons.
Spike correlations between neurons are ubiquitous in the cortex, but their role is not understood. Here we describe the firing response of a leaky integrate-and-fire neuron (LIF) when it receives a temporarily correlated input generated by presynaptic correlated neuronal populations. Input correlations are characterized in terms of the firing rates, Fano factors, correlation coefficients, and correlation timescale of the neurons driving the target neuron. We show that the sum of the presynaptic spike trains cannot be well described by a Poisson process. In fact, the total input current has a nontrivial two-point correlation function described by two main parameters: the correlation timescale (how precise the input correlations are in time) and the correlation magnitude (how strong they are). Therefore, the total current generated by the input spike trains is not well described by a white noise gaussian process. Instead, we model the total current as a colored gaussian process with the same mean and two-point correlation function, leading to the formulation of the problem in terms of a Fokker-Planck equation. Solutions of the output firing rate are found in the limit of short and long correlation timescales. The solutions described here expand and improve on our previous results (Moreno, de la Rocha, Renart, & Parga, 2002) by presenting new analytical expressions for the output firing rate for general IF neurons, extending the validity of the results for arbitrarily large correlation magnitude, and by describing the differential effect of correlations on the mean-driven or noise-dominated firing regimes. Also the details of this novel formalism are given here for the first time. We employ numerical simulations to confirm the analytical solutions and study the firing response to sudden changes in the input correlations. We expect this formalism to be useful for the study of correlations in neuronal networks and their role in neural processing and information transmission.


Origin of gene overlap: the case of TCP1 and ACAT2.
The human acetyl-CoA acetyltransferase 2 gene, ACAT2, codes for a thiolase, an enzyme involved in lipid metabolism. The human T-complex protein 1 gene, TCP1, encodes a molecular chaperone of the chaperonin family. The two genes overlap by their 3'-untranslated regions, their coding sequences being located on opposite DNA strands in a tail-to-tail orientation. To find out how the overlap might have arisen in evolution, the homologous genes of the zebrafish, the African toad, caiman, platypus, opossum, and wallaby were identified. In each species, standard or long polymerase chain reactions were used to determine whether the ACAT2 and TCP1 homologs are closely linked and, if so, whether they overlap. The results reveal that the overlap apparently arose during the transition from therapsid reptiles to mammals and has been retained for >200 million years. Part of the overlapping untranslated region shows remarkable sequence conservation. The overlap presumably arose during the chromosomal rearrangement that brought the two unrelated and previously separated genes together. One or both of the transposed genes found by chance signals that are necessary for the processing of their transcripts to be present on the noncoding strand of the partner gene.


Case From the Eyes of an Anatomist: Fistula Between Proximal of Left Anterior Descending Artery to Pulmonary Artery.
Advanced diagnostic systems and screening services for health care have made it possible to improve the detection of congenital cardio-vascular abnormalities, including coronary artery variations. Many coronary artery fistulas are congenital, and this can also be reported in patients with normal heart anatomy. In this report, we present a patient with a fistula between left anterior descending artery and pulmonary artery which was diagnosed incidentally with conventional angiography.


Effect of partial volume correction on muscarinic cholinergic receptor imaging with single-photon emission tomography in patients with temporal lobe epilepsy.
Animal experiments and preliminary results in humans have indicated alterations of hippocampal muscarinic acetylcholine receptors (mAChR) in temporal lobe epilepsy. Patients with temporal lobe epilepsy often present with a reduction in hippocampal volume. The aim of this study was to investigate the influence of hippocampal atrophy on the quantification of mAChR with single photon emission tomography (SPET) in patients with temporal lobe epilepsy. Cerebral uptake of the muscarinic cholinergic antagonist [123I]4-iododexetimide (IDex) was investigated by SPET in patients suffering from temporal lobe epilepsy of unilateral (n=6) or predominantly unilateral (n=1) onset. Regions of interest were drawn on co-registered magnetic resonance images. Hippocampal volume was determined in these regions and was used to correct the SPET results for partial volume effects. A ratio of hippocampal IDex binding on the affected side to that on the unaffected side was used to detect changes in muscarinic cholinergic receptor density. Before partial volume correction a decrease in hippocampal IDex binding on the focus side was found in each patient. After partial volume no convincing differences remained. Our results indicate that the reduction in hippocampal IDex binding in patients with epilepsy is due to a decrease in hippocampal volume rather than to a decrease in receptor concentration.


