A benefit of high temperature: increased effectiveness of a rice bacterial blight disease resistance gene.
*Continuous planting of crops containing single disease resistance (R) genes imposes a strong selection for virulence in pathogen populations, often rendering the R gene ineffective. Increasing environmental temperatures may complicate R-gene-mediated disease control because high temperatures often promote disease development and reduce R gene effectiveness. Here, performance of one rice bacterial blight disease R gene was assessed in field and growth chamber studies to determine the influence of temperature on R gene effectiveness and durability. *Disease severity and virulence of Xanthomonas oryzae pv. oryzae (Xoo) populations were monitored in field plots planted to rice with and without the bacterial blight R gene Xa7 over 11 yr. The performance of Xa7 was determined in high- and low-temperature regimes in growth chambers. *Rice with Xa7 exhibited less disease than lines without Xa7 over 11 yr, even though virulence of Xoo field populations increased. Xa7 restricted disease more effectively at high than at low temperatures. Other R genes were less effective at high temperatures. *We propose that Xa7 restricts disease and Xoo population size more efficiently in high temperature cropping seasons compared with cool seasons creating fluctuating selection, thereby positively impacting durability of Xa7.


Euthanasia, virtue ethics and the law.
Following the recent revival of virtue ethics, a number of ethicists have discussed the moral problems surrounding euthanasia by drawing on concepts such as compassion, benevolence, death with dignity, mercy, and by inquiring whether euthanasia is compatible with human flourishing. Most of these writers assert, or simply assume, that their arguments concerning the morality of euthanasia also support their views with regard to legislation. I argue, against these writers, that legislation cannot and should not be based on our moral and religious beliefs concerning whether euthanasia allows a person to die a good death. I then outline an Aristotelian approach to the role of law and government in a good society, according to which the task of the legislator is not to ensure that people actually act virtuously, but is instead to make it possible for them to choose to live (and die) well by ensuring that they have access to the goods that are necessary for flourishing. In the second half of the paper I apply this approach to the question of whether voluntary active euthanasia should be legalised by asking (1) whether euthanasia always deprives people of the necessary conditions for flourishing, and (2) whether the option to request euthanasia is ever necessary for flourishing.


The Relationship Between Neonatal Surgery, Postpartum Depression, and Infant Clinical Course.
Postpartum depression (PPD) affects 10-15% of mothers in the general population, and studies show increased incidence for mothers of infants with serious health conditions. This study investigates incidence of PPD in mothers of surgical patients in the neonatal intensive care unit (NICU) and characterizes these patients' clinical and neurodevelopmental outcomes. This retrospective cohort study analyzed Nebraska's Tracking Infant Progress Statewide (TIPS) database and referring hospital medical records from February 2013 to June 2018. Upon NICU discharge, children were referred to the TIPS program, with scheduled follow-up appointments at approximately 6 months corrected age. All patients seen in NICU follow-up clinic with recorded scores for maternal Edinburgh postnatal depression screen (EPDS) were eligible except infants with congenital heart disease as this cohort was previously studied. Patients were stratified into groups based on presence or absence of a general surgical procedure within the first 6 months of life and positive (≥ 10) or negative (< 10) EPDS score. Statistical analyses assessed for significant differences between groups regarding gestational age, birth weight, maternal age, length of NICU stay (LOS), number of days on a ventilator, payment method, ethnicity, developmental testing, and rate of referral for early intervention services. Of 436 patients, 83 were surgical patients (16 with positive EPDS; 19.3% incidence), and 353 were non-surgical patients (44 with positive EPDS; 12.5% incidence). Statistical analysis showed no significant relationship between neonatal surgery and positive EPDS (χ2 = 2.6, p = 0.1). While the surgical cohort had longer LOS and days on ventilator, maternal EPDS did not predict these factors. In the surgical cohort, mothers of children not independent on oral feeding at discharge were more likely to screen positive for depression (7/14, 50% vs. 7/61, 11%; p < 0.05). Mothers of surgical patients are not significantly more likely to screen positive for post-partum depression compared to other NICU mothers. This underscores the importance of routine screening for PPD in mothers of both surgical and non-surgical NICU patients in order to identify parents and children at risk.


Creatine kinase isoform electrophoresis for the early confirmation of myocardial infarction detected by timed sequential CK slope analysis.
Creatine kinase (CK)-MM and -MB isoforms were evaluated for the early diagnosis of myocardial infarction in patients aged over 65 years admitted to a district general hospital with acute chest pain. Samples were collected for standard cardiac enzymes, timed CK slope analysis, and CKMM and CKMB isoform analysis from 48 patients admitted with acute chest pain. CKMM and CKMB isoform analyses were conducted using a Helena Rep electrophoresis system under standard conditions supplied by the company. In addition to the results of the biochemical tests the discharge diagnosis of the patients were also recorded. CKMM isoform analysis resulted in three false-negative classifications of patients and one false-positive. The predictive value of this test was 100% for a positive result and 94% for a negative result. CKMB isoform analysis was less accurate and there were six false-negative results and five false-positive results. The predictive value of a positive result was 75% and 85% for a negative result. CK isoform analysis became unreliable when mean total CK levels in serum were 210 IU/l (+/- 171). CK isoform analysis may be of use in the investigation of patients whose samples have a total CK concentration greater than the reference range but was no better than timed CK slope analysis for the detection of myocardial infarction in patients aged more than 65 years.


Comparative study of the clinical profiles of alcoholic chronic pancreatitis and tropical chronic pancreatitis in Tamil Nadu, south India.
In a comparative study of tropical chronic pancreatitis (TCP) and alcoholic chronic pancreatitis (ACP) occurring in the same population, we analyzed the clinical profile of 50 patients of ACP seen over the past 3 years at our centers and compared this with the profile of our TCP patients. A majority (75%) of patients in both groups belonged to Tamil Nadu and 90% had never consumed cassava. Whereas TCP occurred in young subjects of both sexes, ACP patients were all males and presented at an older age. The frequency of pain, diabetes, and pancreatic calcification was similar in the two groups. Patients in both groups were lean, but signs of severe malnutrition were rare. Prediabetic patients had normal body mass index. There were striking differences in radiological appearance of pancreatic calculi in TCP and ACP. Malignancy of the pancreas was present in three patients with TCP. Benign bile duct stenosis was seen in three patients with ACP but not in TCP. Compared to ACP seen in the West, our ACP patients had a shorter duration of symptoms in spite of having advanced disease. TCP and ACP have distinct clinical profiles and it is possible that some environmental factors may hasten the progress of ACP in the tropics.


The social and community involvement of older Australians with intellectual disabilities.
This paper describes the involvement of older people with intellectual disabilities in residential- and community-based activities and programmes. The 446 participants were selected from a national database of people of 55 years of age and over with intellectual disabilities in Australia. The data indicate that participants made infrequent use of public amenities and social and recreational facilities. With the exception of those living with relatives, most had limited contact with family and friends. The discussion draws attention to the need for independence training which will enable the current generation of middle-aged people with an intellectual disability to make decisions and choices about social and community activities.


Herd-level risk factors for lameness in high-producing holstein cows housed in freestall barns.
The objective of this study was to investigate the association of some herd-level factors with the prevalence of lameness in 53 high-production groups of Holstein cows housed on 50 commercial dairy farms having freestall barns in Minnesota. Cows in the high-production group (n = 5,626) were scored for locomotion (score of 1 to 5, where 1 = normal and 5 = severely lame) to estimate prevalence of lameness (locomotion score >or=3) in the group. Herd-level variables were used to explain the variation in prevalence among groups. Among the variables tested, herd size, pen space per cow, type and size of milking parlor, total mixed ration content of crude protein and neutral detergent fiber, feeding frequency, linear feedbunk space per cow, type of feed barrier, and use of footbath did not show any association with the prevalence of lameness in the univariate analysis screening test and were not included in the multivariate model. Pen stocking density (cows per 100 stalls), total daily distance between pen and milking parlor, number of cows per full-time employee equivalent, cud chewing index, and pen type were eliminated from the multivariate model in the backwards stepwise procedure. Daily time away from the pen for milking was positively associated with the prevalence of lameness, whereas cow comfort quotient was negatively associated with prevalence of lameness. Prevalence of lameness was greater when farms performed hoof trimming only when the manager decided cows needed it because of hoof overgrowth or lameness compared with farms on which the feet of all cows were trimmed on a maintenance schedule once or twice annually. Brisket board height of more than 15.24 cm and presence of the area behind the brisket board filled with concrete were associated with greater prevalence of lameness. Most of these herd-level factors could be managed to reduce lameness prevalence in commercial dairy farms.


Scaling-up treatment for HIV/AIDS: lessons learned from multidrug-resistant tuberculosis.
The UN has launched an initiative to place 3 million people in developing countries on antiretroviral AIDS treatment by end 2005 (the 3 by 5 target). Lessons for HIV/AIDS treatment scale-up emerge from recent experience with multidrug-resistant tuberculosis. Expansion of treatment for multidrug-resistant tuberculosis through the multipartner mechanism known as the Green Light Committee (GLC) has enabled gains in areas relevant to 3 by 5, including policy development, drug procurement, rational use of drugs, and the strengthening of health systems. The successes of the GLC and the obstacles it has encountered provide insights for building sustainable HIV/AIDS treatment programmes.


Relationship between suicidal ideation and family problems among young callers to the Japanese crisis hotline.
Previous studies have reported an association between family relationships and suicidal behavior, and found that people with high suicidal ideation are not likely to consult with others about their distress. An effective consulting service is therefore necessary for such individuals. Crisis hotlines are effective for reducing suicide risk, but their associated suicide ideation rate and odds ratio of family problems children remain unclear. The present study investigated the suicidal ideation rate and odds ratio of callers under 20 years of age (N = 24,333) with family problems to the Japanese crisis hotline in 2012. There were 5,242 (21.5%), 18,061 (74.2%), and 1,030 (4.2%) calls related to family problems, other problems, and both, respectively. The suicidal ideation rate and odds ratio of callers with family problems were 2.2% and 0.426, respectively. This result suggested that callers with family problems have a significantly lower rate and odds ratio for suicidal ideation compared with others. However, some associations with a high suicide ideation rate were found for individual items among callers with family problems such as abuse (20.4%), family breakdown (16.1%), and domestic violence (10.6%). Further studies are needed to understand the suicidal ideation of callers with family problems and develop more effective preventive strategies.


