Glucocorticoid modulation of Ca2+ homeostasis in human B lymphoblasts.
1. We determined the effect of cortisol (200 nM for 48 h) on the intracellular Ca2+ concentration ([Ca2+]i) and parameters of Ca2+i signalling in 19 lymphoblastoid cell lines (LCLs). 2. Using the fluorescent dye fura-2, the basal [Ca2+]i in Ca2+-containing medium was 63.5 +/- 2.4 nM in vehicle (ethanol)-treated LCLs and 55.7 +/- 2. 6 nM (mean +/- s.e.m.) in cortisol-treated LCLs. 3. Ca2+i signalling following platelet-activating factor (PAF, 100 nM) addition was enhanced by cortisol treatment, with LCLs having small PAF responses showing the largest percentage increase after cortisol treatment. Mean peak [Ca2+]i responses to PAF were enhanced 67.0% and 55.7% in Ca2+-free and Ca2+-containing medium, respectively. 4. The endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin (100 nM) caused a transient increase in [Ca2+]i in Ca2+-free medium in which the peak change was increased in cortisol-treated cells (98.5 +/- 5.8 vs. 79.8 +/- 4.5 nM). Peak changes in the freely exchangeable Ca2+ in response to 5 microM ionomycin were also enhanced in cortisol-treated cells (923.7 +/- 113.9 vs. 652.2 +/- 64.5 nM) and correlated to the PAF-evoked [Ca2+]i response. 5. Cortisol-treated LCLs exposed to thapsigargin to empty intracellular Ca2+ stores (10 min treatment in Ca2+-free medium) and exposed to CaCl2 or MnCl2 had a greater rate of Ca2+ entry (18.6 +/- 1.8 vs. 13.8 +/- 1.5 nM s-1) and higher rate constant for Mn2+ entry (0.0345 +/- 0.0029 vs. 0. 0217 +/- 0.0020) than vehicle-treated cells. Peak [Ca2+]i in cells exposed to CaCl2 was also enhanced (869.4 +/- 114.7 vs. 562.6 +/- 61.7 nM). Parameters of divalent cation influx were highly correlated to the peak [Ca2+]i elicited by thapsigargin or ionomycin. 6. Inclusion of RU 486 (a glucocorticoid antagonist) with cortisol prevented the decrease in basal [Ca2+]i and stimulatory actions of cortisol on all Ca2+i parameters. RU 486 alone had no apparent effects on basal [Ca2+]i or Ca2+i signalling. 7. Based on data obtained over a wide range of responses (in the presence and/or absence of cortisol or RU 486), the results show that cortisol stimulation of glucocorticoid receptors decreases basal [Ca2+]i and enhances PAF-evoked [Ca2+]i signalling, most probably through its effects on intracellular Ca2+ stores. In turn, the extent of Ca2+ entry via store-operated plasma membrane Ca2+ channels is closely linked to the size of the Ca2+ stores.


Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.
To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.


Competition and coexistance between Glossiphonia complanata and Helobdella stagnalis (Glossiphoniidae: Hirudinoidea).
The prey utilization of Glossiphonia complanata and Helobdella stagnalis from Bruce Lake, Alberta, Canada was examined quantitatively using serological techniques. While considerable prey range overlap occurred between the species, niche overlap was low during the winter, peaked in March and declined through the summer. Temporal differences in feeding and intraspecific weight class differences in prey utilization were found in both species but more distinctly in G. complanata. It is suggested that co-existance of G. complanata and H. stagnalis is based on adjustments of weight class food resource partitioning on a temporal basis.


Gene polymorphisms and oral cancer risk in tobacco habitués.
Oral cancer incidence of 77,003 poses a major health concern in India, with 5-10 % tobacco habitués developing oral cancer. The current study examined the role of specific genomic variants in oral cancer. We examined five genomic variants represented as single nucleotide polymorphisms (SNPs) in genes associated with cell proliferation and cellular invasion. The SNPs rs2124437 (RASGRP3), rs1335022 (GRIK2), rs4512367 (PREX2), rs4748011 (CCDC3), and rs1435218 (LNX1) were analyzed in 500 histopathologically confirmed oral cancers and 500 healthy controls with a minimum of 10 years of tobacco usage. Allelic discrimination real-time PCR SYBR Green assay was used. The genotypic and allelic frequencies between cases and controls were analyzed using SPSS software (version 19) and odds ratio (OR) using Hutchon.net, indicating increased risk to oral cancers. A significant association of the SNPs in oral cancer was observed in RASGRP3 AA (rs2124437) (p < 0.000, OR 1.34, 95 % confidence interval (CI) 1.01-1.76), GRIK2 TT (rs1335022) (p = 0.008, OR 1.58, 95 % CI 1.23-2.03), PREX2 CC (p = 0.008, OR 1.56, 95 % CI 1.15-2.1), and TT (p < 0.000, OR 2.77, 1.68-4.57) genotypes, whereas the heterozygous genotypes showed higher frequencies in controls, i.e., GRIK2 CT (rs1335022) (p = 0.029, OR 0.68, 95 % CI 0.53-0.87) and PREX2 CT (p = 0.004, OR 0.49, 95 % CI 0.37-0.64), indicating protection. Coinheritance of the SNPs was associated with further increase in the risk. Thus, the SNP genotypes in the three genes, present singly or as a coinherited panel constituted "Predictive Biomarkers" indicating increased risk of oral cancer in tobacco habitués.


Intra-abdominal candidiasis in surgical intensive care unit - epidemiology characteristics and trends.
Intra-abdominal candidiasis (IAC) is an invasive fungal infection representing the most common type of invasive Candida infection in surgical intensive care units (ICUs). Recently, decreased antifungal susceptibility and progressive shift in the aetiology of invasive candidiasis has been observed worldwide. We explored IAC epidemiology in surgical ICU. We retrospectively reviewed the records of 64 patients with IAC admitted at our surgical ICU over a 4-year period (2013-2016). IAC incidence, microbiological results, antifungal therapy, and mortality were analysed. The cumulative IAC incidence was 18.4 cases per 1000 admissions (2013: 12.6; 2014: 17.7; 2015: 16.8; 2016: 24.5), including hospital-acquired IAC incidence (2013: 9.8; 2014: 13.3; 2015 10.1; 2016: 13.3) and community-acquired IAC incidence (2013: 2.8; 2014: 4.4; 2015: 6.7; 2016: 11.2). Candida albicans represented the most common species (n = 35, 50.0%) followed by Candida glabrata (n = 15, 21.4%), Candida tropicalis (n = 6, 8.6%) and other yeasts (each < 5.0%). Incidence rate of C. albicans (2013: 7(78%); 2014: 10(59%); 2015: 6(35%); 2016: 12(44%)) and incidence rate of C. non-albicans (2013: 2(22%); 2014: 7(41%); 2015: 9(53%); 2016: 14(52%)) were different in trend. All fungal isolates were susceptible to echinocandins, amphotericin B and voriconazole. Regarding fluconazole susceptibility, C. krusei (n = 3) was resistant and C. glabrata (n = 9) was susceptible-dose dependent (SDD). The ratio of SDD C. glabrata isolates to all isolated C. glabrata strains was 9/15 (60%) (2013: 0/2; 2014: 0/2; 2015: 1/3; 2016: 8/8). Decreased fluconazole susceptibility for C. glabrata isolates was reported in both community-acquired IAC (n = 3) and hospital-acquired IAC (n = 6). Overall 30-day mortality rate was 25.0% (16/64). We have revealed slowly raising of overall IAC incidence, more increasing trend in incidence of community-acquired IAC compared to rather steady incidence of hospital-acquired IAC. During period 2013-2016 we have observed a significant shift in the aetiology of IAC towards an increased proportion of non-albicans Candida species, particularly C. glabrata. Acquired decreased fluconazole susceptibility was related to C. glabrata isolates exclusively. Emergence of decreased antifungal susceptibility has been preceded by increase of non-albicans Candida isolates.


Development of a blood proteins-based model for bronchopulmonary dysplasia prediction in premature infants.
Bronchopulmonary dysplasia (BPD) is the most common chronic pulmonary disease in premature infants. Blood proteins may be early predictors of the development of this disease. In this study, protein expression profiles (blood samples during their first week of life) and clinical data of the GSE121097 was downloaded from the Gene Expression Omnibus. Weighted gene co-expression network analysis (WGCNA) and differential protein analysis were carried out for variable dimensionality reduction and feature selection. Least absolute shrinkage and selection operator (LASSO) were conducted for BPD prediction model development. The performance of the model was evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. The results showed that black module, magenta module and turquoise module, which included 270 proteins, were significantly correlated with the occurrence of BPD. 59 proteins overlapped between differential analysis results and above three modules. These proteins were significantly enriched in 253 GO terms and 11 KEGG signaling pathways. Then, 59 proteins were reduced to 8 proteins by LASSO analysis in the training cohort. The proteins model showed good BPD predictive performance, with an AUC of 1.00 (95% CI 0.99-1.00) and 0.96 (95% CI 0.90-1.00) in training cohort and test cohort, respectively. Our study established a reliable blood-protein based model for early prediction of BPD in premature infants. This may help elucidate pathways to target in lessening the burden or severity of BPD.


Brazilian propolis ameliorates trinitrobenzene sulfonic acid-induced colitis in mice by inhibiting Th1 differentiation.
Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. We previously demonstrated the inhibitory activity of Brazilian propolis ethanolic extract against the differentiation process of Th17 cells and pathogenesis of collagen-induced arthritis, which is an experimental animal model of rheumatoid arthritis. Th1 cells are also involved in several autoimmune and inflammatory diseases, such as inflammatory bowel disease. In the present study, we demonstrated for the first time that Brazilian propolis significantly inhibited the generation of Th1 cells. Furthermore, we hypothesized that the administration of propolis to a murine model of colitis would suppress Th1 cell differentiation and ultimately ameliorate colitis. CD4 T cells were stimulated under Th1-polarizing conditions (immobilized anti-CD3 and anti-CD28 antibodies with IL-12 plus an anti-IL-4 monoclonal antibody for 5days) with or without the propolis ethanolic extract. Cells were characterized for helper T cell subsets by flow cytometric analysis. Furthermore, we investigated the effects of propolis on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in a mouse model. Propolis dose-dependently reduced the frequency of IFNγ-producing CD4 T cells under Th1-polarizing conditions. Furthermore, the inhibitory effect of propolis on Th1 differentiation was demonstrated in vivo. The severity of colitis in mice fed propolis was significantly lower than that of mice fed the control diet. These findings suggest that the suppressive effect of Brazilian propolis on Th1 differentiation may be useful in controlling unbalanced cytokine networks in autoimmune diseases.


