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Objectives: This systematic review aimed to evaluate the therapeutic effects and safety of Chinese herbal medicine (CHM) formulae for managing menopausal hot flushes (MHF). Methods: Seven English and Chinese databases were searched for studies from respective inceptions to February 2019. Randomized controlled trials investigating the clinical effects and safety of CHM formulae on MHF were considered for inclusion. The outcomes of subjective feelings (MHF and quality of life), objective changes (hormones and peripheral blood flow) and safety were analyzed. The most frequently prescribed formulae and herbs were summarized. Results: Nineteen randomized clinical trials involving 2469 patients were included. When compared to menopausal hormone therapy, CHM had similar effects to menopausal hormone therapy on total effectiveness rate (OR 1.41, 95% CI 0.84 to 2.35) and total Kupperman index (KI) score (SMD -0.13, 95% CI -0.61 to 0.36), and could significantly reduce vasomotor symptom score (MD -0.43, 95% CI -0.55 to -0.31) and upper-body peripheral blood flow (MD -3.56, 95% CI -5.14 to -1.98 under the jaw, MD -7.10, 95% CI -11.01 to -3.19 in the fingertip). When compared to placebo, CHM could reduce MHF severity (MD -0.70, 95% CI-1.00 to -0.40) and improve total KI score (MD -12.61, 95% CI -15.21 to -10.01). However, no statistically significant changes to hormone levels were detected. Most commonly seen adverse events were mild gastrointestinal tract reactions. The most popularly studied formula was Kun Tai capsule and the most frequently prescribed herb was Bai shao (Paeoniae Radix Alba, Paeonia lactiflora Pall.). More than 50% included studies had low risks of bias in the domains of selection, performance, attrition and reporting. Conclusions: This review indicated that CHM formulae were safe to be applied in MHF females and able to improve MHF-related symptom scores as well as the peripheral blood flow. Further studies should focus on specific formulae. [ABSTRACT FROM AUTHOR]

The maturation of photon-counting detector (PCD) technology promises to enhance routine CT imaging applications with high-fidelity spectral information. In this paper, we demonstrate the power of this synergy and our complementary reconstruction techniques, performing 4D, cardiac PCD-CT data acquisition and reconstruction in a mouse model of atherosclerosis, including calcified plaque. Specifically, in vivo cardiac micro-CT scans were performed in four ApoE knockout mice, following their development of calcified plaques. The scans were performed with a prototype PCD (DECTRIS, Ltd.) with 4 energy thresholds. Projections were sampled every 10 ms with a 10 ms exposure, allowing the reconstruction of 10 cardiac phases at each of 4 energies (40 total 3D volumes per mouse scan). Reconstruction was performed iteratively using the split Bregman method with constraints on spectral rank and spatio-temporal gradient sparsity. The reconstructed images represent the first in vivo, 4D PCD-CT data in a mouse model of atherosclerosis. Robust regularization during iterative reconstruction yields high-fidelity results: an 8-fold reduction in noise standard deviation for the highest energy threshold (relative to unregularized algebraic reconstruction), while absolute spectral bias measurements remain below 13 Hounsfield units across all energy thresholds and scans. Qualitatively, image domain material decomposition results show clear separation of iodinated contrast and soft tissue from calcified plaque in the in vivo data. Quantitatively, spatial, spectral, and temporal fidelity are verified through a water phantom scan and a realistic MOBY phantom simulation experiment: spatial resolution is robustly preserved by iterative reconstruction (10% MTF: 2.8–3.0 lp/mm), left-ventricle, cardiac functional metrics can be measured from iodine map segmentations with ~1% error, and small calcifications (615 μm) can be detected during slow moving phases of the cardiac cycle. Given these preliminary results, we believe that PCD technology will enhance dynamic CT imaging applications with high-fidelity spectral and material information. [ABSTRACT FROM AUTHOR]

Objective: To explore clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes mellitus (T2DM). Methods: The data of 118 patients with T2DM were obtained from two previous clinical studies, and were retrospectively analyzed regarding the clinical parameters associated with bacterial translocation defined as detection of bacteremia and levels of plasma lipopolysaccharide binding protein (LBP), the latter of which is thought to reflect inflammation caused by endotoxemia. Results: LBP level was not significantly different between patients with and without bacteremia. No clinical factors were significantly correlated with the detection of bacteremia. On the other hand, plasma LBP level was significantly correlated with HbA1c (r = 0.312), fasting blood glucose (r = 0.279), fasting C-peptide (r = 0.265), body mass index (r = 0.371), high-density lipoprotein cholesterol (r = -0.241), and inflammatory markers (high-sensitivity C-reactive protein, r = 0.543; and interleukin-6, r = 0.456). Multiple regression analysis identified body mass index, HbA1c, high-sensitivity C-reactive protein, and interleukin-6 as independent determinants of plasma LBP level. Conclusion: The plasma LBP level was similar in patients with and without bacteremia. While both bacteremia and LBP are theoretically associated with bacterial translocation, the detection of bacteremia was not associated with LBP level in T2DM. [ABSTRACT FROM AUTHOR]

The ability of DENV2 to display different morphologies (hence different antigenic properties) complicates vaccine and therapeutics development. Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to “bumpy” surfaced morphology when the temperature is switched from 29°C at 37°C. Here we identified five envelope (E) protein residues different between two alternative passage history DENV2 NGC strains exhibiting smooth or bumpy surface morphologies. Several mutations performed on the smooth DENV2 infectious clone destabilized the surface, as observed by cryoEM. Molecular dynamics simulations demonstrated how chemically subtle substitution at various positions destabilized dimeric interactions between E proteins. In contrast, three out of four DENV2 clinical isolates showed a smooth surface morphology at 37°C, and only at high fever temperature (40°C) did they become “bumpy”. These results imply vaccines should contain particles representing both morphologies. For prophylactic and therapeutic treatments, this study also informs on which types of antibodies should be used at different stages of an infection, i.e., those that bind to monomeric E proteins on the bumpy surface or across multiple E proteins on the smooth surfaced virus. [ABSTRACT FROM AUTHOR]

In the course of the Maillard reaction, which occurs during heating of food but also under physiological condition, a broad spectrum of reaction products is formed. Among them, the advanced glycation endproducts (AGEs) Nε-carboxymethyllysine (CML), pyrraline (Pyr), methylglyoxal-derived hydroimidazolone 1 (MG-H1) and Nε-carboxyethyllysine (CEL) are the quantitatively dominating compounds during later reaction stages. Those dietary glycation compounds are under discussion as to be associated with chronic inflammation and the pathophysiological consequences of diseases such as diabetes. In the present study, the concentration of individual glycation compounds in saliva was monitored for the first time and related to their dietary uptake. Fasting saliva of 33 metabolically healthy subjects was analyzed with HPLC-MS/MS. The observed levels of individual glycation compounds ranged from 0.5 to 55.2 ng/ml and differed both intra- and interindividually. Patterns did not correlate with subject-related features such as vegetarianism or sports activities, indicating that dietary intake may play an important role. Therefore, six volunteers were asked to eat a raw food diet free of glycation compounds for two days. Within two days, salivary Pyr was lowered from median 1.7 ng/ml to a minimum level below the limit of detection, and MG-H1 decreased from 3.6 to 1.7 ng/ml in in a time-dependent manner after two days. Salivary CML and CEL concentrations were not affected. Therefore, measuring Pyr and MG-H1 in saliva is a suitable diagnostic tool to monitor the dietary intake and metabolic transit of glycation compounds present in heated foods. [ABSTRACT FROM AUTHOR]

Rhesus macaque is an important animal model in biomedical research, especially human disease, developmental, translational, and pre-clinical research. Blood physiological and biochemical parameters are important markers for physiology, pathology, and toxicology research. However, these parameters have not been systematically reported for Chinese rhesus macaques. To characterize the reference for these parameters, this study collected 1805 Chinese rhesus macaques living in Southwestern China. A total of 24 blood physiological indexes and 27 biochemical parameters were determined. Sex and age were found to affect these parameters. In conclusion, a comprehensive and systematic reference of hematological and biochemical parameters for Chinese rhesus macaque was established in this work on the basis of a large cohort. Such reference will benefit biomedical research employing rhesus macaques as animal models. [ABSTRACT FROM AUTHOR]

