The selectivity of beta-adrenoceptor antagonists on cardiovascular and bronchodilator responses to isoprenaline in the anaesthetized dog.
1 The actions of five beta-adrenoceptor antagonists, chosen because of reported differences in their selectivities, were compared using the positive chronotropic, vasodepressor and bronchodilator responses to isoprenaline in anesthetized dogs. 2 Propranolol was a potent antagonist of the isoprenaline responses in all three systems. 3 Practolol and acebutolol (M & B 17,803) blocked the positive chronotropic responses to isoprenaline to a greater extent than the vasodepressor or bronchodilator responses. 4 Butoxamine and alpha-methyl dichloroisoprenaline showed the opposite selectivity, blocking the vasodepressor and bronchodilator responses to isoprenaline to a greater extent than positive chronotropic responses. However, both drugs were considerably less potent than the other antagonists studied and their selectivities were less clear-cut than those of practolol or acebutolol. 5 All the antagonists lowered the resting heart rate and to a lesser extent the diastolic blood pressure. The effects of propranolol, practolol and acebutolol on heart rate probably result from cardiac beta-adrenoceptor blockade. With butoxamine and alpha-methyl dichloro isoprenaline, however, the effects on heart rate probably result from a direct cardiodepressant action. 6 The relevance of the results to the problem of the sub-classification of beta-adrenoceptors is discussed.


Increased susceptibility of HIF-1α heterozygous-null mice to cardiovascular malformations associated with maternal diabetes.
Cardiovascular malformations are the most common manifestation of diabetic embryopathy. The molecular mechanisms underlying the teratogenic effect of maternal diabetes have not been fully elucidated. Using genome-wide expression profiling, we previously demonstrated that exposure to maternal diabetes resulted in dysregulation of the hypoxia-inducible factor 1 (HIF-1) pathway in the developing embryo. We thus considered a possible link between HIF-1-regulated pathways and the development of congenital malformations. HIF-1α heterozygous-null (Hif1a(+/-)) and wild type (Wt) littermate embryos were exposed to the intrauterine environment of a diabetic mother to analyze the frequency and morphology of congenital defects, and assess gene expression changes in Wt and Hif1a(+/-) embryos. We observed a decreased number of embryos per litter and an increased incidence of heart malformations, including atrioventricular septal defects and reduced myocardial mass, in diabetes-exposed Hif1a(+/-) embryos as compared to Wt embryos. We also detected significant differences in the expression of key cardiac transcription factors, including Nkx2.5, Tbx5, and Mef2C, in diabetes-exposed Hif1a(+/-) embryonic hearts compared to Wt littermates. Thus, partial global HIF-1α deficiency alters gene expression in the developing heart and increases susceptibility to congenital defects in a mouse model of diabetic pregnancy.


Job burnout and its impact on work ability in biosafety laboratory staff during the COVID-19 epidemic in Xinjiang.
The coronavirus disease 2019 (COVID-19) has increased the physical and psychological stress of medical workers. This study was designed to investigate the prevalence and risk factors of job burnout and its impact on work ability among Biosafety Laboratory (BSL) staffs during the COVID-19 epidemic in Xinjiang. A total of 7911 qualified BSL staffs in Xinjiang were investigated by electronic questionnaires. The Maslach Burnout Inventory-General Survey (MBI-GS) was used for job burnout survey. Work Ability Index (WAI) was used for work ability survey. The prevalence and risk factors of job burnout in BSL staffs were analyzed through chi square test, t-test and one-way ANOVA. And then, the influence of demographic and job-related variables, i.e., confounding factors, were eliminated to the greatest extent by the propensity score analysis (PSA) method, to investigate the impact of job burnout on work ability in BSL staffs. A total of 67.6% BSL staffs experienced job burnout. There were significant differences in the detection rate of job burnout among demographic and job-related variables, including gender, age, ethnicity, education, working years, professional title, marital status, number of night shift per month and overall sleep condition (all P < 0.05). The detection rate of job burnout in female was higher than that in male. The detection rates of job burnout in 45-50 years old, Han ethnicity, education of postgraduate or above, 11-20 years of working, intermediate professional title, married, staff with many night shifts per month and poor overall sleep condition were higher than that of other groups. The average burnout scores of the Emotional Exhaustion (EE), Cynicism (CY), Reduced Personal Accomplishment (PA) scale were 10.00 ± 5.99, 4.64 ± 4.59 and 15.25 ± 8.16, respectively. Multiple logistic regression analysis showed that the three dimensions of job burnout, i.e., EE, CY, PE, were negatively correlated with work ability and significantly affected the work ability of BSL staffs (all P < 0.001). Our results suggest that the prevalence of job burnout is extremely common among BSL staffs. In addition, the work ability decreases with the increase of job burnout and the improvement of job burnout can enhance work ability among BSL staffs.


Violent trauma recidivism: Does all violence escalate?
Rates of trauma patients presenting with history of prior trauma range from 25 to 44%. Outcomes involving recidivists in the setting of intentional trauma, especially penetrating trauma, are conflicting. We hypothesized that if violence does escalate with successive incidence, then injuries due to successive violence should escalate or become increasingly severe with successive admissions. The trauma registry from an urban level I adult and pediatric trauma center was queried for injuries due to blunt assault, stabbing, and firearm injury. Primary outcome measures were mortality, injury mechanism, and injury severity for each successive trauma admission. Victims of blunt assault and stabbing were more likely to become recidivists than victims of gun violence (OR 1.53, p < 0.001 and OR 1.57, p < 0.001). Violent re-injury became increasingly severe only in victims of repeated gun violence. Patients with gunshot as the mechanism at every admission are at highest risk for mortality (OR 13.48, p < 0.001). All but one mortality (95.8%) in the recidivist population occurred within 180 days of discharge from a prior injury. Recidivism for interpersonal violence results in a significant number of admissions to trauma centers. In our patient cohort, injury associated with successive blunt assaults did not worsen with subsequent admissions. Recidivism for gunshot wounds tends to be more severe and have a worse prognosis with each successive admission compared to outcomes associated with repeated stab wounds. Focused efforts should include rehabilitation efforts early in the post-injury period, especially in patients with a history of gunshot wounds.


The apoptotic action of estrogen following exhaustive antihormonal therapy: a new clinical treatment strategy.
Long-term antihormonal therapy is effective at controlling the recurrence of estrogen receptor (ER)-positive breast cancer, but there may be unanticipated consequences for the development of new forms of drug resistance. Laboratory studies of exhaustive antihormonal therapy demonstrate there are at least two phases of resistance to selective ER modulators (SERMs; tamoxifen and raloxifene) and to estrogen withdrawal (aromatase inhibitors). In Phase I drug resistance, estrogen or a SERM promote tumor growth, but in Phase II drug resistance estrogen induces apoptosis. Understanding of the new biology of estrogen action has clinical relevance. There are paradoxical interactions between fulvestrant and postmenopausal levels of estrogen that cause robust growth of Phase II tamoxifen resistance or autonomous aromatase-resistant tumors. These new data suggest a rational approach for the treatment of patients with ER-positive breast cancer that have failed exhaustive antihormonal treatment. Low-dose estrogen could be used to debulk patients followed by fulvestrant in a low estrogen environment (aromatase treatment) to maintain tumor control.


Effects of ω-3 Fatty Acids on Toll-like Receptor 4 and Nuclear Factor κB p56 in the Pancreas of Rats With Severe Acute Pancreatitis.
The aims of this study were to determine the effects of ω-3 fatty acids (ω-3FAs) on the Toll-like receptor 4 (TLR4)/nuclear factor κB p56 (NF-κBp56) signaling pathway in the pancreas of rats with severe acute pancreatitis (SAP). Sixty-four Sprague-Dawley rats were randomly divided into 4 groups: the control, SAP-saline, SAP-soybean oil, and SAP-ω-FA groups. Severe acute pancreatitis was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the pancreas was evaluated by immunohistochemistry and Western blot analysis. The levels of the proinflammatory cytokines interleukin 6 and tumor necrosis factor α in the pancreas were measured by enzyme-linked immunosorbent assays. Toll-like receptor 4, NF-κBp56, and inflammatory cytokine expression in the pancreas was increased significantly in the SAP group compared with that in the control group (P < 0.05), but was significantly decreased in the ω-3FA group compared with that in the soybean oil group at 24 and 48 hours (P < 0.05). Our results suggest that during the initial stage of SAP ω-3FAs could efficiently lower the inflammatory response by activating the TLR4/NF-κBp56 signaling pathway.


Hypothalamic volume is associated with body mass index.
The hypothalamus is an important neuroendocrine hub for the control of appetite and satiety. In animal studies it has been established that hypothalamic lesioning or stimulation causes alteration to feeding behaviour and consequently body mass, and exposure to high calorie diets induces hypothalamic inflammation. These findings suggest that alterations in hypothalamic structure and function are both a cause and a consequence of changes to food intake. However, there is limited in vivo human data relating the hypothalamus to obesity or eating disorders, in part due to technical problems relating to its small size. Here, we used a novel automated segmentation algorithm to exploratorily investigate the relationship between hypothalamic volume, normalised to intracranial volume, and body mass index (BMI). The analysis was applied across four independent datasets comprising of young adults (total n = 1,351 participants) spanning a range of BMIs (13.3 - 47.8 kg/m2). We compared underweight (including individuals with anorexia nervosa), healthy weight, overweight and obese individuals in a series of complementary analyses. We report that overall hypothalamic volume is significantly larger in overweight and obese groups of young adults. This was also observed for a number of hypothalamic sub-regions. In the largest dataset (the HCP-Young Adult dataset (n = 1111)) there was a significant relationship between hypothalamic volume and BMI. We suggest that our findings of a positive relationship between hypothalamic volume and BMI is potentially consistent with hypothalamic inflammation as seen in animal models in response to high fat diet, although more research is needed to establish a causal relationship. Overall, we present novel, in vivo findings that link elevated BMI to altered hypothalamic structure. This has important implications for study of the neural mechanisms of obesity in humans.


