Peripartum heart disease: an endomyocardial biopsy study.
Endomyocardial biopsies were performed in 11 African women in Nairobi who presented with the clinical features of peripartum cardiomyopathy. The samples were studied by light and electron microscopy. In five patients there was evidence of a "healing myocarditis", that is the presence of a mild inflammatory cell infiltration within the myocardium with foci of necrosis and variable amounts of hypertrophy and fibrosis. Of the nine patients who were followed up, three out of four with myocarditis had persistent heart failure and four out of five without myocarditis improved. Peripheral blood T lymphocyte cell subsets were measured in nine patients by means of monoclonal antibodies. A high helper:suppressor T cell ratio was found in three patients. Almost half of this group of patients with peripartum cardiomyopathy had myocarditis in their biopsy specimens. The myocarditis may have been due to an inappropriate immunological reaction in some patients.


An experimental comparison of three types of case management for homeless mentally ill persons.
Three types of case management were compared to determine their relative effectiveness in helping people with severe mental illness who were homeless or at risk of homelessness. Subjects recruited from a psychiatric emergency room and inpatient units were randomly assigned to one of the three treatment conditions: broker case management, in which the client's needs were assessed, services were purchased from multiple providers, and the client was monitored; assertive community treatment only, in which comprehensive services were provided for an unlimited period; and assertive community treatment augmented by support from community workers, who assisted with activities of daily living and were available for leisure activities. Of 165 subjects recruited, 135 were followed for 18 months. Compared with clients assigned to broker case management, clients assigned to assertive community treatment only and assertive community treatment with community workers had superior outcomes on several variables. They were number of contacts with the assigned treatment program, resource utilization (for example, use of entitlements), severity of thought disorder, activity level, and client satisfaction. Clients in the assertive community treatment only condition achieved more days in stable housing than those in the other two treatment conditions. No significant treatment group effects were found on income, self-esteem, or substance abuse. Assertive community treatment is superior to broker case management in assisting individuals with serious mental illness who are at risk of homelessness.


Mechanical properties and fracture dynamics of silicene membranes.
As graphene has become one of the most important materials, there is renewed interest in other similar structures. One example is silicene, the silicon analogue of graphene. It shares some of the remarkable graphene properties, such as the Dirac cone, but presents some distinct ones, such as a pronounced structural buckling. We have investigated, through density functional based tight-binding (DFTB), as well as reactive molecular dynamics (using ReaxFF), the mechanical properties of suspended single-layer silicene. We calculated the elastic constants, analyzed the fracture patterns and edge reconstructions. We also addressed the stress distributions, unbuckling mechanisms and the fracture dependence on the temperature. We analysed the differences due to distinct edge morphologies, namely zigzag and armchair.


Scientific evidence for therapeutic effects of Chinese prescription Kangen-karyu from pre-clinical animal experiments.
Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study reports therapeutic evidence for Kangen-karyu from pre-clinical animal experiments related to human diseases. Kangen-karyu showed beneficial effects on type 1 diabetes and related complications through the suppression of protein expression related to advanced glycation endproducts and oxidative stress. Kangen-karyu reduced oxidative stress via the regulation of dyslipidemia, and also exerted a renoprotective effect mainly through its antioxidant properties during the development of diabetic nephropathy in type 2 diabetes. In addition, Kangen-karyu showed neuroprotective effects by attenuating the spatial memory impairment and neuronal death induced by diabetes. Kangen-karyu counteracted oxidative stress and ameliorated tissue damage possibly associated with aging. These findings provide scientific evidence to explain the efficacy of Kangen-karyu based on its underlying therapeutic effects.


