The causation of splenomegaly in schistosomiasis in mice.
1. Mice were infected with fertile bisexual Schistosoma mansoni and compared with similar animals infected with unisexual worms or sterile bisexual worms. 2. A significant increase in splenic weight occurred in all infected animals. 3. Administration of well-tolerated doses of 6-mercaptopurine abolished the increase in relative splenic weight in animals infected with ordinary S. mansoni. 4. In splenectomized uninfected mice leucocytosis but no other haematological changes developed. 5. In splenectomized mice lower values for packed cell volume were observed 8 weeks after, but not 12 weeks after, infection with S. mansoni. 6. Slight prolongation of the life-span of erythrocytes occurred in splenectomized infected mice. 7. It is concluded that anaemia in schistosomiasis depends to a significant extent on immunity developed to adult schistosomal worms and can develop in the absense of schistosomal ova. 8. The anaemia resulting from such an immune response may be suppressed by administration of 6-mercaptopurine. 9. Such anaemia occurs even in splenectomized mice; thus hypersplenism is not necessary for its development although splenectomy slightly prolongs the erythrocyte life-span.


Charge-based engineering of hydrophobin HFBI: effect on interfacial assembly and interactions.
Hydrophobins are extracellular proteins produced by filamentous fungi. They show a variety of functions at interfaces that help fungi to adapt to their environment by, for example, adhesion, formation of coatings, and lowering the surface tension of water. Hydrophobins fold into a globular structure and have a distinct hydrophobic patch on their surface that makes these proteins amphiphilic. Their amphiphilicity implies interfacial assembly, but observations indicate that intermolecular interactions also contribute to their functional properties. Here, we used the class II hydrophobin HFBI from Trichoderma reesei as a model to understand the structural basis for the function of hydrophobins. Four different variants were made in which charged residues were mutated. The residues were chosen to probe the role of different regions of the hydrophilic part of the proteins. Effects of the mutations were studied by analyzing the formation and structure of self-assembled layers, multimerization in solution, surface adhesion, binding of secondary layers of proteins on hydrophobins, and the viscoelastic behavior of the air-water interface during formation of protein films; the comparison showed clear differences between variants only in the last two analyses. Surface viscoelasticity behavior suggests that the formation of surface layers is regulated by specific interactions that lead to docking of proteins to each other. One set of mutations led to assemblies with a remarkably high elasticity at the air-water interface (1.44 N/m). The variation of binding of secondary layers of protein on surface-adsorbed hydrophobins suggest a mechanism for a proposed function of hydrophobins, namely, that hydrophobins can act as a specific adhesive layer for the binding of macromolecules to interfaces.


Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities.
Host-associated microbes comprise an integral part of animal digestive systems and these interactions have a long evolutionary history. It has been hypothesized that the gastrointestinal microbiome of humans and other non-human primates may have played significant roles in host evolution by facilitating a range of dietary adaptations. We have undertaken a comparative sequencing survey of the gastrointestinal microbiomes of several non-human primate species, with the goal of better understanding how these microbiomes relate to the evolution of non-human primate diversity. Here we present a comparative analysis of gastrointestinal microbial communities from three different species of Old World wild monkeys. We analyzed fecal samples from three different wild non-human primate species (black-and-white colobus [Colubus guereza], red colobus [Piliocolobus tephrosceles], and red-tailed guenon [Cercopithecus ascanius]). Three samples from each species were subjected to small subunit rRNA tag pyrosequencing. Firmicutes comprised the vast majority of the phyla in each sample. Other phyla represented were Bacterioidetes, Proteobacteria, Spirochaetes, Actinobacteria, Verrucomicrobia, Lentisphaerae, Tenericutes, Planctomycetes, Fibrobacateres, and TM7. Bray-Curtis similarity analysis of these microbiomes indicated that microbial community composition within the same primate species are more similar to each other than to those of different primate species. Comparison of fecal microbiota from non-human primates with microbiota of human stool samples obtained in previous studies revealed that the gut microbiota of these primates are distinct and reflect host phylogeny. Our analysis provides evidence that the fecal microbiomes of wild primates co-vary with their hosts, and that this is manifested in higher intraspecies similarity among wild primate species, perhaps reflecting species specificity of the microbiome in addition to dietary influences. These results contribute to the limited body of primate microbiome studies and provide a framework for comparative microbiome analysis between human and non-human primates as well as a comparative evolutionary understanding of the human microbiome.


Sensitivity pattern among bacterial isolates in neonatal septicaemia in port Harcourt.
The organisms responsible for neonatal sepsis vary across geographical boundaries and with the time of illness thus periodic bacteriologic surveillance is a neccessity. The present study was therefore carried out to determine the common bacterial pathogens in Port Harcourt and their sensitivity pattern. Four hundred and six neonates were prospectively screened for sepsis over a 6 month period. Sensitivity of the bacterial isolates to different antibiotics was determined using Kirby-Bauer diffusion method. Gram negative organisms predominated (75.1%) with Klebsiella pneumonia (58.2%) being the commonest. The quinolones were the most sensitive antibiotics to the commonly isolated organisms. Klebsiella pneumonia is the commonest organism responsible for neonatal sepsis in Port Harcourt. There is an overall decline in the antibiotic susceptibility to the commonly isolated bacterial pathogens.


Charting a successful course: The academic and clinical success committee's impact on student success.
The road from prematriculation to graduation looks different for each student at each institution. To successfully complete the curriculum, students must often overcome difficulties, both academic and nonacademic. Up to 15% of 3rd-year medical students in the United States are still struggling on the major components of their clerkships and 11% in their 4th year. While there is an established need for medical school remediation, there is little evidence supporting what specifically works across the board. These deficiencies often do not go away on their own and with the need to educate all students, the guidance provided by multiple stakeholders (i.e., administration, staff, faculty, and clinicians) would be necessary to chart a course of success for these students. The Academic and Clinical Success Committee (ACSC) at the Texas A and M University College of Medicine provides a venue to review individual students and provide input, resources, and support on a timely basis. This is a necessary ingredient in guiding the students facing academic and clinical challenges toward successful completion of graduation requirements. Since its incorporation, the work of the ACSC has contributed to a decrease in failures on consecutive block examinations, a decreased failure rate on Step 2 clinical skills (CS), and increased capacity to help students at risk of failing Step 1 to not do so. In this brief report, we illustrate how we developed the ACSC, the impact and levels of success it has had on students, and challenges we have faced.


Why do certain primary health care teams respond better to intimate partner violence than others? A multiple case study.
To analyse how team level conditions influenced health care professionals' responses to intimate partner violence. We used a multiple embedded case study. The cases were four primary health care teams located in a southern region of Spain; two of them considered "good" and two s "average". The two teams considered good had scored highest in practice issues for intimate partner violence, measured via a questionnaire (PREMIS - Physicians Readiness to Respond to Intimate Partner Violence Survey) applied to professionals working in the four primary health care teams. In each case quantitative and qualitative data were collected using a social network questionnaire, interviews and observations. The two "good" cases showed dynamics and structures that promoted team working and team learning on intimate partner violence, had committed social workers and an enabling environment for their work, and had put into practice explicit strategies to implement a women-centred approach. Better individual responses to intimate partner violence were implemented in the teams which: 1) had social workers who were knowledgeable and motivated to engage with others; 2) sustained a structure of regular meetings during which issues of violence were discussed; 3) encouraged a friendly team climate; and 4) implemented concrete actions towards women-centred care.


DNA methylation changes in murine breast adenocarcinomas allow the identification of candidate genes for human breast carcinogenesis.
Epigenetic inactivation due to aberrant promoter methylation is a key process in breast tumorigenesis. Murine models for human breast cancer have been established for nearly every important human oncogene or tumor suppressor gene. Mouse-to-human comparative gene expression and cytogenetic profiling have been widely investigated for these models; however, little is known about the conservation of epigenetic alterations during tumorigenesis. To determine if this key process in human breast tumorigenesis is also mirrored in a murine breast cancer model, we mapped cytosine methylation changes in primary adenocarcinomas and paired lung metastases derived from the polyomavirus middle T antigen mouse model. Global changes in methylcytosine levels were observed in all tumors when compared to the normal mammary gland. Aberrant methylation and associated gene silencing was observed for Hoxa7, a gene that is differentially methylated in human breast tumors, and Gata2, a novel candidate gene. Analysis of HOXA7 and GATA2 expression in a bank of human primary tumors confirms that the expression of these genes is also reduced in human breast cancer. In addition, HOXA7 hypermethylation is observed in breast cancer tissues when compared to adjacent tumor-free tissue. Based on these studies, we present a model in which comparative epigenetic techniques can be used to identify novel candidate genes important for human breast tumorigenesis, in both primary and metastatic tumors.


Smooth pursuit eye tracking and visual fixation in psychosis-prone individuals.
Subjects identified by Perceptual Aberration-Magical Ideation (Per-Mag) scores (n=97), Social Anhedonia (SocAnh) scores (n=45), and Physical Anhedonia (PhysAnh) scores (n=31) as well as normal controls (n=94), underwent psychophysiological and clinical assessment. This is the first published investigation of pursuit system functioning in three groups of questionnaire-identified at-risk individuals. Pursuit during a simple non-monitor tracking task was measured using root-mean-square error (RMSE) scores and pursuit gain scores. Fixation performance was measured in terms of number of saccades away from the central fixation point. The at-risk subjects were more likely to display aberrant smooth pursuit tracking than controls, though there were no significant differences between the at-risk subjects endorsing items relevant to positive-symptom schizotypy and those endorsing items pertaining to negative-symptom schizotypy. The groups did not differ significantly in their visual fixation performance. Participants were also evaluated for the presence of Axis I symptomatology and psychotic-like experiences. Neither the experimental subjects nor the control subjects displayed a significant association between ocular motor performance and psychotic-like experiences. These findings are consistent with prior evidence that pursuit tracking is a trait characteristic, independent of clinical status.


