Impact of Donor Origin on Survival After Orthotopic Heart Transplantation.
Heart transplantation is the definitive management for select patients with end-stage heart failure. Owing to an ongoing organ donor shortage, organs are sometimes allocated from distant locales. These organs may be perceived as less desirable because of donor risk factors and ischemic times. We compared survival after heart transplantation by donors originating from British Columbia (BC), other Canadian provinces, and the United States. This retrospective cohort analysis included all patients transplanted in BC between December 1, 1988, and October 21, 2014, and excluded those with missing data or retransplantation. Among 382 patients, 297 (77.7%) recipients and 238 (62.3%) donors were male. The median recipient age was 54.6 years (interquartile range, 46.0-61.0 years) and the median donor age was 33 years (interquartile range, 22-46 years). Overall 10-year survival was 62.1% (95% confidence interval, 56.3-67.4). There was no difference in 10-year survival when comparing donors from BC, other Canadian provinces, and the United States despite significantly lower median ischemic times in donors from BC. Donor location was not predictive of mortality after controlling for recipient age, donor age, and cold ischemic time. Donor origin did not impact 10-year survival after heart transplantation despite increased ischemic time, suggesting that distant donors result in similar outcomes in BC.


What does the Beck Depression Inventory measure in chronic pain?: a reappraisal.
The Beck Depression Inventory (BDI) is widely used to document the prevalence of depression in suffers of chronic pain and in research designs about this population. Williams and Richardson (1993) initially posed the question, "What does the BDI measure in chronic pain?". Results from their study found 3 independent constructs, which differed somewhat from those obtained in analyses with other non-pain subsamples. In our reappraisal of the question, we used confirmatory factor analytic procedures to assess the dimensionality of the BDI. Specifically, we questioned whether a hierarchical model in which a second-level depression construct underlies 3 constituent first-level constructs is reasonable for the data. Our results, based on a sample of 247 chronic pain patients, corroborated the adequacy of this model. The first-level constituent constructs were labeled Negative Attitudes/Suicide, Performance Difficulty, and Physiological Manifestations and were conceptually similar to first-level constructs obtained with other subsamples. Furthermore, external psychological measures and selected questionnaire items were used to assess convergent and discriminant validity of scales operationalizing the factor-analytically derived constructs. With these analyses, we clarify the constituents of depression as measured by the BDI. The findings from this study have implications for more refined epidemiologic and clinical research with chronic pain patients.


LPS-TLR4 pathway exaggerates alcoholic hepatitis via provoking NETs formation.
Intrahepatic infiltration of neutrophils is a character of alcoholic hepatitis (AH) and neutrophil extracellular traps (NETs) are an important strategy for neutrophils to fix and kill invading microorganisms. The gut-liver axis has been thought to play a critical role in many liver diseases also including AH. However, whether NETs appear in AH and play role in AH is still unsure. Serum samples from AH patients were collected and LPS and MPO-DNA were detected. WT, NE KO, and TLR4 KO mice were used to build the AH model, and the intestinal bacteria were eliminated at the same time and LPS was given. Then the formation of NETs and AH-related markers were detected. The serum MPO-DNA and LPS concentration was increased in AH patients and a correlation was revealed between these two indexes. More intrahepatic NETs formed in AH mice. NETs formation decreased with antibiotic intervention and restored with antibiotic intervention plus LPS supplement. While NETs formation failed to change with gut microbiome or combine LPS supplement in TLR4 KO mice. As we tested AH-related characters, liver injury, intrahepatic fat deposition, inflammation, and fibrosis alleviated with depletion of NE. These related marks were also attenuated with gut sterilization by antibiotics and recovered with a combined treatment with antibiotics plus LPS. But the AH-related markers did show a difference in TLR4 KO mice when they received the same treatment. Intestinal-derived LPS promotes NETs formation in AH through the TLR4 pathway and further accelerates the AH process by NETs.


Quantitative proteomic analysis of mitochondrial proteins differentially expressed between small cell lung cancer cells and normal human bronchial epithelial cells.
Small cell lung cancer (SCLC) is highly aggressive and is associated with a dismal prognosis. However, there are no clinically recognized biomarkers for early diagnosis. In this study, we used quantitative proteomics to build differential mitochondrial protein profiles that may be used for early diagnosis and investigated the pathogenesis of lung cancer. We cultured SCLC cells (NCI-H446) and normal human bronchial epithelial cells (16-HBE); mitochondria were extracted and purified using differential and Percoll density gradient centrifugation. Subsequently, we used Western blot analysis to validate mitochondrial purity and labeled proteins/peptides from NCI-H446 and 16-HBE cells using relative and absolute quantification of ectopic tags. We then analyzed mixed samples and identified proteins using two-dimensional liquid chromatography-tandem mass spectrometry. Additionally, we performed subsequent bioinformatic proteome analyses using the programs ExPASy, GOA, and STRING. Finally, the relationship between ornithine aminotransferase expression and clinicopathological features in lung cancer patients was evaluated using immunohistochemistry. One hundred and fifty-three mitochondrial proteins were differentially expressed between 16-HBE and NCI-H446 cells. The expression of 30 proteins between 16-HBE and NCI-H446 cells increased more than 1.3-fold. The upregulation of ornithine aminotransferase was associated with pathological grade and clinical tumor node metastasis stage. Our experiment represented a promising method for building differential mitochondrial protein profiles between NCI-H446 and 16-HBE cells. Such analysis may also help to identify novel biomarkers of lung cancer.


Association of HLA antigens and primary open-angle glaucoma.
HLA testing of 55 patients with primary open-angle glaucoma revealed no increased frequencies of any of 17 HLA-A and 29 HLA-B antigens. However, the subgroup with a known family history of primary open-angle glaucoma had an increase in the frequency of the HLA-B12 antigen (48%). Intrafamily studies might further define the strength and importance of this association.


Short-Wavelength Automated Perimetry Parameters at Baseline and Following Remission in Patients With Birdshot Retinochoroidopathy.
To identify changes in short-wavelength automated perimetry patterns and parameters between the active and inactive states. Retrospective cohort study with age-matched, normal controls. setting: Private tertiary referral center. Seventy-five eyes of 38 patients with active birdshot retinochoroidopathy and 37 eyes of 37 historical normal controls. Thirty-seven patients received immunomodulatory therapy. A fluocinolone acetonide intravitreal implant (Retisert) was implanted in both eyes of 1 patient as an initial treatment. Changes in short-wavelength automated perimetry total deviation scores, pattern deviation scores, mean deviation, and pattern standard deviation in the active phase and the remission state. Mean deviation (P = .006), pattern standard deviation (P = .001), total deviation score (P = .002), and pattern deviation score (P = .007) were significantly different from the active phase to the remission state. The length of time required to achieve remission did not significantly affect the changes in mean deviation (regression coefficient = 0.01; P = .92), pattern standard deviation (regression coefficient = 0.01; P = .87), total deviation score (regression coefficient = -0.1; P = .32), or pattern deviation score (regression coefficient = 0.1; P = .36) from the active phase to the remission state. There was significant improvement in total deviation score, pattern deviation score, mean deviation, and pattern standard deviation on short-wavelength automated perimetry as patients achieved remission. Short-wavelength automated perimetry appears to be a useful and complementary modality in monitoring disease activity in birdshot retinochoroidopathy.


Spray-On Nanocomposite Coatings: Wettability and Conductivity.
Nanocomposite coatings, i.e., a combination of nanocompounds, and a polymer matrix together with suitable additives and solvents is a very versatile method for producing multifunctional coatings. Some of the most desired coating properties have a high repellency to liquids (e.g., superhydrophobic and/or superoleophobic) and electrical and thermal conductivities. From a practical perspective, coatings that can be sprayed are very suitable for large-scale production, conformity, and reduced time and cost. Carbon-based, metallic, and ceramic are the three groups of nanocompounds commonly used to formulate spray-on nanocomposite coatings. In this invited feature article, we discuss the applications, advantages, and challenges of using such nanocompounds to produce coatings with good water repellency or/and elevated electrical or/and thermal conductivities. We also discuss the role of additives and solvents briefly in relation to the properties of the coatings. Important spraying parameters, such as stand-off distance and its influence on the final coating properties, will also be examined. Our overall aim is to provide a guideline for the production of practical multifunctional nanocomposites utilizing carbon-based, metallic, or ceramic nanoparticles or nanofibers that covers both aspects of in-air wettability and conductivity under one umbrella.


[Effect of biofeedback in regulation of masseter muscle myoelectric activities].
To investigate the effect of the biofeedback in regulating the myoelectric activities of the masseter muscles. Twenty orthodontic patients aged from 10 to 14 years with Angle Class II malocclusion, retrusive mandible, and an ANB angle > 6° were enrolled in this study. The muscular activities of the anterior temporal muscle and the masseter muscle were evaluated before, during, and after biofeedback treatment by assessing the average integrated electromyogram and temporal/masseter (T/M) ratio in the clenching status. The patients' myoelectric activities of the anterior temporal muscle was significantly increased after biofeedback treatment (P<0.05). The patients' T/M ratio in the clenching status was increased after the treatment (1.76 ± 1.46 before treatment, 4.71 ± 4.03 immediately after treatment, and 2.57 ± 2.07 at 1 day after treatment; t=4.86, P<0.05). Biofeedback treatment can regulate the activities of the anterior temporal and masseter muscles and increase the T/M ratio in the clenching status.


The oblique supine decubitus position: technical description and comparison of results with the prone decubitus and dorsal supine decubitus positions.
Our objective was to analyze the advantages of the percutaneous nephrolithotomy in oblique supine decubitus compared to the prone and dorsal supine position. In 87 patients diagnosed with urolithiasis (495.5-530.8 mm(2)), percutaneous nephrolithotomy (PNL) was performed from 2000 to 2011. The patients were divided into three groups: Group A, 32 patients, PNL in the prone decubitus position; Group B, 24 patients, PNL in the dorsal supine position; Group C, 31 patients, PNL in the oblique supine position. We analyzed intraoperative parameters, complications, and results among the three groups. The three procedures were performed with a single access, 24-30 Ch. No statistically significant differences were found among the three groups regarding the patients' characteristics, or the morphology or size of the kidney stone treated. The operation time was shorter in the cases of PNL in dorsal supine and oblique supine compared to the prone position. The complication rate was very similar in the three groups. The main advantage of the PNL in oblique supine compared to the dorsal supine was that the puncture could in all cases be directed by ultrasonography, with greater precision, more safety, and more control of the percutaneous renal access. The oblique supine decubitus position is a safe position for the percutaneous treatment of urolithiasis and it becomes easier when the puncture is guided by ultrasound.