Effects of Awareness on the Control of Attention.
Previous studies show that it is possible to attend to a stimulus without awareness of it. Whether attention and awareness are independent or have a specific relationship, however, remains debated. Here, we tested three aspects of visual attention with and without awareness of the visual stimulus. Metacontrast masking rendered participants either subjectively aware or not aware of the stimulus. Attention drawn to the stimulus was measured by using the stimulus as a cue in a spatial attention task. We found that attention was drawn to the stimulus regardless of whether or not people were aware of it. However, attention changed significantly in the absence of awareness in at least three ways. First, attention to a task-relevant stimulus was less stable over time. Second, inhibition of return, the automatic suppression of attention to a task-irrelevant stimulus, was reduced. Third, attention was more driven by the luminance contrast of the stimulus. These findings add to the growing information on the behavior of attention with and without awareness. The findings are also consistent with our recently proposed account of the relationship between attention and awareness. In the attention schema theory, awareness is the internal model of attention. Just as the brain contains a body schema that models the body and helps control the body, so it contains an attention schema that helps control attention. In that theory, in the absence of awareness, the control of attention should suffer in basic ways predictable from dynamical systems theory. The present results confirm some of those predictions.


The ISPOR Good Practices for Quality Improvement of Cost-Effectiveness Research Task Force Report.
The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Health Science Policy Council recommended and the ISPOR Board of Directors approved the formation of a Task Force to critically examine the major issues related to Quality Improvement in Cost-effectiveness Research (QICER). The Council's primary recommendation for this Task Force was that it should report on the quality of cost-effectiveness research and make recommendations to facilitate the improvement of pharmacoeconomics and health outcomes research and its use in stimulating better health care and policy. Task force members were knowledgeable and experienced in medicine, pharmacy, biostatistics, health policy and health-care decision-making, biomedical knowledge transfer, health economics, and pharmacoeconomics. They were drawn from industry, academia, consulting organizations, and advisors to governments and came from Japan, the Netherlands, Canada and the United States. Face-to-face meetings of the Task Force were held at ISPOR North American and European meetings and teleconferences occurred every few months. Literature reviews and surveys were conducted and the first preliminary findings presented at an open forum at the May 2008 ISPOR meeting in Toronto. The final draft report was circulated to the expert reviewer group and then to the entire membership for comment. The draft report was posted on the ISPOR Web site in April 2009. All formal comments received were posted to the association Web site and presented for discussion at the Task Force forum during the ISPOR 14th Annual International Meeting in May 2009. Comments and feedback from the forums, reviewers and membership were considered in the final report. Once Task Force consensus was reached, the article was submitted to Value in Health. The QICER Task Force recommends that ISPOR implement the following: * With respect to CER guidelines, that ISPOR promote harmonization of guidelines, allowing for differences in application, regional needs and politics; evaluate available instruments or promote development of a new one that will allow standardized quantification of the impact of CER guidelines on the quality of CER studies; report periodically on those countries or regions that have developed guidelines; periodically evaluate the quality of published studies (those journals with CER guidances) or those submitted to decision-making bodies (as public transparency increases). * With respect to methodologies, that ISPOR promote publication of methodological guidelines in more applied journals in more easily understandable format to transfer knowledge to researchers who need to apply more rigorous methods; promote full availability of models in electronic format to combat space restrictions in hardcopy publications; promote consistency of methodological review for all CER studies; promote adoption of explicit best practices guidelines among regulatory and reimbursement authorities; periodically update all ISPOR Task Force reports; periodically review use of ISPOR Task Force guidelines; periodically report on statistical and methodological challenges in HE; evaluate periodically whether ISPOR's methodological guidelines lead to improved quality; and support training and knowledge transfer of rigorous CER methodologies to researchers and health care decision-makers. * With respect to publications, that ISPOR develop standard CER guidances to which journals will be able to refer their authors and their reviewers; lobby to establish these guidances within the International Committee for Medical Journal Editors (ICMJE) Requirements to which most journals refer in their Author Instructions; provide support in terms of additional reviewer expertise to those journals lacking appropriate reviewers; periodically report on journals publishing CER research; periodically report on the quality of CER publications; and support training and knowledge transfer of the use of these guidelines to researchers and reviewers. * With respect to evidence-based health-care decision-making, that ISPOR recognize at its annual meetings those countries/agencies/private companies/researchers using CER well, and those practitioners and researchers supporting good patient use of CER in decision-making; and promote public presentation of case studies of applied use of CER concepts or guidelines.