Stress in the Volunteer Caregiver: Human-Centric Technology Can Support Both Caregivers and People with Dementia.
Background and Objectives: Currently, one in eight people over the age of 65 have dementia, and approximately 75% of caregiving is provided by volunteer family members with little or no training. This study aimed to quantify points of stress for home-based caregivers with the aim of reducing stress for them while concurrently supporting quality of life for the people with dementia whom they cared for. The overreaching purpose was to increase our knowledge of the caregiver stress burden and explore potential technologies and behaviors to ease it. Materials and Methods: We interviewed home-based and professional caregivers regarding causes of emotional and physical stress and methods they used to alleviate it. Results: This study found that: (1) dementia symptoms created a burden of stress for home-based caregivers primarily in the areas of medication management, memory loss, hygiene care and disruptive behaviors; (2) home-based caregivers identified "finding available resources" as the most important source of stress relief; (3) a minority of home-based caregivers possessed a resource network and knew how to find resources but all professional caregivers were able to find resources and support; (4) home-based caregivers combated dementia symptoms with positive distractions and human touch with little use of technology, since it was mostly unknown; and 5) facility-based caregivers were knowledgeable and readily used dementia-based technology. Conclusion: Since professional caregivers have access to technological resources that our home-based caregivers lack, one might logically conclude that we should transfer technology used by professionals to those with dementia. However, great caution needs to be in place before we take that step. Successful technology should address the human experience as home-based caregivers try to use new technologies. Human-centric technology addresses the needs of both people with dementia and the home-based caregiver.


Health consequences of uninsurance among adults in the United States: recent evidence and implications.
Uninsured adults have less access to recommended care, receive poorer quality of care, and experience worse health outcomes than insured adults do. The potential health benefits of expanding insurance coverage for these adults may provide a strong rationale for reform. However, evidence of the adverse health effects of uninsurance has been largely based on observational studies with designs that do not support causal conclusions. Although recent research using more rigorous methods may offer a better understanding of this important subject, it has not been comprehensively reviewed. The clinical and economic literature since 2002 was systematically searched. New research contributions were reviewed and evaluated based on their methodological strength. Because the effectiveness of medical care varies considerably by clinical risk and across conditions, the consistency of study findings with clinical expectations was considered in their interpretation. Updated conclusions were formulated from the current body of research. The quality of research has improved significantly, as investigators have employed quasi-experimental designs with increasing frequency to address limitations of earlier research. Recent studies have found consistently positive and often significant effects of health insurance coverage on health across a range of outcomes. In particular, significant benefits of coverage have now been robustly demonstrated for adults with acute or chronic conditions for which there are effective treatments. Based on the evidence to date, the health consequences of uninsurance are real, vary in magnitude in a clinically consistent manner, strengthen the argument for universal coverage in the United States, and underscore the importance of evidence-based determinations in providing health care to a diverse population of adults.


Lack of association of DRD2 rs1800497 (Taq1A) polymorphism with smoking cessation in a nicotine replacement therapy randomized trial.
We previously reported evidence that the T allele of the dopamine type-2 receptor (DRD2) rs1800497 polymorphism is associated with improved response to nicotine replacement therapy (NRT) relative to placebo and that this association may only be present in females. However, evidence of the poor replication validity of genetic association studies is growing, particularly among those that report subgroup analyses. We therefore attempted to replicate our previous finding of an association between the DRD2 rs1800497 genotype and response to NRT in a new, larger cohort, with greater statistical power. Participants were randomly assigned to one of two levels of smoking cessation behavioral support (usual care vs. weekly support). All participants received 8 weeks of 15-mg NRT transdermal patch. The presence of one or more T alleles was associated with a slightly but not significantly lower likelihood of abstinence at 3 and 6 months. We found evidence of a genotype x sex interaction effect. However, stratified analyses indicated a main effect of genotype opposite to the effect reported previously, with females carrying one or more copies of the T allele less likely to be abstinent. Our results do not support an association between the DRD2 rs1800497 (Taq1A) polymorphism and response to NRT, contrary to our previous study.


Effects of childhood trauma, daily stress, and emotions on daily cortisol levels in individuals vulnerable to suicide.
Suicide is a leading cause of mortality worldwide. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, has been identified as 1 potential risk factor. Evidence has indicated that childhood trauma is associated with dysregulated cortisol reactivity to stress in adulthood. The current study investigated for the first time whether childhood trauma and daily stressors and emotions were associated with diurnal cortisol levels over a 7-day study in individuals vulnerable to suicide. One hundred and forty-two participants were categorized according to their suicidal history into 3 groups: suicide attempt, suicidal ideation, or control group. Participants completed questionnaires before commencing a 7-day study. Cortisol samples were provided immediately upon waking, at 15 min, 30 min, 45 min, 3 hr, 6 hr, 9 hr, and 12 hr on 7 consecutive days. Measures of daily stressors, mood, defeat, and entrapment were completed at the end of each day. Participants in the suicide attempt and ideation groups released significantly lower cortisol upon awakening (CAR) and had a tendency toward flatter wake-peak to 12 hr (WP-12) cortisol slopes compared to controls. Childhood trauma was found to be associated with significantly lower CAR and a tendency toward flatter WP-12 cortisol slope. Childhood trauma also had an indirect effect on suicide vulnerability group membership via lower daily CAR levels. Lower CAR was associated with increased suicide ideation at 1 month but not 6 months. Daily stress and emotion measures were not associated with cortisol levels. This is the first 7-day daily diary investigation of naturally fluctuating cortisol levels in individuals vulnerable to suicide. The results indicate that dysregulated HPA axis activity is associated with suicidal ideation and behavior. Childhood trauma appears to be an important distal factor associated with HPA-axis dysregulation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Preconscious processing biases predict emotional reactivity to stress.
Anxiety vulnerability is associated with biases in attention: a tendency to selectively process negative relative to neutral or positive information. It is not clear whether this bias is: 1) related to the physiological response to stressful events, and 2) causally related to the development of anxiety disorders. We tested the predictive value of both preconscious and conscious attention biases in a prospective study of stress reactivity in a nonclinical sample. One hundred four male participants were assessed at baseline and then again 4 months (n = 82) and 8 months later (n = 70). Salivary cortisol and self-report measures were obtained at the baseline testing session in addition to measures of biased attention. Subsequent emotional reactivity was assessed by means of salivary cortisol and self-reported state-anxiety responses during a laboratory-based stressor (4 months later) as well as during a real-life stressor 8 months later (i.e., examination period). Regression analyses indicated that a preconscious negative processing bias was the best predictor of the cortisol response to stressful events. Importantly, a measure of selective processing provided a better indicator of subsequent emotional reactivity than self-report measures of neuroticism, trait-anxiety, and extraversion. These results suggest that preconscious biases toward negative material play a causal role in heightened anxiety vulnerability. Our results illustrate the potential utility of preconscious biases in attention in providing an early marker of anxiety vulnerability and a potential target for treatment intervention.


Tigecycline attenuates polymorphonuclear leukocyte (PMN) receptors but not functions.
Tigecycline achieves high intracellular concentrations in polymorphonuclear leukocytes (PMNs). To evaluate the effects of tigecycline on human PMNs, PMNs were incubated with tigecycline dilutions (0.1 to 100 mg L-1). Phagocytosis-associated PMN Fcγ- and complement receptors as well as phagocytosis and oxidative burst induced by Staphylococcus aureus were measured by flow cytometry. Incubation with tigecycline caused small but significant decreases in the density of complement receptors CD11b and CD35 (all concentrations) and Fcγ receptors CD16 and CD32 (high concentrations), but not in the percentages of receptor-bearing cells, except for small reductions in the proportions of CD16 positive cells at high concentrations. Tigecycline had no effect on phagocytosis or oxidative burst induced by S. aureus. Tigecycline was thus associated with decreased density of PMN complement and (at high concentrations) Fcγ receptors. Although statistically significant, the differences were small and did not influence the PMN function as measured by phagocytosis and oxidative burst.


The frequency of magnesium consumption directly influences its serum concentration and the amount of elutable bone magnesium in rats.
We investigated the influence of Mg feeding frequency on the variation in serum Mg concentration and tissue Mg levels in Mg-deficient rats. Sprague-Dawley rats, which had been fed a Mg-deficient diet for 14 d, were divided into 3 groups that were kept on 3 diets differing in their Mg content. The rats were fed 0.5-fold (Mg250 group), 1-fold (Mg500 group), or 1.5-fold (Mg750 group) the amounts of recommended Mg in their standard AIN-93G diet (Mg: 478 mg/kg diet) during the recovery period (12 d). The Mg500 and Mg750 groups were intermittently fed (Mg500, every 2 d; Mg750, every 3 d) so that their total intake of Mg during the recovery period could equal the Mg intake of the Mg250 group. The serum Mg concentrations increased in the 3 groups after feeding with a Mg-containing diet. However, serum Mg levels were only maintained within the normal range in the Mg250 group. After feeding on the Mg-deficient diet, in the intermittently fed groups, serum Mg concentrations decreased. Urinary Mg excretion was higher and Mg retention was lower in the Mg500 and Mg750 groups than in the Mg250 group. Moreover, bone Mg, especially elutable bone Mg, was lower in the Mg500 and Mg750 groups than in the Mg250 group. The elutable fraction of bone Mg correlated to the coefficient of variation of serum Mg concentration. In conclusion, for the maintenance of serum Mg concentration, it is important to increase the amount of elutable bone Mg by frequent Mg consumption.


