High-intensity interval training is superior to moderate intensity training on aerobic capacity in rats: Impact on hippocampal plasticity markers.
The use of endurance regimens could be improved by defining their respective effectiveness on aerobic fitness and brain health that remains controversial. We aimed at comparing work-matched high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) on aerobic performance and muscular plasticity markers in healthy rats. Cognitive functions and brain plasticity markers were also investigated following the 8-week training. Rats performed the incremental exercise test and behavioural tests before and after training at day 1 (D1), D15, D29 and D57. Key cerebral markers were assessed by Western blot and quantitative polymerase chain reaction to provide information on brain function related to angiogenesis, aerobic metabolism and neurotrophin activity at D59. Muscular protein levels involved in angiogenesis and aerobic metabolism were measured in both triceps brachii and soleus muscles. HIIT induced superior improvement of aerobic fitness compared to MICT, as indicated by enhancement of speed associated with lactate threshold (SLT) and maximal speed (Smax). In the triceps brachii muscle, markers of angiogenesis and aerobic activity were upregulated as well as myokines involved in neuroplasticity. Moreover, levels of key brain plasticity markers increased in the hippocampus after 8 weeks of HIIT, without improving cognitive functions. These findings might contribute to define physical exercise guidelines for maintaining brain health by highlighting the promising role of HIIT when using SLT for distinguishing low running speed from high running speed. Further studies are required to confirm these brain effects by exploring synaptic plasticity and neurogenesis mechanisms when exercise intensity is standardized and individualized.


Differing roles for B7 and intercellular adhesion molecule-1 in negative selection of thymocytes.
To ensure self tolerance, immature thymocytes with high binding affinity for self peptides linked to major histocompatibility complex (MHC) molecules are eliminated in situ via apoptosis (negative selection). The roles of two costimulatory molecules, B7-1 and intercellular adhesion molecule-1 (ICAM-1), in negative selection was examined by studying apoptosis of T cell receptor transgenic CD4+8+ thymocytes cultured with specific peptides presented by MHC class I-transfected Drosophila cells. When coexpressed on these cells, B7-1 and ICAM-1 act synergistically and cause strong class 1-restricted negative selection of thymocytes. When expressed separately, however, B7-1 and ICAM-1 display opposite functions: negative selection is augmented by B7-1, but is inhibited by ICAM-1. It is notable that B7-1 is expressed selectively in the thymic medulla, whereas ICAM-1 is expressed throughout the thymus. Because of this distribution, the differing functions of B7-1 and ICAM-1 may dictate the sites of positive and negative selection. Thus, in the cortex, the presence of ICAM-1, but not B7-1, on the cortical epithelium may preclude or reduce negative selection and thereby promote positive selection. Conversely, the combined expression of B7-1 and ICAM-1 may define the medulla as the principal site of negative selection.


Direct connections between the spinal epidural space and the venous circulation in humans.
Our previous studies in pigs indicate that direct connections exist between the spinal epidural space and the venous circulation. We wondered if similar connections occur in humans and have extended our investigations to human cadavers awaiting autopsy. We studied 10 recently dead human bodies. We inserted 2 Tuohy needles into the epidural space of the lower thoracic spine at adjacent interspaces. We infused saline with a constant-flow pump into 1 needle and measured the resulting pressure through the other. Epidural pressure increased to a steady plateau during fluid infusion, and this value was recorded at several flow rates. The pressure decay after flow stopped was also recorded. Then we infused radiopaque contrast, removed the needles, and obtained a computed tomographic scan of the spine from the foramen magnum to the coccyx. Pressure in the epidural space increased to a plateau during saline infusion. Higher flow rates produced higher plateau pressures. Plots of plateau pressure versus infusion rate were linear in all bodies. The slope of the flow-pressure plot gave a steady-state resistance (543±638 mm Hg·s/mL). The time constant of the pressure decay curve allowed calculation of initial capacitance (0.090±0.062 mL/mm Hg). Contrast could be identified in veins around the spinal column in all bodies. Contrast was found most commonly in the deep veins of the neck (7 bodies) and in veins originating in the area of the brachial plexus (7 bodies). Contrast was found less commonly and in smaller amounts in veins draining into the azygous system (5 bodies) and the lumbar veins (5 bodies). No contrast was found in veins in the sacral area. A direct connection between the spinal epidural space and the venous circulation has been demonstrated in human cadavers. The connection is most commonly found in the cervical and upper thoracic spine.


Five serum proteins identified using SELDI-TOF-MS as potential biomarkers of gastric cancer.
The aims of this study were to detect serum proteomic patterns in gastric cancer serum samples using Surface-enhanced Laser Desorption/ionization-Time-of-flight-Mass Spectrometry ProteinChip array technology, to screen biomarker candidates, to build diagnostic models and to evaluate their clinical significance. Serum samples from patients with gastric cancer and normal healthy control subjects (n = 125) were analysed using surface-enhanced laser desorption/ionization technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peak clustering and classification analyses were established using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. The diagnostic models were developed and validated by discriminant analysis. In addition, the results of the surface-enhanced laser desorption/ionization model were compared with the biomarkers carcinoembryonic antigen and carbohydrate antigen 199 in a subset of samples using a microparticle enzyme immunoassay. Five protein peaks at 2046, 3179, 1817, 1725 and 1929 m/z were automatically chosen as components of the best biomarker pattern for diagnosis of gastric cancer. In addition, we identified a single protein peak at 4665 m/z, which could distinguish between stage I/II and stage III/IV gastric cancer with a specificity and sensitivity of 91.6% (11/12) and 95.4% (21/22), respectively. When this biomarker was validated in the second set of samples, the specificity and sensitivity were 91.7% (11/12) and 86.3% (19/22), respectively. The present results suggest that serum surface-enhanced laser desorption/ionization protein profiling can distinguish patients with gastric cancer, and in particular stage I/II patients, from normal subjects with a relatively high sensitivity and specificity. Surface-enhanced Laser Desorption/ionization-Time-of-flight-Mass Spectrometry is a potential new diagnostic tool for the screening of gastric cancer.


The Ontogeny and Brain Distribution Dynamics of the Appetite Regulators NPY, CART and pOX in Larval Atlantic Cod (Gadus morhua L.).
Similar to many marine teleost species, Atlantic cod undergo remarkable physiological changes during the early life stages with concurrent and profound changes in feeding biology and ecology. In contrast to the digestive system, very little is known about the ontogeny and the localization of the centers that control appetite and feed ingestion in the developing brain of fish. We examined the expression patterns of three appetite regulating factors (orexigenic: neuropeptide Y, NPY; prepro-orexin, pOX and anorexigenic: cocaine- and amphetamine-regulated transcript, CART) in discrete brain regions of developing Atlantic cod using chromogenic and double fluorescent in situ hybridization. Differential temporal and spatial expression patterns for each appetite regulator were found from first feeding (4 days post hatch; dph) to juvenile stage (76 dph). Neurons expressing NPY mRNA were detected in the telencephalon (highest expression), diencephalon, and optic tectum from 4 dph onward. CART mRNA expression had a wider distribution along the anterior-posterior brain axis, including both telencephalon and diencephalon from 4 dph. From 46 dph, CART transcripts were also detected in the olfactory bulb, region of the nucleus of medial longitudinal fascicle, optic tectum and midbrain tegmentum. At 4 and 20 dph, pOX mRNA expression was exclusively found in the preoptic region, but extended to the hypothalamus at 46 and 76 dph. Co-expression of both CART and pOX genes were also observed in several hypothalamic neurons throughout larval development. Our results show that both orexigenic and anorexigenic factors are present in the telencephalon, diencephalon and mesencephalon in cod larvae. The telencephalon mostly contains key factors of hunger control (NPY), while the diencephalon, and particularly the hypothalamus may have a more complex role in modulating the multifunctional control of appetite in this species. As the larvae develop, the overall progression in temporal and spatial complexity of NPY, CART and pOX mRNAs expression might be correlated to the maturation of appetite control regulation. These observations suggest that teleost larvae continue to develop the regulatory networks underlying appetite control after onset of exogenous feeding.


Critical Appraisal of the Quality of Literature Evaluating Psychometric Properties of Arthritis Work Outcome Assessments: A Systematic Review.
To systematically rate the evidence on the measurement properties of work functioning instruments for people with arthritis and other rheumatologic conditions. A systematic review was conducted through a structured search to identify the quality of articles describing studies of assessment development and studies of their psychometric properties. The Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist was used to appraise the included studies. Finally, an evidence synthesis was performed to combine findings. Nine arthritis-specific work outcome assessments were identified; 17 articles examining the psychometric properties of these instruments were identified and their quality was reviewed. Quality of studies was highly variable. The evidence synthesis showed that the Work Limitations Questionnaire had the strongest quality evidence of internal consistency and content validity (including structural validity and hypothesis testing), followed by the Work Instability Scale. None of the instruments had strong quality evidence of criterion validity or responsiveness. Considering the high variability and the low quality of the literature, we recommend that instrument developers integrate a full psychometric assessment of their instruments, including responsiveness and criterion validity, and consult guidelines (i.e., COSMIN) in reporting their findings.


Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review.
Clostridium difficile is a major cause of antibiotic-associated diarrhea within the hospital setting. The yeast Saccharomyces boulardii has been found to have some effect in reducing the risk of C difficile infection (CDI); however, its role in preventive therapy has yet to be firmly established. To review the effectiveness of S boulardii in the prevention of primary and recurrent CDI. Benefit was defined as a reduction of diarrhea associated with C difficile. Risk was defined as any adverse effects of S boulardii. A literature search in MEDLINE, EMBASE, CINAHL and the Cochrane Library was performed. Included studies were English language, randomized, double-blind placebo controlled trials evaluating S boulardii in CDI prevention. Four studies were reviewed. Two studies investigated the prevention of recurrence in populations that were experiencing CDI at baseline. One trial showed a reduction of relapses in patients experiencing recurrent CDI (RR=0.53; P<0.05). The other demonstrated a trend toward reduction of CDI relapse in the recurrent treatment group of patients receiving high-dose vancomycin (RR=0.33; P=0.05). Two other studies examined primary prevention of CDI in populations that had been recently prescribed antibiotics. These studies lacked the power to detect statistically significant differences. Patients on treatment experienced increased risk for thirst and constipation. S boulardii seems to be well tolerated and may be effective for secondary prevention in some specific patient populations with particular concurrent antibiotic treatment. Its role in primary prevention is poorly defined and more research is required before changes in practice are recommended.


The Relationships of Nurse Staffing Level and Work Environment With Patient Adverse Events.
The purpose of this study was to examine the relationships of nurse staffing level and work environment with patient adverse events. This cross-sectional study used a combination of nurse survey data (N = 4,864 nurses), facility data (N = 58 hospitals), and patient hospital discharge data (N = 113,426 patients) in South Korea. The three most commonly nurse-reported adverse events included administration of the wrong medication or dose to a patient, pressure ulcers, and injury from a fall after admission. Multilevel ordinal logistic regression was employed to explore the relationships of nurse staffing level (number of patients assigned to a nurse) and work environment (Practice Environment Scale of the Nursing Work Index) with patient adverse events after controlling for nurse, hospital, and patient characteristics. A larger number of patients per nurse was significantly associated with a greater incidence of administration of the wrong medication or dose (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 1.007-1.016), pressure ulcer (OR = 1.01, 95% CI = 1.007-1.016), and patient falls with injury (OR = 1.02, 95% CI = 1.013-1.022). A better work environment had a significant inverse relationship with adverse events; the odds of reporting a higher incidence of adverse events were 45% lower for administration of the wrong medication or dose (OR = 0.55, 95% CI = 0.400-0.758), followed by 39% lower for pressure ulcer (OR = 0.61, 95% CI = 0.449-0.834) and 32% lower for falls with injury after admission (OR = 0.68, 95% CI = 0.490-0.939). This study found that a larger number of patients per nurse and poor work environment increase the incidence of patient adverse events, such as administration of the wrong medication or dose to a patient, pressure ulcers, and injury from falling after admission. The findings suggest that South Korean hospitals could prevent patient adverse events by improving nurse staffing and work environment. Healthcare strategies and efforts to modify adequate nurse staffing levels and better work environments for nurses are needed to improve patient outcomes.


NAP-I is a functional homologue of TAF-I that is required for replication and transcription of the adenovirus genome in a chromatin-like structure.
For the activation of replication and transcription from DNA in a chromatin structure, a variety of factors are thought to be needed that alter the chromatin structure. Template activating factor-I (TAF-I) has been identified as such a host factor required for replication of the adenovirus (Ad) genome complexed with viral basic core proteins (Ad core). TAF-I also stimulates transcription from the Ad core DNA. Using mutant TAF-I proteins, we have demonstrated that the acidic stretch present in the carboxyl terminal region is essential for the stimulation of transcription from the Ad core. A genomic footprinting experiment with restriction endonuclease has revealed that TAF-I causes a structural change in the Ad core. TAF-I has been shown to have significant amino acid similarity to nucleosome assembly protein-I (NAP-I), which is involved in the formation of the chromatin structure. We have shown that TAF-I can be substituted by NAP-I in the activation of the cell-free Ad core transcription system. Two of the tripartite acidic regions and the region homologous to TAF-I in NAP-I are required for the maximal TAF-I activity of NAP-I. Furthermore, TAF-I has been shown to have NAP-I activity, and the acidic region of TAF-I is required for this activity. Since TAF-I causes the structural change of the Ad core and thereby activates transcription, TAF-I is thought to be one of the proteins which is involved in chromatin remodeling. NAP-I is structurally related to TAF-I and functionally substitutes for TAF-I. Furthermore, TAF-I has NAP-I activity. These observations suggest that this type of molecule has dual functions, possibly by participating in facilitating the assembly of the chromatin structure as well as perturbing the chromatin structure to allow transcription to proceed.


Single-channel in-ear-EEG detects the focus of auditory attention to concurrent tone streams and mixed speech.
Conventional, multi-channel scalp electroencephalography (EEG) allows the identification of the attended speaker in concurrent-listening ('cocktail party') scenarios. This implies that EEG might provide valuable information to complement hearing aids with some form of EEG and to install a level of neuro-feedback. To investigate whether a listener's attentional focus can be detected from single-channel hearing-aid-compatible EEG configurations, we recorded EEG from three electrodes inside the ear canal ('in-Ear-EEG') and additionally from 64 electrodes on the scalp. In two different, concurrent listening tasks, participants (n = 7) were fitted with individualized in-Ear-EEG pieces and were either asked to attend to one of two dichotically-presented, concurrent tone streams or to one of two diotically-presented, concurrent audiobooks. A forward encoding model was trained to predict the EEG response at single EEG channels. Each individual participants' attentional focus could be detected from single-channel EEG response recorded from short-distance configurations consisting only of a single in-Ear-EEG electrode and an adjacent scalp-EEG electrode. The differences in neural responses to attended and ignored stimuli were consistent in morphology (i.e. polarity and latency of components) across subjects. In sum, our findings show that the EEG response from a single-channel, hearing-aid-compatible configuration provides valuable information to identify a listener's focus of attention.


Food for thought: hedonic experience beyond homeostasis in the human brain.
Food intake is an essential human activity regulated by homeostatic and hedonic systems in the brain which has mostly been ignored by the cognitive neurosciences. Yet, the study of food intake integrates fundamental cognitive and emotional processes in the human brain, and can in particular provide evidence on the neural correlates of the hedonic experience central to guiding behaviour. Neuroimaging experiments provide a novel basis for the further exploration of the brain systems involved in the conscious experience of pleasure and reward, and thus provide a unique method for studying the hedonic quality of human experience. Recent neuroimaging experiments have identified some of the regions involved in the cortical networks mediating hedonic experience in the human brain, with the evidence suggesting that the orbitofrontal cortex is the perhaps strongest candidate for linking food and other kinds of reward to hedonic experience. Based on the reviewed literature, a model is proposed to account for the roles of the different parts of the orbitofrontal cortex in this hedonic network.


Localization and characterization of phenamil-sensitive Na+ influx in isolated rainbow trout gill epithelial cells.
Percoll density-gradient separation, combined with peanut lectin agglutinin (PNA) binding and magnetic bead separation, was used to separate dispersed fish gill cells into sub-populations. Functional characterization of each of the sub-populations was performed to determine which displayed acid-activated phenamil- and bafilomycin-sensitive Na(+) uptake. Analysis of the mechanism(s) of (22)Na(+) influx was performed in control and acid-activated (addition of 10 mmoll(-1) proprionic acid) cells using a variety of Na(+) transport inhibitors (ouabain, phenamil, HOE-694 and bumetanide) and a V-type ATPase inhibitor (bafilomycin). We found that cells migrating to a 1.03-1.05 g ml(-1) Percoll interface [pavement cells (PVCs)] possessed the lowest rates of Na(+) uptake and that influx was unchanged during either bafilomycin (10 nmoll(-1)) treatment or internal acidification with addition of proprionic acid (10 mmoll(-1)). Mitochondria-rich (MR) cells that migrated to the 1.05-1.09 g ml(-1) interface of the Percoll gradient demonstrated acidification-activated bafilomycin and phenamil-sensitive Na(+) influx. Further separation of the MR fraction into PNA(+) and PNA(-) fractions using magnetic separation demonstrated that only the PNA(-) cells (alpha-MR cells) demonstrated phenamil-and bafilomycin-sensitive acid-activated (22)Na(+) uptake. We confirm the coupling of a V-type H(+)-ATPase with phenamil-sensitive Na(+) uptake activity and conclude that high-density alpha-MR cells function in branchial Na(+) uptake in freshwater fish.


[Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia].
Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC <4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count <1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged , white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.


Scattering by multiple parallel radially stratified infinite cylinders buried in a lossy half space.
The theoretical solution for scattering by an arbitrary configuration of closely spaced parallel infinite cylinders buried in a lossy half space is presented in this paper. The refractive index and permeability of the half space and cylinders are complex in general. Each cylinder is radially stratified with a distinct complex refractive index and permeability. The incident radiation is an arbitrarily polarized plane wave propagating in the plane normal to the axes of the cylinders. Analytic solutions are derived for the electric and magnetic fields and the Poynting vector of backscattered radiation emerging from the half space. Numerical examples are presented to illustrate the application of the scattering solution to calculate backscattering from a lossy half space containing multiple homogeneous and radially stratified cylinders at various depths and different angles of incidence.