Forecasting effects of tree species reintroduction strategies on carbon stocks in a future without historical analog.
American chestnut (Castanea dentata) was once an important component forests in the central Appalachians (USA), but it was functionally extirpated nearly a century ago. Attempts are underway to reintroduce blight-resistant chestnut to its former range, but it is uncertain how current forest composition, climate, and atmospheric changes and disturbance regimes will interact to determine future forest dynamics and ecosystem services. The combination of novel environmental conditions (e.g. climate change), a reintroduced tree species and new disturbance regimes (e.g. exotic insect pests, fire suppression) have no analog in the past that can be used to parameterize phenomenological models. We therefore used a mechanistic approach within the LANDIS-II forest landscape model that relies on physiological first principles to project forest dynamics as the outcome of competition of tree cohorts for light and water as a function of temperature, precipitation, CO2 concentration, and life history traits. We conducted a factorial landscape simulation experiment to evaluate specific hypotheses about future forest dynamics in two study sites in the center of the former range of chestnut. Our results supported the hypotheses that climate change would favor chestnut because of its optimal temperature range and relative drought resistance, and that chestnut would be less competitive in the more mesic Appalachian Plateau province because competitors will be less stressed. The hypothesis that chestnut will increase carbon stocks was supported, although the increase was modest. Our results confirm that aggressive restoration is needed regardless of climate and soils, and that increased aggressiveness of chestnut restoration increased biomass accumulation. The hypothesis that chestnut restoration will increase both compositional and structural richness was not supported because chestnut displaced some species and age cohorts. Although chestnut restoration did not markedly enhance carbon stocks, our findings provide hope that this formerly important species can be successfully reintroduced and associated ecosystem services recovered.


Focal 18F-DOPA Uptake in Brain Parenchyma Surrounding Developmental Venous Anomalies.
We report the finding of increased F-DOPA uptake within parenchyma surrounding a developmental venous anomaly, found incidentally in a 64-year-old woman undergoing PET scan to assess for Parkinson's disease. Not identified on previous T1/T2 MRI, susceptibility-weighted imaging MRI performed post-PET scan demonstrated the presence of developmental venous anomaly within the left cerebellar hemisphere. Focal uptake of F-DOPA may suggest the presence of a brain tumor and prompt invasive diagnostic investigations. Nuclear medicine physicians should be aware of this finding when interpreting F-DOPA PET and consider appropriate imaging to identify venous anomalies prior to more invasive investigations for possible brain tumors.


Subclinical arterial wall damage in patients at low to moderate cardiovascular risk.
The aim of this paper is to study the degree of subclinical arterial wall damage in subjects at low and moderate risk of cardiovascular death by the SCORE scale using instrumental research methods. We enrolled 600 patients (mean age 49.0 +/- 7.1 years, 74% women) with a calculated SCORE 5%, who passed a carotid duplex ultrasonography with a measurement of the intima-media thickness (IMT) and carotid plaque (CP) severity. In the study a computer sphygmography was also performed on the subjects to determine ankle-brachial pulse wave velocity (abPWV) and an ankle-brachial index (ABI). We found 389 (64%) patients with subclinical signs of atherosclerosis. CPs were found in 359 patients (60%), thickened IMT in 28 patients (5%), increased abPWV in 227 patients (38%), and ABI of <0.9 in 29 patients (5%). In the patients with a thickened IMT only two had no CPs. In contrast, 92% of the patients with CPs had normal IMT. Increased abPWV was determined in 87% participants with CPs, and only in 30 subjects no CPs were found. All 29 patients with an ABI of less than 0.9 had CPs. The "presence of CP"was the most sensitive parameter in the patients included in the study, in terms of atherosclerosis determination (92%). The identification of individuals with CPs significantly increased in men over 45 years of age (in 68.4% of cases, P = 0.009), and in women over 50 (in 61.8% of cases, P = 0.001). Our data reinforces the importance of non-invasive imaging of atherosclerosis in subjects at low and moderate cardiovascular risk. The study demonstrated a high prevalence of subclinical atherosclerosis signs in patients at low to moderate risk by the SCORE scale and a high detection frequency of carotid plaques. This suggests that wider implementation of carotid ultrasound in primary care algorithms may improve risk stratification with timely initiation of preventive strategies.


Correlation of hydrogen-atom abstraction reaction efficiencies for aryl radicals with their vertical electron affinities and the vertical ionization energies of the hydrogen-atom donors.
The factors that control the reactivities of aryl radicals toward hydrogen-atom donors were studied by using a dual-cell Fourier-transform ion cyclotron resonance mass spectrometer. Hydrogen-atom abstraction reaction efficiencies for two substrates, cyclohexane and isopropyl alcohol, were measured for 23 structurally different, positively charged aryl radicals, which included dehydrobenzenes, dehydronaphthalenes, dehydropyridines, and dehydro(iso)quinolines. A logarithmic correlation was found between the hydrogen-atom abstraction reaction efficiencies and the (calculated) vertical electron affinities (EA) of the aryl radicals. Transition state energies calculated for the reaction of three of the aryl radicals with isopropyl alcohol were found to correlate linearly with their (calculated) EAs. No correlation was found between the hydrogen-atom abstraction reaction efficiencies and the (calculated) enthalpy changes for the reactions. Measurement of the reaction efficiencies for the reactions of 15 different hydrogen-atom donors with two selected aryl radicals revealed a logarithmic correlation between the hydrogen-atom abstraction reaction efficiencies and the vertical ionization energies (IE) of the hydrogen-atom donors, but not the lowest homolytic X-H (X = heavy atom) bond dissociation energies of the hydrogen-atom donors. Examination of the hydrogen-atom abstraction reactions of 29 different aryl radicals and 18 different hydrogen-atom donors showed that the reaction efficiency increases (logarithmically) as the difference between the IE of the hydrogen-atom donor and the EA of the aryl radical decreases. This dependence is likely to result from the increasing polarization, and concomitant stabilization, of the transition state. Thus, the hydrogen-atom abstraction reaction efficiency for an aryl radical can be "tuned" by structural changes that influence either the vertical EA of the aryl radical or the vertical IE of the hydrogen atom donor.


Nurse decision-making influence. A discrepancy between the nursing and hospital literatures.
The associations between participative management and nurse absenteeism, and between work autonomy and nurse turnover, are found to be more negative in nursing than in hospital administration publications. These differences are congruent with what may be different stances of nursing and hospital administration on the subject of nurse decision-making influence. Implications of the apparent discrepancy between the nursing and hospital literatures are discussed.


Mechanisms of hop inhibition include the transmembrane redox reaction.
In this work, a novel mechanistic model of hop inhibition beyond the proton ionophore action toward (beer spoiling) bacteria was developed. Investigations were performed with model systems using cyclic voltammetry for the determination of redox processes/conditions in connection with growth challenges with hop-sensitive and -resistant Lactobacillus brevis strains in the presence of oxidants. Cyclic voltammetry identified a transmembrane redox reaction of hop compounds at low pH (common in beer) and in the presence of manganese (present in millimolar levels in lactic acid bacteria). The antibacterial action of hop compounds could be extended from the described proton ionophore activity, lowering the intracellular pH, to pronounced redox reactivity, causing cellular oxidative damage. Accordingly, a correlation between the resistance of L. brevis strains to a sole oxidant to their resistance to hop could not be expected and was not detected. However, in connection with our recent study concerning hop ionophore properties and the resistance of hop-sensitive and -tolerant L. brevis strains toward proton ionophores (J. Behr and R. F. Vogel, J. Agric. Food Chem. 57:6074-6081, 2009), we suggest that both ionophore and oxidant resistance are required for survival under hop stress conditions and confirmed this correlation according to the novel mechanistic model. In consequence, the expression of several published hop resistance mechanisms involved in manganese binding/transport and intracellular redox balance, as well as that of proteins involved in oxidative stress under "highly reducing" conditions (cf. anaerobic cultivation and "antioxidative" hop compounds in the growth medium), is now comprehensible. Accordingly, hop resistance as a multifactorial dynamic property at least implies distinct resistance levels against two different mechanisms of hop inhibition, namely, proton ionophore-induced and oxidative stress-induced mechanisms. Beyond this specific model of hop inhibition, these investigations provide general insight on the role of electrophysiology and ion homeostasis in bacterial stress responses to membrane-active drugs.


Consumption of Dark Green Leafy Vegetables Predicts Vitamin A and Iron Intake and Status among Female Small-Scale Farmers in Tanzania.
Inadequate consumption of micronutrient-dense foods such as vegetables and meat are an important contributing cause for anemia and deficiencies of iron and vitamin A in rural communities of Tanzania. A cross-sectional study was conducted in 2016 to examine nutritional and micronutrient status and their associations to the diet of female small-scale farmers in the sub-humid Kilosa (n = 333) and the semi-arid Chamwino (n = 333) districts, in the Morogoro and Dodoma region. An overall higher prevalence of overweight (19.7%) and obesity (7.1%) than of underweight (5.9%) was detected. Significantly more women in the two villages of Kilosa (27-40%) than in the two villages of Chamwino district (19-21%) were overweight/obese, but also more frequently had anemia (34-41% vs. 11-17%), iron deficiency (24-32% vs. 15-17%), and low serum retinol (21-24% vs. 8-9%). Overall, only a small proportion of women reached recommended daily micronutrient intakes: 27% for vitamin A, 17% for iron, 7% for zinc, and 12-38% for B-vitamins. The amount of dark green leafy vegetables (DGLV) consumed was the main determinant of vitamin A and iron intake by women in Chamwino and corresponded to higher hemoglobin, serum retinol and iron status than in the villages of the Kilosa district; in agreement, DGLV consumption also predicted iron and vitamin A intake in Kilosa district. DGLV consumed with wholemeal millet was advantageous in terms of women's vitamin A and iron intake and status over the predominantly maize-rice-based diet lacking vegetables.