Diagnostic performance of Strongyloides-specific IgG4 detection in urine for diagnosis of human strongyloidiasis.
Detection of parasite-specific IgG in urine is a sensitive method for diagnosis of strongyloidiasis and gives similar accuracy to serum IgG. However, there are no data concerning detection of IgG subclass in urine. To further explore the utility of diagnosis from urine samples, we evaluated the diagnostic performance of IgG4 in urine compared with parasitological and other immunological methods. The urine and sera included proven strongyloidiasis (group 1, n = 93), other parasitic infections (group 2, n = 40) and parasite negatives (group 3, n = 93). The performance of Strongyloides-specific IgG4 in urine for diagnosis of strongyloidiasis using fecal examinations as the reference standard was assessed. With fecal examination as a gold standard, Strongyloides-specific IgG4 in urine had 91.4% sensitivity and 93.2% specificity while serum IgG4 had 93.6% sensitivity and 91.0% specificity. IgG4 in both urine and serum had almost perfect diagnostic agreements with fecal examination (Cohen's kappa coefficient was > 0.8). Cross-reactivity to Opisthorchis viverrini and Taenia spp. of IgG4 in urine were 7.5% and 12.5% in serum. Concurrent analyses of total IgG in urine and serum showed that the sensitivities (97.9-100%) and specificities (88.7-91.0%) were similar (P > 0.05). The sensitivity for parasitological examination by the formalin-ethyl acetate concentration technique (FECT) was 49.5% and that for agar plate culture technique (APC) it was 92.6%. Our findings showed that specific IgG4 detection in urine yielded similar diagnostic performance to the same biomarkers in serum. This suggests that accurate diagnosis of strongyloidiasis can be performed using urine samples and IgG4 is a valid choice of diagnostic marker. Further assessment is required to assess the utility of urine IgG4 for measuring the response treatment in strongyloidiasis.


Medical Comorbidities of Dementia: Links to Caregivers' Emotional Difficulties and Gains.
To evaluate how eight major medical comorbidities of dementia (arthritis, cancer, diabetes, heart disease, hypertension, lung disease, osteoporosis, and stroke) are associated with caregivers' perceptions of emotional caregiving difficulties and caregiving gains (ie, benefits or rewards from the care role). Nationally representative cross-sectional surveys of community-dwelling persons living with dementia (PLWDs) and their co-resident family caregivers in the United States. The 2011 National Health and Aging Trends Study and National Study of Caregiving. Total of 356 co-resident family caregivers of community-dwelling PLWDs. Caregivers' sociodemographic and health characteristics, caregiving stressors, emotional caregiving difficulties, caregiving gains, and chronic health conditions of PLWDs. Caregivers most commonly cared for a PLWD with arthritis (65.5%), followed by hypertension (64.9%), diabetes (30.1%), stroke (28.8%), osteoporosis (27.1%), heart disease (23.3%), cancer (21.5%), and lung disease (17.2%). Logistic regressions revealed that caregivers were 2.63 and 2.32 times more likely to report higher than median emotional caregiving difficulties when PLWDs had diagnoses of diabetes and osteoporosis, respectively, controlling for caregiver sex, relationship to the PLWD (spouse vs non-spouse), educational attainment, self-rated health, and assistance with activities of daily living and medical care activities. Caregivers were also 2.10 times more likely to report lower than median caregiving gains when PLWDs had a diagnosis of osteoporosis. Comorbid health conditions among PLWDs have distinct implications for caregiving outcomes. Clinical care and interventions to improve the well-being of both care dyad members should support caregivers in managing medical comorbidities of dementia. J Am Geriatr Soc 68:609-613, 2020.


The use of methyl methacrylate bone cement as an internal splint in the treatment of fractures of the canine axis.
Three dogs with fractures of the body of the axis showing moderate to severe displacement were presented for treatment. The fractures were exposed, screws were fixed into each fragment and the heads of the screws were embedded in bone cement to serve as an internal splint. The surgical approach and technique are described.


Crystal structure analysis reveals how the Chordin family member crossveinless 2 blocks BMP-2 receptor binding.
Crossveinless 2 (CV-2) is an extracellular BMP modulator protein belonging to the Chordin family. During development it is expressed at sites of high BMP signaling and like Chordin CV-2 can either enhance or inhibit BMP activity. CV-2 binds to BMP-2 via its N-terminal Von Willebrand factor type C (VWC) domain 1. Here we report the structure of the complex between CV-2 VWC1 and BMP-2. The tripartite VWC1 binds BMP-2 only through a short N-terminal segment, called clip, and subdomain (SD) 1. Mutational analysis establishes that the clip segment and SD1 together create high-affinity BMP-2 binding. All four receptor-binding sites of BMP-2 are blocked in the complex, demonstrating that VWC1 acts as competitive inhibitor for all receptor types. In vivo experiments reveal that the BMP-enhancing (pro-BMP) activity of CV-2 is independent of BMP-2 binding by VWC1, showing that pro- and anti-BMP activities are structurally separated in CV-2.


The efficacy and safety of oxandrolone treatment for patients with severe burns: A systematic review and meta-analysis.
The objective of this systematic review and meta-analysis was to evaluate the efficacy and safety of using oxandrolone in patients with severe burns. PubMed, Medline, Ovid, Cochrane Library, Elsevier Science, ProQuest, and Springer Link databases were searched. Randomized trials were included, and clinically important measures were selected. The outcomes were pooled with Revman 5.2. Other outcomes that could not be pooled were described in detail. Finally, 15 randomized controlled trials (RCTs) were identified for analysis in this review, including 806 participants. 1. Mortality, infection, and hepatic function: Oxandrolone therapy did not affect mortality (relative risk (RR)=0.85, 95% confidence interval (CI)=(0.38, 1.89), P=0.69) or infection (RR=0.87, (0.69, 1.11), P=0.26). The two groups (oxandrolone group vs. control group) showed no significant difference in liver dysfunction (RR=1.15, (0.83, 1.59), P=0.41). All the 15 RCTs reported no incidence of hepatic insufficiency in controls or treatment groups. 2. In the catabolic phase: Treatment with oxandrolone shortened length of stay by 3.02 (2.37, 3.66) days, donor-site healing time by 4.41 (3.41, 5.41) days, the time between surgical procedures by 0.63 (0.11, 1.16) days, as well as reduced weight loss by 5 (3.70, 6.30) kg and nitrogen loss by 8.19 (6.87, 9.52) g/day, with all P<0.00001. 3. In the rehabilitative phase: Treatment with oxandrolone shortened the length of stay to 6.45 (4.20, 8.69) days, as well as decreased weight loss by 0.86 (0.76, 0.96) kg/week and reduction of lean body mass by 5% (3.34, 6.66), with all P<0.00001. 4. Long-term parameters: Oxandrolone treatment led to an additional gain in lean body mass of 3.99% (3.08, 4.89) after 6 months and 10.78% (9.92, 11.64) after 12 months in patients with severe burns, with all P<0.00001. The treatment of severe burns with oxandrolone is significantly effective without obvious side effects.


Capturing Three-Dimensional Genome Organization in Individual Cells by Single-Cell Hi-C.
Hi-C is a powerful method to investigate genome-wide, higher-order chromatin and chromosome conformations averaged from a population of cells. To expand the potential of Hi-C for single-cell analysis, we developed single-cell Hi-C. Similar to the existing "ensemble" Hi-C method, single-cell Hi-C detects proximity-dependent ligation events between cross-linked and restriction-digested chromatin fragments in cells. A major difference between the single-cell Hi-C and ensemble Hi-C protocol is that the proximity-dependent ligation is carried out in the nucleus. This allows the isolation of individual cells in which nearly the entire Hi-C procedure has been carried out, enabling the production of a Hi-C library and data from individual cells. With this new method, we studied genome conformations and found evidence for conserved topological domain organization from cell to cell, but highly variable interdomain contacts and chromosome folding genome wide. In addition, we found that the single-cell Hi-C protocol provided cleaner results with less technical noise suggesting it could be used to improve the ensemble Hi-C technique.


Use of propidium iodide staining and flow cytometry to measure anti-mediated cytotoxicity: resolution of complement-sensitive and resistant target cells.
Propidium iodide uptake as an indicator of cell viability was used to measure antibody-mediated cytotoxicity. In conjunction with analysis using the fluorescence-activated cell sorter, this method is as sensitive as isotope release assay systems and has the advantage of gathering multiparameter data on individual cells. This feature enables the resolution of antibody-binding target cells into a population which is sensitive to complement-mediated killing and another population which is resistant to complement-mediated killing.


Suppressant effects of selective 5-HT2 antagonists on rapid eye movement sleep in rats.
The effects of the novel, highly selective serotonin-2 (5-HT2) antagonists, ICI 169,369 and ICI 170,809, on 24 h EEG sleep-wake activity were studied in the rat. Both compounds caused a dose-related increase in the latency to rapid eye movement sleep (REMS) and significantly suppressed cumulative REMS time up to 12 h postinjection. In contrast, neither drug disrupted slow-wave sleep continuity in as much as the latency to non-REMS (NREMS) and cumulative NREMS time were unchanged. However, at the highest dose tested (20 mg/kg) ICI 170,809 did produce a significant increase in total NREMS time during the second half of the sleep-awake cycle. These results demonstrate effects of selective 5-HT2 antagonists on sleep in rats which appear to be specific for REMS behavior, suggesting that the priming influence of serotonin on REMS may involve 5-HT2 receptor subtypes. The relationship between the REMS suppressant actions of these compounds and their consideration as therapeutic agents in depression is discussed.


The effect of 2,3-diphosphoglycerate on the oxygen dissociation curve of human haemoglobin.
1. Oxygen dissociation curves for concentrated human haemoglobin solutions (1.6 mmol dm-3 in haem) have been measured by mixing known quantities of oxy- and deoxyhaemoglobin solutions and measuring the resulting partial pressure of oxygen with an oxygen electrode. 2. Observations in the presence of 2,3-diphosphoglycerate support previous conclusions derived from experiments at low haemoglobin concentrations, the validity of which has been questioned. 3. The two affinity state model of Monod, Wyman & Changeux (1965) does not fully describe the actions of 2,3-diphosphoglycerate and a model in which this allosteric effector not only binds preferentially to the T state but also lowers the oxygen affinity of this state gives an improved fit to the data.


A portable forced oscillation device for respiratory home monitoring.
The increase in the prevalence of chronic respiratory diseases has resulted in a rise in health services provided at home. The forced oscillation technique (FOT) proves to be a useful tool when it is desired to assess lung function noninvasively, and particularly for patients in whom spirometry cannot be applied. As no portable FOT device is currently available, the aim of this study was to design and test a portable FOT system for ambulatory and home care applications. The system devised is based on a microprocessor, which allows online computation of respiratory resistance (Rrs) and reactance (Xrs) and reliability indices. The portable device was compared with a conventional FOT system by using signals from 14 patients with chronic respiratory disease. This device has the same computation capabilities and flexibility as conventional FOT systems and meets the requirements for home application. Rrs (14.2 +/- 6.0 cmH2O x s x L(-1), mean +/- SD) and Xrs (-5.3 +/- 2.7 cmH2O x s x L(-1)) measured at 5 Hz by the portable system virtually coincided with those computed with the reference conventional FOT system: mean differences +/-SD were 0.074 +/- 0.025 and 0.005 +/- 0.009 cmH2O x s x L(-1), respectively. This portable forced oscillation technique device could be a useful tool for monitoring respiratory mechanics in ambulatory and home care applications.