Heterologous expression as a tool for gene identification and analysis.
These days, genome research mainly concerns the accumulation of sequence data and their theoretical interpretation based on analogies to known genes, proteins and structures. However, a final identification of gene function can only be verified by experimental data. One step in this process is the expression of the isolated gene in pro- and eukaryotes. In this article we will review some of the basic features of expression in Escherichia coli and mammalian cells that are relevant to the design of expression experiments. Emphasis is put on the first instance of attaining a high enough level of expression in order to be able to detect the cellular effects or to isolate the product of the transferred gene.


History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity.
Neuroimaging studies have identified obesity-related differences in the brain's resting state activity. An imbalance between homeostatic and reward aspects of ingestive behaviour may contribute to obesity and food addiction. The interactions between early life adversity (ELA), the reward network and food addiction were investigated to identify obesity and sex-related differences, which may drive obesity and food addiction. Functional resting state magnetic resonance imaging was acquired in 186 participants (high body mass index [BMI]: ≥25: 53 women and 54 men; normal BMI: 18.50-24.99: 49 women and 30 men). Participants completed questionnaires to assess ELA (Early Traumatic Inventory) and food addiction (Yale Food Addiction Scale). A tripartite network analysis based on graph theory was used to investigate the interaction between ELA, brain connectivity and food addiction. Interactions were determined by computing Spearman rank correlations, thresholded at q < 0.05 corrected for multiple comparisons. Participants with high BMI demonstrate an association between ELA and food addiction, with reward regions playing a role in this interaction. Among women with high BMI, increased ELA was associated with increased centrality of reward and emotion regulation regions. Men with high BMI showed associations between ELA and food addiction with somatosensory regions playing a role in this interaction. The findings suggest that ELA may alter brain networks, leading to increased vulnerability for food addiction and obesity later in life. These alterations are sex specific and involve brain regions influenced by dopaminergic or serotonergic signalling.


Pertussis toxin facilitates secretagogue-induced catecholamine release from cultured bovine adrenal chromaffin cells.
Pretreatment of cultured bovine adrenal chromaffin cells with pertussis toxin facilitated nicotine-induced catecholamine release. This facilitation was correlated with the ability of the toxin to catalyze the ADP-ribosylation of an approximately 40-kDa membrane protein. The actions of the toxin were reversed by isonicotinamide, an inhibitor of ADP-ribosylation. Catecholamine release due to high K+ and muscarine was also enhanced by pertussis toxin. In all cases, 45Ca2+ uptake was unaltered in cells treated with the toxin. These results suggest that ADP-ribosylation of a 40-kDa membrane protein facilitates catecholamine release from bovine chromaffin cells without affecting 45Ca2+ uptake.


Hepatolithiasis caused by right hepatic artery branches forming an arterial ring compressing the common hepatic duct.
Anatomic variations of the hepatic artery do not usually cause biliary obstruction. We present a 51-year-old male who developed biliary obstruction and hepatolithiasis due to extrinsic compression of the common hepatic duct (CHD) by an arterial ring formed by the anterior and posterior branches of the right hepatic artery. We performed a surgical bile duct exploration and used intraoperative direct cholangioscopy to guide clearance of hepatolithiasis. Herein, we review the existing literature on CHD compression caused by topographical variants of the hepatic artery and discuss diagnostic and treatment strategies.


Association between maternal decision-making and mental health and the nutritional status of children under 6 years of age in sub-urban Nigeria.
We assessed the association between decision-making power and mental health status of mothers and the nutritional status of their children less than 6 years old in Ile-Ife, Nigeria. This was a secondary data analysis of 1549 mother-child dyads collected through a household survey conducted between December 2019 and January 2020. The independent variables were maternal decision-making and mental health status (general anxiety, depressive symptoms, parental stress). The dependent variable was the child's nutritional status (thinness, stunting, underweight and overweight). Confounders were maternal income, age, and education status, and the child's age and sex. The associations between the dependent and independent variables were determined using multivariable binary logistic regression analysis after adjusting for confounders. The adjusted odds ratios (AORs) were determined. Children of mothers with mild general anxiety had lower odds of stunting than children of mothers with normal anxiety (AOR: 0.72; p = 0.034). Mothers who did not make decisions on children's access to health care (AOR: 0.65; p < 0.001) had children with lower odds of being thin than those whose mothers made decisions on their access to health care. Children of mothers with clinically significant parenting stress levels (AOR: 0.75; p = 0.033), severe depressive symptoms (AOR: 0.70; p = 0.041) and who were not decision makers on the access of their children to health care (AOR: 0.79; p = 0.035) had lower odds of underweight. Maternal decision-making status and mental health status were associated with the nutritional status of children less than 6 years in a sub-urban community in Nigeria. Further studies are needed to understand how maternal mental health is associated with the nutritional status of Nigerian preschool children.


A new method for protein labeling with 99mTc.
A method is described for labeling proteins with 99mTc, the radionuclide of choice in diagnostic nuclear medicine. Labeling efficiency, stability of label attachment and retained biological behaviour, e.g. immunoreactivity of monoclonal antibodies after radiolabeling are demonstrated. An application of a 99mTc-labeled anti-fibrin monoclonal antibody in radioimmunoimaging of thrombi is presented.


Ground water quality in the Kathmandu valley of Nepal.
A study was undertaken to assess the quality of groundwaters in the Kathmandu Valley, Nepal. The groundwater samples were randomly collected from shallow well, tube well, and deep-tube wells located at different places of Kathmandu, Lalitpur, and Bhaktapur districts in the Kathmandu valley. Physical, chemical, and microbiological parameters of the samples were evaluated to estimate the groundwater quality for drinking water. It was found that the groundwater in the valley is vulnerable to drink due to presence of iron and coliform bacteria. Iron was estimated to be much higher then the acceptable limit of World Health Organization (WHO) drinking-water quality guidelines (1.9 mg/L). Total coliform bacteria enumerated in groundwaters significantly exceeded the drinking-water quality standard and observed maximum coliform (267 CFU/100 mL) in shallow wells. The electrical conductivity and turbidity were found to be 875 μS/cm and 55 NTU, respectively, which are above the WHO recommendations for drinking water guidelines. However, pH value was measured within the acceptable limit. Arsenic, chloride, fluoride, and hardness concentrations were found to be in agreement with the recommendations of WHO drinking-water quality guidelines.


Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.
We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.


Surgical outcomes of phakic, pseudophakic and combined phaco-trabeculectomy in a tertiary care centre in Saudi Arabia.
To compare the outcomes of phakic, pseudophakic and combined phaco-trabeculectomy in eyes of Saudi patients. This was a retrospective cohort study. Eyes of patients with primary open angle glaucoma, primary angle closure glaucoma or secondary exfoliation glaucoma (XFG) that underwent phakic (n = 152), pseudophakic (n = 40) or combined phaco-trabeculectomy (n = 45) at the King Khaled Eye Specialist Hospital, Riyadh from January 2012 to December 2017 were included. The primary outcome measure was the success at 3 years after surgery. Complete success was defined as achieving an intraocular pressure (IOP) of ≥ 6 and ≤ 21 mmHg without topical antiglaucoma medications; qualified success as achieving the same IOP criteria with or without the use of glaucoma medications. Cumulative probabilities of failure were computed using Kaplan-Meier survival analysis. We used Cox regression analysis to identify factors associated with treatment failure. Reduction in mean IOP and AGM over time was estimated using mixed-effects linear models. The mean decrease in IOP at 3 years from baseline in the phakic, pseudophakic and combined groups was 12.0 (95% CI, 9.9, 14.1) mmHg, 10.1 (95% 6.3, 13.9) mmHg, and 6.4 (95% CI, 1.9, 11.0) mmHg, respectively, and was not significantly different from each other. The values for qualified success were also comparable: 95.2% (95% CI: 86.7-99.0), 95.3% (95% CI: 76.2-99.9), 92.3% (95% CI: 64.0-99.8). Failure was significantly associated with postoperative suturelysis (p = 0.004), XFG (p = 0.018) and AGM (p = 0.038). This is the first study to provide relative surgical outcomes of trabeculectomy, phaco-trabeculectomy and pseudophakic trabeculectomy in Saudi Arabia and did not show any significant difference in terms of overall success.


G-CSF - A double edge sword in neutrophil mediated immunity.
Neutrophils are vital for the innate immune system's control of pathogens and neutrophil deficiency can render the host susceptible to life-threatening infections. Neutrophil responses must also be tightly regulated because excessive production, recruitment or activation of neutrophils can cause tissue damage in both acute and chronic inflammatory diseases. Granulocyte colony stimulating factor (G-CSF) is a key regulator of neutrophil biology, from production, differentiation, and release of neutrophil precursors in the bone marrow (BM) to modulating the function of mature neutrophils outside of the BM, particularly at sites of inflammation. G-CSF acts by binding to its cognate cell surface receptor on target cells, causing the activation of intracellular signalling pathways mediating the proliferation, differentiation, function, and survival of cells in the neutrophil lineage. Studies in humans and mice demonstrate that G-CSF contributes to protecting the host against infection, but conversely, it can play a deleterious role in inflammatory diseases. As such, neutrophils and the G-CSF pathway may provide novel therapeutic targets. This review will focus on understanding the role G-CSF plays in the balance between effective neutrophil mediated host defence versus neutrophil-mediated inflammation and tissue damage in various inflammatory and infectious diseases.


The impact of reporting magnetic resonance imaging incidental findings in the Canadian alliance for healthy hearts and minds cohort.
In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies. Between 2013 and 2019, 8252 participants (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported. Severe structural abnormalities occurred in 8.3% (95% confidence interval 7.7-8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy. The management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT02220582 .


