Purification of urokinase by affinity chromatography.
Commercially available urokinase (EC 18.104.22.168), though highly active, is still contaminated with unrelated proteins and degradation fragments of urokinase. Further purification of a urokinase preparation by chromatography on benzamidine-Sepharose is described. The final preparation consisted of two molecular forms of urokinase with molecular weights of respectively 31 000 and 54 000. The 54 000-dalton urokinase appears to be composed of two protein chains, one of which is the 31 000-dalton urokinase. A monospecific antiserum against urokinase was raised.


The advantage of early liver transplantation for Wilson's disease using living donors.
The aim of the study was to investigate the surgical timing, results, and advantages of living-donor liver transplantation in patients who underwent liver transplantation due to Wilson's disease. The study included Wilson's patients who underwent liver transplantation and their live donors. Demographic information, preparations for surgery, liver transplant type, grafts used, results, and complications were examined. Between 2006 and 2020, 29 liver transplants were performed for 27 Wilson's patients in our clinic. The study included 11 female and 16 male patients, with a mean age of 20.8 ±11.1 years and a mean body mass index of 20.5 ±3.2 kg/m2. The mean MELD score of the adult patients was 16.5 ±6.3, and the mean PELD score of the paediatric patients was 19.6 ±17.2. Five patients underwent transplantation due to acute liver failure, and 22 patients with low MELD score had liver transplants due to chronic liver disease. Three patients who were referred with acute liver failure died in the perioperative period; no mortality was observed in the 22 elective patients. The overall survival was calculated as 88.8%. The 1-, 3-, and 5-year survival were 100% among elective early transplanted patients. Liver transplant is the most effective treatment for liver failure caused by Wilson' s disease. When performed promptly, living-donor liver transplantation results in high survival rates in cases of both acute liver failure and chronic liver failure, and it no deterioration of the patient's condition is evident.


Genotype-environment interaction for age at first calving in Holstein cows in Brazil.
Dairy cattle production is distributed throughout the Brazilian regions. However, Brazilian producing regions are different in air temperature and humidity, diet, birth season, and other factors that may alter the reproductive performances of cows. The age of the cow at first calving (AFC) is a good indicator of sexual precocity since it shows the beginning of the female reproductive life and has a great influence on cow replacement costs. Researches on genotype-environment interaction (GEI) show the importance of using specific bulls for the different production systems in Brazil since most semen used in the country is imported. The objective of this work was to evaluate GEI for AFC in Holstein cows in Brazil, using reaction norms. The statistical models used were the standard animal model, which disregards the GEI, and hierarchical reaction norm models with homoscedastic (HRNMHO) and heteroscedastic (HRNMHE) residual variance, and one (HRNMHO1S and HRNMHE1S) and two (HRNMHO2S and HRNMHE2S) steps. HRNMHO1S presented better fit to the data, with lower heritability for environments with lower AFC, and higher heritability for environments with higher AFC. The GEI found was complex, with a reclassification of bulls, denoting the importance of considering GEI for evaluation and selection of bulls for different production levels. The reduction of AFC is possible when using breeding bulls adapted to the tropical and subtropical conditions of Brazil.


Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction.
Given the limited accuracy of clinically used risk scores such as the Systematic COronary Risk Evaluation 2 system and the Second Manifestations of ARTerial disease 2 risk scores, novel risk algorithms determining an individual's susceptibility of future incident or recurrent atherosclerotic cardiovascular disease (ASCVD) risk are urgently needed. Due to major improvements in assay techniques, multimarker proteomic and lipidomic panels hold the promise to be reliably assessed in a high-throughput routine. Novel machine learning-based approaches have facilitated the use of this high-dimensional data resulting from these analyses for ASCVD risk prediction. More than a dozen of large-scale retrospective studies using different sets of biomarkers and different statistical methods have consistently demonstrated the additive prognostic value of these panels over traditionally used clinical risk scores. Prospective studies are needed to determine the clinical utility of a biomarker panel in clinical ASCVD risk stratification. When combined with the genetic predisposition captured with polygenic risk scores and the actual ASCVD phenotype observed with coronary artery imaging, proteomics and lipidomics can advance understanding of the complex multifactorial causes underlying an individual's ASCVD risk.


A method of quantitating injury inflicted in acute spinal cord studies.
Spinal cord trauma was induced in cats and Rhesus monkeys using an improved method which allows for accurate quantitation of the force delivered. The materials and methods described consist of a weight which is dropped down a centre shaft on to a strain gauge arch assembly which transfers the force to a teflon impounder resting on the exposed dura of the cord. The force transferred from the weight to the impounder is recorded by the strain gauge and thr force curve can be displayed on a storage oscilloscope. The force delivered to the cord can thus be photographed and quantitated. The construction of the strain gauge assembly and the application of the apparatus are discussed.


CXCL14 is no direct modulator of CXCR4.
C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) signaling is involved in ontogenesis, hematopoiesis, immune function and cancer. Recently, the orphan chemokine CXCL14 was reported to inhibit CXCL12-induced chemotaxis - probably by allosteric modulation of CXCR4. We thus examined the effects of CXCL14 on CXCR4 regulation and function using CXCR4-transfected human embryonic kidney (HEK293) cells and Jurkat T cells. CXCL14 did not affect dose-response profiles of CXCL12-induced CXCR4 phosphorylation, G protein-mediated calcium mobilization, dynamic mass redistribution, kinetics of extracellular signal-regulated kinase 1 (ERK1) and ERK2 phosphorylation or CXCR4 internalization. Hence, essential CXCL12-operated functions of CXCR4 are insensitive to CXCL14, suggesting that interactions of CXCL12 and CXCL14 pathways depend on a yet to be identified CXCL14 receptor.


Personality and emotional disorder in a community sample of migraine headache sufferers.
To investigate whether individuals who suffer from chronic, severe headaches have more personality abnormalities or emotional disorders than their healthy counterparts, 162 young adults with classical migraine, ascertained by community survey, were compared to matched control subjects without migraine. On the General Health Questionnaire, the prevalence of psychological symptoms among the migraine subjects was 2.5 times the prevalence among the control subjects. The migraine sufferers also had significantly higher scores on the psychoticism (women only), neuroticism, and lie scales of the Eysenck Personality Questionnaire. Frequency of migraine attacks was not related to scores on any of the scales. These results suggest that classical migraine is associated with psychological abnormalities.


[Internal electroshock in the treatment of chronic atrial fibrillation resistant to external cardioversion. Initial results apropos of 21 patients].
The authors report their experience involving 21 right endoatrial electroversions aimed at converting chronic atrial fibrillation resistant to external electroversion. All prior precautions were taken to ensure that the shocks were not in contact with an atrial wall nor over the node-His bundle (two dimensional radiological identification, endocavitary recordings). A total of 37 internal electric shocks were administered. Results were: 16 immediate successes out of 21 (72.2 per cent) and 12 short term successes out of 21 (57 per cent). The mean effective energy value was 200 Joules. There were no traumatic complications. The authors conclude that this technique is effective and reliable in the management of atrial fibrillation resistant to external electroversion.


Angiogenesis in Disease.
Angiogenesis is a multi-step process by which new blood capillaries are formed starting from preexisting functional vessels [...].


MarrowQuant 2.0: A Digital Pathology Workflow Assisting Bone Marrow Evaluation in Experimental and Clinical Hematology.
Bone marrow (BM) cellularity assessment is a crucial step in the evaluation of BM trephine biopsies for hematologic and nonhematologic disorders. Clinical assessment is based on a semiquantitative visual estimation of the hematopoietic and adipocytic components by hematopathologists, which does not provide quantitative information on other stromal compartments. In this study, we developed and validated MarrowQuant 2.0, an efficient, user-friendly digital hematopathology workflow integrated within QuPath software, which serves as BM quantifier for 5 mutually exclusive compartments (bone, hematopoietic, adipocytic, and interstitial/microvasculature areas and other) and derives the cellularity of human BM trephine biopsies. Instance segmentation of individual adipocytes is realized through the adaptation of the machine-learning-based algorithm StarDist. We calculated BM compartments and adipocyte size distributions of hematoxylin and eosin images obtained from 250 bone specimens, from control subjects and patients with acute myeloid leukemia or myelodysplastic syndrome, at diagnosis and follow-up, and measured the agreement of cellularity estimates by MarrowQuant 2.0 against visual scores from 4 hematopathologists. The algorithm was capable of robust BM compartment segmentation with an average mask accuracy of 86%, maximal for bone (99%), hematopoietic (92%), and adipocyte (98%) areas. MarrowQuant 2.0 cellularity score and hematopathologist estimations were highly correlated (R2 = 0.92-0.98, intraclass correlation coefficient [ICC] = 0.98; interobserver ICC = 0.96). BM compartment segmentation quantitatively confirmed the reciprocity of the hematopoietic and adipocytic compartments. MarrowQuant 2.0 performance was additionally tested for cellularity assessment of specimens prospectively collected from clinical routine diagnosis. After special consideration for the choice of the cellularity equation in specimens with expanded stroma, performance was similar in this setting (R2 = 0.86, n = 42). Thus, we conclude that these validation experiments establish MarrowQuant 2.0 as a reliable tool for BM cellularity assessment. We expect this workflow will serve as a clinical research tool to explore novel biomarkers related to BM stromal components and may contribute to further validation of future digitalized diagnostic hematopathology workstreams.


The anatomical basis for the sloping N2 plateau.
We examined the influence of asymmetry on the interaction of convection and gas-phase diffusion within the acinus of the lung. Single breaths of O2 were simulated by solving a differential equation for gas transport in two trumpet shaped units which were joined at a branch point and whose relative lengths and volumes were made to vary. Despite synchronous bulk flow to the from the units, in proportion to their relative volumes, the shorter unit always reached a higher O2 concentration (FO2) at end inspiration. Interdependence of gas transport at the branch point resulted in a falling FO2 within the shorter unit during expiration. The FO2 at the exit of the model therefore decreased progressively throughout expiration, simulating a sloping alveolar plateau. The simulations suggest that despite the relatively short distances separating parallel intra-acinar pathways, convective-diffusive interactions in the presence of asymmetry may produce substantial inhomogeneity in alveolar gas concentrations. Furthermore, the slope of the N2 plateau in the normal mammalian lung is explicable on the basis of the asymmetrical airway anatomy and well defined physical processes.