Beat-by-beat modulation of AV conduction. II. Autonomic neural mechanisms.
We examined the mechanism by which autonomic neural activity associated with respiration and blood pressure modulates atrioventricular (AV) conduction in conscious dogs. Mongrel dogs were anesthetized and instrumented under sterile conditions to record atrial and ventricular electrograms and blood pressure. In the conscious state, electrocardiogram (ECG), respiration, blood pressure, and electrograms were recorded continuously, and heart rate and AV interval were plotted graphically as a function of time. To delineate the role(s) of sympathetic and parasympathetic activity, AV conduction was studied during abrupt and linear changes in heart rate after administration of atropine, propranolol, or both. In the basal state and after propranolol, AV interval oscillated with respiration both in the absence of atrial pacing and at pacing rates 10-100 beats/min above control. Following atropine, oscillations in AV interval associated with respiration were abolished; however, linear and abrupt heart rate increases resulted in AV conduction changes that were associated with fluctuations in blood pressure. In contrast, after both atropine and propranolol, alterations in blood pressure or respiration did not influence AV conduction and rate-dependent prolongation of AV conduction occurred. We conclude that in the basal state, AV conduction is influenced predominately by changes in parasympathetic activity which is the major determinant of respiratory-related AV interval oscillations; after atropine, sympathetic activity produces fluctuations in both AV conduction and blood pressure; and intrinsic rate-dependent properties of the AV node are modulated continually by both divisions of the autonomic nervous system.


Employees' experiences of the stigma of HIV in a retail organisation: secrecy, privacy or trust?
This study unveiled the participants' experiences of HIV-related stigma in a retail organisation located in the Western Cape province of South Africa. A qualitative approach was adopted because of its appropriateness for unravelling subjective phenomena such as employees' experiences of HIV-related stigma. In-depth interviews were conducted with 10 HIV-positive employees who volunteered to participate. The findings reveal that the participants concealed their HIV-positive status because they feared that the co-workers and managers might stigmatise them and breach confidentiality. The results also revealed that despite being HIV-positive, the participants seemed not to experience a lower work-related self-concept as they said that they are as competent as other employees. The study draws on these empirical findings to theorise about whether concealment of an HIV-positive status is symptomatic of secrecy, the desire for privacy or low levels of trust.


Laser cyclotrabeculospasis in the system of laser treatment in glaucoma.
Different methods of glaucoma treatment by laser have their specific indications and taken together can be considered a kind of "system." A new method of so-called laser cyclotrabeculospasis was developed for use in open-angle simple glaucoma. The anterior surface of the ciliary body (seen gonioscopically) is coagulated by a conventional (argon-gas) laser close to the scleral spur. Tractional pull onto the trabeculum and the inner wall of Schlemm's canal is a probable explanation for hypotensive effect of the procedure and the improved aqueous outflow. There is no risk of serious complications. The laser cyclotrabeculospasis was used clinically to limit the use of surgery, but potentially the method may have some advantages over therapy by drugs as well.


Promotion of acute-phase skin wound healing by Pseudomonas aeruginosa C4 -HSL.
A Pseudomonas aeruginosa quorum-sensing system, which produces N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12 -HSL) and N-butanoyl-l-homoserine lactone (C4 -HSL), regulates the virulence factors. In our previous study, 3-oxo-C12 -HSL, encoded by lasI gene, was shown to promote wound healing. However, the effect of C4 -HSL, encoded by rhlI gene, remains to be elucidated. We addressed the effect of C4 -HSL on wounds in P. aeruginosa infection. Wounds were created on the backs of Sprague-Dawley SD rats, and P. aeruginosa PAO1 (PAO1) or its rhlI deletion mutant (ΔrhlI) or lasI deletion mutant (ΔlasI) was inoculated onto the wound. Rats were injected intraperitoneally with anti-C4 -HSL antiserum or treated with C4 -HSL at the wound surface. PAO1 inoculation led to significant acceleration of wound healing, which was associated with neutrophil infiltration and TNF-α synthesis. These responses were reversed, except for TNF-α production, when ΔrhlI was inoculated instead of PAO1 or when rats were co-treated with PAO1 and anti-C4 -HSL antiserum. In contrast, the healing process and neutrophil infiltration, but not TNF-α synthesis, were accelerated when C4 -HSL was administered in the absence of PAO1. This acceleration was not affected by anti-TNF-α antibody. These results suggest that C4 -HSL may be involved in the acceleration of acute wound healing in P. aeruginosa infection by modifying the neutrophilic inflammation.


Structural Ecosystems Therapy for recovering HIV-positive women: child, mother, and parenting outcomes.
This study presents results of a subgroup analysis from a randomized trial to examine whether Structural Ecosystems Therapy (SET), a family intervention intended to improve medication adherence and reduce drug relapse of HIV-seropositive (HIV+) women recovering from drug abuse, provided benefits for families with children. Data from 42 children and 25 mothers were analyzed at baseline, and 4, 8, and 12 months post-baseline. Results of longitudinal Generalized Estimating Equations analyses suggested that SET was more efficacious than the Health Group (HG) control condition in decreasing children's internalizing and externalizing problems and reducing mothers' psychological distress and drug relapse. Children in SET reported improvements in positive parenting as compared to the children in HG, but there were no differences in mother-reported positive parenting, or parental involvement as reported by either the children or mothers. These findings suggest that family interventions such as SET may be beneficial for mothers and children. An adaptation of SET specifically for families with children could further enhance benefits and improve acceptability and cost-effectiveness.


Effects of beta-adrenergic stimulation with isoproterenol on glomerular hemodynamics.
To evaluate the contribution of beta 1-2-adrenergic receptor stimulation to the regulation of single-nephron glomerular filtration rate (SNGFR), we examined by micropuncture techniques the effects of systemic and intrarenal infusion of isoproterenol on glomerular hemodynamics in plasma volume-expanded Munich-Wistar rats. Isoproterenol infused systemically was consistently associated with an elevation in glomerular capillary hydrostatic pressure difference (delta P) from 44.2 +/- 1.2 to 50.1 +/- 1.3 mmHg, P less than 0.01, the consequence of a 5.9-mmHg fall in Bowman's space hydrostatic pressure, P less than 0.005. The potentially beneficial effect of increased delta P on SNGFR was overcome by a 40% reduction in the glomerular ultrafiltration coefficient (LpA) from 0.043 +/- 0.003 to 0.026 +/- 0.003 nl.s-1.mmHg-1.g kidney wt-1, P less than 0.005, with a net effect of a modest 13% decline in SNGFR, P less than 0.01. In contrast, the intrarenal infusion of isoproterenol did not modify glomerular hemodynamics. Suppression of angiotensin II activity eliminated the influences of systemic isoproterenol infusion on LpA and delta P, the latter was the consequence of lower efferent arteriolar resistance. The findings suggest that systemic infusion of a beta 1-2-adrenergic agonist results in a decrease in LpA via angiotensin II effects and exerts a vasodilatory action on postglomerular vessels during angiotensin II inhibition.


Ten Open Challenges in Medical Visualization.
The medical domain has been an inspiring application area in visualization research for many years already, but many open challenges remain. The driving forces of medical visualization research have been strengthened by novel developments, for example, in deep learning, the advent of affordable VR technology, and the need to provide medical visualizations for broader audiences. At IEEE VIS 2020, we hosted an Application Spotlight session to highlight recent medical visualization research topics. With this article, we provide the visualization community with ten such open challenges, primarily focused on challenges related to the visualization of medical imaging data. We first describe the unique nature of medical data in terms of data preparation, access, and standardization. Subsequently, we cover open visualization research challenges related to uncertainty, multimodal and multiscale approaches, and evaluation. Finally, we emphasize challenges related to users focusing on explainable AI, immersive visualization, P4 medicine, and narrative visualization.


Mapping polypeptide self-recognition through (1)H off-resonance relaxation.
1H NMR relaxation rates provide a readily available and sensitive probe ideally suited to investigate the weak (KD approximately micromolar to millimolar range) interactions that frequently mediate polypeptide oligomerization in the early steps of amyloid fibrillogenesis. However, the measurement of transverse and longitudinal 1H relaxation rates is experimentally challenging due to J-transfer and selectivity problems in CPMG and inversion-recovery experiments, respectively. We show here that these problems are effectively circumvented by measuring nonselective off-resonance relaxation rates using an effective field tilted by 35.5 degrees . When applied to the Halpha spins of the Abeta (12-28) peptide, the proposed experiment provides a residue-resolution self-recognition map which is fully consistent with previous independent mutational studies. The method is anticipated to be widely applicable not only to the fast growing family of amyloidogenic peptides but also to the screening and mapping of protein-ligand interactions in general.