On the influence of reward on action-effect binding.
Ideomotor theory states that the formation of anticipatory representations about the perceptual consequences of an action [i.e., action-effect (A-E) binding] provides the functional basis of voluntary action control. A host of studies have demonstrated that A-E binding occurs fast and effortlessly, yet little is known about cognitive and affective factors that influence this learning process. In the present study, we sought to test whether the motivational value of an action modulates the acquisition of A-E associations. To this end, we linked specific actions with monetary incentives during the acquisition of novel A-E mappings. In a subsequent test phase, the degree of binding was assessed by presenting the former effect stimuli as task-irrelevant response primes in a forced-choice response task, absent reward. Binding, as indexed by response priming through the former action-effects, was only found for reward-related A-E mappings. Moreover, the degree to which reward associations modulated the binding strength was predicted by individuals' trait sensitivity to reward. These observations indicate that the association of actions and their immediate outcomes depends on the motivational value of the action during learning, as well as on the motivational disposition of the individual. On a larger scale, these findings also highlight the link between ideomotor theories and reinforcement-learning theories, providing an interesting perspective for future research on anticipatory regulation of behavior.


One-pot semisynthesis of exon 1 of the Huntingtin protein: new tools for elucidating the role of posttranslational modifications in the pathogenesis of Huntington's disease.
The natural enzymes involved in regulating many of the posttranslational modifications (PTMs) within the first 17 residues (Nt17) of Huntingtin exon 1 (Httex1) remain unknown. A semisynthetic strategy that allows the site-specific introduction of PTMs within Nt17 by using expressed protein ligation (EPL) was developed. This strategy was used to produce untagged wild-type (wt) and T3-phosphorylated (pT3) Httex1 containing 23 glutamine residues (Httex1-23Q). Our studies show that pT3 significantly slows the oligomerization and fibrillization of Httex1-23Q and that Httex1 variants containing polyQ repeats below the pathogenic threshold readily aggregate and form fibrils in vitro. These findings suggest that crossing the polyQ pathogenic threshold is not essential for Httex1 aggregation. The ability to produce wt or site-specifically modified tag-free Httex1 should facilitate determining its structure and the role of N-terminal PTMs in regulating the functions of Htt in health and disease.


Repetitive hypoglycemia in young rats impairs hippocampal long-term potentiation.
Mechanisms underlying cognitive dysfunction in young diabetic children are poorly understood, and may include synaptic dysfunction from insulin-induced hypoglycemia. We developed a model of repetitive insulin-induced hypoglycemia in young rats and examined hippocampal long-term potentiation, an electrophysiologic assay of synaptic plasticity, 3-5 d after the last hypoglycemic event. Three hypoglycemic events between postnatal d 21-25 produced modest cortical (17 +/- 2.9 dead neurons per section in parasagittal cortex), but not hippocampal, neuron death quantified by Fluoro-Jade B staining. There was no change in neurogenesis in the hippocampal dentate granule cell region by quantification of bromodeoxyuridine incorporation. Although normal baseline hippocampal synaptic responses were elicited from hippocampal slices from hypoglycemic animals, long-term synaptic potentiation could not be induced in hippocampal slices from rats subjected to hypoglycemia. These results suggest that repetitive hypoglycemia in the developing brain can cause selective impairment of synaptic plasticity in the absence of cell death, and without complete disruption of basal synaptic transmission. We speculate that impaired synaptic plasticity in the hippocampus caused by repetitive hypoglycemia could underlie memory and cognitive deficits observed in young diabetic children, and that cortical neuron death caused by repetitive hypoglycemia in the developing brain may contribute to other neurologic, cognitive, and psychological problems sometimes encountered in diabetic children.


Association of electroretinographic parameters and inflammatory factors in branch retinal vein occlusion with macular oedema.
Branch retinal vein occlusion (BRVO) leads to retinal ischaemia, which then induces upregulation of various inflammatory factors, including vascular endothelial growth factor (VEGF). The aim of this study was to determine whether there was a correlation between inflammatory factors and components of the electroretinogram (ERG) in patients with BRVO. In 19 BRVO patients with macular oedema, vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of four inflammatory factors (VEGF, soluble intercellular adhesion molecule-1 (sICAM-1), interleukin (IL)-6 and monocyte chemotactic protein (MCP)-1). The amplitude and implicit time of the a-wave cone, b-wave cone and 30 Hz flicker were calculated automatically from the ERG. Correlations between the different components of the ERG and the four inflammatory factors were investigated. Vitreous fluid levels of two factors (IL-6 and MCP-1) were significantly correlated with the implicit time of the cone b-wave (p=0.035 and p=0.016, respectively). Vitreous fluid levels of all four factors (VEGF, sICAM-1, IL-6, and MCP-1) were significantly correlated with the implicit time of 30 Hz flicker (p=0.047, p=0.031, p=0.002 and p=0.009, respectively). Vitreous fluid levels of VEGF, sICAM-1, IL-6, and MCP-1 were significantly higher in patients with an implicit time ≥36 ms than with an implicit time <36 ms (p=0.042, p=0.048, p=0.003 and p=0.024, respectively). These findings suggest that the implicit times of the cone b-wave and 30 Hz flicker can be used to detect BRVO patients with macular oedema who have a high risk of ischaemia.


Induction of Immunological Tolerance as a Therapeutic Procedure.
A major goal of immunosuppressive therapies is to harness immune tolerance mechanisms so as to minimize unwanted side effects associated with protracted immunosuppressive therapy. Antibody blockade of lymphocyte coreceptor and costimulatory pathways in mice has demonstrated the principle that both naive and primed immune systems can be reprogrammed toward immunological tolerance. Such tolerance can involve the amplification of activity of regulatory T cells, and is maintained through continuous recruitment of such cells through processes of infectious tolerance. We propose that regulatory T cells create around them microenvironments that are anti-inflammatory and endowed with enhanced protection against destructive damage. This acquired immune privilege involves the decommissioning of cells of the innate as well as adaptive immune systems. Evidence is presented that nutrient sensing by immune cells acting through the mammalian target of rapamycin (mTOR) pathway provides one route by which the immune system can be directed toward noninflammatory and regulatory behavior at the expense of destructive functions. Therapeutic control of immune cells so as to harness metabolic routes favoring dominant regulatory mechanisms has offered a new direction for immunosuppressive therapy, whereby short-term treatment may be sufficient for long-term benefit or even cure.


Plant hydraulics, stomatal control, and the response of a tropical forest to water stress over multiple temporal scales.
Many tropical regions are experiencing an intensification of drought, with increasing severity and frequency. The ecosystem response to these changes is still highly uncertain. On short time scales (from diurnal to seasonal), tropical forests respond to water stress by physiological controls, such as stomatal regulation and phenological adjustment, to cope with increasing atmospheric water demand and reduced water supply. However, the interactions among biological processes and co-varying environmental factors that determine the ecosystem-level fluxes are still unclear. Furthermore, climate variability at longer time scales, such as that generated by ENSO, produces less predictable effects because it depends on a highly stochastic combination of factors that might vary among forests and even between events in the same forest. This study will present some emerging patterns of response to water stress from 5 years of water, carbon, and energy fluxes observed on a seasonal tropical forest in central Panama, including an increase in productivity during the 2015 El Niño. These responses depend on the combination of environmental factors experienced by the forest throughout the seasonal cycle, in particular, increase in solar radiation, stimulating productivity, and increasing vapor pressure deficit (VPD) and decreasing soil moisture, limiting stomata opening. These results suggest a critical role of plant hydraulics in mediating the response to water stress over a broad range of temporal scales (diurnal, intraseasonal, seasonal, and interannual), by acclimating canopy conductance to light and VPD during different soil moisture regimes. A multilayer photosynthesis model coupled with a plant hydraulics scheme can reproduce these complex responses. However, results depend critically on parameters regulating water transport efficiency and the cost of water stress. As these costs have not been properly identified and quantified yet, more empirical research is needed to elucidate physiological mechanisms of hydraulic failure and recover, for example embolism repair and xylem regrowth.


Instruction in the responsible conduct of research: an inventory of programs and materials within CTSAs.
The National Institutes of Health (NIH) require instruction in the responsible conduct of research (RCR) as a component of any Clinical and Translational Science Award (CTSA). The Educational Materials Group of the NIH CTSA Consortium's Clinical Research Ethics Key Function Committee (CRE-KFC) conducted a survey of the 38 institutions that held CTSA funding as of January 2009 to determine how they satisfy RCR training requirements. An 8-item questionnaire was sent by email to directors of the Clinical Research Ethics, the Educational and Career Development, and the Regulatory Knowledge cores. We received 78 completed surveys from 38 CTSAs (100%). We found that there is no unified approach to RCR training across CTSAs, many programs lack a coherent plan for RCR instruction, and most CTSAs have not developed unique instructional materials tailored to the needs of clinical and translational scientists. We recommend collaboration among CTSAs and across CTSA key function committees to address these weaknesses. We also requested that institutions send electronic copies of original RCR training materials to share among CTSAs via the CTSpedia website. Twenty institutions submitted at least one educational product. The CTSpedia now contains more than 90 RCR resources.