Tachyphylaxis to 5-HT3-receptor-mediated activation of vagal afferents is prevented by co-activation of 5-HT2 receptors.
Functional studies have provided evidence that 5-HT(3) ion-channel receptors (5-HT(3)Rs) on vagal cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR) rapidly desensitize upon repeated exposure to selective 5-HT(3)R agonists. G-protein-coupled 5-HT(2) receptors (5-HT(2)Rs) also exist on vagal afferents, although activation of these receptors does not elicit the BJR. However, there is in vivo evidence that 5-HT(2)Rs may regulate the activity of 5-HT(3)Rs. The aim of this study was to determine whether co-activation of 5-HT(2)Rs prevents desensitization of 5-HT(3)Rs mediating the BJR in conscious rats. The principal findings were that (1) tachyphylaxis rapidly developed to the BJR-mediated hemodynamic responses elicited by successive injections of 5-HT(3)R agonists and (2) co-injection of the selective 5-HT(2)R agonist, alpha-methyl-5-HT, prevented tachyphylaxis to the BJR-mediated hemodynamic responses elicited by the 5-HT(3)R agonists. Additional studies provided evidence that (1) tachyphylaxis to the 5-HT(3)R agonists was not due to impairment of the central or efferent processing of the BJR, and (2) the pressor responses elicited by alpha-methyl-5-HT were not responsible for preventing tachyphylaxis to the BJR reflex responses elicited by 5-HT(3)R agonists. These results suggest that the loss of response to 5-HT(3)R agonists is due to desensitization of 5-HT(3)Rs on vagal afferents mediating the BJR and that co-activation of 5-HT(2)Rs prevents the desensitization of these 5-HT(3)Rs.


Program enables 50 new initiatives in four months: 'Transforming Care at the Bedside' program.
Program targets bedside care on a standard hospital medical or surgical unit. Each staff nurse took on several projects, and all progressed simultaneously. Post-op order sets were adopted by nearly 100% of OB/GYN and orthopedic surgeons.


rac-12,14-Dicyclo-propyl-5,8,13,18,21-penta-oxapenta-cyclo-[184.108.40.206.0.0]tricosa-1(15),2(11),3,9(10),16,22(23)-hexa-ene.
The mol-ecule of the title compound, C(24)H(24)O(5), has crystallographic twofold symmetry, with the central O atom lying on the rotation axis. The dihedral angle between the best planes of the benzene rings fused to the oxepine fragment is 38.5 (1)°. The dioxine ring adopts a twist form with the ethyl-ene group C atoms deviating by 0.472 (5) and -0.248 (6) Å from the plane defined by the remaining ring atoms.


Association between ambient and household air pollution with carotid intima-media thickness in peri-urban South India: CHAI-Project.
Evidence linking ambient air pollution with atherosclerosis is lacking from low- and middle-income countries. Additionally, evidence regarding the association between household air pollution and atherosclerosis is limited. We evaluated the association between ambient fine particulate matter [particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5)] and biomass fuel use on carotid intima-media thickness (CIMT), a surrogate of atherosclerosis, in India. We analysed the third follow-up of the Andhra Pradesh Children and Parent Study cohort (2010-2012), which recruited participants from 28 peri-urban villages. Our primary outcome was mean CIMT, measured using a standardized protocol. We estimated annual average PM2.5 outdoors at residence using land-use regression. Biomass cooking fuel was self-reported. We fitted a within-between linear-mixed model adjusting for potential confounders. Among 3278 participants (48% women, mean age 38 years), mean PM2.5 was 32.7 [range 24.4-38.2] µg/m3, and 60% used biomass. After confounder adjustment, we observed positive associations between within-village variation in PM2.5 and CIMT in all participants [1.79%, 95% confidence interval (CI), -0.31 to 3.90 per 1 µg/m3 of PM2.5] and in men (2.98%, 95% CI, 0.23-5.72, per 1 µg/m3 of PM2.5). Use of biomass cooking fuel was associated with CIMT in all participants (1.60%, 95% CI, -0.46 to 3.65), especially in women with an unvented stove (6.14%, 95% CI, 1.40-10.89). The point-estimate for the PM2.5 association was larger in sub-groups with higher cardiometabolic risk profile. Ambient and household air pollution were positively associated with CIMT in a peri-urban population of India, although with limited precision for some estimates. We observed differences in the association between ambient and household air pollution and CIMT by gender.


G protein-coupled receptors for free fatty acids.
Free fatty acids (FFAs) are not only an important direct source of energy but they also play key roles in regulating a range of physiological responses. Although it was long assumed that such effects of FFAs must occur following cellular uptake, and potentially via their conversion to fatty acyl-CoAs, it is now apparent that FFAs also function directly as agonists at a number of G protein-coupled receptors (GPCRs). Tissue distribution studies and, subsequently, siRNA knock-down experiments have indicated key roles for these GPCRs in glucose homeostasis, adipogenesis, white cell recruitment and potentially in a range of other processes. Considerable interest is thus now centred on the generation of potent and selective small molecule ligands, both as tool compounds to further unravel the biology and physiological role of this group of GPCRs and as starting points for possible therapeutic intervention in a range of areas, particularly those associated with 'metabolic syndrome'.


Analysis of microsatellite instability in CRISPR/Cas9 editing mice.
Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR- associated (Cas) protein 9 system is a novel and powerful tool which is widely used for genome editing. CRISPR/Cas9 is RNA-guided and can lead to desired genomic modifications. However, whether the CRISPR/Cas9-mediated genome editing causes genomic alterations and genomic instability, such as microsatellite instability (MSI), is still unknown. Here we detected MSI in 21 CRISPR/Cas9 mouse strains using a panel of 42 microsatellite loci which were selected from our previous studies. Surprisingly, MSI occurrence was common in CRISPR/Cas9 modified genome, and most of the strains (19/21, 90.5%) examined showed MSI. Of 42 loci examined, 8 loci (8/42, 19.05%) exhibited MSI in the Cas9 editing mice. The Ttll9 (4/42, 9.5%) were the most unstable strains, and D10Mit3 and D10Mit198 (9/21, 42.9%) were considered to be the most "hot" loci in the Cas9 strains we tested. Through analyzing the mutation of microsatellite loci, we provide new insights into the genomic alterations of CRISPR/Cas9 models and it will help us for a better understanding of this powerful technology.


The feeling of a presence and verbal meaningfulness in context of temporal lobe function: factor analytic verification of the muses?
We hypothesized that the feeling of a presence, particularly during periods of profound verbal creativity (reading or writing prose or poetry), is an endemic cognitive phenomenon. Factor analyses of 12 clusters of phenomenological experiences from 348 men and 520 women supported the hypothesis. We conclude that periods of intense meaningfulness (a likely correlate of enhanced burst-firing in the left hippocampal-amygdaloid complex and temporal lobe) allow access to nonverbal representations that are the right hemispheric equivalents of the sense of self; they are perceived as "a presence." The relevance of our results to the theories of Jaynes, Bear, Edelman, and MacLean is discussed.


JNK Signaling Regulates Cellular Mechanics of Cortical Interneuron Migration.
Aberrant migration of inhibitory interneurons can alter the formation of cortical circuitry and lead to severe neurologic disorders including epilepsy, autism, and schizophrenia. However, mechanisms involved in directing the migration of interneurons remain incompletely understood. Using a mouse model, we performed live-cell confocal microscopy to explore the mechanisms by which the c-Jun NH2-terminal kinase (JNK) pathway coordinates leading process branching and nucleokinesis, two cell biological processes that are essential for the guided migration of cortical interneurons. Pharmacological inhibition of JNK signaling disrupts the kinetics of leading process branching, rate and amplitude of nucleokinesis, and leads to the rearward mislocalization of the centrosome and primary cilium to the trailing process. Genetic loss of Jnk from interneurons also impairs leading process branching and nucleokinesis, suggesting that important mechanics of interneuron migration depend on the intrinsic activity of JNK. These findings highlight key roles for JNK signaling in leading process branching, nucleokinesis, and the trafficking of centrosomes and cilia during interneuron migration, and further implicates JNK signaling as an important mediator of cortical development.


Variation of particulate organic carbon and its relationship with bio-optical properties during a phytoplankton bloom in the Pearl River estuary.
In this study, variations in the particulate organic carbon (POC) were monitored during a phytoplankton bloom event, and the corresponding changes in bio-optical properties were tracked at one station (114.29°E, 22.06°N) located in the Pearl River estuary. A greater than 10-fold increase in POC (112.29-1173.36 mg m⁻³) was observed during the bloom, with the chlorophyll a concentration (Chl-a) varying from 0.984 to 25.941 mg m⁻³. A power law function is used to describe the relationship between POC and Chl-a, and the POC:Chl-a ratio tends to change inversely with Chl-a. Phytoplankton carbon concentration is indirectly estimated using the conceptual model proposed by Sathyendranath et al. (2009), and this carbon is found to contribute 47.21% (±10.65%) to total POC. The estimated carbon-to-chlorophyll ratio of phytoplankton in diatom-dominated waters is found to be comparable with results reported in the literature. Empirical algorithms for determining the concentrations of Chl-a and POC were developed based on the relationships of these variables with the blue-to-green reflectance ratio. With these bio-optical models, the levels of particulate organic carbon and Chl-a could be predicted from the radiometric data measured by a marine optical buoy, which showed much more detailed information about the variability in biogeochemical parameters during this bloom event.


PCR-DGGE analysis of bacterial community dynamics in kava beverages during refrigeration.
Kava beverages are highly perishable even under refrigerated conditions. This study aimed to investigate the bacterial community dynamics in kava beverages during refrigeration. Four freshly made kava beverages were obtained from kava bars and stored at 4°C. On days 0, 3 and 6, the aerobic plate count (APC), lactic acid bacteria (LAB) count and yeast and mould count (YMC) of the samples were determined. Meanwhile, bacterial DNA was extracted from each sample and subjected to the polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). Moreover, species-specific PCR assays were employed to identify predominant Pseudomonas spp. involved in kava spoilage. Over the storage period, the APC, LAB count and YMC of the four kava beverages all increased, whereas their pH values decreased. The DGGE profile revealed diverse bacterial populations in the samples. LAB, such as Weissella soli, Lactobacillus spp. and Lactococcus lactis, were found in the kava beverages. Species-specific PCR assays detected Pseudomonas putida and Pseudomonas fluorescens in the samples; Ps. fluorescens became dominant during refrigeration. LAB and Pseudomonas may play a significant role in the spoilage of kava beverages. This study provides important information that may be used to extend the shelf life of kava beverages.


Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection.
There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.


Managing atopic dermatitis with systemic therapies in adults and adolescents: An Australian/New Zealand narrative.
With the rapid development of new, targeted therapies for the treatment of moderate/severe atopic dermatitis, it is opportune to review the available conventional systemic agents. We assess the published evidence for systemic therapies for atopic dermatitis and amalgamate this with real-world experience. Discussions are centred on when systemic therapy should be considered, which drug(s), what dose, how to sequence or combine these therapies, how long they should be continued for and what is considered success.


Understanding and applying the principles of contemporary medical professionalism: illustration of a suggested approach, part 2.
In recent years, formal professionalism education, training, and assessment have been introduced to medical schools and accredited residency training programs. Current constructs of medical professionalism characterize it as a multidimensional competency rather than a trait. Medical professionalism is a belief system for organizing and delivering care, in which group members (medical professionals) promise patients and the public that they will self-regulate (ie, ensure that medical professionals live up to standards of competence and ethical values). Physicians who are good professionals have lapses in professionalism. Responses to professional lapses should focus on remediation. Failure of groups of professionals to enforce the standards and values can convey to patients and the public a lack of trustworthiness and thereby undermine the foundation of professionalism, the social contract. The Physician Charter sets forth the 3 fundamental principles and 10 commitments that offer guidance in some of the most challenging situations. One example is illustrated herein and is continued from Part 1 of this two-part series.


Sleep Quality in Patients with Rheumatoid Arthritis and Associations with Pain, Disability, Disease Duration, and Activity.
We aimed to assess the subjective sleep quality in patients with rheumatoid arthritis (RA) and its correlation with disease activity, pain, inflammatory parameters, and functional disability. In a cross-sectional study, patients with confirmed RA diagnosis responded to a questionnaire (consisting of socio-demographic data, the Health Assessment Questionnaire Disability Index, and the Medical Outcome Study Sleep Scale). Disease activity was assessed with the Clinical Disease Activity Index, and pain levels using the visual analogue scale. In addition, inflammatory markers (C-reactive protein, interleukin-6, and tumor necrosis factor alpha) were analyzed. Ninety-five patients were analyzed, predominantly female, with an average age of 50.59 (9.61) years. Fifty-seven percent reported non-optimal sleep duration, where functional disability (92.7% vs. 69.8%; p = 0.006) and higher median pain levels (3.75 (2.3⁻6.0) vs. 2.5 (2.0⁻3.5); p = 0.003) were also more prevalent. No differences in sociodemographic variables, disease duration or activity, inflammatory parameters, or use of biological and corticosteroid therapy were observed. The multivariate regression analysis showed that more intense pain was associated with a lower likelihood of optimal sleep (odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.47⁻0.98, p = 0.038). Patients with RA report a high prevalence of non-optimal sleep, which is linked to pain level. Clinicians need to be aware of this issue and the potential effects on health and functional status.


Nothing magical: pantomimed grasping is controlled by the ventral system.
In a recent amendment to the two-visual-system model, it has been proposed that actions must result in tactile contact with the goal object for the dorsal system to become engaged (Whitwell et al., Neuropsychologia 55:41-50, 2014). The present study tested this addition by assessing the use of allocentric information in normal and pantomime actions. To this end, magicians, and participants who were inexperienced in performing pantomime actions made normal and pantomime grasps toward objects embedded in the Müller-Lyer illusion. During pantomime grasping, a grasp was made next to an object that was in full view (i.e., a displaced pantomime grasping task). The results showed that pantomime grasps took longer, were slower, and had smaller hand apertures than normal grasping. Most importantly, hand apertures were affected by the illusion during pantomime grasping but not in normal grasping, indicating that displaced pantomime grasping is based on allocentric information. This was true for participants without experience in performing pantomime grasps as well as for magicians with experience in pantomiming. The finding that the illusory bias is limited to pantomime grasping and persists with experience supports the conjecture that the normal engagement of the dorsal system's contribution requires tactile contact with a goal object. If no tactile contact is made, then movement control shifts toward the ventral system.


Description of the larva of Ochthebius capicola (Coleoptera: Hydraenidae) from marine rockpools of South Africa.
Larval instars II and III of Ochthebius (Ochthebius) capicola (Pdringuey 1892) from South Africa are described and illustrated by SEM, including a detailed analysis of their chaetotaxy and porotaxy. Specimens used in this study were collected with adults of the same species in marine rockpools. The larval morphology of O. capicola is compared to that of other members of the same genus occurring in this habitat, contributing to the current taxonomic and phylogenetic debate on the intrageneric taxonomy of Ochthebiinae.


Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity.
Cyanide is a deadly compound used as a terrorist agent. Current FDA approved antidotes require intravenous administration, limiting their utility in a mass casualty scenario. Dimethyl trisulfide (DMTS), a sulfur-based molecule, binds cyanide converting it to the less toxic by-product thiocyanate. Studies evaluating efficacy in rodents have been performed, but a large, clinically relevant animal model has not been reported. This study evaluates the efficacy of intramuscular DMTS on survival and clinical outcomes in a swine model of acute, severe cyanide toxicity. Anesthetized swine were instrumented for continuous monitoring of hemodynamics. Prior to potassium cyanide infusion animals were acclimated and breathing spontaneously. At 5-minutes post-apnea animals were treated with DMTS or saline. Vital signs, hemodynamics, and laboratory values were evaluated at various time points. Baseline values and time to apnea were similar in both groups. Survival in the DMTS treated group was 83.3% and 0% in saline controls (p = .005). The DMTS group returned to breathing at a mean time of 19.3 ± 10 min after antidote, control animals did not return to breathing (CI difference 8.8, 29.8). At the end of the experiment or time of death, mean lactate was 9.41 mmol/L vs. 4.35 mmol/L (CI difference -10.94,0.82) in the saline and DMTS groups, respectively and pH was 7.20 vs. 7.37 (CI difference -0.04, 0.38). No adverse effects were observed at the injection site. Intramuscular administration of DMTS improves survival and clinical outcomes in our large animal swine model of acute cyanide toxicity.


MRI characteristics of intralabyrinthine schwannoma on post-contrast 4 h-delayed 3D-FLAIR imaging.
The purpose of this study was to describe the MRI characteristics of intralabyrinthine schwannoma (ILS) on post contrast three-dimensional (3D) fluid-attenuation-inversion-recovery (FLAIR) images obtained four hours after intravenous administration of a gadolinium-based contrast agent (4h-3D-FLAIR). This IRB-approved retrospective multi-center study included patients presenting with typical ILS from January 2016 to October 2020. All medical charts were systematically collected. All MRI examinations, including 4h-3D-FLAIR images, were reviewed by two board-certified neuroradiologists. Main outcome measures were location, signal intensity and associated anomalies of ILS. Twenty-seven out of 8730 patients (0.31%) referred for the investigation of a cochleovestibular disorder had a final diagnosis of ILS. There were 13 men and 14 women with a mean age of 52 ± 17 (SD) years (age range: 20-86 years). The most common clinical presentation was unilateral progressive sensorineural hearing loss (16/27; 59%). All ILS were unilateral and 15 (15/27; 55%) were intracochlear. All ILS presented as a hypointense filling defect within the labyrinth on T2-weighted images that enhanced on post-contrast T1-weighted images. On 4h-3D-FLAIR images, all ILS presented as a hypointense filling defect, associated with diffuse perilymphatic hyperintensity. Two patients (2/27; 7%) presented with ipsilateral endolymphatic hydrops. ILS displays consistent features on post-contrast 4h-3D-FLAIR images. ILS should not be confused with endolymphatic hydrops and requires a systematic analysis of the corresponding T2-weighted images.


The efficacy and safety of topical administration of tranexamic acid in spine surgery: a meta-analysis.
We conducted a meta-analysis from randomized controlled trials (RCTs) and non-RCTs to assess the efficacy and safety of tranexamic acid (TXA) in spine surgery. Potentially relevant academic articles were identified from the Cochrane Library, MEDLINE (1966-2017.11), PubMed (1966-2017.11), Embase (1980-2017.11), and ScienceDirect (1985-2017.11). Secondary sources were identified from the references of the included literature. The pooled data were analyzed using RevMan 5.1. Three RCTs and one non-RCT met the inclusion criteria. There were significant differences in total blood loss (MD = - 267.53, 95% CI - 373.04 to - 106.02, P < 0.00001), drainage volume (MD = - 157.00, 95% CI - 191.17 to - 122.84, P < 0.00001), postoperative hemoglobin level (MD = 0.95, 95% CI 0.44 to 1.47, P = 0.0003), and length of hospital stay (MD = - 1.42, 95% CI - 1.92 to - 0.93, P < 0.00001). No significant differences were found regarding transfusion requirement, deep vein thrombosis (DVT), pulmonary embolism (PE), wound hematoma, and infection between the two groups. The present meta-analysis indicated that the topical application of TXA in spinal surgery decreases the total blood loss and drainage volume and preserves higher postoperative hemoglobin level without increasing the risk of DVT infection, hematoma, DVT, and PE.


Improvement of aesthetics in a patient with tetracycline stains using the injectable composite resin technique: case report with 24-month follow-up.
This case report describes the conservative management of generalised tetracycline stains by means of the injectable composite resin technique. This time-efficient technique obtained optimal and satisfactory aesthetic outcomes. Both the patient and the clinician were very satisfied with the results. Composite veneers realised with injected flowable resin composites are an effective treatment, with minimally invasive possibilities, providing the case selection protocol is correct. In addition, it can be considered as a more economical treatment option.