Circulating levels of soluble adhesion molecules in patients with ANCA-associated vasculitis.
During inflammation, activated vascular endothelial cells and other cell types express various adhesion molecules, which facilitate the binding of circulating leukocytes and their extravasation in surrounding tissue (i.e. renal tissue). The serum concentration of circulating soluble adhesion molecules is supposed to reflect the degree of this activation. In the first part of the study, we determined if the serum levels of the soluble intercellular adhesion molecule (sICAM)-1 and the soluble endothelial cell-leukocyte adhesion molecule (sELAM)-1, in patients affected by microscopic polyangiitis (MPA), associated with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibodies (ANCA), were related to the active and the inactive vasculitis phase. In the second part of the study, we examined the changes in circulating sICAM-1 and sELAM-1 levels and the clinical outcome of renal function in these patients. We examined 20 MPO-ANCA-positive MPA patients in an acute phase and in a remission phase, after 6 months of treatment, and 50 subjects as controls, 30 with autosomal dominant polycystic kidney disease (ADPKD) in stable chronic renal failure (CRF) and 20 healthy volunteers (HS) with normal renal function. Regarding serum creatinine (Cr) concentration, no significant differences were found comparing active and inactive phases in the MPA group and the CRF group. Mean serum adhesion molecule levels in the MPA group were higher in the active phase compared to the inactive phase and to the CRF and HS groups. In addition, considering the outcome of serum Cr concentrations in the MPA group, the serum adhesion molecule levels were higher and decreased more slowly in patients with final high serum Cr concentrations than in patients with final normal serum Cr concentrations. Our data suggest that in MPO-ANCA-positive MPA patients, higher sICAM-1 and sELAM-1 levels during the active phase and their slower decline during the treatment period, could be a prognostic risk factor for CRF development.


Reactivation of presumed adenoviral keratitis after laser in situ keratomileusis.
We report a patient with reactivation of presumed adenoviral keratoconjunctivitis after laser in situ keratomileusis (LASIK) to correct high myopia. The preoperative refraction was -13.00 diopters (D) in the right eye and -14.00 D in the left eye, and the best corrected visual acuity was 20/20 in both eyes. On the first postoperative day, mild conjunctival hyperemia and multiple subepithelial infiltrations localized in the flap zone consistent with adenoviral keratoconjunctivitis were seen. After prompt treatment, the lesions resolved. As a consequence, LASIK successfully corrected the high myopia. Adenoviral keratoconjunctivitis can be reactivated after LASIK, unlike after photorefractive keratectomy, despite the absence of symptomatic and clinical findings before the procedure.


Gastrointestinal transit in mice treated with various extracts of date (Phoenix dactylifera L.).
Dates are commonly consumed, especially in the Middle East, but their effect on gastrointestinal transit (GIT) has not been quantified. The effect of water and ethanol extracts from date flesh and date pits on the GIT in mice was studied. Fasted unanaesthetized male mice received by gavage either the vehicle (0.02 m/kg), or the extracts at doses of 0.01, 0.02 or 0.04 ml/kg. Two separate groups received either clonidine (1 mg/kg) or yohimbine (2 mg/kg). Two hours later, all animals were given a test meal containing charcoal and gum arabic in water. Thirty min thereafter, they were killed and the distance the charcoal column had traveled along the small intestine was measured. Compared with the control, the animals that received the ethanol and water extracts of both date flesh and pits emptied, in a dose-dependent manner, more of their gastrointestinal content. The increase in the GIT ranged from 4 to 22%. However, water extract from dialyzed date flesh induced a dose-dependent decrease in GIT that ranged from 4 to 24%. Clonidine exerted a significant decrease (68%), and yohimbine a significant increase (30%) in the GIT. Depending on the method of extraction, the date extracts may exert an increase or a decrease in GIT.


Better off alone? Compared performance of monoclonal and polyclonal stands of a cultivated red alga growth.
The objective of this study was to test, using a field experiment, the effect of genotypic diversity on productivity of farmed populations (Ancud and Chaica, Chile) of the domesticated red alga Agarophyton chilense (formerly known as Gracilaria chilensis), a species considered as economically important in Chile. Monoclonal and polyclonal (4 and 8 genotypes) subplots were outplanted into the mid intertidal in Metri Bay (Puerto Montt, Chile) during summer, a season in which A. chilense face higher temperatures (>18°C) and low nitrogen availability (<4.00 μmol). Ancud farm genotypes show higher growth rates in the monoclonal rather than the two polyclonal subplots. A similar tendency, yet not significant, was discernible in Chaica. In addition, whatever the population of origin of the thalli, no effect of genotypic diversity was detected neither on the agar yield and its quality, nor on the epiphyte load. Such unexpected results of a higher performance in plots with a lower genotypic diversity could be explained (a) by human-assisted selection for dominant-best-performing genotypes that could counterbalance the negative effect caused by the low genotypic diversity in farms and (b) by the fact that the organisms inhabiting the algal mats do not impact the fitness of their host. Overall, the results obtained here suggest that despite farm induced selection lead to impoverished pools of genotypes, they may also have a positive effect of on the resistance of farmed populations to seasonal stressors. However, whether this may have a secondary negative effect on the longer term in a fluctuating environment remains to be determined, but may be avoided by adopting strategy of selection favoring different genotypes in space and time, as implemented in forestry.


Combined hepatocellular-cholangiocarcinoma with stem cell features, ductal plate malformation subtype: a case report and proposal of a new subtype.
In the current WHO blue book, combined hepatocellular-cholangiocarcinoma (C-HCC-CC) was classified into two types; classical type and type with stem cell features. The latter is extremely rare, and is subcategorized into the following three subtypes; typical subtype, intermediate cell subtype, and cholangiocellular subtype. Recently, intrahepatic cholangiocarcinoma (ICC) with features of ductal plate malformations (DPM) have been reported, and the ICC with DPM was proposed as a subtype of ICC. The author herein reports a case of C-HCC-CC with stem cell features. Characteristically, the CC element showed features of DPM. A 51-year-old man of HBV carrier was found to have high AFP. A laboratory test showed an elevated AFP (395 ng/ml, normal 9-10) and hepatitis B virus-related antigens and antibodies. Liver and ductal enzymes and PIVKAII were within normal ranges. Imaging modalities including CT identified a small liver tumor. Hepatocellular carcinoma (HCC) was suspected, and the resection of the hepatic tumor was performed. Grossly, the liver tumor is well-defined white solid tumor measuring 22x16x23 mm. Microscopically, the tumor was a C-HCC-CC, and was composed of following three elements: well differentiated HCC, well differentiated cholangiocarcinoma (CC), and intermediate tumor element. Characteristically, the CC cells formed tortuous markedly irregular tubules with intraluminal cell projections, bridge formations, intraluminal tumor biliary cells; such features very resembled the ductal plate (DP) and DPM. Immunohistochemically, the cells of CC element were positive for stem cell antigens (KIT (CD117), CD56, EMA, CD34), HepPar1, EpCAM, cytokeratin (CK) CAM5.2, AE1/3, CK34BE12 (focal), CK7, CK8, CK18, CK19, CA19-9, p53, MUC1, MUC2, MUC5AC, MUC6, and Ki-67 (labeling=25%). They were negative for CEA, CK5/6, CK20, NSE, chromogranin, synaptophysin, and p63. No mucins were found by histochemically. The background liver showed chronic hepatitis B (a1, f3). Very interestingly, many DPMs were scattered in the non-tumorous parenchyma. This type of C-HCC-CC with DPM features has not been reported. The author herein proposes that this tumor should be included or added in the C-HCC-CC subtype as C-HCC-CC with stem cell features, DMP subtype.


Alveolar macrophage priming by intravenous administration of chitin particles, polymers of N-acetyl-D-glucosamine, in mice.
Intravenous (i.v.) administration of phagocytosable chitin particles (1 to 10 microm) in C57BL/6 mice and SCID mice primed alveolar macrophages (Mphi) within 3 days to yield up to a 50-fold increase in their oxidative burst when elicited in vitro with phorbol myristate acetate (PMA). C57BL/6 mice pretreated with monoclonal antibodies (MAbs) against mouse gamma interferon (IFN-gamma) or NK1.1 showed a markedly decreased level of alveolar Mphi priming following injection of chitin particles. To confirm IFN-gamma production in vitro, spleen cells isolated from normal C57BL/6 mice and SCID mice were cultured with chitin particles. Significant IFN-gamma production was observed following stimulation with chitin but not with chitosan or latex beads. When spleen cells were treated with anti-NK1.1 MAb, IFN-gamma production was significantly inhibited. Another set of experiments showed that when C57BL/6 mice were pretreated i.v. with a small dose IFN-gamma, a higher level of priming was induced with not only phagocytosable chitin particles but also phagocytosable chitosan and even latex beads. Likewise, the spleen cell cultures preconditioned with IFN-gamma provided an up-regulation of IFN-gamma production by these phagocytosable particles. Taken together, the in vivo and in vitro results suggest that (i) the alveolar Mphi priming mechanism is due, at least in part, to direct activation of Mphi by IFN-gamma, which is produced by NK1.1+ CD4- cells; (ii) IFN-gamma would have an autocrine-like effect on Mphi and make them more responsive to particle priming; and (iii) phagocytosis of particulates, probably by a postmembrane event such as interiorization, appears to be important for the up-regulation of alveolar Mphi priming and IFN-gamma production.


Genetic correlations among weight and cumulative productivity of crossbred beef cows.
Mature weight of beef cows in the United States has been increasing as a correlated response to selection for calf growth. Unfavorable genetic correlations between cow weight and various measures of female fertility, stayability, and lifetime production suggest declining cow productivity might also be expected as a correlated response to growth selection. National cattle evaluations, however, show increasing trends for stayability and sustained fertility. Random regression (RR) models were employed to further examine genetic relationships among cow weight and productivity, and to assess cumulative productivity traits observed throughout cows' productive lives. Records were from 13,707 females born in the Germplasm Evaluation (GPE) project and mated to calve first as 2-yr olds. Weights observed at pregnancy testing (n = 65,086) and calf production from each exposure to breeding (n = 71,583) were included in uni- and bivariate RR analyses. Production following each breeding season was added to previous production to obtain cumulative production records for each season that the female was exposed to breeding. Zero was added if the cow failed to produce after a breeding season. The number of pregnancies, calves born and calves weaned, as well as age and weight of weaned calves, were accumulated. Projected age-specific heritability (h2) estimates for cumulative production were low (<0.1) at age 2 but increased with age (0.12 to 0.26 at age 6; 0.32 to 0.48 at age 10). Estimated h2 for cow weight were high, fluctuating between 0.6 and 0.7 from ages 2 through 10. Genetic correlations (rg) were positive among all ages within each trait. Between ages 3 and 9, estimated rg were negative between cumulative weaning productivity and cow weight. The correlations were usually weak enough (<-0.2) that small correlated declines from following yearling weight trends might be overcome by culling females after their first reproductive failure. More noticeable increases might be realized by selection among sires with EBV based on productivity of several daughters. The RR EBV for cow weight and cumulative weight weaned represent major sources of variation in cow costs and income, and can be incorporated into economic selection indexes to project differences in cow profitability and value at any age. The RR approach utilizes all available records, enabling later productivity to be projected from observations on young cows.