Is there a role for vitamin C in preventing osteoporosis and fractures? A review of the potential underlying mechanisms and current epidemiological evidence.
Osteoporosis and related fractures are a major global health issue, but there are few preventative strategies. Previously reported associations between higher intakes of fruits and vegetables and skeletal health have been suggested to be partly attributable to vitamin C. To date, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention but an overall consensus of published studies has not yet been drawn. The present review aims to provide a summary of the proposed underlying mechanisms of vitamin C on bone and reviews the current evidence in the literature, examining a potential link between vitamin C intake and status with osteoporosis and fractures. The Bradford Hill criteria were used to assess reported associations. Recent animal studies have provided insights into the involvement of vitamin C in osteoclastogenesis and osteoblastogenesis, and its role as a mediator of bone matrix deposition, affecting both the quantity and quality of bone collagen. Observational studies have provided some evidence for this in the general population, showing positive associations between dietary vitamin C intake and supplements and higher bone mineral density or reduced fracture risk. However, previous intervention studies were not sufficiently well designed to evaluate these associations. Epidemiological data are particularly limited for vitamin C status and for fracture risk and good-quality randomised controlled trials are needed to confirm previous epidemiological findings. The present review also highlights that associations between vitamin C and bone health may be non-linear and further research is needed to ascertain optimal intakes for osteoporosis and fracture prevention.


Forcing the issue: aromatic tuning facilitates stimulus-independent modulation of a two-component signaling circuit.
Two-component signaling circuits allow bacteria to detect and respond to external stimuli. Unfortunately, the input stimulus remains unidentified for the majority of these circuits. Therefore, development of a synthetic method for stimulus-independent modulation of these circuits is highly desirable because particular physiological or developmental processes could be controlled for biotechnological purposes without the need to identify the stimulus itself. Here, we demonstrate that aromatic tuning, i.e., repositioning the aromatic residues commonly found at the cytoplasmic end of the receptor (EnvZ) transmembrane domain, facilitates stimulus-independent modulation of signal output from the EnvZ/OmpR osmosensing circuit of Escherichia coli. We found that these osmosensing circuits retained the ability to respond appropriately to increased external osmolarity, suggesting that the tuned receptors were not locked in a single conformation. We also noted that circuits containing aromatically tuned variants became more sensitive to changes in the receptor concentration than their wild-type counterpart, suggesting a new way to study mechanisms underpinning receptor concentration-dependent robustness. We believe that aromatic tuning has several advantages compared to previous methods aimed at stimulus-independent modulation of receptors and that it will be generally applicable to a wide-range of two-component circuits.


Regulation of human neutrophil Fcγ receptor IIa by C5a receptor promotes inflammatory arthritis in mice.
Rheumatoid arthritis culminates in joint destruction that, in mouse models of disease, is supported by innate immune molecules, including Fcγ receptors (FcγR) and complement. However, these findings may not be predictive of the outcome in humans, given the structural differences between murine and human activating FcγR on neutrophils, a prominent component of joint exudates. The aim of this study was to examine the role of human neutrophil FcγRIIa in the development of arthritis and probe the underlying mechanism by which FcγRIIa initiates disease. K/BxN mouse serum transfer-induced arthritis was examined in mice expressing human FcγRIIa on neutrophils but lacking their own activating FcγR (γ-chain-deficient mice). The role of mast cells, complement (C3 and C5a), and CD18 integrins in FcγRIIa-initiated disease was examined using cell reconstitution approaches, inhibitors, and functional blocking antibodies, respectively. Crosstalk between the complement receptor C5aR and FcγRIIa on neutrophils was evaluated in vitro. The expression of human FcγRIIa on neutrophils was sufficient to restore susceptibility to K/BxN serum-induced neutrophil recruitment, synovitis, and bone destruction in γ-chain-deficient mice. Joint inflammation was robust and proceeded even in the absence of mast cells and vascular permeability, features shown to contribute to disease in wild-type mice. Neutrophil recruitment was dependent on the presence of a CD18 integrin, lymphocyte function-associated antigen 1, and C5aR. In addition, C5aR significantly enhanced FcγRIIa-mediated phagocytosis and oxidative burst in vitro. Human and murine activating FcγR on neutrophils are not functionally equivalent, and in humans, they may play a primary role in arthritis. Crosstalk between neutrophil C5aR and FcγRIIa is essential for disease progression, thus highlighting a new aspect of complement during the effector phase of inflammatory arthritis.