Inhibitory interaction between the vestibulo-ocular reflexes arising from semicircular canals of rabbits.
In anesthetized albino rabbits, electric pulse stimulation was applied to ampullary branches of the vestibular nerve. Reflex discharges evoked from a canal in an extraocular muscle were depressed very effectively by conditioning stimulation at a certain other canal. The present systematic survey revealed that this reflex depression occurred specifically in 3 combinations of conditioning and testing canals; 1. anterior and posterior canals of the same side; 2. anterior and posterior canals of the opposite sides; and 3. horizontal canals of the two sides. Occurrence of postsynaptic inhibition in oculomotor neurons, on the other hand, was indicated by appearance of slow muscle potentials in extraocular muscles. It was confirmed that this motoneuronal inhibition did not contribute to the reflex depression in the above combination (1). Even in combinations (2) and (3), the accompanying motoneuronal inhibition was eliminated by adjusting intensities of canal stimuli or by severing its pathway in the medulla, or it was discriminated from the reflex depression by their different latencies and time courses. Hence, it was concluded that the reflex depression was attributable, at least largely, to non-motoneuronal inhibition, presumably postsynaptic inhibition at relay neurons for vestibulo-ocular reflexes. Slow muscle potentials evoked from a canal were also used as testing responses, but their depression could not be detected after conditioning at other canals.


Cardiac Shock Wave Therapy in Coronary Artery Disease: A Systematic Review and Meta-Analysis.
Coronary artery disease (CAD) has been one of the leading causes of morbidity and mortality worldwide. Cardiac shock wave therapy (CSWT) is a novel and non-invasive therapy for CAD. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy of CSWT on CAD. We performed a comprehensive search of electronic databases such as PubMed, Embase, the Cochrane Library, and Wanfang Data in October 2021. The results were reported as weighted mean difference (WMD) with a 95% confidence interval (CI). Statistical heterogeneity scores were assessed with the standard Cochran's Q test and the I 2 statistic. A total of 8 randomized trials and 2 prospective cohort studies, together involving 643 patients (n = 336 CSWT and n = 307 control), were included in our study. Eight studies with 371 patients showed significantly improved rest left ventricular ejection fraction (LVEF) with CSWT as compared to that of the control group (WMD 3.88, 95% CI 1.53-6.23, p = 0.001, I 2 = 51.2%). Seven studies with 312 patients reported left ventricular internal diameter in diastole (LVIDd) were markedly decreased in the CSWT group compared to the control group (WMD -1.81, 95% CI -3.23 to -0.39, p = 0.012, I 2 = 20.3%). The summed stress score significantly favored the CSWT group (WMD -3.76, 95% CI -6.15 to -1.37, p = 0.002, I 2 = 56.8%), but there was no significant difference for the summed rest score. Our data were acquired from studies without a perceived high risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. Based on data from our present meta-analysis, CSWT was shown to moderately improve myocardial perfusion and cardiac function among patients with CAD, which would provide the clinicians with a meaningful and valuable option. The meta-analysis was registered on the Open Science Framework (OSF) (https://osf.io/r2xf9).


[Effect of bezafibrate on lipoprotein secretion by cultured human hepatocytes].
The rate of synthesis and secretion of lipid and apoprotein components of lipoprotein fractions and of proteins of the nonlipoprotein fraction d greater than 1.21 g/ml by human hepatocytes in culture was determined. The cells were incubated for 18 hours in the media containing [14C] acetate or [3H]-marked leucine in the presence of bezafibrate or without it. VLDL, HDL and d greater than 1.21 g/ml fractions were separated by differential ultracentrifugation. The lipids were divided using thin-layer chromatography, and the apoprotein-using SDS-electrophoresis in polyacrylamide gel. Bezafibrate in the therapeutic concentration of 10 microM specifically inhibits apoprotein and VLDL lipid secretion. Lowered secretion of all VLDL apoproteins was revealed, which points to a decrease in the number of secreted particles. The effect of bezafibrate was found to be associated with the inhibition of the intracellular synthesis of lipids. The secretion of HDL proteins and of d greater than 1.21 g/ml fraction proteins was unchanged with 10 microM of bezafibrate.


Lipid A, the immunostimulatory principle of lipopolysaccharides?
Lipid A has been found to be an inducer of IL-1 with similar potency as LPS. Partial structures of lipid A or core oligosaccharides are less active or not active at all. We propose that lipid A is the structure responsible for induction of immunostimulatory or immunoregulatory properties of LPS.


Analytical characterization of peptide contaminants of L-tryptophan.
Reversed-phase liquid chromatographic fractions of extracts of 2 preparations of eosinophilia-myalgia syndrome (EMS)-associated L-tryptophan were analyzed by proton nuclear magnetic resonance spectrometry, mass spectrometry, microbial-growth inhibition, and amino acid residue analyses. Fraction components demonstrated properties of an antibiotic peptide resembling bacitracin. Many peptide antibiotics like bacitracin are secondary metabolites of Bacillus species, genus of the tryptophan producer organism for the implicated manufacturer. In order to determine whether a correlation exists between individual EMS cases and the concentration of peptides or bacitracin consumed, reliable methods must be developed for quantification of the total of isoforms.


Disorders of hemostasis and excessive menstrual bleeding: prevalence and clinical impact.
The prevalence and impact of most underlying disorders of hemostasis are reviewed in women with excessive menstrual bleeding. The most common underlying bleeding disorder is von Willebrand disease, which occurs in only 1% to 2% of the general population but in approximately 13% of women with excessive menstrual bleeding.


Contribution of caudal ventrolateral medulla to the cardiovascular responses elicited by activation of bed nucleus of the stria terminalis.
The contribution of caudal ventrolateral medulla (cVLM) to the mean arterial pressure (MAP) and heart rate (HR) responses elicited by microinjections of L-glutamate (GLU) into the cardiovascular responsive region of bed nucleus of the stria terminalis (BST) was investigated in the chloralose-anesthetized, paralysed and artificially ventilated rat. Unilateral injections of GLU into BST elicited decreases in MAP of -25 +/- 3 mmHg (n = 10) and HR of -13 +/- 3 bpm (n = 10). These cardiovascular responses were not altered after a 100 nl microinjection of 0.9% NaCl into cVLM. However, the magnitudes of the decreases in MAP and HR were attenuated (-11 +/- 3 mmHg and HR, -4 +/- 1 bpm, respectively) 5 min after a 100 nl microinjection of the reversible synaptic blocker cobalt chloride (CoCl2) into cVLM. Restimulation of BST 40 min after the 100 nl microinjection of CoCl2 in cVLM elicited cardiovascular responses that were not significantly different in magnitude from those evoked before the microinjection of CoCl2 (MAP, -23 +/- 4 mmHg; HR, -12 +/- 5 bpm). In an additional series of experiments (n = 3), restimulation of BST 1 h after an ipsilateral electrolytic lesion in cVLM elicited decreases in MAP (-11 +/- 2 mmHg) and HR (-8 +/- 4 bpm) that were significantly smaller than those elicited prior to cVLM lesion. These data suggest that a component of the pathways originating in BST involved in mediating depressor responses and cardiac slowing relays in cVLM.


Markedly increased periprocedure mortality of cardiac catheterization in patients with severe narrowing of the left main coronary artery.
In early reports, coronary arteriography in patients with left main (LM) coronary artery disease (CAD) had a substantial risk, but recent reports suggest that arteriography in these subjects is now associated with a low mortality. The present study was performed to examine the periprocedure mortality in patients with LMCAD undergoing catheterization, to compare the periprocedure mortality in these patients with that in subjects with less CAD and to identify the variables associated with pericatheterization mortality in this patient cohort. Of 4,009 patients undergoing elective coronary arteriography from 1978 to 1992, 176 had LMCAD. Of the 10 deaths during or within 24 hours of catheterization, 5 occurred in these 176 subjects. This periprocedure mortality of 2.8% in patients with LMCAD was > 20 times that of those without LMCAD (0.13%). In comparison with the 171 patients with LMCAD who survived, the 5 who died were older (67 +/- 8 vs 58 +/- 12 years), and had more severe LMCAD (92 +/- 10% vs 72 +/- 16%) and a lower cardiac index (1.9 +/- 0.4 vs 2.6 +/- 0.7 liters/min/m2) (p < 0.05 for all 3 variables). Thus, even in the 1980s and early 1990s, patients with LMCAD have a high pericatheterization mortality, especially those who are older and have severe LMCAD.


The need for organization and collaboration: establishing a thymoma registry.
Thymic epithelial tumors (TETs) are rare thoracic malignancies, with an overall incidence of 1.5 per million people. The TET Registry Project aims at federating an international network to provide a resource to support studies on the epidemiology and clinical management and monitoring some standards of clinical care of these tumors. Recorded data span all the specifications of the management of TET: paraneoplastic syndromes, histologic subtypes, diagnostic and staging issues, multimodal treatment strategies, and exceptional surgeries and therapies. Data collection for the registry is done both prospectively and retrospectively through different paths to allow the involvement of as many centers as possible, including data-sharing arrangements with some already established databases. This ambitious project implies the early setting of strong quality assurance measures looking at completeness, consistency, and accuracy of the data. These measures require a significant and long-term financial support that will also be free of possible sources of conflicts of interests.


Flavone acetic acid distribution in human malignant tumors.
The pharmacokinetics of flavone acetic acid (FAA) after a dose of 4.8 mg/m2 given i.v. over 1 h was investigated in 13 patients with different solid tumors. The mean volume of distribution and clearance were 52 +/- 4 l/m2 and 2.6 +/- 0.2 l/h x m2, respectively. A tumor or metastasis biopsy was obtained from six patients 2 h after the end of infusion. Tumor FAA levels ranged from 39.6 to 148.8 micrograms/g and were similar to those obtained after a therapeutic i.v. dose of 200 mg/kg FAA in animals bearing Pan/03 tumor, which is very sensitive to the drug. Although FAA tumor concentration could be detected only during one interval and we therefore cannot draw a definitive conclusion, differences in the agent's antitumor activity in mice and patients (i.e. very active in the former and inactive in the latter) are apparently not due to discrepancies in drug distribution and pharmacokinetics.


The unique enzymatic and mechanistic properties of plant myosins.
Myosins are molecular motors that move along actin-filament tracks. Plants express two main classes of myosins, myosin VIII and myosin XI. Along with their relatively conserved sequence and functions, plant myosins have acquired some unique features. Myosin VIII has the enzymatic characteristics of a tension sensor and/or a tension generator, similar to functions found in other eukaryotes. Interestingly, class XI plant myosins have gained a novel function that consists of propelling the exceptionally rapid cytoplasmic streaming. This specific class includes the fastest known translocating molecular motors, which can reach an extremely high velocity of about 60μms(-1). However, the enzymatic properties and mechanistic basis for these remarkable manifestations are not yet fully understood. Here we review recent progress in understanding the uniqueness of plant myosins, while emphasizing the unanswered questions.