The literature lacks studies investigating the performance of supplemented replacement heifers grazing on intensively managed warm-season pasture. Our objective was to evaluate the effects of supplement composition (energetic or protein) on the performance, muscle development, thermogenisis, nutrient intake, and digestibility of replacement Holstein heifers grazing Mombaça grass. Eighteen Holstein heifers with an average age and initial body weight (BW) of 12.57 ± 2.54 mo and 218.76 ±47.6 kg, respectively, were submitted to a randomized block design, with six replicates on a rotational grazing system of Panicum maximum cv. Mombaça pasture. Treatments were: control (CON; mineral salt ad libitum); energy supplement (ENE; corn meal as supplement, 8% CP and 3.78 Mcal/kg DE); and protein supplement (PRO; corn and soybean meal, 25% CP and 3.66 Mcal/kg DE). Supplements were individually fed at 0.5% BW. The experiment lasted 120 days, subdivided into three periods. Titanium dioxide and indigestible neutral detergent fiber (iNDF) were used to estimate the intakes and digestibility of the nutrients. BW, wither height, thoracic circumference, body length, and ultrasound of ribeye fat thickness measurements were taken once per period. Body condition score (BCS) was assessed twice during the experiment. The MIXED procedure of SAS, including period as a repeated measure, was used and significance was declared at P ≤ 0.05. Dry matter intake (DMI), CP intake (CPI) and DE intake were greater in heifers fed PRO compared to CON and ENE. Heifers supplemented with ENE had the lowest DMI. Treatment affected pasture intake/BW; it was similar between PRO and CON heifers, and lower for the ENE treatment. A treatment × period interaction was observed for NDF intake (%BW), in which heifers fed PRO and CON had the greatest NDF intake and ENE had the lowest. The digestibility of DM was the greatest in PRO-supplemented heifers and the lowest in CON heifers. Heifers fed ENE had decreased CP digestibility compared to PRO and CON heifers. Average daily gain (ADG) and thoracic circumference gain were greatest in the PRO treatment. BCS was greater in PRO compared to CON and ENE heifers. Supplementing Holstein heifers at 0.5% BW using PRO supplementation resulted in better animal performance, primarily greater ADG, than feeding ENE or not supplementing (CON). In conclusion, our results indicate that dairy heifers should be fed a protein supplement when grazing intensively managed Mombaça grass pasture. [ABSTRACT FROM AUTHOR]

The voltage-gated potassium channel KCNQ1 (KV7.1) assembles with the KCNE1 accessory protein to generate the slow delayed rectifier current, IKS, which is critical for membrane repolarization as part of the cardiac action potential. Loss-of-function (LOF) mutations in KCNQ1 are the most common cause of congenital long QT syndrome (LQTS), type 1 LQTS, an inherited genetic predisposition to cardiac arrhythmia and sudden cardiac death. A detailed structural understanding of KCNQ1 is needed to elucidate the molecular basis for KCNQ1 LOF in disease and to enable structure-guided design of new anti-arrhythmic drugs. In this work, advanced structural models of human KCNQ1 in the resting/closed and activated/open states were developed by Rosetta homology modeling guided by newly available experimentally-based templates: X. leavis KCNQ1 and various resting voltage sensor structures. Using molecular dynamics (MD) simulations, the capacity of the models to describe experimentally established channel properties including state-dependent voltage sensor gating charge interactions and pore conformations, PIP2 binding sites, and voltage sensor–pore domain interactions were validated. Rosetta energy calculations were applied to assess the utility of each model in interpreting mutation-evoked KCNQ1 dysfunction by predicting the change in protein thermodynamic stability for 50 experimentally characterized KCNQ1 variants with mutations located in the voltage-sensing domain. Energetic destabilization was successfully predicted for folding-defective KCNQ1 LOF mutants whereas wild type-like mutants exhibited no significant energetic frustrations, which supports growing evidence that mutation-induced protein destabilization is an especially common cause of KCNQ1 dysfunction. The new KCNQ1 Rosetta models provide helpful tools in the study of the structural basis for KCNQ1 function and can be used to generate hypotheses to explain KCNQ1 dysfunction. [ABSTRACT FROM AUTHOR]

Background: This paper is aimed to (i) develop an innovative classification of COPD, multi-dimensional phenotype, based on a multidimensional assessment; (ii) describe the identified multi-dimensional phenotypes. Methods: An exploratory factor analysis to identify the main classificatory variables and, then, a cluster analysis based on these variables were run to classify the COPD-diagnosed 514 patients enrolled in the STORICO (trial registration number: NCT03105999) study into multi-dimensional phenotypes. Results: The circadian rhythm of symptoms and health-related quality of life, but neither comorbidity nor respiratory function, qualified as primary classificatory variables. Five multidimensional phenotypes were identified: the MILD COPD characterized by no night-time symptoms and the best health status in terms of quality of life, quality of sleep, level of depression and anxiety, the MILD EMPHYSEMATOUS with prevalent dyspnea in the early-morning and day-time, the SEVERE BRONCHITIC with nocturnal and diurnal cough and phlegm, the SEVERE EMPHYSEMATOUS with nocturnal and diurnal dyspnea and the SEVERE MIXED COPD distinguished by higher frequency of symptoms during 24h and worst quality of life, of sleep and highest levels of depression and anxiety. Conclusions: Our results showed that properly collected respiratory symptoms play a primary classificatory role of COPD patients. The longitudinal observation will disclose the discriminative and prognostic potential of the proposed multidimensional phenotype. Trial registration: Trial registration number: , date of registration: 10th April 2017. [ABSTRACT FROM AUTHOR]

In many brain areas, sensory responses are heavily modulated by factors including attentional state, context, reward history, motor preparation, learned associations, and other cognitive variables. Modelling the effect of these modulatory factors on sensory responses has proven challenging, mostly due to the time-varying and nonlinear nature of the underlying computations. Here we present a computational model capable of capturing and dissociating multiple time-varying modulatory effects on neuronal responses on the order of milliseconds. The model’s performance is tested on extrastriate perisaccadic visual responses in nonhuman primates. Visual neurons respond to stimuli presented around the time of saccades differently than during fixation. These perisaccadic changes include sensitivity to the stimuli presented at locations outside the neuron’s receptive field, which suggests a contribution of multiple sources to perisaccadic response generation. Current computational approaches cannot quantitatively characterize the contribution of each modulatory source in response generation, mainly due to the very short timescale on which the saccade takes place. In this study, we use a high spatiotemporal resolution experimental paradigm along with a novel extension of the generalized linear model framework (GLM), termed the sparse-variable GLM, to allow for time-varying model parameters representing the temporal evolution of the system with a resolution on the order of milliseconds. We used this model framework to precisely map the temporal evolution of the spatiotemporal receptive field of visual neurons in the middle temporal area during the execution of a saccade. Moreover, an extended model based on a factorization of the sparse-variable GLM allowed us to disassociate and quantify the contribution of individual sources to the perisaccadic response. Our results show that our novel framework can precisely capture the changes in sensitivity of neurons around the time of saccades, and provide a general framework to quantitatively track the role of multiple modulatory sources over time. [ABSTRACT FROM AUTHOR]

Understanding the optimization objectives that shape shoot architectures remains a critical problem in plant biology. Here, we performed 3D scanning of 152 Arabidopsis shoot architectures, including wildtype and 10 mutant strains, and we uncovered a design principle that describes how architectures make trade-offs between competing objectives. First, we used graph-theoretic analysis to show that Arabidopsis shoot architectures strike a Pareto optimal that can be captured as maximizing performance in transporting nutrients and minimizing costs in building the architecture. Second, we identify small sets of genes that can be mutated to shift the weight prioritizing one objective over the other. Third, we show that this prioritization weight feature is significantly less variable across replicates of the same genotype compared to other common plant traits (e.g., number of rosette leaves, total volume occupied). This suggests that this feature is a robust descriptor of a genotype, and that local variability in structure may be compensated for globally in a homeostatic manner. Overall, our work provides a framework to understand optimization trade-offs made by shoot architectures and provides evidence that these trade-offs can be modified genetically, which may aid plant breeding and selection efforts. [ABSTRACT FROM AUTHOR]

Neural correlates of mind wandering: The ability to detect mind wandering as it occurs is an important step towards improving our understanding of this phenomenon and studying its effects on learning and performance. Current detection methods typically rely on observable behaviour in laboratory settings, which do not capture the underlying neural processes and may not translate well into real-world settings. We address both of these issues by recording electroencephalography (EEG) simultaneously from 15 participants during live lectures on research in orthopedic surgery. We performed traditional group-level analysis and found neural correlates of mind wandering during live lectures that are similar to those found in some laboratory studies, including a decrease in occipitoparietal alpha power and frontal, temporal, and occipital beta power. However, individual-level analysis of these same data revealed that patterns of brain activity associated with mind wandering were more broadly distributed and highly individualized than revealed in the group-level analysis. Mind wandering detection: To apply these findings to mind wandering detection, we used a data-driven method known as common spatial patterns to discover scalp topologies for each individual that reflects their differences in brain activity when mind wandering versus attending to lectures. This approach avoids reliance on known neural correlates primarily established through group-level statistics. Using this method for individual-level machine learning of mind wandering from EEG, we were able to achieve an average detection accuracy of 80–83%. Conclusions: Modelling mind wandering at the individual level may reveal important details about its neural correlates that are not reflected when using traditional observational and statistical methods. Using machine learning techniques for this purpose can provide new insight into the varieties of neural activity involved in mind wandering, while also enabling real-time detection of mind wandering in naturalistic settings. [ABSTRACT FROM AUTHOR]

