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Biofluorescence is widely documented in marine organisms, yet few studies exist for decapods. After observing the king crab Paralithodes camtschaticus biofluoresces, we carried out studies on two separately maintained groups of male crabs under controlled conditions. Hyperspectral imaging on Group 1 (n = 18) examined the exoskeleton, whereas fluorospectrometry examined the hemolymph of Group 2 animals (n = 19). Both groups were investigated for fluorescence signals before and after exposure to a live shipping transportation simulation. The spines, chelae, eyestalks and cervical grooves of the cardiac region of P. camtschaticus fluoresce in the green spectra (∼500 nm), while the arthrodial membranes of the joints fluoresce in the red spectrum (∼680 nm). After the shipping simulation, we observed a significant decrease in fluorescence in the eyestalks (p = 0.009), while the cervical grooves showed a less significant change (p = 0.01). The hemolymph examined with 21 excitation wavelengths (250–350 nm) emitted fluorescence in ∼400–550 nm spectrum. We found a significant increase (p < 0.05) in fluorescence for 16 excitation wavelengths after transport simulation. The results presented in this study indicate that king crab fluorescence changes due to external stimuli. Fluorospectroscopy or hyperspectral imaging technology may serve as an effective early indicator of preclinical stress in these commercially important decapods. [ABSTRACT FROM AUTHOR]

Although the effects of openness to experience (OTE) on individual creativity are well‐established, research on how such effects unfold in a team context is scarce. Drawing on theories of group norms and uncertainty reduction, we argue that team mean OTE leads to a climate of team psychological safety which, in turn, facilitates team creativity. We test our hypothesis over three independent studies, the first comprising 35 business student project teams, the second based on 28 professional teams from the automotive industry, both conducted in the United Kingdom, and the third comprising 24 healthcare teams in Portugal. As predicted, across all three studies, team mean OTE was positively associated with team creativity via the affective emergent state of team psychological safety. Furthermore, the mediating role of team psychological safety remained significant even when accounting for team OTE variance, alternative motivational and cognitive emergent states, namely team promotion focus (studies 1 and 2) and team exploration climate (study 3), as well as empowering leadership (study 3). Finally, in study 3, we examined the differential impact of the two major facets of OTE, intellect, and openness, and found that intellect, but not openness, was responsible for driving the indirect effects. Further analysis did not support alternative perspectives concerning team OTE variance or the interaction between mean and variance. Our findings not only contribute to theoretical understanding regarding the relationship between team personality composition, specifically OTE, and team creativity but also provide much‐needed insight into how such effects unfold. We delineate several practical implications for team design and development. [ABSTRACT FROM AUTHOR]

Background: The prevalence of cognitive impairment (CI) and dementia in end‐stage chronic kidney disease (CKD) has been estimated at 30‐60%. Cardiovascular dysfunction accompanies CKD and contributes to CI in humans and animal models. Since CKD occurs more often in females in clinical studies, the aim of this study was to determine whether cardiovascular and renal remodeling is associated with cognitive performance in the female rats with CKD. Methods: Four‐month‐old female Sprague‐Dawley rats were fed with 0.25% adenine diet to induce CKD (n = 19) or a regular control diet (n = 16; CTRL) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), blood urea nitrogen (BUN), sodium, potassium, creatinine, hematocrit, estradiol, and behavioral tests were assessed at the end of the study. The level of anxiety was tested in open field test (OFT) and elevated plus maze (EPM). Spatial memory was tested by the ability to find a hidden platform in Morris water maze (MWM). The data were analyzed by two‐tailed unpaired t‐test and linear regression analysis (LRA). Results: CKD was associated with higher creatinine and BUN, lower hematocrit, and enlarged hearts, aortae and kidneys vs. CTRL (Table 1). There was no difference in BP, estradiol, sodium and potassium, MWM, OFT and EPM performance between the groups. However, the LRA revealed the association of higher heart weights with a reduced spatial memory and higher anxiety level in both CTRL and CKD (Table 2; Figure 1A,B). The association of higher aortic weight with a reduced spatial memory, and higher kidney weight with higher anxiety levels was demonstrated in CKD only (Table 2; Figure 1C,D). Estradiol was associated with better spatial memory in CKD (LRA: R2 = 0.264; p = 0.04). Conclusion: Anxiety‐like behavior and spatial memory were associated with cardiovascular remodeling in young female rats with CKD. We suggest that (1) CKD stimulates development of cardiovascular remodeling, which may affect blood supply of cortex and hippocampus, responsible for anxiety and spatial memory, and (2) estradiol may contribute to a better cognitive performance in the young CKD female rats. The future direction is to investigate whether CKD influences the trajectory of neurocognitive and cardiovascular aging. Supported by NIA/NIH/IRP [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVD), including increased central arterial stiffness (CAS), accompany chronic kidney disease (CKD) development. An increase in pulse wave velocity (PWV), an index for CAS, is implicated in age‐associated changes in the brain and potentiates the development of CI in CVD and CKD in humans and animal models. The aim of this study was to determine whether inducing CKD accelerates the development of CI and CAS in aged male and female rats. Method: Ten months‐old male and female Sprague‐Dawley rats were fed with 0.25% adenine diet to accelerate CKD (n = 10‐12; CKD‐male, CKD‐female) or regular diet (n = 8‐10; CNT‐male, CNT‐female) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), aortic‐PWV (aPWV), behavioral tests, blood urea nitrogen (BUN), creatinine and hematocrit were assessed at the endpoint. The anxiety‐like behavior was tested in open field test (OFT) and elevated plus maze (EPM). Morris water maze (MWM) and cross maze (CM) were used to test spatial memory. The data were analyzed using two‐way ANOVA. Result: CKD development in both sexes was accompanied by kidneys enlargement, increase in BUN and creatinine, and reduction in hematocrit. In CKD‐male the kidney function was more compromised with higher levels of BUN and creatinine vs. CKD‐female (Table 1). CKD‐male had lower BW and SBP vs. CNT‐male (Table 1). CKD induced a reduction in HR, increase in aPWV and aortic weight in both sexes vs. respective CNT‐groups (Figure 1). Both CKD‐male and CKD‐female demonstrated a tendency of increase in path length to find the hidden platform in MWM, e.g., both sexes had numerically impaired spatial memory. CKD‐male spent less time in the center of OFT, a measure of anxiety, and loss of spatial memory, with a reduction of spontaneous alternation task assessed by CM. CKD‐female exhibited higher level of anxiety spending less time in open arm of EPM vs. CNT‐female (Figure 2). Conclusion: CKD development in old male and female Sprague‐Dawley rats was accompanied by an increase in CAS, cardiovascular remodeling, and cognitive dysfunction. In CKD, CI affected different cognitive domains in the old males than in the age‐matched females. Supported by NIA/NIH/IRP [ABSTRACT FROM AUTHOR]