Sildenafil ameliorates cognitive deficits and tau pathology in a senescence-accelerated mouse model.
Aging is associated with a deterioration of cognitive performance and with increased risk of neurodegenerative disorders. In the present study we tested whether the specific phosphodiesterase 5 inhibitor sildenafil could ameliorate the age-dependent cognitive impairments shown by the senescence-accelerated mouse prone-8 (SAMP8). Sildenafil administration (7.5 mg/kg for 4 weeks) to 5-month-old SAMP8 mice attenuated spatial learning and memory impairments shown by these mice in the Morris Water Maze. Tau hyperphosphorylation (AT8 but not PHF-1 epitope) shown by SAMP8 mice at this age was also decreased in the hippocampus of sildenafil-treated mice, an effect probably related to a decrease in cyclin-dependent kinase 5 protein expression and activity (p25/p35 ratio). Interestingly, sildenafil also phosphorylated Akt, which was associated with an increase of glycogen synthase kinase-3β phosphorylation, providing a plausible explanation for the reductions in tau hyperphosphorylation (AT8 and PHF-1 epitopes) and attenuation of cognitive deficits shown by 9-month-old SAMP8 mice. Overall, sildenafil might be beneficial in age-related brain dysfunction and could be an emerging candidate for the treatment of other neurodegenerative diseases.


Synthesis of silver nanowires and their applications in the electrochemical detection of halide.
A silver nanowires modified platinum (Ag NWs/Pt) electrode was developed for simultaneous and selective determination of chloride, bromide and iodide ions by cyclic voltammetry in aqueous solutions. Silver nanowires were synthesized by an l-cysteine-assisted poly (vinyl pyrrolidone) (PVP)-mediated polyol route. X-ray diffraction (XRD) and scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS) were employed to investigate the prepared nanowires. The intrinsic high surface area and the fast electron transfer rate ascribed from the nanowire structure could further improve halide detection performance. The determination was based on measurement of the well-separated oxidation peak currents of respective silver halides formed on the surface of silver during an anodic potential sweep. The concentration range was linear from 50 μM to 20.2mM for bromide and iodide and 200 μM to 20.2mM for chloride, and the sensitivity was 0.059 μA/mM, 0.042 μA/mM and 0.032 μA/mM for chloride, bromide and iodide, respectively. The correlation coefficient was 0.999 in each case. The Ag NWs/Pt electrode offered a useful platform for the development of a highly sensitive halide sensor.


Age, gender and the effectiveness of high-threat letters: an analysis of Oregon's driver improvement advisory letters.
The Oregon Driver Improvement Program monitors driver records and takes corrective action at each of four levels. The advisory letter is the first level. An automated quality control system randomly withholds actions from five percent of drivers, producing a control group. Records of 27,026 advisory letter recipients and 1453 control subjects were analyzed. Of the 27,026 letter recipients, 13,623 received a randomly assigned, experimental soft-sell letter and the rest a standard letter. Records were monitored for 24 subsequent months. Overall, those receiving either advisory letter had fewer traffic accidents than the control group, and the standard letter is significantly more effective than the soft-sell letter. However there are several apparent differences in effectiveness by age and by gender. The standard letter is clearly more effective for younger drivers but the soft-sell letter appears to be most effective for drivers over age 45. Considering gender, both letters reduce collisions but the standard letter is more effective for men. For women, the standard letter is more effective than the soft-sell letter, but not more effective than no letter. In fact, accident-free survival for women receiving no letter was nominally but not significantly higher than for women receiving either letter. There are no significant differences in moving violations. However, with regard to major traffic violations, those receiving letters had significantly higher violation free survival, although there were also notable differences in effectiveness, by age.


Assessment of skeletal age in youth female soccer players: Agreement between Greulich-Pyle and Fels protocols.
The purpose of the study was to evaluate the agreement between the Fels and Greulich-Pyle methods for the assessment of skeletal age (SA) in female youth soccer players. The sample included 441 Portuguese players 10.08-16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand-wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich-Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups: late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods. Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under-13: kappa = 0.48; under-14: kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under-17: 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method. GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status.


An XGBoost-based model for assessment of aortic stiffness from wrist photoplethysmogram.
Carotid-femoral pulse wave velocity (cf-PWV) is the gold standard for non-invasive assessment of aortic stiffness. Photoplethysmography used in wearable devices provides an indirect measurement method for cf-PWV. This study aimed to construct a cf-PWV prediction method based on the XGBoost algorithm and wrist photoplethysmogram (wPPG) for the early screening of arteriosclerosis in primary healthcare. Data from 210 subjects were used for modeling, and 100 subjects were used as an external validation set. The wPPG pulse waves were filtered by discrete wavelet transform, and various features were extracted from each waveform, including two original indexes. The extraction rate (ER) and Pearson P were calculated to evaluate the applicability of each feature for model training. The magnitude of cf-PWV was predicted by an XGBoost-based model using the selected features and basic physiological parameters (age, sex, height, weight and BMI). The level of aortic stiffness was classified by a 3-classification strategy according to the standard cf-PWV (measured by the Complior device). Bland-Altman plot, Pearson correlation analysis, and accuracy tested performance from two aspects: predicting the magnitude of cf-PWV and classifying the level of aortic stiffness. In the external validation set (n = 100, age range 22-79), 97 subjects obtained features (ER = 97%). The predicted cf-PWV was significantly correlated with the standard cf-PWV (r = 0.927, P < 0.001). The accuracy (AC) of the 3-classification was 85.6%. The interrater agreement for assessing aortic stiffness was at least substantial (quadratically weighted Kappa = 0.833). The multi-parameter fusion cf-PWV prediction method based on the XGBoost algorithm and wPPG pulse wave analysis proves the feasibility of atherosclerosis screening in wearable devices.


Reliability and Discriminative Validity of Wearable Sensors for the Quantification of Upper Limb Movement Disorders in Individuals with Dyskinetic Cerebral Palsy.
Background-Movement patterns in dyskinetic cerebral palsy (DCP) are characterized by abnormal postures and involuntary movements. Current evaluation tools in DCP are subjective and time-consuming. Sensors could yield objective information on pathological patterns in DCP, but their reliability has not yet been evaluated. The objectives of this study were to evaluate (i) reliability and (ii) discriminative ability of sensor parameters. Methods-Inertial measurement units were placed on the arm, forearm, and hand of individuals with and without DCP while performing reach-forward, reach-and-grasp-vertical, and reach-sideways tasks. Intra-class correlation coefficients (ICC) were calculated for reliability, and Mann-Whitney U-tests for between-group differences. Results-Twenty-two extremities of individuals with DCP (mean age 16.7 y) and twenty individuals without DCP (mean age 17.2 y) were evaluated. ICC values for all sensor parameters except jerk and sample entropy ranged from 0.50 to 0.98 during reach forwards/sideways and from 0.40 to 0.95 during reach-and-grasp vertical. Jerk and maximal acceleration/angular velocity were significantly higher for the DCP group in comparison with peers. Conclusions-This study was the first to assess the reliability of sensor parameters in individuals with DCP, reporting high between- and within-session reliability for the majority of the sensor parameters. These findings suggest that pathological movements of individuals with DCP can be reliably captured using a selection of sensor parameters.


Upper limb robotic assessment: Pilot study comparing velocity dependent resistance in individuals with acquired brain injury to healthy controls.
Assessment of velocity dependent resistance (VDR) can provide insights into spasticity in individuals with upper motor neuron syndrome. This study investigates the relationship between Modified Ashworth scores and a biomechanical based representation of VDR using a rehabilitation robot. Comparisons in VDR are made for the upper limb (UL) between individuals with acquired brain injury and healthy controls for the para-sagittal plane. The system manipulates the individual's limb through five flexion and extension motions at increasing speeds to obtain force profiles at different velocities. An approximation of VDR is calculated and analyzed statistically against clinical scales and tested for interactions. All individuals (aged 18-65), including healthy controls exhibited VDR greater than 0 (P < 0.05). MAS scores were found to be related to VDR (P < 0.05) with an interaction found between MAS Bicep and Tricep scores (P < 0.01). Considering this interaction, evidence of differences in VDR were found between several neighboring assessment score combinations. The robot can detect and quantify VDR that captures information relevant to UL spasticity. Results suggests a better categorization of VDR is possible and supports further development of rehabilitation robotics for assisting spasticity assessment.


Five probable factors responsible for the COVID-associated mucormycosis outbreak in India.
The second wave of COVID-19 due to the delta variant (B.1.617.2) led to a rapid rise in total coronavirus and COVID-associated mucormycosis cases reported from India. Hence, our study explored the possible causes of a rapid upsurge in COVID-associated mucormycosis, which has accounted for over 70% of global cases. Factors associated with the increase in mucormycosis cases in COVID-19 patients include diabetes mellitus, steroid overdose, high iron levels, and immunosuppression, combined with other possible factors, such as unhygienic conditions, prolonged hospitalization, use of ventilators, and leaky humidifiers in oxygen cylinders. These create an ideal environment for contracting mucormycosis. However, these cases could be reduced by disseminating simple preventive measures and creating awareness among the medical society and general public of this rare and deadly contagion of COVID-associated mucormycosis. The identification of early symptoms will also help to restrict the spread of lethal fungal diseases. Furthermore, a collaborative team of surgeons, ophthalmologists, physicians, and otolaryngologists would be required in the hospital wards to accelerate surgeries on severely impacted patients.