Identification of hemolytic and cytotoxic proteins of Actinobacillus pleuropneumoniae by use of monoclonal antibodies.
Monoclonal antibodies (MAbs) were raised against extracellular hemolytic and cytotoxic proteins of Actinobacillus pleuropneumoniae serotypes 2 and 9. MAbs were tested for inhibition of hemolytic and cytotoxic activities of the reference strains of A. pleuropneumoniae serotypes 1 to 12. Five MAbs inhibited hemolytic or cytotoxic activities of one or more serotypes and were used to probe Western blots (immunoblots) of cytotoxic and hemolytic culture filtrates of serotypes 1 to 12. The MAbs recognized three different proteins: (i) a protein of approximately 103 kDa that was associated with a weak hemolytic activity and a moderate cytotoxic activity, (ii) a protein of approximately 105 kDa that was associated with a strong hemolytic activity and a strong cytotoxic activity, and (iii) a protein of approximately 120 kDa that was associated with a strong cytotoxic activity but not with hemolytic activity. Serotypes 6, 7, and 12 produced only the 103-kDa protein, and serotype 10 produced only the 105-kDa protein. The other serotypes produced two proteins: serotypes 1, 5, 9, and 11 produced the 103- and 105-kDa proteins, and serotypes 2, 3, 4, and 8 produced the 103- and 120-kDa proteins.


Deaths: leading causes for 2001.
This report presents final 2001 data on the 10 leading causes of death in the United States by age, race, sex, and Hispanic origin. Leading causes of infant, neonatal, and postneonatal death are also presented. This report supplements the annual report of final mortality statistics. Data in this report are based on information from all death certificates filed in the 50 States and the District of Columbia in 2001. Causes of death classified by the International Classification of Diseases, Tenth Revision are ranked according to the number of deaths assigned to rankable causes. In 2001, the 10 leading causes of death were (in rank order) Diseases of heart; Malignant neoplasms; Cerebrovascular diseases; Chronic lower respiratory diseases; Accidents (unintentional injuries); Diabetes mellitus; Influenza and pneumonia; Alzheimer's disease; Nephritis, nephrotic syndrome and nephrosis; and Septicemia and accounted for nearly 80 percent of all deaths occurring in the United States. Differences in the rankings are evident by age, sex, race, and Hispanic origin. Leading causes of infant death for 2001 were (in rank order) Congenital malformations, deformations and chromosomal abnormalities; Disorders related to short gestation and low birth weight, not elsewhere classified; Sudden infant death syndrome; Newborn affected by maternal complications of pregnancy; Newborn affected by complications of placenta, cord and membranes; Respiratory distress of newborn; Accidents (unintentional injuries); Bacterial sepsis of newborn; Diseases of the circulatory system; and Intrauterine hypoxia and birth asphyxia. Important variation in the leading causes of infant death is noted for the neonatal and postneonatal periods.


Spontaneous and therapeutic prognostic factors in adult hemispheric World Health Organization Grade II gliomas: a series of 1097 cases: clinical article.
The spontaneous prognostic factors and optimal therapeutic strategy for WHO Grade II gliomas (GIIGs) have yet to be unanimously defined. Specifically, the role of resection is still debated, most notably because the actual amount of resection has seldom been assessed. Cases of GIIGs treated before December 2007 were extracted from a multicenter database retrospectively collected since January 1985 and prospectively collected since 1996. Inclusion criteria were a patient age ≥ 18 years at diagnosis, histological diagnosis of WHO GIIG, and MRI evaluation of tumor volume at diagnosis and after initial surgery. One thousand ninety-seven lesions were included in the analysis. The mean follow-up was 7.4 years since radiological diagnosis. Factors significant in a univariate analysis (with a p value ≤ 0.1) were included in the multivariate Cox proportional hazard regression model analysis. At the time of radiological diagnosis, independent spontaneous factors of a poor prognosis were an age ≥ 55 years, an impaired functional status, a tumor location in a nonfrontal area, and, most of all, a larger tumor size. When the study starting point was set at the time of first treatment, independent favorable prognostic factors were limited to a smaller tumor size, an epileptic symptomatology, and a greater extent of resection. This large series with its volumetric assessment refines the prognostic value of previously stressed clinical and radiological parameters and highlights the importance of tumor size and location. The results support additional arguments in favor of the predominant role of resection, in accordance with recently reported experiences.


Percutaneous cholecystostomy using a central venous catheter is effective for treating high-risk patients with acute cholecystitis.
Percutaneous cholecystostomy (PC) using a pigtail catheter is performed on high-risk patients with acute cholecystitis as their general condition does not usually allow them to undergo a "definite" cholecystectomy. However, this method of PC is time-consuming and expensive and requires an interventional radiologist and specially designed radiologic equipment. To determine whether another PC approach was viable, we retrospectively compared patients who underwent PC using a central venous catheter (group A, n = 15) with those who underwent standard pigtail catheter PC (group B, n = 29). The waiting time prior to undergoing the PC was 1.8 days in group A and 3.5 days in group B (P < 0.05). The cost per patient was 293,364 won (254.44 dollars) for group A, and 438,719 won (380.50 dollars) for group B (P < 0.05). There were 4 complications in group A and 5 in group B. Following PC, 7 patients in group A and 15 patients in group B underwent delayed definite cholecystectomy, and there were no differences between these groups in terms of complications, mortality, and the delayed definite cholecystectomy surgical method. We conclude that in combination with careful patient selection, PC using a central venous catheter in high-risk patients with acute cholecystitis is a viable alternative to pigtail catheter PC.


Isolation of syncytiotrophoblast microvesicles and exosomes and their characterisation by multicolour flow cytometry and fluorescence Nanoparticle Tracking Analysis.
The human placenta releases multiple types and sizes of syncytiotrophoblast (STB) extracellular vesicles (EV) into the maternal circulation that exhibit diverse biological activities. The placental perfusion technique enables isolation of these STBEV, but conventional flow cytometry can only be used to phenotype EV down to ∼300 nm in size. Fluorescence Nanoparticle Tracking Analysis (fl-NTA) has the potential to phenotype EV down to ∼50 nm, thereby improving current characterisation techniques. The aims of this study were to prepare microvesicle and exosome enriched fractions from human placental perfusate (n=8) and improve fl-NTA STBEV detection. Differential centrifugation and filtration effectively removed contaminating red blood cells from fresh placental perfusates and pelleted a STB microvesicle (STBMV) fraction (10,000×g pellet - 10KP; NTA modal size 395±12 nm), enriched for the STB marker placental alkaline phosphatase (PLAP) and a STB exosome (STBEX) fraction (150,000×g pellet - 150KP; NTA modal size 147±6 nm), enriched for PLAP and exosome markers Alix and CD63. The PLAP positivity of 'standard' 10KP and 150KP pools (four samples/pool), determined by immunobead depletion, was used to optimise fl-NTA camera settings. Individual 10KP and 150KP samples (n=8) were 54.5±5.7% (range 17.8-66.9%) and 30.6±5.6% (range 3.3-51.7%) PLAP positive, respectively. We have developed a reliable method for enriching STBMV and STBEX from placental perfusate. We also standardised fl-NTA settings and improved measurement of PLAP positive EV in STBMV. However, fl-NTA is not as sensitive as anti-PLAP Dynabead capture for STBEX detection, possibly due to STBEX having lower surface expression of PLAP. These important developments will facilitate more detailed studies of the role of STBMV and STBEX in normal and pathological pregnancies.


"Engaging in my rural community": perceptions of people aged 85 years and over.
Globally, numbers of people aged 85 years and over are increasing. Many older people, including those 85 years and over, are ageing in rural areas. For successful ageing in place, physical and social environments must be appropriate. The aim of this study is to understand the influence the physical and social environments have on enabling those aged 85 years and over to remain engaged in a rural community. Method: Utilizing an environmental gerontological approach, semi-structured interviews were undertaken with 15 people who lived independently in a rural community. Following transcription data were analyzed and themes identified. Results: Two themes were identified; "Negotiating the physical environment: 'Getting there and back'" and "Maintaining social networks: 'Places to go, people to see'". The findings provide insight into the importance of driving, parking close to amenities and negotiating the local environment to this group of older people and their ability to engage with their community. All participants agreed social engagement with friends, family or neighbors was important to them. Conclusion: These findings highlight the interconnection between physical and social environments. An enabling physical environment is essential to support social participation of people aged 85 years and over.