Effects of fluorocarbons with and without oxygen supplementation on cardiac hemodynamics and energetics.
Because of uncertainty about the mechanism by which fluorocarbons ameliorate myocardial ischemia, the effects of a fluorocarbon emulsion, perfluorodecalin and perfluorotripropylamine (Fluosol-DA 20% TM) with and without 100% O2 inhalation, on cardiac hemodynamics and energetics were studied in the anesthetized dog. Left ventricular (LV) intramural partial pressure of oxygen (PmO2) was measured by mass spectrometry before and after intravenous infusion of Fluosol-DA 20% (40 ml/kg), and was compared with measurements made in another group of dogs receiving the volume expander dextran (36 ml/kg). Both groups of dogs were then ventilated with 100% O2 and repeat measurements were performed. In the 11 animals receiving fluorocarbons, there were increases in left atrial pressure, LV myocardial blood flow, and LV myocardial O2 consumption (MVO2) compatible with volume expansion. After 100% O2, LV MVO2 decreased to control values, while PmO2 increased to 127 +/- 48 mm Hg (p less than 0.001). There were no significant changes in heart rate, arterial pressure or first derivative of LV pressure (dP/dt) during the study. In 10 dogs treated with dextran there was no change in heart rate or dP/dt, but arterial and left atrial pressures were higher after dextran infusion and remained elevated after 100% O2 inhalation. LV MVO2 increased with volume expansion, and remained increased after 100% O2. PmO2 (66 +/- 18 mm Hg) after 100% O2 was lower (p less than 0.02) than in the fluorocarbon-treated dogs after O2 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)


Calmodulin binds to a tubulin binding site of the microtubule-associated protein tau.
Previous studies have demonstrated that the microtubule-associated proteins MAP-2 and tau interact selectively with common binding domains on tubulin defined by the low-homology segments alpha (430-441) and beta (422-434). It has been also indicated that the synthetic peptide VRSKIGSTENLKHQPGGG corresponding to the first tau repetitive sequence represents a tubulin binding domain on tau. The present studies show that the calcium-binding protein calmodulin interacts with a tubulin binding site on tau defined by the second repetitive sequence VTSKCGSLGNIHHKPGGG. It was shown that both tubulin and calmodulin bind to tau peptide-Sepharose affinity column. Binding of calmodulin occurs in the presence of 1 mM Ca 2+ and it can be eluted from the column with 4 mM EGTA. These findings provide new insights into the regulation of microtubule assembly, since Ca2+/calmodulin inhibition of tubulin polymerization into microtubules could be mediated by the direct binding of calmodulin to tau, thus preventing the interaction of this latter protein with tubulin.


HLA-A, B, C gene and haplotype frequencies in Vienna. An analysis of family data.
The HLA-A, B, C haplotype frequencies determined through family investigations in 500 unrelated individuals of the Viennese population were calculated, as well as the gene frequencies of 37 HLA determinants and the linkage disequilibria between the three HLA SD loci (HLA-A, HLA-B, and HLA-C). The existence of HLA-A, B, C superhaplotypes could be confirmed.


A Comparison of Liver-Directed Therapy and Systemic Therapy for the Treatment of Liver Metastases in Patients with Gastrointestinal Neuroendocrine Tumors: Analysis of the California Cancer Registry.
To compare the outcomes of patients with gastrointestinal neuroendocrine tumor liver metastases treated with liver-directed therapy (LDT) to those treated with systemic therapy (ST) in a statewide cancer database. A retrospective study was performed of patients with metastatic gastrointestinal tract neuroendocrine tumors treated with either LDT or ST alone between the years 2000-2012 in the California Cancer Registry. Overall survival and disease-specific survival were assessed using multivariable Cox proportional hazards analysis and propensity score matching. A total of 154 patients (ST, n = 87 and LDT, n = 67) were studied. The median overall survival and disease-specific survival for patients that received ST was 29 and 35 months versus 51 and >60 months for patients that received LDT. On multivariate analysis, LDT and the resection of the primary tumor were associated with improved survival (hazard ratio [HR] 0.52, P = .002; HR 0.43, P = .001). Non-white race, Medicaid/uninsured status, and the presence of lung metastases were associated with poor survival (HR 1.76, P = .014; HR 2.29, P = .009; and HR 1.79, P = .031). Propensity score matching demonstrated an improvement in disease-specific survival for LDT compared to ST (HR 0.53, P = .036). The improvement in overall survival on propensity score matching did not achieve statistical significance (HR 0.70, P = .199). LDT is associated with improved overall and disease-specific survival as compared to ST in patients with gastrointestinal neuroendocrine tumor liver metastases. Further investigation is needed to determine whether combination or sequential treatment can improve outcomes in this population.


Study on the susceptibility of Sahel goats to experimental Trypanosoma vivax infection.
Sahel goats, also known as Borno whites are found in the northern semi-arid, tsetse free Sahel region of Nigeria. They are transported alongside cattle from this zone to all other zones in the country, including the tsetse-infested zones, for commercial purposes and are kept for some time in these tsetse-infested zones until they are sold. This study therefore assessed the susceptibility of this breed of goats to trypanosome infection and its response to treatment with Berenil. Six bucks were inoculated intravenously with Trypanosoma vivax through the jugular vein while two served as uninfected control. The mean pre-patent period was 4.5 days and increasing parasitaemia followed the establishment of infection. Onset of parasitaemia was associated with increase in rectal temperature in all the infected goats and the temperature peak coincided with the only parasitaemic peak second week post-infection. The infected goats were treated with Berenil (Hoechst, Germany) 3.5mg/kg body weight at 4 weeks post-infection. The packed cell volume (PCV) continued to fall from a mean 30.73+/-0.01% pre-infection to a mean 13.21+/-0.18% at 1 week post-treatment. Deaths were recorded for 4 of the infected goats 1 week post-treatment while the remaining two died 2 weeks post-treatment, not responding to treatment.


[Genetic diversity of populations of the earthworm Lumbricus rubellus (Hoffm.) (Oligochaeta, Lumbricidae)].
The genetic diversity of Lumbricus rubellus Hoffm. earthworms collected in different parts of the Moscow and Kiev regions was studied by means of electrophoresis in polyacrylamide gel, using the loci encoding unspecific esterases and generic proteins as biochemical-genetic markers. A considerable diversity of samples in all alleles of these loci was revealed. With respect to allele frequencies of the locus My1, the samples from the Moscow and Kiev regions formed two genetically distinct spatial groups. Within these groups, the samples were genetically heterogeneous, and each of them could be regarded as an individual population.


Input parameters in a one-dimensional neuronal model with reversal potentials.
An equation for a stochastic neuronal model describing the initiation of action potentials is studied for the case in which the depolarization of the membrane potential is restricted by the reversal potentials. It is assumed that the values of the membrane potential can be continuously recorded between consecutive spikes. Under this assumption, the estimators of the model parameters are derived and the methods for testing the model are proposed. The objective of the methods presented in this contribution is to provide neuroscientists with quantitative means in order to estimate parameters of stochastic neuronal models.


Deregulation of the phosphatidylinositol-3 kinase signaling cascade is associated with neurodegeneration in Npc1-/- mouse brain.
Niemann-Pick type C (NPC) disease is caused by mutations to genes that encode proteins critical to intracellular lipid homeostasis. The events underlying NPC progressive neurodegeneration are poorly understood but include neurofibrillary tangles of the type found in Alzheimer's disease. Here we investigated possible contributions of a phosphatidylinositol-3 kinase cascade [PI3K, Akt, glycogen synthase kinase-3beta (GSK-3beta)] that is linked to apoptosis and various degenerative conditions. Brain concentrations of phosphorylated Akt, which phosphorylates and inactivates GSK-3beta, were significantly elevated in Npc1-/- mice relative to Npc1+/+ mice. Accordingly, levels of inactive GSK-3beta were 50 to 100% higher in mutant brains than in controls. Increases in inactive GSK-3beta occurred early in postnatal development, well before neuronal loss, and were most prominent in structures with intracellular cholesterol accumulation, suggesting a contribution to subsequent degeneration. Perturbations of nuclear factor (NF)-kappaB, which is regulated by GSK-3beta, occurred in Npc1-/- mouse brains. Nuclear concentrations and DNA binding activity of NF-kappaB's transactivation subunit, p65, were significantly reduced in Npc1-/- mice compared to Npc1+/+ mice. Cytoplasmic levels of the p50 subunit and its precursor, p105, were higher in Npc1-/- mice. These results suggest that excessive activity in the PI3K-Akt pathway depresses GSK-3beta, thereby disrupting the formation and/or nuclear import of p50/p65 NF-kappaB dimers and contributing to neuronal degeneration.


Biochemical and structural evidence for ethanol-induced impairment of testicular development: apparent lack of Leydig cell involvement.
The present study was conducted to provide biochemical and morphological evidence for ethanol-induced impairment of testicular development. The specific activities of testicular postmeiotic enzyme markers--sorbitol dehydrogenase (SDH), lactate dehydrogenase (LDH), and alpha-glycerophosphate dehydrogenase (GDH)--increased with age in CFW mice from ages 23 to 60 days, providing a biochemical measure of testicular development during puberty. Chronic ethanol treatment via liquid diets from ages 20 to 55 days resulted in decreased activities of SDH and LDH at ages 40 and 44 days, and of GDH at ages 34, 40, and 44 days. These decreases were consistent with an arrest in the developmental increase in SDH, LDH, and GDH at ages 31 +/- 0.6, 31 +/- 2.6, and 24 +/- 0.5 days, respectively. After 29 days of ethanol treatment (age 50 days), testicular weights, epididymal sperm content, and sperm motility were reduced, relative to controls, by 37, 83, and 60%, respectively (p less than 0.05). Epididymal weights were unaffected. Light microscopic evaluation of testes revealed disorganization of spermatogenesis, germ cell degeneration, decreased tubular luminal diameter, and vacuolation of Sertoli cells in ethanol-treated mice at age 50 days. Electron microscopic analysis showed that germ cell degeneration was not restricted to a specific cell type. Stage IX-XI tubules were observed in which spermatids had been retained and underwent phagocytosis within the Sertoli cell. Sertoli cells showed evidence of atypical nuclear invaginations. Sertoli cells underwent degenerative changes and were sloughed into the rete testis. However, relative Leydig cell size, as well as fractional volume occupied by the nucleus, mitochondria, and endoplasmic reticulum were unaffected by ethanol. The data (1) confirm previous findings suggesting ethanol-induced delayed testicular development; (2) suggest that certain aspects of testicular development are arrested relatively early in ethanol treatment (4-11 days); and (3) indicate that the Sertoli cell, rather than the Leydig cell, is the primary target with regard to the deleterious effect of chronic ethanol treatment on testicular maturation.