Obesity-related indicators and their relationship with serum antioxidant activity levels in Mexican adults.
Obesity has been associated with an oxidative process, however there are controversies regarding the potential role of circulating antioxidant activity attributed to non-protein compounds. The purpose of the present study was to examine the relation between antioxidant activity levels and obesity related-indicators in Mexican young adults. Anthropometric measures, serum lipids and uric acid were determined in 78 men and 90 women (a total of 168 individuals). Serum antioxidant activity in different fractions also was measured by using TEAC assay (TEACNP, TEACP and TEACTotal). TEACNP was positively correlated (p<0.05) BMI (r=0.307), WC (r=0.322), LDL (r=0.274), TC (r=0.293), TG (r=0.409) and UA (r=0.441). The antioxidant activity measured as TEACNP in individuals with obesity related-indicators was higher compared to those individuals without obesity-related indicators. When BMI, WC, HDL, LDL, TC, TG and UA were considered as obesity related-indicators, the higher the number of obesity related indicators (p<0.05) the higher the TEACNP values. However, when TEACP values decreased, the number of obesity related-indicators (p<0.05) increased. The positive association between TEACNP and obesity related-indicators suggests that apparently increase in TEACNP may not always indicate a healthier condition.


Maternal deprivation increases behavioural reactivity to stressful situations in adulthood: suppression by the CCK2 antagonist L365,260.
Maternal deprivation can result in long-term impairment of neuronal functions and in the development of long-lasting behavioural disorders. This study analysed the effects of a selective cholecystokinin-2 (CCK2) antagonist, 3R-(+)-N-(2,3-dihydro-1methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3yl)-N'-(3-methyl phenyl) urea (L365,260), in anxiety- and stress-related behaviours of adult rats that were deprived (D) from their mother and littermates for 3 h everyday during 14 days after birth. The behaviour was studied in actimeter, in open field and after food and water deprivation. Corticosterone plasma levels were quantified after food and water deprivation. The effects of L365,260 were studied in the behavioural changes observed in D rats. No differences in circadian motor activity between non-deprived (ND) and D rats were observed. D rats showed a 50% decrease in their number of visits to the central (aversive) part of the open field compared to ND rats. This effect was suppressed by L365,260. After 20 h of food and water deprivation, an increase in plasma corticosterone was observed in D and ND rats. However, the raise of corticosterone secretion in D rats was dramatically increased (300%) compared to ND rats, indicating a hypersensitised state revealed by this stressful situation. Consumption of sucrose solution (1%) was higher for D rats than for ND rats after food and water deprivation. Sucrose consumption returned to control values following L365,260 treatment. These results suggest that maternal deprivation led to an increase in anxiety and stress reactivity in adulthood. We propose that these long-lasting changes are partly dependent on CCKergic transmission involving the activation of CCK2 receptors.


Prenatally diagnosed cystic lymphangioma in infants.
Prenatally diagnosed cystic lymphangioma (CL) is often associated with chromosomal anomalies, hydrops fetalis, and, in the case of cervical CL, occasionally respiratory distress just after birth. Often it is difficult to treat prenatally diagnosed CL because of the large size and associated symptoms. Between 1988 and 1997, 11 cases of prenatally diagnosed CL were treated. Five pregnancies were terminated electively and one aborted spontaneously (nondelivered, non-D group), and another five delivered (delivered, D group). Thirteen infants nondiagnosed prenatally were also seen in the same period (prenatally nondiagnosed, without pre-D group). In the non-D group, massive CLs were diagnosed by ultrasound scan between 16 and 20 weeks' gestation. They occurred in the head and neck in all six cases, and four had associated pleural effusions or hydrops. In the D group, CL occurred in the face and neck in four cases. Three were born by cesarean section with neonatologists and surgeons standing by, then transferred to our hospital immediately after birth. Respiratory distress appeared in two cases; tracheostomy was carried out in one case. One patient with a huge CL in the chest and abdominal wall necessitated partial resection after OK-432 sclerotherapy. In the without pre-D group, there was CL in the face or neck in 10 cases, abdominal wall in two cases, and chest wall in one case. Respiratory distress was observed in three cases of cervical CL, and tracheostomy was required in two cases. One patient with hypoxic brain damage sequela died of pneumonia afterward. Prenatal diagnosis permits planned delivery, prompt postnatal resuscitation, and improve prognosis. Infants with massive CL diagnosed early in pregnancy have other associated anomalies as well as hydrops fetalis, and a poor outcome or difficult management can be expected.


Pembrolizumab for previously treated, microsatellite instability-high/mismatch repair-deficient advanced colorectal cancer: final analysis of KEYNOTE-164.
Pembrolizumab demonstrated durable clinical benefit and manageable safety in previously treated advanced or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer (CRC) in the phase 2 KEYNOTE-164 study. Results from the final analysis are presented. Eligible patients had unresectable or metastatic MSI-H/dMMR CRC and ≥2 prior systemic therapies (cohort A) or ≥1 prior systemic therapy (cohort B). Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤35 cycles. The primary end-point was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors, version 1.1 by blinded independent central review. Secondary end-points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Sixty-one patients in cohort A and 63 patients in cohort B were enroled; median follow-up was 62.2 months and 54.4 months, respectively. ORR was 32.8% (95% CI, 21.3%-46.0%) in cohort A and 34.9% (95% CI, 23.3%-48.0%) in cohort B. Median DOR was not reached (NR) in either cohort. Median PFS was 2.3 months (95% CI, 2.1-8.1) in cohort A and 4.1 months (95% CI, 2.1-18.9) in cohort B. Median OS was 31.4 months (95% CI, 21.4-58.0) in cohort A and 47.0 months (95% CI, 19.2-NR) in cohort B. No new safety signals were observed. Nine patients who initially responded experienced disease progression off therapy and received second-course pembrolizumab. Six patients (66.7%) completed an additional 17 cycles of pembrolizumab, and 2 patients achieved a partial response. Pembrolizumab continued to show durable antitumor activity, prolonged OS, and manageable safety in patients with previously treated MSI-H/dMMR CRC. ClinicalTrials.gov, NCT02460198.


Auxotrophic-precursor directed biosynthesis of nonribosomal lipopeptides with modified tryptophan residues.
Feeding 5-hydroxy and 5-fluorotryptophan to a Streptomyces coelicolor Trp-auxotrophic strain WH101 results in the production of a number of new calcium-dependent antibiotics (CDAs) possessing modified Trp residues. It is anticipated that this method could be used to modulate the biological properties of Trp-containing nonribosomal peptide natural products, or to generate analogues with useful fluorescent properties for studying biological mechanisms of action.


Drug-Dosing Adjustment in Dogs and Cats with Chronic Kidney Disease.
Chronic kidney disease is a common kidney disorder in adult and aged dogs and cats; the management of associated complications and comorbidities generally requires a life-long medical treatment to ensure a good quality of life of affected patients. However, indications and the literature on drug dosing in dogs and cats with chronic kidney disease are often lacking. The aim of this review is to revise the current literature on drug dosing in canine and feline patients with renal impairment, with a special focus on the most commonly used medications to manage chronic kidney disease and possible comorbidities.


A Contemporary Appraisal on Impending Industrial and Agricultural Applications of Thermophilic-Recombinant Chitinolytic Enzymes from Microbial Sources.
The ability of chitinases to degrade the second most abundant polymer, chitin, into potentially useful chitooligomers and chitin derivatives has not only rendered them fit for chitinous waste management but has also made them important from industrial point of view. At the same time, they have also been recognized to have an imperative role as promising biocontrol agents for controlling plant diseases. As thermostability is an important property for an industrially important enzyme, various bacterial and fungal sources are being exploited to obtain such stable enzymes. These stable enzymes can also play a role in agriculture by maintaining their stability under adverse environmental conditions for longer time duration when used as biocontrol agent. Biotechnology has also played its role in the development of recombinant chitinases with enhanced activity, thermostability, fungicidal and insecticidal activity via recombinant DNA techniques. Furthermore, a relatively new approach of generating pathogen-resistant transgenic plants has opened new ways for sustainable agriculture by minimizing the yield loss of valuable crops and plants. This review focuses on the potential applications of thermostable and recombinant microbial chitinases in industry and agriculture.


Multiplex Immunostaining Method to Distinguish HSP Isoforms in Cancer Tissue Specimens.
Heat shock proteins (HSPs) are often expressed in all nucleated cells, but their expression profiles differ. In particular, HSP90α and HSP90β have high sequence identity and have not been fully examined for their individual and compensatory functions as molecular chaperones, differences in client proteins, and extracellular distributions with exosomes. Immunohistochemical staining is a technique to visualize the presence and localization of target antigens using specific antibodies, of which the multiplex immunostaining method can reveal differences in protein expression in the same tumor tissue and the localization of proteins of interest within tumor tissue or single cells. The common multiplex immunostaining method uses multiple secondary antibodies of different reacting animal species to identify and detect different antigens, thus requiring different animals to be immunized with each primary antibody. Furthermore, the fluorescent-antibody method is the predominant multiplex staining method but has the critical disadvantage that permanent specimens cannot be prepared. Here, we outline a multiplex staining method for HSP90α and HSP90β based on the enzyme-antibody method that allows permanent specimens to be prepared without the restriction of immunized animal species.


Continuous glucose monitoring: a review of biochemical perspectives and clinical use in type 1 diabetes.
Self-monitoring of blood glucose is a fundamental part of diabetes management. It is mandatory for tight glucose control. For the past 30 years, intermittent measurement of capillary blood glucose has been the method of choice for self-monitoring. The main disadvantage of such measurements is that they provide isolated glucose values which do not reflect variations occurring throughout the day and night. Hence systems monitoring blood glucose concentrations on a "continuous basis" have been developed. In clinical studies, different devices were shown to provide useful information on glycemic excursions in people with diabetes with sufficient accuracy. Thus, in clinical practice, this approach has also been shown to help in the medical management leading to a reduction in glycated hemoglobin and glycemic variability. However, because of lack of experience, this technology has yet to replace standard capillary blood glucose monitoring. In this paper, we review the biochemical perspectives of continuous glucose monitoring and its clinical use in type 1 diabetes.