Background: Advanced‐staging radiography is used inconsistently for patients with early‐stage (stage I + II) breast cancer. However, accurate and appropriate staging of newly diagnosed breast cancer may significantly impact treatment decisions. Methods: Four hundred and ninety‐nine patients with stages II and III breast cancer were seen in the breast service at Waitemata DHB, New Zealand from 2013 to 2018 were enrolled in the study and audited for radiological staging. Results: One hundred and two stage II patients had computed tomography (CT) at baseline; 88 of 102 (86%) of stage II patients were node‐positive (≥N1) with six patients (6.8%) having distant metastatic disease, and were upstaged to stage IV. Fifty‐two stage III patients out of 72 (72%) had baseline staging CTs. Nine out of 52 patients (17%) of stage III patients were upstaged to stage IV. Despite guideline recommendations, baseline staging for T4 disease (stage IIIB) was poor, with only 7 out of 13 patients with stage IIIB disease radiologically staged. Conclusion: Consideration for baseline radiological staging should be given to stages II and III, cN1 breast cancer patients, in which diagnosis of distant metastatic disease would change the treatment plan. Regional guidelines for baseline radiological staging for breast cancer patients may have an impact on patient management in breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Photobiological modulation (PBM) therapy, a form of low‐dose light therapy, is beneficial in treating various disease conditions including Alzheimer's disease (AD). Double‐transgenic mice (APPswe/PS1dE9) develop progressive accumulation of amyloid‐β (Aβ) plaques, cognitive impairment, and alterations in cardiovascular structure and function, and represent a model of AD. Prior studies have shown that PBM therapy reduces the size and number of Aβ plaques in the neocortex and hippocampus in the mouse models of AD. The aim of this study was to investigate the effects of PBM on cardiovascular structure and function and cognitive function in the aged AD mice. Methods: Six‐month old female AD (APPswe/PS1dE9; AD‐PBM, n = 8) and wild type mice (WT‐PBM, n = 8) were exposed to near‐infrared light (wavelength 850 nm, 4.5 J/cm2, 3min/day, 5 days/week) for 6 months. Control mice (AD‐CNT, n = 6; WT‐CNT, n = 6) were placed under the PBM apparatus without turning the light on for 3min/day, 5 days/week. Cardiac parameters were measured by echocardiography. Gait analysis (DigiGait), home cage activity (HCA), and spatial working memory (indicated by alternation rate in cross maze test, CM) were assessed after 6 months of treatment. Group differences were identified by two‐way ANOVA. Results: In HCA test, the AD‐CNT mice exhibited circadian locomotor hyperactivity at night‐time relative to WT‐CNT mice (Figure 1A, B), which was reduced by PBM. AD‐CNT mice had lower alternation rates in CM, indicating spatial working memory impairment. PBM had minimal effect on this parameter (Table 1). The AD‐CNT vs. WT‐CNT mice manifested differences in several gait parameters, specifically, they demonstrated a lower fore propel time than WT‐CNT. PBM normalized this parameter in AD‐PBM mice to the level of WT‐CNT (Figure 1C). Both WT‐PBM and AD‐PBM mice had improved cardiovascular structure, which was demonstrated by lower relative wall thickness of left ventricle (LV) and LV mass, and higher LV volume at the end of diastole in PBM‐treated vs. correspondent CNT groups (Table 1, Figure 2). Conclusion: PBM improved cardiovascular structure and AD‐associated cognitive impairment in the APP/PS1 mouse model. It is possible that more effective cardiovascular structure and function contributes to Aβ removal from the brain after PBM treatment. Supported by NIA/NIH/IRP [ABSTRACT FROM AUTHOR]

The radiotracer 1‐(2‐[18F]fluoroethyl)‐L‐tryptophan (L‐[18F]FETrp or [18F]FETrp) is a substrate of indoleamine 2,3‐dioxygenase, the initial and key enzyme of the kynurenine pathway associated with tumoral immune resistance. In preclinical positron emission tomography studies, [18F]FETrp is highly accumulated in a wide range of primary and metastatic cancers, such as lung cancer, prostate cancer, and gliomas. However, the clinical translation of this radiotracer into the first‐in‐human trial has not been reported, partially due to its racemization during radiofluorination which renders the purification of the final product challenging. However, efficient purification is essential for human studies in order to assure radiochemical and enantiomeric purity. In this work, we report a fully automated radiosynthesis of [18F]FETrp on a Synthra RNPlus research module, including a one‐pot two steps radiosynthesis, dual independent chiral and reverse‐phase semipreparative high‐performance liquid chromatography purifications, and solid‐phase extraction‐assisted formulation. The presented approach has led to its Investigational New Drug application and approval that allows the testing of this tracer in humans. [ABSTRACT FROM AUTHOR]

This article describes the second blind simulation competition (BSC) organized by the fib WG 2.4.1, which aims to assess the predictive performance of models based on the finite element method (FEM) for the analysis and design of fiber reinforced concrete (FRC) structures. Slabs supported on columns or piles have becoming competitive applications for FRC due to the technical and economic benefits may be obtained by combining properly the fiber reinforcement mechanisms to those provided by conventional reinforcement placed, as a strip, in the alignment of columns/piles. Therefore, a representative zone of this structural system, namely a hybrid fiber reinforced concrete (R/FRC) shallow beam, is chosen in this BSC to show the potentialities of FRC in these types of applications, as well as to assess the predictive performance of FEM‐based computational models on the design verification at serviceability and at ultimate limit state conditions (SLS and ULS, respectively). Two statically indeterminate shallow beams of two equal spans were tested up to their failure, by recording the applied loads, the strains in the conventional reinforcements and in the FRC of the critical zones of the structure. By using digital image correlation, the average crack width at the level of the flexural reinforcements was recorded. The participants had to predict these results by receiving information about the mechanical properties of the materials, the geometry of the prototypes and their loading and support conditions. In this article, the rules and the results of this 2nd BSC competition are presented, and the data obtained experimentally is thoroughly analyzed. [ABSTRACT FROM AUTHOR]

Skeletal muscle plays a major role in whole‐body glucose metabolism. Insulin resistance in skeletal muscle is characterized by decreased insulin‐stimulated glucose uptake resulting from impaired intracellular trafficking and decreased glucose transporter 4 (GLUT4) expression. In this study, we illustrated that tilorone, a low‐molecular‐weight antiviral agent, improves glucose uptake in vitro and in vivo. Tilorone increased bone morphogenetic protein (BMP) signaling in C2C12 myoblasts, the transcription of multiple BMPs (BMP2, BMP4, BMP7, and BMP14), Smad4 expression, and the phosphorylation of BMP‐mediated Smad1/5/8. The activation of Akt2/AS160 (TBC1D4) signaling, the critical regulator of GLUT4 translocation, was also increased, as well as the levels of GLUT4 and GLUT1, leading to enhanced uptake of the radioactively labeled glucose analog 18F‐fluoro‐2‐deoxyglucose (18FDG). However, this excess glucose content did not result in increased ATP formation by mitochondrial respiration; both basal and ATP‐linked respiration were diminished, thereby contributing to the induction of AMPK. In differentiated myotubes, AS160 phosphorylation and 18FDG uptake also increased. Moreover, tilorone administration further increased insulin‐stimulated phosphorylation of Akt2 and glucose uptake of myotubes indicating an insulin‐sensitizing effect. Importantly, during in vivo experiments, the systemic administration of tilorone resulted in increased 18FDG uptake of skeletal muscle, liver, and adipose tissue in C57BL/6 mice. Our results provide new perspectives for the treatment of type 2 diabetes, which has a limited number of treatments that regulate protein expression or translocation. [ABSTRACT FROM AUTHOR]