Variation in Complexity of Infection and Transmission Stability between Neighbouring Populations of Plasmodium vivax in Southern Ethiopia.
P. vivax is an important public health burden in Ethiopia, accounting for almost half of all malaria cases. Owing to heterogeneous transmission across the country, a stronger evidence base on local transmission dynamics is needed to optimise allocation of resources and improve malaria interventions. In a pilot evaluation of local level P. vivax molecular surveillance in southern Ethiopia, the diversity and population structure of isolates collected between May and November 2013 were investigated. Blood samples were collected from microscopy positive P. vivax patients recruited to clinical and cross-sectional surveys from four sites: Arbaminch, Halaba, Badawacho and Hawassa. Parasite genotyping was undertaken at nine tandem repeat markers. Eight loci were successfully genotyped in 197 samples (between 36 and 59 per site). Heterogeneity was observed in parasite diversity and structure amongst the sites. Badawacho displayed evidence of unstable transmission, with clusters of identical clonal infections. Linkage disequilibrium in Badawacho was higher (IAS = 0.32, P = 0.010) than in the other populations (IAS range = 0.01-0.02) and declined markedly after adjusting for identical infections (IAS = 0.06, P = 0.010). Other than Badawacho (HE = 0.70), population diversity was equivalently high across the sites (HE = 0.83). Polyclonal infections were more frequent in Hawassa (67%) than the other populations (range: 8-44%). Despite the variable diversity, differentiation between the sites was low (FST range: 5 x 10-3-0.03). Marked variation in parasite population structure likely reflects differing local transmission dynamics. Parasite genotyping in these heterogeneous settings has potential to provide important complementary information with which to optimise malaria control interventions.


Epidemiology of Occupational Electrical Injuries.
Electrical injuries are an uncommon but very destructive type of burn, with serious complications and disabilities for the victims. This study was conducted due to the importance of understanding the epidemiology of electrical accidents in planning to prevent their occurrence. This is a retrospective cross-sectional study that was performed on patients with electrical burns referred to Shahid Motahari Educational and Medical Center from 2017 to 2018. Patients' information was entered in the researcher-made information registration form, including demographic and accident-related information. In this study, most of the accidents occurred in the workplace with high-voltage electricity. Contact with overhead cables and wires was the most common cause of injury. Excision and graft surgeries were the most common type of surgery. The variables of sex, age, length of hospital stay, and type of job had a significant relationship with the type of voltage (P < .05). The difference between the ratio of men to women and the length of hospitalization in the group of injured with high-voltage electricity was greater and most of these patients were construction workers. The variables of sex, nationality, length of hospital stay, and cause of the accident had a significant relationship with the type of job (P < .05). Construction workers are the main group at risk of electrical damage in Iran. Therefore, it is recommended to conduct more extensive studies in the field of recognizing and implementing practical methods of preventing electrical injuries, especially in high-risk work environments.


Phylogenetically driven sequencing of extremely halophilic archaea reveals strategies for static and dynamic osmo-response.
Organisms across the tree of life use a variety of mechanisms to respond to stress-inducing fluctuations in osmotic conditions. Cellular response mechanisms and phenotypes associated with osmoadaptation also play important roles in bacterial virulence, human health, agricultural production and many other biological systems. To improve understanding of osmoadaptive strategies, we have generated 59 high-quality draft genomes for the haloarchaea (a euryarchaeal clade whose members thrive in hypersaline environments and routinely experience drastic changes in environmental salinity) and analyzed these new genomes in combination with those from 21 previously sequenced haloarchaeal isolates. We propose a generalized model for haloarchaeal management of cytoplasmic osmolarity in response to osmotic shifts, where potassium accumulation and sodium expulsion during osmotic upshock are accomplished via secondary transport using the proton gradient as an energy source, and potassium loss during downshock is via a combination of secondary transport and non-specific ion loss through mechanosensitive channels. We also propose new mechanisms for magnesium and chloride accumulation. We describe the expansion and differentiation of haloarchaeal general transcription factor families, including two novel expansions of the TATA-binding protein family, and discuss their potential for enabling rapid adaptation to environmental fluxes. We challenge a recent high-profile proposal regarding the evolutionary origins of the haloarchaea by showing that inclusion of additional genomes significantly reduces support for a proposed large-scale horizontal gene transfer into the ancestral haloarchaeon from the bacterial domain. The combination of broad (17 genera) and deep (≥5 species in four genera) sampling of a phenotypically unified clade has enabled us to uncover both highly conserved and specialized features of osmoadaptation. Finally, we demonstrate the broad utility of such datasets, for metagenomics, improvements to automated gene annotation and investigations of evolutionary processes.


Current status of insecticide resistance among malaria vectors in Kenya.
Insecticide resistance has emerged as one of the major challenges facing National Malaria Control Programmes in Africa. A well-coordinated national database on insecticide resistance (IRBase) can facilitate the development of effective strategies for managing insecticide resistance and sustaining the effectiveness of chemical-based vector control measures. The aim of this study was to assemble a database on the current status of insecticide resistance among malaria vectors in Kenya. Data was obtained from published literature through PubMed, HINARI and Google Scholar searches and unpublished literature from government reports, research institutions reports and malaria control programme reports. Each data source was assigned a unique identification code and entered into Microsoft Excel 2010 datasheets. Base maps on the distribution of insecticide resistance and resistance mechanisms among malaria vectors in Kenya were generated using ArcGIS Desktop 10.1 (ESRI, Redlands, CA, USA). Insecticide resistance status among the major malaria vectors in Kenya was reported in all the four classes of insecticides including pyrethroids, carbamates, organochlorines and organophosphates. Resistance to pyrethroids has been detected in Anopheles gambiae (s.s.), An. arabiensis and An. funestus (s.s.) while resistance to carbamates was limited to An. gambiae (s.s.) and An. arabiensis. Resistance to the organochlorine was reported in An. gambiae (s.s.) and An. funestus (s.s.) while resistance to organophosphates was reported in An. gambiae (s.l.) only. The mechanisms of insecticide resistance among malaria vectors reported include the kdr mutations (L 1014S and L 1014F) and elevated activity in carboxylesterase, glutathione S-transferases (GST) and monooxygenases. The kdr mutations L 1014S and L 1014F were detected in An. gambiae (s.s.) and An. arabiensis populations. Elevated activity of monooxygenases has been detected in both An. arabiensis and An. gambiae (s.s.) populations while the elevated activity of carboxylesterase and GST has been detected only in An. arabiensis populations. The geographical maps show the distribution of insecticide resistance and resistance mechanisms among malaria vectors in Kenya. The database generated will provide a guide to intervention policies and programmes in the fight against malaria.


Integrating oculomotor and perceptual training to induce a pseudofovea: A model system for studying central vision loss.
People with a central scotoma often adopt an eccentric retinal location (Preferred Retinal Locus, PRL) for fixation. Here, we proposed a novel training paradigm as a model system to study the nature of the PRL formation and its impacts on visual function. The training paradigm was designed to effectively induce a PRL at any intended retinal location by integrating oculomotor control and pattern recognition. Using a gaze-contingent display, a simulated central scotoma was induced in eight normally sighted subjects. A subject's entire peripheral visual field was blurred, except for a small circular aperture with location randomly assigned to each subject (to the left, right, above, or below the scotoma). Under this viewing condition, subjects performed a demanding oculomotor and visual recognition task. Various visual functions were tested before and after training at both PRL and nonPRL locations. After 6-10 hr of the training, all subjects formed their PRL within the clear window. Both oculomotor control and visual recognition performance significantly improved. Moreover, there was considerable improvement at PRL location in high-level function, such as trigram letter-recognition, reading, and spatial attention, but not in low-level function, such as acuity and contrast sensitivity. Our results demonstrated that within a relatively short time, a PRL could be induced at any intended retinal location in normally-sighted subjects with a simulated scotoma. Our training paradigm might not only hold promise as a model system to study the dynamic nature of the PRL formation, but also serve as a rehabilitation regimen for individuals with central vision loss.


Efficacy of a hybrid online training for panic symptoms and agoraphobia: study protocol for a randomized controlled trial.
Recently, internet-based interventions have been proposed as effective treatments for people with panic disorder (PD). However, little is known about the clinical effects of integrating mobile technology into these interventions. Because users carry their smartphones with them throughout the day, we hypothesize that this technology can be used to significantly support individuals with monitoring and overcoming their PD symptoms. The aim of the present study is to evaluate the efficacy and cost-effectiveness of a newly developed hybrid intervention that combines internet/PC with smartphone delivery to treat the symptoms of PD. The intervention is based on cognitive behavioral therapy and consists of six modules over a total of six weeks. A two-arm randomized controlled trial (RCT) will be conducted to evaluate the effects of a hybrid online training module for PD. Based on a power calculation (d =0.60; 1-β of 80%; α =0.05), 90 participants with mild to moderate panic symptoms with or without agoraphobia (as assessed by the Panic and Agoraphobia Scale) will be recruited from the general population and randomly assigned to either the intervention group or a six-month waitlist control group. The primary outcome measure will be the severity of panic symptoms. Secondary outcomes will include depression, quality of life, and an observer-based rating of panic severity. Furthermore, data regarding acceptance and the usability of the smartphone app will be assessed. Assessments will take place at baseline as well as eight weeks, three months, and six months after randomization. Moreover, a cost-effectiveness analysis will be performed from a societal perspective. Data will be analyzed on an intention-to-treat basis and per protocol. To our knowledge, this RCT is one of the first to examine the efficacy of a hybrid online training for adult PD. This study seeks to contribute to the emerging field of hybrid online training. If the intervention is efficacious, then research on this hybrid online training should be extended. The cost-effectiveness analysis will also indicate whether online training is an economical tool for treating PD among adults. German Clinical Trial Register: DRKS00005223 (registered on 15 August 2013).