Highly accelerated dynamic contrast enhanced imaging.
Dynamic contrast-enhanced imaging provides unique physiological information, notably the endothelial permeability (K(trans)), and may improve the diagnosis and management of multiple pathologies. Current acquisition methods provide limited spatial-temporal resolution and field-of-view, often preventing characterization of the entire pathology and precluding measurement of the arterial input function. We present a method for highly accelerated dynamic imaging and demonstrate its utility for dynamic contrast-enhanced modeling. We propose a novel Poisson ellipsoid sampling scheme and enforce multiple spatial and temporal l1-norm constraints during image reconstruction. Retrospective and prospective analyses were performed to validate the approach. Retrospectively, no mean bias or diverging trend was observed as the acceleration rate was increased from 3× to 18×; less than 10% error was measured in K(trans) at any individual rates in this range. Prospectively accelerated images at a rate of 36× enabled full brain coverage with 0.94 × 0.94 × 1.9 mm(3) spatial and 4.1 s temporal resolutions. Images showed no visible degradation and provided accurate K(trans) values when compared to a clinical population. Highly accelerated dynamic MRI using compressed sensing and parallel imaging provides accurate permeability modeling and enables full brain, high resolution acquisitions.


Does travel distance influence length of stay in elective colorectal surgery?
Length of stay following elective colorectal surgery is being reported as a quality measure in surgical outcome registries, such as the National Surgical Quality Improvement Program. Regional referral centers with large geographic catchment areas attract patients from significant distances. The aim of this study was to examine the effect of patient distance traveled, from primary residence to a tertiary care hospital, on length of stay in elective colorectal surgery patients. Retrospective population-based cohort study uses data obtained from the National Surgical Quality Improvement Program database. This study was conducted at a tertiary referral hospital. Data on 866 patients undergoing elective colorectal surgery from May 2003 to April 2011 were reviewed. Demographics, surgery-related variables, and distance traveled were analyzed relative to the length of stay. Of the 866 patients, 54% were men, mean age was 57 years, mean distance traveled was 145 miles (range, 2-2984 miles), and mean length of stay was 8.8 days. Univariate analysis showed a significant increase in length of stay with increased distance traveled (p = 0.02). Linear regression analysis revealed a significant association between increased length of stay and male sex (p = 0.006), increasing ASA score (p = 0.000), living alone (p = 0.009), and increased distance traveled (p = 0.028). For each incremental increase in log distance traveled, the length of stay increases by 2.5%. This is a retrospective review that uses National Surgical Quality Improvement Program data. It is not known how many patients left the hospital and did not return to their primary residence. In a model that controlled for variables, increased travel distance from a patient's residence to the surgical hospital was associated with an increase in length of stay. If length of stay is a reportable quality measure in patients undergoing colorectal surgery, significant travel distance should be accounted for in the risk adjustment model calculations.


New hominid fossils from the Swartkrans formation (1979-1986 excavations): craniodental specimens.
Seventy-two individually numbered hominid craniodental fossils from recent excavations at Swartkrans are described. All derive from in situ decalcified breccia and/or unconsolidated sediments. A total of 20 specimens, representing 13 to 16 individuals derive from Member 1 "Lower Bank," two teeth derive from sediments along the Member 1-2 Interface, 38 fossils representing 19 to 24 individuals come from Member 2, and 12 teeth representing 9 to 11 individuals derive from Member 3. All but four of the specimens are attributable at the generic level; one specimen from Member 1 "Lower Bank" and five specimens from Member 2 are attributed to Homo, while the others represent Paranthropus. The proportional representation of Homo in the Swartkrans Formation is markedly higher in Member 2 (c. 33%) than in the Member 1 "Lower Bank" (c. 8%) and Member 1 "Hanging Remnant" (c. 5%) samples.


Comparison of Clinical Scoring Tools to Predict Heparin-Induced Thrombocytopenia in Cardiac Surgery.
The 4Ts and HIT-Expert Probability (HEP) scoring tools for heparin-induced thrombocytopenia (HIT) have not been validated in cardiac surgery patients, and the reported sensitivity and specificity of the Post-Cardiopulmonary Bypass (CPB) scoring tool vary widely in the 2 available analyses. It remains unclear which of the available scoring tools most accurately predicts HIT in this population. Forty-nine HIT-positive patients who underwent on-pump cardiac surgery within a 6-year period were loosely matched to 98 HIT-negative patients in a 1:2 case-control design. The 4Ts, HEP, and CPB scores were calculated for each patient. Sensitivity and specificity of each tool were calculated using standard cut-offs. The Youden method was utilized to determine optimal cut-offs within receiver operating characteristic (ROC) curves of each score, after which sensitivities and specificities were recalculated. Using standard cut-offs, the sensitivities for the CPB, HEP, and 4Ts scores were 100%, 93.9%, and 69.4%, respectively. Specificities were 51%, 49%, and 71.4%, respectively. The AUC of the scoring tool ROC curves were 0.961 for the CPB score, 0.773 for the HEP score, and 0.805 for the 4Ts score. Using the Youden method-derived optimal cut-off of ≥3 points on the CPB score, sensitivity remained 100% with improved specificity to 88.9%. The CPB score is the preferred HIT clinical scoring tool in adult cardiac surgery patients, whereas the 4Ts score performed less effectively. A cut-off of ≥ 3 points on the CPB score could increase specificity while preserving high sensitivity, which should be validated in a prospective evaluation.


Refractory Pulmonary Edema and Upper Body Hypoxemia During Veno-Arterial Extracorporeal Membrane Oxygenation-A Case for Atrial Septostomy.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical circulatory support for patients with advanced cardiogenic shock, facilitating myocardial recovery and limiting multi-organ failure. In patients with severely limited left ventricular ejection, peripheral VA-ECMO can further increase left ventricular and left atrial pressures (LAP). Failure to decompress the left heart under these circumstances can result in pulmonary edema and upper body hypoxemia, that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in these situations. However, the effects of atrial septostomy on upper body oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult VA-ECMO patients between January 2011 and June 2016 who also underwent atrial septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), Pa O2 /Fi O2 ratios (blood samples from right radial artery), intrathoracic volume status, and resolution of pulmonary edema before and up to 48 h after septostomy. There were no procedure-related complications. Thirty-day survival was 44%. LAP/PCWP decreased by approximately 40% immediately following septostomy and remained so for at least 24 h. Pa O2 /Fi O2 ratios significantly increased from 0.49 (0.38-2.12) before to 5.35 (3.01-7.69) immediately after septostomy and continued so for 24 h, 6.6 (4.49-10.93). Radiographic measurements also indicated a significant improvement in thoracic intravascular volume status after atrial septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and intrathoracic vascular volume status in patients developing severe refractory pulmonary edema while undergoing peripheral VA-ECMO. Atrial septostomy therefore appears safe and suitable to reduce the risk of upper body ischemia under these circumstances.


Genetic control of the renal clearance of urate: a study of twins.
Although a genetic predisposition to gout has been recognised for centuries, its mechanism has never been defined. This study was designed to determine whether this factor might be the renal clearance of urate, which is an important determinant of the concentration of urate in serum. In this study the renal clearance of urate was examined in 37 pairs of normouricaemic twins to determine whether this resemblance was genetically mediated. Monozygotic twins had more similar values of urate clearance and fractional excretion of urate than dizygotic twins. The heritability of the renal clearance of urate was estimated as about 60% (95% confidence limits 40 to 100%), whereas the heritability of the fractional excretion of urate was 87% (confidence limits 45 to 100%). This study supports the hypothesis that genetic factors exert an important control on the renal clearance of urate, which determines some of the familiarity of hyperuricaemia and gout.


Reversal of drug-resistance by exposure of mcf-7 or mcf-7 cddp human breast-carcinoma cells to sr-4233 or etanidazole under hypoxic conditions.
Drug resistance is a major problem in cancer therapy. The MCF-7/CDDP cell line, a subline of the MCF-7 human breast carcinoma cell line which is resistant to cis-diamminedichloroplatinum(II), is also resistant to carboplatin, D-tetraplatin and to a lesser degree to melphalan, thiotepa and BCNU compared with the MCF-7 parental cell line. This resistance persists both under normally oxygenated conditions and after 2 h of exposure to hypoxic conditions prior to exposure to the antitumor alkylating agents under normally oxygenated conditions. When the MCF-7 parental cells and MCF-7/CDDP cells were treated with SR-4233 (20 muM) or etanidazole (5 mM) for 2 h prior to and during exposure to the antitumor alkylating agents there was no change in the sensitivity and resistance patterns of the cell lines. However, if the MCF-7 parental cells and the MCF-7/CDDP cells were exposed to SR-4233 (20 muM) or etanidazole (5 mM) for 2 h under hypoxic conditions followed by release of the hypoxia and exposure to the antitumor alkylating agents for 1 h under normally oxygenated conditions the resistance of the MCF-7/CDDP was reversed so that both the MCF-7 parental and MCF-7/CDDP cell lines were essentially equally sensitive to the six antitumor alkylating agents. These results indicate that non-cytotoxic concentrations of modulators such as SR-4233 or etanidazole may be useful in reversing resistance to the.