This study is the first known observation of biofluorescence in the lumpfish (Cyclopterus lumpus). Individual lumpfish were illuminated with blue excitation lighting for photography with both hyperspectral and filtered multispectral cameras. All photographed juvenile lumpfish (n = 11) exhibited green biofluorescence. Light emissions were characterised with two peaks observed at 545 and 613 nm, with the greatest intensity along the tubercles of the high crest and the three longitudinal ridges. Further research on the dynamics of biofluorescence through the lifecycle of this species is required. [ABSTRACT FROM AUTHOR]

Background and Purpose: The small molecule BGP‐15 has been reported to alleviate symptoms of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP‐15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental Approach Rabbits were maintained on standard chow (control) or atherogenic diet (hypercholesterolemic) for 16 weeks. BGP‐15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium‐dependent vasorelaxation was assessed and key molecules in the protein kinase G (PKG) pathway were examined by enzyme‐linked immunosorbent assay (ELISA) and western blot. Passive force generation was investigated in skinned cardiomyocytes. Key Results: Both acute and chronic BGP‐15 treatments improved the diastolic performance of the diseased heart. However, vasorelaxation and serum lipid markers were unaffected. Myocardial cyclic guanosine monophosphate (cGMP) levels were elevated in the BGP‐15‐treated group, along with preserved PKG activity and increased phospholamban Ser16‐phosphorylation. PDE5 expression decreased in the BGP‐15‐treated group and PDE1 was inhibited. Cardiomyocyte passive tension reduced in BGP‐15‐treated rabbits, the ratio of titin N2BA/N2B isoforms increased and PKG‐dependent N2B‐titin phosphorylation elevated. Conclusions and Implications: BGP‐15 treatment improves diastolic function, reduces cardiomyocyte stiffness and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP‐PKG pathway. As BGP‐15 has been proven to be safe, it may be clinically useful in the treatment of diastolic dysfunction. [ABSTRACT FROM AUTHOR]

The current cross‐cultural study examined the construct of workaholism across European and Asian cultures during the pandemic caused by coronavirus disease 2019 (COVID‐19). A total of 2,617 recipients, aged 18–80 years from three Asian countries (China, India, and Indonesia) with higher levels of collectivistic values, and three European countries (Bulgaria, Germany, and Hungary) supposing to have higher individualistic values. The participants completed the online version of the two‐dimensional measure, dubbed the Dutch Workaholism Scale (DUWAS). The goal of the study was to demonstrate that during the COVID‐19 pandemic, it is the cultural context that mediates and influences the way of change in workaholics' attitudes. The results led to the conclusion that the way in which the COVID‐19 crisis affects workaholism and workaholics' behavior depends on cultural and sex differences, and stages of the human life cycle. The data analysis revealed that cultural differences and sex affect the configuration of workaholism (excessive/compulsive): in the Asian sample, unlike the European, there was a significant increase in the level of workaholism compulsive; European female participants reported higher levels of workaholism compulsive and workaholism excessive, but the sex difference was not found in Asian sample. Along with cultural context, and sex differences, age also influences the configuration of workaholism. In this case, the separate stages of the human life cycle contribute in different ways to changes in levels of workaholism excessive and workaholism compulsive. [ABSTRACT FROM AUTHOR]

This study investigates whether facets of rumination statistically mediate the relationships between Big Five personality traits and depressive symptoms. Self‐reported personality traits and rumination were investigated as predictors of depressive symptoms in a cross‐sectional sample of 3043 participants aged 18–60 years (68.8% female). Multiple regression analysis investigated which personality traits and rumination facets best explained variance in depressive symptoms. Structural equation modelling was used to determine whether facets of rumination mediated the relationships between personality traits and depressive symptoms. Multiple regression analysis found that variance in depressive symptoms was best explained by the personality traits neuroticism, extroversion, conscientiousness; and both facets of rumination, brooding and reflection. Structural equation modelling added that the effects of neuroticism, extroversion, conscientiousness and openness on depressive symptoms were statistically mediated by brooding; the effects of neuroticism, extroversion and openness to depressive symptoms were statistically mediated by reflection. Rumination facets statistically mediated the effects of various personality traits on depressive symptoms. These results provide insights into which individuals may be best suited to treatments for depression targeting rumination. [ABSTRACT FROM AUTHOR]

Dermatomyositis is a rare disease affecting primarily skin and muscles and is associated with malignancies, especially in at‐risk patients. Clinical presentations vary widely but proximal muscle weakness and typical skin findings should prompt consideration of the diagnosis. Immunosuppressive therapy is required, as is continued screening for malignant disease during follow‐up. [ABSTRACT FROM AUTHOR]

In January 2019, the Safe Food for Canadians Act/Safe Food for Canadians regulations (heretofore identified as SFCR) came into force across Canada and brought a more streamlined process to food safety practice in Canada. Food trade and production processes have evolved rapidly in recent decades, as Canada imports and exports food products; therefore it is critically important to remain aware of the latest advances responding to a range of challenges and opportunities in the food safety value chain. Looking through the optics of the recent SFCR framework, this paper places the spotlight on leading domestic and international research and practices to help strengthen food safety policies of the future. By shedding some light on new research, we also draw attention to international developments that are noteworthy, and place those in context as to how new Canadian food safety policy and regulation can be further advanced. The paper will benchmark Canada through a review study of food safety best practices by juxtaposing (i) stated aspirations with, (ii) actual performance in leading Organization for Economic Cooperation and Development (OECD) jurisdictions. [ABSTRACT FROM AUTHOR]

Objective: Utilize simulation to evaluate if living wills (LW) or POLST achieves goal concordant Care (GCC) in a medical crisis. Methods: Nurses and resident‐physicians from a single center were randomized to a clinical scenario with a living will (LW), physician orders for life sustaining treatment (POLST) or no document. Primary outcomes were resuscitation decision and time to decision. Secondary outcome was the effect of education. Results: Total enrollment was 57 and less than 30% received prior training. Types of directives were linked to resuscitation decisions (P =.019). Participants randomized to "No Document" or POLST specifying "CPR" performed resuscitation. If a terminal condition presented with a POLST/ do not resuscitate‐comfort measures only (DNR‐CMO), 73% resuscitated. The LW or POLST specifying DNR combined with medical support resulted in resuscitations in 29% or more of the scenarios. Documents did not significantly affect median time‐to‐decision (P =.402) but decisions for "No Document" and POLST/CPR were at least 10 s less than other scenarios. Scenarios involving POLST DNR/Limited Treatment had the highest median time of 43 s. Prior training in LWs and POLST exerted a 10% improvement in decision making (P =.537). Conclusion: GCC was not always achieved with a LW or POLST. This conclusion supports prior research identifying problems with the interpretation and discordance with LW's and POLST. [ABSTRACT FROM AUTHOR]