Learning needs of hospitalized veteran patients: developing a tool for practice.
The purpose of the study was to develop a practical tool for easy administration by staff to identify Veteran patients' perceived learning needs. Initial development of the tool was based upon a comprehensive literature review, an expert panel review using a modified Delphi Method, and pilot testing of select patients. Two study phases each involved 200 patient interviews from the Department of Veterans Affairs Medical Center in Buffalo, New York. The first phase showed that the tool, the 'Perceived Health Education Needs Scale' had strong internal consistency. Exploratory factor analysis suggested one dominant factor of health. Similar results showing strong internal consistency and one dominant factor were found during a second phase. Veteran patients placed importance on a wide range of educational learning needs, independent of their immediate health concerns.


Signalling across the blood brain barrier by angiotensin II: novel implications for neurogenic hypertension.
Angiotensin II (AngII) is a major culprit in essential hypertension. Based on a genetic rodent model of hypertension, we review here evidence that AngII may signal across the blood brain barrier to affect neuronal circuits within the nucleus tractus solitarii (NTS) of the brainstem, a pivotal region regulating both the baroreceptor reflex and set point control of arterial pressure. We have termed this form of signalling as vascular-neuronal signalling. We describe that the depressant action of AngII in NTS on the baroreceptor reflex is mediated via activation of endothelial nitric oxide synthase (eNOS) releasing NO that promotes release of the inhibitory transmitter-GABA. This could shunt the incoming excitatory baroreceptor afferent traffic impinging on NTS neurones. Chronic studies recording arterial pressure in conscious unrestrained rats using radio-telemetry have revealed that eNOS in NTS plays an endogenous physiological role in the homeostatic regulation of the gain of the cardiac baroreceptor reflex. However, in the spontaneously hypertensive rat, eNOS mRNA was higher (compared to normotensive rats), and its chronic blockade in NTS restored the abnormally depressed cardiac baroreceptor reflex to levels akin to normotensive rats, improved heart rate variability and lowered arterial pressure. Hence, it seems that excessive eNOS activity in NTS of the SHR contributes to the pathological state of this animal model's cardiovascular autonomic nervous system. We speculate on why eNOS activity may be up regulated in the NTS of the SHR and propose that it is a consequence of high cerebral vascular resistance and inadequate blood perfusion of the brainstem.


Cost-effective imaging for resectability of liver lesions in colorectal cancer: an economic decision model.
This study aimed to determine the cost-effectiveness of contrast-enhanced magnetic resonance imaging (CE-MRI) compared with multiphase CE computed tomography (CE-CT) scan to characterize suspected liver lesions in patients with known colorectal carcinoma. A decision analytic model linking diagnostic accuracy to health outcomes in patients with colorectal carcinoma was constructed. The model assumed that CE-MRI has superior sensitivity and equivalent specificity to CE-CT, and patients with a colorectal liver metastasis could be eligible for curative surgery or chemotherapy and palliation. Delayed diagnosis or misdiagnosis was associated with worse health outcomes (disutility). Cost-effectiveness was calculated as the incremental cost relative to the incremental benefit, the benefit was estimated using quality-adjusted life years. Sensitivity analyses were conducted to test the robustness of the results. The clinical evidence supports increased sensitivity of CE-MRI compared with CE-CT (0.943 versus 0.768). CE-MRI was more effective and more costly than CE-CT. The incremental cost-effectiveness ratio was estimated to be $40 548 per quality-adjusted life year gained. The model is most sensitive to the cost of MRI, cost of palliative treatment and the disutility associated with delayed palliative care. The results were also sensitive to the assumptions made about the clinical algorithm. The results provide evidence of the potential cost-effectiveness associated with CE-MRI for the diagnosis of liver metastases in patients with identified colorectal carcinoma. CE-MRI can be recommended as cost-effective provided it replaces CE-CT and that improved diagnostic accuracy results in earlier, curative, disease management.


Enablers and determinants of the provision of written action plans to patients with asthma: a stratified survey of Canadian physicians.
Despite national recommendations, most patients with asthma are not given a written action plan . The objectives were to ascertain physicians' endorsement of potential enablers to providing a written action plan, and the determinants and proportion, of physician-reported use of a written action plan. We surveyed 838 family physicians, paediatricians, and emergency physicians in Quebec. The mailed questionnaire comprised 102 questions on asthma management, 11 of which pertained to written action plan and promising enablers. Physicians also selected a case vignette that best corresponded to their practice and reported their management. The survey was completed by 421 (56%) physicians (250 family physicians, 115 paediatricians and 56 emergency physicians); 43 (5.2%) reported providing a written action plan to ≥70% of their asthmatic patients and 126 (30%) would have used a written action plan in the selected vignette. Most (>60%) physicians highly endorsed the following enablers: patients requesting a written action plan, adding a blank written action plan to the chart, receiving a copy of the written action plan completed by a consultant, receiving a monetary compensation for its completion, and having another healthcare professional explain the completed written action plan to patients. Four determinants were significantly associated with providing a written action plan: being a paediatrician (RR:2.1), treating a child (RR:2.0), aiming for long-term asthma control (RR:2.5), and being aware of national recommendations to provide a written action plan to asthmatic patients (RR:2.9). A small minority of Quebec physicians reported providing a written action plan to most of their patients, revealing a huge care gap. Several enablers to improve uptake, highly endorsed by physicians, should be prioritised in future implementation efforts. ENCOURAGING DOCTORS TO PROVIDE WRITTEN ACTION PLANS: Changes to practice organization and doctors' perceptions should encourage the provision of written action plans for all asthma patients. International guidelines state that effective long-term treatment of asthma requires educated self-management, regular reviews and provision of a written action plan (WAP). However, many patients have poor asthma control and as few as 30 per cent have a WAP. Fabienne Djandji at the Saint-Justine University Central Hospital in Montreal, Canada, and co-workers conducted a survey of 421 doctors to determine their attitudes and provision of WAPs. Only 5.2 per cent of respondents provided WAPs to patients; those treating children or aiming for long-term asthma control were more likely to do so. The doctors said that incentives to provide WAPs would include requests from patients themselves, being paid to complete WAPs and having extra support from specialists or other health care professionals such as pharmacists.


Effects of high salinity and constituent organic compounds on treatment of photo-processing waste by a sulfur-oxidizing bacteria/granular activated carbon sludge system.
To achieve practical treatment of photo-processing waste (PW) using our previously proposed sulfur-oxidizing bacteria (SOB)/granular activated carbon (GAC) sludge system, this paper elucidates why 3- to 5-X dilution of PW was required. That is, a series of experiments were carried out to show the effects of high salinity and constituent organic compounds in PW, respectively. Both an inorganic salts system and calcination PW system showed that SOB completely oxidizes S2O(3)2- -S to SO(4)2- -S even at 12.3 or 13.6% salinity, respectively; hence the dilution requirement is not attributable to high salinity. In experiments employing SOB and SOB/GAC systems to investigate the effects of 23 constituent compounds in PW, compounds were classified into Groups I, II, IIIa, and IIIb. Even with 10 g/l GAC, the nine compounds in Group IIIb still exhibited a toxic effect on SOB activity at 1- and 3-X dilutions; thus it is these compounds that are responsible for requiring dilution of PW. Accordingly, a reduction in their use within the photodeveloping and fix-stabilizing industry, and/or use of > 10g/l GAC, are new considerations for establishing a more practical PW treatment process.


Variations in sociodemographic and health-related factors are linked to distinct clusters of individuals with depression based on the PHQ-9 instrument: NHANES 2007-2018.
Depression is a heterogeneous disease. Identification of latent depression subgroups and differential associations across these putative groups and sociodemographic and health-related factors might pave the way toward targeted treatment of individuals. We used model-based clustering to identify relevant subgroups of 2900 individuals with moderate to severe depression (defined as scores ≥10 on the PHQ-9 instrument) from the NHANES cross-sectional survey. We used ANOVA and chi-squared tests to assess associations between cluster membership and sociodemographics, health-related variables, and prescription medication use. We identified six latent clusters of individuals, three based on depression severity and three differentially loaded by somatic and mental components of the PHQ-9. The Severe mental depression cluster had the most individuals with low education and income (P < 0.05). We observed differences in the prevalence of numerous health conditions, with the Severe mental depression cluster showing the worst overall physical health. We observed marked differences between the clusters regarding prescription medication use: the Severe mental depression cluster had the highest use of cardiovascular and metabolic agents, while the Uniform severe depression cluster showed the highest use of central nervous system and psychotherapeutic agents. Due to the cross-sectional design we cannot make conclusions about causal relationships. We used self-reported data. We did not have access to a replication cohort. We show that socioeconomic factors, somatic diseases, and prescription medication use are differentially associated with distinct and clinically relevant clusters of individuals with moderate to severe depression.


Short alpha/beta-peptides as catalysts for intra- and intermolecular aldol reactions.
Short alpha/beta-peptides, containing conformationally restricted cis-beta-aminocyclopropylcarboxylic acid units as turn-inducing elements, have been found to be efficient catalysts for inter- and intramolecular aldol reactions. The tripeptide H-(L)-Pro-black triangle-(L)-Pro-OH was identified to perform especially well in homogeneous and heterogeneous aqueous solutions as well as in organic solvents.