The effects of a novel personal comfort system on thermal comfort, physiology and perceived indoor environmental quality, and its health implications - Stimulating human thermoregulation without compromising thermal comfort.
The classical textbook interpretation of thermal comfort is that it occurs when the thermoregulatory effort is minimized. However, stimulating human thermoregulatory systems may benefit health and increase body thermal resilience. To address this gap, we tested a novel personal comfort system (PCS) that targets only the extremities and the head, leaving the rest of the body exposed to a moderately drifting temperature (17-25°C). A randomized, cross-over study was conducted under controlled laboratory conditions, mimicking an office setting. Eighteen participants completed two scenarios, one with a PCS and another one without a PCS in 17-25°C ambient conditions. The results indicate that the PCS improved thermal comfort in 17-23°C and retained active thermoregulatory control. The torso skin temperature, underarm-finger temperature gradients, energy expenditure, substrate oxidations and physical activity were not affected by the PCS in most cases. Only slight changes in cardiovascular responses were observed between the two scenarios. Moreover, the PCS boosted pleasure and arousal. At 25°C, the PCS did not improve thermal comfort, but significantly improved air quality perceptions and mitigated eye strain. These findings suggest that human physiological thermoregulation can be stimulated without compromising thermal comfort by using a PCS that only targets the extremities in cold conditions.


Projections of fire probability and ecosystem vulnerability under 21st century climate across a trans-Andean productivity gradient in Patagonia.
Warming trends are altering fire regimes globally, potentially impacting on the long-term persistence of some ecosystems. However, we still lack clear understanding of how climatic stressors will alter fire regimes along productivity gradients. We trained a Random Forests model of fire probabilities across a 5°lat × 2° long trans-Andean rainfall gradient in northern Patagonia using a 23-year long fire record and biophysical, vegetation, human activity and seasonal fire weather predictors. The final model was projected onto mid- and late 21st century fire weather conditions predicted by an ensemble of GCMs using 4 emission scenarios. We finally assessed the vulnerability of different forest ecosystems by matching predicted fire return intervals with critical forest persistence fire return thresholds developed with landscape simulations. Modern fire activity showed the typical hump-shaped relationship with productivity and a negative distance relationship with human settlements. However, fire probabilities were far more sensitive to current season fire weather than to any other predictor. Sharp responsiveness of fire to the accelerating drier/warmer fire seasons predicted for the remainder of the 21st century in the region led to 2 to 3-fold (RCPs 4.5 and 8.5) and 3 to 8-fold increases in fire probabilities for the mid- and late 21st century, respectively. Contrary to current generalizations of larger impacts of warming on fire activity in fuel-rich ecosystems, our modeling results showed first an increase in predicted fire activity in less productive ecosystems (shrublands and steppes) and a later evenly amplified fire activity-productivity relationship with it shape resembling (at higher fire probabilities) the modern hump-shaped relationship. Despite this apparent homogeneous effect of warming on fire activity, vulnerability to predicted late 21st century shorter fire intervals were higher in most productive ecosystems (subalpine deciduous and evergreen Nothofagus-dominated rainforests) due to a general lack of fire-adapted traits in the dominant trees that compose these forests.


Analysis of the efficiency of the rabbit whey acidic protein gene 5' flanking region in controlling the expression of homologous and heterologous linked genes.
For 10 years, the regulatory regions of the mouse and rabbit whey acidic protein gene have been used to express heterologous proteins in the milk of transgenic mice, as well as to produce pharmaceutical proteins, on a large scale, in the milk of transgenic livestock. To date, a broad range of expression levels have been detected, and elucidation of the structure-function relationship in these regulatory regions might help to achieve high levels of expression, reproducibly. An extended 5' regulatory region (17.6 kb v. 6.3 kb) of the rabbit whey acidic promoter resulted in an increased frequency of rabbit whey acidic protein expression in transgenic mice. However, the expression levels were low compared with the high expression levels achieved in both transgenic mice and rabbits using the heterologous kappa-casein in the 6.3 kb rabbit whey acidic protein 5' regulatory region. These results underline the importance of the 3' downstream regulatory regions, which still need to be better characterized in the whey acidic protein gene.


Genetic determinants of circulating galectin-3 levels in patients with coronary artery disease.
Galectin-3 plays a crucial role in the regulation of inflammation. The aim of this study was to elucidate the association between LGALS3 genotypes, galectin-3 levels, and inflammatory marker levels in patients with coronary artery disease (CAD). A total of 474 patients with CAD were enrolled. Significant correlations were discerned between galectin-3 levels and leukocyte counts, C-reactive protein, soluble intercellular adhesion molecule-1, and matrix metalloproteinase 9 levels (all p < .05). The LGALS3 rs2274273, rs4644, rs4652 genotypes, and haplotypes CAC, CCC, and ACT exhibited a significant association with galectin-3 levels (for genotypes, p = 1.05 × 10-25 , 3.54 × 10-25 , and 2.74 × 10-7 , respectively). Multivariate analysis showed LGALS3 rs2274273 and rs4644 genotypes contributing to 20.8% variation of galectin-3 levels. However, there was no association between LGALS3 genotypes and other inflammatory marker levels. Our data showed strong genetic determinants of galectin-3 levels in patients with CAD. The galectin-3 levels, but not LGALS3 genotypes, were associated with multiple inflammatory marker levels. Further study may be necessary to elucidate the molecular mechanism of galectin-3 in the pathogenesis of chronic inflammatory disorders.


Opportunities to improve feasibility, effectiveness and costs associated with a total joint replacements high-volume hospital registry.
Clinical registries are powerful tools for collecting uniform data longitudinally, thus making it possible to evaluate the outcome of patients affected by a specific pathology. In the context of total joint arthroplasty, registries serve also as post-market surveillance. Adoption of registries is a heavy burden for clinical settings in terms of resources and infrastructures. Excessive workload leads to incomplete data collection which undermines the effectiveness of a registry and consequently the workload needs to be optimised. Starting from the use case of the Istituto Ortopedico Galeazzi, the time and personnel dedicated to the registry was estimated. Analysis of the data collected in the first years enabled us to propose a methodology for workload reduction. Different Machine Learning models were leveraged to predict patients with excellent satisfaction to reduce the number of assessments in their clinical post-operative follow-up. Moreover, feature selection was used to identify any unnecessary clinical scale to collect. Given an acceptance rate of 3500 patients per year, 22 doctors and 6 non-medical employees were required to adopt a registry properly. Among the tested models, the Naïve Bayes gave the best performance (AUPRC = 0.81) in predicting patient satisfaction at six months. Moreover, we found that the 12-item Short Form was poorly informative in predicting satisfaction at six-months. In this study machine learning was leveraged to provide a methodology to reduce workload in the use of pathology registries. Such workload reduction can have a considerable impact at a larger scale, and improve registry feasibility in high-volume hospitals.


EEG event-related potentials and signal detection.
The purpose of this study was to determine whether certain previously reported relationships between event-related potentials and measures of signal detection performance occur in vigilance as well as psychophysical settings. In the course of the study, evidence was found which challenges previously proposed psychological correlates of "P300". EEG was recorded while 15 subjects carried out a 40-min signal detection test. CNV was measured between a warning click and the brief offset of a dim light denoting the possible (p = 0.5) occurrence of the signal, a faint tone in the constant background noise. P300 was measured at a point 300 msec following offset of the dim light. As reported previously in psychophysical settings, P300 amplitude was positively related to signal intensity and response confidence, and was larger for correct detections (Hits) than for correct rejections, misses or false alarms. From first to second half of the test both Hits and false alarms fell, response criterion beta rose, and the amplitude of both CNV and P300 fell. The latter negative relationship between beta and P300 contrasted with a positive one when subjects rated their signal reports at three levels of confidence; here the most confident ratings (high beta) were associated with the highest amplitude of P300. CNV reflected individual ability to sustain performance. Results are explained in terms of a two-factor version (Wilkinson, 1976) of the prior state/reactive change hypothesis (Karlin, 1970). It is suggested that time on task constitutes a prior state influence on P300, whereas other variables influence P300 by means of either reactive change or 'real' change in an endogenous P300 component.


Interaction effects of multimorbidity and frailty on adverse health outcomes in elderly hospitalised patients.
We quantified the interaction of multimorbidity and frailty and their impact on adverse health outcomes in the hospital setting. Using aretrospective cohort study of persons aged ≥ 75 years, admitted to hospital during 2010-2012 in New South Wales, Australia, and linked with mortality data, we constructed multimorbidity, frailty risk and outcomes: prolonged length of stay (LOS), 30-day mortality and 30-day unplanned readmissions. Relative risks (RR) of outcomes were obtained using Poisson models with random intercept for hospital. Among 257,535 elderly inpatients, 33.6% had multimorbidity and elevated frailty risk, 14.7% had multimorbidity only, 19.9% had elevated frailty risk only and 31.8% had neither. Additive interactions were present for all outcomes, with a further multiplicative interaction for mortality and LOS. Mortality risk was 4.2 (95% CI 4.1-4.4), prolonged LOS 3.3 (95% CI 3.3-3.4) and readmission 1.8 (95% CI 1.7-1.9) times higher in patients with both factors present compared with patients with neither. In conclusion, multimorbidity and frailty coexist in older hospitalized patients and interact to increase the risk of adverse outcomes beyond the sum of their individual effects. Their joint effect should be considered in health outcomes research and when administering hospital resources.


Insulin and progesterone increase 32PO4-labeling of phospholipids and inositol 1,4,5-trisphosphate mass in Xenopus oocytes.
After a 4-6 h induction period, insulin or progesterone induces Xenopus oocytes to enter prophase of meiosis. During the period of induction, both insulin and progesterone induced an increase in 32PO4 labeling of phosphatidylcholine and phosphatidylinositol. Through a mass assay, we found that insulin and progesterone increase inositol 1,4,5-trisphosphate (IP3) at about 15-30 s, 15 min and at about 2-3 h (0.5 GVBD50) after hormone addition. Since IP3 increases were small (from a basal of 66 to 104 nM), the results agree with prior conclusions that progesterone does not induce a large, cytosolic calcium elevation. Insulin is probably acting through the insulin-like growth factor-1 receptor as insulin concentrations greater than about 50 nM are required to increase IP3.