Long-term effects of appendectomy in humans: is it the optimal management of appendicitis?
Appendectomy remains the gold standard for treating uncomplicated and complicated appendicitis. However, the vermiform appendix may play a significant role in the immune system (secondary immune function) and maintain a reservoir of the normal microbiome for the human body. The aim of this study was to summarize the long-term effects after appendectomy and discuss whether appendectomy is suitable for all appendicitis patients. A comprehensive and unbiased literature search was performed in PubMed. The terms 'appendix,' 'appendicitis,' 'appendectomy,' and 'endoscopic retrograde appendicitis therapy' were searched in the title and/or abstract. This review summarizes the long-term effects of appendectomy on some diseases in humans and describes three methods including appendectomy, medical treatment, and an 'organ-sparing' technique, named endoscopic retrograde appendicitis therapy (ERAT) to treat appendicitis. Appendectomy remains the first-line therapy for appendicitis. The patient's problem is appendix, not appendicitis. If we treat appendicitis, the problem should be resolved. During COVID-19, an initial antibiotic treatment of mild appendicitis represents a promising strategy. For patients who are worried about the long-term adverse effect after appendectomy and have a strong desire to preserve the appendix and are aware of the risk of appendicitis recurrence, medical treatment, or ERAT could be proposed.


Discovering Genetic Factors for psoriasis through exhaustively searching for significant second order SNP-SNP interactions.
In this paper, we aim at discovering genetic factors of psoriasis through searching for statistically significant SNP-SNP interactions exhaustively from two real psoriasis genome-wide association study datasets (phs000019.v1.p1 and phs000982.v1.p1) downloaded from the database of Genotypes and Phenotypes. To deal with the enormous search space, our search algorithm is accelerated with eight biological plausible interaction patterns and a pre-computed look-up table. After our search, we have discovered several SNPs having a stronger association to psoriasis when they are in combination with another SNP and these combinations may be non-linear interactions. Among the top 20 SNP-SNP interactions being found in terms of pairwise p-value and improvement metric value, we have discovered 27 novel potential psoriasis-associated SNPs where most of them are reported to be eQTLs of a number of known psoriasis-associated genes. On the other hand, we have inferred a gene network after selecting the top 10000 SNP-SNP interactions in terms of improvement metric value and we have discovered a novel long distance interaction between XXbac-BPG154L12.4 and RNU6-283P which is not a long distance haplotype and may be a new discovery. Finally, our experiments with the synthetic datasets have shown that our pre-computed look-up table technique can significantly speed up the search process.


Humans, lipids and evolution.
The genetically ordered physiology of contemporary humans was selected over eons of evolutionary experience for a nutritional pattern affording much less fat, particularly less saturated fat. Current dietary recommendations do not accord exactly with those generated by an understanding of prior hominoid/hominid evolution. Similarly, widely advocated standards for serum cholesterol values fail to match those observed in recently studied hunter-gatherers, whose experience represents the closest living approximation of "natural" human lipid metabolism. The evolutionary paradigm suggests that fats should comprise 20-25% of total energy intake, that the ratio of polyunsaturated to saturated fat should exceed 1.0, and that total serum cholesterol levels should be below 150 mg/dL (approximately 4 mM/L).


Immediate Postpartum Long-Acting Reversible Contraception: Review of Insertion and Device Reimbursement Policies.
Previous assessment of statewide policies on long-acting reversible contraception (LARC) indicate that an increasing number of states are implementing policies specifically for provision immediately postpartum, supported by current clinical guidelines. Less is known about how state policies describe payment methodologies for the insertion procedure and device costs. We conducted a systematic, web-based review of publicly available statewide policy language on immediate postpartum LARC among all 50 states. We examined the payor/s identified in the policy and policy type, if the policy included language on the global obstetric fee, whether providers and/or facilities were authorized to bill for procedure or device costs, and if the billing mechanism was identified as inpatient and/or outpatient services. Three-fourths of states (76%; n = 38) had statewide policies on immediate postpartum LARC. All policies identified Medicaid as the payor, although two also included non-Medicaid plans. Language allowing for reimbursement separate from the global obstetric fee for insertion procedures was present in 76% of states; 23 states permit it and 6 do not. Device cost reimbursement separate from the fee was identified in more state policies (92%); 31 states allow it and 4 do not. More policies included inpatient or outpatient billing mechanisms for device costs (82%; n = 31) than insertion procedures (50%; n = 19). Medicaid reimbursement policies for immediate postpartum LARC services vary by state reimbursement process, type, and mechanism. Observed differences indicate payment methodologies more often include the cost of the device than provider reimbursement (31 states vs. 23 states). Fewer than one-half of states offer reimbursement for provider insertion fees, a significant systems barrier to contraceptive access for women who choose LARC immediately postpartum.


[Anal cancer and human papillomaviruses: a perspective based on the cervical cancer model].
Anal cancer is a rare pathology in the general population but the incidence of this cancer has been on the rise for certain high-risk groups, such as homosexual men and immunodepressed subjects. The incidence of anal cancer is 10 times higher in the HIV-positive population than in the female population in general. Moderate to severe dysplasias (AIN2-3) are types of precancerous lesions that usually precede the appearance of the cancer. HPV16 infection is the most common (3/4 of the cases) followed by HPV18 (less than 10%). In anal cancer, HPV16 is present in over 75% of the cases. The prevalence of HPV in anal cancer is higher in women (90%) than in men (75%). Squamous cervical and anal cancers have strong similarities founded on the causal association to HPV, in particular HPV16. Recent data indicate that anti-HPV vaccination has a significant potential in preventing HPV infections, precancerous lesions, and anal cancer in the general population as well as in the high-risk groups.


Latency of breast cancer stigma during survivorship and its influencing factors: A qualitative study.
Breast cancer diagnosis and treatment have been shown in studies to have a negative impact on patients' physical, psychological, and social well-being, as well as overall quality of life. Psychologically, it's linked to sadness, anxiety, and demoralisation. Stigma contributes to the hidden burden of breast cancer as a chronic illness. Research on the elements that breast cancer survivors encounter as influences on stigma associated to the disease is lacking. Based on the lived experiences of breast cancer survivors, this study sought to investigate the factors that lead to the manifestations of both self- and public breast cancer stigma. Individual semi-structured interviews with 24 patients diagnosed with breast cancer were performed, followed by five focus groups with 25 patients diagnosed with breast cancer. Interviews were verbatim transcribed and analysed using thematic framework analysis. Two major themes have emerged from the data: a) Breast cancer stigma among breast cancer survivors, highlighting the various manifestations of stigma and the variables that influence them; including disease-related factors, patients' views of cancer, public perceptions of breast cancer, family and interpersonal dynamics, and b) Stigma resilience and empowerment, emphasising the necessity of sociocultural transformation and coping strategies to preserve resilience. To improve the well-being of breast cancer survivors, practitioners and health policymakers should be aware of the breast cancer stigma that underpins patients' emotional and behavioural outlooks and its potential consequences on patients' quality of life. They need to develop interventions to address the different stages of cancer stigma taking into consideration sociocultural influences, norms, and beliefs.


Generation and analysis of mixed chlorinated/brominated homologs of the halogenated natural product heptachloro-1'-methyl-1,2'-bipyrrole.
The 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'-bipyrrole (Q1, MBP-79) and further halogenated 1'-methyl-1,2'-bipyrroles (MBPs) are a class of marine natural products repeatedly detected in seafood and marine mammals from all over the world. Only Q1 is currently commercially available as reference standard and the full synthesis of mixed brominated-chlorinated compound is rather complicated. For this reason, synthetic Q1 (240 mg) was transferred into bromine-containing MBPs by UV-irradiation in the presence of bromine. Bromine, which rapidly vanished from the solutions, was renewed during the reaction in order to generate higher amounts of Br-containing MBPs. A total of ∼150 mg Q1 was transferred after ∼10 min irradiation with high amounts of Br(2) to give 30.5mg BrCl(6)-MBPs along with lower proportions of Br(2)Cl(5)-, Br(3)Cl(4)-, Br(4)Cl(3)- and traces of Br(5)Cl(2)-MBPs. Longer UV-irradiation in the presence of Br(2) even allowed for the detection of Br(6)Cl-MBPs and traces of Br(7)-MBP. However, this reaction also provided some unknown by-products. A sample stored in the dark and later in in-door light (no UV irradiation) also eliminated Q1 after 76 d in favour of heptahalogenated MBPs with up to three bromine substituents. The irradiation products were separated on silica, and fractions containing only Q1 and BrCl(6)-MBPs were then further fractionated by non-aqueous RP-HPLC. A pure isolate of the major BrCl(6)-MBP (∼1.5mg) was characterized by GC/MS and (13)C NMR to be 2-bromo-3,3',4,4',5,5'-hexachloro-1-methyl-1,2'-bipyrrole (Br-MBP-75). Partial GC enantioseparation of the axially chiral Br-MBP-75 was achieved on a β-PMCD column. A full enantioseparation was managed by enantioselective HPLC using a NUCLEOCEL DELTA S column. Low amounts of pure BrCl(6)-MBP enantiomers could be trapped.


Conorenal dysplasia: a syndrome of cone-shaped epiphysis, renal disease in childhood, retinitis pigmentosa and abnormality of the proximal femur.
Conorenal dysplasia is a rare syndrome which includes cone shaped epiphysis, renal disease in childhood, retinitis pigmentosa and abnormality of the proximal physis and metaphysis of the femur. A long term followup of one patient is presented along with a review of the reported cases.


Population pharmacokinetics and exposure-response modeling for evinacumab in homozygous familial hypercholesterolemia.
Evinacumab, an angiopoietin-like protein 3 (ANGPTL3) inhibitor, has been shown to significantly reduce low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). This work characterized the population pharmacokinetics (PK)/pharmacodynamics (PD) of evinacumab using pooled phase III clinical data. Total evinacumab PK were described by a two-compartment model with combined linear and saturable (Michaelis-Menten) elimination, and first-order absorption. At clinically relevant concentrations, plasma drug concentrations were mainly influenced by the linear clearance pathway. Although the maximum target-mediated rate of elimination (Vmax ) parameter for the saturable pathway was found to be positively related to baseline ANGPLTL3, variability in body weight contributed more to the variability in evinacumab exposure than variability in ANGPTL3. An effect of HoFH versus healthy volunteers on Vmax was also identified. Weight-based dosing regimens resulted in consistent evinacumab exposure across weight ranges. An indirect exposure-response model adequately described the relationship between evinacumab and LDL-C, where drug concentration is assumed to inhibit LDL-C production. The final population PK/PD model included two nonclinically significant covariates (race and baseline body weight) on the maximum drug-induced inhibitory effect (Imax ) and one (baseline LDL-C) on the evinacumab concentration inducing 50% of Imax (IC50 ). A smaller IC50 was observed in patients with higher baseline LDL-C, suggesting greater sensitivity to treatment. Population exposure-response analysis permitted estimation of derived PD parameters and individual LDL-C levels over time for patients with HoFH. The model accurately predicted the proportion of patients with HoFH achieving prespecified LDL-C goals with evinacumab during the ELIPSE HoFH study, further supporting a dosing strategy.


