Role demands and turnover intention among Covid-19 frontline nurses: The mediating and moderating roles of compassion fatigue and spiritual leadership.
The working conditions created by the Covid-19 pandemic have been proven to amplify frontline nurses' desire to leave their profession in recent years; thus, exploring new causing variables is vital. This cross-sectional study examined role demands' direct and indirect effects on turnover intention through compassion fatigue and tested the various dimensions of spiritual leadership as moderators on the relationship between compassion fatigue and turnover intention. A total of 527 valid responses were collected from frontline nurses working in designated hospitals across Zhejiang province in China using a survey questionnaire. The outcomes from the hierarchical regression analysis indicated that role demands positively and significantly impacted turnover intention and compassion fatigue. Besides, compassion fatigue significantly and positively affected turnover intention and mediated its relationship with role demands. However, vision and altruistic love moderated the relationship between compassion fatigue and turnover intention, which was not true for the dimension hope/faith. This study's findings are a steppingstone for medical firms' managers and policymakers in demonstrating the likelihood of frontline nurses developing turnover thoughts arising from ambiguous and conflicting roles and the emotional strain from patients' burdens. Furthermore, an exemplary implementation of spiritual leadership could help enhance nurses' sense of calling and membership, essential in embracing the organization's vision and achieving its goals.


Prostate Artery Embolization in Patients with Prostate Volumes of 80 mL or More: A Single-Institution Retrospective Experience of 93 Patients.
To evaluate the safety and efficacy of prostate artery embolization (PAE) for the treatment of benign prostatic hyperplasia for prostates ≥ 80 mL. A retrospective review was conducted of 93 patients with prostate volumes (PVs) ≥ 80 mL treated with PAE from April 2014 through October 2017. Mean patient age was 68.5 years (range 52-88) and mean age-adjusted Charlson comorbidity index was 3.2 (range 1-8). Exclusion criteria included history of biopsy-proven prostate cancer or catheter dependency. Clinical and urodynamic outcomes were reviewed at 1, 3, 6, and 12 months. Adverse events were graded according to the Clavien-Dindo classification. Mean PV decreased significantly from 141.7 mL to 98.1 mL at 3 months (P < .01) and 82.2 mL at 12 months (P < .01). Significant improvements were seen in 3- and 12-month mean International Prostate Symptom Scores (IPSS) (22.3 vs 7.1 and 7.3, respectively; P < .01 for both), quality of life (QOL) (4.4 vs 1.2 and 1.3; P < .01 for both), and postvoid residual volume (196.7mL vs 92.1 and 61.2 mL; P < .01 and P < .01, respectively). Significant improvement was also seen in 3-month mean maximum urinary flow: 7.7 mL/s vs 12.8 mL/s (P < .01). One grade II complication of stroke occurred; all other complications were self-limited and grade I. PAE achieved a clinically and statistically significant improvement in symptom burden and secondary outcome measures in patients with PVs ≥ 80 mL. PAE may be an alternate treatment for patients for whom conventional surgical options are limited or associated with significant morbidity.


Investigating the Relationship Between Eye Movement and Brain Wave Activity Using Video Games: Pilot Study.
All eye movements are related in one way or another to our mental processes with lateral eye movements being associated with the different hemispheres of the brain. Eye movement techniques form the basis of eye movement desensitization and reprocessing therapy, wherein forced eye movements activate neurological pathways to treat the subject. The objective of our study was to examine the relationship between players' eye movements and their brain wave activities using a video game. We used similar eye movement techniques in the form of a video game called Lifeguard that could potentially stimulate different eye movement mode and create a more engaging experience for the user. By designing an experiment, we further explored the differences in electroencephalogram spectral power activity for the alpha, beta, theta, delta, and gamma frequency bands in Lifeguard and Tetris. The game based on eye movement technologies resulted in decreased delta power and increased beta power, but significant difference between 2 games was not found. The applied uses of this research could mean that eye movement desensitization and reprocessing can be conducted in a more fun and engaging way through the use of gaming technology.


The impact of obesity on cardiovascular risk factors in Turner's syndrome.
To evaluate risk factors for coronary artery disease in women with Turner's syndrome which may contribute to the increased incidence of premature cardiovascular death noted in this disorder. Comparison of clinical and biochemical parameters in women with Turner's syndrome with those in women with normal karyotype. Ninety-one women with Turner's syndrome attending a dedicated adult Turner's syndrome clinic and 22 control subjects were studied. Recumbent blood pressure, body mass index (BMI), fasting total cholesterol, triglycerides and high density lipoproteins (HDL) were measured in both study groups. Women with Turner's syndrome were more obese compared with women with a normal karyotype. They were more likely to be hypertensive and the obese patients had higher serum triglyceride concentrations. Hypertension was independent of obesity and may be under-recognized because of failure to compare with age-matched normal ranges. Lipoprotein changes were accounted for by the obesity. Women with Turner's syndrome may be at increased risk of developing coronary artery disease as a result of the higher frequency of hypertension and obesity. Routine screening of this population for risk factors for ischaemic heart disease is recommended.


Auditory processing indexed by stimulus-induced alpha desynchronization in children.
By means of magnetoencephalography (MEG), we investigated event-related synchronization and desynchronization (ERS/ERD) in auditory cortex activity, recorded from twelve children aged four to six years, while they passively listened to a violin tone and a noise-burst stimulus. Time-frequency analysis using Wavelet Transform was applied to single-trials of source waveforms observed from left and right auditory cortices. Stimulus-induced changes in non-phase-locked activities were evident. ERS in the beta range (13-30 Hz) lasted only for 100 ms after stimulus onset. This was followed by prominent alpha ERD, which showed a clear dissociation between the upper (12 Hz) and lower (8 Hz) alpha range in both left and right auditory cortices for both stimuli. The time courses of the alpha ERD (onset around 300 ms, peak at 500 ms, offset after 1500 ms) were similar to those previously found for older children and adults with auditory memory related tasks. For the violin tone only, the ERD lasted longer in the upper than the lower alpha band. The findings suggest that induced alpha ERD indexes auditory stimulus processing in children without specific cognitive task requirement. The left auditory cortex showed a larger and longer-lasting upper alpha ERD than did the right auditory cortex, likely reflecting hemispheric differences in maturational stages of neural oscillatory mechanisms.


Effects of 1.25 dihydroxyvitamin D3 on calcium uptake, into rat intestine after chronic oral cadmium administration.
Calcium influx into rat intestine was investigated, in vitro, after cadmium chronic oral exposure. In active calcium transport, pretreatment by 1.25 dihydroxyvitamin D3 prevents the effect of cadmium on the maximal influx value Jm and leads to an increase of the half-saturation constant Kt.


Serum cholesterol increase in statin users associated with antibiotic use: Case-crossover study.
3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors ("statins") reduce risk of atherosclerotic disease. However, statins need secondary bile acids, produced by the gut microbiota, for absorption. Our hypothesis was that a change in the gut microbiota induced by antibiotics might cause a decrease in statin absorption, and decreased statin effectiveness. Our objective was to study the association between antibiotic treatment and increased cholesterol level in statin users. Case-crossover study, in which an individual serves as his own control, by comparing outcome risk among the same individual at different times, adjusting for time-dependent comorbidity index. The study is based on adherent statin users' cohort and two cohorts of patients not treated with statins, in Clalit Health Services. Exposure were antibiotic prescriptions dispensed in the 3 months prior to LDL-C measurements. There were 25,496 statin users and 72,638 time-points. A significant association was found between LDL-C increase and exposure to macrolides and clindamycin, OR = 1.237 (1.138-1.345), p = 6.5*10-7, number needed to harm (NNH) = 19. There was no association between LDL-C increase and negative control objects such as anti-viral treatments; nor between LDL-C and exposure to antibiotics in non-statin users. As a secondary outcome, we have found an association between LDL-C increase and a following atherosclerotic ischemic event. An increase in LDL-C in highly adherent statin users is associated with precedent macrolides or clindamycin treatment.


The role of Intraoperative cholangiography (IOC) and methylene blue tests in reducing bile leakage after living donor hepatectomy.
Liver transplantation remains the only curative treatment in end stage liver disease. Biliary complications remain the most common major morbidity causes in hepatic resection. We aimed to determine and eliminate the bile leakage in donor hepatectomy of LDLT. This study was conducted retrospective and one center study. The study population included 110 consequential liver donors with major liver resection (more than three segments). The population was divided into three groups for data analyses. Primary study groups included 40 donors subjected to methylene blue test starting in April 2013 and 40 donors subjected to intraoperative cholangiography started in March 2014. A total of 110 liver donors (42.7% women) were included in the study. Postoperative biliary complications were less in methylene blue and intraoperative cholangiography (IOC) groups. Bile leakage was significantly higher in control group (23.3%) compared to methylene blue (5%) and IOC groups (2%) Average duration of hospital stay and duration of operation were significantly higher in control group compared to methylene blue and IOC groups. In our study we conducted to establish biliary leakage in living donor hepatectomy which intraoperative cholangiography test was used to determine. Many intraoperative methods have been introduced to prevent biliary leakage and development of complications. We have showed that IOC test used in the present study could be easily applied in both living liver donor hepatectomy and other major hepatectomy cases. IOC test reduced postoperative biliary leakage incidence and did not increase incidence of other complications.


Indefinite storage of dried Gm and Km (Inv) antigens: (examination of bloodstains 33 years old).
We confirm the great stability of the A and B antigens in dried blood, and the markedly lesser stability of antigen H. We demonstrate that it is possible to determine the immunoglobulin groups Gm(1), Gm(10) and Km(1)--formerly Inv(1)--in bloodstains 29 to 33 years old.