The formation of hybrid complexes between isoenzymes of glyceraldehyde-3-phosphate dehydrogenase regulates its aggregation state, the glycolytic activity and sphingolipid status in Saccharomyces cerevisiae.
The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been traditionally considered a housekeeping protein involved in energy generation. However, evidence indicates that GAPDHs from different origins are tightly regulated and that this regulation may be on the basis of glycolysis-related and glycolysis-unrelated functions. In Saccharomyces cerevisiae, Tdh3 is the main GAPDH, although two other isoenzymes encoded by TDH1 and TDH2 have been identified. Like other GAPDHs, Tdh3 exists predominantly as a tetramer, although dimeric and monomeric forms have also been isolated. Mechanisms of Tdh3 regulation may thus imply changes in its oligomeric state or be based in its ability to interact with Tdh1 and/or Tdh2 to form hybrid complexes. However, no direct evidence of the existence of these interactions has been provided and the exact function of Tdh1,2 is unknown. Here, we show that Tdh1,2 immunopurified with a GFP-tagged version of Tdh3 and that lack of this interaction stimulates the Tdh3's aggregation. Furthermore, we found that the combined knockout of TDH1 and TDH2 promotes the loss of cell's viability and increases the growing rate, glucose consumption and CO2 production, suggesting a higher glycolytic flux in the mutant cells. Consistent with this, the tdh3 strain, which displays impaired in vitro GAPDH activity, exhibited the opposite phenotypes. Quite remarkably, tdh1 tdh2 mutant cells show increased sensitivity to aureobasidin A, an inhibitor of the inositolphosphoryl ceramide synthase, while cells lacking Tdh3 showed improved tolerance. The results are in agreement with a link between glycolysis and sphingolipid (SLs) metabolism. Engineering Tdh activity could be thus exploited to alter the SLs status with consequences in different aspects of yeast biotechnology.


Gas chromatography/mass spectrometry in metabolic profiling of biological fluids.
One of the objectives of metabonomics is to identify subtle changes in metabolite profiles between biological systems of different physiological or pathological states. Gas chromatography mass spectrometry (GC/MS) is a widely used analytical tool for metabolic profiling in various biofluids, such as urine and blood due to its high sensitivity, peak resolution and reproducibility. The availability of the GC/MS electron impact (EI) spectral library further facilitates the identification of diagnostic biomarkers and aids the subsequent mechanistic elucidation of the biological or pathological variations. With the advent of new comprehensive two dimensional GC (GC x GC) coupled to time-of-flight mass spectrometry (TOFMS), it is possible to detect more than 1200 compounds in a single analytical run. In this review, we discuss the applications of GC/MS in the metabolic profiling of urine and blood, and discuss its advances in methodologies and technologies.


Isoelectric focusing in polyacrylamide gel carried out with a simple device for power regulation. Application to mammalian growth hormones.
A unit is described to regulate the electrical power delivered to an isoelectric focusing cell. The device consists in a resistance set, in series with a power supply, which can be adjusted to a suitable resistance value in order to permit only minor changes in wattage. Simultanoeus monitoring of voltage and current is also carried out with a pen-recorder adaptor. The improvements in operative conditions achieved by these means are tested by the fractionation of mammalian growth hormones.


ScaffComb: A Phenotype-Based Framework for Drug Combination Virtual Screening in Large-Scale Chemical Datasets.
Combinational therapy is used for a long time in cancer treatment to overcome drug resistance related to monotherapy. Increased pharmacological data and the rapid development of deep learning methods have enabled the construction of models to predict and screen drug pairs. However, the size of drug libraries is restricted to hundreds to thousands of compounds. The ScaffComb framework, which aims to bridge the gaps in the virtual screening of drug combinations in large-scale databases, is proposed here. Inspired by phenotype-based drug design, ScaffComb integrates phenotypic information into molecular scaffolds, which can be used to screen the drug library and identify potent drug combinations. First, ScaffComb is validated using the US food and drug administration dataset and known drug combinations are successfully reidentified. Then, ScaffComb is applied to screen the ZINC and ChEMBL databases, which yield novel drug combinations and reveal an ability to discover new synergistic mechanisms. To our knowledge, ScaffComb is the first method to use phenotype-based virtual screening of drug combinations in large-scale chemical datasets.


The use of reservoir devices for the simultaneous delivery of two metered-dose aerosols.
Many patients benefit from using metered-dose inhalers (MDIs) with spacer or reservoir devices. Concomitant therapy with separate MDI doses of cromolyn sodium and a beta-agonist is common practice. If two puffs from each drug could be placed into a chamber, the patient could administer both medications at once, enhancing compliance. A multistage liquid impinger (a four-stage inertial impaction device incorporating an inlet bend and an absolute filter, which separates an aerosol cloud into six fractions) was used to investigate such a possibility. Cromolyn sodium and albuterol MDIs were used with an Aerochamber (Monaghan Medical Corp., Plattsburgh, N.Y.) and an Inspirease (Schering Corp., Kenilworth, N.J.). Results are reported by analyzing milligrams of cromolyn sodium per actuation retrieved. With the Aerochamber, two puffs of cromolyn sodium followed by two puffs of albuterol resulted in the total "dose to patient" being reduced by 75% (0.19 versus 0.05 mg) and the effective dose of fine particles (less than 6.5 microns) being reduced by 80% (0.13 versus 0.03 mg) compared to two puffs of cromolyn sodium alone. With the Inspirease, total dose was decreased by 80% (0.32 versus 0.06 mg), whereas the effective dose of fine particles was reduced by 60% (0.19 versus 0.05 mg) compared to one puff of cromolyn sodium alone. The use of cromolyn sodium and albuterol MDIs in a multipuff combination with the Aerochamber or the Inspirease is not recommended because this leads to a loss of the dose delivered compared to a single administration.


On the Calculation of Atomic Forces in Classical Simulation Using the Charge-on-Spring Method To Explicitly Treat Electronic Polarization.
An expression for the atomic forces in simulations using the charge-on-spring (COS) polarizable model is rederived. In previous implementations of COS-based models, contributions arising from the dependence of the induced dipoles (i.e., the positions of the charges-on-spring) on the coordinates of the other sites in the system were not taken into account. However, from calculations on gas-phase dimers we found a significant contribution of these terms. Errors in the forces when neglecting these contributions in condensed-phase calculations can be significantly reduced by choosing an appropriately large value for the size of the charge-on-spring.


A word of caution against excessive protein intake.
Dietary protein is crucial for human health because it provides essential amino acids for protein synthesis. In addition, dietary protein is more satiating than carbohydrate and fat. Accordingly, many people consider the protein content when purchasing food and beverages and report 'trying to eat more protein'. The global market for protein ingredients is projected to reach approximately US$90 billion by 2021, largely driven by the growing demand for protein-fortified food products. This Perspective serves as a caution against the trend of protein-enriched diets and provides an evidence-based counterpoint that underscores the potential adverse public health consequences of high protein intake.


Differences in switching away from cigarettes and JUUL use characteristics among adult menthol and nonmenthol smokers who purchased the JUUL System.
Studies have assessed switching away from cigarettes among adult smokers who use electronic nicotine delivery systems (ENDS), but there is little data assessing differences in likelihood of switching or ENDS use characteristics by menthol smoking. Adult (age ≥ 21) established smokers who purchased a JUUL Starter Kit (N = 15,036) completed baseline and 1-, 2-, 3-, 6-, 9- and 12-month assessments. Switching (no past-30-day cigarette smoking) and flavor use were assessed at each follow-up. Repeated-measure logistic regression models evaluated association of menthol smoking and switching across 1 year. Across the 6 follow-ups, more menthol smokers primarily used Menthol/Mint-flavored JUULpods (53.8%) than nonmenthol smokers (22.9%). Only 6.4% of menthol smokers primarily used Tobacco flavors (vs. 25.9% of nonmenthol smokers). Across all follow-ups menthol smokers (41.2% of sample) were more likely to switch than nonmenthol smokers (42.6% vs. 38.8%: OR [95% CI] = 1.17 [1.11, 1.23]); this association remained significant after adjustment for sociodemographic, smoking and JUUL use covariates (aOR [95% CI] = 1.13 [1.05, 1.21]). Nonmenthol smokers, but not menthol smokers, were significantly more likely to switch when primarily using Menthol/Mint-flavored (vs. Tobacco-flavored) JUULpods (aOR [95% CI] = 1.14 [1.04, 1.25]). Differences in baseline smoking characteristics between menthol and nonmenthol smokers were small in magnitude. Adult menthol (vs. nonmenthol) smokers using JUUL were more likely to switch. More than twice as many menthol (vs. nonmenthol) smokers primarily used Menthol/Mint-flavor JUULpods; few menthol smokers used tobacco flavors. Given these pronounced differences in flavor preferences, availability of ENDS in menthol flavors may be particularly important for menthol smokers, but may also benefit some nonmenthol smokers.


Treatment-resistant anxiety disorders.
Several epidemiological studies confirmed that Anxiety Disorders as a group are the most prevalent psychiatric conditions in the United States. The importance of these conditions is underlined by the fact that they cause significant disability, poor quality of life, alcohol and drug abuse. Anxiety disorders are treatable conditions and respond to the front-line interventions such as serotonin reuptake inhibitors and cognitive behavioral therapy. However, only about 60% of patients respond to those treatments to any significant degree. Many still have residual symptoms or stay treatment refractory. The group of anxiety patients that is resistant to the treatment has been shown to have very poor quality of life and have highest rate of suicidal attempts than any other disorders. Many biological, treatment specific and social factors are affecting treatment resistance. In this paper, we are attempting to review reasons for the treatment resistance. In addition, we would like to review current strategies that could be helpful in reducing treatment resistance and aiding people chronically suffering from these severe and disabling conditions.