Corporoplasty using tunica albuginea free grafts for penile curvature: surgical technique and long-term results.
A Nesbit or plication procedure for correcting penile deformities is associated with penile shortening, especially in patients with excessive curvature and/or rotation. On the other hand, grafting procedures are associated with poor postoperative results due to graft shrinkage and veno-occlusive dysfunction. To minimize penile shortening and preserve potency we describe a new surgical technique combining the Nesbit procedure with tunica albuginea free grafting. Long-term functional results and patient satisfaction are reported. We treated 17 potent patients with a mean age plus or minus standard deviation of 46.1 +/- 14.5 years, including 4 with congenital penile deviation and 13 with stabilized Peyronie's disease. Opposite the point of maximal curvature a typical Nesbit procedure was performed. The excised tunica albuginea segment consequently served as a free graft. A symmetrical incision was made at the opposite site and the preserved elliptical tunica albuginea graft was placed in the defect. Further elliptical excisions and grafting followed as needed to correct the deformity. At a mean followup of 39.5 +/- 13.7 months (range 18 to 62) all patients reported penile straightening and functional erection, while ultrasonography of the corpora cavernosa revealed no changes in graft ultrastructure. There was penile shortening in 8 patients (47%) but only 2 (11.7%) considered it significant. All patients with a minimum 2-year followup were positive in regard to recommending the operation to others or repeating it if necessary. The newly described technique may be considered as a treatment option in patients with excessive penile curvature since shortening of the penile shaft is eliminated by 50% compared with the result of the Nesbit procedure. Tunica albuginea seems to be an appropriate grafting material since it prevents postoperative corporeal veno-occlusive dysfunction.


Stiffness, strength and adhesion characterization of electrochemically deposited conjugated polymer films.
Conjugated polymers such as poly(3,4-ethylenedioxythiphene) (PEDOT) are of interest for a variety of applications including interfaces between electronic biomedical devices and living tissue. The mechanical properties, strength, and adhesion of these materials to solid substrates are all vital for long-term applications. We have been developing methods to quantify the mechanical properties of conjugated polymer thin films. In this paper, the stiffness, strength and the interfacial shear strength (adhesion) of electrochemically deposited PEDOT and PEDOT-co-1,3,5-tri[2-(3,4-ethylene dioxythienyl)]-benzene (EPh) were studied. The estimated Young's modulus of the PEDOT films was 2.6±1.4GPa, and the strain to failure was around 2%. The tensile strength was measured to be 56±27MPa. The effective interfacial shear strength was estimated with a shear-lag model by measuring the crack spacing as a function of film thickness. For PEDOT on gold/palladium-coated hydrocarbon film substrates an interfacial shear strength of 0.7±0.3MPa was determined. The addition of 5mole% of a tri-functional EDOT crosslinker (EPh) increased the tensile strength of the films to 283±67MPa, while the strain to failure remained about the same (2%). The effective interfacial shear strength was increased to 2.4±0.6MPa. This paper describes methods for estimating the ultimate mechanical properties of electrochemically deposited conjugated polymer (here PEDOT and PEDOT copolymers) films. Of particular interest and novelty is our implementation of a cracking test to quantify the shear strength of the PEDOT thin films on these solid substrates. There is considerable interest in these materials as interfaces between biomedical devices and living tissue, however potential mechanisms and modes of failure are areas of continuing concern, and establishing methods to quantify the strengths of these interfaces are therefore of particular current interest. We are confident that these results will be useful to the broader biological materials community and are worthy of broader dissemination.


Understanding the support needs of parents of children with obsessive-compulsive disorder: a qualitative descriptive study in the UK.
Caring for a child with obsessive-compulsive disorder (OCD) can be extremely difficult, yet evidence-based support strategies for parents/carers are limited. A detailed understanding of parent support needs is an important first step in intervention development and qualitative research with this focus is currently lacking. In this study, the viewpoints of parents and professionals were used to understand support needs and preferences when caring for a child with OCD. This qualitative descriptive study formed part of a wider UK-based project aimed at developing better support for parents of children with OCD. Individual semi-structured interviews (and an optional one-week journal) with a purposive sample of parents of children and young people (CYP) with OCD, aged 8-18, and focus groups (or individual interviews where preferred) with a purposive sample of professionals supporting CYP with OCD. Data comprised transcripts of audio-recorded interviews and focus groups, and text from journals. Analysis was informed by the Framework approach involving inductive and deductive coding, supported by NVivo 12.0 software. Co-production methods were adopted throughout the research process, including the involvement of a parent co-researcher and charity collaborators. Interviews were undertaken with 20 parents, of which 16 completed a journal. Twenty-five professionals took part in a focus group or interview. Five key themes relating to parent support challenges and support needs/preferences were identified (1) Coping with the impact of OCD; (2) Getting help for my child; (3) Understanding parents' role; (4) Making sense of OCD; (5) Joined-up care. Parents caring for children with OCD have clear caregiver support needs which are currently not being met. Through triangulation of parent and professional accounts, this study has identified parent support challenges (e.g., emotional impact of OCD, visibility of caring role, misunderstanding about OCD) and support needs/ preferences (e.g., headspace/respite, compassion/sensitivity, guidance on accommodation) to lay the vital foundations for the development of effective parent support interventions. There is now an urgent need to develop and test an intervention to support parents in their caregiving role, with the aim of preventing and/or reducing their levels of burden and distress and ultimately, improving their quality of life.


The physician and attorney in work-related disorders.
This article discusses the roles of the treating physician and attorney regarding work-related disorders. The authors have emphasized the need for commitment to returning the injured worker back to gainful employment as soon as medically safe. The need for communication between physician and attorney is discussed. The authors have also called for greater "cross teaching" between professions to increase awareness of the issues surrounding care and representation of the injured worker.


Peri-implant bone microstructure determines dynamic implant cut-out.
Dynamic implant cut-out is a frequent complication associated with surgical fracture fixation. In this in vitro study, we investigated the influence of the local trabecular bone microstructure on the rate and path of implant migration. Dynamic hip screws were implanted into six human femoral head specimens with a wide range of bone volume fractions. The specimens were subjected to image-guided failure assessment using physiological dynamic hip loading. Mechanical testing was used intermittently with high-resolution computed tomography scanning. A high correlation was found between the bone volume fraction and implant migration (R(2)=0.95). Profiles of the bone-implant interface were computed based on the positions of the screw and the femoral head. With a larger interface, the implant migration rate was smaller. The bone-implant interface was significantly smaller on the approximated screw migration path than if it had been on a straight line in loading direction. We thus hypothesize that implants migrate on a path of least resistance. This would indicate a relevant mechanism for targeted surgical intervention.


Hemodialysis-associated soft tissue amyloidomas of the chest and abdominal wall.
Amyloidoma is a highly unusual presentation of amyloidosis in tumoral or nodular form. Isolated soft tissue amyloidomas in individuals with end-stage renal disease on chronic hemodialysis is exceedingly rare, particularly in the era of advanced dialysis technologies. We report the case of a 55-year-old male with end-stage renal disease due to autosomal-dominant polycystic kidney disease, on HD for over 30 years, who was found to have soft-tissue, dialysis-related (β2 -microglobulin) amyloidomas (DRA). He presented with painful, palpable masses within the thoracic and abdominal walls. Serum β2 -microglobulin level was only mildly elevated at 24.9 mg/L. Biopsy confirmed amyloidosis with positivity for Congo Red staining and apple-green birefringence under polarized light. Amyloid subtyping with immunohistochemistry showed positive β2 -microglobulin staining within the deposits. Conservative therapy involving pain management and close monitoring resulted in eventual improvement in symptoms and thus proved to be a viable option for treatment.


Heads Up: Communication Is Key in School Nurses' Preparedness for Facilitating "Return to Learn" Following Concussion.
Recent literature advocates for a school academic team, including school nurses, to support concussed students' return to the classroom. This study aimed to assess the current understanding and practices of a sample of school nurses regarding the concept of "return to learn" in concussed students. Cross-sectional survey of New England school nurses. The greatest barrier to the school nurses' functioning within the academic rehabilitation team for students with concussion was "inadequate communication with the provider that diagnosed the concussion" (73%). Of the 151 school nurses surveyed, 19% felt that they did not have the training necessary for this role. Other barriers included "inadequate concussion training" (38%) and "inadequate time necessary to care for a student with concussion" (30%). By identifying specific gaps in knowledge and challenges at the school level, these results inform interdisciplinary medical teams about the importance of educating and facilitating effective "return to learn" academic plans.


Right-sided Aortic Arch with Aberrant Left Subclavian Artery from Kommerell's Diverticulum.
A previously healthy 52-year-old man had a chest radiograph for medical check-up and found to have a right-sided aortic arch. Computed tomography of the thorax revealed a right-sided aortic arch with aberrant left subclavian artery originated from Kommerell's diverticulum. Barium swallow examination showed compression of the posterior wall of the esophagus. He was asymptomatic and no surgical intervention was performed.


Severe Maternal Morbidity and Infant Mortality in Canada.
Severe maternal morbidity (SMM) comprises an array of conditions and procedures denoting an acutely life-threatening pregnancy-related condition. SMM may further compromise fetal well-being. Empirical data are lacking about the relation between SMM and infant mortality. This population-based cohort study included 1 892 857 singleton births between 2002 and 2017 in Ontario, Canada, within a universal health care system. The exposure was SMM as an overall construct arising from 23 weeks' gestation up to 42 days after the index delivery. The primary outcome was infant mortality from birth to 365 days. Multivariable modified Poisson regression generated relative risks and 95% confidence intervals (CIs), adjusted for maternal age, income, rurality, world region of origin, diabetes mellitus, and chronic hypertension. Infant mortality occurred among 174 of 19 587 live births with SMM (8.9 per 1000) vs 5289 of 1 865 791 live births without SMM (2.8 per 1000) (an adjusted relative risk of 2.93 [95% CI 2.51-3.41]). Of 19 587 pregnancies with SMM, 4523 (23.1%) had sepsis. Relative to births without SMM, the adjusted odds ratio for infant death from sepsis was 1.95 (95% CI 1.10-3.45) if SMM occurred without maternal sepsis and 6.36 (95% CI 3.50-11.55) if SMM included sepsis. SMM confers a higher risk of infant death. There is also coupling tendency (concurrent event of interest) between SMM with sepsis and infant death from sepsis. Identification of preventable SMM indicators, as well as the development of strategies to limit their onset or progression, may reduce infant mortality.


Effective drug treatment identified by in vivo screening in a transplantable patient-derived xenograft model of chronic myelomonocytic leukemia.
To establish novel and effective treatment combinations for chronic myelomonocytic leukemia (CMML) preclinically, we hypothesized that supplementation of CMML cells with the human oncogene Meningioma 1 (MN1) promotes expansion and serial transplantability in mice, while maintaining the functional dependencies of these cells on their original genetic profile. Using lentiviral expression of MN1 for oncogenic supplementation and transplanting transduced primary mononuclear CMML cells into immunocompromised mice, we established three serially transplantable CMML-PDX models with disease-related gene mutations that recapitulate the disease in vivo. Ectopic MN1 expression was confirmed to enhance the proliferation of CMML cells, which otherwise did not engraft upon secondary transplantation. Furthermore, MN1-supplemented CMML cells were serially transplantable into recipient mice up to 5 generations. This robust engraftment enabled an in vivo RNA interference screening targeting CMML-related mutated genes including NRAS, confirming that their functional relevance is preserved in the presence of MN1. The novel combination treatment with azacitidine and the MEK-inhibitor trametinib additively inhibited ERK-phosphorylation and thus depleted the signal from mutated NRAS. The combination treatment significantly prolonged survival of CMML mice compared to single-agent treatment. Thus, we identified the combination of azacitidine and trametinib as an effective treatment in NRAS-mutated CMML and propose its clinical development.