Repetitive peripheral magnetic stimulation for impairment and disability in people after stroke.
Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive treatment method that can penetrate to deeper structures with painless stimulation to improve motor function in people with physical impairment due to brain or nerve disorders. rPMS for people after stroke has proved to be a feasible approach to improving activities of daily living and functional ability. However, the effectiveness and safety of this intervention for people after stroke currently remain uncertain. This is an update of the review published in 2017. To assess the effects of rPMS in improving activities of daily living and functional ability in people after stroke. On 7 January 2019, we searched the Cochrane Stroke Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); PsycINFO; the Allied and Complementary Medicine Database (AMED); Occupational Therapy Systematic Evaluation of Evidence (OTseeker); the Physiotherapy Evidence Database (PEDro); ICHUSHI Web; and six ongoing trial registries. We screened reference lists, and we contacted experts in the field. We placed no restrictions on the language or date of publication when searching electronic databases. We included randomised controlled trials (RCTs) conducted to assess the therapeutic effect of rPMS for people after stroke. Comparisons eligible for inclusion were (1) active rPMS only compared with 'sham' rPMS (a very weak form of stimulation or a sound only); (2) active rPMS only compared with no intervention; (3) active rPMS plus rehabilitation compared with sham rPMS plus rehabilitation; and (4) active rPMS plus rehabilitation compared with rehabilitation only. Two review authors independently assessed studies for inclusion. The same review authors assessed methods and risk of bias, undertook data extraction, and used the GRADE approach to assess the quality of evidence. We contacted trial authors to request unpublished information if necessary. We resolved all disagreements through discussion. We included four trials (three RCTs and one cross-over trial) involving 139 participants. Blinding of participants and physicians was well reported within all trials. We judged the overall risk of bias across trials as low. Only two trials (with 63 and 18 participants, respectively) provided sufficient information to be included in the meta-analysis. We found no clear effect of rPMS on activities of daily living at the end of treatment (mean difference (MD) -3.00, 95% confidence interval (CI) -16.35 to 10.35; P = 0.66; 1 trial; 63 participants; low-quality evidence) and at the end of follow-up (MD -2.00, 95% CI -14.86 to 10.86; P = 0.76; 1 trial; 63 participants; low-quality evidence) when comparing rPMS plus rehabilitation versus sham plus rehabilitation. We found no statistical difference in improvement of upper limb function at the end of treatment (MD 2.00, 95% CI -4.91 to 8.91; P = 0.57; 1 trial; 63 participants; low-quality evidence) and at the end of follow-up (MD 4.00, 95% CI -2.92 to 10.92; P = 0.26; 1 trial; 63 participants; low-quality evidence) when comparing rPMS plus rehabilitation versus sham plus rehabilitation. We observed a significant decrease in spasticity of the elbow at the end of follow-up (MD -0.48, 95% CI -0.93 to -0.03; P = 0.03; 1 trial; 63 participants; low-quality evidence) when comparing rPMS plus rehabilitation versus sham plus rehabilitation. In terms of muscle strength, rPMS treatment was not associated with improved muscle strength of the ankle dorsiflexors at the end of treatment (MD 3.00, 95% CI -2.44 to 8.44; P = 0.28; 1 trial; 18 participants; low-quality evidence) when compared with sham rPMS. No studies provided information on lower limb function or adverse events, including death. Based on the GRADE approach, we judged the quality of evidence related to the primary outcome as low, owing to the small sample size of the studies. Available trials provided insufficient evidence to permit any conclusions about routine use of rPMS for people after stroke. Additional trials with large sample sizes are needed to provide robust evidence for rPMS after stroke.