Vaginal temperature modeling in Holstein cows and cluster analysis by the cophenetic correlation coefficient.
The objective was to establish a model for the prediction and characterization of vaginal temperature in Holstein cows, based on environmental predictors and thermal comfort indices, through cluster analysis, validation by the cophenetic correlation coefficient, and multiple regression analysis. The micrometeorological characterization of the site was carried out by recording the air temperature (Tair), the relative humidity (RH), the black globe temperature (BGT), the black globe temperature and humidity (BGHI), and dew point temperature (TDP). The recording of vaginal temperature (Tv) was performed in eight dairy cows using temperature sensors, equipped with data loggers, coupled with intravaginal devices. The data were analyzed using descriptive statistics and cluster analysis (CA) by using the hierarchical agglomerative method based on the value of the cophenetic correlation coefficient (CCC >0.70), in which representative physiological models were established, characterizing the Tv through multiple regression. In the afternoon the coefficient of variation (CV) was low for all variables, indicating homogeneity of the meteorological variables and efficiency of the ventilation system. The temperature and humidity index (THI) was mild only on the morning. There was a variation of 0.28 °C of Tv between shifts, sufficient to characterize the condition of comfort and stress of the animal, with values above 39 °C indicating animal stress. Tv showed strong correlation with BGT, Tair, TDP and RH, assuming that physiological variables, such as Tv, tend to have greater relationship with abiotic variables. Empirical models were established for estimating Tv based on the analyses performed in this study. Model 1 is recommended for TDP ranges of 14.00-21.00 °C and RH of 30-100%, while model 2 can be used for Tair situations up to 35 °C. The regression models for estimating Tv are promising for characterizing the thermal comfort of dairy cows housed in compost barn systems.


Retrovirus-like particles in EBV-negative Burkitt's lymphoma cell line but not in EBV-DNA-positive lines from patients with ataxia telangiectasia and Down's syndrome.
Retrovirus-like particles can be recovered by arginine deprivation from the BJAB-1 Epstein-Barr virus (EBV) negative cell line derived from an African patient with typical Burkitt's lymphoma. These particles resemble retroviruses in their morphology and in their physicochemical properties. Particles with a similar morphology were obtained from derivative cell lines established by infecting BJAB-1 cells with EBV. On the other hand, retrovirus-like particles could not be induced in EBV-DNA-positive lymphoblastoid cell lines derived from non-leukaemic patients with ataxia telangiectasia and Down's syndrome and from a patient with infectious mononucleosis.


Mapping anti-müllerian hormone (Amh) and related sequences in the mouse: identification of a new region of homology between MMU10 and HSA19p.
A panel of 78 backcross progeny, BALB/cJ x (BALB/cJ x CAST/Ei)F1, was used to map the gene encoding anti-Müllerian hormone (Amh), also called Müllerian inhibiting substance, to mouse Chromosome 10 (MMU10). This analysis identified a new region of linkage homology between human Chromosome 19p (HSA 19p) and MMU10 and localized an apparent recombinational hot spot in (C57BL/6J x Mus spretus)F1 females [compared with (BALB/cJ x CAST/Ei)F1 males] to the interval between phenylalanine hydroxylase (Pah) and mast cell growth factor (Mgf). In addition, eight unlinked polymorphic sequences, provisionally designated Amh-related sequences (Amh-rs1 through Amh-rs8), were identified by Southern blot analysis using Amh probes. Amh-rs1, -rs2, -rs4, and -rs7 were mapped to MMU1, 13, 12, and 15, respectively, by recombinant inbred (RI) strain and intraspecific backcross analyses. The NXSM RI strain distribution patterns for the four unmapped loci are also presented.


Novel prescribed performance neural control of a flexible air-breathing hypersonic vehicle with unknown initial errors.
A novel prescribed performance neural controller with unknown initial errors is addressed for the longitudinal dynamic model of a flexible air-breathing hypersonic vehicle (FAHV) subject to parametric uncertainties. Different from traditional prescribed performance control (PPC) requiring that the initial errors have to be known accurately, this paper investigates the tracking control without accurate initial errors via exploiting a new performance function. A combined neural back-stepping and minimal learning parameter (MLP) technology is employed for exploring a prescribed performance controller that provides robust tracking of velocity and altitude reference trajectories. The highlight is that the transient performance of velocity and altitude tracking errors is satisfactory and the computational load of neural approximation is low. Finally, numerical simulation results from a nonlinear FAHV model demonstrate the efficacy of the proposed strategy.


Key mechanisms and in vitro reconstitution of fetal oocyte development in mammals.
During fetal oocyte development in mammals, germ cells progress through meiotic prophase I to form primordial follicles with pregranulosa cells. The primordial follicles remain dormant until oogenesis resumes during puberty. Studies in mice have elucidated mechanisms governing oogenesis, leading to the successful induction of functional oocytes from mouse pluripotent stem cells in vitro. Based on the in vivo/in vitro knowledge in mice and the histological and transcriptomic evidence for fetal oocyte development in humans and primates, human/primate oocyte-like cells corresponding to the early stage of oocytes in vivo have been successfully induced in vitro. Here, we discuss recent advances in our understanding of the mechanisms of fetal oocyte development in mammals, as well as in in vitro oogenesis.


Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning.
We present RBPNet, a novel deep learning method, which predicts CLIP-seq crosslink count distribution from RNA sequence at single-nucleotide resolution. By training on up to a million regions, RBPNet achieves high generalization on eCLIP, iCLIP and miCLIP assays, outperforming state-of-the-art classifiers. RBPNet performs bias correction by modeling the raw signal as a mixture of the protein-specific and background signal. Through model interrogation via Integrated Gradients, RBPNet identifies predictive sub-sequences that correspond to known and novel binding motifs and enables variant-impact scoring via in silico mutagenesis. Together, RBPNet improves imputation of protein-RNA interactions, as well as mechanistic interpretation of predictions.


Usefulness of expanding the indications of early rescue intracytoplasmic sperm injection.
Early rescue intracytoplasmic sperm injection (ICSI) is often performed in cases in which not even a single oocyte has extruded a second polar body 6 h after insemination. We evaluated the usefulness of expanding the indications of early rescue ICSI to cases in which <80% of oocytes have extruded second polar bodies 6 h after insemination. Early rescue ICSI was performed on oocytes that were denuded 2.5 h post-insemination and whose extrusion of the second polar bodies had been examined 6 h post-insemination with a PolScope. In vitro fertilization was performed on 24 496 oocytes of 4944 cycles, and 1438 cycles had <80% rate of the second polar body extrusion. Rescue ICSI was performed on 3933 oocytes. Three pronuclei (3PN) incidence of rescue ICSI was 3.0% in oocytes with ≥50% rate of the second polar body extrusion. With respect to the second polar body extrusion rate, no differences were observed in normal fertilization, blastocyst development, implantation, miscarriage, or live birth rates for rescue ICSI. By expanding the indications of early rescue ICSI using the PolScope to cases in which <80% of oocytes have extruded the second polar bodies, many fertilized oocytes can be obtained without considerably increasing the 3PN rate.


A comparative study of the psychological impacts of tasks related and unrelated to COVID-19 on nurses: a cross-sectional study.
This study assessed the psychological impact of the outbreak of coronavirus disease 2019 (COVID-19) on university hospital nurses. It provides an assessment of mental health issues, including depression, anxiety, distress, and burnout of nurses dealing directly and indirectly with COVID-19. In a web-based, cross-sectional study, 111 nurses from Daegu Catholic University Hospital in Korea were enrolled from August 4 to August 9, 2020. Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Impact of Event Scale-Revised, and Maslach Burnout Inventory were used to assess the psychological symptoms of depression, anxiety, psychological distress, and burnout among the study participants. Of 111 nurses, 35 (31.5%), nine (8.1%), 26 (23.4%), and 49 (44.1%) experienced depression, anxiety, distress, and burnout, respectively. Nurses who performed COVID-19-related tasks were more likely to have moderate depression (related vs. unrelated, 52.0% vs. 25.6%; p=0.037). There were no differences in anxiety, distress, and burnout between nurses with and without COVID-19-related tasks. More than 50% of the participants showed receptive and positive attitudes toward caring for COVID-19 patients. Nurses who performed COVID-19-related tasks had a higher risk of depression. There were no significant differences in anxiety, distress, and burnout between the two groups. Since nurses who perform COVID-19-related tasks are more prone to psychological distress, continued psychiatric interventions are required for infectious disease outbreaks with a high mortality rate for healthcare workers who are emotionally vulnerable.


Triptolide alters mitochondrial functions.
Triptolide (TPL), a small molecule purified from the herb Tripterygium wilfordii, has potential clinical application for suppression of chronic autoimmune disorders and inhibition of tumor growth. However, its mechanism of action is largely unknown. In this study, the effect of TPL on mitochondria was explored with a panel of molecular probes that detect the alteration of mitochondrial functions. When Lewis lung carcinoma (LLC) cells were treated with different doses of TPL for four hours, impaired mitochondrial functions were detected. This included an increased production of reactive oxygen species, the opening of the transition pore of mitochondria, the depolarization of the mitochondria membrane, the inhibition of the production of ATP and increased release of ATP as well as the induction of apoptosis. It is likely that by impairment of mitochondrial function, TPL exerts its inhibitory effect on growth of tumor and progression of inflammatory disease.


[The role of the Federal Government in the prevention and control of infectious diseases. Organizational structures, responsibilities and duties--an overview].
Health policy is faced today with the challenge of keeping the health care system up to a high standard and affordable at the same time. A comprehensive health protection system that is efficient and readily accessible to all is required. Although it is to a great extent the responsibility of every citizen to promote and sustain their own health, it is the duty of the Federal Government to provide for risks that can emanate from pathogens, products or environmental factors. Protection against all known risks should be improved, new health threats have to be countered and new scientific findings must be considered. Prevention, health promotion and health protection are important key factors to improve health in the general population and to reduce health care costs. The prevention of and protection from infectious diseases are high priority tasks in the further development of an effective health care system in Germany. In order to accomplish these tasks in the control of infectious diseases close collaboration between a number of federal agencies and federal institutes under the responsibility of the Ministry of Health and Social Security as well as the Ministry of Consumer Protection, Food and Agriculture has to be ensured.