Protective effect of flavonoids on drug-induced hepatotoxicity in vitro.
Primary cell cultures of neonatal hepatocytes were used to examine the protective effect of flavonoids in the presence of hepatotoxins. Catechin (CAT) and silybin (SIL) protected the hepatocytes against cell injury produced by erythromycin estolate (EE), amitriptyline (AT), nortriptyline (NT), and tert-butylhydroperoxide (TBOOH). Leakage of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as morphological parameters, were used as indices of hepatotoxicity. Hepatocytes were exposed to EE (1 X 10(-4) M and 2 X 10(-4) M), AT, NT, and TBOOH (1 X 10(-4) M and 1 X 10(-3) M) for a 2-h period. These hepatotoxins caused significant LDH, AST, and ALT leakage (P less than 0.05) when compared to untreated control groups. NT was less toxic than its parent compound, AT. Changes in morphology were evident after 1 h of treatment with the toxicants, including: vacuole formation, size deformation and cell necrosis. As the concentration of hepatotoxins was increased, the changes were more pronounced. Pretreatment of the cultures with either CAT or SIL resulted in less enzyme leakage and morphological alterations by the hepatotoxins. The results of this study suggest that CAT and SIL may act by stabilizing the plasma membrane against toxic insult.


Smooth and conductive DNA-templated Cu₂O nanowires: growth morphology, spectroscopic and electrical characterization.
DNA strands have been used as templates for the self-assembly of smooth and conductive cuprous oxide (Cu₂O) nanowires of diameter 12-23 nm and whose length is determined by the template (16 μm for λ-DNA). A combination of spectroscopic, diffraction and probe microscopy techniques showed that these nanowires comprise single crystallites of Cu₂O bound to the DNA molecules which fused together over time in a process analogous to Ostwald ripening, but driven by the free energy of interaction with the template as well as the surface tension. Electrical characterization of the nanowires by a non-contact method, scanned conductance microscopy and by contact mode conductive AFM showed the wires are electrically conductive. The conductivity estimated from the AFM cross section and the zero-bias conductance in conductive AFM experiments was 2.2-3.3 S cm⁻¹. These Cu₂O nanowires are amongst the thinnest reported and show evidence of strong quantum confinement in electronic spectra.


[Molecular pathology of plasma cell neoplasms].
Plasma cell myeloma (PCM) and related immunosecretory disorders are a group of B-cell proliferations with a wide clinical and prognostic spectrum, characterized by the production of monoclonal immunoglobulin by immortalized plasma cells. Recent years have seen an explosion in knowledge on the genetic basis and biology of these diseases, followed by improved clinical risk stratification and the introduction of novel therapeutic concepts, such as treatment with proteasome inhibitors or immunomodulatory substances. PCM is a common malignancy, accounting for approximately 10% of all hematological neoplasms. There is good evidence to support a multistep transformation process in plasma cell neoplasms, which corresponds to clinically discernible disease stages. Monoclonal gammopathy of unknown significance is a common asymptomatic precursor lesion for PCM which carries an approximately 1% annual risk for progression. Terminal disease stages are characterized by increasing genetic complexity and independence from bone marrow stromal cells and show a rapidly increasing tumour load with severe clinical symptoms. Modern diagnostics of plasma cell neoplasms require inclusion of clinical, morphological, immunophenotypical and cytogenetic features to allow for individual risk assessment and therapy planning.


Minimally invasive surgery for obstructed labour: a review of symphysiotomy during the twentieth century (including 5000 cases).
To compile and make available essential data on symphysiotomy for evaluation in the struggle against maternal and fetal mortality and morbidity from obstructed labour, which causes the death of 50,000 women each year in low-resourced countries. Retrospective review of literature. Five thousand symphysiotomies and 1200 caesarean sections from 28 countries on four continents. The review is based on original papers published 1900 to 1999, stepwise traced through reference lists. Inclusion criteria were: firstly, that the cases reported be consecutive, secondly the presence of an acceptable description of methodology and thirdly, the study size was set at a minimum of 25 cases for analysis of maternal and fetal mortality. Papers comprising only five to 24 cases were included in other analyses. All studies were retrospective, except the follow up studies. Maternal and fetal mortality; causes of maternal death; fetal mortality in previous deliveries; mode of delivery in subsequent pregnancies; symphyseal width after symphysiotomy; immediate, short and long term complications; maternal and fetal mortality comparing symphysiotomy and caesarean section. Symphysiotomy has been extensively studied, modified and refined over the last century, and the scientific documentation is substantial. The results indicate that symphysiotomy is safe for the mother from a vital perspective, confers a permanent enlargement of the pelvis and facilitates vaginal delivery in future pregnancies, and is a life saving operation for the child. Severe complications are rare. Symphysiotomy compares favourably with caesarean section in terms of risk for the mother's life. If valid conclusions can be drawn from one hundred years of retrospective studies, there is considerable evidence to support a reinstatement of symphysiotomy in the obstetric arsenal, for the benefit of women in obstructed labour and their offspring.


A statistical analysis of human lymphocyte transformation data.
The lymphocytes from 107 maternal-foetal pairs were examined for their in vitro responsiveness, as determined by the incorporation of tritiated thymidine following stimulation with phytohaemagglutinin (PHA), candida, varicella, mumps, streptokinase-streptodornase (SKSD) and tetanus toxoid. The data were collected and analysed in two sequential groups (forty-seven and sixty) in order to determine whether the results were reproducible. The variable chosen for analysis was the difference (d) between the square roots of the isotope incorporation in the stimulated and control cultures because it gave the most symmetrical distribution of the data. The experimental error in the determination of maternal lymphocyte stimulation was 1.4--8.6% and of the foetal lymphocytes, 1.0--16.6%, depending upon the antigen or mitogen and its concentration. The data in the two sets of patients were statistically the same in forty-eight of the fifty-six analyses (fourteen antigen or mitogen concentrations in autologous and AB plasma for maternal and foetal lymphocytes). The statistical limits of the distribution of responses for stimulation or suppression were set by an analysis of variance taking two standard deviations from the mean as the limits. When these limits were translated into stimulation indices, they varied for each antigen or mitogen and for different concentrations of the same antigen. Thus, a detailed statistical analysis of a large volume of lymphocyte transformation data indicates that the technique is reproducible and offers a reliable method for determing when significant differences from control values are present.


Dog assisted education in children with rheumatic diseases and adolescents with chronic pain in Germany.
Animal assisted intervention is an increasingly accepted tool to improve human well-being. The present study was performed to assess whether dog assisted education has a positive effect on children suffering from rheumatic disorders with pain and adolescents with chronic pain syndrome. Two groups of juvenile patients were recruited: 7-17-year-old children in children with rheumatic diseases and adolescents with chronic pain syndromes. Overall, n=26 participated in the intervention, and n=29 in the control group. The intervention group met once a month, 12 times overall, for working with man trailing dogs in various locations. The influence of dog assisted education on quality of life (PedsQLTM Scoring Algorithm), pain intensity, perception, coping (Paediatric Pain Coping Inventory-Revised), and state anxiety (State Trait Anxiety Inventory) was assessed. The quality of life increased significantly in the investigated period, but for both, the intervention and the control group. The state anxiety of children was lower after the dog assisted education than before. After the dog training sessions, state anxiety was 18% to 30% lower than before the intervention. Some participants noted subjectively improved pain coping and changes in pain perception, which were not found in the data. Our results indicate that for children with rheumatic diseases and adolescents with chronic pain syndromes dog assisted education (1) might lead to an increase of the quality of life, (2) leads to decreased state anxiety from pre to post intervention and (3) does not influence pain perception, frequency and intensity.


Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes.
In a simple procedure, the intramolecular hydroarylation of N-propargyl-pyrrole-2-carboxamides was accomplished with the aid of gold(III) catalysis. The reaction led to differently substituted pyrrolo[2,3-c]pyridine and pyrrolo[3,2-c]pyridine derivatives arising either from direct cyclization or from a formal rearrangement of the carboxamide group. Terminal alkynes are essential to achieve bicyclic pyrrolo-fused pyridinones by a 6-exo-dig process, while the presence of a phenyl group at the C-C triple bond promotes the 7-endo-dig cyclization giving pyrrolo-azepines.


Elevated levels of adiponectin and other cytokines in drug naïve, first episode schizophrenia patients with normal weight.
The study was to examine the levels of adiponectin (APN) and other cytokines, and body metabolism in drug naïve, first episode schizophrenia patients with normal weight. Ninety-six drug naïve, first episode schizophrenia patients with normal weight (SZ group), 60 healthy individuals with normal weight (control group), and 60 overweight or obese but otherwise healthy individuals (obesity group) were enrolled in the study. Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and APN were measured using enzyme linked immunosorbent assay (ELISA). Glucose oxidase was used to measure plasma glucose level. Lipid levels were measured using the enzymatic colorimetric method. Serum levels of IL-1β, IL-6 and TNF-α in both the SZ group and the obesity group were significantly higher than those in the control group (p's<0.001). There were no significant differences between the SZ group and the obesity group on those cytokines (p's>0.05). In addition, the levels of APN were significantly higher in the SZ group (p<0.001), and significantly lower in the obesity group (p<0.01) compared with the control group. Further, there were significant positive relationships between levels of APN and levels of other cytokines within the SZ group (p's<0.05); in contrast, there were significant negative relationships between levels of APN and levels of other cytokines within the obesity group (p's<0.05). Fasting serum levels of glucose, LDL, triglycerides and total cholesterol were significantly higher, and fasting serum levels of HDL were significantly lower in the obesity group compared with the other two groups (p's<0.01). There were no significant differences in any of the metabolic parameters between the control group and the SZ group (p's>0.05). Drug naïve, first episode schizophrenia patients with normal weight seem to present an up-regulated inflammatory status as reflected by elevated levels of IL-1β, IL-6, and TNF-α. APN may play a unique pro-inflammatory role in this patient population. Implications of the findings in relation to the pathogenesis of schizophrenia and the vulnerability for metabolic problems were discussed.