Feed accounts for the greatest proportion of egg production costs and there is substantial variation in feed to egg conversion ratio (FCR) efficiency between individual hens. Despite this understanding, there is a paucity of information regarding layer hen feeding behaviour, diet selection and its impact on feed efficiency. It was hypothesised that variation in feed to egg conversion efficiency between hens may be influenced by feeding behaviour. For this experiment, two 35-bird groups of ISA Brown layers were selected from 450 individually caged hens at 25–30 weeks of age for either low FCR < 1.8 ± 0.02 (high feed efficiency (HFE) or high FCR > 2.1 ± 0.02 (low feed efficiency (LFE)). For each of these 70 hens, intake of an ad-libitum mash diet at 2-minute time intervals, 24 h a day, for 7 days was determined alongside behavioural assessment and estimation of the selection of components of the mash. The group selected for HFE had a lower feed intake, similar egg mass and associated lower FCR when compared with the LFE group. Whilst feed intake patterns were similar between HFE and LFE hens, there was a distinct intake pattern for all layer hens with intake rate increasing from 0300 to 1700 h with a sharp decline to 2200 h. High feed efficiency hens selected a diet with 25% more ash and 4% less gross energy than LFE hens. The LFE hens also spent more time eating with more walking events, but less time spent resting, drinking, preening and cage pecking events as compared with HFE hens. In summary, there was no contrasting diurnal pattern of feed consumption behaviour between the groups ranked on feed efficiency, however high feed efficiency hens consumed less feed and selected a diet with greater ash content and lower gross energy as compared with LFE hens. Our work is now focused on individual hen diet selection from mash diets with an aim of formulating precision, targeted diets for greater feed efficiency. [ABSTRACT FROM AUTHOR]

Objective: Systematic Review was used to evaluate the efficacy and safety of Dalfampridine (DAP) in the treatment of Mobility Disability (MS) in patients with Multiple Sclerosis. Methods: Clinical randomized controlled studies about DAP and placebo in the treatment of Mobility Disability in patients with Multiple Sclerosis until March 2019 were explored by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Literature screening, data extraction, quality assessment, and statistical analysis were performed by using Stata 14.0. Results: 10 papers were included in the meta-analysis, and the number of patients was 2100. In conclusion, the application of DAP in clinical can significantly improve the Mobility Disability of patients [OR = 2.73, 95%CI (1.66, 4.50), P<0.001, I2 = 74.1%] and boost the mobility speed of patients in Timing 24 Minute Walk Test (T24FW) [SMD = 3,08, 95%CI(1,58, 4.58), P<0.001, I2 = 98.7%]. There are no significant differences of the incidence of adverse events [RR = 1.06, 95%CI (0.99, 1.14), P = 0.928, I2 = 0.0%] and urinary tract infection [RR = 1.21, 95%CI(0.91, 1.60), P = 0.145, I2 = 37.2%] between the DAP test group (Doses≤10 mg) and the placebo control group, and the incidence of adverse events [RR = 1.14, 95%CI(1.02, 1.28), P = 0.793, I2 = 0.0%] and urinary tract infection[RR = 3.05, 95%CI(1.04, 8.99), P = 0.680, I2 = 0.0%] for the DAP test group (Doses>10 mg) is a litter higher than the placebo control group. Conclusion: DAP can effectively improve Mobility Disability in patients with Multiple Sclerosis, which is safe and reliable in specific DAP usage doses. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSI) are associated with high mortality. Therefore, reliable methods of detection are of paramount importance. Efficient strategies to improve diagnostic yield of bacteraemia within the emergency department (ED) are needed. We conducted a retrospective analysis of all ED encounters in a high-volume, city-centre university hospital within Germany during a five-year study period from October 2013 to September 2018. A time-series analysis was conducted for all ED encounters in which blood cultures (BCs) were collected. BC detection rates and diagnostic yield of community-onset bacteraemia were compared during the study period (which included 45 months prior to the start of a new diagnostic Antibiotic Stewardship (ABS) bundle and 15 months following its implementation). BCs were obtained from 5,191 out of 66,879 ED admissions (7.8%). Bacteraemia was detected in 1,013 encounters (19.5% of encounters where BCs were obtained). The overall yield of true bacteraemia (defined as yielding clinically relevant pathogens) was 14.4%. The new ABS-related diagnostic protocol resulted in an increased number of hospitalised patients with BCs collected in the ED (18% compared to 12.3%) and a significant increase in patients with two or more BC sets taken (59% compared to 25.4%), which resulted in an improved detection rate of true bacteraemia (2.5% versus 1.8% of hospital admissions) without any decrease in diagnostic yield. This simultaneous increase in BC rates without degradation of yield was a valuable finding that indicated success of this strategy. Thus, implementation of the new diagnostic ABS bundle within the ED, which included the presence of a skilled infectious disease (ID) team focused on obtaining BCs, appeared to be a valuable tool for the accurate and timely detection of community-onset bacteraemia. [ABSTRACT FROM AUTHOR]

Aging is associated with peripheral and central declines in vestibular processing and postural control. Here we used functional MRI to investigate age differences in neural vestibular representations in response to pneumatic tap stimulation. We also measured the amount of body sway in multiple balance tasks outside of the MRI scanner to assess the relationship between individuals’ balance ability and their vestibular neural response. We found a general pattern of activation in canonical vestibular cortex and deactivation in cross modal sensory regions in response to vestibular stimulation. We found that activation amplitude of the vestibular cortex was correlated with age, with younger individuals exhibiting higher activation. Deactivation of visual and somatosensory regions increased with age and was associated with poorer balance. The results demonstrate that brain activations and deactivations in response to vestibular stimuli are correlated with balance, and the pattern of these correlations varies with age. The findings also suggest that older adults exhibit less sensitivity to vestibular stimuli, and may compensate by differentially reweighting visual and somatosensory processes. [ABSTRACT FROM AUTHOR]

Background: As a recognised effective and economical agent for dental caries prevention, fluoride has been used in many different fluoridation schemes implemented across the world. Considering the narrow ‘dose-gap’ between the benefit of caries reduction and the risk of dental fluorosis, it is recommended that fluoride intake is monitored by measuring urinary fluoride excretion. The aim of this scoping review is to map the current literature/evidence on fluoride intake and excretion studies in relation to the study population, settings, type of study design, methodology, and analytical approach. Methods: Embase/Ovid, MEDLINE/Ovid, CINAHL/EBSCO, Scopus/Elsevier were searched for relevant articles until April 2018. Studies were included if they reported intake and excretion of fluoride in healthy humans of all age groups. Findings were explored using a narrative synthesis to summarise studies characteristics and outcome measures. Results: Removal of duplicates from the originally 2295 identified records yielded 1093 studies of which 206 articles were included. Only 21.6% of the studies were conducted in children (<8-year-olds). Most studies (38.8%) used drinking water concentration as a proxy for fluoride intake, whereas only 11.7% measured fluoride intake from all sources. Of the 72 studies that measured dietary fluoride intake, only 10 reported the validity of the employed dietary assessment method. Only 14 studies validated the urine sample collection methods. No information on the validity of the employed analytical method was reported by the majority (64.6%) of studies. Only a small proportion (8.7%) of the included studies investigated the association between fluoride intake and excretion. Conclusion: The findings reveal much variability in terms of conducting the studies and reporting the findings, illustrating a high heterogeneity in data collection across settings and populations. Future studies should provide more detail on sampling technique, measurement protocols (including validation), and on clearly defining the relationship between intake and urinary excretion of fluoride. [ABSTRACT FROM AUTHOR]

Aims: We aimed to provide reference values for speckle-tracking derived systolic and diastolic myocardial deformation markers, and to determine their relation with age, sex, and cardiovascular risk factors. Methods and results: The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study recruited a representative sample of the population of Würzburg, Germany, aged 30–79 years. In a sample of 1818 participants (52% female, mean age 54±12 years) global longitudinal peak systolic strain (GL-PSS, n = 1218), systolic (GL-SSR, n = 1506), and early (GL-EDSR, n = 1506) and late diastolic strain rates (GL-LDSR, n = 1500) were derived from 2D speckle tracking analysis. From a subgroup of 323 individuals without any cardiovascular risk factor, sex- and age-specific reference values were computed. GL-PSS, GL-SSR, and GL-EDSR were associated with sex, GL-EDSR decreased and GL-LDSR increased with age. In the total sample, dyslipidemia was associated with altered GL-PSS, GL-SSR, and GL-EDSR in women but not in men, whereas obesity was associated with less favorable GL-PSS and GL-EDSR in either sex. Hypertension impacted more adversely on systolic and diastolic myocardial deformation in women compared to men (all p<0.01). Conclusion: The female myocardium appeared more vulnerable to high blood pressure and dyslipidemia when compared to men, while obesity was associated with adverse myocardial deformation in either sex. The reference values for echocardiographic myocardial deformation provided for a non-diseased population and their here reported associations with cardiovascular risk factors will inform future observational and intervention studies regarding i) effect sizes and power calculation, ii) cross-study comparisons, and iii) categorization of myocardial deformation in specific patient groups. [ABSTRACT FROM AUTHOR]