[What are the implications of the new radiation protection ordinance?]
The new regulatory basis in Germany for medical radiation protection ("Strahlenschutzverordnung" and "Strahlenschutzgesetz") went into effect on 31 December 2018 and has brought many changes. A system for record keeping and analysis of unintended exposures must be established and the occurrence of significant events must be reported to the competent authority. In the future, medical physics experts have to be consulted for equipment with high doses. Further programs for the early detection of diseases may be considered and approved by the federal office for radiation protection. Changes have been defined for teleradiology, procedure descriptions, tasks of the medical institutions for quality assurance and dose limits. Because of extended requirements for documentation and evaluations, the functionality of a dose management system will practically be necessary in bigger radiology departments or offices. Uncertainties in interpretation still exist for several parts of the regulations. The existing complementing guidelines shall be used for the time being.


General hospital psychiatry: are its roles and functions adjunctive or pivotal?
General hospital psychiatric divisions are an important part of the mental health care delivery system; however, in Canada and the United States, their role and function have not been well defined. In most places, the general hospital is peripheral to the mental hospital, and is thus an adjunctive element in the resulting two-tier mental health care delivery system. The adjunctive type of general hospital psychiatric division provides brief treatment to highly selective types of patients, and is relatively inaccessible to a wide variety of patients. In contrast, the general hospital can be central to the mental health care delivery system--in a pivotal position to patients, other mental health facilities, and community agencies. Important features of the pivotal type are: defined catchment areas, broad admitting criteria and effective discharge planning, linkages with extramural and community programs, staff reorientation, appropriate architectural features, and the ability to hear and respond to the needs of the community. The pivotal type of general hospital psychiatric division can provide appropriate levels of inpatient care, as well as the linkages and backup to extramural and community programs for the long-term mentally ill. The mental hospital would no longer be used as a backup for general clinical disorders, involuntary patients, or patients usually rejected by adjunctive hospitals. There would be collaboration with other agencies in developing programs for special clinical groups (low prevalence disorders), as well as for alcoholism, psychogeriatrics, and adolescent disorders. This article reviews the current polemic on the role and function of the general hospital psychiatric division, as part of the mental health care delivery system.


Bone marrow-targetable Green Tea Catechin-Based Micellar Nanocomplex for synergistic therapy of Acute myeloid leukemia.
Currently available anti-leukemia drugs have shown limited success in the treatment of acute myeloid leukemia (AML) due to their poor access to bone marrow niche supporting leukemic cell proliferation. Herein, we report a bone marrow-targetable green tea catechin-based micellar nanocomplex for synergistic AML therapy. The nanocomplex was found to synergistically amplify the anti-leukemic potency of sorafenib via selective disruption of pro-survival mTOR signaling. In vivo biodistribution study demonstrated about 11-fold greater bone marrow accumulation of the nanocomplex compared to free sorafenib. In AML patient-derived xenograft (AML-PDX) mouse model, administration of the nanocomplex effectively eradicated bone marrow-residing leukemic blasts and improved survival rates without noticeable off-target toxicity. This study may provide insights into the rational design of nanomedicine platforms enabling bone marrow-targeted delivery of therapeutic agents for the treatment of AML and other bone marrow diseases.


Sensors and microarrays in protein biomarker monitoring: an electrochemical perspective spots.
The development of clinically applicable portable sensors and multiplex protein biomarker assays is one of the most important goals of laboratory medicine today. Sensing strategies based on electrochemical devices are discussed in this overview, with special emphasis on detection principles derived from voltammetry, electrogenerated chemiluminescence, bipolar electrochemistry and impedance-based measurements. Up-to-date examples of electrochemical methods in biomedical research and development are highlighted here, including critical evaluation and future directions of the analysis, development and validation of new protein biomarkers.


Does vibration frequency and location influence the effect of neck muscle vibration on postural sway? A cross-sectional study in asymptomatic participants.
Postural control is of utmost importance for human functioning. Cervical proprioception is crucial for balance control. Therefore, any change to it can lead to balance problems. Previous studies used neck vibration to change cervical proprioception and showed changes in postural control, but it remains unknown which vibration frequency or location causes the most significant effect. Therefore, this study aimed to investigate the effect of different vibration frequencies and locations on postural sway and to serve as future research protocol guidance. Seventeen healthy young participants were included in the study. We compared postural sway without vibration to postural sway with six different combinations of vibration frequency (80, 100, and 150 Hz) and location (dorsal neck muscles and sternocleidomastoid). Postural sway was evaluated using a force platform. The mean center of pressure (CoP) displacement, the root mean square (RMS), and the mean velocity in the anteroposterior and mediolateral direction were calculated, as well as the sway area. The aligned rank transform tool and a three-way repeated measures ANOVA were used to identify significant differences in postural sway variables. Neck vibration caused a significant increase in all postural sway variables (p < 0.001). Neither the vibration frequency (p > 0.34) nor location (p > 0.29) nor the interaction of both (p > 0.30) influenced the magnitude of the change in postural sway measured during vibration. Neck muscle vibration significantly changes CoP displacement, mean velocity, RMS, and area. However, we investigated and found that there were no significant differences between the different combinations of vibration frequency and location.


Synchronous targeted delivery of TGF-β siRNA to stromal and tumor cells elicits robust antitumor immunity against triple-negative breast cancer by comprehensively remodeling the tumor microenvironment.
The poor permeability of therapeutic drugs, limited T-cell infiltration, and strong immunosuppressive tumor microenvironment of triple-negative breast cancer (TNBC) acts as a prominent barrier to the delivery of drugs and immunotherapy including programmed cell death ligand-1 antibody (anti-PD-L1). Transforming growth factor (TGF)-β, an important cytokine produced by cancer-associated fibroblasts (CAFs) and tumor cells contributes to the pathological vasculature, dense tumor stroma and strong immunosuppressive tumor microenvironment (TME). Herein, a nanomedicine platform (HA-LSL/siTGF-β) employing dual-targeting, alongside hyaluronidase (HAase) and glutathione (GSH) triggered release was elaborately constructed to efficiently deliver TGF-β small interference RNA (siTGF-β). It was determined that this system was able to improve the efficacy of anti-PD-L1. The siTGF-β nanosystem efficiently silenced TGF-β-related signaling pathways in both activated NIH 3T3 cells and 4T1 cells in vitro and in vivo. This occurred firstly, through CD44-mediated uptake, followed by rapid escape mediated by HAase in endo/lysosomes and release of siRNA mediated by high GSH concentrations in the cytoplasm. By simultaneous silencing of TGF-β in stromal and tumor cells, HA-LSL/siTGF-β dramatically reduced stroma deposition, promoted the penetration of nanomedicines for deep remodeling of the TME, improved oxygenation, T cells infiltration and subsequent anti-PD-L1 deep penetration. The double suppression of TGF-β has been demonstrated to promote blood vessel normalization, inhibit an epithelial-to-mesenchymal transition (EMT), and further modify the immunosuppressive TME, which was supported by an overall increase in the proportion of dendritic cells and cytotoxic T cells. Further, a reduction in the proportion of immunosuppression cells such as regulatory T cells and myeloid-derived suppressor cells was also observed in the TME. Based on the comprehensive remodeling of the tumor microenvironment by this nanosystem, subsequent anti-PD-L1 therapy elicited robust antitumor immunity. Specifically, this system was able to suppress the growth of both primary and distant tumor while preventing tumor metastasis to the lung. Therefore, the combination of the dual-targeted siTGF-β nanosystem, alongside anti-PD-L1 may serve as a novel method to enhance antitumor immunotherapy against stroma-rich TNBC.


The Self- and Other-Deception Questionnaires-Intellectual Disabilities (SDQ-ID and ODQ-ID): component analysis and reliability.
The objectives of this research were to: (1) investigate the component structure and psychometric properties of the Self- and Other-Deception Questionnaires-Intellectual Disabilities (SDQ-ID and ODQ-ID), (2) examine the relationship between social desirability and IQ, and (3) compare social desirability scores of those with intellectual disabilities (IDs) and a history of criminal offending to the social desirability scores of participants with IDs and those without IDs and no such history, controlling for general intellectual functioning. Men with mild to borderline IDs detained within medium secure inpatient forensic mental health services (N=40) completed the SDQ-ID and ODQ-ID at Time 1 and then two-weeks later at Time 2. Data for the men with and without IDs and no known criminal offending history were taken from a previous study (N=60). Following exploratory Principal Components Analysis, the number of questionnaire items were reduced, and a two-factor structure was found for the SDQ-ID which was labelled: (1) Positive Self Representation and (2) Denial of Intrusive Thoughts. A two-factor structure was also found for the ODQ-ID and these two factors were labelled: (1) Denial of Negative Social Interaction and (2) Untrustworthiness. Both the SDQ-ID and ODQ-ID had acceptable internal consistency and test-retest reliability. Fifteen percent of the variance in SDQ-ID scores was explained by Full Scale IQ, while 21% of the variance in ODQ-ID scores was explained by Full Scale IQ. Between group comparisons controlling for intelligence did not yield any significant differences. The shortened SDQ-ID and ODQ-ID have promising psychometric properties, and their component structures appear robust. Differences between men with and without IDs on these two measures of social desirability can be accounted for by differences in general intellectual functioning.


The reliability of cardiogenic impedance and correlation with echocardiographic and plethysmographic parameters for predicting CRT time intervals post implantation.
Encouraging data have been reported on the use of cardiogenic impedance (CI) in cardiac resynchronization therapy (CRT) optimization. The purposes of this study were to: evaluate the stability of certain CI vectors 24 h postimplantation, study the correlation between these CI signals and selected echocardiographic parameters, and examine the possibility of non-invasive calibration of the patient-specific impedance-based prediction model. Thirteen patients received a CRT-defibrillator device with monitor capability of the dynamic impedance between several electrodes. At implantation, a patient-specific impedance-based prediction model was created for identification of optimal atrioventricular and interventricular (VV) delays and calibrated on invasive measurements of left ventricular contractility (LV dP/dtmax). Simultaneously, non-invasive measurements of LV dP/dtmax and stroke volume (SV) were obtained using a finger plethysmograph. Patients were re-evaluated with echocardiography and new CI measurements the day after implantation. The hemodynamic benefit achieved by optimal VV setting according to the patient-specific impedance-based prediction model at follow-up was not as large as the one obtained at implantation. In a multivariate partial least square regression analysis, a correlation was found between aortic velocity time integral (VTI) and a generic linear combination of CI features (P < 0,005). No correlation was found between the patient-specific impedance-based prediction models and the non-invasive measurements of LV dP/dtmax and SV. Cardiogenic impedance signals can be used to optimize CRT settings but seem less feasible as an ambulatory tool since calibration is required. The positive correlation between aortic VTI and CI measurements seems promising, although a larger cohort is required to create an echocardiography-based patient-specific model.