Assessing Industrial Robot agility through international competitions.
Manufacturing and Industrial Robotics have reached a point where to be more useful to small and medium sized manufacturers, the systems must become more agile and must be able to adapt to changes in the environment. This paper describes the process for creating and the lessons learned over multiple years of the Agile Robotics for Industrial Automation Competition (ARIAC) being run by the National Institute of Standards and Technology.


Determination of 15-keto-13,14-dihydro-metabolites of PGE2 and PGF2alpha in plasma using high performance liquid chromatography and gas chromatography-mass spectrometry.
A method is described for the measurement of 15-keto-13,14-dihydrometabolites of PGE2 and PGF2alpha in peripheral human plasma. This involves purification by high performance liquid chromatography followed by determination of levels by combined gas chromatography-mass spectrometry using tetradeuterated analogs of the metabolites as internal standards. The levels of these metabolites in plasma are considered to be a more reasonable index of the entry of PGE2 and PGF2alpha into peripheral blood than are the levels of the corresponding primary prostaglandins. The endogenous levels of 15-keto-13, 14-dihydro-PGE2 and 15-keto-13,14-dihydro-PGF2alpha found in peripheral plasma are 33 +/- 10 pg/ml (SD; n=6) and 40 +/- 16 pg/ml (SD; n=6), respectively.


Does vaccinating ED health care workers against influenza reduce sickness absenteeism?
This study aims to investigate the association between influenza vaccination of health care workers (HCWs) and sickness absenteeism. A retrospective cohort study was conducted in an emergency department (ED) of an acute care hospital. All full-time HCWs except physicians (73 nurses and health care attendants) were included. Influenza vaccine was administered to HCWs on a voluntary basis commencing November 2004. Absenteeism due to influenza-like illness during the period from January to October 2005 was noted. The mean number of cumulative sick leave days per person was smaller (1.0 days against 1.75 days) in vaccine recipients than in vaccine nonrecipients although the difference was not statistically significant. A significantly larger proportion of subjects took sick leave because of influenza-like illness in the vaccine nonrecipient group (55% against 30.3%, P = .034). Influenza vaccination of HCWs in the ED setting is significantly associated with a fewer number of HCWs requiring sick leave.


Intraoperative application of three-dimensional imaging for breast surgery.
The planning of an operation based on three-dimensional imaging has been used mainly in orthognathic surgery. It is a useful way to plan the preoperative treatment as well as to make the postoperative evaluation. We used this technique in breast reconstruction. For the evaluation of breast volume and contour, we used three-dimensional photography by laser scanner, and these were analysed intraoperatively. Three-dimensional data obtained during the operation gave us precise information about the volume and contour of the breast.


[Tobacco and male infertility: a retrospective study in infertile couples].
Different studies have shown an association between smoking habits and the presence of abnormal spermograms. However these reports have not been consistent throw out the literature. To analyze the effects of cigarette consumption in semen parameters from men attending our infertility outpatient clinic. Retrospective comparative study of 327 men (417 spermograms) from an initial population of 372 men attending the infertility outpatient clinic of our institution during the year of 2007. The semen parameters were first compared between smokers and nonsmokers and then a heavy smokers/light smokers analysis took place. From the 327 men included in the study, 135 (41%) were smokers and 55 (40.7%) were heavy smokers. The demographic characteristics were similar between groups. The tobacco use was associated with an increased incidence of oligo/zoosperm, without difference in the other semen parameters. It was also noted a negative correlation between heavy smoking habits and semen volume abnormalities. The results of the present study suggest that smoking negatively affects male fertility.


Novel Dihydropyrimidinone-Derived Selenoesters as Potential Cytotoxic Agents to Human Hepatocellular Carcinoma: Molecular Docking and DNA Fragmentation.
Evidence point out promising anticancer activities of Dihydropyrimidinones (DHPM) and organoselenium compounds. This study aimed to evaluate the cytotoxic and antiproliferative potential of DHPM-derived selenoesters (Se-DHPM), as well as their molecular mechanisms of action. Se-DHPM cytotoxicity was evaluated against cancer lines (HeLa, HepG2, and MCF-7) and normal cells (McCoy). HepG2 clonogenic assay allowed verifying antiproliferative effects. The propidium iodide/ orange acridine fluorescence readings showed the type of cell death induced after treatments (72h). Molecular simulations with B-DNA and 49H showed docked positions (AutoDock Vina) and trajectories/energies (GROMACS). In vitro molecular interactions used CT-DNA and 49H applying UV-Vis absorbance and fluorescence. Comet assay evaluated DNA fragmentation of HepG2 cells. Flow cytometry analysis verified HepG2 cell cycle effects. Levels of proteins (β-actin, p53, BAX, HIF-1α, γH2AX, PARP-1, cyclin A, CDK-2, and pRB) were quantified by immunoblotting. Among Se-DHPM, 49H was selectively cytotoxic to HepG2 cells, reduced cell proliferation, and increased BAX (80%), and p53 (66%) causing apoptosis. Molecular assays revealed 49H inserted in the CT-DNA molecule causing the hypochromic effect. Docking simulations showed H-bonds and hydrophobic interactions, which kept the ligand partially inserted into the DNA minor groove. 49H increased the DNA damage (1.5 fold) and γH2AX level (153%). Besides, treatments reduced PARP-1 (60%) and reduced pRB phosphorylation (21%) as well as decreased cyclin A (46%) arresting cell cycle at the G1 phase. Together all data obtained confirmed the hypothesis of disruptive interactions between Se-DHPM and DNA, thereby highlighting its potential as a new anticancer drug.


Extent of Lymphadenectomy and Long-term Survival in Esophageal Cancer.
To examine the hypothesis that survival in esophageal cancer increases with more removed lymph nodes during esophagectomy up to a plateau, after which it levels out or even decreases with further lymphadenec-tomy. There is uncertainty regarding the ideal extent of lymphadenectomy during esophagectomy to optimize long-term survival in esophageal cancer. This population-based cohort study included almost every patient who underwent esophagectomy for esophageal cancer in Sweden or Finland in 2000-2016 with follow-up through 2019. Degree of lymphadenectomy, divided into deciles, was analyzed in relation to all-cause 5-year mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for all established prognostic factors. Among 2306 patients, the second (4-8 nodes), seventh (21-24 nodes) and eighth decile (25-30 nodes) of lymphadenectomy showed the lowest all-cause 5-year mortality compared to the first decile [hazard ratio (HR) = 0.77, 95% CI 0.61-0.97, HR = 0.76, 95% CI 0.59-0.99, and HR = 0.73, 95% CI 0.57-0.93, respectively]. In stratified analyses, the survival benefit was greatest in decile 7 for patients with pathological T-stage T3/T4 (HR = 0.56, 95% CI0.40-0.78), although it was statistically improved in all deciles except decile 10. For patients without neoadjuvant chemotherapy, survival was greatest in decile 7 (HR = 0.60, 95% CI 0.41-0.86), although survival was also statistically significantly improved in deciles 2, 6, and 8. Survival in esophageal cancer was not improved by extensive lymphadenectomy, but resection of a moderate number (20-30) of nodes was prognostically beneficial for patients with advanced T-stages (T3/T4) and those not receiving neoadjuvant therapy.


Spatio-temporal organization of the somaesthetic projections in the red nucleus transmitted through the spino-rubral pathway in the cat.
Although it has been known for a long time that in awake cats, natural stimulation of the skin induces short latency responses in rubrospinal cells, the pathway possibly involved has been identified only recently (Padel et al. 1988). This tract, which was described in acute, chloralose anaesthetized cats, ascends in the ventromedial spinal cord and is activated via collaterals of primary afferent fibres running in the dorsal columns of the spinal cord. The present study demonstrates that this newly described spino-rubral tract is able to send detailed somaesthetic information to the red nucleus. After lesions leaving intact only the spino-rubral pathway, excitatory and inhibitory responses to natural peripheral stimulations were recorded in identified rubral efferent cells. The most effective stimuli were touching the skin, passive joint rotation and hair displacement. Each cell was found to possess a particular receptive field. These fields which could be ipsi-, contra-, or bi-lateral were generally located on a single limb, although they could include two or more limbs, or even exceptionally the whole body with or without preferential zones. The topographic organization of receptive fields was arranged somatotopically in the red nucleus and overlapped the motor representation. The somaesthetic inputs transmitted through the spino-rubral pathway to the red nucleus are very similar to those previously observed in the intact cat, which supports the idea that this pathway may play a functional role in motor control. The spino-rubro-spinal loop may provide a fast adaptation of the descending motor command, thus producing a fine and harmonious tuning between the changing surroundings and the animal's movements.


Factor analysis of spatiotemporal and ethological measures in the murine elevated plus-maze test of anxiety.
Recent research employing the elevated plus-maze to assess anxiety in rodents has incorporated a variety of behavioral elements in addition to the standard parameters of entries onto and time spent in the aversive open arms. In the present study, we have used a large database comprising the behavioral profiles of 90 undrugged mice to examine the relationship between the standard spatiotemporal measures and a range of specific behaviors related to the defensive repertoire of the mouse. A factor analysis applied to the standard measures revealed two factors related to anxiety and locomotor activity. The simple addition of center time (an infrequently recorded measure) to the analysis yielded a third factor, most probably related to decision making. A large-scale factor analysis applied to all measures further confirmed the existence of factors related to anxiety, locomotor activity, and decision making, and revealed three further factors thought to represent risk assessment, vertical activity, and exploratory behavior. Thus, the inclusion of ethological measures not only confirmed prior knowledge based on a very limited range of measures, but also demonstrated the existence of additional behavioral dimensions. The potential applications of this knowledge are discussed.