Metabolic bone disease in asymptomatic men after partial gastrectomy with Billroth II anastomosis.
We sought to determine whether gastric surgery might be associated with metabolic bone disease in a well-characterized population, and if so to explore its etiology. Sixteen asymptomatic middle-aged men who had had partial gastrectomy with Billroth II anastomosis but no other risk factors for metabolic bone disease were compared with unoperated healthy controls. Studies included a dietary survey, biochemical tests of bone and mineral metabolism, radiographs of the spine, determinations of bone mineral content, and bone histomorphometry. The gastric surgery subjects exhibited frequent vertebral fractures and an unusual constellation of bone abnormalities characterized by decreased bone mineral content and hyperosteoidosis without evidence of osteomalacia. Although serum immunoreactive parathyroid hormone and 25-hydroxyvitamin D levels were not different, 1,25-dihydroxyvitamin D levels were significantly higher (p = 0.037), and 24,25-dihydroxyvitamin D levels were significantly lower (p less than 0.0001) in subjects than in controls. Partial gastrectomy with Billroth II anastomosis may be associated with asymptomatic but clinically important metabolic bone disease. The pathophysiology is uncertain, but appears to involve alterations in vitamin D metabolism.


Characterization of Foot-and-Mouth Disease Viruses in Zambia-Implications for the Epidemiology of the Disease in Southern Africa.
The livestock industry supports livelihood and nutritional security of at least 42% of people in the Southern African Development Community region. However, presence of animal diseases such as foot-and-mouth disease poses a major threat to the development of this industry. Samples collected from FMD outbreaks in Zambia during 2015-2020, comprising epithelial tissues samples (n = 47) and sera (n = 120), were analysed. FMD virus was serotyped in 26 samples, while 92 sera samples tested positive on NSP-ELISA. Phylogenetic analysis revealed notable changes in the epidemiology of FMD in Zambia, which included: (i) introduction of a novel FMDV SAT-3 (topotype II) causing FMD cases in cattle in Western Province; (ii) emergence of FMDV serotype O (topotype O/EA-2) in Central, Southern, Copperbelt, Western, Lusaka Provinces; and (iii) new outbreaks due to SAT -2 (topotypes I) in Eastern Zambia. Together, these data describe eight different epizootics that occurred in Zambia, four of which were outside the known FMD high-risk areas. This study highlights the complex epidemiology of FMD in Zambia, where the country represents an interface between East Africa (Pool 4) and Southern Africa (Pool 6). These changing viral dynamics have direct impacts on FMD vaccine selection in the SADC region.


Management of venous thromboembolism in patients with cancer.
Patients with cancer are at increased risk of venous thromboembolism (VTE). In these patients VTE is associated with substantial morbidity and complicates the clinical management of cancer. Emerging research indicates a probable detrimental effect of VTE on cancer survival. Although VTE may develop at any stage of cancer disease, the risk of VTE is particularly high in association with three clinical settings including surgery for cancer, use of a central vein catheter (CVC) and chemotherapy. Guidelines recommend post-operative prophylaxis (for at least 7-10 days) for patients undergoing elective cancer surgery. A prolonged prophylaxis (for upto four post-operative weeks) is recommended in cancer patients at high risk for VTE. The role of antithrombotic prophylaxis in the prevention of CVC-related thrombosis remains controversial. The PROTECHT study has recently evaluated the benefit of antithrombotic prophylaxis in cancer patients receiving chemotherapy, showing a statistically significant 50% relative risk reduction in symptomatic thromboembolic events. The international guidelines currently agree in non-recommending routine prophylaxis in ambulatory patients who receive anticancer chemotherapy but suggest an individual risk-based evaluation. To better identify cancer patients at high risk for VTE, simple predictive models have been validated. Further intervention studies are currently on-going to explore the benefit of antithrombotic prophylaxis in individual high-risk groups of patients. The long-term treatment of cancer-related VTE is based on therapeutic doses of LMWH in preference to warfarin. The optimal duration of antithrombotic treatment in cancer patients remains to be fully defined.


Use of statistical analysis in the biomedical informatics literature.
Statistics is an essential aspect of biomedical informatics. To examine the use of statistics in informatics research, a literature review of recent articles in two high-impact factor biomedical informatics journals, the Journal of American Medical Informatics Association (JAMIA) and the International Journal of Medical Informatics was conducted. The use of statistical methods in each paper was examined. Articles of original investigations from 2000 to 2007 were reviewed. For each journal, the results by statistical methods were analyzed as: descriptive, elementary, multivariable, other regression, machine learning, and other statistics. For both journals, descriptive statistics were most often used. Elementary statistics such as t tests, chi(2), and Wilcoxon tests were much more frequent in JAMIA, while machine learning approaches such as decision trees and support vector machines were similar in occurrence across the journals. Also, the use of diagnostic statistics such as sensitivity, specificity, precision, and recall, was more frequent in JAMIA. These results highlight the use of statistics in informatics and the need for biomedical informatics scientists to have, as a minimum, proficiency in descriptive and elementary statistics.


Genome-wide association analysis of adaptation to oxygen stress in Nile tilapia (Oreochromis niloticus).
Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 16th generation of a Genetically Improved Farmed Tilapia population. In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such as igf1rb, rora, efna3 and aurk were also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways were involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage. There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.


Flexibility and control of thorax deformation during hawkmoth flight.
The interaction between neuromuscular systems and body mechanics plays an important role in the production of coordinated movements in animals. Lepidopteran insects move their wings by distortion of the thorax structure via the indirect flight muscles (IFMs), which are activated by neural signals at every stroke. However, how the action of these muscles affects thorax deformation and wing kinematics is poorly understood. We measured the deformation of the dorsal thorax (mesonotum) of tethered flying hawkmoths, Agrius convolvuli, using a high-speed laser profilometer combined with simultaneous recordings of electromyograms and wing kinematics. We observed that locally amplified mesonotum deformation near the wing hinges ensures sufficient wing movement. Furthermore, phase asymmetry in IFM activity leads to phase asymmetry in mesonotum oscillations and wingbeats. Our results revealed the flexibility and controllability of the single structure of the mesonotum by neurogenic action of the IFMs.


7-HYDROXYCHLORPROMAZINE: POTENTIAL TOXIC DRUG METABOLITE IN PSYCHIATRIC PATIENTS.
7-Hydroxychlorpromazine was isolated from liver and urine of psychiatric patients treated with high dosages of chlorpromazine for long periods. These patients developed a purple pigmentation limited to areas of skin exposed to sunlight, as well as opacities of the cornea and lens. Large amounts of melanin were found only in the pigmented skin. It seems likely that a toxic compound is produced by the action of ultraviolet light on a 7-hydroxylated chlorpromazine derivative deposited in skin, cornea, and lens, and that this in turn leads to excessive melanin production and eye changes.


Instruments for assessing the preferences for everyday living of older people with various care needs: protocol for an evidence map.
Consideration of the preferences for everyday living of older people with various care needs is a prerequisite for person-centred and evidence-based nursing care. Knowledge of and respect for these preferences by nursing staff are associated with better care outcomes for older people with various care needs. To assess preferences in a structured way, instruments focusing on different topics of everyday living appear to be useful. It is unclear which instruments exist for assessing preferences for everyday living. The aim of this planned review is to identify relevant instruments for assessing the preferences for everyday living of older people with various care needs in the form of an evidence map. Additionally, gaps requiring further research will be presented. To identify the different instruments, we will conduct a systematic search in the electronic databases MEDLINE (via PubMed), CINAHL and PsycINFO (via EBSCO). In addition, we will perform backward and forward citation tracking via reference lists and Google Scholar. The identified records will be independently screened (title/abstract and full text) by two reviewers. Data from the included studies will be extracted independently by the same two reviewers. In all three steps, the results will be checked for deviations, and if there are any deviations, they will be discussed. If no consensus can be achieved through discussion, a third reviewer will be engaged. All study designs will be included, and there will be no limitations regarding the publication status or time period. We will include all studies published in English and German that use instruments focusing on the assessment of preferences for everyday living in people older than 60 years of age with various care needs. For data charting, we will extract the number, categories and types of preferences, the care setting for which the instrument was developed and, if available, psychometric properties. Finally, the various extracted results will be presented in the form of tables and a bubble plot. There are no ethical concerns related to the construction of an evidence map, and ethical approval was given by the Witten/Herdecke University (application number 226/2020). We will discuss our results with practitioners in the field of nursing care and persons with various care needs. We will also make our results available to practitioners in an upcoming Project (PELI-D II) and to the public at (inter)national conferences and in the form of practice and peer-reviewed articles.


Optimal cooling rates for sperm cryopreservation in a threatened lizard conform to two-factor hypothesis of cryo-injury.
Assisted reproductive technologies provide important tools for wildlife conservation but have rarely been developed for reptiles. A critical step in developing cryopreservation protocols is establishing optimal cooling rates for cell survival. The two-factor hypothesis explaining cryoinjury to cells originates from an inverted 'U' shape of recovery curves generated in many cell types thawed after cryopreservation, due to cell recovery declining at cooling rates either side of a single optimum. We generated such a curve for the yellow-spotted monitor lizard Varanus panoptes, the first for any reptile. We cryopreserved sperm using two cooling devices (LN2 dry shipper; LN2 bath vapour) and two sperm-holding vessels (Cassou sperm straws; Nunc CryoTubes) to generate four different cooling-rate curves during freezing. Sperm motility and viability (47.3% and 76.5% respectively) were highest when frozen in straws suspended in a LN2 bath at an intermediate cooling rate of 73 °C/min between 0 and -50 °C, whereas sperm frozen in straws suspended in a dry shipper at the fastest cooling rate (231 °C/min between 0 and -50 °C) produced the lowest recovery (10.4% and 36.4% motility and viability, respectively). Sperm frozen in cryotubes at the lowest cooling rates in either LN2 bath vapour or dry shipper produced intermediate recovery. The shape of the optimal cooling curve conformed to the two-factor hypothesis of cryoinjury, the first such evidence in reptile sperm. This in turn led to the identification of simple cryopreservation setups (LN2 vapour with straws and cryotubes; dry shipper with cryotubes but not straws) suitable for cryopreserving lizard sperm in the field.