Evaluation of single sensor transcutaneous measurement of PO2 and PCO2 in the neonate.
A single combined transcutaneous sensor for PO2 and PCO2 was evaluated in a neonatal intensive care unit. The values obtained with the combined sensor were compared with the values obtained with two separate electrodes monitoring respectively PO2 and PCO2. Adequate correlations were found. The combined sensor represents an improvement on individual electrodes as it spares available skin surface and needs less handling.


Application of CdS quantum dots modified carbon paste electrode for monitoring the process of acetaminophen preparation.
In this research article, a novel, selective, and sensitive modified carbon paste electrode (CPE) using CdS quantum dots (QDs) is presented. The highly stable CdS QDs were successfully synthesized in an in situ process using Na2S2O3 as a precursor and thioglycolic acid as a catalyst and capping agent. The synthesis of CdS QDs was studied using X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. The synthesized CdS QDs were used for preparation of a modified carbon paste electrode (CdS/CPE). The electrochemical behavior of the electrode toward p-aminophenol (PAP) and acetaminophen (Ac) was studied, and the results demonstrated that the CdS/CPE exhibited good electrocatalytic performance toward PAP and Ac oxidation. The oxidation peak potential of each analyte in the mixture was well separated. As a result, a selective and reliable method was developed for the determination of PAP and Ac simultaneously without any chemical separations. Application of the fabricated electrode for monitoring the process of Ac preparation from PAP was investigated. The obtained results show that CdS/CPE has satisfactory analytical performance; it could be a kind of attractive and promising nanomaterial-based sensor for process monitoring via the electrochemical approach.


Mathematics coordinators as school team PD leaders before and during COVID-19.
This study explored a professional development (PD) program preparing mathematics coordinators to lead effective PD in their schools. Due to the COVID-19 pandemic emerging in the midst of this study, the PD program and school team PD were performed online instead of face-to-face. We explored the PD program and school team PD design before and during COVID-19 period, and the coordinators' expertise-based PD leadership professional identity (LPI). Findings revealed structural stability of the PD program design, and support of coordinators' LPI. Coordinators enacted a structural transition of effective PD design into the school team PD, demonstrating their LPI in practice.


Variant acute promyelocytic leukemia translocation (15;17) originating from two subsequent balanced translocations involving the same chromosomes 15 and 17 while preserving the PML/RARA fusion.
Fluorescence in situ hybridization (FISH) analysis of the bone marrow of a 24-year-old man diagnosed with acute promyelocytic leukemia (APL) revealed a variant pattern with one fusion signal instead of the typical two fusions expected with the probe set used. The combined FISH and conventional chromosome analyses suggested that two subsequent translocations had occurred in this patient involving the same chromosomes 15 and 17. As the prognostic outcome in APL is strictly associated with the presence of a PML/RARA fusion, it is useful and necessary to perform both cytogenetic and FISH analyses of a variant t(15;17) to determine the status of the PML/RARA fusion.


Gonadal function in young adult males with metabolic syndrome.
Aim of the study was to assess the gonadal function of young adult males with metabolic syndrome and to compare them with healthy age matched controls. Forty young male subjects of age group 20-40 years who fulfilled the IDF criteria (2005) for diagnosis of metabolic syndrome were included in the study. Thorough evaluation of the subjects was done and history of sexual dysfunction if any was noted. Pooled blood samples were collected from each subject in fasting state for total testosterone, SHBG, FSH, LH, prolactin and insulin levels. All hormonal analyses were done by radio immune assay (RIA). Hypogonadism was defined as total testosterone less than 3ng/ml. Eighteen healthy age matched controls were also taken for the study. Twenty percent of subjects with metabolic syndrome had eugonadotropic hypogonadism compared to 5.5% controls. Subjects with metabolic syndrome also had significantly lower SHBG level compared to the controls. From this study it has been observed that eugonadotropic hypogonadism with low total testosterone and normal or low normal gonadotropin levels may be a feature of the metabolic syndrome in young adult males. Significant low SHBG levels as compared to controls could be one of the factors responsible for various biochemical alteration seen in these cases. This study highlights the importance of evaluating gonadal function in young adult males with the metabolic syndrome and has therapeutic implications in the management of such subjects with gonadal dysfunction.


Gel compression considerations for chromatography scale-up for protein C purification.
This work is to establish theoretical and experimental relationships for the scale-up of Immobilized Metal Affinity Chromatography (IMAC) and Immuno Affinity Chromatography for the low cost production of large quantities of Protein C. The external customer requirements for this project have been established for Protein C deficient people with the goal of providing prophylactic patient treatment. Deep vein thrombosis is the major symptom for protein C deficiency creating the potential problem of embolism transport to important organs, such as, lung and brain. Gel matrices for protein C separation are being analyzed to determine the relationship between the material properties of the gel and the column collapse characteristics. The fluid flow rate and pressure drop is being examined to see how they influence column stability. Gel packing analysis includes two considerations; one is bulk compression due to flow rate, and the second is gel particle deformation due to fluid flow and pressure drop. Based on the assumption of creeping flow, Darcy's law is being applied to characterize the flow through the gel particles. Biot's mathematical description of three-dimensional consolidation in porous media is being used to develop a set of system equations. Finite difference methods are being utilized to obtain the equation solutions. In addition, special programs such as finite element approaches, ABAQUS, will be studied to determine their application to this particular problem. Experimental studies are being performed to determine flow rate and pressure drop correlation for the chromatographic columns with appropriate gels. Void fraction is being measured using pulse testing to allow Reynolds number calculations. Experimental yield stress is being measured to compare with the theoretical calculations. Total Quality Management (TQM) tools have been utilized to optimize this work. For instance, the "Scatter Diagram" has been used to evaluate and select the appropriate gels and operating conditions via Taguchi techniques. Targeting customer requirements under the structure of TQM represents a novel approach to graduate student research in an academic institution which is designed to simulate an industrial environment.


Physical and biological processes in a Macrocystis pyrifera community near Valdivia, Chile.
From October 10, 1979 to August 26, 1981 we investigated the effect of physical disturbance, herbivory and algal-algal competition on the dynamics of the Macrocystis community near Valdivia, Chile. The most abundant herbivore, Tegula atra, was continuously removed from one of two sites with high initial Tegula density (control and Tegula-removal rocks) and added to one of two sites where Tegula was initially absent (Tegula-addition and addition-control rocks). Macrocystis was rare at the beginning of the study. From October 1980 to April 1981 we continuously removed Macrocystis from an additional rock near the addition-control rock. On each site the response of the algal community was monitored by photographing 9, 0.25 m2 permanent quadrats at 2-4 week intervals. Tegula had little effect on Macrocystis and there were no other important herbivores present. Each summer Macrocystis dominated all 4 sites of the Tegula experiment and Tegula migrated towards the intertidal to feed. Macrocystis was reduced each winter by winter storms, the holdfasts (but not the canopy) surviving the first winter but not the second. The Macrocystis removal rock was dominated by lower growing perennial algae, indicating a competitive hierarchy among the algae of the form: Macrocystis>perennial algae>ephemeral algae>encrusting algae.Except for the presence of a competitive hierarchy among the algae and the importance of winter storms, Chilean kelp communities share few of the organizational features of their northern hemisphere counterparts. Marine mammals (excluding man) do not prey on algal consumers (Tegula and the urchin, Loxechinus albus) and these consumers have little effect on perennial macroscopic algae. Urchins apparently feed only on drift algae. Species richness in the algal community is low.


The Relationship Between Wild-Type Transthyretin Amyloid Load and Ligamentum Flavum Thickness in Lumbar Stenosis Patients.
One key contributor to lumbar stenosis is thickening of the ligamentum flavum (LF), a process still poorly understood. Wild-type transthyretin amyloid (ATTRwt) has been found in the LF of patients undergoing decompression surgery, suggesting that amyloid may play a role. However, it is unclear whether within patients harboring ATTRwt, the amount of amyloid is associated with LF thickness. From an initial cohort of 324 consecutive lumbar stenosis patients whose LF specimens from decompression surgery were sent for analysis (2018-2019), 33 patients met the following criteria: 1) Congo red-positive amyloid in the LF, 2) ATTRwt by mass spectrometry-based proteomics, and 3) an available preoperative magnetic resonance imaging. Histological specimens were digitized, and amyloid load was quantified through Trainable Weka Segmentation machine learning. LF thicknesses were manually measured on axial T2-weighted preoperative magnetic resonance imaging scans at each lumbar level, L1-S1. The sum of thicknesses at every lumbar LF level (L1-S1) equals "lumbar LF burden". Patients had a mean age of 72.7 years (range = 59-87), were mostly male (61%) and white (82%), and predominantly had surgery at L4-L5 levels (73%). Amyloid load was positively correlated with LF thickness (R = 0.345, P = 0.0492) at the levels of surgical decompression. Furthermore, amyloid load was positively correlated with lumbar LF burden (R = 0.383, P = 0.0279). Amyloid load is positively correlated with LF thickness and lumbar LF burden across all lumbar levels, in a dose-dependent manner. Further studies are needed to validate these findings, uncover the underlying pathophysiology, and pave the way toward using therapies that slow LF thickening.


Reporting intellectual capital in health care organizations: specifics, lessons learned, and future research perspectives.
This article analyzes the concept of intellectual capital (IC) in the health sector sphere by studying the case of a major nonprofit research organization in this sector, which has for some time been publishing IC reports. In the last few years, health care organizations have been the object of great attention in the implementation and transfer of managerial models and tools; however, there is still a lack of attention paid to the strategic management of IC as a fundamental resource for supporting and enhancing performance improvement dynamics. The main aim of this article is to examine the IC reporting model used by the Center of Molecular Medicine (CMM), a Swedish health organization which is an outstanding benchmark in reporting its IC. We also consider the specifics of IC reporting for health organizations, the lessons learned by analyzing CMM's IC reporting, and future perspectives for research.