Summary: Klebsiella pneumoniae is a common cause of potentially life‐threatening infection. This report describes a relapsing healthcare‐associated Klebsiella pneumoniae meningitis in a 60‐year‐old patient who had SARS‐CoV‐2 infection. During their initial admission for COVID‐19 pneumonitis and treatment with corticosteroids, the patient developed signs and symptoms suggestive of bacterial meningitis. Blood and cerebrospinal fluid cultures confirmed Klebsiella pneumoniae as the causative organism. The patient was treated with a prolonged course of high‐dose meropenem and made an apparent recovery. Four days after hospital discharge, the patient re‐presented critically unwell. Klebsiella pneumoniae was once again isolated from cerebrospinal fluid. During their second admission, the patient deteriorated despite antimicrobial treatment, and life‐sustaining therapies were withdrawn. This case highlights that all COVID‐19 patients receiving immunosuppressive therapy should be monitored for potential opportunistic infection. Prompt recognition and early antimicrobial therapy are key to improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: While single‐omics analyses on human atherosclerotic plaque have been very useful to map stage‐ or disease‐related differences in expression, they only partly capture the array of changes in this tissue and suffer from scale‐intrinsic limitations. In order to better identify processes associated with intraplaque hemorrhage and plaque instability, we therefore combined multiple omics into an integrated model. Methods: In this study, we compared protein and gene makeup of low‐ versus high‐risk atherosclerotic lesion segments from carotid endarterectomy patients, as judged from the absence or presence of intraplaque hemorrhage, respectively. Transcriptomic, proteomic, and peptidomic data of this plaque cohort were aggregated and analyzed by DIABLO, an integrative multivariate classification and feature selection method. Results: We identified a protein‐gene associated multiomics model able to segregate stable, nonhemorrhaged from vulnerable, hemorrhaged lesions at high predictive performance (AUC >0.95). The dominant component of this model correlated with αSMA−PDGFRα+ fibroblast‐like cell content (p = 2.4E‐05) and Arg1+ macrophage content (p = 2.2E‐04) and was driven by serum response factor (SRF), possibly in a megakaryoblastic leukemia‐1/2 (MKL1/2) dependent manner. Gene set overrepresentation analysis on the selected key features of this model pointed to a clear cardiovascular disease signature, with overrepresentation of extracellular matrix synthesis and organization, focal adhesion, and cholesterol metabolism terms, suggestive of the model's relevance for the plaque vulnerability. Finally, we were able to corroborate the predictive power of the selected features in several independent mRNA and proteomic plaque cohorts. Conclusions: In conclusion, our integrative omics study has identified an intraplaque hemorrhage‐associated cardiovascular signature that provides excellent stratification of low‐ from high‐risk carotid artery plaques in several independent cohorts. Further study revealed suppression of an SRF‐regulated disease network, controlling lesion stability, in vulnerable plaque, which can serve as a scaffold for the design of targeted intervention in plaque destabilization. [ABSTRACT FROM AUTHOR]

Experimental research has shown the extraordinary potential of the addition of short fibers to cement‐based materials by improving significantly the behavior of concrete structures for serviceability and ultimate limit states. Software based on the finite element method has been used for the simulation of the material nonlinear behavior of fiber‐reinforced concrete (FRC) structures. The applicability of the existing approaches has often been assessed by simulating experimental tests with structural elements, in general of a small scale, where the parameter values of the material constitutive laws are adjusted for the aimed predicting level, which constitutes an inverse technique of arguable utility for structural design practice. For assessing the predictive performance of these approaches, a blind simulation competition was organized. Two twin T‐cross section steel FRC beams, flexurally reinforced with steel bars and without conventional shear reinforcement in the critical shear span, were experimentally tested up to failure. Despite the experimental data provided for the definition of the relevant model parameters, inaccuracies on the load capacity, deflection, and strain at peak load attained 40, 113, and 600%, respectively. Inadequate failure modes and highly different results were estimated with the same commercial software, indicating the need for deeper analysis and understanding of the models and influence of their parameters on their predictive performance. [ABSTRACT FROM AUTHOR]

Background: Historically, persons with albinism (PWA) were thought to develop squamous cell carcinoma (SCC) more frequently than basal cell carcinoma (BCC). Recent evidence suggests BCCs in PWA are more common than initially hypothesized. Objective: To characterize the presentation of BCC in PWA. Methods: Fifty‐four PWA with lesions suspicious for non‐melanoma skin cancer sought care at Tanzanian dermatologic clinics from 2017 to 2019. Demographic and clinical presentation data were recorded. Histologic analysis of each sample was completed. Results: The majority of PWA were female (53.7%), with a mean age of 34.6 ± 14.9 years and a mean duration of disease of 0.70 ± 0.73 years. Physician description of histologically proven BCC included ulceration (41.7%), erythema (16.7%), and scale (16.7%). Lesions were most commonly located on the trunk (47.1%) and face (41.2%). Histologic analysis demonstrated 30.2% of lesions were BCC, 26.4% SCC, and 17% Bowen's disease. Limitations: Patient population was limited to those visiting clinics, and data were limited by accuracy of the medical record. Conclusions: Basal cell carcinoma occurs at a higher rate than SCC in our population, suggesting BCC in PWA is underdiagnosed. It is important to recognize BCC early in PWA to avoid large disease burden and high rates of morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background: Topical minoxidil has been used for almost 40 years to treat alopecia. There is growing evidence supporting off‐label use of low‐dose oral minoxidil. Objective: To conduct a systematic review evaluating the use of oral minoxidil for all types of alopecia. Methods: A primary literature search was conducted using PubMed in May 2019, utilizing the search term "oral minoxidil AND (hair loss OR alopecia OR baldness)". Reviews, non‐English studies, and articles concerning only topical minoxidil were excluded. Results: Ten articles were included for review comprising a total 19,218 patients (215 women and 19,003 men). Oral minoxidil dose ranged from 0.25 to 5 mg daily to twice daily. The strongest evidence existed for androgenetic alopecia and alopecia areata (AA), with 61–100% and 18–82.4% of patients demonstrating objective clinical improvement. Successful treatment of female pattern hair loss, chronic telogen effluvium, monilethrix, and permanent chemotherapy‐induced alopecia was also reported. The most common adverse effects with oral minoxidil included hypertrichosis and postural hypotension. Conclusion: Oral minoxidil is a safe and successful treatment of androgenic alopecia and AA. In addition to its therapeutic benefits, practical advantages over topical minoxidil stem from improved patient compliance. [ABSTRACT FROM AUTHOR]