Risk factors and survival outcomes of laryngeal squamous cell carcinoma patients with lung metastasis: A population-based study.
It remains elusive which factors may influence the morbidity and mortality of lung metastasis (LM) in Laryngeal Squamous Cell Carcinoma (LSCC) patients. The aim of the present study was to investigate factors influencing LM and the survival outcomes of LSCC patients with LM. We identified 10,935 patients with LSCC from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Multivariate logistic regression analysis was used to determine the factors associated with the presence of LM. Multivariate cox regression analysis was used to identify covariates associated with increased all-cause mortality in patients with LM. Among 10,935 patients with LSCC, 232 (2.12%) patients had LM. The median survival time of patients with LM was 8 months, and 8.37% of patients survived after 3 years. Patients with age ≥ 60 years old, unmarried status, supraglottis, overlapping lesion of larynx, subglottis, pathological grade III, T4 stage, N1 stage, N2 stage, N3 stage and bone, brain or liver metastases were more likely to have LM. Survival analysis showed that chemotherapy and radiotherapy suggested better survival of LSCC patients with LM while pathological grade IV was associated with an increased all-cause mortality. The incidence of LSCC patients with LM varied by age, married status, and tumor subtypes. LSCC patients with LM had poor survival, and only 8.37% of patients survived after 3 years. However, chemotherapy and radiotherapy were found as independent favorable prognostic factors for survival.


Comparative biochemical analysis of purified S-antigen from human, bovine, porcine and rat retina.
Highly purified S-antigen from human, bovine, porcine and rat retina was used to ascertain the molecular weights, isoelectric points, amino-acid composition and presence of carbohydrate moieties. All S-antigen preparations comigrate to 50,000 MW on SDS-polyacrylamide gels and demonstrate microheterogeneity upon isoelectric focusing. Human S-antigen exhibits two bands at pH 5.9 and 5.6, whilst with bovine S-antigen a broad band at pH 5.9 was observed. Porcine and rat S-antigen gave four bands, focusing between pH 5.0-5.6. Two-dimensional gel analysis revealed that all the four focused porcine polypeptides migrate to 50,000 MW. Western-blot analysis following isoelectric focusing of human and porcine S-antigen showed that all polypeptide bands react specifically with polyclonal and monoclonal antibodies to S-antigen. The reasons for the apparent heterogeneity of S-antigen by isoelectric focusing are discussed. All S-antigen preparations were weakly positive for periodic acid Schiff staining, and specifically bound radiolabelled Lens culinaris lectin on Western-blot analysis. These results confirm the glycoprotein nature of S-antigen which may explain the finding of multiple bands found on isoelectric focusing. Amino-acid analysis reveals the high percentage of non-polar amino acids and may explain the apparent hydrophobic behaviour of the isolated protein.


The fidelity, occasional promiscuity, and versatility of T cell receptor recognition.
Although there are multiple structures showing how alphabeta T cell receptors (TCRs) specifically recognize antigenic peptides bound to the major histocompatibility complex (MHC) molecules (pMHC-I and pMHC-II), we have little data on how TCRs interact with lipid-based antigens presented by members of the CD1 family. Here, we review recent findings in the field of TCR recognition, including TCR-pMHC complexes and the structure of a TCR in complex with CD1d-glycolipid. Collectively, these studies have revealed the versatility of the TCR in recognizing the distinct yet evolutionarily related proteinaceous and lipid-presenting molecules of the immune system.


Opposite effects of angiotensin II and IV in the lateral nucleus of the amygdala.
In this study the effects of angiotensin II and norleucine1-angiotensin IV have been studied in a horizontal in vitro slice preparation of female rat brains. Extracellular field potentials of the lateral nucleus of the basolateral amygdala were recorded. The results show that angiotensin II significantly increased the amplitude of field potentials induced by the electrical stimulation of the lateral nucleus, whereas norleucine1-angiotensin IV caused a significant decrease in the amplitude of field potentials. The angiotensin-induced effects could be blocked by specific angiotensin receptor antagonists. These opposite effects of angiotensin II and IV on electrophysiological parameters are in agreement with behavioral studies that have demonstrated that angiotensin II and IV produce opposite effects on the retention of an inhibitory shock-avoidance response and correlate with their different effects on the blood vessels.


Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers.
Strategic design and synthesis of nanoparticle based preparations could improve diagnostic screening of several cancer types, thereby facilitating better clinical management of the disease. Towards this, the present work aims to develop and evaluate a radioactive technetium-99m (99mTc) labeled gold nanoparticle (NP) preparation modified with folic acid, so as to diagnose folate receptor positive cancers viz. ovarian, breast, etc. METHODS: 11-Bromoundecanoic acid (UA) was synthetically modified both with folic acid and Hydrazinonicotinic acid (HYNIC) chelate at the carboxylic acid end and subsequently converted to thiol functionality at the bromo terminal to yield folic acid-UA-SH and HYNIC-UA-SH ligands respectively. Gold NPs modified with folic acid and HYNIC chelator were obtained on direct addition of folic acid-UA-SH and HYNIC-UA-SH to chloroauric acid in polysorbate 80 solution under reducing conditions. These NPs were then radiolabeled with 99mTc following HYNIC labeling approach. Both the inactive and 99mTc-labeled gold NPs were then tested for their biological efficacy in folate receptor (FR) positive KB cancer cell lines. Also, biodistribution studies of 99mTc-labeled gold NPs were carried in KB tumor xenografts to ascertain the efficacy towards FR in in vivo system. Polysorbate 80 could stabilize the gold NP preparation with average size <10 nm as determined by TEM. Inhibition of [3H]folic acid with functionalized gold nanoparticle revealed affinity towards FR positive KB cell lines with an IC50 ~ 9 μM. Biodistribution studies of 99mTc-labeled gold NP preparation in SCID mice bearing KB tumor showed an uptake of 1.39 ± 0.18%ID/g in tumor and 5.48 ± 0.72%ID/g in kidneys at 3 h post-injection. In vivo distribution in folic acid pre-treated animals could not establish the specificity towards folate receptors. Biological evaluation of functionalized gold NP showed affinity towards FR positive cancer cell lines. 99mTc-labeled NP exhibited target uptake in both in vitro and in vivo models, but folic acid inhibition could not establish the target specificity. Nevertheless, in vivo pharmacokinetics envisaged in the present design was achieved using the present gold functionalized NP preparation.


Chronic toxicity of PFAS-free AFFF alternatives in terrestrial plant Brassica rapa.
Fluorine (F)-free firefighting foams will be replacing per- and polyfluoroalkyl substances (PFAS)-containing aqueous film-forming foams (AFFFs) at U.S. military installations imminently, yet the environmental impacts of F-free foams are largely unknown. Ecotoxicity assessment of F-free foams is urgently needed to avoid replacement regret. In this study, we comparatively assessed phytotoxicity of six F-free formulations and one current short-chain fluorinated AFFF in terrestrial plant Brassica rapa. Five of six F-free formulations exerted higher toxicity than the short-chain AFFF to the growth and reproduction of B. rapa, with 8-51 times and > 10 times lower EC50 values, respectively. Nontargeted analysis indicated the occurrence of transformation products of the test formulations in the above-ground plant tissues. In agreement with their phytotoxicity, the five highly toxic F-free formulations generated more transformation products with higher peak intensities in plant tissues than the two weakly toxic formulations. The most abundant transformation products detected in plant extracts were suspect transformation products derived from diethylene glycol monobutyl ether, a common ingredient of the five toxic formulations. This study provides ecotoxicological data that, combined with data from all related ongoing research, should be used in decision making regarding recommendations for manufacturing and use of candidate F-free foams.


Zwitterionic Nanofibers of Super-Glue for Transparent and Biocompatible Multi-Purpose Coatings.
Here we show that macrozwitterions of poly(ethyl 2-cyanoacrylate), commonly called Super Glue, can easily assemble into long and well defined fibers by electrospinning. The resulting fibrous networks are thermally treated on glass in order to create transparent coatings whose superficial morphology recalls the organization of the initial electrospun mats. These textured coatings are characterized by low liquid adhesion and anti-staining performance. Furthermore, the low friction coefficient and excellent scratch resistance make them attractive as solid lubricants. The inherent texture of the coatings positively affects their biocompatibility. In fact, they are able to promote the proliferation and differentiation of myoblast stem cells. Optically-transparent and biocompatible coatings that simultaneously possess characteristics of low water contact angle hysteresis, low friction and mechanical robustness can find application in a wide range of technological sectors, from the construction and automotive industries to electronic and biomedical devices.


Developmental effects of child abuse: a review.
Most research investigating the effects of physical child abuse on children's development has been based on uncontrolled or poorly controlled studies having small samples, no long-term follow-up, and weak instrumentation. These studies, as well as some which have been more carefully designed, have generally suggested seriously detrimental developmental consequences in physical, intellectual, behavioral, and emotional areas. Some recent controlled follow-up studies challenge such a negative picture of abuse. In particular, a study by Elmer, which is probably the most carefully conducted study yet done, found that the harmful effects of abuse dissipated years after the abusive incident and that socioeconomic status (SES) and related factors may be more important than abuse in determining the course of child development. To improve the quality and clarity of future research on developmental effects of child abuse, this paper discusses, in four major areas, problems which plague the research. The extent, type, and frequency of abuse should be more carefully defined to allow studies to be compared. The types and amounts of social service interventions should also be specified. Generalization: Research should include more middle and upper SES children, more of the mildly and moderately abused, and more neglected children to allow generalization to the total population of maltreated children. Causality: Since developmental deficits may be the cause as well as the effects of abuse and because outside factors such as SES may lead to both the abuse and the deficits, there is a need for large-scale longitudinal studies which can untangle the cause and effect web of abuse by following children from birth and measuring many factors which might affect development (e.g., SES, birth abnormalities, abuse).(ABSTRACT TRUNCATED AT 250 WORDS)


Ischemia deteriorates spike encoding at cortical GABAergic neurons and cerebellar Purkinje cells by increasing the intracellular Ca2.
GABAergic neurons play a critical role in the central nervous system, such as well-organized behaviors. The ischemic cell death is presumably initiated by neuronal excitotoxicity resulted from the dysfunction of GABAergic neurons. It is not clear how ischemia influences different types of GABAergic neurons and whether intracellular Ca2+ plays a key role in the ischemic excitotoxicity. We have investigated this issue at cortical GABAergic neurons and cerebellar Purkinje cells by whole-cell recording in mouse brain slices, and the roles of intracellular Ca2+ are examined by BABTA infusion. Compare with the data from a group of control, ischemia causes by lowering purfusion rate lowers spike encoding at cortical GABAergic neurons and enhances encoding ability at cerebellar Purkinje cells. These differential effects of ischemia on spike encoding are mechanistically associated with the changes in the refractory periods and threshold potentials of sequential spikes. These ischemia-induced dysfunction of spike encoding at two types of GABAergic cells are prevented by BABTA infusion. Therefore, the ischemia destabilizes the spike encoding of GABAergic cells via raising intracellular Ca2+. Our findings indicate that ischemia preferentially causes the dysfunction of spike encoding at GABAergic neurons by the up-regulation of intracellular Ca2+ level, which leads to neuronal excitotoxicity.