A technique using parallel-opposed high energy electron beams for reirradiation of tumors near the spinal cord.
Previous radiation treatment of patients with recurrent Hodgkin's lymphoma hampers attempts to give these patients further radiation treatment for their recurrence, because of the potential for serious radiation damage to critical normal structures within the treatment volume. The purpose of this paper is to present a technique we developed for treatment of recurrent Hodgkin's lymphoma in mediastinum and hilum. The technique is based on parallel-opposed electron beams with a spinal cord shield in the posterior electron beam. The patient was treated with parallel-opposed 20 MeV electron beams and the spinal cord shield was shaped in such a way that the total dose from both the anterior and posterior electron beams did not exceed 33% of the prescribed tumor dose. Wax bolus was used to obtain the desired separation for the electron beams. In an electron beam, the dose under the spinal cord shield depends not only on the depth of the spinal cord but also on the width of the shield. For a given shield width, as the cord depth increases the relative dose under the shield first increases, reaches a maximum, and then decreases to approach the open field depth dose data at large depths. The depth at which the relative dose maximum occurs increases slowly with the shielded width. At a given depth, the relative dose decreases with an increasing shield width. Parallel-opposed electron beams with a spinal cord shield in the posterior electron beam provide a viable option in treatment of tumors enveloping the spinal cord. A high tumor dose may be prescribed with a concurrent low dose to the spinal cord obtained with an appropriately shaped spinal cord shield.


Nutritional support of the mechanically ventilated patient.
Mechanically ventilated patients generally depend on artificial means for nutritional supplementation. In this article we review the magnitude, pathophysiology, and clinical significance of proteolysis, and evidence that nutritional repletion is beneficial. Methods for assessing nutritional status and response to nutritional intervention are briefly discussed, as well as basic principles of anabolic and anticatabolic therapy.


MRI findings in juvenile Huntington's disease.
Juvenile Huntington's disease is a rare neurodegenerative disorder that first affects the basal ganglia. Presented here is a case of juvenile Huntington's disease in an 8-year-old male. Clinical features included epilepsy and developmental delay. Imaging findings showed severe atrophy of the caudate nuclei and putamina which prompted a genetic evaluation. The diagnosis was confirmed via molecular analysis which revealed the amplified CAG triplet characteristic of this disorder. This case report highlights the imaging features common in this rare cause of pediatric epilepsy.


Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation in children: a propensity score-matched analysis.
To investigate the incidence, risk factors, and clinical outcomes of pleuroparenchymal fibroelastosis (PPFE) in pediatric hematopoietic stem cell transplantation (HSCT) recipients. This single-center, retrospective, case-control study included 738 consecutive patients who underwent chest CT more than 3 months after HSCT. We identified patients who fulfilled the diagnostic criteria for PPFE and assessed their clinical characteristics and radiologic findings. Propensity score-matched analysis was performed using four covariates (age, sex, HSCT type, and primary disease). The risk factors and clinical outcomes of PPFE were analyzed using the Fine and Gray regression model and stratified log-rank test in the matched groups. PPFE was identified in 4% (31/738, 8.3 ± 3.1 years, 15 males) of the pediatric HSCT recipients with a median time of 2.7 years after HSCT, and it occurred following allogeneic (5%, 15/317), autologous (4%, 15/379), or both (2%, 1/42). Matching yielded 30 and 130 cases in the PPFE and control groups, respectively. The PPFE group showed more frequent late-onset noninfectious pulmonary complications (LONIPCs) and pneumonia more than 3 months after HSCT (p < 0.05). Multivariable analysis showed a significantly higher risk of PPFE in HSCT recipients who had pneumonia more than 3 months after HSCT (hazard ratio = 10.78 [95% confidence interval: 4.29, 27.13], p < 0.001). The PPFE group showed higher mortality (73%, 22/30) and poorer median overall survival (6.8 years [95% confidence interval: 4.1, 9.5]) than the control group (p < 0.001). PPFE represents a severe type of LONIPC after HSCT. HSCT recipients with pneumonia after HSCT may have an increased risk of PPFE. • The incidence of pleuroparenchymal fibroelastosis is not negligible (4%), and it can occur after either allogeneic or autologous hematopoietic stem cell transplantation. • Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation showed poor outcome with a high mortality rate of 73% and median overall survival of 6.8 years. • After hematopoietic stem cell transplantation, pneumonia may increase the risk of pleuroparenchymal fibroelastosis development in children. • Lung biopsy should not be indicated in patients with pleuroparenchymal fibroelastosis findings on chest CT as it can cause refractory pneumothorax without helping the diagnosis.


Plants-Microorganisms-Based Bioremediation for Heavy Metal Cleanup: Recent Developments, Phytoremediation Techniques, Regulation Mechanisms, and Molecular Responses.
Rapid industrialization, mine tailings runoff, and agricultural activities are often detrimental to soil health and can distribute hazardous metal(loid)s into the soil environment, with harmful effects on human and ecosystem health. Plants and their associated microbes can be deployed to clean up and prevent environmental pollution. This green technology has emerged as one of the most attractive and acceptable practices for using natural processes to break down organic contaminants or accumulate and stabilize metal pollutants by acting as filters or traps. This review explores the interactions between plants, their associated microbiomes, and the environment, and discusses how they shape the assembly of plant-associated microbial communities and modulate metal(loid)s remediation. Here, we also overview microbe-heavy-metal(loid)s interactions and discuss microbial bioremediation and plants with advanced phytoremediation properties approaches that have been successfully used, as well as their associated biological processes. We conclude by providing insights into the underlying remediation strategies' mechanisms, key challenges, and future directions for the remediation of metal(loid)s-polluted agricultural soils with environmentally friendly techniques.


High rate of unexpected positive cultures in presumed aseptic revision of stiff shoulders after proximal humerus osteosynthesis.
The aim of this study was to investigate the prevalence of positive microbiology samples after osteosynthesis of proximal humerus fractures at the time of revision surgery and evaluate clinical characteristics of patients with positive culture results. All patients, who underwent revision surgery after locked platting, medullary nailing or screw osteosynthesis of proximal humeral fractures between April 2013 and July 2018 were retrospectively evaluated. Patients with acute postoperative infections, those with apparent clinical signs of infection and those with ≤1 tissue or only sonication sample obtained at the time of implant removal were excluded. Positive culture results of revision surgery and its correlation with postoperative shoulder stiffness was analyzed in patients with an interval of ≥6 months between the index osteosynthesis and revision surgery. Intraoperatively obtained cultures were positive in 31 patients (50%). Cutibacterium acnes was the most commonly isolated microorganism, observed in 21 patients (67.7%), followed by coagulase negative staphylococci in 12 patients (38.7%). There were significantly more stiff patients in the culture positive group compared to the culture-negative group (19/21, 91% vs. 15/26, 58%, p = 0.02). Furthermore, 11 of 12 (91.7%) patients with growth of the same microorganism in at least two samples had a stiff shoulder compared to 23 of 35 (65.7%) patients with only one positive culture or negative culture results (p = 0.14). Infection must always be considered as a possibility in the setting of revision surgery after proximal humerus osteosynthesis, especially in patients with postoperative stiffness.


An unusual presentation of congenital infantile myofibromatosis arising from the interspinous ligament.
The authors describe an extremely rare presentation of congenital infantile myofibromatosis. A full-term newborn boy presented with a thumb-sized subcutaneous mass on the mid-spinal line between the 2nd and 3rd lumbar spinous processes. A solid tumor arising from the interspinous ligament was resected. Microscopic and immunohistochemical studies revealed myofibromatosis.


Adsorption behavior of some aromatic compounds on hydrophobic magnetite for magnetic separation.
In this study, a hydrophobic magnetite coated with an alkyl chain or a phenyl group on the surface was prepared and used as an adsorbent to investigate the adsorption behavior of aromatic compounds having various values of log P(ow) (phenol 1.46, benzonitrile 1.56, nitrobenzene 1.86, benzene 2.13, toluene 2.73, chlorobenzene 2.84 and o-dichlorobenzene 3.38) onto hydrophobic magnetite. The hydrophobic magnetites were modified with stearic acid and phenyltrimethoxysilane, and the modification amounts were 9.84 × 10(-3) and 4.17 × 10(-2)mmol/g, respectively. The aromatic compounds used in this study were divided into 3 groups depending on the log P(ow): 1<log P(ow)<2, 2<log P(ow)<3 and 3<log P(ow). The adsorption amounts of above each group on the magnetite at an initial concentration of 100 ppm were 3.62 × 10(-3) (nitrobenzene), 1.92 × 10(-2) (phenol), 1.13 × 10(-1) (chlorobenzene), 2.42 × 10(-1) (benzene), and 3.10 × 10(-1)mmol/g (dichlorobenzene), respectively. This indicates that the adsorption behaviors depend on the strength of hydrophobicity of aromatic compounds. The adsorption mechanism for 2<log P(ow)<3 and 3<log P(ow) is hydrophobic interaction and that for 1<log P(ow)<2 is π-electron interaction. The quantitative relationship between the amount of adsorbed compounds and modified functional groups and the fitting for adsorption isotherm models suggested that this adsorption might form a multi-layer adsorption in the most cases.


Sweet Relief: Reprogramming Gastric Endocrine Cells to Make Insulin.
Two promising approaches toward a cell-based cure for diabetes are the directed differentiation of pluripotent stem cells or lineage reprogramming of other cell types to generate beta cells. In this issue of Cell Stem Cell, Ariyachet et al. (2016) reprogrammed gastric endocrine cells to generate a renewable source of insulin-producing cells.


NMDA and AMPA receptors are involved in the antidepressant-like activity of tianeptine in the forced swim test in mice.
It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was to investigate the involvement of the glutamate pathway in the antidepressant-like action of tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on tianeptine-induced activity in the forced swim test (FST) in mice. The antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover, low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg, ip) administered together with low, ineffective doses of tianeptine (20 mg/kg, ip) exhibited a significant reduction of immobility time in the FST. These doses of the examined agents, which did have an effect in the FST, did not alter locomotor activity. The present study indicates that the antidepressant-like activity of tianeptine in the FST involves both NMDA and AMPA receptors and suggests that the interaction between serotonergic and glutamatergic transmission may play an important role in the action of tianeptine.