Summary: Clays and surfactant‐modified clays (organoclays) are becoming popular as pollutant sorbents due to their high reactivity and low‐cost availability. However, the lack of field testing and data on ecotoxicity limits their application. Considering such aspects, this study assessed the impact of clay amendments to polycyclic aromatic hydrocarbons (PAHs)/cadmium (Cd)‐contaminated soil on microbial respiration profiles (active vs. inactive cells) using redox staining and the relative abundance and diversity of bacteria and archaea. These clay products are bentonite, cationic surfactant‐modified bentonite and palmitic acid‐grafted surfactant‐modified bentonite). After 70 days, the addition of bentonite and its modified forms altered microbial community structure mainly among dominant groups (Actinobacteria, Proteobacteria, Firmicutes and Chloroflexi) with effects varying depending on material loading to soil. Among amendments, fatty acid (palmitic acid) tailored cationic surfactant‐modified bentonite proved to be microbial growth supportive and significantly increased the number of respiration‐active microbial cells by 5% at a low dose of material (e.g. 1%). Even at high dose (5%), the similarity index using operational taxonomic units (OTUs) also indicates that this modified organoclay‐mixed soil provided only slightly different environment than control soil, and therefore, it could offer more biocompatibility than its counterpart organoclay at similar dose (e.g. cationic surfactant‐modified bentonite). This study promotes designing 'eco‐safe' clay‐based sorbents for environmental remediation. [ABSTRACT FROM AUTHOR]

Climate change can impact ecosystems by reshaping the dynamics of resource exploitation for predators and their prey. Alterations of these pathways could be especially intense in ecosystems characterized by a simple trophic structure and rapid warming trends, such as in the Arctic. However, quantifying the multiple direct and indirect pathways through which climate change is likely to alter trophic interactions and their relative strength remains a challenge.Here, we aim to identify direct and indirect causal mechanisms driven by climate affecting predator–prey interactions of species sharing a tundra food web.We based our study on relationships between one Arctic predator (Arctic fox) and its two main prey – lemmings (preferred prey) and snow geese (alternate prey) – which are exposed to variable local and regional climatic factors across years. We used a combination of models mapping multiple causal links among key variables derived from a long‐term dataset (21 years).We obtained several possible scenarios linking regional climate factors (Arctic oscillations) and local temperature and precipitation to the breeding of species. Our results suggest that both regional and local climate factors have direct and indirect impacts on the breeding of foxes and geese. Local climate showed a positive causal link with goose nesting success, while both regional and local climate displayed contrasted effects on the proportion of fox breeding. We found no impact of climate on lemming abundance. We observed positive relationships between lemming, fox and goose reproduction highlighting numerical and functional responses of fox to the variability of lemming abundance.Our study measures causal links and strength of interactions in a food web, quantifying both numerical response of a predator and apparent interactions between its two main prey. These results improve our understanding of the complex effects of climate on predator–prey interactions and our capacity to anticipate food web response to ongoing climate change. [ABSTRACT FROM AUTHOR]

The modification of erythrocyte membrane properties provides a new tool towards improved drug delivery and biomedical applications. The fabrication of hybrid erythrocyte liposomes is presented by doping red blood cell membranes with synthetic lipid molecules of different classes (PC, PS, PG) and different degrees of saturation (14:0, 16:0–18:1). The respective solubility limits are determined, and material properties of the hybrid liposomes are studied by a combination of X‐ray diffraction, epi‐fluorescent microscopy, dynamic light scattering (DLS), Zeta potential, UV‐vis spectroscopy, and Molecular Dynamics (MD) simulations. Membrane thickness and lipid orientation can be tuned through the addition of phosphatidylcholine lipids. The hybrid membranes can be fluorescently labelled by incorporating Texas‐red DHPE, and their charge modified by incorporating phosphatidylserine and phosphatidylglycerol. By using fluorescein labeled dextran as an example, it is demonstrated that small molecules can be encapsulated into these hybrid liposomes. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by disruption of epidermal barrier function and aberrant immune response to antigens. Current therapies focus on symptom management by restoring epidermal barrier function with emollients and reducing inflammation. Given the prevalence of "steroid phobia" and reported dissatisfaction with first‐line therapies, oral vitamins and supplements have been proposed as promising complementary and alternative therapies. The purpose of this systematic review is to evaluate the evidence for various oral vitamins and supplements for the treatment of AD. A literature search was performed in February 2018 in MEDLINE, EMBASE, and Cochrane databases. Included studies were clinical trials and meta‐analyses on the oral supplementation of vitamins and supplements for the treatment or prevention of AD. The search identified over 300 articles, of which 37 were included for review. Supplementation with vitamins E and D have the most robust evidence for AD symptom management. Probiotics may play a role in the prevention of infantile AD. Fatty acids such as docosahexaenoic acid, sea buckthorn oil, and hempseed oil also have preliminary evidence for use as supplements to decrease AD severity, but randomized controlled trials are needed. Vitamins and supplements may have a role in the management of AD, however, many of the studies reviewed are limited by small sample size. More studies are needed to better inform medical providers and patients about the role of these treatments in the management of AD. [ABSTRACT FROM AUTHOR]

Aging is associated with a progressive loss of tissue and metabolic homeostasis. This loss can be delayed by single‐gene perturbations, increasing lifespan. How such perturbations affect metabolic and proteostatic networks to extend lifespan remains unclear. Here, we address this question by comprehensively characterizing age‐related changes in protein turnover rates in the Drosophila brain, as well as changes in the neuronal metabolome, transcriptome, and carbon flux in long‐lived animals with elevated Jun‐N‐terminal Kinase signaling. We find that these animals exhibit a delayed age‐related decline in protein turnover rates, as well as decreased steady‐state neuronal glucose‐6‐phosphate levels and elevated carbon flux into the pentose phosphate pathway due to the induction of glucose‐6‐phosphate dehydrogenase (G6PD). Over‐expressing G6PD in neurons is sufficient to phenocopy these metabolic and proteostatic changes, as well as extend lifespan. Our study identifies a link between metabolic changes and improved proteostasis in neurons that contributes to the lifespan extension in long‐lived mutants. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acid consumption has been shown to improve insulin sensitivity. We studied if administration of broth with beef meat enriched with polyunsaturated fatty acids influenced glucose‐stimulated insulin release in healthy male volunteers. Broth was made either from cattles undergone dietary supplementation with lightly bruised whole linseed in addition to feeding ad libitum on grass silage (test meal) or from those fed grass silage alone (control meal). Oral glucose tolerance tests (OGTT) were performed in patients after a 6‐day period of eating 300 ml broth containing 100 g meat once a day in addition to their otherwise normal mixed nourishment. During OGTT, blood samples were taken for blood glucose level and plasma insulin immunoreactivity before and 15, 30, 60, 90, 120, and 180 min after the glucose load. Glucose‐stimulated maximum increase in plasma insulin immunoreactivity was 42 ± 6.6 and 81 ± 7.4 mU/ml (p < 0.05) after the test and the control meals, respectively. However, both fasting and postload blood glucose levels were the same after either meal period. The results suggest an insulin‐sensitizing effect of food produced from beef cattle maintained on linseed diet in healthy human volunteers. [ABSTRACT FROM AUTHOR]