The role of iron in learning and memory.
Iron deficiency (ID) is the most common nutrient deficiency, affecting 2 billion people and 30% of pregnant women and their offspring. Early life ID affects at least 3 major neurobehavioral domains, including speed of processing, affect, and learning and memory, the latter being particularly prominent. The learning and memory deficits occur while the infants are iron deficient and persist despite iron repletion. The neural mechanisms underlying the short- and long-term deficits are being elucidated. Early ID alters the transcriptome, metabolome, structure, intracellular signaling pathways, and electrophysiology of the developing hippocampus, the brain region responsible for recognition learning and memory. Until recently, it was unclear whether these effects are directly due to a lack of iron interacting with important transcriptional, translational, or post-translational processes or to indirect effects such as hypoxia due to anemia or stress. Nonanemic genetic mouse models generated by conditionally altering expression of iron transport proteins specifically in hippocampal neurons in late gestation have led to a greater understanding of iron's role in learning and memory. The learning deficits in adulthood likely result from interactions between direct and indirect effects that contribute to abnormal hippocampal structure and plasticity.


Early identification of refractory epilepsy.
More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy, but why this happens and whether it can be predicted are unknown. We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures. We prospectively studied 525 patients (age, 9 to 93 years) who were given a diagnosis, treated, and followed up at a single center between 1984 and 1997. Epilepsy was classified as idiopathic (with a presumed genetic basis), symptomatic (resulting from a structural abnormality), or cryptogenic (resulting from an unknown underlying cause). Patients were considered to be seizure-free if they had not had any seizures for at least one year. Among the 525 patients, 333 (63 percent) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped. The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy (40 percent vs. 26 percent, P=0.004) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer (51 percent vs. 29 percent, P<0.001). The seizure-free rate was similar in patients who were treated with a single established drug (67 percent) and patients who were treated with a single new drug (69 percent). Among 470 previously untreated patients, 222 (47 percent) became seizure-free during treatment with their first antiepileptic drug and 67 (14 percent) became seizure-free during treatment with a second or third drug. In 12 patients (3 percent) epilepsy was controlled by treatment with two drugs. Among patients who had no response to the first drug, the percentage who subsequently became seizure-free was smaller (11 percent) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects (41 percent) or an idiosyncratic reaction (55 percent). Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy.


Transduction-mediated transfer of unmarked deletion and point mutations through use of counterselectable suicide vectors.
A challenge in strain construction is that unmarked deletion and nucleotide substitution alleles generally do not confer selectable phenotypes. We describe here a rapid and efficient strategy for transferring such alleles via generalized transduction. The desired allele is first constructed and introduced into the chromosome by conventional allelic-exchange methods. The suicide vector containing the same allele is then integrated into the mutant chromosome, generating a tandem duplication homozygous for that allele. The resulting strain is used as a donor for transductional crosses, and selection is made for a marker carried by the integrated suicide vector. Segregation of the tandem duplication results in haploid individuals, each of which carries the desired allele. To demonstrate this mutagenesis strategy, we used bacteriophage P22HTint for generalized transduction-mediated introduction of unmarked mutations to Salmonella enterica serovar Typhimurium. This method is applicable to any species for which generalized transduction is established.


THE ROLE OF RADIATION THERAPY IN THE TREATMENT OF PTCL-NOS.
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders, accounting for about 10 % of all non-Hodgkin lymphomas. The most common subtype is peripheral T-cell lymphoma, unclassified (PTCL-NOS), accounting for about 26 % of all PTCLs. PTCL-NOS is associated with less favorable overall survival (OS) and progression-free survival (PFS) compared with aggressive B-cell lymphomas. The role of radiation therapy in the treatment of PTCL-NOS is still not definitively defined. The results of many studies show that the addition of radiation therapy to the treatment regimen is associated with a significant improvement in survival in patients with early-stage PTCL-NOS, but in the later stages, the benefit of radiation therapy is not obvious. peripheral T-cell lymphoma, unspecified is a clinically and biologically heterogeneous disease with a poor prognosis. Since the role of radiation therapy is still unclear, a study was conducted to evaluate the effectiveness of radiation therapy in peripheral T-cell lymphoma, unspecified. The work is based on clinical observations and treatment results of patients who were diagnosed between 2013 and 2023 at the National Cancer Institute (in the period from 2020 to 2023, patients were observed and treated as part of research). 56 patients were included in the study. The work analyzed the immediate results of the treatment of patients with peripheral T-cell lymphoma, unspecified depending on the stage and type of treatment, as well as the overall survival of these patients. When analyzing the overall response to the treatment of patients with I/II stages of the disease, it was proven that this indicator is higher in the group of patients who received chemoradiotherapy, compared to patients who received only chemotherapy (100 % versus 83.3 %), and this indicator was higher due to patients who demonstrated a complete response to therapy (75 % vs. 50 %). Analyzing the response to treatment of patients with III/IV stages of the pathological process, it was established that there was no difference in the overall response to treatment, the level of complete and partial response to treatment. Analysis of the overall survival of patients with I/II stages of the disease, with a median follow-up of 60 months, demonstrated a significant improvement in overall survival in the group of patients who received chemoradiotherapy compared to the group of patients who received only radiation therapy (median 48 vs. 22 months). Overall 1-year (78 % vs. 69 %), 3-year (64 % vs. 40 %), and 5-year (48 % vs. 35 %) were also higher in the chemoradiotherapy group. In the group of patients with III/IV stages of the disease, there was no difference in overall survival between patients who received chemoradiotherapy and patients who received only chemotherapy (median 16 vs. 13 months, 1-year survival 54 vs. 52, 3-year survival 33 vs. 30 and 5-year overall survival of 23 vs. 20 %. The addition of radiation therapy to the treatment plan demonstrated a significant improvement in the overall response and overall survival of patients with peripheral T-cell lymphomas, unspecified with I and II stages of the pathological process, but in III and IV stages of the disease, the benefit of radiation therapy has not been proven.


The Complex Metabolomics Crosstalk Triggered by Four Molecular Elicitors in Tomato.
The elicitation of plant secondary metabolism may offer interesting opportunities in the framework of sustainable approaches in plant science and in terms of their ability to prime resistance to biotic and abiotic stressors. The broad metabolic reprogramming triggered by different molecular elicitors, namely salicylate (SA), polyamines (PAs), and chitosan, was comprehensively investigated using a metabolomics approach and the tomato (Solanum lycopersicum L.) as the model crop. Six different treatments were compared: a negative control (no treatments), a second negative control treated with 1 M acetic acid (the reference for chitosan, since chitosan was solubilized in acetic acid), and four molecular elicitors, 1 mM 2,1,3-benzothiadiazole (BTH, a positive control), 10 mg/mL chitosan, 0.01 mM SA, and a 0.1 mM PA (putrescine, spermidine, and spermine). All treatments determined a slight increase in biomass, in particular following PA treatment. A broad reprogramming of secondary metabolism could be observed, including membrane lipid remodeling, phenylpropanoid antioxidants, and phytohormone crosstalk. Overall, our results suggest that PAs, SA, and BTH shared a systemic acquired resistance (SAR)-related response, whereas chitosan induced a more distinct induced systemic resistance (ISR)-like jasmonate-related response. These results pave the way towards the possible use of elicitors as a sustainable tool in plant science and agriculture by increasing crop resilience to biotic and abiotic stressors without detrimental effects on plant biomass.


Honokiol attenuates high glucose-induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC-1α pathway in Schwann cells.
Schwann cells injury induced by high glucose (HG) contributes to the development of diabetic peripheral neuropathy (DPN). Honokiol has been reported to regulate glucose metabolism, however, its effect on DPN and the precise molecular mechanisms remain unclear. This study aimed to investigate the role of AMPK/SIRT1/PGC-1α axis in the protective effects of honokiol on DPN. The biochemical assay and JC-1 staining results demonstrated that honokiol reduced HG-induced oxidative stress and ferroptosis as well as mitochondrial dysfunction in Schwann cells. RT-qPCR and western blotting were utilized to investigate the mechanism of action of honokiol, and the results showed that HG-induced inhibition of AMPK/SIRT1/PGC-1α axis and changes of downstream gene expression profile were restored by honokiol. Moreover, silencing of Sirt1 by siRNA delivery markedly diminished the changes of gene expression profile induced by honokiol in HG-induced Schwann cells. More importantly, we found that administration of honokiol remarkably attenuated DPN via improving sciatic nerve conduction velocity and increasing thermal and mechanical sensitivity in streptozotocin-induced diabetic rats. Collectively, these results demonstrate that honokiol can attenuate HG-induced Schwann cells injury and peripheral nerve dysfunction, suggesting a novel potential strategy for treatment of DPN.