Risk communication clarity and insurance demand: The case of the COVID-19 pandemic.
We study how the clarity of COVID-19 risk communications affects COVID-19 insurance demand using proprietary prefecture-level insurance data from China. We find that when local disclosures of COVID-19 risk contain case origin information, local purchases of COVID-19 insurance and local Internet searches for COVID-19 information increase, even after controlling for newly confirmed local cases and new deaths. Our results are robust to using the disclosure clarity of a major neighboring city. The findings suggest that providing improved knowledge about risk to individuals lead them to engage in more risk management. Our evidence contributes to the debate over how risk communication affects individuals' risk-related behaviors.


LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.
Human aortic medial smooth muscle cells (SMC) and umbilical vein endothelial cells (EC) in culture were exposed to various concentrations of plasma low density (LDL) and high density (HDL) lipoproteins prepared from normolipemic donors in order to assess their effects on cell growth. So that the effects of each lipoprotein could be evaluated separately and in combination, lipoproteins were added to culture medium containing lipoprotein deficient serum (LPDS, d greater than 1.25 g/ml at a protein concentration of 4.5 mg/ml of medium). The addition of LDL at cholesterol concentrations of 160 microgram/ml of culture medium, resulted in significant reductions in both the number of SMC and EC cells per dish within 3 days of exposure (P less than 0.001, SMC; P less than 0.01, EC), when compared with LPDS controls and the starting cell numbers. This cytotoxic phenomenon was dose-related, and only at LDL cholesterol concentrations equal to or below 50 microgram/ml were no marked changes observed. In contrast, HDL at all concentrations tested produced no such deleterious effects. Autoradiographic assessment of DNA synthesis confirmed these findings. After 48 h of continuous exposure to tritiated thymidine, labeling indexes reached much lower plateaus in the LDL-treated groups.


Synergism between subthreshold doses of phenylbutazone and prednisolone in rat hind-paw carrageenan edema.
When phenylbutazone (PhB) and prednisolone (PD) or cortisol acetate (HC) were administered together by oral route a synergic inhibitory effect on rat hind-paw carrageenan edema occurred, marked antiphologistic effect being obtained by associating subthreshold doses of drugs. By administering a fixed subthreshold dose of PD with increasing subthreshold doses of PhB, statistically significant phlogosis inhibition was obtained, the degree of which was directly related to the amount of PhB. Finally, the association of near maximal effective doses of PhB and PD gave an inhibition greater than that produced by a maximally effective dose of each of the associated drugs.


Pharmacological inhibition of na/ca exchange results in increased cellular Ca2+ load attributable to the predominance of forward mode block.
Block of Na/Ca exchange (NCX) has potential therapeutic applications, in particular, if a mode-selective block could be achieved, but also carries serious risks for disturbing the normal Ca2+ balance maintained by NCX. We have examined the effects of partial inhibition of NCX by SEA-0400 (1 or 0.3 micromol/L) in left ventricular myocytes from healthy pigs or mice and from mice with heart failure (MLP-/-). During voltage clamp ramps with [Ca2+](i) buffering, block of reverse mode block was slightly larger than of forward mode (by 25+/-5%, P<0.05). In the absence of [Ca2+](i) buffering and with sarcoplasmic reticulum (SR) fluxes blocked, rate constants for Ca2+ influx and Ca2+ efflux were reduced to the same extent (to 36+/-6% and 32+/-4%, respectively). With normal SR function the reduction of inward NCX current (I(NCX)) was 57+/-10% (n=10); during large caffeine-induced Ca2+ transients, it was larger (82+/-3%). [Ca2+](i) transients evoked during depolarizing steps increased (from 424+/-27 to 994+/-127 nmol/L at +10 mV, P<0.05), despite a reduction of I(CaL) by 27%. Resting [Ca2+](i) increased; there was a small decrease in the rate of decline of [Ca2+](i). SR Ca2+) content increased more than 2-fold. Contraction amplitude of field-stimulated myocytes increased in healthy myocytes but not in myocytes from MLP-/- mice, in which SR Ca2+ content remained unchanged. These data provide proof-of-principle that even partial inhibition of NCX results in a net gain of Ca2+. Further development of NCX blockers, in particular, for heart failure, must balance potential benefits of I(NCX) reduction against effects on Ca2+ handling by refining mode dependence and/or including additional targets.


Associations of Sugar-Sweetened Beverages, Artificially Sweetened Beverages, and Pure Fruit Juice With Nonalcoholic Fatty Liver Disease: Cross-sectional and Longitudinal Study.
We aimed to test the associations of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and pure fruit juice (PJ) consumption with the risk of nonalcoholic fatty liver disease (NAFLD). Data for 136 277 UK Biobank participants who completed the dietary questionnaire and did not have a history of liver disease were included. Logistic regression was used for the cross-sectional setting where NAFLD was defined by a fatty liver index (FLI) ≥60. Cox proportional hazard regression was used for the longitudinal setting where hospitalized NAFLD was defined as hospital admission with Internationl Classification of Diseases-10 codes K76.0 and K75.8. Compared with 0 L/wk for corresponding beverages, multivariate-adjusted odds ratios (95% confidence intervals) for NAFLD in consumption ≤1, 1 to 2, and >2 L/wk were 1.06 (1.02-1.10), 1.24 (1.19-1.29), and 1.42 (1.35-1.49) for SSB; 1.43 (1.37-1.50), 1.73 (1.65-1.82), and 2.37 (2.25-2.50) for ASB, and 0.87 (0.84-0.89), 0.91 (0.88-0.94), and 1.07 (1.02-1.13) for PJ, respectively. Consumption of SSB and ASB were both positively correlated with FLI (P for line < .001). During a median follow-up of 10.2 years, 1043 cases of hospitalized NAFLD were recorded. ASB consumption of 1 to 2 and >2 L/wk was associated with a 22% (0.99-1.50) and 35% (1.11-1.65) increased risk of hospitalized NAFLD, respectively (P for trend = .002). However, the associations of SSB and PJ with the risk of hospitalized NAFLD were not significant. Consumption of SSB, ASB, and PJ were all related to the risk of NAFLD. Excessive consumption of ASBs was associated with an increased risk of incident hospitalized NAFLD.


Effect of Early Postoperative Rehabilitation on Length of Hospital Stay after Robot-assisted Radical Prostatectomy.
: This study assessed how early postoperative rehabilitation interventions affected the duration of hospital stay in patients with prostate cancer who had radical prostatectomy with robotic assistance. : From the Japanese Diagnosis Procedure Combination database, we extracted case data for patients discharged between April 2014 and March 2020. Patients were recognized by code C61 from the International Classification of Diseases, 10th Edition. We ran a multilevel linear regression analysis to investigate the impact of early rehabilitation on the duration of hospital stay. : There were 2151 participants in the trial. In patients with prostate cancer who had resection utilizing robotic-assisted devices, early rehabilitation was related to a substantial decrease in duration of hospital stay (coefficient, -0.86; 95% CI, -1.64 to -0.07; P=0.032). : Early postoperative rehabilitation may contribute to shorter hospital stays in patients with prostate cancer at high risk of both postoperative complications and a decline in their ability to perform activities of daily living.


Estimating the risk of collisions between bicycles and motor vehicles at signalized intersections.
Collisions between bicycles and motor vehicles have caused severe life and property losses in many countries. The majority of bicycle-motor vehicle (BMV) accidents occur at intersections. In order to reduce the number of BMV accidents at intersections, a substantial understanding of the causal factors for the collisions is required. In this study, intersection BMV accidents were classified into three types based on the movements of the involved motor vehicles and bicycles. The three BMV accident classifications were through motor vehicle related collisions, left-turn motor vehicle related collisions, and right-turn motor vehicle related collisions. A methodology for estimating these BMV accident risks was developed based on probability theory. A significant difference between this proposed methodology and most current approaches is that the proposed approach explicitly relates the risk of each specific BMV accident type to its related flows. The methodology was demonstrated using a 4-year (1992-1995) data set collected from 115 signalized intersections in the Tokyo Metropolitan area. This data set contains BMV accident data, bicycle flow data, motor vehicle flow data, traffic control data, and geometric data for each intersection approach. For each BMV risk model, an independent explanatory variable set was chosen according to the characteristics of the accident type. Three negative binomial regression models (one corresponding to each BMV accident type) were estimated using the maximum likelihood method. The coefficient value and its significance level were estimated for each selected variable. The negative binomial dispersion parameters for all the three models were significant at 0.01 levels. This supported the choice of the negative binomial regression over the Poisson regression for the quantitative analyses in this study.


Cutaneous epithelioid malignant schwannoma: review of the literature and case report.
A case of malignant epithelioid schwannoma in the skin is reported. This was a rare variant of a malignant tumour that arose on the back of a 35-year-old male without neurofibromatosis. Clinically the nodule appeared to be a benign cyst but as it was painful it was decided to remove it. Ultrastructural and immunohistochemical features of the lesion were consistent with those of malignant epithelioid schwannoma so a radical excision was performed. Most ordinary malignant schwannoma are located in the deep soft tissue of the proximal portions of the upper and lower extremities and trunk; to the best of our knowledge only 26 cases of malignant epithelioid schwannoma in the skin and subcutis have been described in the literature. For the 14 male and 12 female patients reviewed, the median age was 43 years (range 19-84). Upper extremities were the most common sites (10 of 26). Seven patients developed local recurrences and four developed metastases: two to lung, one to lung and lymph node, and one to lung, liver and brain. All patients with local recurrence and all except one who developed metastases did not undergo wide local excision. We can conclude that malignant epithelioid schwannoma in the skin and subcutis is eminently curable if treated with wide local excision.