Background: Obesity is highly prevalent worldwide. More and more studies have been conducted on the relationship between H. pylori infection and obesity or overweight. But the relationship between them is controversial in the literatures and there is no comprehensive evidence for the correlation. Aim: To evaluate the prevalence of H. pylori infection in Chinese adult subjects who received routine physical examinations and the relationship between H. pylori and obesity. Methods: Literatures on H. pylori infection and obesity in Chinese population were searched in online databases. Relevant data were extracted independently by two researchers and meta-analysis was performed by using Review manager 5.3 software. Results: 22 articles were selected with a total sample size of 178033. The pooled prevalence of H. pylori was 42% (95%CI: 37% to 47%) and mean difference of BMI between subjects with and without H. pylori infection was 0.94 (95%CI: -0.04 to 1.91). 9 eligible studies with 27111 subjects were used to calculated pooled OR value because they contained obesity groups. The OR value showed that H. pylori-positive subjects tended to be obese at a risk of 1.20 (95% CI: 1.13 to 1.28). Conclusion: In China, obesity has association with H. pylori infection. H. pylori infection may be one of the risk factors for obesity. [ABSTRACT FROM AUTHOR]

Congenital nystagmus, involuntary oscillating small eye movements, is commonly thought to originate from aberrant interactions between brainstem nuclei and foveal cortical pathways. Here, we investigated whether nystagmus associated with congenital stationary night blindness (CSNB) results from primary deficits in the retina. We found that CSNB patients as well as an animal model (nob mice), both of which lacked functional nyctalopin protein (NYX, nyx) in ON bipolar cells (BCs) at their synapse with photoreceptors, showed oscillating eye movements at a frequency of 4–7 Hz. nob ON direction-selective ganglion cells (DSGCs), which detect global motion and project to the accessory optic system (AOS), oscillated with the same frequency as their eyes. In the dark, individual ganglion cells (GCs) oscillated asynchronously, but their oscillations became synchronized by light stimulation. Likewise, both patient and nob mice oscillating eye movements were only present in the light when contrast was present. Retinal pharmacological and genetic manipulations that blocked nob GC oscillations also eliminated their oscillating eye movements, and retinal pharmacological manipulations that reduced the oscillation frequency of nob GCs also reduced the oscillation frequency of their eye movements. We conclude that, in nob mice, synchronized oscillations of retinal GCs, most likely the ON-DCGCs, cause nystagmus with properties similar to those associated with CSNB in humans. These results show that the nob mouse is the first animal model for a form of congenital nystagmus, paving the way for development of therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Identification of blood sources of hematophagous arthropods is crucial for understanding the transmission cycles of vector-borne diseases. Many different approaches towards host determination were proposed, including precipitin test, ELISA, DNA- and mass spectrometry-based methods; yet all face certain complications and limitations, mostly related to blood degradation. This study presents a novel method for blood meal identification, peptide mass mapping (PMM) analysis of host-specific hemoglobin peptides using MALDI-TOF mass spectrometry. Methodology/Principal findings: To identify blood meal source, proteins from abdomens of engorged sand fly females were extracted, cleaved by trypsin and peptide fragments of host hemoglobin were sequenced using MALDI-TOF MS. The method provided correct host identification of 100% experimentally fed sand flies until 36h post blood meal (PBM) and for 80% samples even 48h PBM. In females fed on two hosts, both blood meal sources were correctly assigned for 60% of specimens until 36h PBM. In a validation study on field-collected females, the method yielded unambiguous host determination for 96% of specimens. The suitability of PMM-based MALDI-TOF MS was proven experimentally also on lab-reared Culex mosquitoes. Conclusions/Significance: PMM-based MALDI-TOF MS analysis targeting host specific hemoglobin peptides represents a sensitive and cost-effective method with a fast and simple preparation protocol. As demonstrated here on phlebotomine sand flies and mosquitoes, it allows reliable and rapid blood source determination even 48h PBM with minimal material input and provides more robust and specific results than other currently used methods. This approach was also successfully tested on field-caught engorged females and proved to be a promising useful tool for large-scale screening of host preferences studies. Unlike other methods including MALDI-TOF protein profiling, it allows correct identification of mixed blood meals as was demonstrated on both experimentally fed and field-collected sand flies. [ABSTRACT FROM AUTHOR]

A number of studies have shown variable grades of cytotoxicity and genotoxicity in in vitro cell cultures, laboratory animals and humans when directly exposed to particle debris generated from tires. However, no study has compared the effects of particles generated from passenger tires with the effects of particles from truck tires. The aim of this study was to investigate and relate the cyto- and genotoxic effects of different types of particles (PP, passenger tire particles vs. TP, truck tire particles) in vitro using the phagocytic cell line RAW 264.7 (mouse leukaemic monocyte macrophage cell line). The viability of RAW 264.7 cells was determined by the 3- (4,5-dimethylthiazol-2-yl) -5- (3-carboxymethoxyphenyl) -2- (4-sulfophenyl) -2H-tetrazolium (MTS) assay following exposure for 4, 24 and 48 hours to different particle concentrations (10 μg / ml, 25 μg / ml, 50 μg / ml, 100 μg / ml). The effects of particles of passenger and truck tires on cell proliferation and genotoxicity were evaluated by means of the cytokinesis-block micronucleus (CBMN) assay following exposure for 24 hours to different particle concentrations (10 μg / ml, 25 μg / ml, 50 μg / ml, 100 μg / ml). In MTS assay, after 24 hours, it was found that PP induced a 30% decrease in metabolic activity at a concentration of 10 μg/ml, while TP caused reductions of 20% and 10% at concentrations of 10 μg/ml and 50 μg/ml, respectively. At 48 hours after the treatments, we observed increased metabolic activity at 50 μg/ml and 100 μg/ml for the PP while only at 50 μg/ml for the TP. The CBMN assay showed a significant increase in the number of micronuclei in the cells incubated with PP in all experimental conditions, while the cells treated with TP showed a meaningful increase only at 10 μg /ml. We utilized the TNF-α ELISA mouse test to detect the production of tumour necrosis factor-alpha (TNF-α) in RAW 264.7 cells. The effect of passenger and truck particles on TNF-α release was evaluated following exposure for 4 and 24 hours. After 4 hours of incubation, the cells treated with PP and TP at 100 μg / ml showed a slight but significant increase in TNF-α release, while there was a significant increase in the release of TNF-α after 24 hours of incubation with both tire samples in the cells treated with 50 and 100 μg / ml PP. The data obtained show a higher cytotoxic, clastogenic/genotoxic and inflammatory effects of passenger compared to the truck tire particles. [ABSTRACT FROM AUTHOR]

Comparing the efficacy of inhaled antibiotics can be difficult in small groups of patients with cystic fibrosis and mild lung disease. In a feasibility study we compared Aztreonam lysine for inhalation solution (AZLI; Cayston®) to standard inhaled antibiotic therapy in patients with cystic fibrosis and near normal spirometry. To detect treatment responses we used both lung clearance index (LCI) and forced expiratory volume in one second (FEV1). At baseline, median FEV1 was 87% pred. and median LCI was 8.6 (upper limit of normal: 7.0). After 4 weeks, LCI improved by -0.36 after AZLI and deteriorated by +0.12 after tobramycin treatment (p = 0.039). No significant differences between treatments (p = 0.195) were observed using FEV1. These results suggest that lung clearance index can be used to detect treatment induced changes in subjects with mild lung disease. [ABSTRACT FROM AUTHOR]

Aims: Glucocorticoid (GC) stimulation has been shown to increase cardiac contractility by elevated intracellular [Ca] but the sources for Ca entry are unclear. This study aims to determine the role of store-operated Ca entry (SOCE) for GC-mediated inotropy. Methods and results: Dexamethasone (Dex) pretreatment significantly increased cardiac contractile force ex vivo in Langendorff-perfused Sprague-Dawley rat hearts (2 mg/kg BW i.p. Dex 24 h prior to experiment). Moreover, Ca transient amplitude as well as fractional shortening were significantly enhanced in Fura-2-loaded isolated rat ventricular myocytes exposed to Dex (1 mg/mL Dex, 24 h). Interestingly, these Dex-dependent effects could be abolished in the presence of SOCE-inhibitors SKF-96356 (SKF, 2 μM) and BTP2 (5 μM). Ca transient kinetics (time to peak, decay time) were not affected by SOCE stimulation. Direct SOCE measurements revealed a negligible magnitude in untreated myocytes but a dramatic increase in SOCE upon Dex-pretreatment. Importantly, the Dex-dependent stimulation of SOCE could be blocked by inhibition of serum and glucocorticoid-regulated kinase 1 (SGK1) using EMD638683 (EMD, 50 μM). Dex preincubation also resulted in increased mRNA expression of proteins involved in SOCE (stromal interaction molecule 2, STIM2, and transient receptor potential cation channels 3/6, TRPC 3/6), which were also prevented in the presence of EMD. Conclusion: Short-term GC-stimulation with Dex improves cardiac contractility by a SOCE-dependent mechanism, which appears to involve increased SGK1-dependent expression of the SOCE-related proteins. Since Ca transient kinetics were unaffected, SOCE appears to influence Ca cycling more by an integrated response across multiple cardiac cycles but not on a beat-to-beat basis. [ABSTRACT FROM AUTHOR]