Summary : In wheat (Triticum aestivum) grain yield and grain protein content are negatively correlated, making the simultaneous increase of the two traits challenging. Apart from genetic approaches, modification of nitrogen fertilization offers a feasible option to achieve this aim. In this study, a range of traits related to nitrogen‐use efficiency in six Australian bread wheat varieties were investigated under different nitrogen treatments using 3‐year multisite field trials. Changes in the individual storage protein composition were detected by high‐performance liquid chromatography. Our results indicated that wheat grain yield and grain protein content reacted similarly to nitrogen availability, with grain yield being slightly more sensitive than grain protein content, and that genotype is a vital determinant of grain protein yield. Measurement of the glutamine synthetase activity of flag leaves and developing grains revealed that high nitrogen availability prompted the participation of glutamine in biological processes. In addition, a more significant accumulation of gluten macropolymer was observed under the high‐nitrogen treatment from 21 days post‐anthesis, and the underlying mechanism was elucidated by a comparative proteomics study. A yeast two‐hybrid experiment confirmed this mechanism. The results of this study revealed that peptidyl‐prolyl cis–trans isomerase (PPIase) was SUMOylated with the assistance of small ubiquitin‐related modifier 1 and that high nitrogen availability facilitated this connection for the subsequent protein polymerization. Additionally, luminal‐binding protein 2 in the endoplasmic reticulum played a similar role to PPIase in the aggregation of protein under high‐nitrogen conditions. Significance Statement: A large‐scale study of wheat nitrogen‐use efficiency under different nitrogen fertilization regimes revealed a mechanism of wheat grain protein biosynthesis mediated by nitrogen availability, which was confirmed through proteomics, bioinformatics and yeast two‐hybrid experiments. The results revealed that peptidyl‐prolyl cis–trans isomerase (PPIase) is SUMOylated with the assistance of SUMO1 and high nitrogen availability facilitates this connection for the subsequent protein polymerization. Additionally, BIP2 in the endoplasmic reticulum played a similar role to PPIase in the aggregation of protein under high‐nitrogen conditions. [ABSTRACT FROM AUTHOR]

Summary: Background: Pigmentation of the skin occurs as a result of increased melanin production or deposition due to various reasons including age, hormonal imbalances, endocrine disease, inflammation, and/or exposure to damaging radiation, resulting in dermatologic conditions such as lentigines, melasma, or postinflammatory hyperpigmentation. Although numerous topical therapies exist for skin lightening, they are limited by efficacy and pigmentation recurrence after treatment cessation. New research into systemic therapies for hyperpigmentation has been promising. Objective: To summarize the current literature for systemic skin lightening therapies. Methods: A review of the literature surrounding systemic skin lightening therapies was completed using PubMed (US National Library of Medicine). Results: Multiple systemic therapies for skin lightening exist including oral carotenoids, glutathione, melatonin, Polypodium leucotomos hydrophilic extract, procyanidin, and tranexamic acid. Preliminary data for the treatment of hyperpigmentation are promising, and currently, these oral treatments appear safe. It is not suggested to use intravenous glutathione for skin lightening due to the increased risk of adverse events. Conclusion: With the patient population seeking effective systemic treatments for skin pigmentation, it is important for dermatologists to understand the properties, the efficacy, and the adverse events profile of each compound, thus ensuring proper use by patients, and that patients are appropriately counseled regarding treatment expectation and safety. [ABSTRACT FROM AUTHOR]

Background: Dementia is characterized by progressive cognitive impairment (CI), which is accompanied by decline in reasoning, planning and memory. Cardiovascular diseases are the major contributors to the pathogenesis of vascular dementia and affect mainly the aging population. Even on a normal salt diet, Dahl salt‐sensitive (DSS) rats exhibit age‐associated hypertension and CI. We hypothesized, that anti‐hypertensive treatment with the angiotensin II receptor blocker losartan (LOS) would improve cardiovascular and cognitive function in aged DSS rats. Method: Male DSS rats (n=30) were kept on a normal salt diet (0.5% NaCl) for the duration of the study. Baseline measurements were taken at 6‐mo of age. After that, treatment with 30mg/kg/day of LOS, added to the drinking water (n=14), or control (n=16) was started and continued for 6‐mo. Systolic blood pressure (SBP), aortic pulse wave velocity (aPWV), a measure of aortic stiffness, and behavioral testing in a visually cued reaction task to assess attention and inhibitory control were assessed every 3‐mo. Elevated plus maze (EPM) and Morris Water Maze (MWM) tests were performed at 12‐mo of age to measure anxiety‐like behavior and to evaluate spatial memory, respectively. Data were analyzed by 2‐way repeated measures ANOVA or t‐tests as applicable. Result: Prior to the treatment, LOS and control groups did not display differences in any parameter analyzed. Control rats exhibited gradual increase in SBP and aPWV from 6 to 12‐mo of age. Following 3‐ and 6‐mo of treatment, LOS rats exhibited lower SBP and aPWV vs. controls (Table 1). At 12‐mo of age, LOS rats had improved performance in the reaction task (Figure 1), and exhibited lower anxiety levels, spending less time on the closed arm in EPM and 1.5‐fold more time in the open arm vs. control rats. LOS rats also spent less time to find a hidden platform in the MWM vs. controls, indicating that LOS treatment improved spatial memory (Table 1). Conclusion: Improvement of cardiovascular function and reduction in aortic stiffness by LOS were associated with better attentional control and memory and lower anxiety levels, demonstrating an association of CI with cardiovascular changes in the DSS rat model of vascular dementia. [ABSTRACT FROM AUTHOR]