Missing data imputation with adversarially-trained graph convolutional networks.
Missing data imputation (MDI) is the task of replacing missing values in a dataset with alternative, predicted ones. Because of the widespread presence of missing data, it is a fundamental problem in many scientific disciplines. Popular methods for MDI use global statistics computed from the entire dataset (e.g., the feature-wise medians), or build predictive models operating independently on every instance. In this paper we propose a more general framework for MDI, leveraging recent work in the field of graph neural networks (GNNs). We formulate the MDI task in terms of a graph denoising autoencoder, where each edge of the graph encodes the similarity between two patterns. A GNN encoder learns to build intermediate representations for each example by interleaving classical projection layers and locally combining information between neighbors, while another decoding GNN learns to reconstruct the full imputed dataset from this intermediate embedding. In order to speed-up training and improve the performance, we use a combination of multiple losses, including an adversarial loss implemented with the Wasserstein metric and a gradient penalty. We also explore a few extensions to the basic architecture involving the use of residual connections between layers, and of global statistics computed from the dataset to improve the accuracy. On a large experimental evaluation with varying levels of artificial noise, we show that our method is on par or better than several alternative imputation methods. On three datasets with pre-existing missing values, we show that our method is robust to the choice of a downstream classifier, obtaining similar or slightly higher results compared to other choices.


JAKs to STATs: A tantalizing therapeutic target in acute myeloid leukemia.
The Janus Associated Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) signaling pathway plays a pivotal role in hematopoietic growth factor signaling. Hyperactive JAK-STAT signaling is implicated in the pathogenesis of myeloid malignancies, including acute myeloid leukemia (AML). The significant headway in understanding the biology of AML has led to an explosion of novel therapeutics with mechanistic rationale for the treatment of newly diagnosed and relapsed/refractory (R/R) AML. Most importantly, selective targeting of the JAK-STAT pathway has proven to be an effective therapeutic strategy in myeloproliferative neoplasms and is also being evaluated in related myeloid malignancies, including AML. This comprehensive review will focus on the apparent and evolving potential of JAK-STAT pathway inhibition in AML with emphasis on JAK inhibitors, highlighting both success and failure with this experimental approach in the clinic, and identifying rationally based combinatorial approaches.


Resolution effects on ox-bow lake mapping and inundation consistency analysis in moribund deltaic flood plain of India.
Research on investigating spatial resolution effect on image-based wetland mapping was done, and reported finer resolution is more appropriate. But is Sentinel image more effective than Landsat image for delineating ox-bow lake, a cut-off channel of a river, and for mapping inundation frequency? Inundation frequency means regularly, water appears in a pixel. In order to obtain these answers, the present study used frequently used spectral indices like normalized difference water index (NDWI), modified NDWI (MNDWI), re-modified NDWI (RmNDWI) and ensemble vegetation inclusive aggregated water index (ViAWI). For obtaining inundation consistency character, the water presence frequency (WPF) approach was adopted. A set of accuracy matrices was applied for validating the resolution effect. Results revealed that among the used indices, MNDWI was found suitable for ox-bow lake mapping. But this index is not able to map vegetated part of the ox-bow lakes. This problem was resolved using ensemble ViAWI. Inundation frequency analysis exhibited that about 70% of the area is consistent with water presence and therefore is hydro-ecologically and economically viable, and no such major differences were recorded between Sentinel and Landsat images. The study further revealed that finer resolution Sentinel images are more effective in ox-bow lake mapping and characterising inundation frequency, but they were not significantly better. Accuracy difference between them was found at the very minimum. Therefore, the study recommended that in a Sentinel image sparse condition, Landsat images could alternatively be used without much accuracy departure, particularly on those water bodies where water appearance is not highly erratic.


The use of prehospital variables to predict acute coronary artery disease in failed resuscitation attempts for out-of-hospital cardiac arrest.
To determine the ability of readily available prehospital variables to predict acute coronary artery disease (CAD) as the cause of arrest in failed out-of hospital cardiac arrest (OHCA) resuscitations. Retrospective analysis of a prospectively collected database of all adult cases of OHCA who underwent resuscitation attempts and later post-mortem examination by the state Medical Examiner (ME) over a 6 year period. Multivariable logistic regression modeling was used to identify predictors. Among the 151 cases linked to ME reports, CAD was judged to be the cause of arrest in 65/151 (43%). In multivariable modeling, CAD was more likely to be found at autopsy among older victims (Odds ratio [OR] 2.3 per decade of life, 95% confidence interval [CI] 1.6-3.4), males (OR 7.3, 95% CI 1.9-27.4), and those with an initial shockable rhythm (OR 5.3, 95% CI 2.0-14.2). The combination of these three variables correctly classified 75% of victims with an area under the ROC curve (AUC) of 0.85. As hospital-based salvage therapies offer opportunities to extend survival for victims of OHCA who fail prehospital treatment, an ability to predict CAD may help guide protocols for appropriate use. In this derivation analysis, a simple set of variables available on scene can be used to predict CAD with good accuracy among OHCA victims who fail prehospital resuscitation attempts. An initial shockable rhythm should still be considered the result of acute coronary artery disease until proven otherwise.


Low recurrence rate after mini surgery outside the tendon combined with short rehabilitation in patients with midportion Achilles tendinopathy.
There is a general opinion that a structured and specific rehabilitation is needed after treatment of midportion Achilles tendinopathy to minimize recurrence of the condition. There is sparse knowledge about the recurrence rates in large patient materials after specific treatments for midportion Achilles tendinopathy. This study aimed to investigate the recurrence rates in a large number of patients with chronic painful midportion Achilles tendinopathy that had been surgically treated with the ultrasound (US) and Doppler (DP)-guided mini-surgical scraping technique. Postoperatively, a relatively simple rehabilitation protocol, including a range of movement exercises and gradually increased walking and biking before allowing free activity, was used. From a database, information about the recurrence rates after US + DP-guided mini-surgical scraping, performed by a single surgeon on 519 tendons with US + DP-verified chronic painful midportion Achilles tendinopathy, was obtained. Recurrence of painful midportion Achilles tendinopathy was found in 26 of 519 (5%) operated tendons, 13 from women and 13 from men. In 13 tendons, a close by located plantaris tendon was extirpated during the reoperation. In this large material on patients treated with US + DP-guided mini-surgical scraping for midportion Achilles tendinopathy, there were few recurrences, although only a simple and nonspecific rehabilitation protocol was used.


[The benefit of self-assessment in rehabilitation].
The clinical stabilisation of the patient is a phase which is favourable for carrying out self-assessment to help them determine their resources. Adapted assessment scales are useful tools. On the basis of these, an initial care project is put in place which takes shape as and when the assessments are carried out. Ensuring the patient follows a therapeutic education programme aims particularly at improving their knowledge of their health.


Effects of ketamine on nociception and gastrointestinal motility in mice are unaffected by naloxone.
The present study investigates the effects of ketamine on nociception towards chemical and thermic stimuli and on gastrointestinal transit in mice. The reversibility of these effects by the opioid antagonist naloxone (10 mg/kg) was also assessed. Ketamine promoted dose-related analgesia in both the acetic acid-induced writhing and hot plate tests. Analgesia was not influenced by pretreatment with naloxone. Contrasting the constipation induced by opioids, ketamine enhanced gastrointestinal transit in a dose-dependent manner and this was not modified by naloxone. These results suggest that although ketamine can elicit analgesia, it does not activate opioid mechanisms in subanesthetic doses.


Comparison of the EP receptor subtypes mediating relaxation of the rabbit jugular and pig saphenous veins.
A fourth PGE receptor subtype, the EP4 receptor, has recently been described in the pig saphenous vein (PSV). Similar to the EP2 receptor, it mediates relaxation and is linked to stimulation of adenylate cyclase. The aim of this study was to determine whether or not the EP receptor present in the rabbit jugular vein (RJV), currently classified as an atypical EP2 receptor, is of the EP4 subtype. The relaxant activities of four EP2 agonists, 11-deoxy PGE1, 16,16-dimethyl PGE2, butaprost, and AH 13205, on the RJV and PSV have been examined, and the effect of the EP4 receptor antagonist AH 23,848B studied. The EP2 agonists showed a similar order of potency on the two preparations. 11-Deoxy PGE1 and 16,16-dimethyl PGE2 were potent agonists on the EP4 receptors of the PSV and on the RJV giving approximately equi-effective concentration ratios (EECs) of 2.0-6.6 and 2.8-9.9, respectively, compared to PGE2 (EEC = 1), and so do not discriminate between EP2 and EP4 receptors. Butaprost was less active on these preparations (EEC 42-43) than on classical EP2 receptors, and AH 13205 was much less active (EEC 3100-2780). While these results suggest that the EP receptors on the RJV are of the EP4 subtype, this was not confirmed using the EP4 receptors antagonist AH 23,848B.


Validation of Academic Research Consortium for High Bleeding Risk Definition in East-Asian Patients.
Clinical applicability of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in East-Asian patients receiving potent antiplatelet therapy for acute coronary syndromes (ACS) is still undetermined. The purpose of this study was to validate the ARC definition for HBR in East-Asian patients with ACS for invasive management. We analyzed data from the TICAKOREA (Ticagrelor Versus Clopidogrel in Asian/Korean Patients With ACS Intended for Invasive Management) trial and randomly assigned 800 Korean ACS subjects to receive, in a 1:1 ratio, ticagrelor or clopidogrel. Patients were considered HBR if they met at least 1 major or 2 minor ARC-HBR criteria. The primary bleeding endpoint was Bleeding Academic Research Consortium 3 or 5 bleeding and the primary ischemic endpoint was a major adverse cardiovascular event (MACE) (a composite of cardiovascular death, myocardial infarction, or stroke) at 12 months. Among 800 randomized patients, 129 (16.3%) were categorized HBR patients. HBR patients, compared with non-HBR patients, had a higher incidence of Bleeding Academic Research Consortium 3 or 5 bleeding (10.0% vs 3.7%; HR: 2.98; 95% CI: 1.52-5.86; P < 0.001) and MACE (14.3% vs 6.1%; HR: 2.35; 95% CI: 1.35-4.10; P = 0.002). The relative treatment effect of ticagrelor or clopidogrel on primary bleeding and ischemic outcomes were different between each group. This study validates the ARC-HBR definition in Korean ACS patients. Approximately 15% of patients qualified as HBR patients who were at increased risk not only for bleeding but also for thrombotic events. The clinical application of ARC-HBR to determine the relative effect of different antiplatelet regiments should be further investigated. (Safety and Efficacy of Ticagrelor Versus Clopidogrel in Asian/KOREAn Patients with Acute Coronary Syndromes Intended for Invasive Management [TICA KOREA]; NCT02094963).