Quality and Safety in Healthcare, Part LXXXIII: The Culture of Safety in High Reliability Organizations.
A safety culture encourages the reporting of mistakes so that all can learn from them and remedy underlying system problems. However, errors will only be reported in a culture in which most types of common human errors are not punished because all humans make errors, and usually there are underlying system problems contributing to this. All healthcare errors must be viewed partly as opportunities to improve. A safety culture includes good leadership, communication, learning, collaboration, mindfulness, medicine that is based on evidence and best practice, and care that is centered on the patient.


Furanocoumarin metabolism in Papilio polyxenes: biochemistry, genetic variability, and ecological significance.
The ubiquitous occurrence of series of biosynthetically related plant secondary compounds within individual species has given rise to the suggestion that such multiplicity is adaptive; one possible mechanism that would serve to maintain such within-plant diversity is analog synergism. In a series of experiments, we provide evidence that synergism may account for the presence of multiple structurally related furanocoumarins in apiaceous plants. The black swallowtail, Papilio polyxenes, feeds exclusively on plant species containing furanocoumarins. Growth of larvae fed parsley leaves treated with both xanthotoxin and angelicin, two furanocoumarins that co-occur widely in swallowtail hostplants, was significantly slower than that of larvae fed leaves with an equimolar concentration of either xanthotoxin or angelicin. A multivariate combination of growth, food consumption and frass excretion differed significantly between larvae fed leaves treated with both xanthotoxin and angelicin and larvae fed leaves treated with angelicin alone. In addition, we measured rates of in vitro cytochrome P450-mediated metabolism of three furanocoumarins - bergapten, xanthotoxin, and angelicin. While bergapten and xanthotoxin, both linear furanocoumarins, were metabolized at similar rates (8.07 and 9.86 nmoles/min/g fw caterpillar, respectively), angelicin, an angular furanocoumarin, was metabolized more slowly (2.76 nmoles/min/g fw caterpillar). When all three furanocoumarins were assayed together, overall rates of metabolism were significantly reduced, suggesting substrate inhibition. Thus, the pattern of growth of larvae is consistent with the pattern of in vitro metabolism and is evidence in support of analog synergism. In a separate experiment, metabolism of xanthotoxin and angelicin individually and together were compared in six maternal families. Again, angelicin was metabolized more slowly than xanthotoxin and each furanocoumarin inhibited metabolism of the other. That significant family effects were found for rates of metabolism and for the ratio of moles of angelicin metabolized for each mole of xanthotoxin metabolized raises the possibility that genetic variation exists for the rate and specificity of metabolism and suggests that insect herbivores may be able to adapt to analog synergism.


Formula method for stimulus setting in bilateral electroconvulsive therapy: relevance of age.
Seizure thresholds were determined by titration in consecutive electroconvulsive therapy (ECT) patients at the first (n = 146) and sixth (N = 83) ECT sessions. Equations to predict the threshold at the first and sixth ECT were computed from these data using a stepwise linear regression model. These equations were tested prospectively at the first ECT (n = 48) and sixth ECT (n = 26) sessions. Stimulus dose derived from the corresponding equations yielded adequate seizure (successful) in 82% and 84% of patients, respectively. Predictions based on age alone (disregarding two other significant variables--illness severity and inion-nasion distance) were estimated at these two ECT sessions. This would not appreciably compromise the success rate. The "formula" method using age alone may therefore be used in routine clinical practice.


Reactivity of Horse Sera to Antigens Derived From Sarcocystis falcatula-Like and Sarcocystis neurona.
Sarcocystis neurona and Sarcocystis falcatula are protozoan parasites endemic to the Americas. The former is the major cause of equine protozoal myeloencephalitis, and the latter is associated with pulmonary sarcocystosis in birds. The opossum Didelphis virginiana is the definitive host of these parasites in North America. Four Didelphis species are found in Brazil, and in most reports in this country, Sarcocystis species shed by opossums have been classified as S. falcatula-like. It is unknown whether reports on S. neurona-seropositive horses in Brazil are also derived from exposure of horses to S. falcatula-like. The aim of this study was to test the sera reactivity of 409 horses in Brazil using antigens derived from a Brazilian strain of S. falcatula-like (Sarco-BA1) and from a North American strain of S. neurona (SN138). Samples were examined by immunofluorescent antibody tests (IFATs) at start dilutions of 1:20, and a selected number of samples was tested by Western blot (WB). Sera from 43/409 (10.5%) horses were reactive to S. falcatula-like and 70 of 409 (17.1%) were reactive to S. neurona antigen; sera from 25 animals (6.1%) were positive for both parasites by IFAT. A poor agreement was observed between the two employed IFATs (κ = 0.364), indicating that horses were exposed to more than one Sarcocystis species. Horse sera evaluated by WB consisted of four sera reactive to S. falcatula-like by IFAT, six sera positive to S. neurona by IFAT, two sera that tested negative to both parasites by IFAT, and a negative control horse serum from New Zealand. Proteins in the range of 16 and 30 kDa were recognized by part of IFAT-positive sera using both antigen preparations. We concluded that Brazilian horses are exposed to distinct Sarcocystis species that generate different serological responses in exposed animals. Antigens in the range of 16 and 30 kDa are probably homologous in the two parasites. Exposure of the tested horses to other Sarcocystis species, such as Sarcocystis lindsayi, Sarcocystis speeri, and Sarcocystis fayeri, or Sarcocystis bertrami cannot be excluded in the current study.


Intramolecular interactions in ortho-methoxyalkylphenylboronic acids and their catechol esters.
Catechol esters of ortho-methoxyalkylphenylboronic acids have been synthesized and characterized by (17)O NMR spectroscopy. The results were compared with the data for the parent acids. The influence of intramolecular and intermolecular hydrogen bonds on the properties of the boronic acids has been discussed. The (17)O NMR data for the boronic esters proved that there are no O → B interactions in the investigated compounds. This fact is connected with weak Lewis acidity of the parent acids and their low sugars' receptors activity. Crystal structure of ortho-methoxyphenylboronic acid catechol ester was determined.


Continuous-infusion vinorelbine for the treatment of advanced non-small-cell lung cancer: a phase I/II study.
In this phase I/II trial, the maximum tolerated dose (MTD) and activity of vinorelbine administered in continuous infusion as first-line treatment for advanced non-small-cell lung cancer (NSCLC) was determined in 25 consecutive chemotherapy-naive patients with advanced NSCLC. Vinorelbine was administered as an initial intravenous (I.V.) bolus of 8 mg/m(2) on day 1 followed by a 4-day continuous I.V. infusion at 5 different 24-hour dose levels to be repeated every 21 days. All 25 patients (159 cycles) were evaluable for response. The MTD was 8 mg/m(2) bolus followed by a continuous I.V. infusion of 11 mg/m(2) per day over 4 days. The dose-limiting toxicities were febrile neutropenia in 6 patients and grade 3 mucositis in 2 patients. There was less neurotoxicity and constipation and more mucositis compared with the weekly bolus scheme. There was no significant cumulative toxicity after 3 cycles. Treatment responses were observed in 6 patients: 1 complete response and 5 partial responses. The overall response rate was 24% (95% confidence interval [CI], 8%-40%). Median time to progression was 4 months (95% CI, 2-11 months), and median survival was 6 months (95% CI, 2-18 months). The results demonstrate that, in this setting of first-line treatment of NSCLC, vinorelbine administered as an 8 mg/m(2) bolus followed by a continuous infusion of 11 mg/m(2) per day over 4 days is the recommended schedule. Further trials are necessary to establish activity and possible benefits of combination with other agents.


Attention Bias and Anxiety: The Moderating Effect of Sociocultural Variables in Rural Latinx Youth.
Attention bias confers risk for anxiety development, however, the influence of sociodemographic variables on the relationship between attention bias and anxiety remains unclear. We examined the association between attention bias and anxiety among rural Latinx youth and investigated potential moderators of this relationship. Clinical symptoms, demographic characteristics, and a performance-based measure of attention bias were collected from 66 rural Latinx youth with clinical levels of anxiety (33.3% female; Mage = 11.74; 92.4% Latinx, 7.6% Mixed Latinx). No moderating effects for age or gender were found. Youth below the poverty line displayed an attention bias away from threat in comparison to youth above the poverty line, who displayed an attention bias towards threat. Among youth below the poverty line, this bias away from threat was associated with increased anxiety. Findings highlight the importance of economic adversity in understanding the relationship between attention bias and anxiety.


Assessment of directional Doppler ultrasound techniques in the diagnosis of carotid artery diseases.
Three diagnostic techniques based on the use of directional doppler ultrasound have been evaluated in comparison with direct percutaneous carotid angiography and arch aortography. The results indicate that the non-invasive techniques provide a safe, atraumatic method of assessing patients with symptoms of extracranial occlusive arterial disease.