Drug treatment for spinal muscular atrophy type I.
Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells of the spinal cord, which leads to progressive muscle weakness. Children with SMA type I will never be able to sit without support and usually die by the age of two years. There are no known efficacious drug treatments that influence the course of the disease. This is an update of a review first published in 2009. To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA type I, and to assess if such therapy can be given safely. Drug treatment for SMA types II and III is the topic of a separate updated Cochrane review. We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to 8 March 2011). We searched the Clinical Trials Registry of the U.S. National Institute of Health (www.ClinicalTrials.gov) (8 March 2011) to identify additional trials that had not yet been published. We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA type I. Participants had to fulfil the clinical criteria and have a deletion or mutation of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis.The primary outcome measure was time from birth until death or full time ventilation. Secondary outcome measures were development of rolling, sitting or standing within one year after the onset of treatment, and adverse events attributable to treatment during the trial period. Two authors (RW and AV) independently reviewed and extracted data from all potentially relevant trials. For included studies, pooled relative risks and standardised mean differences were to be calculated to assess treatment efficacy. One small randomised controlled study comparing riluzole treatment to placebo for 10 SMA type 1 children was identified and included in the original review. No further trials were identified for the update in 2011. Regarding the primary outcome measure, three of seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months, whereas all three children in the placebo group died; but the difference was not statistically significant. Regarding the secondary outcome measures, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand, and no adverse effects were observed. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and because of baseline differences. Follow-up of the 10 included children was complete. No drug treatment for SMA type I has been proven to have significant efficacy.


Self-administered acupressure for insomnia disorder: a pilot randomized controlled trial.
Self-administered acupressure has potential as a low-cost alternative treatment for insomnia. To evaluate the short-term effects of self-administered acupressure for alleviating insomnia, a pilot randomized controlled trial was conducted. Thirty-one subjects (mean age: 53.2 years; 77.4% female) with insomnia disorder were recruited from a community. The participants were randomized to receive two lessons on either self-administered acupressure or sleep hygiene education. The subjects in the self-administered acupressure group (n = 15) were taught to practise self-administered acupressure daily for 4 weeks. The subjects in the comparison group (n = 16) were advised to follow sleep hygiene education. The primary outcome was the Insomnia Severity Index (ISI). Other measures included a sleep diary, Hospital Anxiety and Depression Scale and Short-form Six-Dimension. The subjects in the self-administered acupressure group had a significantly lower ISI score than the subjects in the sleep hygiene education group at week 8 (effect size = 0.56, P = 0.03). However, this observed group difference did not reach a statistically significant level after Bonferroni correction. With regard to the secondary outcomes, moderate between-group effect sizes were observed in sleep onset latency and wake after sleep onset based on the sleep diary, although the differences were not significant. The adherence to self-administered acupressure practice was satisfactory, with 92.3% of the subjects who completed the lessons still practising acupressure at week 8. In conclusion, self-administered acupressure taught in a short training course may be a feasible approach to improve insomnia. Further fully powered confirmatory trials are warranted.


Temperature Sensing Is Distributed throughout the Regulatory Network that Controls FLC Epigenetic Silencing in Vernalization.
Many organisms need to respond to complex, noisy environmental signals for developmental decision making. Here, we dissect how Arabidopsis plants integrate widely fluctuating field temperatures over month-long timescales to progressively upregulate VERNALIZATION INSENSITIVE3 (VIN3) and silence FLOWERING LOCUS C (FLC), aligning flowering with spring. We develop a mathematical model for vernalization that operates on multiple timescales-long term (month), short term (day), and current (hour)-and is constrained by experimental data. Our analysis demonstrates that temperature sensing is not localized to specific nodes within the FLC network. Instead, temperature sensing is broadly distributed, with each thermosensory process responding to specific features of the plants' history of exposure to warm and cold. The model accurately predicts FLC silencing in new field data, allowing us to forecast FLC expression in changing climates. We suggest that distributed thermosensing may be a general property of thermoresponsive regulatory networks in complex natural environments.


Biomarkers of peripheral muscle fatigue during exercise.
Biomarkers of peripheral muscle fatigue (BPMFs) are used to offer insights into mechanisms of exhaustion during exercise in order to detect abnormal fatigue or to detect defective metabolic pathways. This review aims at describing recent advances and future perspectives concerning the most important biomarkers of muscle fatigue during exercise. BPMFs are classified according to the mechanism of fatigue related to adenosine-triphosphate-metabolism, acidosis, or oxidative-metabolism. Muscle fatigue is also related to an immunological response. impaired calcium handling, disturbances in bioenergetic pathways, and genetic responses. The immunological and genetic response may make the muscle susceptible to fatigue but may not directly cause muscle fatigue. Production of BPMFs is predominantly dependent on the type of exercise. BPMFs need to change as a function of the process being monitored, be stable without appreciable diurnal variations, correlate well with exercise intensity, and be present in detectable amounts in easily accessible biological fluids. The most well-known BPMFs are serum lactate and interleukin-6. The most widely applied clinical application is screening for defective oxidative metabolism in mitochondrial disorders by means of the lactate stress test. The clinical relevance of most other BPMFs, however, is under debate, since they often depend on age, gender, physical fitness, the energy supply during exercise, the type of exercise needed to produce the BPMF, and whether healthy or diseased subjects are investigated. Though the role of BPMFs during fatigue is poorly understood, measuring BPMFs under specific, standardised conditions appears to be helpful for assessing biological states or processes during exercise and fatigue.


Integrated primary care for patients with mental and physical multimorbidity: cluster randomised controlled trial of collaborative care for patients with depression comorbid with diabetes or cardiovascular disease.
To test the effectiveness of an integrated collaborative care model for people with depression and long term physical conditions. Cluster randomised controlled trial. 36 general practices in the north west of England. 387 patients with a record of diabetes or heart disease, or both, who had depressive symptoms (≥ 10 on patient health questionaire-9 (PHQ-9)) for at least two weeks. Mean age was 58.5 (SD 11.7). Participants reported a mean of 6.2 (SD 3.0) long term conditions other than diabetes or heart disease; 240 (62%) were men; 360 (90%) completed the trial. Collaborative care included patient preference for behavioural activation, cognitive restructuring, graded exposure, and/or lifestyle advice, management of drug treatment, and prevention of relapse. Up to eight sessions of psychological treatment were delivered by specially trained psychological wellbeing practitioners employed by Improving Access to Psychological Therapy services in the English National Health Service; integration of care was enhanced by two treatment sessions delivered jointly with the practice nurse. Usual care was standard clinical practice provided by general practitioners and practice nurses. The primary outcome was reduction in symptoms of depression on the self reported symptom checklist-13 depression scale (SCL-D13) at four months after baseline assessment. Secondary outcomes included anxiety symptoms (generalised anxiety disorder 7), self management (health education impact questionnaire), disability (Sheehan disability scale), and global quality of life (WHOQOL-BREF). 19 general practices were randomised to collaborative care and 20 to usual care; three practices withdrew from the trial before patients were recruited. 191 patients were recruited from practices allocated to collaborative care, and 196 from practices allocated to usual care. After adjustment for baseline depression score, mean depressive scores were 0.23 SCL-D13 points lower (95% confidence interval -0.41 to -0.05) in the collaborative care arm, equal to an adjusted standardised effect size of 0.30. Patients in the intervention arm also reported being better self managers, rated their care as more patient centred, and were more satisfied with their care. There were no significant differences between groups in quality of life, disease specific quality of life, self efficacy, disability, and social support. Collaborative care that incorporates brief low intensity psychological therapy delivered in partnership with practice nurses in primary care can reduce depression and improve self management of chronic disease in people with mental and physical multimorbidity. The size of the treatment effects were modest and were less than the prespecified effect but were achieved in a trial run in routine settings with a deprived population with high levels of mental and physical multimorbidity. ISRCTN80309252.


Live imaging of protein kinase activities in transgenic mice expressing FRET biosensors.
Genetically-encoded biosensors based on the principle of Förster resonance energy transfer (FRET) have been widely used in biology to visualize the spatiotemporal dynamics of signaling molecules. Despite the increasing multitude of these biosensors, their application has been mostly limited to cultured cells with transient biosensor expression, due to particular difficulties in the development of transgenic mice that express FRET biosensors. In this study, we report the efficient generation of transgenic mouse lines expressing heritable and functional biosensors for ERK and PKA. These transgenic mice were created by the cytoplasmic co-injection of Tol2 transposase mRNA and a circular plasmid harbouring Tol2 recombination sites. High expression of the biosensors in a wide range of cell types allowed us to screen newborn mice simply by inspection. Observation of these transgenic mice by two-photon excitation microscopy yielded real-time activity maps of ERK and PKA in various tissues, with greatly improved signal-to-background ratios. Our transgenic mice may be bred into diverse genetic backgrounds; moreover, the protocol we have developed paves the way for the generation of transgenic mice that express other FRET biosensors, with important applications in the characterization of physiological and pathological signal transduction events in addition to drug development and screening.


Early life humoral response of ducks to DNA immunization against hepadnavirus large envelope protein.
DNA vaccination may represent an interesting strategy for early life immunization. However, in some cases, this approach has been shown to induce a tolerance rather than immunity. We have compared the efficiency of neonatal DNA or protein immunization against hepadnavirus envelope protein using the duck hepatitis B virus (DHBV) model. Three-day-old ducklings were immunized with either a plasmid encoding the DHBV pre-S/S large envelope protein (L), or a recombinant preS protein, followed by sequential DNA or protein boosts at weeks 4 and 15. Our results showed that genetic immunization of duck neonates induced specific humoral response to DHBV L protein. Interestingly, an enhanced antibody response was elicited when animals received DNA priming-DNA boosting as compared to DNA priming-protein boosting.