Zinc deficiency: its role in gastric secretion and stress-induced gastric ulceration in rats.
The effects of zinc deficiency on gastric secretion and on cold-restraint stress-induced ulceration in rat stomachs have been studied. Administration of graded zinc deficient diets for 5 weeks significantly depressed the serum zinc concentration and decreased body weight gain in the rats. These diets significantly increased the gastric secretory volume, acid and pepsin. Zinc deficiency produced or aggravated the formation of glandular ulceration in the absence or presence of stress, respectively; it also decreased the mast cell count in the gastric glandular mucosa. It is concluded that zinc deficiency adversely affects the rats by reducing the body weight gain and producing ulceration which is probably mast cell-mediated. On the other hand, it increases gastric secretory functions.


Comparison of osseointegration of Ti-Al6V4 and Ti-Al6Nb7 implants: An experimental study.
In this study we aimed to investigate bone-implant connections (BICs) with Ti-Al6V4 and Ti-Al6Nb7 alloys. Two types of surface morphology, resorbable blast material (RBM) and sandblasted and acid-etched surfaces (SLA), were used for implants. Thirty female Sprague Dawley rats aged 0.5-1 year were used. The rats were randomly separated into three groups: 1) Ti-Al6V4 RBM surface (n = 10), 2), Ti-Al6Nb7 RBM surface (n = 10), and 3) Ti-Al6Nb7 SLA (n = 10) surface implants were surgically integrated in femoral bones. The average roughness (Ra) values for these implants were 1-2 Ra. The rats were sacrificed four weeks after the surgical procedure. For each section, the BIC ratio (%) was determined as a percentage of the total implant surface that was in direct contact with the bone. The BIC ratio was found to be higher in the Ti-Al6Nb7 RBM and Ti-Al6Nb7 SLA groups than in the Ti-Al6V4 RBM group (p < 0.05). There was no statistically significant difference in the BIC ratios between the Ti-Al6Nb7 RBM and Ti-Al6Nb7 SLA groups (p > 0.05). Ti-Al6Nb7 exhibited good biocompatibility with bone cells. Ti-Al6Nb7 alloy could be a candidate material for dental implant production.


Modern trends in anterior cruciate ligament rehabilitation: nonoperative and postoperative management.
Rehabilitation following ACL injury or reconstruction should be based on sound scientific and rehabilitation principles. Basic science principles related to rehabilitation following ACL injury and reconstruction have been reviewed. Guidelines incorporating these basic science principles as well as clinical experience were presented for rehabilitation following ACL injury and reconstruction.


A unique enzyme catalyzing the formation of 4-hydroxyaniline from 4-amino-benzoic acid in Agaricus bisporus.
A unique enzyme that catalyzes the formation of 4-hydroxyaniline from 4-aminobenzoic acid was found in the homogenate of Agaricus bisporus. The enzyme was prepared from the homogenate by (NH4)2SO4 fractionation, gel filtration and ion-exchange chromatography. The products formed from 4-aminobenzoic acid by the enzyme were shown to be 4-hydroxyaniline and CO2. The reaction required FAD, NAD(P)H and O2. These results indicate that the enzyme is a new FAD-dependent monooxygenase.


High homocysteine is associated with idiopathic normal pressure hydrocephalus in deep perforating arteriopathy: a cross-sectional study.
The pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Homocysteine may reduce the compliance of intracranial arteries and damage the endothelial function of the blood-brain barrier (BBB), which may be the underlying mechanism of iNPH. The overlap cases between deep perforating arteriopathy (DPA) and iNPH were not rare for the shared risk factors. We aimed to investigate the relationship between serum homocysteine and iNPH in DPA. A total of 41 DPA patients with iNPH and 49 DPA patients without iNPH were included. Demographic characteristics, vascular risk factors, laboratory results, and neuroimaging data were collected. Multivariable logistic regression analysis was performed to investigate the relationship between serum homocysteine and iNPH in DPA patients. Patients with iNPH had significantly higher homocysteine levels than those without iNPH (median, 16.34 mmol/L versus 14.28 mmol/L; P = 0.002). There was no significant difference in CSVD burden scores between patients with iNPH and patients without iNPH. Univariate logistic regression analysis demonstrated that patients with homocysteine levels in the Tertile3 were more likely to have iNPH than those in the Tertile1 (OR, 4.929; 95% CI, 1.612-15.071; P = 0.005). The association remained significant after multivariable adjustment for potential confounders, including age, male, hypertension, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia, and eGFR level. Our study indicated that high serum homocysteine levels were independently associated with iNPH in DPA. However, further research is needed to determine the predictive value of homocysteine and to confirm the underlying mechanism between homocysteine and iNPH.


Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis.
Aristolochic acid (AA) is considered to be a causative agent for progressive interstitial renal fibrosis, leading to AA nephropathy. Lysophosphatidic acid (LPA) is a mediator in the onset of renal fibrosis. In this study, we analyzed the molecular species of LPA and its precursor lysophospholipids in kidney tissue from rats exposed to AA. Daily intraperitoneal injections of AA for 35 days to rats gave rise to fibrosis in kidney, decreased the kidney levels of LPA, lysophosphatidylserine and lysophosphatidylinositol. In rat renal cell lines (NRK52E and NRK49F), AA-induced cytotoxicity was potentiated by Ki16425, LPA1,3 receptor antagonist. The level of mRNA encording α-smooth muscle actin was significantly increased by AA-treatment only in NRK52E cells, while the mRNA level of collagen III was decreased in both NRK52E and NRK49F cells. These results suggest that endogenous LPA in rat kidney prevents AA-induced renal fibrosis.


Association between plasma CD36 levels and incident risk of coronary heart disease among Danish men and women.
CD36 is a cholesterol receptor involved in the uptake of oxidized low-density lipoprotein cholesterol and development of atherosclerotic plaques. Cross-sectional studies have shown correlations between plasma CD36 and atherosclerosis but no prospective study has examined the association yet. We prospectively examined the association between plasma CD36 levels and risk of incident coronary heart disease (CHD) in a Danish population. Plasma CD36 levels were measured in a case-cohort study nested within the Danish population-based cohort, the Diet, Cancer and Health Study. A total of 1963 incident CHD events occurred between baseline (1993-1997) and 2008, and a sub-cohort of 1759 participants were randomly selected as reference. Cox proportional hazard regression models were used to compute the hazard ratio (HR) and corresponding 95% confidence interval (CI). After adjusting for CHD risk factors, including history of hypercholesterolemia and diabetes, elevated plasma CD36 levels were not associated with higher CHD risk in the total population, and the HR comparing the highest versus lowest tertile of CD36 levels was 1.02 (95% CI: 0.84-1.23). High CD36 levels were only found to be associated with risk of CHD in combination with prevalent diabetes (HR = 2.83, 95% CI: 1.08-7.45) vs. the joint reference group of lowest CD36 tertile and no diabetes. Plasma CD36 levels were not predictive of CHD risk in the general population.


Neonatal Supplementation of Oleamide During Suckling Promotes Learning Ability and Memory in Adolescent Mice.
Fatty acid amides (FAMs) are present in breast milk. Oleamide (ODA), a member of the FAM family, has been reported to affect learning and memory-related abilities in animal experiments. This study aimed to characterize the temporal changes of FAMs in human milk and sought to examine the effect of ODA supplementation during suckling on postweaning cognitive performance in mice. FAMs were measured in human milk (postpartum 1-24 wk) by ultra-performance liquid chromatography-triple quadruple mass spectrometry (UPLC-TQ-MS) analysis. We supplemented neonatal C57BL/6J mice of both sexes with vehicle (control), 5 mg/(kg · day) ODA (L-ODA), or 25 mg/(kg · day) ODA (H-ODA) throughout suckling by oral gavage. After weaning, the Morris water maze test and novel object recognition test were performed. Neurogenesis, spinal morphogenesis in the dentate gyrus (DG) region, and hippocampal expression of synaptic markers were analyzed. Data were analyzed by ANOVA and repeated-measures ANOVA. ODA (0.566-1.31 mg/L) was the most abundant FAM in breast milk, followed by palmitamide (0.135-0.269 mg/L) and linoleamide (0.046-0.242 mg/L). Compared with the control group, the H-ODA group demonstrated shorter escape latency, shorter travel distance, 113% more platform crossing, and 48% greater discrimination index in behavioral tests (P < 0.05). Additionally, the H-ODA group showed a higher density of 5-ethynyl-2'-deoxyuridine (EdU)+ and EdU+& doublecortin (DCX)+ cells (62% and 53%, respectively), and 52% greater spine density in the DG region than the control group (P < 0.05). The synaptic markers, postsynaptic density protein 95 (PSD95) and synaptophysin (SYP), were upregulated in the H-ODA group compared with the control group (P < 0.05). The L-ODA group also showed shorter escape latency in behavioral tests and 27% greater spine density in the DG region than the control group (P < 0.05). ODA is the most common FAM in human milk. ODA supplementation during suckling promotes learning and memory-related abilities in adolescent mice by augmenting hippocampal neuronal proliferation and boosting synaptic plasticity.


The plasminogen activator inhibitor-1 paradox in cancer: a mechanistic understanding.
The paradoxical pro-tumorigenic function of plasminogen activator inhibitor 1 (PAI-1, aka Serpin E1) in cancer progression and metastasis has been the subject of an abundant scientific literature that has pointed to a pro-angiogenic role, a growth and migration stimulatory function, and an anti-apoptotic activity, all directed toward promoting tumor growth, cancer cell survival, and metastasis. With uPA, PAI-1 is among the most reliable biomarkers and prognosticators in many cancer types. More recently, a novel pro-tumorigenic function of PAI-1 in cancer-related inflammation has been demonstrated. These multifaceted activities of PAI-1 in cancer progression are explained by the complex structure of PAI-1 and its multiple functions that go beyond its anti-fibrinolytic and anti-plasminogen activation activities. However, despite the multiple evidences supporting a pro-tumorigenic role of PAI-1 in cancer, and the development of several inhibitors, targeting PAI-1, has remained elusive. In this article, the various mechanisms responsible for the pro-tumorigenic functions of PAI-1 are reviewed with emphasis on its more recently described contribution to cancer inflammation. The challenges of targeting PAI-1 in cancer therapy are then discussed.