A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force.
Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.


Relationship in obese Chilean schoolchildren between physical fitness, physical activity levels and cardiovascular risk factors.
Background: obesity and lower physical fitness levels in children are related to the development of cardiometabolic risk factors. Objective: to determine the relationship between health-related physical fitness and physical activity levels, blood pressure, and anthropometric parameters for different weight statuses of Chilean schoolchildren. Material and methods: the participants were 272 girls and 333 boys having a mean age of 12.00 ± 1.23 years. Maximal oxygen consumption (VO2max), standing long jump test (SLJ), handgrip strength, physical activity (PA) levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC) and body fat (BF) were measured. To establish the relationship between the variables, partial correlations adjusted by sex were carried out and the Chi-square test was applied to compare the proportions between groups. Results: VO2max (p < 0.001) was higher in schoolchildren of normal weight. SBP and DBP were higher in obese schoolchildren (p < 0.001). Physical fitness was inversely related to SBP: VO2max (r = -0.26, p < 0.001), SLJ (r = -0.11, p = 0.007) and handgrip strength (r = -0.10, p = 0.021), and had a positive relationship with PA: VO2max (r = 0.31, p < 0.001), SLJ (r = 0.18, p < 0.001), and handgrip strength (r = 0.26, p < 0.001). Moreover, VO2max and SLJ were inversely related to BMI and WC (p < 0.05). The group of obese schoolchildren contained the highest percentage of individuals with hypertension (p < 0.001). Conclusion: the results obtained in this study show that physical fi tness has an inverse relationship with SBP and a positive relationship with PA levels. Besides, cardiorespiratory fitness (CRF) and SLJ are inversely associated with the predictors of risk factors for cardiovascular diseases. Finally, obese children presented lower physical fitness and included a higher proportion of individuals with hypertension.


Abiotic stress miRNomes in the Triticeae.
The continued growth in world population necessitates increases in both the quantity and quality of agricultural production. Triticeae members, particularly wheat and barley, make an important contribution to world food reserves by providing rich sources of carbohydrate and protein. These crops are grown over diverse production environments that are characterized by a range of environmental or abiotic stresses. Abiotic stresses such as drought, heat, salinity, or nutrient deficiencies and toxicities cause large yield losses resulting in economic and environmental damage. The negative effects of abiotic stresses have increased at an alarming rate in recent years and are predicted to further deteriorate due to climate change, land degradation, and declining water supply. New technologies have provided an important tool with great potential for improving crop tolerance to the abiotic stresses: microRNAs (miRNAs). miRNAs are small regulators of gene expression that act on many different molecular and biochemical processes such as development, environmental adaptation, and stress tolerance. miRNAs can act at both the transcriptional and post-transcriptional levels, although post-transcriptional regulation is the most common in plants where miRNAs can inhibit the translation of their mRNA targets via complementary binding and cleavage. To date, expression of several miRNA families such as miR156, miR159, and miR398 has been detected as responsive to environmental conditions to regulate stress-associated molecular mechanisms individually and/or together with their various miRNA partners. Manipulation of these miRNAs and their targets may pave the way to improve crop performance under several abiotic stresses. Here, we summarize the current status of our knowledge on abiotic stress-associated miRNAs in members of the Triticeae tribe, specifically in wheat and barley, and the miRNA-based regulatory mechanisms triggered by stress conditions. Exploration of further miRNA families together with their functions under stress will improve our knowledge and provide opportunities to enhance plant performance to help us meet global food demand.


Hologram-moiré interferometry for transparent objects.
A modification of hologram interferometry applicable to the study of transparent objects of moderate optical quality has been devised which combines hologram and moiré techniques and allows the observation of high contrast, relatively unlocalized, interferometric fringes under conditions less critical than those of the conventional hologram interferometer. By spatially modulating one beam of the interferometer during exposure, moiré fringes may be obtained in the reconstruction which distort and move with optical phase changes in either beam of the interferometer. An analysis of the origin and nature of these distortions is given and experimental verification of the analysis is presented.