Describing the relationship between cat bites and human depression using data from an electronic health record.
Data mining approaches have been increasingly applied to the electronic health record and have led to the discovery of numerous clinical associations. Recent data mining studies have suggested a potential association between cat bites and human depression. To explore this possible association in more detail we first used administrative diagnosis codes to identify patients with either depression or bites, drawn from a population of 1.3 million patients. We then conducted a manual chart review in the electronic health record of all patients with a code for a bite to accurately determine which were from cats or dogs. Overall there were 750 patients with cat bites, 1,108 with dog bites, and approximately 117,000 patients with depression. Depression was found in 41.3% of patients with cat bites and 28.7% of those with dog bites. Furthermore, 85.5% of those with both cat bites and depression were women, compared to 64.5% of those with dog bites and depression. The probability of a woman being diagnosed with depression at some point in her life if she presented to our health system with a cat bite was 47.0%, compared to 24.2% of men presenting with a similar bite. The high proportion of depression in patients who had cat bites, especially among women, suggests that screening for depression could be appropriate in patients who present to a clinical provider with a cat bite. Additionally, while no causative link is known to explain this association, there is growing evidence to suggest that the relationship between cats and human mental illness, such as depression, warrants further investigation.


A survey of malaria in Indochinese refugees arriving in the United States, 1980.
During the months April-June and October-November 1980, a survey was conducted among Indochinese refugees arriving in California to assess the prevalence of malaria. During the two study periods, 3,433 refugees were met and 3,289 (95.8%) of the arriving refugees were screened for malaria by examining thick blood smears and by indirect fluorescent malaria antibody tests of blood absorbed on filter paper. Examination of the blood smears showed that the overall patency rates were 1.7% and 0.6% for the first and second surveys, respectively. The Cambodian Refugees and refugees from camps in Thailand had the highest patency rate in the first survey. In the second survey, the Cambodian refugees and refugees from camps in Indonesia had the highest patency rate. The average malaria seropositivity rate was 15% in the first and 13.6% in the second survey. The Laotian refugees had the highest rate of malaria seropositivity in both surveys. Plasmodium vivax was the most commonly identified species in blood examination, while a higher rate of seropositivity to P. falciparum was found in both surveys. This study indicates that the malaria infection rate was at least 1.7% based on blood smear examination but might be as high as 45% based on serologic examinations. The results of this study when combined with malaria surveillance indicate that the likelihood of introduced malaria in the United States from the Indochinese refugees is low.


Cdc2 and Mos regulate Emi2 stability to promote the meiosis I-meiosis II transition.
The transition of oocytes from meiosis I (MI) to meiosis II (MII) requires partial cyclin B degradation to allow MI exit without S phase entry. Rapid reaccumulation of cyclin B allows direct progression into MII, producing a cytostatic factor (CSF)-arrested egg. It has been reported that dampened translation of the anaphase-promoting complex (APC) inhibitor Emi2 at MI allows partial APC activation and MI exit. We have detected active Emi2 translation at MI and show that Emi2 levels in MI are mainly controlled by regulated degradation. Emi2 degradation in MI depends not on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), but on Cdc2-mediated phosphorylation of multiple sites within Emi2. As in MII, this phosphorylation is antagonized by Mos-mediated recruitment of PP2A to Emi2. Higher Cdc2 kinase activity in MI than MII allows sufficient Emi2 phosphorylation to destabilize Emi2 in MI. At MI anaphase, APC-mediated degradation of cyclin B decreases Cdc2 activity, enabling Cdc2-mediated Emi2 phosphorylation to be successfully antagonized by Mos-mediated PP2A recruitment. These data suggest a model of APC autoinhibition mediated by stabilization of Emi2; Emi2 proteins accumulate at MI exit and inhibit APC activity sufficiently to prevent complete degradation of cyclin B, allowing MI exit while preventing interphase before MII entry.


Semi-analytical method for light interaction with 1D-periodic nanoplasmonic structures.
We present a detailed description of a computationally efficient, semi-analytical method (SAM) to calculate the electomagnetic field distribution in a 1D-periodic, subwavelength-structured metal film placed between dielectric substrates. The method is roughly three orders of magnitude faster than the finite-element method (FEM). SAM is used to study the resonant transmission of light through nanoplasmonic structures, and to analyze the role of fundamental and higher-order Bloch surface plasmons in transmission enhancement. The method is also suitable for solving the eigenvalue problem and finding modes of the structure. Results obtained with SAM, FEM, and the finite-difference time-domain method show very good agreement for various parameters of the structure.


New perspectives on dairy and cardiovascular health.
CVD are the leading cause of mortality and morbidity worldwide. One of the key dietary recommendations for CVD prevention is reduction of saturated fat intake. Yet, despite milk and dairy foods contributing on average 27 % of saturated fat intake in the UK diet, evidence from prospective cohort studies does not support a detrimental effect of milk and dairy foods on risk of CVD. The present paper provides a brief overview of the role of milk and dairy products in the diets of UK adults, and will summarise the evidence in relation to the effects of milk and dairy consumption on CVD risk factors and mortality. The majority of prospective studies and meta-analyses examining the relationship between milk and dairy product consumption and risk of CVD show that milk and dairy products, excluding butter, are not associated with detrimental effects on CVD mortality or risk biomarkers that include serum LDL-cholesterol. In addition, there is increasing evidence that milk and dairy products are associated with lower blood pressure and arterial stiffness. These apparent benefits of milk and dairy foods have been attributed to their unique nutritional composition, and suggest that the elimination of milk and dairy may not be the optimum strategy for CVD risk reduction.


Effects of time perspective and self-control on procrastination and Internet addiction.
Background and aims College students experiencing stress show tendencies to procrastinate and can develop Internet addiction problems. This study investigated the structural relationship between time perspective and self-control on procrastination and Internet addiction. Methods College students (N = 377) residing in South Korea completed the following questionnaires: the Pathological Internet Use Behavior Symptom Scale for Adults, the Zimbardo Time Perspective Inventory, the Self-Control Rating Scale, and the Aitken Procrastination Inventory. The sample variance-covariance matrix was analyzed using AMOS 20.0. Results Time perspective had a direct effect on self-control and an indirect effect on Internet use and procrastination. In addition, self-control affected procrastination and Internet use. Conclusions Individuals with a present-oriented time perspective tend to evidence poorer self-control, increasing the likelihood of procrastination and Internet addiction. Individuals with a future-oriented time perspective, on the other hand, tend to have stronger self-control, decreasing their risk of procrastination and Internet addiction.


Implementation and evaluation of a primary care preceptorship.
As part of overall curricular reform, the University of Michigan Medical School developed and implemented a required primary care clerkship for third-year students in July 1993. The clerkship was intended to help students develop an understanding of the principles of comprehensive health care and of disease prevention and the knowledge and skills to manage common problems in primary care. The successful implementation of the program was based on agreement across primary care specialties on a common set of goals and objectives, which were developed with the involvement of community practitioners; frequent communication with preceptors to identify problems and students at risk; active feedback to preceptors; and thorough formal and informal evaluations of students and preceptors. Students and preceptors felt the program was beneficial to them; still, the medical school must in the future address concerns about more accurately grading students, retaining preceptors, and ensuring that students be exposed to the broadest possible range of primary care patients and services.


Clinical and immunological features of severe and moderate coronavirus disease 2019.
BACKGROUNDSince December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODSIn this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTSThe median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSIONThe SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATIONThis is a retrospective observational study without a trial registration number.FUNDINGThis work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).


Attitudes among dentists and dental hygienists towards extended scope and independent practice of dental hygienists.
Attitudes of dentists and dental hygienists towards extended scope and independent dental hygiene practice are described in several studies, but the results are heterogenous. The purpose of this systematic review was to compare the attitudes of dentists and dental hygienists towards extended scope and independent dental hygiene practice. PubMed, AMED and CINAHL were screened by two independent assessors to identify relevant studies. Only quantitative studies that reported the percentages of dentists' and dental hygienists' attitude towards extended scope and independent dental hygiene practice were included. The random-effects model was used to synthesise possible heterogenous influences. Meta proportions with regard to a positive attitude towards extended scope of practice are 0.54 for dentists and 0.81 for dental hygienists. Meta proportions of a positive attitude towards independent practice are 0.14 for dentists and 0.59 for dental hygienists. A meta analysis with regard to negative attitudes could only be performed on extended scope of practice and did not reveal a difference between the two professions. We obtained homogeneous outcomes of the studies included regarding negative attitudes of dentists . A minority of dentists hold negative attitudes towards extended scope of dental hygiene practice. Study outcomes regarding negative attitudes of dental hygienists were heterogeneous. Positive attitudes are present among a majority of dentists and dental hygienists with regard to extended scope of dental hygiene practice, while for independent dental hygiene practice this holds for a minority of dentists and a majority of dental hygienists.