Energy Expenditure, Body Composition, and Skeletal Muscle Oxidative Capacity in Patients with Myotonic Dystrophy Type 1.
Myotonic dystrophy type 1 (DM1) patients are at risk for metabolic abnormalities and commonly experience overweight and obesity. Possibly, weight issues result from lowered resting energy expenditure (EE) and impaired muscle oxidative metabolism. This study aims to assess EE, body composition, and muscle oxidative capacity in patients with DM1 compared to age-, sex- and BMI-matched controls. A prospective case control study was conducted including 15 DM1 patients and 15 matched controls. Participants underwent state-of-the-art methodologies including 24 h whole room calorimetry, doubly labeled water and accelerometer analysis under 15-days of free-living conditions, muscle biopsy, full body magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DEXA), computed tomography (CT) upper leg, and cardiopulmonary exercise testing. Fat ratio determined by full body MRI was significantly higher in DM1 patients (56 [49-62] %) compared to healthy controls (44 [37-52] % ; p = 0.027). Resting EE did not differ between groups (1948 [1742-2146] vs (2001 [1853-2425>] kcal/24 h, respectively; p = 0.466). In contrast, total EE was 23% lower in DM1 patients (2162 [1794-2494] vs 2814 [2424-3310] kcal/24 h; p = 0.027). Also, DM1 patients had 63% less steps (3090 [2263-5063] vs 8283 [6855-11485] steps/24 h; p = 0.003) and a significantly lower VO2 peak (22 [17-24] vs 33 [26-39] mL/min/kg; p = 0.003) compared to the healthy controls. Muscle biopsy citrate synthase activity did not differ between groups (15.4 [13.3-20.0] vs 20.1 [16.6-25.8] μM/g/min, respectively; p = 0.449). Resting EE does not differ between DM1 patients and healthy, matched controls when assessed under standardized circumstances. However, under free living conditions, total EE is substantially reduced in DM1 patients due to a lower physical activity level. The sedentary lifestyle of DM1 patients seems responsible for the undesirable changes in body composition and aerobic capacity.


A hypothesis on the role of pheromones on age of menarche.
Over the last century and a half there has been a secular decline in the age of menarche in Western, industrialized cultures. This trend has been largely ascribed to improved nutrition and health, and we offer an alternative hypothesis that changes in socio-economic conditions have resulted in changes in the pheromonal climate to which prepubertal females are exposed, thereby affecting onset of menarche. Extensive data from non-human mammalian studies indicate that puberty in females is delayed by exposure to adult females, and accelerated by exposure to adult males. The mechanism is pheromonal. The pheromonal climate of the home may have changed since mothers are in the home less (more women now work) and fathers are in the home more (work day of 8 rather than 14 hr). Assuming humans respond similarly to pheromones, this change would contribute to a decline in age of menarche.


Inhibition of replication and transcription activator and latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus by morpholino oligomers.
Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma and primary effusion lymphoma (PEL). The KSHV replication and transcription activator (RTA) and latency-associated nuclear antigen (LANA) play key roles in activating KSHV lytic replication and maintaining KSHV latency, respectively. Phosphorodiamidate morpholino oligomers (PMO) are similar to short single-stranded DNA oligomers, but possess a modified backbone that confers highly specific binding and resistance to nucleases. In this study, RTA and LANA mRNA in PEL cells were targeted by antisense peptide-conjugated PMO (P-PMO) in an effort to suppress KSHV replication. Highly efficient P-PMO uptake by PEL cells was observed. Treatment of PEL cells with a RTA P-PMO (RP1) reduced RTA expression in a dose-dependent and sequence-specific manner, and also caused a significant decrease in several KSHV early and late gene products, including vIL-6, vIRF-1, and ORF-K8.1A. KSHV viral DNA levels were reduced both in cells and culture supernatants of RP1 P-PMO-treated cells, indicating that KSHV lytic replication was suppressed. Treatment of BCBL-1 cells with P-PMO against LANA resulted in a reduction of LANA expression. Cell viability assays detected no cytotoxicity from P-PMO alone, within the concentration range used for the experiments in this study. These results suggest that RP1 P-PMO can specifically block KSHV replication, and further study is warranted.


A rapid and accurate quantification method for real-time dynamic analysis of cellular lipids during microalgal fermentation processes in Chlorella protothecoides with low field nuclear magnetic resonance.
The rapid and real-time lipid determination can provide valuable information on process regulation and optimization in the algal lipid mass production. In this study, a rapid, accurate and precise quantification method of in vivo cellular lipids of Chlorella protothecoides using low field nuclear magnetic resonance (LF-NMR) was newly developed. LF-NMR was extremely sensitive to the algal lipids with the limits of the detection (LOD) of 0.0026g and 0.32g/L in dry lipid samples and algal broth, respectively, as well as limits of quantification (LOQ) of 0.0093g and 1.18g/L. Moreover, the LF-NMR signal was specifically proportional to the cellular lipids of C. protothecoides, thus the superior regression curves existing in a wide detection range from 0.02 to 0.42g for dry lipids and from 1.12 to 8.97gL(-1) of lipid concentration for in vivo lipid quantification were obtained with all R(2) higher than 0.99, irrespective of the lipid content and fatty acids profile variations. The accuracy of this novel method was further verified to be reliable by comparing lipid quantification results to those obtained by GC-MS. And the relative standard deviation (RSD) of LF-NMR results were smaller than 2%, suggesting the precision of this method. Finally, this method was successfully used in the on-line lipid monitoring during the algal lipid fermentation processes, making it possible for better understanding of the lipid accumulation mechanism and dynamic bioprocess control.


Restoration of sensibility in fingers repaired with free sensory flaps from the toe.
The sensibility of 25 fingers reconstructed with three different types of free sensory flaps from the toe was evaluated. The relationships between sensory restoration and the patient's age, type of sensory flap, selection of sutured nerves, and circulatory complications in the flap were analyzed. Wrap-around flaps were used in 5 fingers, hemipulp flaps in 11, and toe-to-finger transfers in 9. The follow-up period ranged from 16 to 79 months. Restoration of sensibility in the flap was closely related to the patient's age and vascular insufficiency of the flap. Therefore, establishing and maintaining and adequate circulation in the flap at operation is essential for good sensory restoration.


Effect of atmospheric factors on the incidence of Bell's palsy.
To assess the possible influence of atmospheric factors on the incidence of Bell's palsy, a retrospective case review of patients seen between 1 January 1992 and 30 June 1996, was designed. The population included all Bell's palsy patients in whom the exact date of onset of paralysis (day, month, year) was known. The following parameters were registered daily by the Spanish National Service of Meteorology throughout the period of survey: temperature, atmospheric pressure and air pollutants (total number of particles and levels of SO2, CO, O3, NO2, NO, CH4 and total organic carbon). The only factor significantly related to Bell's palsy was temperature (P = 0.0164). Lower temperatures were associated with a higher incidence of Bell's palsy. A relationship between atmospheric pressure and/or air pollutants and Bell's palsy was not found.


Split-bolus single scan CTA for evaluation of mesenteric ischemia.
To evaluate split-bolus single scan CTA protocol for evaluation of acute mesenteric ischemia. In this HIPAA-compliant IRB-approved study, consecutive patients evaluated for mesenteric ischemia between 11/2015 and 10/2016 were included. Patients scanned prior to 4/2016 were scanned with multiphasic CTA protocol and after with split-bolus single scan CTA. Objective and subjective evaluation was performed by three board-certified readers. Findings were correlated to composite clinical reference outcome. Eighty patients were included: 40 with split-bolus and 40 with multiphasic CTA protocol with similar age (60.3 ± 16.2 years vs. 64.7 ± 17.0 years, p = 0.19) and BMI (28.0 ± 6.7 vs. 27.0 ± 8.7, p = 0.56). SMA attenuation was higher in multiphasic protocol compared to split-bolus protocol (336.5 ± 97.5 HU vs. 258.0 ± 67.3 HU, p < 0.001) with similar SMV attenuation (multiphasic 213.7 ± 58.4 HU vs. split-bolus 194.2 ± 52.2 HU, p = 0.14). Optimal phase of bowel, liver, and spleen enhancement was seen in similar high proportion (94-99%) in both protocols. There were 8/40 (20%) positive cases of mesenteric ischemia in each group. There was no difference in the diagnostic confidence of the readers for evaluation of the mesenteric vessels and bowel ischemia. There were no missed cases of mesenteric ischemia in either group. Mean effective dose was 42% lower in the split-bolus group, p < 0.001. There was a higher number of axial images to review in multiphasic protocol compared to split-bolus protocol (437.9 ± 48.7 vs. 263.5 ± 31.2, p < 0.001). The split-bolus protocol for evaluation of mesenteric ischemia is clinically feasible with confident and accurate diagnostic ability, while reducing number of images and decreasing radiation exposure to the patient.


Transcatheter treatment of life-threatening lower gastrointestinal bleeding due to advanced pelvic malignancy.
We present two patients with life-threatening, massive, lower gastrointestinal (GI) bleeding and locally advanced cervical carcinoma. Selective pelvic arteriography demonstrated that the site of bleeding originated from a pseudoaneurysm of the right internal iliac artery with fistulous communication to the sigmoid colon in one patient and from the left internal iliac artery into the rectum in the second patient. Transcatheter embolotherapy was then performed using balloon occlusion in one patient and coil embolization in the second patient. The iliac arteries should also be evaluated in patients with pelvic cancer who present with lower GI bleeding.


Gsslasso Cox: a Bayesian hierarchical model for predicting survival and detecting associated genes by incorporating pathway information.
Group structures among genes encoded in functional relationships or biological pathways are valuable and unique features in large-scale molecular data for survival analysis. However, most of previous approaches for molecular data analysis ignore such group structures. It is desirable to develop powerful analytic methods for incorporating valuable pathway information for predicting disease survival outcomes and detecting associated genes. We here propose a Bayesian hierarchical Cox survival model, called the group spike-and-slab lasso Cox (gsslasso Cox), for predicting disease survival outcomes and detecting associated genes by incorporating group structures of biological pathways. Our hierarchical model employs a novel prior on the coefficients of genes, i.e., the group spike-and-slab double-exponential distribution, to integrate group structures and to adaptively shrink the effects of genes. We have developed a fast and stable deterministic algorithm to fit the proposed models. We performed extensive simulation studies to assess the model fitting properties and the prognostic performance of the proposed method, and also applied our method to analyze three cancer data sets. Both the theoretical and empirical studies show that the proposed method can induce weaker shrinkage on predictors in an active pathway, thereby incorporating the biological similarity of genes within a same pathway into the hierarchical modeling. Compared with several existing methods, the proposed method can more accurately estimate gene effects and can better predict survival outcomes. For the three cancer data sets, the results show that the proposed method generates more powerful models for survival prediction and detecting associated genes. The method has been implemented in a freely available R package BhGLM at https://github.com/nyiuab/BhGLM .