We compared a published computational model of the action potential of a specific type of human induced pluripotent stem cell -derived cardiomyocytes (hiPSC-CM) with experimental field potential data with regard to their inter-beat interval and the duration of repolarization. In particular, concomitant changes in inter-beat interval and duration of repolarization were calculated after reduction and/or augmentation of specific ion channel conductances as a surrogate for pharmacological manipulation. The observed mismatches between calculations and experimental data indicate that there is information missing about the cellular test system. Based on our results we hypothesize that, among other currents, the actual If (“funny current”) may deviate from the prediction. We show that replacement of the If formulation by alternative equations causes the model predictions to change qualitatively, however, none of the available formulations is actually achieving a satisfactory match with experimental data. We suggest a strategy to clarify whether the mismatch can be completely resolved at all using single cell models and, if yes, how this goal could be reached. [ABSTRACT FROM AUTHOR]

Personal control relies on the expectation that events are contingent upon one’s own behavior. A common ‘inconsistency compensation approach’ posits that a violation of expectancies in social interaction triggers aversive arousal and compensatory effort. Following this approach, we tested the hypothesis that interventions affecting participants' decisions violate the expected personal control. In a modified version of the established cyberball paradigm, participants were not excluded, but consistently included. However, their decisions regarding the recipient of a ball throw in the virtual game were occasionally overruled (expectancy violation). We hypothesized that this intervention will trigger a P3 response in event-related brain potentials (ERP). Since this component is related to subjective expectancies, its amplitude was assumed to depend on the frequency of interventions (independent factor: loss of control). Further, we manipulated the vertical position of the participants’ avatar on the computer screen (independent factor: verticality). Building on research showing that verticality is related to the self-assigned power and influences the expected level of control, we hypothesized that the ERP effects of intervention should be more pronounced for participants with avatars in superior position. As predicted, both experimental factors interactively affected the expression of the ERP response: In case of low intervention frequency, P3 amplitudes were significantly pronounced if the participants’ avatar was positioned above as compared to below co-players (high > low self-assigned power). The effect of verticality could be traced back to a lack of adaptation of P3 amplitudes to recurring aversive events. By demonstrating that loss of control triggers ERP effects corresponding to those triggered by social exclusion, this study provides further evidence for a common cognitive mechanism in reactions to aversive events based on an inconsistency in expectancy states. [ABSTRACT FROM AUTHOR]

Objective: The mechanism by which G-protein-coupled receptor 40 (GPR40) signaling amplifies glucose-stimulated insulin secretion through activation of protein kinase C (PKC) is unknown. We examined whether a GPR40 agonist, GW9508, could stimulate conventional and novel isoforms of PKC at two glucose concentrations (3 mM and 20 mM) in INS-1D cells. Methods: Using epifluorescence microscopy, we monitored relative changes in the cytosolic fluorescence intensity of Fura2 as a marker of change in intracellular Ca2+ ([Ca2+]i) and relative increases in green fluorescent protein (GFP)-tagged myristoylated alanine-rich C kinase substrate (MARCKS-GFP) as a marker of PKC activation in response to GW9508 at 3 mM and 20 mM glucose. To assess the activation of the two PKC isoforms, relative increases in membrane fluorescence intensity of PKCα-GFP and PKCε-GFP were measured by total internal reflection fluorescence microscopy. Specific inhibitors of each PKC isotype were constructed and synthesized as peptide fusions with the third α-helix of the homeodomain of Antennapedia. Results: At 3 mM glucose, GW9508 induced sustained MARCKS-GFP translocation to the cytosol, irrespective of changes in [Ca2+]i. At 20 mM glucose, GW9508 induced sustained MARCKS-GFP translocation but also transient translocation that followed sharp increases in [Ca2+]i. Although PKCα translocation was rarely observed, PKCε translocation to the plasma membrane was sustained by GW9508 at 3 mM glucose. At 20 mM glucose, GW9508 induced transient translocation of PKCα and sustained translocation as well as transient translocation of PKCε. While the inhibitors (75 μM) of each PKC isotype reduced GW9508-potentiated, glucose-stimulated insulin secretion in INS-1D cells, the PKCε inhibitor had a more potent effect. Conclusion: GW9508 activated PKCε but not PKCα at a substimulatory concentration of glucose. Both PKC isotypes were activated at a stimulatory concentration of glucose and contributed to glucose-stimulated insulin secretion in insulin-producing cells. [ABSTRACT FROM AUTHOR]

How muscles are used is a key to understanding the internal driving of fish swimming. However, the underlying mechanisms of some features of the muscle activation patterns and their differential appearance in different species are still obscure. In this study, we explain the muscle activation patterns by using 3D computational fluid dynamics models coupled to the motion of fish with prescribed deformation and examining the torque and power required along the fish body with two primary swimming modes. We find that the torque required by the hydrodynamic forces and body inertia exhibits a wave pattern that travels faster than the curvature wave in both anguilliform and carangiform swimmers, which can explain the traveling wave speeds of the muscle activations. Notably, intermittent negative power (i.e., power delivered by the fluid to the body) on the posterior part, along with a timely transfer of torque and energy by tendons, explains the decrease in the duration of muscle activation towards the tail. The torque contribution from the body elasticity further clarifies the wave speed increase or the reverse of the wave direction of the muscle activation on the posterior part of a carangiform swimmer. For anguilliform swimmers, the absence of the aforementioned changes in the muscle activation on the posterior part is consistent with our torque prediction and the absence of long tendons from experimental observations. These results provide novel insights into the functions of muscles and tendons as an integral part of the internal driving system, especially from an energy perspective, and they highlight the differences in the internal driving systems between the two primary swimming modes. [ABSTRACT FROM AUTHOR]

Light traps are used to determine the temporal and spatial dynamics of the migratory brown planthoppers (BPHs) Nilaparvata lugens. But very little is known whether newly emerged adults respond to local light traps during the emigration period. Thus, it is important to evaluate the efficiency of light traps in attracting emigrant and immigrant populations to improve forecasting and control of this pest. The migration periods of N. lugens were determined by field surveys in Fuyang, Zhejiang province in 2012 and Yongfu, Guangxi Zhuang Autonomous Region in 2013. Mark-release-recapture experiments with both newly emerged (unflown) and flight experienced (flown) N. lugens were conducted at the two study sites. The marking method did not have any significant effect on the survival or flight capability of the N. lugens. A total of 4800 marked flown and 8400 unflown BPHs were released at a distance of 10, 20 and 30 m from 45-watt fluorescent actinic light traps. The results showed that without wind (< 3.2 m/s) or rainfall conditions, the overall recapture rate of flown BPHs was higher than that of unflown BPHs (9.60% and 0.92%, respectively; χ21 = 589.66, P < 0.0001). Curve estimation regression analysis showed that flown BPHs were attracted to the light source at a distance of 19.77 m, and unflown BPH at a distance of 5.35 m, with these distances corresponding to a 5% recapture rate. Given that the population dynamics of BPHs in the light traps were not synchronous with that in the fields, our results indicate that only a few emerging BPHs in an infested site can be captured locally by light traps. Therefore, care must be taken in estimating the abundance of the sample to absolute local abundance during sedentary and emigration period. [ABSTRACT FROM AUTHOR]

Objectives: The study aim was to determine if a difference exists in skinfold thickness measured by two interchangeable approaches; (1) supraspinale skinfold recommended in the Heath-Carter method and (2) iliac crest skinfold measurement. The question arises as to whether each approach has a similar or different effect on endomorphy determination, and whether there is a possibility to estimate the supraspinale skinfold based on other skinfold measurements. Methods: A group of 186 male and 161 female students participated in this study. Anthropometric examination included all somatic measurements, as recommended in the Heath-Carter protocol, and the iliac crest skinfold measurement. Estimation of the supraspinale skinfold was performed based on the multiple linear regression procedure. Results: Skinfold thickness measured in the supraspinale and iliac crest differed (p<0.001) in both men (5.41±1.65 mm and 9.55±4.05 mm, respectively) and women (8.87±4.08 mm and 15.20±6.85 mm), respectively. Endomorphy was significantly higher (0.46 in men, 0.63 in women) when the iliac crest skinfold was used. Subscapular skinfold and iliac crest skinfolds were included in the linear regression model for supraspinale skinfold estimation (R2 = 0.724, SE = 0.9 mm and R2 = 0.947, SE = 2.3 mm for men and women, respectively). Conclusion: Two common skinfold approaches produced different measurements between the supraspinale and iliac crest skinfolds, which subsequently affected estimated endomorphy. Regression equations for supraspinale skinfold enabled correction of endomorphy in the case of improperly applied measurement (i.e. iliac crest) and thus, could allow for uniform somatotype estimation according to Carter and Heath approach. [ABSTRACT FROM AUTHOR]