Background: The prevalence of cognitive impairment (CI) and dementia in end‐stage chronic kidney disease (CKD) has been estimated at 30‐60%. Cardiovascular diseases (CVD) including increased central arterial stiffness (CAS) accompany CKD development and contribute to CI. Elevated pulse wave velocity (PWV) is associated with higher mortality in CVD and CKD independently of blood pressure (BP). Marinobufagenin (MBG) is a pro‐fibrotic factor, which increases in CKD and contributes to CAS. The aim of this study was to determine whether CKD potentiates CI development via CAS and cardiovascular remodeling in a rat model of CKD. Method: Four months old male Sprague‐Dawley rats were fed with 0.25% adenine (n=19; CKD group) diet to induce CKD or regular diet (n=16; CTRL group) for 8 weeks. Body weight (BW), BP, heart rate (HR), aortic PWV (aPWV), and behavioral tests were conducted at the end of the study. The level of anxiety was tested in an open field test (OFT). Morris water maze (MWM) was used to test spatial memory. Blood was collected for measurements of plasma sodium, potassium, blood urea nitrogen (BUN), hematocrit and MBG. The data were analyzed using two‐tailed unpaired t‐test and linear regression. Result: Animals in the CKD group had higher levels of plasma creatinine and BUN, which indicate the development of CKD, higher plasma sodium, potassium, and MBG, and higher aPWV, lower hemoglobin, hematocrit, BW, HR, enlarged hearts, aortae, and kidneys, vs. CTRL group (Table 1). BP was similar in both groups..Rats in CKD group spent less time in the center of open field compared to their CTRL counterparts, indicating increased anxiety‐like behavior (Figure 1 A, B). Although there was no difference in performance in MWM between the groups, there was a positive correlation between aortic weight and ability to find a hidden platform in the CKD group (Figure 1C). Conclusion: We demonstrated that CKD development in young Sprague‐Dawley rats was accompanied by increased CAS, estimated as aPWV, which developed in blood pressure‐independent manner. Higher PWV was associated with a higher level of anxiety, and aortic tissue remodeling was associated with spatial memory in CKD model. Supported by NIH/NIA IRP [ABSTRACT FROM AUTHOR]

Background: Double‐mutant mice (APPswe/PS1dE9; 2xTg‐AD) represent a model of Alzheimer's disease (AD). 2xTg‐AD mice develop progressive accumulation of amyloid plaques and cognitive impairment (CI) with age in >12 months old animals. The aim of the present study was to investigate the associations of CI and cardiovascular function in 2xTg‐AD mice. Methods: Aortic pulse wave velocity (aPWV), an estimation of aortic stiffness, and cardiac parameters were measured by echocardiography in 16‐mo old male 2xTg‐AD (n=11) and wild type (WT; n=17) mice. Spatial memory (using Morris water maze; MWM) and the anxiety level (using open field test; OFT) were assessed. The relationship between cardiovascular and behavioral parameters were modeled using a linear regression analysis (LRA) with a backward elimination. P‐values <0.05 were considered significant, and 0.05≤P<0.1 were considered near significant and were included in the models. Results: 2xTg‐AD mice exhibited an increase in aPWV and had a thicker left ventricle (LV) posterior wall in diastole (LVPWd) and narrower LV internal diameter (LVIDd) vs. WT mice (Table 1). 2xTg‐AD mice spent less time in the center of OF vs. WT mice (Table 1). LRA revealed a negative association between time spent in the center of OF and LVPWd, and a positive association with LV volume in diastole (LVvold) in 2xTg‐AD mice (Table 2). In MWM, 2xTg‐AD mice exhibited impaired spatial memory estimated as prolonged average escape latency during their training vs. WT counterparts (Table 1). Although there was no difference between performance in the MWM probe trial, LRA showed a negative association between LVPWd and the mean distance from the platform in the probe trial in 2xTg‐AD mice, and a positive association of LVPWd with number of entries to the platform zone (Table 2). There was a positive association between aPWV and mean distance from the platform in the probe trial in both 2xTg‐AD and WT mice. Conclusions: LRA results indicate that LV remodeling is associated with anxiety‐like behavior in 2xTg‐AD mice, but not with spatial memory impairment. Positive association of aPWV with spatial memory impairment in both groups suggests that aortic stiffness contributes to the age‐associated CI. Supported by the NIH/NIA IRP. [ABSTRACT FROM AUTHOR]

Patients with grade 2-3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160-190 mm Hg and 24-hour SBP 140-175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL-M) monotherapy for 4 weeks. "Nonresponders" were then randomized to 8 weeks of double-blind treatment with AZL-M 40 mg, AZL-M/chlortalidone (CLD) 40/25, or AZL-M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was -21.1 (±1.04) mm Hg for AZL-M/CLD 40/25 mg, -15.8 (±1.08) mm Hg for AZL-M/CLD 40/12.5 mg, and -6.4 (±1.05) mm Hg for AZL-M 40 mg (P < 0.001 for both AZL-M/CLD vs AZL-M, ANCOVA). Drug discontinuation rates were 8.9% (AZL-M/CLD 40/25 mg), 7.5% (AZL-M 40 mg), and 3.9% (AZL-M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL-M/CLD 40/25), 3.1% (AZL-M/CLD 40/12.5 mg), and 3.0% (AZL-M 40 mg) of patients. AZL-M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL-M. [ABSTRACT FROM AUTHOR]

Abstract: This paper examines parents' legal argumentation in 15 appealed care order (child removal) cases in one Norwegian district court, asking on what grounds parents appeal their case. I investigate the pragmatic, ethical, and moral bases in arguments by applying a discourse ethics framework, viewing argumentation as either justifications or excuses of the parenting in question. The analysis reveals complex reasons for appealing, displaying parents both justifying and excusing both specific situations and the totality of their parenthood. Parents primarily apply pragmatic and ethical adversarialism, followed by pragmatic blaming and claims of change, moral justifications about due process, and ethical excuses about age and own life histories. Interestingly, normalization emerges as a third strategy, where parents explicitly aim to widen the scope of parental normality and adequacy, challenging the common defense dichotomy. The study provides new insight into an important and sensitive field, and indicates that parents engage in similar concrete strategies when, most often unsuccessfully, defending their parenthood. [ABSTRACT FROM AUTHOR]