Serum endocan as a survival predictor for patients with liver cirrhosis.
The relationship between endocan expression and outcome in patients with chronic liver disease is not fully understood. To examine whether serum endocan level is predictive of outcome in patients with liver cirrhosis. A total of 68 patients with liver cirrhosis were enrolled. Outcome predictors were analyzed using the Cox proportional hazards model. The overall survival rates were calculated using the Kaplan-Meier method, and differences were evaluated using the log-rank test. During the median follow-up period (7.1 years), nine patients had hepatocellular carcinoma (HCC) and 10 patients died. Of the deceased patients, nine died due to hepatic decompensation or associated conditions. No significant factors were found to be predictive of the occurrence of HCC. In contrast, an elevated serum endocan level (≥2.0 ng⁄mL; HR 2.34 [95% CI 1.05 to 7.03]; P=0.037) and high Child-Pugh grade B⁄C (HR 2.65 [95% CI 1.30 to 6.89; P=0.006) were predictive of poor survival. Kaplan-Meier analysis revealed that the respective cumulative survival rates at five and 10 years were 97.1% and 87.4% in patients with serum endocan levels <2.0 ng⁄mL and 85.8% and 64.4% in patients with levels ≥2.0 ng⁄mL (P=0.009), respectively. Moreover, the cumulative survival rates were significantly different among the patient groups divided according to serum endocan level and Child-Pugh grade (P=0.002). These findings suggest that serum endocan level may be a survival predictor for patients with liver cirrhosis.


Association of Initial Low Serum Selenium Level with Infectious Complications and 30-Day Mortality in Multiple Trauma Patients.
Low serum selenium levels are commonly observed in critically injured multiple trauma patients. This study aimed to identify the association between initial serum selenium levels and in-hospital infectious complications in multiple trauma patients. We retrospectively reviewed multiple trauma patients admitted between January 2015 and November 2017. We selected 135 patients whose serum selenium levels were checked within 48 h of admission. Selenium deficiency was defined as a serum selenium level <70 ng/mL. Survival analyses of selenium deficiency and 30-day mortality were performed. Multivariate logistic regression analysis was performed to identify the association between initial serum selenium level and in-hospital infectious complications. Thirty-day mortality (8.3% vs. 0.0%; p = 0.018) and incidence rates of pneumonia (66.7% vs. 28.3%; p < 0.001) and infectious complications (83.3% vs. 46.5%; p < 0.001) were higher in patients with selenium deficiency than in patients without selenium deficiency. Kaplan-Meier survival cures also showed similar results (log rank test, p = 0.021). Of 135 patients, 76 (56.3%) experienced at least one infectious complication during admission. High injury severity score (ISS, odds ratio (OR) 1.065, 95% confidence interval (CI) 1.024-1.108; p = 0.002) and selenium deficiency (OR 3.995, 95% CI 1.430-11.156; p = 0.008) increased the risk of in-hospital infectious complications in multiple trauma patients. Patients with selenium deficiency showed higher 30-day mortality and higher risks of pneumonia and infectious complications.


The nation in context: How intergroup relations shape the discursive construction of identity continuity and discontinuity.
The perceived collective continuity (PCC) of a national identity serves as a crucial source of stability and self-esteem for group members. Recent work has explored the consequences of perceived continuity when the meaning of a nation's past is seen in a negative light, and the challenges this brings for the negotiation of a positive identity in the present, signalling the potential value of perceived discontinuity The current paper extends this literature by examining the role of intergroup relations in the construction of both collective continuities and discontinuities. Through analysing the discursive management of national identity in nine focus groups in a post-conflict context (Serbia, N = 67), we reveal how the tensions between continuity and discontinuity are embedded within a broader discussion of the nation's relationship with relevant national outgroups across its history. The findings contribute to theoretical knowledge on the interlinking of national identity and PCC by illustrating the ways in which intergroup relations of the past shape the extent to which continuity is seen as desirable or undesirable. We argue that despite the psychological merits of collective continuity, discontinuity can become attractive and useful when there is limited space to challenge how a nation's history is remembered and the valence given to the past. The paper concludes by offering an account of how social and political contexts can influence the nature, functions, and valence of PCC within national identities.