Introduction: Heart rate recovery (HRR) is a marker of parasympathetic activity recovery after exercise, and it is associated with cardiovascular mortality and total mortality. Impaired renal function is also associated with cardiac mortality. The aim of this study was to investigate the association between HRR after exercise and renal function in patients referred for a treadmill exercise test. Patients and methods: This cross-sectional study was conducted at a regional hospital in southern Taiwan. Patients who completed a symptom-limited treadmill exercise test from January 2015 to February 2018 were recruited. Before the treadmill exercise test, patients were asked to complete a questionnaire on the past disease history and lifestyle factors. Serum creatinine measurement within two years prior to or after the date of the treadmill exercise test of the patients was also obtained from the medical records for these patients. Estimated glomerular filtration rate (eGFR) was calculated. Simple and multiple linear regression analyses were performed to investigate the association between one-minute HRR and eGFR. Results: A total of 2,825 patients completed the treadmill exercise test, and serum creatinine measurement was identified from medical records for 2,153 patients (76.2%). Multiple linear regression analysis revealed that a lower eGFR was significantly associated with lower one-minute HRR (P< 0.001), adjusting for other significant independent factors, including age, waist circumference, type 2 diabetes mellitus, and smoking. Conclusions: In this cross-sectional observational study, a lower eGFR was significantly and independently associated with decreased one-minute HRR, suggesting that parasympathetic activity recovery after exercise could be impaired by a decrease in renal function. [ABSTRACT FROM AUTHOR]

Introduction: Moderate to vigorous physical activity (MVPA) has been shown to be associated with autonomic regulation of the heart measured with heart rate variability (HRV). Only a limited amount of studies have examined this relationship among adolescents, and the effects of increasing PA on HRV is not well established. The aim of this study was to investigate how overall self-reported PA associates with HRV in a large population of adolescent men. Methods: The study was part of the Finnish MOPO study consisting of 3629 young men (mean age 18, SD 1 years) enrolled for military call-ups in 2009–2013. Overall PA, including both the intensity and frequency of habitual exercise, was assessed by a questionnaire and the respondents categorized into four groups of PA (low, moderate, high and top). Short-term HRV, physical performance and body composition were measured. Results: HRV, as indicated by mean ln rMSSD, increased according the PA categories as follows: low (3.65 ms (SD 0.7), p<0.001 vs. other groups), moderate (3.78 ms (0.6) p<0.001), high (3.85 ms (0.6) p<0.001) and top activity (3.93 ms (0.6) p<0.001) According to the multivariable linear regression analysis, a significant positive relationship (β = 0.129, p<0.05) was observed between self-reported PA and ln rMSSD independent of body mass index, waist circumference and fat percentage. Conclusions: Physical activity was positively associated with cardiac autonomic regulation, in adolescent men. A linear increase in HRV according to PA was observed, suggesting that even slight increments in PA might be beneficial for cardiac autonomic regulation The results emphasize the importance of physical activity in improving cardiac health in young people. [ABSTRACT FROM AUTHOR]

This paper examines whether tobacco expenditure leads to the crowding out or crowding in of different expenditure items in South Africa. We apply genetic matching to expenditure quartiles of the 2010/2011 South African Income and Expenditure Survey. Genetic matching is a more appealing approach for dealing with the endogeneity of tobacco expenditure that often plagues studies using systems of demand equations. Further, genetic matching provides transparent measures of covariate balance giving the analyst objective means of assessing match success. We find that the poorest tobacco consuming households in South Africa consistently allocate smaller budget shares towards food items than non-smoking households. Specifically, we find that dairy, fruits, nuts and oils are displaced in favour of tobacco expenditure in the two poorest quartiles. Unsurprisingly, food items are never displaced for households in the top two quartiles, given these households’ greater access to resources. Like other studies in the literature, we find that tobacco expenditure consistently crowds-in alcohol across all quartiles confirming the strong complementarities between the two. [ABSTRACT FROM AUTHOR]

Bladder urine volume has been estimated using an ellipsoid method based on triaxial measurements of the bladder extrapolated from two-dimensional ultrasound images. This study aimed to automate this process and to determine the accuracy of the automated estimation method for normal and small amounts of urine. A training set of 81 pairs of transverse and longitudinal ultrasound images were collected from healthy volunteers on a tablet-type ultrasound device, and an automatic detection tool was developed using them. The tool was evaluated using paired transverse/longitudinal ultrasound images from 27 other healthy volunteers. After imaging, the participants voided and their urine volume was measured. For determining accuracy, regression coefficients were calculated between estimated bladder volume and urine volume. Further, sensitivity and specificity for 50 and 100 ml bladder volume thresholds were evaluated. Data from 50 procedures were included. The regression coefficient was very similar between the automatic estimation (β = 0.99, R2 = 0.96) and manual estimation (β = 1.05, R2 = 0.97) methods. The sensitivity and specificity of the automatic estimation method were 88.5% and 100.0%, respectively, for 100 ml and were 94.1% and 100.0%, respectively, for 50 ml. The newly-developed automated tool accurately and reliably estimated bladder volume at two different volume thresholds of approximately 50 ml and 100 ml. [ABSTRACT FROM AUTHOR]

Physicochemical properties of water molecules as the main compositions of the freezing media can be affected by the electromagnetic fled. The purpose of this study was to apply extremely low repetition rate electromagnetic fields (ELEFs) to change the molecular network of water molecules existing in freezing media used for human sperm cryopreservation. First, different time periods and pulsed electromagnetic fields were used to evaluate the physiochemical properties of water. The lowest rate of cluster size, surface tension, viscosity, and density was observed for water samples exposed to 1000 Hz ELEF for 60 min (P < 0.05) that could be results in small ice crystal formation. Therefore, this treatment was selected for further evaluations in human sperm freezing because there was minimal probability of amorphous ice crystallization in this group. To assess fertilizing potential, human semen samples were subjected to ELEF (1000 Hz) water-made freezing medium and cryopreserved. The highest percentage of total motility, progressive motility, viability, membrane integrity, mitochondrial membrane potential, DNA integrity, and TAC were obtained in frozen ELEF as compared to other groups. The percentage of viable spermatozoa (Annexin V-/PI-) in frozen ELEF was significantly higher than in frozen control. The level of ROS was significantly lower in frozen ELEF when compared to frozen control. It can be concluded that the modification of physicochemical properties of water existing in cryopreservation media by ELEF is a suitable strategy to improve the outcome of cryopreservation. [ABSTRACT FROM AUTHOR]

Proteases are multifunctional, promiscuous enzymes that degrade proteins as well as peptides and drive important processes in health and disease. Current technology has enabled the construction of libraries of peptide substrates that detect protease activity, which provides valuable biological information. An ideal library would be orthogonal, such that each protease only hydrolyzes one unique substrate, however this is impractical due to off-target promiscuity (i.e., one protease targets multiple different substrates). Therefore, when a library of probes is exposed to a cocktail of proteases, each protease activates multiple probes, producing a convoluted signature. Computational methods for parsing these signatures to estimate individual protease activities primarily use an extensive collection of all possible protease-substrate combinations, which require impractical amounts of training data when expanding to search for more candidate substrates. Here we provide a computational method for estimating protease activities efficiently by reducing the number of substrates and clustering proteases with similar cleavage activities into families. We envision that this method will be used to extract meaningful diagnostic information from biological samples. [ABSTRACT FROM AUTHOR]

Multiple cross-sectional studies have shown that regular complex exercises, which require cognitive demands (e.g., decision making) and various motions, are associated with greater positive effects on executive functions compared to simple exercises. However, the evidence of a single bout of complex exercises is mixed, and investigations on the acute effect of complex exercise using a well-controlled within-subjects research design are few. Therefore, we compared the acute effects of complex exercise on inhibitory functions with those of simple running. Twenty young adults performed three interventions, which were running, badminton, and seated rest as a control condition for 10 min each. During each intervention, oxygen consumption and heart rate were monitored. A Stroop test and a reverse-Stroop test were completed before and after each intervention. The intensities of the badminton and running were equivalent. Badminton significantly improved performance on the Stroop task compared to seated rest; however, running did not enhance performance on the Stroop task relative to seated rest. A single bout of complex exercise elicits a larger benefit to inhibitory function than a single bout of simple exercise. However, the benefit of complex exercise may vary depending on the type of executive functions. [ABSTRACT FROM AUTHOR]

Inducing unconsciousness in fish using electrical stunning prior to slaughter may improve fish welfare and fillet quality if such practises can be disseminated into wild capture fisheries. The objectives of this study were to: 1) evaluate if an established slaughter protocol consisting of dry electrical stunning (using a coupled AC/DC current at ≈ 110 Vrms) followed by chilling could be used to stun the wild captured species Atlantic mackerel (Scomber scombrus) unconscious within 0.5 s; 2) determine if death could be induced without consciousness recovery by longer duration stunning (5 s) combined with chilling in an ice/water slurry for 6 min; and 3) examine the extent of quality defects arising from the applied slaughter protocol. We determined consciousness by examination of behavioural responses in a standardised vitality assessment. Out of a sample of 10 mackerel, 9 were assumed to be rendered unconscious by the 0.5 s stun, as determined by the presence of tonic and/or clonic muscle cramping consistent with a general epileptic insult. Assumed unconsciousness was maintained throughout chilling treatment in all fish (n = 25) following a full stun of 5 s. All fish were assumed to have died as a result of the protocol. There was no evidence of spinal damage or haematoma quality defects post filleting. These results suggest that the examined protocol is effective at slaughtering mackerel in a manner consistent with good welfare and without inducing quality defects, but further research is required to verify the unconscious condition via electroencephalogram (EEG) and before the procedure can be applied in wild capture fisheries. [ABSTRACT FROM AUTHOR]