Short variation of the sheep PDGFD gene is correlated with litter size.
Platelet-derived growth factor (PDGF) family, exert plays a key role in embryonic development, cell proliferation, cell migration, angiogenesis and reproduction. Related studies about GWAS analyses have found that PDGFD significantly affected deposition of tail fat in sheep, but there are no studies on reproduction in animals. In this study, three breed of sheep were used to find insertion/deletion (indel) fragment polymorphism of PDGFD which including Australian white (AUW) sheep (Meat type, n = 932), Guiqian semi-fine wool (GSFW) sheep (wool type, n = 60) and East Friensian milk (EFM) sheep (dairy type, n = 60). Only a 18-bp variation was polymorphic in the study AUW sheep population and the genotypes of different sheep breed are also specific. Moreover, the association analysis indicated that this variant was associated with litter size of AUW sheep in the first parity (p < 0.05). The litter size of II genotype was significantly lower than other genotypes in the first parity (p < 0.05). We also revealed that the PDGFD gene was relatively conservative in eight species, PDGFD mRNA expression in 832 sheep samples implying this gene was related to reproduction traits. Hence, these finding demonstrated the one-cause multipotency of PDGFD gene. Collectively, these results suggest that this indel can be used as an effective marker for sheep breeding.


Digoxin-induced ventricular arrhythmias in the guinea pig heart in vivo: evidence for a role of endogenous catecholamines in the genesis of delayed afterdepolarizations and triggered activity.
The mechanisms of digoxin-induced ventricular arrhythmias were studied in vivo using a novel experimental model. Anesthetized guinea pigs were instrumented with custom-made electrode catheters which enabled the monitoring and recording of right atrial, right ventricular, and His bundle electrograms, midmyocardial monophasic action potentials (MAP), and systemic arterial blood pressure. Intravenous digoxin induced ventricular arrhythmias ranging from ventricular premature contractions (VPCs) to ventricular fibrillation (VF). These were associated with delayed afterdepolarizations (DADs) observed on the MAP recordings. The severity of the arrhythmias depended on the dose of digoxin. Short bursts of ventricular pacing neither terminated nor suppressed episodes of ventricular tachycardias (VTs). A direct relationship existed between the paced ventricular cycle length and the coupling interval between the last paced beat and the first ectopic beat (r = 0.913, P < 0.001, n = 10) and between the amplitude of the DADs and the pacing rate (r = 0.972, P < 0.05, n = 7). The increased contractility (LV dp/dt) and heart rate evoked by isoproterenol (0.1 microgram/kg) did not induce DADs in the absence of digoxin. Verapamil terminated the digoxin-induced VTs in 15 of 16 animals and abolished the associated DADs in 7 of 7 animals. Adenosine terminated the VTs in 15 of 19 animals and abolished the DADs in 8 of 10 animals. Digoxin induced VT in only 1 of 6 animals treated with reserpine (5 + 5 mg/kg) 24 and 48h prior to experimentation. However, subsequent intravenous isoproterenol (0.2 micrograms/kg) induced VT and DADs, both of which were abolished by verapamil, in all 6 animals.(ABSTRACT TRUNCATED AT 250 WORDS)


No transmission of SARS-CoV-2 in a patient undergoing allogeneic hematopoietic cell transplantation from a matched-related donor with unknown COVID-19.
The Hematology Department and its Hematopoietic Cell Transplantation (HCT) program implemented several measures during COVID-19 outbreak in order to keep clinical activities with the maximum security for both donors and recipients. Nevertheless, there was a lack of evidence whether blood products and specifically bone marrow can cause transfusion-transmitted infection. Initially, there were many uncertainties and did not exist formal recommendations. Before official statements were available, we performed an allogeneic HCT in a 57-year-old male from a related matched donor in the incubation period of COVID-19 where the patient did not develop the disease. Actual epidemiology data suggest that transmission may occur early in the course of infection, even from asymptomatic patients in the incubation period. In our knowledge this is the first case report of an adult hematopoietic cell donor with COVID-19 in the incubation period where the transplant is successfully completed with no transmission of SARS-CoV-2. The low concentration of viral RNA in plasma of patients with COVID-19 could support the safety of blood products, including peripheral blood hematopoietic cells. In conclusion, blood products including hematopoietic stem cells are safe in the context of COVID-19 pandemic.


Studies of biochemical changes in cultured skin fibroblasts derived from sporadic and familial Alzheimer's disease individuals: qualitative and quantitative changes in double-stranded DNA-stimulated phosphorylation of endogenous nucleoproteins.
Endogenous proteins phosphorylated in vitro with nuclear extracts prepared from skin fibroblasts of familial and sporadic AD subjects and age/sex-matched controls show qualitative/quantitative changes which were dependent upon the addition of natural and synthetic double-stranded DNA (dsDNA) to assay mixtures. Control and AD cell-free homogenates showed a pronounced increase in four proteins migrating with molecular weights of 180- (p180), 75-(p75), 65- (p65), and 34-kD (p34). Optimal stimulation of each protein required a different concentration of dsDNA. In AD samples, an additional dsDNA-stimulated protein, p40, was observed. In extracts prepared from sporadic AD individuals, synthetic dsDNA stimulated the phosphorylation of two additional proteins, with molecular weights of 73- and 37-kD, which were not found in familial AD or control samples. These results suggest that dsDNA-stimulated phosphoprotein changes may be used to distinguish between familial and sporadic forms of AD.


Heritabilities of the metabolic syndrome and its components in the Northern Manhattan Family Study.
Growing evidence suggests that the traits comprising the metabolic syndrome have a genetic basis. However, studies of genetic contributions to the syndrome are sparse. Against this background, we sought to estimate the heritability of the metabolic syndrome and its component traits. We investigated 803 subjects from 89 Caribbean-Hispanic families who have enrolled to date in the current Northern Manhattan Family Study and for whom metabolic syndrome information was available. Metabolic syndrome was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII) criteria. Variance component methods were used to estimate age and sex-adjusted heritability of the metabolic syndrome and its components. To obtain the structures underlying the metabolic syndrome, we performed principal component factor analyses using six quantitative phenotypes included in the ATPIII definition. The heritability for the metabolic syndrome was 24% (p=0.009), and ranged from 16 to 60% for its five components. Factor analysis yielded two independent factors (factor 1: lipids/glucose/obesity; factor 2: blood pressure). Heritability analysis revealed significant genetic effects on both factors (44% for lipids/glucose/obesity, and 20% for blood pressure). In the Caribbean-Hispanic families investigated, we demonstrated moderate and significant heritabilities for the metabolic syndrome itself, as well as for individual components and independent factors of the syndrome. These results provide evidence that could support future tasks of mapping susceptibility loci for this syndrome.


Clinical implications of preterm infant gut microbiome development.
Perturbations to the infant gut microbiome during the first weeks to months of life affect growth, development and health. In particular, assembly of an altered intestinal microbiota during infant development results in an increased risk of immune and metabolic diseases that can persist into childhood and potentially into adulthood. Most research into gut microbiome development has focused on full-term babies, but health-related outcomes are also important for preterm babies. The systemic physiological immaturity of very preterm gestation babies (born earlier than 32 weeks gestation) results in numerous other microbiome-organ interactions, the mechanisms of which have yet to be fully elucidated or in some cases even considered. In this Perspective, we compare assembly of the intestinal microbiome in preterm and term infants. We focus in particular on the clinical implications of preterm infant gut microbiome composition and discuss the prospects for microbiome diagnostics and interventions to improve the health of preterm babies.


Isoflurane and sevoflurane produce a dose-dependent reduction in the shivering threshold in rabbits.
All general anesthetics markedly impair thermoregulatory responses; nonetheless, sufficient hyperthermia or hypothermia will trigger most protective reflexes. Shivering, however, remains an exception among thermo-regulatory responses: it is common during postanesthetic recovery, but is rare at typical anesthetic concentrations. This observation suggests that general anesthesia impairs shivering far more than other thermoregulatory defenses. Accordingly, we tested the hypothesis that low concentrations of isoflurane and sevoflurane would virtually obliterate shivering. Japanese white rabbits were anesthetized with isoflurane or sevoflurane at end-tidal concentrations of 0.2, 0.3, and 0.4 minimum alveolar anesthetic concentration (MAC) (n = 6 in each group); the normal core temperature for these rabbits is approximately 39 degrees C. Core temperatures were subsequently reduced by a water-perfused thermode positioned in the colon. The core temperature triggering shivering identified the threshold for this response. Five of the six rabbits given 0.2 MAC isoflurane shivered at a mean core temperature of 36.3 +/- 0.3 degrees C (mean +/- SD), and one rabbit failed to shiver at a minimum core temperature of 35.0 degrees C. Four of the six rabbits given 0.3 MAC isoflurane shivered at a mean core temperature of 36.2 +/- 0.6 degrees C, and two of these rabbits failed to shiver at a minimum core temperature of 35.0 degrees C. However, no rabbit given 0.4 MAC isoflurane shivered, even at minimum core temperatures of 35.0 degrees C. All of the rabbits given 0.2 MAC sevoflurane shivered at a mean core temperature of 36.6 +/- 0.7 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


Latex agglutination test for cytomegalovirus antibody screening of transplant donors. Important aspects.
In a retrospective study, false negative readings of CMV Scan results were detected. In a following prospective survey of 72 transplant donor sera, CMV Scan had a sensitivity and a negative predictive value of greater than 95%. Although CMV Scan is a rapid and useful test, a higher reliability can be achieved if results are controlled by another sensitive test or, at the least, CMV Scan is read by two different persons.


The reliability and validity of the Korean version of the Pittsburgh Sleep Quality Index.
The Pittsburgh Sleep Quality Index (PSQI) is a self-reported questionnaire that measures sleep quality during the previous month. The aims of this study were to analyze the reliability and validity of the Korean version of the PSQI (PSQI-K) and to evaluate its usefulness. We developed the PSQI-K, which involved translating the original PSQI into Korean and then translating back into English to check its accuracy. We tested the validity of the PSQI-K on a total of 394 individuals: 261 with poor sleep (primary insomnia, n = 211; narcolepsy, n = 50) and 133 with good sleep. All subjects completed the PSQI-K, 285 had overnight nocturnal polysomnography, and 53 were randomly selected for a retest with the questionnaire after 2-4 weeks without any intervening treatment. The mean PSQI-K global scores in each group were analyzed after adjusting for age and sex. Cronbach's α coefficient for internal consistency of the total score of the PSQI-K was 0.84 which shows high reliability. Sensitivity and specificity for distinguishing poor and good sleepers were 0.943 and 0.844 using the best cutoff point of 8.5. The total and component scores of the PSQI-K for insomnia and narcolepsy were significantly higher than those for controls (p < 0.05). The test-retest correlation coefficient was 0.65 for the total score (p < 0.001). There was no significant difference between the two values using the paired t tests. The PSQI-K is a reliable and valid questionnaire for evaluating sleep quality in patients with sleep disorders.