Effects of a honeybee lactic acid bacterial microbiome on human nasal symptoms, commensals, and biomarkers.
Lactic acid bacteria (LAB) can restore commensal microbiomes and prevent infections. Arguably, nasal administrations of LAB may therefore be beneficial in chronic rhinosinusitis (CRS). Previous studies have examined effects of topical/nasal LAB in children with secretory otitis media, but little is as yet known about their effects on the human nasal airway. The aim of this pilot study was to examine effects on nasal symptoms and commensal bacteria in healthy subjects of nasal administration of a honeybee LAB microbiome; ie, a mixture of 9 Lactobacillus spp. and 4 Bifidobacterium spp. obtained from the honeybee Apis mellifera. Furthermore, we aimed to assess whether or not the honeybee LAB produced a local inflammatory response. Twenty-two healthy subjects received a single administration of honeybee LAB in a sham-controlled, double-blinded, and crossover design. Using questionnaires, microbiological methods, and nasal lavages, they were assessed regarding symptoms, changes to commensal bacteria, and inflammatory products in nasal lavage fluids. The honeybee LAB did not produce any symptoms or other untoward effects. No changes were observed of commensal bacteria by the honeybee LAB, and no inflammatory response was detected (compared to sham); ie, unaffected nasal lavage fluid levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), monokine induced by interferon-γ (MIG), interleukin-15 (IL-15), epidermal growth factor (EGF), eotaxin, interferon gamma-induced protein-10 (IP-10), and interleukin-1 receptor antagonist (IL-1RA). A single human nasal administration of a honeybee LAB microbiome is well tolerated. Specifically, it does not affect commensal bacteria and does not produce an inflammatory response.


Mass is all that matters in the size-weight illusion.
An object in outer space is weightless due to the absence of gravity, but astronauts can still judge whether one object is heavier than another one by accelerating the object. How heavy an object feels depends on the exploration mode: an object is perceived as heavier when holding it against the pull of gravity than when accelerating it. At the same time, perceiving an object's size influences the percept: small objects feel heavier than large objects with the same mass (size-weight illusion). Does this effect depend on perception of the pull of gravity? To answer this question, objects were suspended from a long wire and participants were asked to push an object and rate its heaviness. This way the contribution of gravitational forces on the percept was minimised. Our results show that weight is not at all necessary for the illusion because the size-weight illusion occurred without perception of weight. The magnitude of the illusion was independent of whether inertial or gravitational forces were perceived. We conclude that the size-weight illusion does not depend on prior knowledge about weights of object, but instead on a more general knowledge about the mass of objects, independent of the contribution of gravity. Consequently, the size-weight illusion will have the same magnitude on Earth as it should have on the Moon or even under conditions of weightlessness.


Automated discovery of local search heuristics for satisfiability testing.
The development of successful metaheuristic algorithms such as local search for a difficult problem such as satisfiability testing (SAT) is a challenging task. We investigate an evolutionary approach to automating the discovery of new local search heuristics for SAT. We show that several well-known SAT local search algorithms such as Walksat and Novelty are composite heuristics that are derived from novel combinations of a set of building blocks. Based on this observation, we developed CLASS, a genetic programming system that uses a simple composition operator to automatically discover SAT local search heuristics. New heuristics discovered by CLASS are shown to be competitive with the best Walksat variants, including Novelty+. Evolutionary algorithms have previously been applied to directly evolve a solution for a particular SAT instance. We show that the heuristics discovered by CLASS are also competitive with these previous, direct evolutionary approaches for SAT. We also analyze the local search behavior of the learned heuristics using the depth, mobility, and coverage metrics proposed by Schuurmans and Southey.


Dynamic reprogramming of 5-hydroxymethylcytosine during early porcine embryogenesis.
DNA active demethylation is an important epigenetic phenomenon observed in porcine zygotes, yet its molecular origins are unknown. Our results show that 5-methylcytosine (5mC) converts into 5-hydroxymethylcytosine (5hmC) during the first cell cycle in porcine in vivo fertilization (IVV), IVF, and SCNT embryos, but not in parthenogenetically activated embryos. Expression of Ten-Eleven Translocation 1 (TET1) correlates with this conversion. Expression of 5mC gradually decreases until the morula stage; it is only expressed in the inner cell mass, but not trophectoderm regions of IVV and IVF blastocysts. Expression of 5mC in SCNT embryos is ectopically distinct from that observed in IVV and IVF embryos. In addition, 5hmC expression was similar to that of 5mC in IVV cleavage-stage embryos. Expression of 5hmC remained constant in IVF and SCNT embryos, and was evenly distributed among the inner cell mass and trophectoderm regions derived from IVV, IVF, and SCNT blastocysts. Ten-Eleven Translocation 3 was highly expressed in two-cell embryos, whereas TET1 and TET2 were highly expressed in blastocysts. These data suggest that TET1-catalyzed 5hmC may be involved in active DNA demethylation in porcine early embryos. In addition, 5mC, but not 5hmC, participates in the initial cell lineage specification in porcine IVV and IVF blastocysts. Last, SCNT embryos show aberrant 5mC and 5hmC expression during early porcine embryonic development.


8-Hydroxy-2-deoxy-guanosine identifies oxidative DNA damage in a rural prediabetes cohort.
Rising levels of oxidative stress play an important role in the pathogenesis of type 2 diabetes mellitus. Therefore, we investigated the serum level of 8-hydroxy-2-deoxy-guanosine (8-OHdG) as an early oxidative stress marker in patients with prediabetes and with type 2 diabetes mellitus. Convenience sampling from people attending a diabetes screening clinic. Participants at the rural diabetes screening clinic had their medical history recorded as well as body mass index, blood glucose, cholesterol, glutathione, malondialdehyde, fasting blood glucose and 8-OHdG measured. Statistical analysis was performed using ANOVA followed by Sheffe posthoc test for between-group differences. The 8-OHdG level was significantly greater in the prediabetes (516.5 +/- 260 pg/ml) compared to control group (177.8 +/- 91 pg/ml; P < 0.01). The diabetes group (1926.9 +/- 1197 pg/ml) had the highest level of 8-OHdG, being approximately four times greater compared to the prediabetes group (P < 0.001). No significant change in the cholesterol profile, MDA level indicative of lipid peroxidation and antioxidant activity as measured by erythrocyte reduced glutathione was observed in the prediabetes group compared to the control group (P > 0.05). 8-OHdG levels in both the prediabetes and diabetes group were increased from control values suggesting a role for 8-OHdG as an early disease marker that may be more sensitive compared to cholesterol, MDA and erythrocyte reduced glutathione levels, which were within normal limits. This is of clinical significance as 8-OHdG is a strong indicator of oxidative stress related DNA damage within blood vessel walls and other tissue that increases the risk of cardiovascular disease.


Prevalence of Emanuel syndrome: theoretical frequency and surveillance result.
Constitutional t(11;22)(q23;q11) is the most frequent recurrent non-Robertsonian translocation in humans. Balanced carriers of t(11;22) usually manifest no clinical symptoms, and are often identified after the birth of offspring with an unbalanced form of this translocation, known as Emanuel syndrome. To determine the prevalence of the disorder, we sent surveillance questionnaires to 735 core hospitals in Japan. The observed number of Emanuel syndrome cases was 36 and that of t(11;22) balanced translocation carriers, 40. On the basis of the de novo t(11;22) translocation frequency in sperm from healthy men, we calculated the frequency of the translocations in the general population. Accordingly, the prevalence of Emanuel syndrome was estimated at 1 in 110,000. Based on this calculation, the estimated number of Emanuel syndrome cases in Japan is 1063 and of t(11;22) balanced translocation carriers, 16,604, which are much higher than the numbers calculated from the questionnaire responses. It is possible that this discordance is partly attributable to a lack of disease identification. Further efforts should be made to increase the awareness of Emanuel syndrome to ensure a better quality of life for affected patients and their families.


Mechanistic basis of altered morphine disposition in nonalcoholic steatohepatitis.
Morphine is metabolized in humans to morphine-3-glucuronide (M3G) and the pharmacologically active morphine-6-glucuronide (M6G). The hepatobiliary disposition of both metabolites relies upon multidrug resistance-associated proteins Mrp3 and Mrp2, located on the sinusoidal and canalicular membrane, respectively. Nonalcoholic steatohepatitis (NASH), the severe stage of nonalcoholic fatty liver disease, alters xenobiotic metabolizing enzyme and transporter function. The purpose of this study was to determine whether NASH contributes to the large interindividual variability and postoperative adverse events associated with morphine therapy. Male Sprague-Dawley rats were fed a control diet or a methionine- and choline-deficient diet to induce NASH. Radiolabeled morphine (2.5 mg/kg, 30 µCi/kg) was administered intravenously, and plasma and bile (0-150 or 0-240 minutes), liver and kidney, and cumulative urine were analyzed for morphine and M3G. The antinociceptive response to M6G (5 mg/kg) was assessed (0-12 hours) after direct intraperitoneal administration since rats do not produce M6G. NASH caused a net decrease in morphine concentrations in the bile and plasma and a net increase in the M3G/morphine plasma area under the concentration-time curve ratio, consistent with upregulation of UDP-glucuronosyltransferase Ugt2b1. Despite increased systemic exposure to M3G, NASH resulted in decreased biliary excretion and hepatic accumulation of M3G. This shift toward systemic retention is consistent with the mislocalization of canalicular Mrp2 and increased expression of sinusoidal Mrp3 in NASH and may correlate to increased antinociception by M6G. Increased metabolism and altered transporter regulation in NASH provide a mechanistic basis for interindividual variability in morphine disposition that may lead to opioid-related toxicity.