The Association between Moral Distress and Moral Courage in Nurses: A Cross-Sectional Study in Iran.
Moral distress and moral courage among healthcare professionals have received considerable attention in recent years. However, there is a paucity of studies investigating these topics among nurses. Thus, the present study aimed to evaluate the association between moral distress and moral courage among nurses in an Iranian sample population. The present cross-sectional study was conducted during February-December 2018. Corley's Moral Distress (MDS-R) and Sekerka's moral courage scales were used to collect the data. MDS-R is a 21-items scale which includes frequency and intensity ranges from 0 (never) to 4 (very frequently) and 0 (none) to 4 (great extent), respectively. In addition, the moral courage scale contains 15 items ranging from "never true" (1 point) to "always true" (7 points). In total, 225 eligible nurses were entered into this study. Finally, SPSS-16 was used for statistical analysis at the α = 0.05 level. The mean scores of the frequency and intensity of moral distress and moral courage were 45.41 (95% CI = 43.37-47.45), 44.24 (95% CI = 42.98-45.42), and 59.63 (95% CI = 58.50-60.87), respectively. Eventually, a significant relationship was found between the moral courage and frequency of moral distress (r = 0.46, p < 0.001) and the intensity of moral distress (r = 0.73, p < 0.001). In general, encouraging healthcare managers and administrators is considered as crucial for developing supportive structures and highly sensitive management which promotes moral courage while reducing moral distress in nurses' work setting.


Careful: An administrative child welfare and electronic health records linked dataset.
Between 2012 and 2017, N = 2814 youth between the ages of 4 and 20 were in child protective services (CPS) custody in Hamilton County, Ohio, and placed in out-of-home care. Child welfare administrative records were extracted and linked to electronic health records for all encounters at Cincinnati Children's Hospital Medical Center, with n = 2787 (99.1%) of records successfully linked prior to de-identifying the data for research purposes. Child welfare administrative data fields in the dataset include demographics, dates of entry into and exit from protective custody and out-of-home care, reasons for entry into custody, dates of placement changes, reasons for placement changes, and types of placement (e.g., foster home, kinship home, group home, residential treatment, independent living). Electronic health records (EHR) data fields include demographics, all inpatient and outpatient encounters with medications, diagnoses, screening results, laboratory test results, flowsheet data, and problem list entries. Data have been coded to capture broader categories of health needs and encounter details, medications, and other health concerns. Due to the high representation of children in CPS custody and out-of-home care who are also represented in the EHR data, this dataset provides a comprehensive view of the medical needs and health concerns for school-aged children in CPS custody in an entire county. As a result, these data can be useful for understanding the emergence of global and specific health concerns, frequency of healthcare use, and placement stability for all youth in CPS custody in this community, accounting for variation due to other health and child welfare factors. These data are likely generalizable to other mid-sized urban communities where academic medical centers provide healthcare for children in CPS custody. De-identified data may be made available to other researchers with approved data transfer agreements between academic institutions in place.


Naked-eye chemosensor with high absolute fluorescence quantum yield for selective detection of Cu(II) and cell imaging.
The regulation of copper in the human body is important for the prevention of several diseases. Therefore, a rhodamine B-based chemosensor 1 that demonstrates substantial affinity and selectivity was synthesized for the fluorescence imaging of copper(II). In the presence of Cu2+, the chemosensor underwent a color change from colorless to amaranth that was visible to the naked eye, and the fluorescence intensity did not change when excess EDTA was added to the solution. Furthermore, strong fluorescence was observed at 575 nm. The limit of detection was determined as 12.1 nM. The absolute fluorescence quantum yield was as high as 77 % and the stoichiometry between 1 and Cu2+ was determined to be 1:1 using a job plot. An analytical method was developed and successfully used to evaluate the sensor's ability for the fluorescence imaging of Cu2+ in HeLa tumor cells.


Complete rescue of the nude mutant phenotype by a wild-type Foxn1 transgene.
In this paper we describe the production and analysis of mice carrying a 110-kb transgene that encompasses the wild-type Foxn1 genomic locus. Mutations in Foxn1 cause the nude phenotype. We show that in the hair follicles, transgenic mice with increased Foxn1 gene dosage exhibited increased Foxn1 expression that was restricted correctly to the nascent, post-mitotic cells of the differentiating hair cortex and hair cuticle lineages. We also demonstrate for the first time that a Foxn1 transgene rescues completely both the hair follicle and the thymus defects in animals that are also homozygous for the nude mutation at the endogenous Foxn1 locus, causing the development of a full coat of hair and a normal population of peripheral blood T lymphocytes. We conclude that sufficient cis-acting regulatory information resides within this 110-kb transgene to direct reliable and appropriate tissue-specific expression of the Foxn1 gene.


Spatial extent and historical context of North Sea oxygen depletion in August 2010.
Prompted by recent observations of seasonal low dissolved oxygen from two moorings in the North Sea, a hydrographic survey in August 2010 mapped the spatial extent of summer oxygen depletion. Typical near-bed dissolved oxygen saturations in the stratified regions of the North Sea were 75-80 % while the well-mixed regions of the southern North Sea reached 90 %. Two regions of strong thermal stratification, the area between the Dooley and Central North Sea Currents and the area known as the Oyster Grounds, had oxygen saturations as low as 65 and 70 % (200 and 180 μmol dm-3) respectively. Low dissolved oxygen was apparent in regions characterised by low advection, high stratification, elevated organic matter production from the spring bloom and a deep chlorophyll maximum. Historical data over the last century from the International Council for the Exploration of the Sea oceanographic database highlight an increase in seasonal oxygen depletion and a warming over the past 20 years. The 2010 survey is consistent with, and reinforces, the signal of recent depleted oxygen at key locations seen in the (albeit sparse) historical data.


Quantitative neuropathological assessment to investigate cerebral multi-morbidity.
The aging brain is characterized by the simultaneous presence of multiple pathologies, and the prevalence of cerebral multi-morbidity increases with age. To understand the impact of each subtype of pathology and the combined effects of cerebral multi-morbidity on clinical signs and symptoms, large clinico-pathological correlative studies have been performed. However, such studies are often based on semi-quantitative assessment of neuropathological hallmark lesions. Here, we discuss some of the new methods for high-throughput quantitative neuropathological assessment. These methods combine increased quantitative rigor with the added technical capacity of computers and networked analyses. There are abundant new opportunities - with specific techniques that include slide scanners, automated microscopes, and tissue microarrays - and also potential pitfalls. We conclude that quantitative and digital neuropathologic approaches will be key resources to further elucidate cerebral multi-morbidity in the aged brain and also hold the potential for changing routine neuropathologic diagnoses.


The North-West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort.
To determine the incidence of, and clinically relevant risk factors for, new foot ulceration in a large cohort of diabetic patients in the community healthcare setting. Diabetic patients (n = 9710) underwent foot screening in six districts of North-west England in various healthcare settings. All were assessed at baseline for demographic information, medical and social history, neuropathy symptom score, neuropathy disability score, cutaneous pressure perception (insensitivity to the 10 g monofilament), foot deformities, and peripheral pulses. Two years later, patients were followed up via postal questionnaire to determine the incidence of new foot ulcers. Cox's proportional hazards regression analysis was used to determine the independent, relative risk of baseline variables for new foot ulceration. New foot ulcers occurred in 291/6613 patients who completed and returned their 2-year follow-up questionnaire (2.2% average annual incidence). The following factors were independently related to new foot ulcer risk: ulcer present at baseline (relative risk (95% confidence interval)) 5.32 (3.71-7.64), past history of ulcer 3.05 (2.16-4.31), abnormal neuropathy disability score (> or = 6/10) 2.32 (1.61-3.35), any previous podiatry attendance 2.19 (1.50-3.20), insensitivity to the 10 g monofilament 1.80 (1.36-2.39), reduced pulses 1.80 (1.40-2.32), foot deformities 1.57 (1.22-2.02), abnormal ankle reflexes 1.55 (1.01-2.36) and age 0.99 (0.98-1.00). More than 2% of community-based diabetic patients develop new foot ulcers each year. The neuropathy disability score, 10 g monofilament and palpation of foot pulses are recommended as screening tools in general practice.


Ink colours as task-irrelevant information decrease memory accuracy with the Associative Memory Stroop Task.
Previous research by Hazan-Liran & Miller (2017) developed a new Stroop-like task to examine how ink colours as task-irrelevant information affects paired-associate learning (see also Miller, Hazan-Liran, & Cohen, 2018). The task was to learn word-number pairs (e.g. blue-5) whilst only numbers were coloured in either congruent ink colours (e.g. number 5 printed in blue ink), incongruent ink colours (e.g. 5 printed in brown ink) or neutral ink colours (e.g. 5 printed in black ink). The present paper refers to this task as the Associative Memory Stroop Task (AMST). Hazan-Liran & Miller (2017) found that incongruent ink colours interfere and congruent ink colour facilitate the speed of learning word-number pairs. The present experiments employed the AMST to examine the effects of irrelevant ink colours (with colour names) on memory accuracy in cued recall and associative recognition. Memory impairment was found with incongruent ink colours on both memory tests whilst improved memory accuracy with congruent ink colours was not reliable. We discuss possible explanations for these findings.


Redox mechanism of anticancer drug idarubicin and in-situ evaluation of interaction with DNA using an electrochemical biosensor.
Idarubicin (IDA), 4-demethoxydaunorubicin, is an anthracycline derivative and widely used treatment of leukemia. The electrochemical behavior of IDA was examined at a glassy carbon electrode (GCE) in different aqueous supporting electrolyte using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The oxidation process of IDA was found to be pH dependent and irreversible proceeding with a transfer of 1 proton and 1 electron under the diffusion controlled mechanism. The electroactive center is the hydroxyl group on the aromatic ring which produces a final quinonic product. The diffusion coefficient of IDA was calculated to be DIDA=7.47×10(-6) cm(2) s(-1) in pH=4.3 0.1 M acetate buffer. The interaction of IDA and double stranded deoxyribonucleic acid (ds-DNA) was investigated using electrochemical ds-DNA biosensor and incubation solution by means of DPV. The DNA damage was detected following the changes in the oxidation peaks of guanosine and adenosine residues. The results obtained showed that IDA interacts with DNA which causes the change in the DNA morphological structure. In addition to these polynucleotides, PolyG and PolyA, biosensors were also used to confirm the interaction between ds-DNA and IDA. However, no oxidation peaks of the purine base oxidation products, 8-oxoGua and 2,8-oxoAde, were observed.