[Thrombosis of the pulmonary artery associated with maternal deficiency of antithrombin III].
Authors report a case of newborn with thrombosis of the pulmonary artery, probably caused by a maternal deficit of antithrombin III. Deficit of antithrombin III (AT III) as the possible cause of thrombosis is discussed.


Complete nitrogen removal via simultaneous nitrification and denitrification by a novel phosphate accumulating Thauera sp. strain SND5.
Bacteria capable of simultaneous nitrification and denitrification (SND) and phosphate removal could eliminate the need for separate reactors to remove nutrients from wastewater and alleviate competition for carbon sources between different heterotrophs in wastewater treatment plants (WWTPs). Here we report a newly isolated Thauera sp. strain SND5, that removes nitrogen and phosphorus from wastewater via SND and denitrifying-phosphate accumulation, respectively, without accumulation of metabolic intermediates. Strain SND5 simultaneously removes ammonium, nitrite, and nitrate at an average rate of 2.85, 1.98, and 2.42 mg-N/L/h, respectively. Batch testing, detection of functional genes, nitrogenous gas detection and thermodynamic analysis suggested that nitrogen gas, with hydroxylamine produced as an intermediate, was the most likely end products of heterotrophic ammonium oxidation by strain SND5. The generated end products and intermediates suggest a novel nitrogen removal mechanism for heterotrophic ammonium oxidation in strain SND5 (NH4+→NH2OH→N2). Strain SND5 was also found to be a denitrifying phosphate-accumulating organism, capable of accumulating phosphate, producing and storing polyhydroxybutyrate (PHB) as an intracellular source of carbon while using nitrate/nitrite or oxygen as an electron acceptor during PHB catabolism. This study identifies a novel pathway by which simultaneous nitrogen and phosphorus removal occurs in WWTPs via a single microbe.


Growth of Paramecium tetraurelia in bacterized, monoxenic cultures.
Wild type and mutant Paramecium tetraurelia were grown in monoxenic cultures by first growing Enterobacter aerogenes on a defined medium and then adding the Paramecium to the stationary phase bacterial culture. The bacterial growth was proportional to the concentration of the carbon source (citrate), and the Paramecium growth was dependent upon both the bacterial density and the starting density of Paramecium. The behavior, electrophysiological properties, ciliary lipid composition, and growth characteristics were similar to the commonly used bacterized medium (Cerophyl) except that 5-10 times greater Paramecium yields were reliably obtained.


DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA repair function of APE1.
Although inflammation-induced peripheral sensitization oftentimes resolves as an injury heals, this sensitization can be pathologically maintained and contribute to chronic inflammatory pain. Numerous inflammatory mediators increase the production of reactive oxygen (ROS) and nitrogen species (RNS) during inflammation and in animal models of chronic neuropathic pain. Our previous studies demonstrate that ROS/RNS and subsequent DNA damage mediate changes in neuronal sensitivity induced by anticancer drugs and by ionizing radiation in sensory neurons, thus we investigated whether inflammation and inflammatory mediators also could cause DNA damage in sensory neurons and whether that DNA damage alters neuronal sensitivity. DNA damage was assessed by pH2A.X expression and the release of the neuropeptide, calcitonin gene-related peptide (CGRP), was measured as an index of neuronal sensitivity. Peripheral inflammation or exposure of cultured sensory neurons to the inflammatory mediators, LPS and MCP-1, elicited DNA damage. Moreover, exposure of sensory neuronal cultures to LPS or MCP-1 resulted in changes in the stimulated release of CGRP, without altering resting release or CGRP content. Genetically enhancing the expression of the DNA repair enzyme, apurinic/apyrimidinic endonuclease (APE1) or treatment with a small-molecule modulator of APE1 DNA repair activity, both which enhance DNA repair, attenuated DNA damage and the changes in neuronal sensitivity elicited by LPS or MCP-1. In conclusion, our studies demonstrate that inflammation or exposure to inflammatory mediators elicits DNA damage in sensory neurons. By enhancing DNA repair, we demonstrate that this DNA damage mediates the alteration of neuronal function induced by inflammatory mediators in peptidergic sensory neurons.


Bacterial prostatitis: an unusual cause of total urinary incontinence and its surgical management.
A case of total urinary incontinence as a late sequela of bacterial prostatitis is reported. The etiology of the incontinence and its surgical management are discussed. The patient is continent and is gainfully employed.


International impacts of pesticides on children.
Pesticide exposures among children fall into a range of regulatory concerns. A survey encompassing children's exposures in rural farming communities in Honduras illustrates the complexity and magnitude of the problem. Further study and international guidelines for prevention are recommended.


The temporal pattern of synaptic activation determines the longevity of structural plasticity at dendritic spines.
Learning is thought to involve physiological and structural changes at individual synapses. Synaptic plasticity has predominantly been studied using regular stimulation patterns, but neuronal activity in the brain normally follows a Poisson distribution. We used two-photon imaging and glutamate uncaging to investigate the structural plasticity of single dendritic spines using naturalistic activation patterns sampled from a Poisson distribution. We showed that naturalistic activation patterns elicit structural plasticity that is both NMDAR and protein synthesis-dependent. Furthermore, we uncovered that the longevity of structural plasticity is dependent on the temporal structure of the naturalistic pattern. Finally, we found that during the delivery of the naturalistic activity, spines underwent rapid structural growth that predicted the longevity of plasticity. This was not observed with regularly spaced activity. These data reveal that different temporal organizations of the same number of synaptic stimulations can produce rather distinct short and long-lasting structural plasticity.


Relative immunogenicity in mice of different regions of the human IgG.
Monoclonal mouse antibodies to human IgG myeloma proteins were produced and characterized by determining their binding to a series of different purified myeloma proteins. Two types of immunization schedules were used. When the same myeloma protein was used for priming and boosting the mouse, all determinants of the molecule were effectively immunogenic. Of the 353 clones originating from these experiments 42% secreted anti-Fv antibodies, 57% anti-CH antibodies, and 0.85% anti-CL antibodies. In another schedule only the CL and CH regions were the same in priming and boosting; 270 anti-CH (94%), 18 anti-CL (16%), and no anti-FV hybridomas were found. Our results indicate that a unit mass of the FV region was 1.3 times more antigenic than a unit mass of the CH region. A unit mass of the CH region was nearly five times more antigenic than a unit mass of the CL domain when the antigenicity of the FV region had been excluded. When the antigenicity of the FV region had not been excluded, a unit mass of the CH region was about twenty times more antigenic than a unit mass of the CL domain. The data suggest that an antigenic competition was taking place between different parts of the molecule and that the strongly antigenic region (FV) was more efficient in competing out the nearest neighbour (CL) than in competing out other parts of the molecule.


[Effect of phenothiazines on the viscosity and electrical stability of model phospholipid membranes].
The effect of five phenothiazine derivatives on the viscosity of model phospholipid membranes (by eximerization of pyrene) and on their electrical stability has been studied All the phenothiazines tested (chlorpromazine, propazine, triftazin and nonachlazine), except for chloracyzine, considerably increase the viscosity of phospholipid liposome bilayer at a concentration of 10(-5)-10(-4) M. Phenothiazines have been also shown to decrease liposome break-down potential even at a concentration of 10(-7) M. No correlation between the magnitude of break-down potential and changes in liposome membrane viscosity has been revealed.


Generation of a WWTR1 mutation induced pluripotent stem cell line, MUSIi012-A-1, using CRISPR/Cas9.
WWTR1 or TAZ (WWTR1/TAZ) is a transcriptional coactivator that acts as a downstream regulatory target in the Hippo signaling pathway, which plays a pivotal role in regulating cell proliferation and anti-apoptosis. It has been shown in other cell types that WWTR1/TAZ plays a redundant role to its homolog YAP1. Using CRISPR/Cas9 gene editing, we established the WWTR1/TAZ-KO cell line, which features homozygous deletion of WWTR1 gene from human iPSCs. The established WWTR1/YAZ-KO cell line maintained the pluripotent phenotype, the ability to differentiate into all three embryonic germ layers, and normal karyotype.


Co-localization of hypoxia and apoptosis in irradiated and untreated HCT116 human colon carcinoma xenografts.
HCT116 human colon carcinoma xenografts were grown in nude mice. Frozen sections of control and irradiated tumors were stained and analysed for the distribution and extent of hypoxia and apoptosis. Tissue oxygen partial pressure was measured by immunohistochemical staining of hypoxia-dependent metabolites of the 2-nitroimidazole EF5. Apoptosis was assessed using a commercial kit which stains damaged DNA. Although the apoptosis stain was unlikely to exclude other forms of cell death (necrosis, pyknosis) all staining was found to associate with regions of near anoxia.


Management of direct oral anticoagulants-associated bleeding in the trauma patient.
This article emphasizes the differentiated management of direct oral anticoagulants (DOACs)-associated bleeding in trauma patients to generate a severity adjusted treatment protocol. The management of DOAC-associated bleeding should take severity, mortality risk, and haemodynamic effects of the trauma-induced bleeding into account. The different pharmacological properties of DOACs are important for the management of trauma-induced bleeding. Comorbidities like renal impairment and liver dysfunction prolong their half-life. Patients with minor bleeding in stable clinical condition can be managed by a 'wait and see' approach. Moderate bleeding is suggested to be managed by a primarily conservative approach. In life-threatening bleeding, the administration of activated or nonactivated factor concentrates seems justified, together with supportive measures as part of an advanced management protocol. The administration of specific antidotes may be an alternative in the future. A monoclonal antibody to dabigatran (idarucizumab) has recently been approved by the Food and Drug Administration, whereas antidotes to Factor X activated inhibitors (andexanet and aripazine) are still under development. Sufficiently powered studies with clinical and safety outcome measures are still missing for all specific antidotes at this time.


Effect of a 400-kilocalorie carbohydrate diet on human plasma uridine and hypoxanthine concentrations.
Seven healthy female volunteers were fed a 400-kcal carbohydrate diet for 4 days after eating a standardized diet for 3 days. Plasma uridine and hypoxanthine concentrations were measured by high-performance liquid chromatography. After 4 days on the 400-kcal diet, the plasma uridine concentration decreased by 35% but the plasma hypoxanthine concentration remained stable.