Ultrastructural studies of time-course and cellular specificity of interleukin-1 mediated islet cytotoxicity.
Previous electron-microscopic studies of isolated islets of Langerhans exposed to the monokine interleukin-1 for 7 days have indicated that interleukin-1 is cytotoxic to all islet cells. To study the time-course and possible cellular specificity of interleukin-1 cytotoxicity to islets exposed to interleukin-1 for short time periods, isolated rat or human islets were incubated with or without 25 U/ml highly purified human interleukin-1 for 24 h. Samples of rat islets were taken after 5 min, 30 min, 1, 2, 4, 6, 8, 10, 12, 16, 20 and 24 h and samples of human islets after 5 min, 30 min and 24 h of incubation and examined by electron microscopy in a blinded fashion. Already after 30 min, accumulation of opaque intracytoplasmic bodies without apparent surrounding membranes, and autophagic vacuoles were seen in about 20% of the beta cells examined in rat islets exposed to interleukin-1. After 16 h of incubation with interleukin-1, more than 80% of rat beta cells showed signs of degeneration. Beta cell specific changes similar to those observed in rat islets exposed to IL-1 for 30 min were seen in human islets exposed to IL-1 for 24 h. The described changes were not observed in alpha cells in interleukin-1-treated rat or human islets, or in alpha and beta cells in control islets. Passing interleukin-1 over columns containing Sepharose-coupled anti-interleukin-1 antibody completely removed the beta cell cytotoxic action on rat islets.(ABSTRACT TRUNCATED AT 250 WORDS)


Hearing loss associated with repeated MRI acquisition procedure-related acoustic noise exposure: an occupational cohort study.
To study the effects of repeated exposure to MRI-related acoustic noise during image acquisition procedures (scans) on hearing. A retrospective occupational cohort study was performed among workers of an MRI manufacturing facility (n=474). Longitudinal audiometry data from the facility's medical surveillance scheme collected from 1973 to 2010 were analysed by studying the association of cumulative exposure to MRI-related acoustic noise from voluntary (multiple) MRI scans and the hearing threshold of the volunteer. Repeated acoustic noise exposure during volunteer MRI scans was found to be associated with a small exposure-dependent increased rate change of hearing threshold level (dB/year), but the association was only found related to the number of voluntary MRI scans and not to modelled cumulative noise exposure (dB*hour) based on MRI-system type. The increased rate change of hearing threshold level was found to be statistically significant for the frequencies 500, 1000, 2000, 3000 and 4000 Hz in the right ear. From our longitudinal cohort study, it appeared that exposure to noise from voluntarily MRI scans may have resulted in a slight amount of hearing loss. Mandatory use of hearing protection might have prevented more severe hearing loss. Lack of consistency in findings between the left and right ears and between the two exposure measures prohibits definitive conclusions. Further research that addresses the study's methodological limitations is warranted to corroborate our findings.


Effects of Brain Atlases and Machine Learning Methods on the Discrimination of Schizophrenia Patients: A Multimodal MRI Study.
Recently, machine learning techniques have been widely applied in discriminative studies of schizophrenia (SZ) patients with multimodal magnetic resonance imaging (MRI); however, the effects of brain atlases and machine learning methods remain largely unknown. In this study, we collected MRI data for 61 first-episode SZ patients (FESZ), 79 chronic SZ patients (CSZ) and 205 normal controls (NC) and calculated 4 MRI measurements, including regional gray matter volume (GMV), regional homogeneity (ReHo), amplitude of low-frequency fluctuation and degree centrality. We systematically analyzed the performance of two classifications (SZ vs NC; FESZ vs CSZ) based on the combinations of three brain atlases, five classifiers, two cross validation methods and 3 dimensionality reduction algorithms. Our results showed that the groupwise whole-brain atlas with 268 ROIs outperformed the other two brain atlases. In addition, the leave-one-out cross validation was the best cross validation method to select the best hyperparameter set, but the classification performances by different classifiers and dimensionality reduction algorithms were quite similar. Importantly, the contributions of input features to both classifications were higher with the GMV and ReHo features of brain regions in the prefrontal and temporal gyri. Furthermore, an ensemble learning method was performed to establish an integrated model, in which classification performance was improved. Taken together, these findings indicated the effects of these factors in constructing effective classifiers for psychiatric diseases and showed that the integrated model has the potential to improve the clinical diagnosis and treatment evaluation of SZ.


Nucleotide sequence polymorphism in a hotspot mutation region of the p53 gene.
By screening for mutations in the p53 coding sequence by means of single-strand conformation polymorphism (SSCP) in a series of breast tumors we detected a novel polymorphism. This change in the SSCP pattern was detected in 6.2% of the tumor DNAs analysed and implied an A to G substitution at the last base of codon 213, thus representing a neutral change. First suspecting a somatic mutation we confirmed its presence in matched sets of DNAs from normal tissues. Extending our study to a series of 60 ovarian carcinomas and 70 healthy blood donors we noticed that this polymorphism represented only 3% and 2.6% respectively. We wondered if the difference in frequency in the breast cancer population might not be related to familial breast cancer and analysed 26 DNAs from patients showing predisposition to the disease. Two patients presented this polymorphism and one corresponding kindred was analysed, revealing a mendelian mode of transmission but no correlation with the cancer phenotype.


Genetic and developmental analysis of irreC, a genetic function required for optic chiasm formation in Drosophila.
Irregular chiasm C (irreC) is an X-linked genetic function necessary for the correct projection of visual fibers in the optic chiasms of Drosophila optic ganglia. In addition to a severe disorganization of the inner optic chiasm irreC mutants display a subtle phenotype in the outer optic chiasm, in which some bundles of axons that leave the posterior equatorial part of the lamina on their way to the anterior medulla take a long detour before eventually finding their specific targets in the medulla neuropile. Deletion and recombination mapping of two irreC alleles (one P-element induced, the other associated with an inversion) have yielded a precise cytogenetic location in 3C4-5. A complex complementation pattern between roughest (rst) and irreC alleles indicates that both genetic functions are structurally and/or functionally closely interrelated. Flies in which the irreC locus is completely deleted by overlapping deficiencies are viable and their defects in the optic chiasms are similar to those seen in the two alleles. The defects in the outer and inner optic chiasms are not epigenetically connected and mosaic analyses have shown them to be independent from the genotype of the compound eye. Although the larval visual nerve looks normal, we have found that in the optic lobes of irreC mutants a group of early differentiating larval neurons is misplaced, suggesting a pioneering function of these cells during organization of the outer optic chiasms.


Exploring views and experiences of how infections are detected and managed in practice by nurses, care workers and manager's in nursing homes in England and Sweden: a survey protocol.
In order to avoid unnecessary hospital admission and associated complications, there is an urgent need to improve the early detection of infection in nursing home residents. Monitoring signs and symptoms with checklists or aids called decision support tools may help nursing home staff to detect infection in residents, particularly during the current COVID-19 pandemic.We plan to conduct a survey exploring views and experiences of how infections are detected and managed in practice by nurses, care workers and managers in nursing homes in England and Sweden. An international cross-sectional descriptive survey, using a pretested questionnaire, will be used to explore nurses, care workers and managers views and experiences of how infections are detected and managed in practice in nursing homes. Data will be analysed descriptively and univariate associations between personal and organisational factors explored. This will help identify important factors related to awareness, knowledge, attitudes, belief and skills likely to affect future implementation of a decision support tool for the early detection of infection in nursing home residents. This study was approved using the self-certification process at the University of Surrey and Linköping University ethics committee (Approval 2018/514-32) in 2018. Study findings will be disseminated through community/stakeholder/service user engagement events in each country, publication in academic peer-reviewed journals and conference presentations. A LAY summary will be provided to participants who indicate they would like to receive this information.This is the first stage of a plan of work to revise and evaluate the Early Detection of Infection Scale (EDIS) tool and its effect on managing infections and reducing unplanned hospital admissions in nursing home residents. Implementation of the EDIS tool may have important implications for the healthcare economy; this will be explored in cost-benefit analyses as the work progresses.


First Report of Quinoa Downy Mildew Caused by Peronospora variabilis in the United States.
Quinoa, Chenopodium quinoa Willd., is an Andean crop prized for its high nutritional value and adaptability to harsh environments. Quinoa is plagued by downy mildew caused by Peronospora variabilis Gäum (formerly Peronospora farinosa f. sp. chenopodii Byford) (1). Quinoa production has spread beyond native Andean ranges and quinoa downy mildew has been reported in India, Canada, and Denmark (1). During the summer of 2011, quinoa trials were established to determine the ability of quinoa to grow under Mid-Atlantic conditions and monitor for regional disease problems. In July, after cool, rainy conditions, downy mildew-like symptoms were observed on quinoa at research plots in Centre and Lancaster counties of Pennsylvania. Symptoms and signs consisted of irregularly shaped areas of foliar chlorosis or pink discoloration accompanied by dense, gray sporulation on both leaf surfaces. Sporangia were tan to gray-brown, semi-ovoid, often with a pedicel, mean length of 31 μm, and mean width of 23 μm. Sporangiophores branched dichotomously, and the terminal branchlets curved and tapered to a point. Orange oospores were present in field samples of leaf tissue. DNA was extracted from infected foliar tissue and sporangial suspensions. A seminested PCR protocol (2) was used to obtain partial internal transcribed spacer (ITS) sequences of six Peronospora isolates. The sequences shared 99% maximum identity to a known P. variabilis accession (FM863721.2) in GenBank. A voucher specimen was deposited into the U.S. National Fungus Collections (BPI 882064). Pathogenicity of each of two strains of P. variabilis was confirmed by inoculating quinoa with sporangia (4). Sporangia were shaken from leaves in sterile distilled water and the suspension was filtered through cheesecloth. A 0.01% Tween solution was added and the suspension diluted to 103 sporangia/ml. With an atomizer, a 10-ml sporangial suspension (or sterile water for noninoculated control plants) was sprayed onto one flat of 18 2-week-old quinoa plants, and relative humidity was increased to saturation using a humidity dome for 24 h. After 1 week, chlorosis and pink discoloration were noted on leaves of inoculated quinoa, and after 18 h of subsequent increased humidity (>95% relative humidity), dense gray sporulation was observed. No symptoms were noted on noninoculated control plants. Sporangia and sporangiophores were examined morphologically and confirmed to be P. variabilis, confirming Koch's postulates. For culture maintenance, 2-week-old quinoa leaves were placed onto a sporangial suspension on top of 1% water agar and maintained in a growth chamber at 20°C with 16 h of light per day. Quinoa downy mildew is seedborne (3) and initial infections may have occurred from oospores in the pericarp, despite intensive processing of consumable quinoa seeds to remove saponins. To our knowledge, this is the first report of quinoa downy mildew in the United States and also the first report of P. variabilis in the United States. References: (1) Y. Choi et al. Mycopathologia 169:403, 2010. (2) D. Cooke et al. Fungal Genet. Biol. 30:17, 2000. (3) S. Danielson et al. Seed Sci. Technol. 32:91, 2004. (4) J. Ochoa et al. Plant Pathol. 48:425, 1999.