Seeing the glass half full: optimistic expressive writing improves mental health among chronically stressed caregivers.
This study explored treatment mediators among caregivers of older adults who did not benefit from expressive writing in a recently published randomized clinical trial. Twenty-seven expressive writing and time management participants completed questionnaires prior to writing, following their fourth writing session, and 1 month later. We examined the effect of group differences in linguistic markers on health improvements. Our hypothesis concerning narrative development received no support, and expected links between function words and health were partially confirmed. Results most strongly supported the hypothesis that expressive writing benefited caregivers who used increasingly positive, optimistic, and future-focused language.


Aspergillus terreus myocarditis: report of a case and review of the literature.
Aspergillus terreus is an uncommon cause of myocarditis, with only six reported cases in the world literature. This report describes a case of severe disseminated Aspergillus terreus infection with extensive involvement of the heart in an immunosuppressed patient after aortic valve replacement surgery. Pathologic findings are similar to those found in Aspergillus fumigatus myocarditis. All six previously reported cases of A. terreus carditis occurred in postoperative cardiac surgery or immunocompromised patients. This pathogen should not be dismissed as simply a colonizing organism or a contaminant in fungal cultures, particularly those from hospitalized or seriously ill patients.


Predictive modelling using pathway scores: robustness and significance of pathway collections.
Transcriptomic data is often used to build statistical models which are predictive of a given phenotype, such as disease status. Genes work together in pathways and it is widely thought that pathway representations will be more robust to noise in the gene expression levels. We aimed to test this hypothesis by constructing models based on either genes alone, or based on sample specific scores for each pathway, thus transforming the data to a 'pathway space'. We progressively degraded the raw data by addition of noise and examined the ability of the models to maintain predictivity. Models in the pathway space indeed had higher predictive robustness than models in the gene space. This result was independent of the workflow, parameters, classifier and data set used. Surprisingly, randomised pathway mappings produced models of similar accuracy and robustness to true mappings, suggesting that the success of pathway space models is not conferred by the specific definitions of the pathway. Instead, predictive models built on the true pathway mappings led to prediction rules with fewer influential pathways than those built on randomised pathways. The extent of this effect was used to differentiate pathway collections coming from a variety of widely used pathway databases. Prediction models based on pathway scores are more robust to degradation of gene expression information than the equivalent models based on ungrouped genes. While models based on true pathway scores are not more robust or accurate than those based on randomised pathways, true pathways produced simpler prediction rules, emphasizing a smaller number of pathways.


Direct and indirect pulmonary vascular effects of tolazoline in the newborn lamb.
The pulmonary vascular effects of tolazoline were studied in unsedated newborn lambs during normal oxygenation and hypoxia. Direct and indirect pulmonary vascular responses were analyzed separately. During normal oxygenation, tolazoline (1 mg/kg) given into a branch pulmonary artery increased cardiac output while decreasing systemic and pulmonary resistances. Pulmonary flow distribution did not change, suggesting that the fall in pulmonary resistance was due to an indirect rather than a direct action of the drug. Tolazoline had similar effects on systemic and pulmonary resistances in the hypoxic lamb; however, there was a shift in blood flow toward the injected lung, indicating local pulmonary vasodilation induced by the drug. In either case, tolazoline did not alter the resistance ratio between the injected lung and the systemic circulation. We conclude that tolazoline is a direct pulmonary vasodilator in the hypoxic lamb, but does not appear to lower the pulmonary to systemic resistance ratio.


Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration.
The pharmacokinetics of ketorolac tromethamine, a potent non-narcotic analgesic agent used for relief of moderate to severe pain, has been studied in 15 healthy volunteers who received single 10 mg doses intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.) in a three-way cross-over design. The kinetics of i.v. ketorolac were characterized by a terminal half-life of 5.09 h, a small plasma clearance (CL = 0.35 ml.min-1.kg-1) and a small tissue distribution (Vss = 0.11 l.kg-1, V beta = 0.17 l.kg-1; mean (SD). Following i.m. and p.o. administration, peak levels of approximately 0.8 microgram/ml were rapidly attained (tmax = 0.8 and 0.9 h, respectively) and the systemic bioavailability was essentially complete.


Patella displacement and osteoarthrosis of the knee joint in mice.
Surgical stabilisation of the normally medially--subluxing patella of STR/ORT male mice, prevented the normal development of osteoarthrosis in the medial compartment of the femoro-tibial joint. Surgically produced medial dislocation of the patella in non-arthrosis-prone male CBA/ORT mice often gave rise to osteoarthrosis of the medial condyles. This, with further evidence from previous studies, strongly indicates that the high incidence of degenerative joint disease in male STR/ORT mice occurs because of a tendency of the patella to dislocate medially due to some unknown cause.


The pan-caspase inhibitor Q-VD-OPh has anti-leukemia effects and can interact with vitamin D analogs to increase HPK1 signaling in AML cells.
Caspase function is known to be essential for cell death by apoptosis, but it is now increasingly recognized that these proteases also play important roles in other cellular events. Here we report for the first time that inhibition of cellular caspase activity can induce differentiation of AML blasts, and can enhance vitamin D-induced cell differentiation of these cells. This was studied in blasts obtained from nine patients with AML and one patient with CML by ex vivo culture in the presence of Q-VD-OPh (QVD), a pan caspase inhibitor. Cell differentiation was manifested by the expression of markers of monocytic differentiation CD11b and CD14. Differentiation induced by 1α,25-dihydroxyvitamin D3 (1,25D) or its analogs PRI-1906 and PRI-2191 was enhanced by QVD to a varying degree, depending on the subtype of the leukemia. QVD and 1,25D-induced differentiation was accompanied by increased signaling by Hematopoietic Progenitor Kinase 1(HPK1), and the expression of transcription factors known to be involved in monocytic differentiation was increased. Although the magnitude and nature of these changes were not invariable, it is clear that caspase inhibitors warrant attention as components of differentiation therapy of leukemia, perhaps in combination with derivatives of vitamin D.


Prenatal titanium exposure and child neurodevelopment at 1 year of age: A longitudinal prospective birth cohort study.
Previous animal studies provided the evidence that prenatal titanium exposure can cause neurotoxicity in their offspring, while human data is vacant. Our aim was to identify the associations of prenatal titanium exposure with the child neurodevelopment. Participants in present study were recruited during early pregnancy between 2014 and 2017. Urinary concentrations of titanium at first trimester were determined. We assessed child neurodevelopment using the Chinese version of Gesell Developmental Schedules at first year follow-up. The multivariable linear regressions and the robust modified Poisson regressions were used to estimate the associations of specific gravity corrected urinary titanium concentrations with the child neurodevelopment. In adjusted models, children's developmental quotient scores in the language domain were 2.03 points (95% CI: -3.66, -0.40) lower in the highest tertile of prenatal urinary titanium than in the lowest tertile. Also, children with prenatal urinary titanium in the highest tertile had 1.42 times (95% CI: 1.17, 1.72) increased risk of language development delay compared to those in the lowest tertile. No statistically significant associations were observed between titanium exposure and child development delay in motor, adaptive and social areas. The findings indicated that prenatal higher titanium exposure was associated with impaired language development, suggesting that titanium might act as developmental neurotoxicants.


Measurement of neo-Pavlovian properties of higher nervous activity by motor reaction-time tasks.
A preliminary study involving 80 paid subjects, 40 of each sex, investigated the usefulness of motor response-time tasks as measures of three neo-Pavlovian properties of higher nervous activity, excitatory strength, dynamism, and mobility. Six independent factors were extracted from a set of variables measuring those properties. These factors demonstrated the independence of the three properties, of the excitatory and inhibitory processes in dynamism and mobility, and of strength and sensitivity at least when such tasks are used as measures of properties in the auditory modality. These findings are promising, however, further investigation is required to validate these tasks against the classical tests of properties of higher nervous activity.


Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers.
Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response. Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4-5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined. After 72-80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10×) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone. Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.


Neurocysticercosis.
Neurocysticercosis results when the ingested eggs of the pork tapeworm, Taenia solium, hatch into larval forms that penetrate the gut wall, disseminate hematogenously, and then encyst in the brain. The subsequent symptoms and associated morbidity are variable. Worldwide, cysticercosis is the most common parasitic disease affecting the central nervous system, but it is not a common autopsy finding in the United States. Neurocysticercosis may be an incidental finding, a contributing cause of death, or the underlying cause of death. It is also important for the forensic pathologist to be aware of the possibility of neurocysticercosis in the autopsy population for purposes of epidemiology studies and infection control. The authors use cases of neurocysticercosis found at autopsy at their institution to give examples of each scenario and to review the clinical and pathologic features of this parasitic disease.


Effect of posture on expiratory muscle use during breathing in the dog.
The electromyographic (EMG) activity of the triangularis sterni and abdominal external oblique muscles was studied in 10 lightly anesthetized, spontaneously breathing dogs during postural changes from supine to head up and head down. The triangularis sterni was active during expiration in all animals when breathing in supine posture, whereas the external oblique was active in only 6 animals. A change from the supine to head up posture elicited a marked increase in triangularis sterni and external oblique expiratory EMG activity in all animals. A change from the supine to head down posture conversely caused the triangularis sterni expiratory activity to decrease and the external oblique expiratory activity, when present in supine posture, to be markedly reduced or abolished. The external oblique was generally silent after bilateral cervical vagotomy and no longer responded to posture. In contrast, bilateral vagotomy had no clear-cut effect on either the active use of the triangularis sterni in supine posture or on the muscle response to posture. These results indicate that: the active nature of spontaneous quiet expiration in the dog is not specific to the supine posture; the adoption of the head up posture actually is associated with considerable phasic expiratory recruitment of the triangularis sterni and abdominal muscles, so that moving the chest wall during breathing is proportionately more an expiratory act and less an inspiratory act than in supine posture; and in contrast to the abdominal muscles, the postural changes in triangularis sterni use during breathing are largely independent of vagal inputs.


Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: relevance of circulating basophils to measurements of plasma histamine.
The relationship of airway cooling during exercise to changes in airway caliber, plasma histamine levels, and circulating basophils was investigated in eight allergic asthmatic and eight normal subjects. In asthma matched RHE during exercise and ICH produced almost identical bronchoconstriction with maximum falls in SGaw of 61.0 +/- 4.5% and 57.9 +/- 5.2%, respectively. A similar RHE in normal subjects was associated with a 7.9 +/- 3.3% fall in SGaw. The resting plasma-histamine levels were higher in the asthmatic (0.52 +/- 0.06 ng/ml) than in the normal (0.31 +/- 0.07 ng/ml, p less than 0.05) subjects. No significant change in plasma histamine occurred after exercise in either group nor in the asthmatic subjects with ICH. In contrast, exercise but not ICH stimulated an increase in leukocytes, basophils, and total blood histamine in parallel with the airway response that reached a maximum at 2 to 5 min in both normal and asthmatic subjects. There was a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p less than 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 +/- 2%) than in normal subjects (6.46 +/- 7%, p less than 0.005), which is consistent with the higher resting plasma-histamine levels in the asthmatic subjects. These findings suggest that plasma-histamine changes with exercise in asthma but not ICH may be related to the associated basophilia and sample handling rather than intrapulmonary mast cell degranulation.


Impaired phagocytic capacity driven by downregulation of major phagocytosis-related cell surface molecules elicits an overall modulatory cytokine profile in neutrophils and monocytes from the indeterminate clinical form of Chagas disease.
The distinct ability of phagocytes to present antigens, produce cytokines and provide co-stimulatory signals may contribute to the severity of the outcome of Chagas disease. In this paper, we evaluate the phenotypic features of phagocytes along with the cytokine signature of circulating T-cells from Chagas disease patients with indeterminate (IND) and cardiac (CARD) clinical forms of the disease. Our data demonstrated that neutrophils from IND patients displayed an impaired ability to produce cytokines. A lower Trypanosoma cruzi phagocytic index and higher nitric oxide levels were characteristics of monocytes from IND. The impaired phagocytic capacity did not reflect on the levels of anti-T. cruzi IgG, but was detectable in the downregulation of Fc-γR, TLR and CR1 molecules. The monocyte-derived cytokine signature demonstrated that a down-regulated synthesis of IL-12 and a modulatory state were evidenced by a positive correlation between IL-12 and IL-10 with a lower synthesis of TNF-α. The down-regulation of MHC-II and CD86 in monocytes supports the occurrence of particularities in the APC-activation-arm in IND, and may be involved in the T-cell pro-inflammatory pattern counterbalanced by a potent IL-10 response. Our findings support the hypothesis that differential phenotypic features of monocytes from IND may be committed to the induction of a distinct immune response related to low morbidity in chronic Chagas disease.


Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis.
To compare the bone-mass effects of calcium supplementation and intermittent cyclic etidronate in patients with established corticosteroid-induced osteoporosis. Eighteen male and 21 female patients who had established corticosteroid-induced osteoporosis and were receiving chronic prednisone therapy (> or = 10 mg/d) were enrolled in a prospective 12-month, open-label study. In addition to continuing prednisone therapy, patients received continuous calcium supplementation 500 mg/d (n = 20) or four cycles of intermittent cyclic etidronate therapy consisting of etidronate 400 mg/d for 14 days followed by calcium 500 mg/d for 76 days (n = 19). Bone mineral density (BMD) of the spine (L1 through L4) and proximal femur (total hip, femoral neck, trochanter, Ward's triangle) was measured by dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months by staff blinded to the treatment. Serum calcium, phosphorus, and alkaline phosphatase were also measured at these times. Treatment with intermittent cyclic etidronate for 12 months resulted in significant increases of 5.7% and 6.8% in BMD of the spine and proximal femur (total hip), respectively (P < 0.02 versus baseline; P < 0.001 versus calcium group). Calcium supplementation alone did not prevent significant losses of 3.4% and 4.1% in BMD at the respective sites (P < 0.02 versus baseline). At the end of the study Z scores reflected significant increases in BMD of the spine and proximal femur (all regions) in the etidronate group (P < 0.01), and significant decreases at the spine, proximal femur, and trochanter in the calcium group (P < 0.01). After 12 months, the difference between the groups was 9.1% (P < 0.01; 95% CI 6.3% to 11.9%) at the spine and 10.9% (P < 0.01; 95% CI 7.8% to 14.1%) at the proximal femur (total hip). Seventeen (89%) of the etidronate-treated patients had increases in BMD of both skeletal sites, whereas only 2 (10%) and 3 (15%) of the calcium-treated patients had positive changes in BMD of the spine and proximal femur (total hip), respectively (P < 0.01). Serum calcium, phosphorus, and alkaline phosphatase levels did not change significantly during the study in either treatment group. Both treatment regimens were well tolerated, with no interactions between prednisone therapy and the study medications. Analyses of response by subgroups (female/male, pulmonary/nonpulmonary indication for prednisone) showed no significant attribute-dependent changes during the 12-month study. At baseline, women had significantly lower BMD of the spine and proximal femur (total hip) (P < 0.01), and patients with pulmonary disease had significantly longer duration of prednisone therapy and cumulative prednisone dose (P < 0.03). Intermittent cyclic etidronate reversed the progressive loss of bone mineral density of the spine and proximal femur in female and male patients with established osteoporosis secondary to chronic corticosteroid (prednisone) therapy for pulmonary and nonpulmonary diseases. Calcium supplementation alone did not prevent or attenuate corticosteroid-induced losses.


Endothelial endoplasmic reticulum and nitrative stress in endothelial dysfunction in the atherogenic rabbit model.
Oxidative stress causes endothelial dysfunction which ultimately leads to atherogenesis, yet anti-oxidant therapy has failed to reduce human clinical outcomes. We hypothesise that endoplasmic reticulum stress and oxidative stress are both present in the endothelial layer of aorta with atherosclerosis. Rabbits were fed for 4 weeks a diet supplemented with 1% methionine +0.5% cholesterol (MC). Control animals received a normal diet. The endothelial function of the abdominal aorta was examined using organ bath techniques. Semi-quantitative immunohistochemistry was used to determine endothelial nitrotyrosine (for nitrative/oxidative stress) and glucose regulated protein 78 (GRP 78) and CHOP to determine endoplasmic reticulum stress. Endothelium dependent relaxation in response to acetylcholine significantly decreased in MC. Stress markers were significantly elevated in endothelia in MC compared to control. The total endothelial area examined for GRP78 increased by 8.4±0.25% in MC vs control (p=0.026) and C/EBP homologous protein (CHOP) increased by 21.9±0.05% in MC vs control (p=0.014). Nitrotyrosine increased by 13.3±0.03% in MC vs control (p=0.012). Both endoplasmic reticulum stress and nitrative stress are present during endothelial dysfunction. Treatment directed at both stresses might be beneficial in the prevention of atherosclerosis.


Preparation of standards and determination of sizes of long-chain polyphosphates by gel electrophoresis.
Procedures are presented for isolating fractions of long-chain polyphosphates which have a narrow range of sizes and for determining their chain lengths. The polyphosphates are isolated by elution from preparative polyacrylamide gels. Then, the lengths of these polymers are determined by a method of successive approximations of length from data obtained by electrophoresis on several different gels of varying polyacrylamide concentrations. Once sized, these isolated polyphosphates may be used as electrophoresis standards, making it possible to rapidly and accurately ascertain the size of other samples having unknown chain lengths. By comparison with two other procedures for sizing polyphosphates, it is shown that the method is definitely valid to a length of 450 and most likely to a length of at least 900. This electrophoresis procedure allows, for the first time, the determination of the range of sizes present and the average chain length with only 2-20 micrograms of polyphosphate.


Neuronal Migration on Silicon Microcone Arrays with Different Pitches.
Neuronal migration is a complicated but fundamental process for proper construction and functioning of neural circuits in the brain. Many in vivo studies have suggested the involvement of environmental physical features of a neuron in its migration, but little effort has been made for the in vitro demonstration of topography-driven neuronal migration. This work investigates migratory behaviors of primary hippocampal neurons on a silicon microcone (SiMC) array that presents 14 different pitch domains (pitch: 2.5-7.3 µm). Neuronal migration becomes the maximum at the pitch of around 3 µm, with an upper migration threshold of about 4 µm. Immunocytochemical studies indicate that the speed and direction of migration, as well as its probability of occurrence, are correlated with the morphology of the neuron, which is dictated by the pitch and shape of underlying SiMC structures. In addition to the effects on neuronal migration, the real-time imaging of migrating neurons on the topographical substrate reveals new in vitro modes of neuronal migration, which have not been observed on the conventional flat culture plate, but been suggested by in vivo studies.


Polymorphisms of the fibrinogen-beta gene are related to 2-hour glucose level after oral glucose tolerance test in Hong Kong Chinese.
Fibrinogen, an acute phase protein, is an important inflammatory marker that is associated with cardiovascular diseases. We studied the association of three common human fibrinogen-beta gene (FGB) variants, -455G>A, -249C>T, and -148C>T with glycemic parameters in 265 non-diabetic Hong Kong Chinese subjects. Both FGB variants, -455G>A and -148C>T were in complete linkage disequilibrium and were associated with higher levels of plasma fibrinogen and 2-h glucose after a 75-g oral glucose load (p<0.01). Carriers of FGB AC-haplotype, comprising the two nucleotide variants at positions -455 and -249, had higher fibrinogen level (2.64 +/- 0.65 vs 2.42 +/- 0.52 g/L, p=0.002) and 2-h glucose after a 75-g oral glucose load (5.87 +/- 1.14 vs 5.47 +/- 1.22 g/L, p=0.006). The associations were significant in men, but not women. In stepwise multiple regression analysis, AC-haplotype was independently associated with plasma fibrinogen level and 2-h glucose (p=0.002 and 0.010 respectively). This suggests that fibrinogen may play a role in the development of impaired glucose tolerance.