Similarity between targets and distracters is a key factor in generating distractibility, and exerts a large detrimental effect on aging. The present EEG study tested the role of a new stimulus dimension in generating distractibility in visual Working Memory (vWM), namely numerical similarity. In a change detection paradigm a varying number of relevant and irrelevant stimuli were presented simultaneously in opposite hemifields. Behavioral results indicated that young participants outperformed older individuals; however, in both groups numerical similarity per se did not modulate performance. At the electrophysiological level, in young participants the Contralateral Delay Activity (CDA, a proxy for item maintenance in vWM) was modulated by the numerosity of the relevant items regardless of numerical similarity. In older participants, the CDA was modulated by target numerosity only in the same numerical condition, where the total number of (relevant and irrelevant) items increased with increasing target numerosities. No effect was present in the dissimilar numerical condition, where the total number of items did not vary substantially across target numerosity. This pattern was suggestive of an age-related effect of the total number of (relevant and irrelevant) items on vWM. The additional analyses on alpha-band lateralization measures support this interpretation by revealing that older adults lacked selective deployment of attentional and vWM resources towards the relevant hemifield. Overall, the results indicate that, while numerical similarity does not modulate distractibility, there is an age-related redistribution of vWM resources across the two visual fields, ultimately leading to a general decrease in task performance of older adults. [ABSTRACT FROM AUTHOR]

This study reevaluates the tooth morphology used to define species within the genus Edestus (Chondrichthyes, Euchondrocephali). Known as the scissor tooth shark, Edestus produced a unique dentition of spiraled tooth families positioned in the symphysis (midline) of the upper and lower jaws. Morphometric analysis of more than 200 ejected teeth and intact spiral tooth whorls demonstrates that teeth from the upper and lower whorls differ in shape and ontogeny. Comparison of these data to the type specimens of 13 existing species reduces the number of morphologically distinct Edestus to just four species and refines the stratigraphic occurrence and expansion of the group. E. triserratus has a narrow bullet-shaped crown that points anteriorly and has roots of intermediate length. E. minor crowns have a wider triangular base, whereas the crowns of E. heinrichi form nearly equilateral triangles and are supported by an elongated root. E. vorax, which also has roughly equilateral triangular crowns, has short and deep roots, and is only known from very large specimens that are distinct from the growth series of E. heinrichi. Tooth and whorl morphologies among the species are consistent with cranial anatomy observed in a juvenile E. heinrichi and with transverse tooth-wear patterns to suggest Edestus used a forward to backward slicing motion to bite its prey. Extrapolating body size from tooth whorl length provides a conservative estimate that E. heinrichi could exceed 6.7 m in length. Edestus fossils are recovered from coastal marine to estuarine deposits spanning roughly six million years (313–307 Ma). Edestus first appears in England during the latest Bashkirian (313 Ma, Carboniferous), a few million years after its most closely resembling genus Lestrodus. Diversification and range expansion of Edestus coincides with the Moscovian transgression that flooded Laurentia and the Russian platform. [ABSTRACT FROM AUTHOR]

Side effects caused by radiation are a limiting factor to the amount of dose that can be applied to a tumor volume. A novel method to reduce side effects in radiotherapy is the use of spatial fractionation, in which a pattern of sub-millimeter beams (minibeams) is applied to spare healthy tissue. In order to determine the skin reactions in dependence of single beam sizes, which are relevant for spatially fractionated radiotherapy approaches, single pencil beams of submillimeter to 6 millimeter size were applied in BALB/c mice ears at a Small Animal Radiation Research Platform (SARRP) with a plateau dose of 60 Gy. Radiation toxicities in the ears were observed for 25 days after irradiation. Severe radiation responses were found for beams ≥ 3 mm diameter. The larger the beam diameter the stronger the observed reactions. No ear swelling and barely reddening or desquamation were found for the smallest beam sizes (0.5 and 1 mm). The findings were confirmed by histological sections. Submillimeter beams are preferred in minibeam therapy to obtain optimized tissue sparing. The gradual increase of radiation toxicity with beam size shows that also larger beams are capable of healthy tissue sparing in spatial fractionation. [ABSTRACT FROM AUTHOR]

Functional variability among boys with Duchenne muscular dystrophy (DMD) is well recognised and complicates interpretation of clinical studies. We hypothesised that boys with DMD could be clustered into groups sharing similar trajectories of ambulatory function over time, as measured by the North Star Ambulatory Assessment (NSAA) total score. We also explored associations with other variables such as age, functional abilities, and genotype. Using the NorthStar Clinical Network database, 395 patients with >1 NSAA assessment were identified. We utilised latent class trajectory analysis of longitudinal NSAA scores, which produced evidence for at least four clusters of boys sharing similar trajectories versus age in decreasing order of clinical severity: 25% of the boys were in cluster 1 (NSAA falling to ≤ 5 at age ~10y), 35% were in cluster 2 (NSAA ≤ 5 ~12y), 21% in were cluster 3 (NSAA≤ 5 ~14y), and 19% in cluster 4 (NSAA > 5 up to 15y). Mean ages at diagnosis of DMD were similar across clusters (4.2, 3.9, 4.3, and 4.8y, respectively). However, at the first NSAA assessment, a significant (p<0.05) association was observed between earlier declining clusters and younger age, worse NSAA, slower rise from supine, slower 10 metre walk/run times, and younger age of steroid initiation. In order to assess the probability of observing complete loss of function for individual NSAA items, we examined the proportion of patients who shifted from a score of 1 or 2 at baseline to a score of 0. We also assessed the probability of gain of function using the inverse assessment and stratified the probability of deterioration, improvement–or static behavior–by age ranges and using baseline functional status. Using this tool, our study provides a comprehensive assessment of the NSAA in a large population of patients with DMD and, for the first time, describes discrete clusters of disease progression; this will be invaluable for future DMD clinical trial design and interpretation of findings. [ABSTRACT FROM AUTHOR]

uman ther-à-go-go-elated ene (Kv11.1, or hERG) is a potassium channel that conducts the delayed rectifier potassium current (IKr) during the repolarization phase of cardiac action potentials. hERG channels have a larger pore than other K+channels and can trap many unintended drugs, often resulting in acquired LQTS (aLQTS). R-roscovitine is a cyclin-dependent kinase (CDK) inhibitor that induces apoptosis in colorectal, breast, prostate, multiple myeloma, other cancer cell lines, and tumor xenografts, in micromolar concentrations. It is well tolerated in phase II clinical trials. R-roscovitine inhibits open hERG channels but does not become trapped in the pore. Two-electrode voltage clamp recordings from Xenopus oocytes expressing wild-type (WT) or hERG pore mutant channels (T623A, S624A, Y652A, F656A) demonstrated that compared to WT hERG, T623A, Y652A, and F656A inhibition by 200 μM R-roscovitine was ~ 48%, 29%, and 73% weaker, respectively. In contrast, S624A hERG was inhibited more potently than WT hERG, with a ~ 34% stronger inhibition. These findings were further supported by the IC50 values, which were increased for T623A, Y652A and F656A (by ~5.5, 2.75, and 42 fold respectively) and reduced 1.3 fold for the S624A mutant. Our data suggest that while T623, Y652, and F656 are critical for R-roscovitine-mediated inhibition, S624 may not be. Docking studies further support our findings. Thus, R-roscovitine’s relatively unique features, coupled with its tolerance in clinical trials, could guide future drug screens. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe the physical demands during U18 elite basketball games according to the game quarter and to identify a smaller subset of variables and threshold scores that distinguish players’ physical performance in each quarter. Methods: Data was collected from ninety-four players who participated in the study (age: 17.4 ± 0.74 years; height: 199.0 ± 0.1 cm; body mass: 87.1 ± 13.1 kg) competing in the Euroleague Basketball Next Generation Tournament. Players’ movements during the games were measured using a portable local positioning system (LPS) (WIMU PRO®, Realtrack Systems SL, Almería, Spain) and included relative distance (total distance / playing duration), relative distance in established speed zones, high-intensity running (18.1–24.0 km·h-1) and sprinting (> 24.1 km·h-1). player load, peak speed (km·h-1) and peak acceleration (m·s-2) number of total accelerations and total decelerations, high intensity accelerations (> 2 m·s-2) and decelerations (< -2 m·s-2). Results: There was an overall decrease in distance covered, player load, number of high intensity accelerations and decelerations between the first and last quarter of the games in all playing positions. A classification tree analysis showed that the first quarter had much influence of distance covered (above 69.0 meters), distance covered <6.0 km·h-1 and accelerations (> 2 m·s-2), whereas the fourth quarter performance had much influence of distance covered (below 69.0) and distance covered 12.1–18.0 km·h-1. Conclusions: A significant reduction in physical demands occurs during basketball, especially between first and last quarter for players in all playing positions during basketball games of under 18 elite players. [ABSTRACT FROM AUTHOR]