A PCR-based method for monitoring Legionella pneumophila in water samples detects viable but noncultivable legionellae that can recover their cultivability.
Legionella pneumophila is the causative agent of Legionnaires' disease. This bacterium is ubiquitous in aqueous environments and uses amoebae as an intracellular replicative niche. Real-time PCR has been developed for rapid detection of Legionella DNA in water samples. In addition to culturable bacteria, this method may also detect dead and viable but noncultivable (VBNC) legionellae. In order to understand the significance of positive PCR results in this setting, we prepared water samples containing known concentrations of L. pneumophila and analyzed them comparatively by means of conventional culture, real-time PCR, viability labeling, and immunodetection (solid-phase cytometry). We also examined the influence of chlorination on the results of the four methods. The different techniques yielded similar results for nonchlorinated water samples but not for chlorinated samples. After treatment for 24 h with 0.5 and 1 ppm chlorine, all cultures were negative, PCR and immunodetection showed about 10(6) genome units and bacteria/ml, and total-viable-count (TVC) labeling detected 10(5) and 10(2) metabolically active bacteria/ml, respectively. Thus, PCR also detected bacteria that were VBNC. The recoverability of VBNC forms was confirmed by 5 days of coculture with Acanthamoeba polyphaga. Therefore, some TVC-positive bacteria were potentially infective. These data show that L. pneumophila PCR detects not only culturable bacteria but also VBNC forms and dead bacterial DNA at low chlorine concentrations.


Lead and cadmium in foods/drinking water from Slovenian market/taps: Estimation of overall chronic dietary exposure and health risks.
Approximately 3000 food samples from the Slovenian market and 2500 drinking (tap) water samples in the period 2011 - 2016 were evaluated for the presence of toxic elements lead (Pb) and cadmium (Cd) and the overall chronic dietary exposure was assessed for each element. The highest mean concentrations were found for Pb in products for special nutritional use - dietary supplements (0.383 mg/kg) and for Cd in fish and seafood (0.117 mg/kg). The consumption data were obtained from the national study of the household budget and from the European Food Safety Authority (EFSA) summary statistics. Chronic dietary exposure was estimated deterministically. The average Pb and Cd intakes from food and drinking (tap) water ranged for children from 0.90 to 1.021 µg/kg bw/day and 4.65 to 5.65 µg/kg bw/week, respectively, and for adults, including adolescents, from 0.40 to 0.53 µg/kg bw/day and 1.98 to 2.82 µg/kg bw/week, respectively. The high consumption of cereal-based foods and vegetables contributed most to overall Pb and Cd intake in the majority of the age groups. The exposure to Pb was generally lower and that to Cd was higher compared to the average EU values. The most exposed were children, as the health-based guidance values were exceeded for both elements, which indicates a health concern. An important contribution to Cd exposure can be attributed to grains and potatoes grown in Slovenia, where the soil contains more Cd than that in other EU countries. Further efforts to reduce Pb and Cd intake are required to minimize potential health risks.


Adult outcomes of being born late preterm or early term - What do we know?
The literature on adult outcomes of people born late preterm (LPT, 34-36 completed weeks) or early term (ET, 37-38 weeks) was reviewed. In PubMed, 9547 articles were identified; 53 were eligible. Of these, 12 were based on clinical cohorts, 32 on medical birth register linkages, and nine on historical birth cohorts; 48 out of 53 on Nordic countries; 50 out of 53 reported on LPT and eight out of 53 reported on ET. LPT plus ET have increased early (<45 years) adult all-cause mortality. Despite increased cardiometabolic risk factors and slightly lower cardiorespiratory fitness in LPT, no studies showed increased risk for coronary heart disease, some showed increased risk for stroke, and all showed increased risk for type 2 diabetes. Most show increased risk for asthma and decreased allergic rhinitis. LPT have slightly lower cognitive abilities and higher rates of several mental disorders; ET have intermediate values. LPT and ET adults have slightly lower education, occupational status, and income. We recommend that authors report findings of LPT/ET separately from those born more preterm.


Reactions to a health threat: dispositional threat orientations and message characteristics.
This study explored the interactive effects of dispositional threat orientation, type of message, and having children on reactions to a message about exposure to bisphenol A (BPA) in plastics. The study used a 2 (message: Fear Arousal or Plain)×2 (parenting status: child or no child)×2 (threat orientation: high or low) mixed factorial design. Adults (N= 200) recruited via the Internet completed measures of threat orientations, reported whether they were a parent, and read either a low or high fear-arousal message about the risks of BPA exposure. They then completed measures of reactions to the message (perceived susceptibility to BPA effects, negative emotions, and behavioural intentions to engage in protection). Depending on threat orientations, the fear arousal version of the message and parenthood had strikingly different effects, ranging from no effect (for those high in a control-based approach) to prompting change (for those low in a control-based approach) to counterproductive (for those high in an optimistic denial approach). These findings suggest that considering individual differences and their interactions with situational factors could improve both the predictive ability of threat protection theories and the delivery of messages intended to change behaviour.


Partial rupture of the distal biceps tendon.
Partial rupture of the distal biceps tendon is a relatively rare event, and various degrees of partial tendon tears have been reported. In the current study four patients with partial atraumatic distal biceps tendon tears (mean age, 59 years; range, 40-82 years) are reported. In all four patients, a common clinical pattern emerged. Pain at the insertion of the distal biceps tendon in the radius unrelated to any traumatic event was the main symptom. In all patients the diagnosis was based on magnetic resonance imaging or computed tomography imaging. In three of four patients the partial rupture of the tendon caused a significant bursalike lesion. The typical appearance was a partially ruptured biceps tendon, with contrast enhancement signaling the degree of degeneration, tenosynovitis, and soft tissue swelling extending along the tendon semicircular to the proximal radius. In three patients, conservative treatment was successful. Only one patient needed surgery, with reinsertion of the tendon resulting in total functional recovery.


Single-cell RNA sequencing identifies celltype-specific cis-eQTLs and co-expression QTLs.
Genome-wide association studies have identified thousands of genetic variants that are associated with disease 1 . Most of these variants have small effect sizes, but their downstream expression effects, so-called expression quantitative trait loci (eQTLs), are often large 2 and celltype-specific3-5. To identify these celltype-specific eQTLs using an unbiased approach, we used single-cell RNA sequencing to generate expression profiles of ~25,000 peripheral blood mononuclear cells from 45 donors. We identified previously reported cis-eQTLs, but also identified new celltype-specific cis-eQTLs. Finally, we generated personalized co-expression networks and identified genetic variants that significantly alter co-expression relationships (which we termed 'co-expression QTLs'). Single-cell eQTL analysis thus allows for the identification of genetic variants that impact regulatory networks.


The significance of gratitude for palliative care professionals: a mixed method protocol.
In palliative care (PC) patients and relatives (P/R) often show their gratitude to the healthcare professionals (HP) who care for them. HP appreciate these displays of gratitude, although the impact of the same has not been examined in detail. Publications analysed tell personal experiences in which HP say that displays of gratitude create sensations of well-being, pride and increased motivation to carry on caring. No systematic examination in PC was found. These aspects related to gratitude may be important in the field of PC, where there is constant exposure to suffering and the preoccupation which arises from wanting to help HP to go on with their work, but it needs closer study and systemisation. The purpose of this study is to understand the significance and the role of the gratitude received from P/R for palliative care health professionals (PCHP). A suitable mixed method will be used. The first phase will be quantitative and will consist of a survey, piloted by experts, whose goal is to explore the current situation in Spain as regards displays of gratitude received by HP at PC services. It will be sent by e-mail. The results from this part will be incorporated into the second part which will be qualitative and whose goal is to understand the significance of the experience of receiving displays of gratitude from the perspective of PCHP, using a phenomenological approach. Interviews will be undertaken amongst PCHP. The interview guide will be designed after taking the survey results into account. The project has been granted ethical approval. These results are set to provide a key contribution within the context of the growing preoccupation on how to care for HP, how to ensure retention and keep them from resigning, as well as preventing burnout, emotional fatigue and boosting their resilience. In order to do this, it is both interesting and ground breaking, to analyse the repercussion of spontaneous gratitude shown by P/R towards PCHP, to see if this is a useful resource to reduce these problems and to encourage the greater presence of dignity and humanisation, for both those receiving care and for those providing it. This gratitude may be one of these strategies.