The biochemistry and physiology of metallic fluoride: action, mechanism, and implications.
Fluoride is a well-known G protein activator. Activation of heterotrimeric GTP-binding proteins by fluoride requires trace amounts of Al3+ or Be2+ ions. AlFx mimics a gamma-phosphate at its transition state in a Galpha protein and is therefore able to inhibit its GTPase activity. AlFx also forms complexes with small GTP-binding proteins in the presence of their GTPase-activating proteins (GAP). As phosphate analogs, AlFx or BeFx affect the activity of a variety of phosphoryl transfer enzymes. Most of these enzymes are fundamentally important in cell signal transduction or energy metabolism. Al3+ and F- tend to form stable complexes in aqueous solution. The exact structure and concentration of AlFx depend on the pH and the amount of F- and Al3+ in the solution. Humans are exposed to both F and Al. It is possible that Al-F complexes may be formed in vivo, or formed in vitro prior to their intake by humans. Al-F complexes may play physiological or pathological roles in bone biology, fluorosis, neurotoxicity, and oral diseases such as dental caries and periodontal disease. The aim of this review is to discuss the basic chemical, biochemical, and toxicological properties of metallic fluoride, to explore its potential physiological and clinical implications.


Management of type II odontoid fractures in the geriatric population: outcome of treatment in a rigid cervical orthosis.
Retrospective study. To analyze geriatric patients with Type II odontoid fractures treated either with rigid cervical orthosis (CO) or surgery (Odontoid Screw or Transarticular screw). Our literature search did not yield any studies on the outcome of Type II odontoid fractures in geriatric population treated with the rigid CO. We therefore designed a study to analyze geriatric patients with Type II odontoid fractures treated with either rigid cervical collar or surgery. This is a retrospective chart review of patients with Type II odontoid fractures between July 1998 and June 2006. Inclusion criteria consists of males and females of 70 years of age or older with Type II odontoid fractures who were treated with rigid cervical collar or surgery. Exclusion criteria were displacement >4 mm, posteriorly displaced fracture, neurologic compromise, multilevel cervical spine injury, and treatment in a halo vest. Medical comorbidities were assessed using the Modified Cumulative Illness Rating Scale for Geriatrics. Primary outcomes were mortality and fusion (union, stable nonunion, nonunion). Minimum of 3 months follow-up was acceptable. One hundred eighty four odontoid fractures were identified in 8 years. Twenty patients met our inclusion criteria (9 treated in rigid collar and 11 treated surgically). Median follow-up was 5.5 months. Out of 20 patients, 4 patients died (1 treated in CO, 3 treated surgically). Cumulative Illness Rating Scale for Geriatrics index was highest in patient treated in CO. In the rigid collar group, 6 patients had union (66.6%), and 2 developed stable nonunion (22.2%); whereas in the surgically treated group, 7 patients had union (87.5%), and 1 patient developed nonunion (12.5%). Patients treated nonoperatively in rigid collar seem to have an overall favorable outcome. A well-designed prospective study, to compare the outcomes of surgical intervention with nonsurgical management of Type II odontoid in elderly is recommended.


The Role of Religion in Suicidal Behavior, Attitudes and Psychological Distress Among University Students: A Multinational Study.
The purpose of this study was to determine the associations between religion, suicidal behavior, attitudes and psychological distress in 5572 students from 12 countries by means of a self-report questionnaire. Our results showed that an affiliation with Islam was associated with reduced risk for suicide ideation, however affiliating with Orthodox Christianity and no religion was related to increased risk for suicide ideation. While affiliating with Buddhism, Catholic religion and no religion was associated with lowered risk for attempting suicide, affiliation with Islam was related to heightened risk for attempting suicide. Affiliation with Hinduism, Orthodox Christianity, Catholicism, other religions and with no religion was associated with decreased risk for psychological distress but those reported affiliating with Islam evinced greater risk for psychological distress. The associations of the strength of religious belief to suicidal ideation and attempts were in the expected direction for most but had a positive relation in respondents affiliating with Catholicism and other religions. Students reporting affiliation with Islam, the Christian Orthodox religion and Buddhism were the least accepting of suicide but they displayed a more confronting interpersonal style to an imagined peer with a suicidal decision. It was concluded that the protective function of religion in educated segments of populations (university students) and in university students residing in Muslim countries where freedom from religion is restricted or religion is normative and/or compulsory is likely to be limited. Our findings suggest that public policies supporting religious freedom may augment the protective function of religion against suicide and psychological distress.