Caspase-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity.
Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was stromal vascular fraction rather than adipocytes in the adipose tissue. These findings demonstrate a critical role of caspase-1 in macrophage-driven inflammation in the adipose tissue and the development of obesity. These data provide novel insights into the mechanisms underlying inflammation in the pathophysiology of obesity.


A model of indispensability of a large glial layer in cerebrovascular circulation.
We formulate the problem of oxygen delivery to neural tissue as a problem of association. Input to a pool of neurons in one brain area must be matched in space and time with metabolic inputs from the vascular network via the glial network. We thus have a model in which neural, glial, and vascular layers are connected bidirectionally, in that order. Connections between neuro-glial and glial-vascular stages are trained by an unsupervised learning mechanism such that input to the neural layer is sustained by the precisely patterned delivery of metabolic inputs from the vascular layer via the glial layer. Simulations show that the capacity of such a system to sustain patterns is weak when the glial layer is absent. Capacity is higher when a glial layer is present and increases with the layer size. The proposed formulation of neurovascular interactions raises many intriguing questions about the role of glial cells in cerebral circulation.


The variance reaction time model.
The variance reaction time model (VRTM) is proposed to account for various recognition data on reaction time, the mirror effect, receiver-operating-characteristic (ROC) curves, etc. The model is based on simple and plausible assumptions within a neural network: VRTM is a two layer neural network where one layer represents items and one layer represents contexts. The recognition decision is based on a random walk of nodes activated at recognition. VRTM suggests theoretical constraints on the distributions of nodes activated at recognition and the noise in the random walk. The variability in the net inputs to nodes depends on the item frequency (the number of times that the item has been encoded) and the list length. The essential mechanism that accounts for the empirical data is a non-linear activation function. The mean activation threshold in the non-linear activation function is placed to achieve efficient discriminability between new and old items and there is variability in the activation threshold. VRTM predicts the mirror effect for low and high frequency words, a strength based mirror effect between conditions but not within one condition, appropriate ROC-curves for old/new and high/low frequency items, and list-length effects. Furthermore, it predicts appropriate means and distributions of reaction times for old/new, correct/incorrect, and high/low frequency items as well as speed/accuracy tradeoffs. VRTM has an explicit mathematical solution, it is simulated in a neural network, and it is fitted to a number of datasets.


Preventing Lck Activation in CAR T Cells Confers Treg Resistance but Requires 4-1BB Signaling for Them to Persist and Treat Solid Tumors in Nonlymphodepleted Hosts.
Chimeric antigen receptor (CAR) T cells have shown promise against solid tumors, but their efficacy has been limited, due in part, to immunosuppression by CD4+FoxP3+ regulatory T cells (Tregs). Although lymphodepletion is commonly used to deplete Tregs, these regimens are nonspecific, toxic, and provide only a narrow window before Tregs repopulate hosts. Importantly, CARs have also been shown to inadvertently potentiate Tregs by providing a source of IL2 for Treg consumption. We explored whether disruption of the IL2 axis would confer efficacy against solid tumors without the need for lymphodepletion. We developed second- (CD28z) and third- (CD28-4-1BBz) generation CARs targeting EGFRvIII. To eliminate secretion of IL2, 2 amino acid substitutions were introduced in the PYAP Lck-binding motif of the CD28 domain (ΔCD28). We evaluated CARs against B16 melanomas expressing EGFRvIII. CD28z CARs failed to engraft in vivo. Although 4-1BB addition improved expansion, CD28-4-1BBz CARs required lymphodepletion to treat solid tumors. CARs deficient in Lck signaling, however, significantly retarded tumor growth without a need for lymphodepletion and this was dependent on inclusion of 4-1BB. To evaluate CAR vulnerability to Tregs, we lymphodepleted mice and transferred CARs alone or with purified Tregs. Cotransfer with Tregs abrogated the efficacy of CD28-4-1BBz CARs, whereas the efficacy of ΔCD28-4-1BBz CARs remained unperturbed. In the absence of lymphodepletion, CARs targeting solid tumors are hindered by Treg immunosuppression and poor persistence. Here, CARs were modified to circumvent Treg suppression and to simultaneously improve in vivo engraftment. Modified CARs treated solid tumors without a need for lymphodepletion.


Adherence to the obesity-related lifestyle intervention targets in the IDEFICS study.
To address behaviours associated with childhood obesity, certain target values are recommended that should be met to improve children's health. In the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study such lifestyle recommendations were conveyed as six key messages. Here, we investigate the adherence of European children to these messages. The IDEFICS intervention was based on the intervention mapping approach with the following six targets: increase water consumption (to replace sugar-containing beverages), increase fruit/vegetable consumption, reduce daily screen time, increase daily physical activity, improve the quality of family life and ensure adequate sleep duration. Internationally recommended target values were applied to determine the prevalence of children meeting these targets. In a cohort of 18,745 children participating in the IDEFICS baseline survey or newly recruited during follow-up, data on the above lifestyle behaviours were collected for a varying number of 8302 to 17,212 children. Information on all six behaviours was available for 5140 children. Although 52.5% of the cohort was classified in the highest category of water consumption, only 8.8% met the target of an intake of fruits/vegetables five times a day. The prevalence of children adhering to the recommendation regarding total screen time-below 1 h for pre-school children and 2 h for school children-was 51.1%. The recommended amount of at least 60 min of moderate-to-vigorous physical activity per day was fulfilled by 15.2%. Family life of the child measured by various indicators was considered as satisfactory in 22.8%. Nocturnal sleep duration of 11 (10) hours or more in pre-school (school) children was achieved by 37.9%. In general, children in northern countries and younger children showed better adherence to the recommendations. Only 1.1% of the children adhered to at least five of these recommendations. Current adherence of children to lifestyle recommendations to prevent childhood obesity is low where observed differences with respect to country, age and gender call for targeted intervention.


Comprehensive Genetic Analysis of Follicular Thyroid Carcinoma Predicts Prognosis Independent of Histology.
Follicular thyroid carcinoma (FTC) is classified into minimally invasive (miFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wiFTC) subtypes, according to the 2017 World Health Organization guidelines. The genetic signatures of these subtypes may be crucial for diagnosis, prognosis, and treatment but have not been described. Identify and describe the genetic underpinnings of subtypes of FTC. Thirty-nine tumors, comprising 12 miFTCs, 17 eaFTCs, and 10 wiFTCs, were whole-exome sequenced and analyzed. Somatic mutations, constitutional sequence variants, somatic copy number alterations, and mutational signatures were described. Clinicopathologic parameters and mutational profiles were assessed for associations with patient outcomes. Total mutation burden was consistent across FTC subtypes, with a median of 10 (range 1 to 44) nonsynonymous somatic mutations per tumor. Overall, 20.5% of specimens had a mutation in the RAS subfamily (HRAS, KRAS, or NRAS), with no notable difference between subtypes. Mutations in TSHR, DICER1, EIF1AX, KDM5C, NF1, PTEN, and TP53 were also noted to be recurrent across the cohort. Clonality analysis demonstrated more subclones in wiFTC. Survival analysis demonstrated worse disease-specific survival in the eaFTC and wiFTC cohorts, with no recurrences or deaths for patients with miFTC. Mutation burden was associated with worse prognosis, independent of histopathological classification. Though the number and variety of somatic variants are similar in the different histopathological subtypes of FTC in our study, mutational burden was an independent predictor of mortality and recurrence.


Dexamethasone prodrug treatment prevents nephritis in lupus-prone (NZB × NZW)F1 mice without causing systemic side effects.
To evaluate the potentially improved therapeutic efficacy and safety of nephrotropic macromolecular prodrugs of glucocorticoids (GCs) for the treatment of lupus nephritis. Lupus-prone female (NZB × NZW)F1 mice received monthly injections of N-(2-hydroxypropyl) methacrylamide copolymer-based dexamethasone prodrug (P-Dex) or daily injections of dexamethasone phosphate sodium (Dex; overall dose equivalent to that of P-Dex) for 2 months. During treatment, the mice were monitored for albuminuria, mean arterial pressure, and serum autoantibody levels. Nephritis, renal immune complex levels, and macrophage infiltration were evaluated histologically. Bone quality was analyzed using peripheral dual x-ray absorptiometry and micro-computed tomography. The in vivo distribution of P-Dex was investigated using optical imaging, immunohistochemistry, and fluorescence-activated cell sorting (FACS). The antiinflammatory effect of P-Dex was validated using lipopolysaccharide-activated human proximal tubule epithelial (HK-2) cells. Monthly P-Dex injections completely abolished albuminuria in the (NZB × NZW)F1 mice; this approach was significantly more efficacious than daily Dex treatment. P-Dex treatment did not reduce serum levels of anti-double-stranded DNA antibodies or renal immune complexes but did decrease macrophage infiltration, which is a marker of chronic inflammation. Immunohistochemical and FACS analyses revealed that P-Dex was primarily sequestered by proximal tubule epithelial cells, and that it could attenuate the inflammatory response in HK-2 cell culture. In contrast to Dex treatment, P-Dex treatment did not lead to any significant deterioration of bone quality or reduction in the level of total serum IgG. Macromolecularization of GCs renders them nephrotropic. Protracted retention, subcellular processing, and activation of GC prodrugs by kidney cells would potentiate nephritis resolution, with a reduced risk of systemic toxicities.