Higher-Order Chromosomal Structures Mediate Genome Function.
How chromosomes are organized within the tridimensional space of the nucleus and how can this organization affect genome function have been long-standing questions on the path to understanding genome activity and its link to disease. In the last decade, high-throughput chromosome conformation capture techniques, such as Hi-C, have facilitated the discovery of new principles of genome folding. Chromosomes are folded in multiple high-order structures, with local contacts between enhancers and promoters, intermediate-level contacts forming Topologically Associating Domains (TADs) and higher-order chromatin structures sequestering chromatin into active and repressive compartments. However, despite the increasing evidence that genome organization can influence its function, we are still far from understanding the underlying mechanisms. Deciphering these mechanisms represents a major challenge for the future, which large, international initiatives, such as 4DN, HCA and LifeTime, aim to collaboratively tackle by using a conjunction of state-of-the-art population-based and single-cell approaches.


Urgent transcatheter aortic valve replacement may be performed with acceptable long-term outcomes.
The wide availability of transcatheter aortic valve replacement (TAVR) and broadening of its indications to most patients with aortic stenosis may increase its utilization in the urgent setting. However, a comparison of long-term outcomes of patients undergoing urgent TAVR when compared to elective TAVR have not been well studied. All patients that underwent TAVR from 2011 to 2018 were included. Primary outcomes included operative (30-day), 1-, and 5-year survival and readmissions. The total patient population undergoing TAVR was divided into urgent (n = 247) and elective (n = 946) cohorts. Thirty days mortality (6.5% vs. 2.3%; p = .001), acute kidney injury (2.8% vs. 0.6%; p = .003), and length of stay (12 vs. 3 days; p < .001) were higher for the urgent cohort. There was no significant difference between cohorts for 30-day all-cause (14.6% vs. 10.8%; p = .097) readmissions. Freedom from readmission for heart failure at 1-year (73.6% vs. 83.4%; p < .001) was lower for the urgent cohort. One- (79.0% vs. 87.1%; p < .001) and five-year (39.6% vs. 43.5%; p = .005) survival was lower for the urgent cohort. This difference was eliminated after risk adjustment (hazard ratio [HR]: 1.3; p = .158 and HR: 1.1; p = .639, respectively). Unadjusted survival was significantly worse for the urgent cohort up to 1 year. This trend continued for 5-year survival, however, after risk adjustment there was no significant difference in survival between cohorts. Although urgent TAVR is associated with increased periprocedural risk due to more comorbid disease, outcomes and long-term survival are encouraging and support the consideration of urgent TAVR as a viable alternative for this patient population.


Imaging multiple biomarkers in captured rare cells by sequential immunostaining and photobleaching.
Several technologies recently have been developed for separating and counting circulating tumor cells (CTCs) in the human blood. CTCs play an important role in the metastasis of cancer. Most of the current applications are focused on the enumeration of CTCs; however, analysis of the enumerated CTCs has been proven to be increasingly important. Ensemble-decision aliquot ranking (eDAR) is a high-throughput method that allows the isolation of the CTCs from the whole blood with high recovery and a zero false-positive rate. Coupling a CTC separation and capturing method, such as eDAR, with a downstream immunostaining test provides information about the cell's expression of certain protein biomarkers. In this article, we introduce a semi-automated system for sequential immunolabeling and photobleaching on the eDAR platform. With our new technique, we were able to evaluate the expression of eight different biomarkers on isolated CTCs.


Failure of Implanon contraception in a patient taking carbamazepin for epilepsia.
Until now, no pregnancies have been reported in association with the implantable hormonal contraceptive Implanon (Organon, Roseland, NJ, USA), resulting in a pearl index of 0. We present a 24-year-old patient who conceived despite the correct application of Implanon for one and a half year. The patient was concurrently taking carbamazepin for epilepsia. Special care should be taken to patients demanding hormonal contraceptives while taking carbamezepin. Even Implanon seems to possibly fail in this combination.


Incidence and prognosis of gastroesophageal cancer in rural, urban, and metropolitan areas of the United States.
The objective of this study was assess differences in the incidence, late-stage diagnosis, and prognosis of squamous cell carcinoma of the esophagus (SCCE), adenocarcinoma of the esophagus (AE), and adenocarcinoma of the gastric cardia (AGC) in metropolitan, urban, and rural areas in the United States. The authors identified 29,527 patients with SCCE, AE, or AGC who were reported to the Surveillance, Epidemiology, and End Results Program between 2004 and 2009. Incidence estimates for each malignancy were compared across metropolitan, urban, and rural areas. Multivariable logistic regression models were applied to evaluate the association between residential setting and late (distant-stage) diagnosis, and the results were reported as adjusted odds ratios and 95% confidence intervals (CIs). Cox proportional hazard models were used to examine the association between residential setting and cause-specific survival. When residential setting was analyzed using metropolitan population centers as the reference category, the incidence of AE was higher in urban areas (rate ratio [RR], 1.13; 95% CI, 1.06-1.20) and rural areas (RR, 1.15; 95% CI, 1.05-1.25), whereas the incidence of SCCE was lower in rural areas (RR, 0.80; 95% CI, 0.70-0.91). Rural patients were less likely to be diagnosed with stage IV AE compared with patients residing in metropolitan areas (odds ratio, 0.79; 95% CI, 0.65-0.97). No differences in prognosis were observed when patients from large metropolitan centers were compared with their rural counterparts. The current findings indicated that preconceptions regarding disparities in the time of diagnosis and survival between patients from metropolitan and rural areas in the United States are either unwarranted or out of date, at least with respect to gastroesophageal cancers.


Disease perception and social behaviour in persistent rhinitis: a comparison between patients with allergic and nonallergic rhinitis.
Although the understanding of the pathophysiology and pharmacology of rhinitis has increased within recent years, few studies have examined the impact of rhinitis on patients' behaviour. To compare perennial allergic rhinitis (PAR) and perennial nonallergic rhinitis (PNR) in terms of patients' perception of their disease and its psychosocial concomitants. Thirty-one PAR patients and 32 PNR patients responded to a standard symptom list and were interviewed in-depth regarding their complaints and the impact of rhinitis on their daily lives. PAR and PNR patients reported similar somatic and psychosocial complaints. In both disease groups the adverse effects of rhinitis were reported to be substantially limiting, particularly in social contacts, the impact appearing to be more severe in the women. Rhinitis has a severe impact on the daily lives of patients, women reporting more severe psychosocial effects. Disease perception and social adjustment appear to not depend appreciably on whether or not an objective diagnosis of rhinitis can be established.


Attitudes of Neurosurgeons Toward Social Media: A Multi-Institutional Study.
Social media has become an important communication tool in modern life, and its use is undoubtedly increasing worldwide. Given the rising importance of social media in the health care system, little is known about neurosurgeons' social media use and interactions in the context of professional purposes. This study aimed to analyze social media usage and opinions among neurosurgeons in terms of age, gender, and practice setting. An online survey was administered to neurosurgeons worldwide. A total of 1119 neurosurgeons from 104 different countries responded to the questionnaire. All respondents were members of at least 1 social media platform. Older neurosurgeons and neurosurgeons in nonacademic settings spent less time on social media (P < 0.05). Communication with peers via social media decreased with age, while communication via e-mail increased (P < 0.05). Most respondents perceived the effect of social media to be beneficial to neurosurgery (very beneficial [28.73%], somewhat beneficial [35.55%]). More women than men considered that social media platforms provided a greater chance for networking opportunities, learning about a new study or conference, and providing rapid and widespread knowledge transfer (P < 0.05). False guidance (44.68%) and violation of privacy (41.64%) were thought to be the main disadvantages. Social media use, opinions, and attitudes among neurosurgeons vary depending on their age, gender, and practice setting. Most neurosurgeons stated that the use of social media could have beneficial and advantageous effects on neurosurgery practice, while the frequency of misleading information and lack of privacy were perceived as barriers.


Fluorescence-labeled sphingosines as substrates of sphingosine kinases 1 and 2.
Fluorescently labeled d-erythro-sphingosines have been successfully synthesized in 9 and 12 steps starting from commercially available Garner aldehyde. Determining the influence of the nature, position and linkage of the label on the in vitro phosphorylation rate by sphingosine kinases 1 and 2 resulted in the identification of a pyrene- and a NBD-labeled sphingosine which are both phosphorylated with efficiency comparable to the natural substrate.


The ultrastructural and morphological characteristics of the anterior cruciate ligament of the pig: a study using 7.0-Tesla diffusion tensor imaging.
Diffusion tensor imaging research on the anterior cruciate ligament (ACL) is limited, and no study has revealed the ACL fibrous microstructure by 7.0-Tesla magnetic resonance imaging. Therefore, we used magnetic resonance imaging to assess the ACL. Eight porcine ACLs were investigated by diffusion tensor imaging. Imaging was performed with a 7.0-Tesla scanner using a diffusion-weighted two-dimensional spin-echo echo-planar imaging pulse sequence optimised for muscle. The diffusion tensor eigenparameters, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) were used for bones and muscles. Three-dimensional projection maps of the principal eigenvectors were plotted to visualise the microstructure. The mean FA and ADC for the ACL were 0.27 ± 0.079 and 0.0012 ± 0.0005, respectively. There were no significant differences between the values in the proximal and distal portions . However, the ADC was smaller in the centre than on the sides (0.0015 ± 0.0007), and the mean FA was larger in the centre than on the sides (0.42 ± 0.23). The ACL fibres were parallel on the proximal and distal sides but interweaved in the centre. These findings may be beneficial for artificial ligaments.