Intron polymorphism in MYL1 gene is associated with individual cardiac trainability to endurance training in human myocardium.
The aim of this study was to examine the association between polymorphism of the intron MYL1 and the genetic predisposition or trainability to endurance exercise in human myocardium. The research consisted of two studies. The first study examined distributional differences in genotypes and alleles of MYL1 in endurance athletes (n=31) and untrained adults (N.=206). The second study examined association between the distributional differences in the genotypes and cardiac ability or trainability. Ninety-nine previously untrained men participated in an 18-week endurance training program with intensity between 95% and 105% of the ventilatory threshold. Cardiac output and cardiac index were assessed by echocardiography before and after training. The first study demonstrated that the frequency of the genotype AA at RS1472955 was higher (0.48 vs. 0.30), and that of GG was lower (0.00 vs. 0.16) in the athlete group than that in the Control (all P<0.05, χ2 Test). The second study showed that:1) GG carriers had a lower training responsiveness than AA and GA carriers (P<0.05, z test);2) a decrease of cardiac output (10580±1461 to 10060±1421 mL/min, P<0.05, one-way ANOVA) and cardiac index (6511.8±962.3 to 6110.3±817.1 mL/m2, P<0.05) only occurred in AA carriers during low-intensity exercise (50W);3) the genotypes were significantly correlated to the magnitude of change caused by the endurance training in cardiac output (r=0.215, P<0.05, Pearson correlation) and cardiac index (r=0.221, P<0.05) in low-intensity exercise. The findings suggested that the polymorphism of intron MYL1 was associated with endurance performance, specifically in endurance trainability, but not genetic predisposition, in human adults.


On Known Unknowns: Fluency and the Neural Mechanisms of Illusory Truth.
The "illusory truth" effect refers to the phenomenon whereby repetition of a statement increases its likelihood of being judged true. This phenomenon has important implications for how we come to believe oft-repeated information that may be misleading or unknown. Behavioral evidence indicates that fluency, the subjective ease experienced while processing information, underlies this effect. This suggests that illusory truth should be mediated by brain regions previously linked to fluency, such as the perirhinal cortex (PRC). To investigate this possibility, we scanned participants with fMRI while they rated the truth of unknown statements, half of which were presented earlier (i.e., repeated). The only brain region that showed an interaction between repetition and ratings of perceived truth was PRC, where activity increased with truth ratings for repeated, but not for new, statements. This finding supports the hypothesis that illusory truth is mediated by a fluency mechanism and further strengthens the link between PRC and fluency.


Effects of chronic omega-3 polyunsaturated fatty acid supplementation on human atrial mechanical function after reversion of atrial arrhythmias to sinus rhythm: reversal of tachycardia-mediated atrial cardiomyopathy with fish oils.
Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm. This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning. Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion. After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02). Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias.


Potential DNA barcodes for Melilotus species based on five single loci and their combinations.
Melilotus, an annual or biennial herb, belongs to the tribe Trifolieae (Leguminosae) and consists of 19 species. As an important green manure crop, diverse Melilotus species have different values as feed and medicine. To identify different Melilotus species, we examined the efficiency of five candidate regions as barcodes, including the internal transcribed spacer (ITS) and two chloroplast loci, rbcL and matK, and two non-coding loci, trnH-psbA and trnL-F. In total, 198 individuals from 98 accessions representing 18 Melilotus species were sequenced for these five potential barcodes. Based on inter-specific divergence, we analysed sequences and confirmed that each candidate barcode was able to identify some of the 18 species. The resolution of a single barcode and its combinations ranged from 33.33% to 88.89%. Analysis of pairwise distances showed that matK+rbcL+trnL-F+trnH-psbA+ITS (MRTPI) had the greatest value and rbcL the least. Barcode gap values and similarity value analyses confirmed these trends. The results indicated that an ITS region, successfully identifying 13 of 18 species, was the most appropriate single barcode and that the combination of all five potential barcodes identified 16 of the 18 species. We conclude that MRTPI is the most effective tool for Melilotus species identification. Taking full advantage of the barcode system, a clear taxonomic relationship can be applied to identify Melilotus species and enhance their practical production.


[Serological investigations on patients with hemolytic uremic syndromes due to enterohemorrhagic Escherichia coli O157:H7 infection].
To investigate the etiological agent of patients with diarrhea followed by acute kidney failure symptoms in China, 1999. Western blot was used to detect serum specific antibodies of patients against entero-haemorrhagic Escherichia coli hemolysin (EHEC-Hly) and lipo-polysaccharide of E. coli O157. Twenty-one and 16 of 42 patients showed positive reaction of specific IgG or IgM antibodies against EHEC-Hly respectively. Eleven of 42 serum samples were positive for having both IgG and IgM antibodies while 26 of 42 samples were positive for IgG or IgM. For E. coli O157 LPS test, 24 and 24 of 42 samples showed positive for IgG or IgM antibodies respectively. In 42 samples, 20 were positive for IgG and IgM while 29 were positive for IgG or IgM. Twenty-two of 42 samples were reacted with EHEC-Hly and E. coli O157 LPS, but 34 of 42 samples were positive for EHEC-Hly or E. coli O157. In combination of western blot results, bacterial isolation clinical symptoms and epidemiological investigation findings, it was reasonable to conclude that this cluster of patients with distinguish clinical symptoms was caused by E. coli O157:H7, which had never been reported in China. Hence serological methods with EHEC-Hly and E. coli O157 LPS are valuable for diagnosis of infections of E. coli O157:H7, when bacterial isolation is failed.


Mouse oviduct-specific glycoprotein gene: genomic organization and structure of the 5'-flanking regulatory region.
A member of the chitinase protein family, oviduct-specific glycoprotein (OGP), can directly associate with gametes or with the early embryo in the oviduct. Although the glycoprotein is widely distributed among mammalian species and there is indirect evidence concerning the involvement of the molecule in the fertilization process, its physiological functions are far from completely understood. To understand the fundamental mechanisms that direct gene expression as well as to know the physiological significance of OGP, we have isolated and characterized a mouse OGP gene (mogp-1). The gene was found to span 13.4 kilobases (kb) including 11 exons and 10 introns. The genomic organization of mogp-1 is well conserved compared to the other members of the chitinase family. Two transcription initiation sites were found at positions 18 and 14 upstream from the first ATG codon. Fluorescence in situ hybridization analysis demonstrated that the mogp-1 was located on the R-positive F3 band of mouse chromosome 3. Although the putative promoter region of mogp-1 lacked typical TATA, CAAT, or GC box sequences, the region contained several motif sequences of transcription factor binding sites including 10 half-palindromic estrogen responsive elements (ERE) and an imperfect ERE. Transient transfection experiments demonstrated that promoter activity could be modulated by various sequences within the 2.2 kb of the 5'-flanking region, and that the mogp-1 promoter was transactivated in an estrogen receptor-positive cell line, MCF-7, by the addition of estradiol-17beta (E(2)). In addition, relevant promoter activity for E(2) responsiveness resides within the first 270 base pairs upstream of the mogp-1. These findings should facilitate our understanding of the regulation of OGP gene expression, and they may be helpful for designing experiments to unravel the role of OGP in the process of mammalian fertilization.


A prospective national survey of management and clinical outcome of acute myocardial infarction in Israel, 2000.
Little information is available on the clinical practice and implementation of guidelines for treating acute myocardial infarction patients in Israel. To assess patient characteristics, hospital course, management, and 30 day clinical outcome of all AMI patients hospitalized in Israel during a 2 month period in 2000. We conducted a prospective 2 month survey of consecutive AMI patients admitted to 82 of 96 internal medicine departments and all 26 cardiac departments operating in Israel in 2000. Data were collected uniformly by means of a hospital and 30 day follow-up form. During the survey 1,683 consecutive patients with a discharge diagnosis of AMI were included. Their mean age was 66 years; 73% were male. The electrocardiographic pattern on admission revealed ST elevation, non-ST elevation and an undetermined ECG in 63%, 34% and 4% of patients respectively. Aspirin and heparin were given to 95% of patients. Beta-blockers and angiotensin-converting enzyme inhibitors were given to 76% and 65% of patients respectively. Among hospital survivors, 45% received lipid-lowering drugs. Thrombolytic therapy was administered in 28% of patients, coronary angiography was used in 45%, and 7% of patients underwent primary percutaneous coronary intervention. The 7 and 30 day mortality rates were 7% and 11% respectively. This nationwide survey shows that one-third of the AMI patients in Israel are elderly (> or = 75 years). The survey suggests that clinical guidelines for the management of patients with AMI are partially implemented in the community. Data from large surveys representing the "real world" practice are of utmost importance for the evaluation of clinical guidelines, research and educational purposes.


Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.
Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age. SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68-1.2, p = 0.496). A reduction of 60% (95% CI 54%-64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%-72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%-33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%-35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%-68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%-85%) p = 0.002 in 2008, 84% (95% CI 58%-94%, p < 0.001) in 2009, and 30% (95% CI -130%-79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. ClinicalTrials.gov NCT00712374.


An mre11 mutation that promotes telomere recombination and an efficient bypass of senescence.
Preventing the formation of dysfunctional telomeres is essential for genomic stability. In most organisms, the ribo-nucleoprotein reverse transcriptase telomerase is responsible for telomere GT-strand elongation. However, in telomerase-negative cells, low-frequency recombination mechanisms can avert lethality by elongating critically short telomeres. This study focuses on the involvement of the budding yeast Mre11 in telomere recombination and homeostasis. We have identified a novel allele of MRE11, mre11-A470T, that, in telomerase-positive cells, confers a semidominant decrease in telomere size and a recessive defect in telomere healing. In addition, mutant cells lack normal telomere size homeostasis. Telomerase-negative mre11-A470T cells display a Rad51-dependent bypass of replicative senescence via induction of a highly efficient type I-related recombination pathway termed type IA. The type IA pathway involves an amplification of subtelomeric Y' elements, coupled with elongated and more heterogeneous telomere tracts relative to the short telomere size of type I survivors. The data have led us to propose the involvement of break-induced replication in telomere expansion. The differing phenotypes elicited by the mre11-A470T mutants in telomerase-positive and telomerase-negative cells have also led us to speculate that the telomere end structure may be modified differentially in mre11-A470T cells, directing the telomere into specific pathways.