Web-based vestibular rehabilitation in persistent postural-perceptual dizziness.
The aims of the study were to investigate the feasibility and preliminary outcome of a Norwegian web-based self-help application for vestibular rehabilitation (VR) among patients with high symptom burden of chronic dizziness fulfilling the criteria for persistent postural-perceptual dizziness (PPPD). The web application consists of six weekly online sessions, with written information and video presentations. It is self-instructive and freely available on NHI.no (https://nhi.no/for-helsepersonell/vestibular-rehabilitering/). Ten consecutive patients referred to a neurologic outpatient clinic for chronic dizziness were included. They signed informed consent forms and were examined at inclusion and after three months. State of health and symptom burden were recorded using Vertigo symptom score (VSS), Niigata symptom score (NPQ), Patient Health Questionnaire (PHQ-9) and health-related quality of life score (EQ5D-5L). Experiences with the program were measured using a semi-structured interview at the end of the study. Nine out of ten patients completed the program. The findings suggest that the web application was easy to use, instructive and educatable. Challenges were the load of exercises, motivation to continue training during relapses and performing the body rolling on the floor. Participants had high symptom burden (VSS mean 32.9) and long duration of symptoms in years (mean 11.5). The participants improved on average 6.9 points on the VSS score. This web application for chronic dizziness appears to be feasible and may reduce symptoms in patients who have struggled with serious and long-lasting dizziness.


Galectin-3 functions as an adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.
Allergic inflammation involves the mobilization and trafficking of eosinophils to sites of inflammation. Galectin-3 (Gal-3) has been shown to play a critical role in eosinophil recruitment and airway allergic inflammation in vivo. The role played by Gal-3 in human eosinophil trafficking was investigated. Eosinophils from allergic donors expressed elevated levels of Gal-3 and demonstrated significantly increased rolling and firm adhesion on immobilized VCAM-1 and, more surprisingly, on Gal-3 under conditions of flow. Inhibition studies with specific mAbs as well as lactose demonstrated that: 1) eosinophil-expressed Gal-3 mediates rolling and adhesion on VCAM-1; 2) alpha(4) integrin mediates eosinophil rolling on immobilized Gal-3; and 3) eosinophil-expressed Gal-3 interacts with immobilized Gal-3 through the carbohydrate recognition domain of Gal-3 during eosinophil trafficking. These findings were further confirmed using inflamed endothelial cells. Interestingly, Gal-3 was found to bind to alpha(4) integrin by ELISA, and the two molecules exhibited colocalized expression on the cell surface of eosinophils from allergic donors. These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.


Closed-Loop Neuromorphic Benchmarks.
Evaluating the effectiveness and performance of neuromorphic hardware is difficult. It is even more difficult when the task of interest is a closed-loop task; that is, a task where the output from the neuromorphic hardware affects some environment, which then in turn affects the hardware's future input. However, closed-loop situations are one of the primary potential uses of neuromorphic hardware. To address this, we present a methodology for generating closed-loop benchmarks that makes use of a hybrid of real physical embodiment and a type of "minimal" simulation. Minimal simulation has been shown to lead to robust real-world performance, while still maintaining the practical advantages of simulation, such as making it easy for the same benchmark to be used by many researchers. This method is flexible enough to allow researchers to explicitly modify the benchmarks to identify specific task domains where particular hardware excels. To demonstrate the method, we present a set of novel benchmarks that focus on motor control for an arbitrary system with unknown external forces. Using these benchmarks, we show that an error-driven learning rule can consistently improve motor control performance across a randomly generated family of closed-loop simulations, even when there are up to 15 interacting joints to be controlled.


Predictive validity and adjustment of ideal partner preferences across the transition into romantic relationships.
Although empirical research has investigated what we ideally seek in a romantic partner for decades, the crucial question of whether ideal partner preferences actually guide our mating decisions in real life has remained largely unanswered. One reason for this is the lack of designs that assess individuals' ideal partner preferences before entering a relationship and then follow up on them over an extended period. In the Göttingen Mate Choice Study (GMCS), a preregistered, large-scale online study, we used such a naturalistic prospective design. We investigated partner preferences across 4 preference domains in a large sample of predominantly heterosexual singles (N = 763, aged 18-40 years) and tracked these individuals across a period of 5 months upon a possible transition into romantic relationships. Attesting to their predictive validity, partner preferences prospectively predicted the characteristics of later partners. This was equally true for both sexes, except for vitality-attractiveness where men's preferences were more predictive of their later partners' standing on this dimension than women's. Self-perceived mate value did not moderate the preference-partner characteristics relations. Preferences proved to be relatively stable across the 5 months interval, yet were less stable for those who entered a relationship. Subgroup analyses using a newly developed indicator of preference adjustment toward (vs. away from) partner characteristics revealed that participants adjusted their preferences downward when partners fell short of initial preferences, but showed no consistent adjustment when partners exceeded them. Results and implications are discussed against the background of ongoing controversies in mate choice and romantic relationship research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Efficacy of a Novel Nematicidal Seed Treatment against Meloidogyne incognita on Cotton.
The efficacy of abamectin as a seed treatment for control of Meloidogyne incognita on cotton was evaluated in greenhouse, microplot, and field trials in 2002 and 2003. Treatments ranging from 0 to 100 g abamectin/100 kg seed were evaluated. In greenhouse tests 35 d after planting (DAP), plants from seed treated with abamectin were taller than plants from nontreated seed, and root galling severity and nematode reproduction were lower where treated seed were used. The number of second stage juveniles that had entered the roots of plants from seed treated with 100 g abamectin/kg seed was lower during the first 14 DAP than with nontreated seed. In microplots tests, seed treatment with abamectin and soil application of aldicarb at 840 g/kg of soil reduced the number of juveniles penetrating seedling roots during the first 14 DAP compared to the nontreated seedlings. In field plots, population densities of M. incognita were lower 14 DAP in plots that received seed treated with abamectin at 100 g/kg seed than where aldicarb (5.6 kg/ha) was applied at planting. Population densities were comparable for all treatments, including the nontreated controls, at both 21 DAP and harvest. Root galling severity did not differ among treatments at harvest.


Effects of dietary glutamine on adhesion molecule expression and oxidative stress in mice with streptozotocin-induced type 1 diabetes.
Glutamine (Gln) is known to have immunomodulatory effects. Previous studies reported that Gln promotes insulin secretion in type 2 diabetes. However, the effects of Gln on insulin-deficient type 1 diabetes are not clear. This study investigated the effects of dietary Gln supplementation on adhesion molecule expression and oxidative damage in type 1 diabetic mice. There were 1 normal control (NC) group and 2 diabetic groups in this study. Mice in the NC group were fed a regular chow diet. One diabetic group (DM) was fed a common semipurified diet while the other diabetic group received a diet in which part of the casein was replaced by Gln (DM-Gln), which provided 25% of the total amino acid nitrogen for 6 wk. Diabetes was induced by an intraperitoneal injection of streptozotocin at a dose of 150 mg/kg body weight. Blood samples and the liver and kidneys of the animals were collected at the end of the study for further analysis. Plasma glucose, fructosamine contents and adhesion molecule expressions were significantly higher in the diabetic groups than in the NC group. The DM group had higher leukocyte CD11a/CD18 expression. In diabetic mice, nitrotyrosine concentrations and myeloperoxidase activities were higher and the reduced to oxidized glutathione ratio was lower in liver and/or kidney. These alterations were not found in diabetic mice supplemented with Gln. These results suggest that supplemental dietary Gln increased the antioxidant potential and consequently decreased leukocyte adhesion molecule expression and oxidative stress in organs of mice with type 1 diabetes.


Intervention development of a brief messaging intervention for a randomised controlled trial to improve diabetes treatment adherence in sub-Saharan Africa.
Brief messaging interventions, including Short Message Service (SMS) text-messages, delivered via mobile device platforms, show promise to support and improve treatment adherence. To understand how these interventions work, and to facilitate transparency, we need clear descriptions of the intervention development process. We describe and reflect on the process of designing and pretesting an evidence- and theory-informed brief messaging intervention, to improve diabetes treatment adherence in sub-Saharan Africa. We followed the stepwise approach recommended by the Medical Research Council, United Kingdom (MRC UK) Framework for Development and Evaluation of Complex Health Interventions and guidance for mobile health intervention development. We used a four-phase, iterative approach that first generated primary and secondary evidence on the lived experience of diabetes, diabetes treatment services and mobile-phone use. Second, we designed a type 2 diabetes-specific, brief text-message library, building on our previous hypertension text-message library, as well as drawing on the primary and secondary data from phase one, and on expert opinion. We then mapped the brief text-messages onto behaviour change (COM-B) theoretical constructs. Third, we refined and finalised the newly developed brief text-message library through stakeholder consultation and translated it into three local languages. Finally, we piloted the intervention by pre-testing the automated delivery of the brief text-messages in the trial sites in Malawi and South Africa. The final SMS text Adherence suppoRt for people with type 2 diabetes (StAR2D) intervention was tested in a randomised controlled trial in Malawi and South Africa (trial registration: ISRCTN70768808 ). The complexity of public health interventions requires that we give more attention to intervention development work. Our documentation and reflection on the StAR2D intervention development process promotes transparency, replicability, assessment of intervention quality, and comparison with other studies.