Modulation of mGlu5 improves sensorimotor gating deficits in rats neonatally treated with quinpirole through changes in dopamine D2 signaling.
This study analyzed whether the positive allosteric modulator of metabotropic glutamate receptor type 5 (mGlu5) 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) would alleviate deficits in prepulse inhibition (PPI) and affect dopamine (DA) D2 signaling in the dorsal striatum and prefrontal cortex (PFC) in the neonatal quinpirole (NQ) model of schizophrenia (SZ). Male and female Sprague-Dawley rats were neonatally treated with either saline (NS) or quinpirole HCL (1 mg/kg; NQ), a DAD2 receptor agonist, from postnatal days (P) 1-21. Rats were raised to P44 and behaviorally tested on PPI from P44-P48. Before each trial, rats were subcutaneous (sc) administered saline or CDPPB (10 mg/kg or 30 mg/kg). On P50, rats were given a spontaneous locomotor activity test after CDPPB or saline administration. On P51, the dorsal striatum and PFC were evaluated for both arrestin-2 (βA-2) and phospho-AKT protein levels. NQ-treated rats demonstrated a significant deficit in PPI, which was alleviated to control levels by the 30 mg/kg dose of CDPPB. There were no significant effects of CDPPB on locomotor activity. NQ treatment increased βA-2 and decreased phospho-AKT in both the dorsal striatum and PFC, consistent with an increase DAD2 signaling. The 30 mg/kg dose of CDPPB significantly reversed changes in βA-2 in the dorsal striatum and PFC and phospho-AKT in the PFC equivalent to controls. Both doses of CDPPB produced a decrease of phospho-AKT in the PFC compared to controls. This study revealed that a mGlu5 positive allosteric modulator was effective to alleviate PPI deficits and striatal DAD2 signaling in the NQ model of SZ.


Real-World Evidence of COVID-19 Patients' Data Quality in the Electronic Health Records.
Despite the importance of electronic health records data, less attention has been given to data quality. This study aimed to evaluate the quality of COVID-19 patients' records and their readiness for secondary use. We conducted a retrospective chart review study of all COVID-19 inpatients in an academic healthcare hospital for the year 2020, which were identified using ICD-10 codes and case definition guidelines. COVID-19 signs and symptoms were higher in unstructured clinical notes than in structured coded data. COVID-19 cases were categorized as 218 (66.46%) "confirmed cases", 10 (3.05%) "probable cases", 9 (2.74%) "suspected cases", and 91 (27.74%) "no sufficient evidence". The identification of "probable cases" and "suspected cases" was more challenging than "confirmed cases" where laboratory confirmation was sufficient. The accuracy of the COVID-19 case identification was higher in laboratory tests than in ICD-10 codes. When validating using laboratory results, we found that ICD-10 codes were inaccurately assigned to 238 (72.56%) patients' records. "No sufficient evidence" records might indicate inaccurate and incomplete EHR data. Data quality evaluation should be incorporated to ensure patient safety and data readiness for secondary use research and predictive analytics. We encourage educational and training efforts to motivate healthcare providers regarding the importance of accurate documentation at the point-of-care.


The solvent dependence of hydrogen exchange kinetics of folded proteins.
The effects of ethanol, ethylene glycol, dioxane, and other organic co-solvents upon the hydrogen exchange rates of randomly coiled oxidized RNase, native RNase, and native trypsin have been measured. The exchange rate of oxidized RNase, the model compound for the proton transfer step in hydrogen exchange, is decreased by all of the co-solvents studied at temperatures in the range 3-20 degrees. This has been ascribed to the combined effects of the disruption of peptide bond solvation due to a reduction in the concentration of water, and of changes in [OH-] ion concentration due to changes in the acid dissociation constant of water, Kw. The solvent dependence for both native RNase and native trypsin is similar in all of the solvents studied. At a low temperature (3-20 degrees), the exchange rates go through a minimum as the solvent concentration is increased. At higher temperatures (20-35 degrees) the exchange rates are increased at all concentrations of the co-solvent. The apparent rate minimum at lower temperatures is due to two opposing effects. Co-solvents decrease the rate of exchange that occurs directly from the folded molecule. At higher concentrations and higer temperature. The decrease in rates for exchange directly from folded protein is primarily due to the effects on the proton transfer step, and not to binding or the solvent effects on protein structure. The solvents used in this study have no apparent effect on conformational processes contributing to the hydrogen exchange process in folded proteins.


Toxoplasmosis in rams: possible significance of venereal transmission.
Three rams were infected with tick-borne fever eight months after infection with toxoplasma. There was no clinical evidence of reactivation of the latent toxoplasma infection and semen samples from the rams were not infective to mice. Semen samples from 77 apparently normal rams were tested for toxoplasma infection by passage through mice; none of the samples produced patent infections in mice. Two rams with chronic toxoplasma infection were repeatedly mated with seronegative ewes. None of the ewes showed serological evidence of acquired infection and all lambed satisfactorily.


Beyond conventional healthcare for mental health problems: Experiences of existential group conversations.
Mental health problems (MHP) are a major public health challenge. Conventional healthcare has shown limitation on reducing MHP and there is a call for offering methods beyond healthcare as well as improve access to healthcare. To explore experiences among people having MHP of (i) taking part in existential conversations in groups beyond conventional healthcare and (ii) seeking and receiving conventional healthcare. Four focus group interviews were conducted after finishing existential conversations in groups. Data was analyzed following thematic analysis. The theme Access to a community for exploration and acceptance describes communication through impressions and expressions together with others. A reflective perspective on everyday life, describes re-evaluation through reflection. Within the theme Experiences of healthcare related encounters, referring to the second aim, participants recollected feelings of disconnectedness, difficulties verbalizing MHP and dealing with rigid, standardized measures. Existential conversations in group may contribute to a more reflected doing in accordance with one's own values as well as improved mental health literacy. Design and measures within healthcare need to explicitly address MHP and consider individual's own preferences. This study contributes to understanding of coping with MHP in everyday life from an existential perspective.


Two similar but nonallelic rat pancreatic trypsinogens. Nucleotide sequences of the cloned cDNAs.
We have cloned and identified mRNA sequences for two rat pancreatic trypsinogens. Nucleotide sequence analysis of the cloned sequences revealed two mRNAs that encode similar, though noallelic, pretrypsinogens. Trypsinogen I mRNA is 804 nucleotides in length, plus an estimated poly(A) tract of 100 nucleotides, and contains a short (13 nucleotide) 5' noncoding region and a 3' noncoding region of 54 nucleotides. It encodes a preproenzyme of 246 amino acids comprising a hydrophobic prepeptide (signal peptide) of 15 amino acids, an activation peptide characteristic of trypsinogens, and an active form of trypsin, 223 amino acids in length, that has 78% amino acid sequence identity with porcine trypsin. Trypsinogen II mRNA has a nucleotide sequence 88% homologous with that of trypsinogen I mRNA and encodes a protein with 89% amino acid sequence identity with trypsinogen I. The enzymes encoded by trypsinogen I and II mRNAs retain the key amino acid residues that determine the characteristic substrate cleavage preference of trypsins and, therefore, represent the rat counterparts of this digestive enzyme. Trypsinogen I mRNA is a major pancreatic mRNA comprising an estimated 2-5% of the total, whereas trypsinogen II mRNA is present at much lower levels.


[The creation of laosun yutie plaster and safety experiment].
To create an externally-applied TCD plaster (Laosun Yutie plaster) for the lumbar muscle strain (LMS). (1) The raw material such as angelica, safflower, frankincense, myrrh, clove and so on were turned into solid TCD plaster by a serial of modern treatment technology-distillation, extraction, condense, dehydration. Meanwhile, the naphtha from the distillation process and borneol were dissolved into ethanol solution and the dilution was thus made; (2) The solid TCD plaster and the dilution from the aboved-mentioned process were put together to form the TCD plaster and the corresponding safety experiments were applied to rabits' skin. The experimental results showed that it is neither of urgent toxicity, stimulary function, nor of allergy-inducing response. The laosun Yutie plaster was a newly externally-applied TCD plaster which could be used safely and handily.


Liposome-based homogeneous luminescence resonance energy transfer.
There is an increasing need for developing simple assay formats for biomedical screening purposes. Assays on cell membranes have become important in studies of receptor-ligand interactions and signal pathways. Here luminescence energy transfer was studied on liposomes containing europium ion chelated to 4,4,4-trifluoro-1-(2-naphthalenyl)-1,3-butanedione and trioctylphosphine oxide. Energy transfer efficiency was characterized with biotin-streptavidin interaction, and a model assay concept for a homogeneous time-resolved luminescence resonance energy transfer (LRET) assay was developed. Acceptor-labeled streptavidin was bound to biotinylated lipids on the liposomes, leading to close proximity of the LRET pair. The liposome-based LRET assay was optimized for dye incorporation and concentration, biotinylation degree, liposome size, and kinetics. Sensitivity for a competitive biotin assay was at a picomolar range with a coefficient of variation from 7 to 20%. The developed lipid membrane-based system was feasible in separation free LRET assay concept with high sensitivity, indicating that the assay principle can potentially be used for biologically more relevant target molecules.


Comparison of nursing interventions performed by medical-surgical nurses in Korea and the United States.
To compare the Nursing Interventions Classification (NIC) interventions used in two countries, Korea and the United States. Data were collected from 167 nurses working in eight hospitals in Korea and analyzed with descriptive statistics. Korean nurses selected 202 interventions, nine of which were used by more than 50% of nurses surveyed. In comparison, the Academy of Medical-Surgical Nurses (AMSN) in the United States identified 68 interventions as core interventions. Among the top ranked 68 interventions selected by Korean nurses, 29 (43%) matched those selected by U.S. nurses. The nursing interventions selected by Korean nurses were more heavily focused on the physiologic domain than those selected by the U.S. nurses. The identified intervention lists can be used to develop nursing information systems, staff education, competency evaluation, referral networks, certification and licensing exams, and educational curricula for nursing students.


High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis.
A 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has now been continued for >3½ years. We were also able to induce remission of iFSGS in this patient by treatment with high cut-off haemodialysis using the Theralite™ dialyser. This observation lends support for the pathophysiological role of an as yet unknown, circulating glomerular filtration barrier permeability factor with an estimated weight of between 30 and 50 kDa.