Epidemiology of healthcare associated infections in Germany: Nearly 20 years of surveillance.
To describe the epidemiology of healthcare-associated infections (HAI) in hospitals participating in the German national nosocomial infections surveillance system (KISS). The epidemiology of HAI was described for the surveillance components for intensive care units (ITS-KISS), non-ICUs (STATIONS-KISS), very low birth weight infants (NEO-KISS) and surgical site infections (OP-KISS) in the period from 2006 to 2013. In addition, risk factor analyses were performed for the most important infections of ICU-KISS, NEO-KISS and OP-KISS. Data from a total of 3,454,778 ICU patients from 913 ICUs, 618,816 non-ICU patients from 142 non-ICU wards, 53,676 VLBW from 241 neonatal intensive care units (NICU) and 1,005,064 surgical patients from operative departments from 550 hospitals were used for analysis. Compared with baseline data, a significant reduction of primary bloodstream infections (PBSI) and lower respiratory tract infections (LRTI) was observed in ICUs with the maximum effect in year 5 (or longer participation) (incidence rate ratio 0.60 (CI95 0.50-0.72) and 0.61 (CI95 0.52-0.71) respectively). A significant reduction of PBSI and LRTI was also observed in NEO-KISS when comparing the baseline situation with the 5th year of participation (hazard ratio 0.70 (CI95 0.64-0.76) and 0.43 (CI95 0.35-0.52)). The effect was smaller in operative departments after the introduction of OP-KISS (OR 0.80; CI95 0.64-1.02 in year 5 or later for all procedure types combined). Due to the large database, it has not only been possible to confirm well-known risk factors for HAI, but also to identify some new interesting risk factors like seasonal and volume effects. Participating in a national surveillance system and using surveillance data for internal quality management leads to substantial reduction of HAI. In addition, a surveillance system can identify otherwise not recognized risk factors which should - if possible - be considered for infection control management and for risk adjustment in the benchmarking process.


Utility of the ovariectomized rat as a model for human osteoporosis in drug discovery.
Ovariectomy-induced osteopenia in the rat produces skeletal responses similar to that in a post-menopausal woman. In the ovariectomized (ovx) rat, high bone turnover, and subsequent bone loss, like in the human post-menopausal condition, can be prevented by estrogen replacement. Because of the striking resemblance of skeletal responses in humans and rats in the state of estrogen deficiency, the ovx rat is considered to be a gold standard model for evaluating drugs for prevention and reversal of osteoporosis. This chapter describes the procedure for performing ovariectomy on the rat and the utility of the ovx rat model we have utilized over the last two decades in our laboratory.


Adult brainstem gliomas: Correlation of clinical and molecular features.
Brainstem gliomas are rare in adults and overall have superior survival outcomes compared to pediatric brainstem gliomas. We conducted a retrospective data and tissue analysis of all adult patients (≥ 18 years old) with World Health Organization (WHO) Grade II, III, and IV brainstem gliomas in the University of Texas MD Anderson Cancer Center institutional database from 1990 to 2012. We identified 143 cases in adults ages 18 and over. There were 28 glioblastomas, 43 anaplastic astrocytomas, 15 diffuse astrocytomas, and 11 gliomas not otherwise specified, and in 46 cases the diagnosis was made radiographically. 128 (89.5%) cases were classified radiographically as diffuse and of the focal tumors, 9 of the 15 were WHO Grade III or IV tumors. Increasing tumor grade and contrast enhancement were associated with significantly reduced overall survival. The median overall survival for the entire cohort was 32.1 months similar to previously published studies. Two of 25 grade II and III tumors, and 1 of 17 glioblastomas had IDH1 mutations on immunohistochemical testing. Nine cases had sufficient tissue for mutation profiling, 1 case had a BRAF V600E mutation and 2 had 2 PIK3CA mutations. Survival outcomes for adult WHO Grade II to IV brainstem gliomas were similar to supratentorial IDH1 wild-type tumors of similar grade and histology. Potentially actionable mutations can be identified from small biopsy samples in a subset of adult brainstem gliomas.


Radiographic characterisation of spinal curvature development in farmed New Zealand Chinook salmon Oncorhynchus tshawytscha throughout seawater production.
Spinal anomalies are a recognised source of downgrading in finfish aquaculture, but identifying their cause(s) is difficult and often requires extensive knowledge of the underlying pathology. Late-onset spinal curvatures (lordosis, kyphosis, scoliosis) can affect up to 40% of farmed New Zealand Chinook (king) salmon (Oncorhynchus tshawytscha) at harvest, but little is known about their pathogenesis. Curvature development was radiographically documented in two related cohorts of commercially-farmed Chinook salmon throughout seawater production to determine (1) the timing of radiographic onset and relationships between (2) the curvature types, (3) the spinal regions in which they develop and (4) their associations with co-existing vertebral body anomalies (vertebral compression, fusion and vertical shift). Onset of curvature varied between individuals, but initially occurred eight months post-seawater transfer. There were strong associations between the three curvature types and the four recognised spinal regions: lordosis was predominantly observed in regions (R)1 and R3, kyphosis in R2 and R4, manifesting as a distinct pattern of alternating lordosis and kyphosis from head to tail. This was subsequently accompanied by scoliosis, which primarily manifested in spinal regions R2 and R3, where most of the anaerobic musculature is concentrated. Co-existing vertebral body anomalies, of which vertebral compression and vertical shift were most common, appeared to arise either independent of curvature development or as secondary effects. Our results suggest that spinal curvature in farmed New Zealand Chinook salmon constitutes a late-onset, rapidly-developing lordosis-kyphosis-scoliosis (LKS) curvature complex with a possible neuromuscular origin.


[The lymphocyte transformation test in patients with recurrent herpes simplex diseases (author's transl)].
The in vivo stimulation of lymphocytes was used to assess cell mediated immunity to herpes simplex virus (hsv) in patients with recurrent skin eruptions caused by this virus. 1. Phytohaemagglutinine stimulation of lymphocytes was normal in all examined patients. There was no difference in the PHA-stimulation of a control group. 2. Specific lymphocytes stimulation by hsv-antigen may be regarded as a sensitive parameter for a previous hsv-infection. 3. In 6 patients with severe infections of hsv type I or II and more than 10 recurrences per year we found a lower stimulation than in patients with occasionally (up to 10 times a year) skin eruptions. 4. An antigen used as vaccine, Lupidon H, ten times more concentrated (100,000 EID/ml) than the commercially available antigen is able to stimulate lymphocytes in vitro.


Successful treatment of Aspergillus peritonitis in a peritoneal dialysis patient.
Aspergillus peritonitis is a rare, potentially fatal complication of continuous ambulatory peritoneal dialysis (CAPD). We report the successful treatment of refractory fungal peritonitis in an 8-year-old girl treated by peritoneal dialysis for 3.3 years. This is the second report of Aspergillus thermomutatus(telemorph: Neosartorya pseudofischeri) in humans. Comprehensive treatment included early removal of the CAPD catheter, the use of liposomal amphotericin B, and the use of itraconazole.


Enhancement of the embryotoxicity of acrolein, but not phosphoramide mustard, by glutathione depletion in rat embryos in vitro.
The intracellular thiol glutathione is known to protect cells against the toxicity of certain drugs and reactive intermediates. In this study, the role of glutathione in protecting the embryo against two embryolethal and teratogenic metabolites of cyclophosphamide, and anticancer drug, was assessed in vitro using the rat whole embryo culture system. Day 10.5 rat embryos were cultured in rat serum medium containing phosphoramide mustard (1, 10, or 25 microM) or acrolein (10, 25, 50 or 100 microM), with and without buthionine sulfoximine (10 or 100 microM), a compound which depletes glutathione by inhibiting its synthesis. After 45 hr, embryos were assessed for viability, malformations, growth and development, and the glutathione content of embryos exposed to buthionine sulfoximine alone was assayed. The glutathione levels of the embryos and their yolk sacs were decreased significantly by 100 microM buthionine sulfoximine, whereas 10 microM buthionine sulfoximine decreased glutathione levels in the yolk sacs only. Phosphoramide mustard alone, at concentrations of 10 and 25 microM, did not produce embryo deaths but did cause malformations and growth retardation in 100% of the exposed embryos. The addition of buthionine sulfoximine (100 microM) had no effect on the teratogenicity or growth-retarding effects of phosphoramide mustard. Acrolein alone produced a 25 and 48% incidence of embryo deaths at 50 and 100 microM, respectively, and a 46% incidence of embryo malformations, as well as significant growth retardation, among the surviving embryos at 100 microM. Buthionine sulfoximine (10 or 100 microM) significantly enhanced the embryotoxic effects of acrolein. The addition of 10 microM buthionine sulfoximine resulted in 100% embryolethality at 100 microM acrolein; this buthionine sulfoximine concentration decreased the EC50 values for embryo deaths and malformations to 50% of those for acrolein alone. The addition of 100 microM butionine sulfoximine significantly potentiated the embryolethality of acrolein at 25, 50 and 100 microM; the combination of 100 microM acrolein plus 100 microM buthionine sulfoximine was 100% embryolethal. The incidence of embryo malformations was enhanced significantly at 10 and 25 microM acrolein by 100 microM buthionine sulfoximine. The EC50 values for embryo deaths and malformations were decreased to 50 and 20%, respectively, of those values for acrolein alone. Both butionine sulfoximine concentrations produced significant growth retardation at all acrolein concentrations compared to either acrolein or buthionine sulfoximine alone.(ABSTRACT TRUNCATED AT 400 WORDS)