Beyond water homeostasis: Diverse functional roles of mammalian aquaporins.
Aquaporin (AQP) water channels are best known as passive transporters of water that are vital for water homeostasis. AQP knockout studies in whole animals and cultured cells, along with naturally occurring human mutations suggest that the transport of neutral solutes through AQPs has important physiological roles. Emerging biophysical evidence suggests that AQPs may also facilitate gas (CO2) and cation transport. AQPs may be involved in cell signalling for volume regulation and controlling the subcellular localization of other proteins by forming macromolecular complexes. This review examines the evidence for these diverse functions of AQPs as well their physiological relevance. As well as being crucial for water homeostasis, AQPs are involved in physiologically important transport of molecules other than water, regulation of surface expression of other membrane proteins, cell adhesion, and signalling in cell volume regulation. Elucidating the full range of functional roles of AQPs beyond the passive conduction of water will improve our understanding of mammalian physiology in health and disease. The functional variety of AQPs makes them an exciting drug target and could provide routes to a range of novel therapies.


Effect of blood transfusion on the carbon monoxide transfer factor of the lung in man.
1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion. 2. The mean haemoglobin concentration increased from 7.7 to 11.1 g/dl. 3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations. TLCO (standardized) = TLCO (observed). (10.2 + Hb)/1.7 Hb, where haemoglobin (Hb) is expressed as g/dl. 4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.


A nanobody binding to non-amyloidogenic regions of the protein human lysozyme enhances partial unfolding but inhibits amyloid fibril formation.
We report the effects of the interaction of two camelid antibody fragments, generally called nanobodies, namely cAb-HuL5 and a stabilized and more aggregation-resistant variant cAb-HuL5G obtained by protein engineering, on the properties of two amyloidogenic variants of human lysozyme, I56T and D67H, whose deposition in vital organs including the liver, kidney, and spleen is associated with a familial non-neuropathic systemic amyloidosis. Both NMR spectroscopy and X-ray crystallographic studies reveal that cAb-HuL5 binds to the α-domain, one of the two lobes of the native lysozyme structure. The binding of cAb-HuL5/cAb-HuL5G strongly inhibits fibril formation by the amyloidogenic variants; it does not, however, suppress the locally transient cooperative unfolding transitions, characteristic of these variants, in which the β-domain and the C-helix unfold and which represents key early intermediate species in the formation of amyloid fibrils. Therefore, unlike two other nanobodies previously described, cAb-HuL5/cAb-HuL5G does not inhibit fibril formation via the restoration of the global cooperativity of the native structure of the lysozyme variants to that characteristic of the wild-type protein. Instead, it inhibits a subsequent step in the assembly of the fibrils, involving the unfolding and structural reorganization of the α-domain. These results show that nanobodies can protect against the formation of pathogenic aggregates at different stages in the structural transition of a protein from the soluble native state into amyloid fibrils, illustrating their value as structural probes to study the molecular mechanisms of amyloid fibril formation. Combined with their amenability to protein engineering techniques to improve their stability and solubility, these findings support the suggestion that nanobodies can potentially be developed as therapeutics to combat protein misfolding diseases.


High resolution observed in 800 MHz DNP spectra of extremely rigid type III secretion needles.
The cryogenic temperatures at which dynamic nuclear polarization (DNP) solid-state NMR experiments need to be carried out cause line-broadening, an effect that is especially detrimental for crowded protein spectra. By increasing the magnetic field strength from 600 to 800 MHz, the resolution of DNP spectra of type III secretion needles (T3SS) could be improved by 22 %, indicating that inhomogeneous broadening is not the dominant effect that limits the resolution of T3SS needles under DNP conditions. The outstanding spectral resolution of this system under DNP conditions can be attributed to its low overall flexibility.


Double color image encryption using iterative phase retrieval algorithm in quaternion gyrator domain.
This paper describes a novel algorithm to encrypt double color images into a single undistinguishable image in quaternion gyrator domain. By using an iterative phase retrieval algorithm, the phase masks used for encryption are obtained. Subsequently, the encrypted image is generated via cascaded quaternion gyrator transforms with different rotation angles. The parameters in quaternion gyrator transforms and phases serve as encryption keys. By knowing these keys, the original color images can be fully restituted. Numerical simulations have demonstrated the validity of the proposed encryption system as well as its robustness against loss of data and additive Gaussian noise.


Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations.
A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype-phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containing PSD4, MUC21 and MUC22, TOX2, ANXA6, and ABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.


An integrative analysis of transcriptomic response of ethanol tolerant strains to ethanol in Saccharomyces cerevisiae.
The accumulation of ethanol is one of the main environmental stresses that Saccharomyces cerevisiae cells are exposed to in industrial alcoholic beverage and bioethanol production processes. Despite the known impacts of ethanol, the molecular mechanisms underlying ethanol tolerance are still not fully understood. Novel gene targets leading to ethanol tolerance were previously identified via a network approach and the investigations of the deletions of these genes resulted in the improved ethanol tolerance of pmt7Δ/pmt7Δ and yhl042wΔ/yhl042wΔ strains. In the present study, an integrative system based approach was used to investigate the global transcriptional changes in these two ethanol tolerant strains in response to ethanol and hence to elucidate the mechanisms leading to the observed tolerant phenotypes. In addition to strain specific biological processes, a number of common and already reported biological processes were found to be affected in the reference and both ethanol tolerant strains. However, the integrative analysis of the transcriptome with the transcriptional regulatory network and the ethanol tolerance network revealed that each ethanol tolerant strain had a specific organization of the transcriptomic response. Transcription factors around which most important changes occur were determined and active subnetworks in response to ethanol and functional clusters were identified in all strains.


C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device.
People with type 1 diabetes (T1D) must administer insulin exogenously due to the destruction of their pancreatic β-cells. Endogenous insulin is stored in β-cell granules along with C-peptide, a 31 amino acid peptide that is secreted from these granules in amounts equal to insulin. Exogenous co-administration of C-peptide with insulin has proven to reduce diabetes-associated complications in animals and humans. The exact mechanism of C-peptide's beneficial effects after secretion from the β-cell granules is not completely understood, thus hindering its development as an exogenously administered hormone. Monitoring tissue-to-tissue communication using a 3D-printed microfluidic device revealed that zinc and C-peptide are being delivered to erythrocytes by albumin. Upon delivery, erythrocyte-derived ATP increased by >50%, as did endothelium-derived NO, which was measured downstream in the 3D-printed device. Our results suggest that hormone replacement therapy in diabetes may be improved by exogenous administration of a C-peptide ensemble that includes zinc and albumin.


Mini-thoracotomy versus median sternotomy for atrial septal defect closure: Should mini-thoracotomy be applied as a standard technique?
This study aims to compare outcomes of minithoracotomy versus median sternotomy for atrial septal defect closure. Between January 2012 and May 2017, a total of 44 patients (8 males, 36 females; mean age 33.86 years; range, 14 to 63 years) who underwent atrial septal defect repair through mini-thoracotomy or median sternotomy in our clinic were retrospectively analyzed. Pre-, intra-, and postoperative data of the patients were recorded. There was no significant difference in the cardiopulmonary bypass and cross-clamp times between the groups, although the duration of operation was shorter in the mini-thoracotomy group (p=0.001). No significant difference was observed between the groups in terms of early mortality, neurological complications, and residual atrial septal defect. The mean mechanical ventilation time and length of intensive care unit and hospital stay were statistically significantly shorter, and the amount of bleeding was statistically significantly lower in the mini-thoracotomy group (p=0.001 for all). Mini-thoracotomy should be kept in mind as a favorable alternative to sternotomy following a satisfactory learning curve period with less cost and higher patient benefit.


Advocacy evaluation: challenges and emerging trends.
Devising, promoting, and implementing changes in policies and regulations are important components of population-level health promotion. Whether advocating for changes in school meal nutrition standards or restrictions on secondhand smoke, policy change can create environments conducive to healthier choices. Such policy changes often result from complex advocacy efforts that do not lend themselves to traditional evaluation approaches. In a challenging fiscal environment, allocating scarce resources to policy advocacy may be particularly difficult. A well-designed evaluation that moves beyond inventorying advocacy activities can help make the case for funding advocacy and policy change efforts. Although it is one thing to catalog meetings held, position papers drafted, and pamphlets distributed, it is quite another to demonstrate that these outputs resulted in useful policy change outcomes. This is where the emerging field of advocacy evaluation fits in by assessing (among other things) strategic learning, capacity building, and community organizing. Based on recent developments, this article highlights several challenges advocacy evaluators are currently facing and provides new resources for addressing them.