Objectives: To analyze health effects of mindfulness- and acceptance-based interventions, including mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT) and acceptance and commitment therapy (ACT). Additionally, we aimed to explore content and delivery components in terms of procedure, instructors, mode, length, fidelity and adherence in the included interventions. Methods: We performed a systematic literature search in the databases MEDLINE, PsychINFO, CINAHL, EMBASE, Cochrane Central and AMED from 1990 to January 2019. We included randomized and quasi-randomized controlled trials analyzing health effects of mindfulness- and acceptance-based interventions for patients with fibromyalgia compared to no intervention, wait-list control, treatment as usual, or active interventions. MBSR combined with other treatments were included. Predefined outcomes were pain, fatigue, sleep quality, psychological distress, depression, anxiety, mindfulness, health-related quality of life and work ability. The Template for Intervention Description and Replication (TIDieR) checklist and guide was used to explore content and delivery components in the interventions. Meta-analyses were performed, and GRADE was used to assess the certainty in the evidence. Results: The search identified 4430 records, of which nine original trials were included. The vast majority of the participants were women. The analyses showed small to moderate effects in favor of mindfulness- and acceptance-based interventions compared to controls in pain (SMD -0.46 [95% CI -0.75, -0.17]), depression (SMD -0.49 [95% CI -0.85, -0.12]), anxiety (SMD -0.37 [95% CI -0.71, -0.02]), mindfulness (SMD -0.40 [-0.69, -0.11]), sleep quality (SMD -0.33 [-0.70, 0.04]) and health-related quality of life (SMD -0.74 [95% CI -2.02, 0.54]) at end of treatment. The effects are uncertain due to individual study limitations, inconsistent results and imprecision. Conclusion: Health effects of mindfulness- and acceptance-based interventions for patients with fibromyalgia are promising but uncertain. Future trials should consider investigating whether strategies to improve adherence and fidelity of mindfulness- and acceptance-based interventions can improve health outcomes. [ABSTRACT FROM AUTHOR]

Previously we have described the V2-directed CAP256-VRC26 lineage that includes broadly neutralizing antibodies (bNAbs) that neutralize globally diverse strains of HIV. We also identified highly mutated “off-track” lineage members that share high sequence identity to broad members but lack breadth. Here, we defined the mutations that limit the breadth of these antibodies and the probability of their emergence. Mutants and chimeras between two pairs of closely related antibodies were generated: CAP256.04 and CAP256.25 (30% and 63% breadth, respectively) and CAP256.20 and CAP256.27 (2% and 59% breadth). Antibodies were tested against 14 heterologous HIV-1 viruses and select mutants to assess breadth and epitope specificity. A single R100rA mutation in the third heavy chain complementarity-determining region (CDRH3) introduced breadth into CAP256.04, but all three CAP256.25 heavy chain CDRs were required for potency. In contrast, in the CAP256.20/27 chimeras, replacing only the CDRH3 of CAP256.20 with that of CAP256.27 completely recapitulated breadth and potency, likely through the introduction of three charge-reducing mutations. In this individual, the mutations that limited the breadth of the off-track antibodies were predicted to occur with higher a probability than those in the naturally paired bNAbs, suggesting a low barrier to the evolution of the off-track phenotype. Mapping studies to determine the viral immunotypes (or epitope variants) that selected off-track antibodies indicated that unlike broader lineage members, CAP256.20 preferentially neutralized viruses containing 169Q. This suggests that this globally rare immunotype, which was common in donor CAP256, drove the off-track phenotype. These data show that affinity maturation to counter globally rare viral immunotypes can drive antibodies within a broad lineage along multiple pathways towards strain-specificity. Defining developmental pathways towards and away from breadth may facilitate the selection of immunogens that elicit bNAbs and minimize off-track antibodies. [ABSTRACT FROM AUTHOR]

Background: In Fetal Growth Restriction ‘fetal programming’ may take place via DNA methylation, which has implications for short-term and long-term health outcomes. Small-for-gestational age fetuses are considered fetal growth restricted, characterized by brain-sparing when fetal Doppler hemodynamics are abnormal, expressed as a cerebroplacental ratio (CPR) <1. We aimed to determine whether brain-sparing is associated with altered DNA methylation of selected genes. Methods: We compared DNA methylation of six genes in 41 small-for-gestational age placentas with a normal or abnormal CPR. We selected EPO, HIF1A, VEGFA, LEP, PHLDA2, and DHCR24 for their role in angiogenesis, immunomodulation, and placental and fetal growth. DNA methylation was analyzed by pyrosequencing. Results: Growth restricted fetuses with an abnormal CPR showed hypermethylation of the VEGFA gene at one CpG (VEGFA-309, p = .001) and an overall hypomethylation of the LEP gene, being significant at two CpGs (LEP-123, p = .049; LEP-51, p = .020). No differences in methylation were observed for the other genes. Conclusions: VEGFA and LEP genes are differentially methylated in placentas of small-for-gestational age fetuses with brain-sparing. Hypermethylation of VEGFA-309 in abnormal CPR-placentas could indicate successful compensatory mechanisms. Methylation of LEP-51 is known to suppress LEP expression. Hypomethylation in small-for-gestational age placentas with abnormal CPR may result in hyperleptinemia and predispose to leptin-resistance later in life. [ABSTRACT FROM AUTHOR]

Background: Mobile accelerometry is a powerful and promising option to capture long-term changes in gait in both clinical and real-world scenarios. Increasingly, gait parameters have demonstrated their value as clinical outcome parameters, but validation of these parameters in elderly patients is still limited. Objective: The aim of this study was to implement a validation framework appropriate for elderly patients and representative of real-world settings, and to use this framework to test and improve algorithms for mobile accelerometry data in an orthogeriatric population. Methods: Twenty elderly subjects wearing a 3D-accelerometer completed a parcours imitating a real-world scenario. High-definition video and mobile reference speed capture served to validate different algorithms. Results: Particularly at slow gait speeds, relevant improvements in accuracy have been achieved. Compared to the reference the deviation was less than 1% in step detection and less than 0.05 m/s in gait speed measurements, even for slow walking subjects (< 0.8 m/s). Conclusion: With the described setup, algorithms for step and gait speed detection have successfully been validated in an elderly population and demonstrated to have improved performance versus previously published algorithms. These results are promising that long-term and/or real-world measurements are possible with an acceptable accuracy even in elderly frail patients with slow gait speeds. [ABSTRACT FROM AUTHOR]

Introduction: Eating breakfast has been proved to positively influence human health. However, evidence for the association between breakfast consumption and depressive symptoms is lacking, especially among young adults. The aim of this study was to determine whether breakfast consumption is associated with depressive symptoms among Chinese university students. Methods: A cross-sectional study involving 10,174 undergraduate students (6,287 males and 3,887 females) was conducted in 2015. Breakfast consumption was assessed using a self-reported questionnaire. Depressive symptoms were assessed using the Zung self-rating depression scale (SDS) score. Three cut-off values of the SDS score (40, 45, and 50) were used to assess the severity of the depressive symptoms. Logistic regression models were used to analyze the association between the frequency of breakfast consumption and depressive symptoms. Results: The mean SDS score was 37.1±8.0 in present study. In crude model, a higher frequency of breakfast consumption was primarily associated with a lower prevalence of depressive symptoms in all three SDS groups (p = 0.001, < 0.001, = 0.009 for SDS cut-off value 40, 45, and 50 points, respectively). These associations remained significant after adjustment for confounding factors. Conclusions: A higher frequency of breakfast consumption was strongly associated with a lower prevalence of depressive symptoms among Chinese university students. These results corroborate the evidence that the habit of eating breakfast may be beneficial to mental health. [ABSTRACT FROM AUTHOR]

Rats are highly social creatures that produce ultrasonic vocalizations (USVs) during social interactions. Brattleboro rats, a Long-Evans derived rat that lacks vasopressin (AVP) due to a mutation in the Avp gene, exhibit atypical social behavior, including fewer USVs with altered spectrotemporal characteristics during social interactions. It is unclear why Brattleboro rats produce atypical USVs, but one factor could be differences in auditory acuity between them and wild-type Long Evans rats with functional vasopressin. Previous studies have suggested a link between increased levels of AVP and auditory processing. Additionally, few studies have investigated sex differences in auditory perception by Long-Evans rats. Sex differences in auditory acuity have been found throughout the animal kingdom, but have not yet been demonstrated in rat audiograms. This study aimed to measure auditory brainstem response (ABR) derived audiograms for frequencies ranging from 1 to 64 kHz in male and female homozygous Brattleboro (Hom), heterozygous Brattleboro (Het), and wild-type (WT) Long-Evans rats to better understand the role of AVP and sex differences in auditory processing by these rats. We failed to detect significant differences between the ABR audiograms of Hom, Het, and WT Long-Evans rats, suggesting that varying levels of AVP do not affect auditory processing. Interestingly, males and females of all genotypes did differ in their ABR thresholds, with males exhibiting higher thresholds than females. The sex differences in auditory acuity were significant at the lowest and highest frequencies, possibly affecting the perception of USVs. These are the first known sex differences in rat audiograms. [ABSTRACT FROM AUTHOR]