Abstract: Dysregulation of neuropeptides may play an important role in aging‐induced impairments. Among them, pituitary adenylate cyclase‐activating polypeptide (PACAP) is a potent cytoprotective peptide that provides an endogenous control against a variety of tissue‐damaging stimuli. We hypothesized that the progressive decline of PACAP throughout life and the well‐known general cytoprotective effects of PACAP lead to age‐related pathophysiological changes in PACAP deficiency, supported by the increased vulnerability to various stressors of animals partially or totally lacking PACAP. Using young and aging CD1 PACAP knockout (KO) and wild type (WT) mice, we demonstrated pre‐senile amyloidosis in young PACAP KO animals and showed that senile amyloidosis appeared accelerated, more generalized, more severe, and affected more individuals. Histopathology showed age‐related systemic amyloidosis with mainly kidney, spleen, liver, skin, thyroid, intestinal, tracheal, and esophageal involvement. Mass spectrometry‐based proteomic analysis, reconfirmed with immunohistochemistry, revealed that apolipoprotein‐AIV was the main amyloid protein in the deposits together with several accompanying proteins. Although the local amyloidogenic protein expression was disturbed in KO animals, no difference was found in laboratory lipid parameters, suggesting a complex pathway leading to increased age‐related degeneration with amyloid deposits in the absence of PACAP. In spite of no marked inflammatory histological changes or blood test parameters, we detected a disturbed cytokine profile that possibly creates a pro‐inflammatory milieu favoring amyloid deposition. In summary, here we describe accelerated systemic senile amyloidosis in PACAP gene‐deficient mice, which might indicate an early aging phenomenon in this mouse strain. Thus, PACAP KO mice could serve as a model of accelerated aging with human relevance. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background and Purpose: Oxycodone is a potent semi-synthetic opioid that is commonly used for the treatment of severe acute and chronic pain. However, treatment with oxycodone can lead to cardiac electrical changes, such as long QT syndrome, potentially inducing sudden cardiac arrest. Here, we investigate whether the cardiac side effects of oxycodone can be explained by modulation of the cardiac Nav 1.5 sodium channel.Experimental Approach: Heterologously expressed human Nav 1.5, Nav 1.7 (HEK293 cells) or Nav 1.8 channels (mouse N1E-115 cells) were used for whole-cell patch-clamp electrophysiology. A variety of voltage-clamp protocols were used to test the effect of oxycodone on different channel gating modalities. Human stem cell-derived cardiomyocytes were used to measure the effect of oxycodone on cardiomyocyte beating.Key Results: Oxycodone inhibited Nav 1.5 channels, concentration and use-dependently, with an IC50 of 483 μM. In addition, oxycodone slows recovery of Nav 1.5 channels from fast inactivation and increases slow inactivation. At high concentrations, these effects lead to a reduced beat rate in cardiomyocytes and to arrhythmia. In contrast, no such effects could be observed on Nav 1.7 or Nav 1.8 channels.Conclusions and Implications: Oxycodone leads to an accumulation of Nav 1.5 channels in inactivated states, with a slow time course. Although the concentrations needed to elicit cardiac arrhythmias in vitro are relatively high, some patients under long-term treatment with oxycodone as well as drug abusers and addicts might suffer from severe cardiac side effects induced by the slowly developing effects of oxycodone on Nav 1.5 channels. [ABSTRACT FROM AUTHOR]

An open-label, long-term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL-M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up-titrated (AZL-M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4-52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL-M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL-M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long-term follow-up (P = .588). A greater proportion of participants up-titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL-M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL-M/CLD and OLM/HCTZ showed similar efficacy and tolerability. [ABSTRACT FROM AUTHOR]

This article examines the confidence the population (N = 4,003) has in the child welfare system in four countries - England, Finland, Norway and the USA (California). We find that about half or less of the population reports having confidence in the system, which is slightly higher than the confidence in the civil servants in the same countries. The Nordic countries display more confidence in the child welfare system than the Anglo-American countries. The similarity between the countries is, however, greater than anticipated. As for independent variables that can shed light on differences in confidence levels, we find three variables to be related to a higher confidence level, and these are a left wing political orientation, lower age, and higher education. This study contributes in filling a knowledge gap on studies about trust in the child welfare system, but we emphasize that we have studied an aspect of trust that rests on the population's impressions of a system, and not their substantial knowledge about, or identification with, this system. [ABSTRACT FROM AUTHOR]

We explore a direct approach to estimating household equivalence scales from income satisfaction data. Our method differs from previous approaches to using satisfaction data for this purpose in that it can be used to directly fit and evaluate closed-form and non-parametric equivalence scales of any desired form. Its flexibility makes it easy to consider specific aspects such as income dependence or more specific information on household composition (such as whether household members live in a partner relationship). We estimate and evaluate a number of scales used in the literature. If the equivalence scale is assumed to be independent of income and to depend only on household size, we do not reject the validity of the widely used square-root scale at conventional significance levels. We also test GESE and GAESE restrictions (Donaldson and Pendakur, 2003, 2006) and investigate in detail to what extent household economies of scale depend on income. Our results suggest that the income dependence differs fundamentally across household types (rising economies of scale for 'family' households, falling economies of scale for multi-adult households without children and no income dependence for other households). [ABSTRACT FROM AUTHOR]

One of the main effects of the endocannabinoid system in the brain is stress adaptation with presynaptic endocannabinoid receptor 1 ( CB1 receptors) playing a major role. In the present study, we investigated whether the effect of the CB1 receptor coding CNR1 gene on migraine and its symptoms is conditional on life stress. In a cross-sectional European population ( n = 2426), recruited from Manchester and Budapest, we used the ID-Migraine questionnaire for migraine screening, the Life Threatening Experiences questionnaire to measure recent negative life events ( RLE), and covered the CNR1 gene with 11 SNPs. The main genetic effects and the CNR1 × RLE interaction with age and sex as covariates were tested. None of the SNPs showed main genetic effects on possible migraine or its symptoms, but 5 SNPs showed nominally significant interaction with RLE on headache with nausea using logistic regression models. The effect of rs806366 remained significant after correction for multiple testing and replicated in the subpopulations. This effect was independent from depression- and anxiety-related phenotypes. In addition, a Bayesian systems-based analysis demonstrated that in the development of headache with nausea all SNPs were more relevant with higher a posteriori probability in those who experienced recent life stress. In summary, the CNR1 gene in interaction with life stress increased the risk of headache with nausea suggesting a specific pathological mechanism to develop migraine, and indicating that a subgroup of migraine patients, who suffer from life stress triggered migraine with frequent nausea, may benefit from therapies that increase the endocannabinoid tone. [ABSTRACT FROM AUTHOR]

The article offers information on an observational study related to the characterization of hair loss (HL) in the elderly. Topics discussed include causes of HL such as ageing of hair follicles, hormonal changes and various systemic diseases and medications; data regarding demographic and clinical characteristics of elderly patients with hair loss; and approval of study by the Cleveland Clinic Institutional Board Review.

Functional reorganization after focal brain injury can lead to altered cerebral metabolism of glucose. Sturge-Weber syndrome (SWS) with unilateral involvement is a clinical model for evaluating the effects of early focal brain injury on brain metabolism and function. In this study, 2-deoxy-2[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET) was used to measure glucose metabolism in cortex and basal ganglia, both ipsilateral and contralateral to the angioma, in 17 children (eight males, nine females; age range 1y 8mo-10y 4mo; mean 5y 7mo [SD 2y 11mo]) with unilateral SWS and epilepsy. The PET findings were compared with those of a control group of 11 age-matched children (four males, seven females; age range 3y-10y 8mo; mean 6y [SD 2y 10mo]) with partial epilepsy but normal magnetic resonance imaging and PET scans. In the SWS group, visual and parietal cortex showed decreased glucose metabolism on the side of the angioma (p=0.001) but increased metabolism on the contralateral side (p=0.002). In particular, glucose metabolism was very high in contralateral visual cortex of childrenwith SWS, showing severe occipital hypometabolism on the side of the angioma. Eight children with visual field defect showed increased metabolism in the contralateral visual cortex (p=0.012). These findings indicate that early, severe unilateral cortical damage in SWS may induce increased glucose metabolism in the contralateral visual cortex, probably reflecting reorganization. [ABSTRACT FROM AUTHOR]