Partial biochemical characterization of cell surface hydrophobicity and hydrophilicity of Candida albicans.
Hydrophobic yeast cells of Candida albicans are more virulent than hydrophilic yeast cells in mice. Results of experiments performed in vitro suggest that surface hydrophobicity contributes to virulence in multiple ways. Before definitive studies in vivo concerning the contribution of fungal surface hydrophobicity to pathogenesis can be performed, biochemical, physiological, and immunochemical characterization of the macromolecules responsible for surface hydrophobicity must be accomplished. This report describes our initial progress toward this goal. When hydrophobic and hydrophilic yeast cells of C. albicans were exposed to various enzymes, only proteases caused any change in surface hydrophobicity. Hydrophobic cell surfaces were sensitive to trypsin, chymotrypsin, pronase E, and pepsin. This indicates that surface hydrophobicity is due to protein. Papain, however, had no significant effect. The hydrophobicity of hydrophilic cells was altered only by papain. The proteins responsible for surface hydrophobicity could be removed by exposure to lyticase, a beta 1-3 glucanase, for 30 to 60 min. When 60-min lyticase digests of hydrophobic and hydrophilic cell walls were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 12.5% resolving gel, each protein population contained a single unique protein that was not evident in the other protein population. However, when the cell wall surface proteins of hydrophobic and hydrophilic cells were first labeled with 125I and then removed by lyticase and analyzed by SDS-PAGE, at least four low-molecular-mass (less than 65 kilodaltons) proteins associated with hydrophobic cells were either absent or much less abundant in the hydrophilic cell digests. This result was seen for both C. albicans strains that we tested. When late-exponential-phase hydrophilic cells were treated with tunicamycin, high levels of surface hydrophobicity were obtained by stationary phase. These results indicate that the surface hydrophobicity of C. albicans reflects changes in external surface protein exposure and that protein mannosylation may influence exposure of hydrophobic surface proteins.


Regulation of cyclic adenosine 3',5'- monophosphate signaling and pulsatile neurosecretion by Gi-coupled plasma membrane estrogen receptors in immortalized gonadotrophin-releasing hormone neurons.
Immortalized GnRH neurons (GT1-7) express receptors for estrogen [estrogen receptor-alpha and-13(ERa and ERI3)] and progesterone (progesterone receptor A) and exhibit positive immunostaining for both intracellular and plasma membrane ERs. Exposure of GT1-7 cells to picomolar estradiol concentrations for 5-60 min caused rapid, sustained,and dose-dependent inhibition of cAMP production. In contrast, treatment with nanomolar estradiol concentrations for 60 min increased cAMP production. The inhibitory and stimulatory actions of estradiol on cAMP formation were abolished by the ER antagonist, ICI 182,780. The estradiol-induced inhibition of cAMP production was prevented by treatment with pertussis toxin, consistent with coupling of the plasma membrane ER to an inhibitory G protein. Coimmunoprecipitation studies demonstrated an estradiol-regulated stimulatory interaction between ERa and G,3 that was prevented by the ER antagonist, ICI 182,780. Exposure of perifused GT1-7 cells and hypothalamic neurons to picomolar estradiol levels increased the GnRH peak interval, shortened peak duration, and increased peak amplitude. These findings indicate that occupancy of the plasma membrane-associated ERs expressed in GT1-7 neurons by physio-logical estradiol levels causes activation of a G, protein and modulates cAMP signaling and neuropeptide secretion.


[Sonography of malignant ovarian tumors].
For the diagnosis and differential diagnosis of malignant tumors of the ovaries, transvaginal ultrasound is currently the preferred method. Ultrasound is indispensable for the pre-operative assessment of the biological significance of an ovarian tumor. With its aid,the indication for a surgical procedure can be established with a high degree of sensitivity and specificity and, where appropriate, the therapeutic approach definitively established. A further important application is screening for the early detection of an ovarian cancer. Although a high level of sensitivity and specificity can also be achieved for such an indication, an otherwise desirable screening procedure--at least in high-risk groups and post-menopausal women--is nevertheless controversial on account of the low prevalence of ovarian carcinoma and the associated poor positive predictive value (PPV).


Cavum Septi Pellucidi in Symptomatic Former Professional Football Players.
Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared with noncontact sports athletes. Seventy-two symptomatic former professional football players (mean age 54.53 years, standard deviation [SD] 7.97) as well as 14 former professional noncontact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within National Football League players, an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC] 0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001). A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared with athlete controls. In addition, a greater length of CSP was associated with decreased performance on a list learning task (Neuropsychological Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth Edition Reading Test, p = 0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP after repetitive head impacts, and its potential association with neuropathologically confirmed CTE.


Stability of antibody productivity is improved when hybridoma cells are entrapped in calcium alginate beads.
Loss of monoclonal antibody (MAb) productivity in long-term, free-suspended cell culture is often attributed to the appearance of a nonproducing population of hybridoma cell (NP) in the culture which has a growth advantage over the producing population (P). However, when an NP appears in long-term culture of entrapped cells, it may not be able to take over the whole culture in a short period of time due to the limited growth of the entrapped cells. In order to examine the hypothesis that entrapped cells can have improved stability of MAb productivity due to limited cell growth, free-suspended cell culture and calcium alginate-entrapped cell culture with inocula consisting of a P and an NP were compared with regard to stability of MAb productivity in a repeated fed-batch culture. In free-suspended cell culture, the NP appeared to take over the whole culture within three batches, and thereby MAb production completely disappeared. In entrapped cell culture, an NP appeared to outgrow the P rapidly only during an exponential growth phase, resulting in a significant decrease in specific MAb productivity, q(MAb), from 11.58 microg/10(6) cell/day to 2.76 microg/10(6) cell/day. However, when the cell growth was limited in entrapped cell culture, the NP no longer outgrew the P rapidly, as indicated by the stable value of q(MAb). In addition, when the cells recovered from the alginate beads by citrate buffer treatment were subcultured in free-suspended cell culture, MAb production rapidly deteriorated and completely disappeared within two batches. Thus, the P present at a small fraction of viable cell concentration in the beginning of the free-suspended cell culture, which were previously entrapped in alginate beads, seemed to be outgrown rapidly by the NP. Taken together, the results obtained from these experiments support the hypothesis that the limited cell growth in entrapped cell culture, which keeps an NP from taking over the whole culture, is responsible, in part, for the improved stability of MAb productivity.


Impaired olfactory neurogenesis affects the performance of olfactory-guided behavior in aged female opossums.
Increasing evidence has indicated that adult neurogenesis contributes to brain plasticity, although function of new neurons is still under debate. In opossums, we performed an olfactory-guided behavior task and examined the association between olfactory discrimination-guided behavior and adult neurogenesis in the olfactory bulb (OB). We found that young and aged opossums of either sex learned to find food buried in litter using olfactory cues. However, aged females required more time to find food compared to aged males and young opossums of both sexes. The levels of doublecortin, that is used as a marker for immature neurons, were the lowest in the OB of aged female opossums. Another protein, HuD that is associated with learning and memory, was detected in all layers of the OB, except the granule cell layer, where a high density of DCX cells was detected. The level of HuD was higher in aged opossums compared to young opossums. This indicates that HuD is involved in plasticity and negatively regulates olfactory perception. The majority of 2-year-old female opossums are in the post-reproductive age but males of this age are still sexually active. We suggest that in aged female opossums neural plasticity induced by adult neurogenesis decreases due to their hormonal decline.


Effects of Danhong injection on cardiac function and blood lipid in patients with angina pectoris of coronary heart disease: A protocol for randomized, double-blind, placebo-controlled clinical trial.
Angina pectoris of coronary heart disease is the leading cause of death worldwide. Danhong injection is a supplement for angina pectoris of coronary heart disease. A large number of studies have confirmed its efficacy and safety. However, there is no rigorous clinical study to evaluate the effects of Danhong injection on cardiac function and blood lipid in patients with angina pectoris of coronary heart disease. This is a prospective, randomized, double-blind, placebo-controlled trial to study the effects of Danhong injection on cardiac function and lipid profile in patients with angina pectoris of coronary heart disease. Participants will be randomly divided into treatment group and control group. The treatment group will be treated with Danhong injection and the control group will be treated with placebo under basic treatment according to recommended guideline, and followed up for 3 months after 14 consecutive days of treatment. Outcomes include: cardiac function (left ventricular end-diastolic diameter); left ventricular end-systolic diameter; left ventricular ejection fraction, blood lipid levels (total cholesterol; triacylglycerol; low density lipoprotein cholesterol; high density lipoprotein cholesterol), the number of angina attacks per week, total amount of nitroglycerin tablets, and adverse reactions. This study will evaluate the efficacy of Danhong injection in improving cardiac function and blood lipid in patients with angina pectoris of coronary heart disease. The results of this study will provide reference for clinical use of Danhong injection to improve cardiac function and blood lipid in patients with angina pectoris of coronary heart disease.Trial registration: OSF Registration number: DOI 10.17605/OSF.IO/TPZJ5.


Salicylate inhibits thrombopoiesis in rat megakaryocytes by changing the membrane micro-architecture.
Salicylate causes drug-induced immune thrombocytopenia. However, some clinical studies indicate the presence of additional mechanisms in the drug-induced thrombocytopenia, by which the platelet production from megakaryocytes may directly be affected. Since salicylate is amphiphilic and preferentially partitioned into the lipid bilayers of the plasma membrane, it can induce some structural changes in the megakaryocyte membrane surface and thus affect the process of thrombopoiesis. Employing the standard patch-clamp whole-cell recording technique, we examined the effects of salicylate on the membrane capacitance in rat megakaryocytes. Taking electron microscopic imaging of the cellular surface, we also examined the effects of salicylate on the membrane micro-architecture of megakaryocytes. Salicylate significantly decreased the membrane capacitance of megakaryocytes, indicating the decreased number of invaginated plasma membranes, which was not detected by the fluorescent imaging technique. As shown by electron microscopy, salicylate actually halted the process of pro-platelet formation in megakaryocytes. This study demonstrated for the first time that salicylate inhibits the process of thrombopoiesis in megakaryocytes, as detected by the decrease in the membrane capacitance. Salicylate-induced changes in the membrane micro-architecture are thought to be responsible for its effects.


Mother and daughter with adolescent-onset severe frontal lobe dysfunction and epilepsy.
Familial cases of early-onset prominent frontal lobe dysfunction associated with epilepsy have not been reported to date. We report a mother and her only daughter with incapacitating behavioral manifestations of frontal lobe dysfunction and epilepsy of variable severity. The possibility of a hitherto undescribed genetic condition is discussed.