Effect of test expectancy on preferred study strategy use and test performance.
Among undergraduates in a carefully controlled design, 9 students who took notes studied longer than groups of 30 and 17 who did not. No differences were observed on test scores, retention interval, comprehension scores, or reading rate. Whether students expected multiple-choice or free-recall testing, strategies were similar, suggesting study oriented to rote learning.


CHECK: A randomized trial evaluating the efficacy and cost-effectiveness of home visitation in pediatric weight loss treatment.
Socioeconomically-disadvantaged households have a high prevalence of pediatric overweight/obesity, and also face barriers to accessing weight loss treatment in healthcare settings. Delivering family-based pediatric weight loss treatment in the home setting may enhance its efficacy by facilitating treatment attendance, enabling more tailored treatment recommendations informed by observations of the home environment, and increasing accountability. This paper describes the design of the Creating Health Environments for Chicago Kids (CHECK) Trial, which evaluates the efficacy, cost-effectiveness, and mechanisms of home visitation in family-based pediatric weight loss treatment for children in low-income households. CHECK is a two-arm, parallel group, randomized controlled trial that is enrolling N = 266 children, ages 6-12 y, who have overweight/obesity (BMI percentile ≥85) and live in a low-income household. Participants are randomized in a 1:1 ratio to either standard of care family-based weight loss treatment delivered in the home, or the identical intervention delivered in an academic medical center. The primary outcome is change in child BMI z-score from baseline to 12 months. Program delivery costs are rigorously documented to enable cost-effectiveness analyses from the societal and payer perspectives. Objectively-documented changes to the home environment and aspects of intervention delivery (e.g., hours of in-person contact received, quantity of behavioral goals set per session) will be tested as hypothesized treatment mechanisms. Findings will inform the design of future interventions, and treatment dissemination decisions by public health agencies and third-party payers. ClinicalTrials.gov identifier: NCT03195790.


N, S-co-doped carbon/Co1-xS nanocomposite with dual-enzyme activities for a smartphone-based colorimetric assay of total cholesterol in human serum.
We fabricated a novel N,S-co-doped carbon/Co1-xS nanocomposite (NSC/Co1-xS) using a facile sol-gel approach, which featured a multiporous structure, abundant S vacancies and Co-S nanoparticles filling the carbon-layer pores. When the Co1-xS nanoparticles were anchored onto the surface of N,S-co-doped carbon, a synergistic catalysis action occurred. The NSC/Co1-xS nanocomposites possessed both peroxidase-like and oxidase-mimetic dual-enzyme activities, in which the oxidase-mimetic activity dominated. By scavenger capture tests, the nanozyme was demonstrated to catalyze H2O2 to produce h+, •OH and •O2-, among which the strongest and weakest signals were h+ and •OH, respectively. The multi-valence states of Co atoms in the NSC/Co1-xS structure facilitated electronic transfer that enhanced redox reactions, thereby improving the resultant color reaction. Based on the NSC/Co1-xS's enzyme-mimetic catalytic reaction, a visual colorimetric assay and Android "Thing Identify" application (app), installed on a smartphone, offered detection limits of 1.93 and 2.51 mg/dl, respectively, in human serum samples. The selectivity/interference experiments, using fortified macromolecules and metal ions, demonstrated that this sensor had high selectivity and low interference potential for cholesterol analysis. Compared to standard assay kits and previously reported visual detection, the Android smartphone-based assays provided higher accuracy (recoveries up to 93.6-104.1%), feasibility for trace-level detection, and more convenient on-site application for cholesterol assay due to the superior enzymatic activity of NSC/Co1-xS. These compelling performance metrics lead us to posit that the NSC/Co1-xS-based nanozymic sensor offers a promising methodology for several practical applications, such as point-of-care diagnosis and workplace health evaluations.


Mortality among hourly motor vehicle manufacturing workers.
We evaluated mortality among 198,245 motor vehicle industry workers during the period of 1973 to 1995. Workers' mortality rates were lower than expected overall (40,131 observed/43,859 expected deaths, standardized mortality ratio [SMR] = 92, CI = 91-92) and for all major cause of death categories except cancer (SMR = 100, CI = 98-102). Mortality rates were higher than expected for lung cancer overall (SMR = 110, CI = 107-113) and among employees in transmission/gear manufacturing (SMR = 121, CI = 112-130), casting operations (SMR = 122, CI = 110-135), engine manufacturing (SMR = 111, CI = 101-123), and vehicle assembly (SMR = 111, CI = 105-117); for stomach cancer in engine manufacturing (SMR = 147, CI = 110-192); and for prostate cancer in casting operations (SMR = 128, CI = 102-158). Excesses of lung cancer in transmission, vehicle assembly, and casting operations and of stomach cancer in engine manufacturing have been observed in other investigations. Further information on employees' occupational exposures and personal attributes is required to clarify the interpretation of these results.


The mechanism of acceptor reactions of Leuconostoc mesenteroides B-512F dextransucrase.
Reactions of dextransucrase and sucrose in the presence of sugars (acceptors) of low molecular weight have been observed to give a dextran of low molecular weight and a series of oligosaccharides. The acceptor reaction of dextransucrase was examined in the absence and presence of sucrose by using D-[14C]glucose, D-[14C]fructose, and 14C-reducing-end labeled maltose as acceptors. A purified dextransucrase was preincubated with sucrose, and the resulting D-fructose and unreacted sucrose were removed from the enzyme by chromatography of columns of Bio-Gel P-6. The enzyme, which migrated at the void volume was collected and referred to as "charged enzyme". The charged enzyme was incubated with 14C-acceptor in the absence of sucrose. Each of the three acceptors gave two fractions of labeled products, a high molecular weight product, identified as dextran, and a product of low molecular weight that was an oligosaccharide. It was found that all three of the acceptors were incorporated into the products at the reducing end. Similar results were obtained when the reactions were performed in the presence of sucrose, but higher yields of labeled products were obtained and a series of homologous oligosaccharides was produced when D-glucose or maltose was the acceptor. We propose that the acceptor reaction proceeds by nucleophilic displacement of glucosyl and dextranosyl groups from a covalent enzyme-complex by a specific, acceptor hydroxyl group, and that this reaction effects a glycosidic linkage between the D-glucosyl and dextranosyl groups and the acceptor. We conclude that the acceptor reactions serve to terminate polymerization of dextran by displacing the growing dextran chain from the active site of the enzyme; the acceptors, thus, do not initiate dextran polymerization by acting as primers.


Mass casualty medicine: time for a 21st century refresh.
Mass casualty events are on the rise globally, as we face increasing pressures from scarcity of resources, population growth, systemic inequalities, geopolitical instabilities, and polarised discourse. Although they are rare events for an individual practitioner, they are going to happen to someone, somewhere, this week, this month, this year. And whilst they are often the last consideration for healthcare systems under constant pressures from daily routine work, individuals, departments, hospitals, and systems have to step up effectively in times of crisis. Failure to do so can lead to suboptimal outcomes for casualties, and even perceived failures can have crippling consequences on staff, families, and communities for years.


Phosphatidylserine biosynthesis pathways in lipid homeostasis: Toward resolution of the pending central issue for decades.
Enzymatic control of lipid homeostasis in the cell is a vital element in the complex organization of life. Phosphatidylserine (PS) is an essential anionic phospholipid of cell membranes, and conducts numerous roles for their structural and functional integrity. In mammalian cells, two distinct enzymes phosphatidylserine synthases-1 (PSS1) and -2 (PSS2) in the mitochondria-associated membrane (MAM) in the ER perform de novo synthesis of PS. It is based on base-exchange reactions of the preexisting dominant phospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE). While PSS2 specifically catalyzes the reaction "PE → PS," whether or not PSS1 is responsible for the same reaction along with the reaction "PC → PS" remains unsettled despite its fundamental impact on the major stoichiometry. We propose here that a key but the only report that appeared to have put scientists on hold for decades in answering to this issue may be viewed consistently with other available research reports; PSS1 utilizes the two dominant phospholipid classes at a similar intrinsic rate. In this review, we discuss the issue in view of the current information for the enzyme machineries, membrane structure and dynamics, intracellular network of lipid transport, and PS synthesis in health and disease. Resolution of the pending issue is thus critical in advancing our understanding of roles of the essential anionic lipid in biology, health, and disease.


Distribution and origin of vasoactive intestinal polypeptide (VIP)-immunoreactive, acetylcholinesterase-positive and adrenergic nerves of the cerebral arteries in the bent-winged bat (Mammalia: Chiroptera).
The overall distribution and origins of vasoactive intestinal polypeptide (VIP)-immunoreactive (IR), acetylcholinesterase (AChE)-positive and adrenergic nerves in the walls of the cerebral arteries were investigated in the bent-winged bat. VIP-IR and AChE-positive nerves innervating the bat cerebral vasculature appear to arise mainly from VIP-IR and AChE-positive cell bodies within microganglia found in the nerve bundle accompanying the sympathetic nerve bundle within the tympanic cavity. These microganglia, as well as the nerve bundle containing them, do not emit catecholamine fluorescence, suggesting that they are of the cranial parasympathetic outflow, probably the facial or glossopharyngeal one. The axons from VIP-IR and AChE-positive microganglia run intermingled with sympathetic adrenergic nerves in the same thick fiber bundles, and reach the cranial cavity through the carotid canal. In addition, some of the VIP-IR fibers innervating the vertebro-basilar system, at least the basilar artery, originate from VIP-IR nerve cells located in the wall of this artery. The supply of VIP-IR fibers to the bat major cerebral arteries is the richest among mammals in that it is much greater in the vertebro-basilar system than in the internal carotid system: plexuses of VIP-IR nerves are particularly dense along the walls from the posterior ramus to posterior cerebral and basilar arteries. Small pial and intracerebral arteries of the vertebro-basilar system, especially those of the posterior cerebral artery which supply most parts of the diencephalon and cerebrum, are also richly innervated by peripheral VIP-IR fibers. This pattern corresponds well with the innervation pattern of adrenergic and AChE-positive nerves.


Myasthenia gravis and pregnancy.
Myasthenia Gravis with pregnancy is a rare concomitance. This case report describes successful outcome of all pregnancies in a lady with this problem. The management is described.