The epidemiology of bloodstream infection contributing to mortality: the difference between community-acquired, healthcare-associated, and hospital-acquired infections.
The epidemiology of bloodstream infection (BSI) is well-established; however, little is known about the contribution of different pathogens to mortality. To understand true burden of BSI, pathogens contributing to mortality were investigated and compared according to where the BSI was acquired. Data from deceased patients in two teaching hospitals in the Republic of Korea were collected. BSI contributing mortality was defined as BSI within 2-weeks before death. Cases were grouped by acquisition sites: community-acquired (CA)-, healthcare-associated (HCA)-, and hospital-acquired (HA)-BSI. Drug resistance, BSI focus, and appropriateness of empirical antimicrobial therapy were also compared. Among 1849 deceased patients in the hospitals, 280 (15.1%) patients experienced BSI within 2-weeks before death. In all, 71, 53, and 156 patients in the CA-, HCA-, and HA-BSI groups, respectively, with 316 total isolated pathogens were analyzed. The three most common pathogens were Klebsiella pneumoniae (17.1%), Escherichia coli (16.4%), and Staphylococcus aureus (11.4%). While K. pneumoniae and E. coli were the most common pathogens in CA- and HCA-BSI, Acinetobacter baumannii and Candida species were in HA-BSI. 26.3% (41/156) of patients experienced breakthrough HCA-BSI during administration of carbapenem and/or vancomycin. The proportion of central venous catheter-related infection (0%, 3.4% and 28.3%), carbapenem resistant-Gram negative bacilli (0%, 6.9% and 21.9%), and inappropriate empirical antimicrobial therapy (21.1%, 37.7% and 51.9%; all P < 0.001) were more frequently observed in HA-BSI. The epidemiology of BSI related to mortality had unique characteristics according to the acquisition site. Given the epidemiology of HA-BSI, infection control and antibiotics stewardship programs should be emphasized.


Sleep apnea may be associated with suicidal ideation in adolescents.
Suicide is a major threat to adolescent health. Sleep problems increase the risk of adolescent suicidal behavior, but the role of sleep-disordered breathing (e.g., sleep apnea) is unclear. We investigated whether sleep apnea had an effect on suicidal ideation that was independent of depression and perceived stress. We examined a series of sleep variables with suicidal ideation in 746 fifth and seventh graders using self-reported questionnaires to assess time in bed, sleep quality, insomnia, and sleep apnea while controlling depression and perceived stress. Overall, 8.8% of students aged 10-14 years reported having recent suicidal ideation, and 33% or 3.8%, depending on the screening criteria, reported having suspected sleep apnea. The sleep variables were all associated with an increased risk of suicidal ideation, but the magnitude of effects was largely attenuated when depression and perceived stress were included in the models. Suspected sleep apnea using daytime sleepiness as a screening criterion was independently associated with suicidal ideation (odds ratio = 2.25, p < 0.05). Suspected sleep apnea was associated with suicidal ideation that was partly independent of depression and stress, which reveals the pertinence of screening for sleep apnea among school students and designing proper prevention strategies for reducing youth suicidal behavior.


The different clonal origins of metachronous and synchronous metastases.
Metastases are the leading cause of mortality in cancer patients. Linear and parallel are the two prominent models of metastatic progression. Metastases can be detected synchronously along with the primary tumor or metachronously, following treatment of localized disease. The aim of the study was to determine whether synchronous metastases (SM) and metachronous metastases (MM) differ only in lead-time or stem from different biological processes. We retrospectively studied the chest CTs of 791 patients inflicted by eleven malignancy types that were treated in our institution in the years 2010-2020. Patient's population included 396 with SM and 395 with MM. The diameter of 15,427 lung metastases was measured. Clonal origin was deduced from the linear/parallel ratio (LPR)-a computerized analysis of metastases diameters. LPR of 1 suggests pure linear dissemination and - 1 pure parallel. Patients with MM were significantly older (average of 62.9 vs 60.7 years, p = 0.02), and higher percentage of them were males (58.7% vs 51.1%, p = 0.03). Median overall survival of patients with MM and SM was remarkably similar (23 months and 26 months respectively, p = 0.774) when calculated from the time of metastases diagnosis. Parallel dissemination (LPR ≤ 0) was found in 35.4% of patients with MM compared to only 19.8% of the patients with SM (p < 0.00001). Patients with SM and MM differ in demography and in clonal origin. Different therapeutic approaches may be considered in these two conditions.


Temperature and thermal dose distributions during intradiscal electrothermal therapy in the cadaveric lumbar spine.
Human cadaveric lumbar spines were used to assess the temperature and thermal dose distribution during intradiscal electrothermal therapy in vitro. To determine whether intradiscal electrothermal therapy produces adequate tissue temperatures to denature annular collagen or ablate nerve cells. Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested and include: 1) shrinkage of the nucleus and/or the annulus fibrosus by contraction of collagen fibers; and 2) thermal ablation of sensitive nerve fibers in the outer annulus. Intradiscal electrothermal therapy was performed using the standard clinical protocol on 12 lumbar specimens in a 37.0 degrees C water bath using the SpineCath by Oratec. Temperatures were recorded simultaneously at 40 different locations in the disc. Thermal dose (Equivalent Minutes 43.0 degrees C) was calculated at each temperature point. The highest temperature measured (out of 520 points) was 64.0 degrees C and was within 1 mm of the heating coil. Temperatures in excess of 60 degrees C were all within 1 to 2 mm of the intradiscal electrothermal therapy catheter surface, the 50 to 60 degrees C range extended approximately 6 mm, above 48 degrees C extended approximately 7 mm, and above 45 degrees C extended to approximately 10 mm. Less than 2% of points achieved temperatures sufficient for collagen denaturation (>60 degrees C). On average, 42.5% of points accumulated >250 Equivalent Minutes 43.0 degrees C, a conservative common dose threshold for thermal necrosis of cells. The time history of thermal measurements demonstrated that the disc temperature had not reached steady state by the end of the heating protocol (16.5 minutes). Except for a very limited margin (1-2 mm) around the catheter, the temperature necessary to induce collagen shrinkage was not observed within the disc. Temperatures sufficient to ablate nerves were developed in some areas but were not reliably produced in clinically relevant regions, such as the posterior annulus. These results suggest that beneficial clinical outcomes may be critically dependent on probe placement or other factors unknown.


Object-based attention in Chinese readers of Chinese words: beyond Gestalt principles.
Most object-based attention studies use objects defined bottom-up by Gestalt principles. In the present study, we defined objects top-down, using Chinese words that were seen as objects by skilled readers of Chinese. Using a spatial cuing paradigm, we found that a target character was detected faster if it was in the same word as the cued character than if it was in a different word. Because there were no bottom-up factors that distinguished the words, these results showed that objects defined by subjects' knowledge--in this case, lexical information--can also constrain the deployment of attention.


Is he a healthy weight? Exposure to obesity changes perception of the weight status of others.
The prevalence of obesity has increased dramatically in recent years. As exposure to obesity increases, perceptions of what is a 'normal' weight are likely to change and this may result in overweight and obese people being perceived as healthier weights than they actually are. We tested whether exposure to obesity results in individuals being more likely to perceive an overweight person as being of healthy weight and whether this would impact upon evaluations of whether an overweight person should consider losing weight. Across three experiments with over 350 participants, we examined the effect that exposing participants to photographs of either obese or healthy weight young males had on visual judgements of whether an overweight young male was of healthy weight. We also tested whether exposure influenced participants' perceptions of what a 'normal' weight is, as we predicted that this might mediate the effect that obesity exposure has on weight perceptions. In all studies, exposure to obesity resulted in an overweight male being perceived to be of healthier weight. There was also evidence that this effect was explained by changes to perceptions of what is a 'normal' weight (Experiment 2). Obesity exposure also resulted in participants being more likely to believe that an overweight person did not need to consider losing weight (Experiment 3). These findings provide causal evidence that perceptions of weight and health status are strongly influenced by the body weight of the people we see around us.


The Impact of COVID-19-Related Psychological Stress on Fetoplacental Circulation: A Doppler Scan of Umbilical Vessels in Third-Trimester Antenatal Women.
The placenta is an important organ of pregnancy. A multitude of physiological and pathological factors influence blood flow in the placenta during pregnancy. However, the fetal effects of maternal psychological stress were inconclusive. The recent COVID-19 pandemic had unprecedented economic, social, and psychological effects. The effect of COVID-19-induced psychological stress in antenatal women and its resultant fetal impact were studied by observing the Doppler waveforms of the uterine and umbilical arteries. The cross-sectional study was conducted on 26 healthy third-trimester antenatal women who satisfied pre-set inclusion and exclusion criteria. A pandemic-related pregnancy stress scale (PREPS) was used to evaluate the stress in pregnant women and categorize it into mild, moderate, and severe levels. The Doppler ultrasound of the uterine and umbilical vessels was done along with a routine growth scan in the third trimester of pregnancy. The arterial waveforms, Pulsatility index (PI) of uterine and umbilical arteries, umbilical vein blood flow, and biometric parameters of the fetus were recorded and analyzed. Seventeen of the 26 participants were found to be moderately stressed. Among the three dimensions of the PREPS tool, the perinatal infection stress dimension was expressed predominantly. A strong expression of the positive affirmation dimension was seen in antenatal women. The mean Pulsatility index in the mild, moderate, and severe groups was 0.74, 0.93, and 0.63, respectively. The association between the PREPS score and the Pulsatility index of the umbilical artery alone was found to be significant at p=0.02. The COVID-19 pandemic caused moderate to severe levels of psychological stress in pregnant women. The statistically significant association between the PREPS score and the umbilical artery PI indicates possible fetoplacental compromise, suggesting the need for cognitive therapy to manage psychological stress in antenatal women.


Isolation and differential expression of two isoforms of the ROBO2/Robo2 axon guidance receptor gene in humans and mice.
Expression of Robo receptor molecules is important for axon guidance across the midline of the mammalian central nervous system. Here we describe novel isoform a of human ROBO2, which is initially strongly expressed in the fetal human brain but thereafter only weakly expressed in adult brain and a few other tissues. The known isoform b of ROBO2 shows a more or less ubiquitous expression pattern, suggesting diverse functional roles. The genomic structure and distinct expression patterns of Robo2a and Robo2b have been conserved in the mouse, but in contrast to human ROBO2a mouse Robo2a is also abundant in adult brain. Exons 1 and 2 of human ROBO2a lie in an inherently unstable DNA segment at human chromosome 3p12.3 that is associated with segmental duplications, independent chromosome rearrangements during primate evolution, and homozygous deletion and loss of heterozygosity in various human cancers. The 5' end of mouse Robo2a lies in a <150-kb DNA segment of break in synteny between mouse chromosome 16C3.1 and the human genome.