Propolis emulgel: a natural remedy for burn and wound.
To develop an alternative medicine, propolis, in emulgel formulation for burn and wound treatment. The effect of two independent variables: emulsifying agent concentration and oil concentration on the cumulative amount of propolis release (dependent variable) from liquid paraffin and isopropyl palmitate emulgels was investigated. Eight formulations were prepared and evaluated for physical appearance, pH, propolis content, viscosity, and in vitro propolis release. The release results were fitted into different kinetic equations and analyzed using contour plot, interaction surface plot and one-way ANOVA. The selected emulgel formulation was investigated for its wound and burn healing activity in rats. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, and pH value. The concentration of emulsifying agent had more pronounced effect on propolis release than oil concentration. Formulations F1-F6 showed "anomalous" drug release, while Formulations F7 and F8 showed zero-order kinetic. The formulation F7 with 5% isopropyl palmitate, 5% emulsifier mixture, 1% hydroxyl propyl methyl cellulose, 1% oleic acid, and 10% propylene glycol is a promising formula for better management of wound and burn.


Implications of Regurgitative Feeding on Plastic Loads in Northern Fulmars (Fulmarus glacialis): A Study from Svalbard.
Procellariiform seabirds like northern fulmars (Fulmarus glacialis) are prone to ingest and accumulate floating plastic pieces. In the North Sea region, there is a long tradition to use beached fulmars as biomonitors for marine plastic pollution. Monitoring data revealed consistently lower plastic burdens in adult fulmars compared to younger age classes. Those findings were hypothesized to partly result from parental transfer of plastic to chicks. However, no prior study has examined this mechanism in fulmars by comparing plastic burdens in fledglings and older fulmars shortly after the chick-rearing period. Therefore, we investigated plastic ingestion in 39 fulmars from Kongsfjorden (Svalbard), including 21 fledglings and 18 older fulmars (adults/older immatures). We found that fledglings (50-60 days old) had significantly more plastic than older fulmars. While plastic was found in all fledglings, two older fulmars contained no and several older individuals barely any plastic. These findings supported that fulmar chicks from Svalbard get fed high quantities of plastic by their parents. Adverse effects of plastic on fulmars were indicated by one fragment that perforated the stomach and possibly one thread perforating the intestine. Negative correlations between plastic mass and body fat in fledglings and older fulmars were not significant.


The prodigious halo of the other Huygens.
At the height of the ceremony in the Principality of Orange of the restoration of the sovereignty of the House of Nassau in 1665, a ceremony led by Christiaan's father, Constantijn Huygens, a "solar crown" appeared in the sky, apparently a divine sign of approval. A nearly forgotten contemporary color engraving of this miraculous event has survived. Constantijn seized the opportunity by using to his advantage the general euphoria among the citizens caused by the appearance. We argue that Constantijn knew exactly what was going on in the sky because of his son's work on halo theory. Given its brightness and its time of appearance, it seems plausible that the most prominent halo in the Orange halo display was a circumscribed halo rather than the more familiar but bleaker circular 22° halo. The same probably holds for most of the other high-sun halos that caused general consternation, dating from the Octavian halo of 44 BC, to the Chernobyl halo of 1986, and indeed up to bright high-sun halos of the present.


Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats.
Methionine restriction increases life span in rats and mice and reduces age-related accretion of adipose tissue in Fischer 344 rats. Recent reports have shown that adipose tissue mitochondrial content and function are associated with adiposity; therefore, the expression of genes involved in mitochondrial biogenesis and oxidative capacity was examined in white adipose tissue, liver, and skeletal muscle from Fischer 344 rats fed control (0.86% methionine) or methionine-restricted (0.17% methionine) diets for 3 months. Methionine restriction induced transcriptional changes of peroxisome proliferator-activated receptors, peroxisome proliferator-activated receptor coactivators 1alpha and 1beta, and some of their known target genes in all of these tissues. In addition, tissue-specific responses were elicited at the protein level. In inguinal adipose tissue, methionine restriction increased protein levels of peroxisome proliferator-activated receptor and peroxisome proliferator-activated receptor coactivator target genes. It also induced mitochondrial DNA copy number, suggesting mitochondrial biogenesis and corresponding with the up-regulation of citrate synthase activity. In contrast, methionine restriction induced changes in mitochondrial glycerol-3-phosphate dehydrogenase activity and stearoyl-coenzyme A desaturase 1 protein levels only in liver and uncoupling protein 3 and cytochrome c oxidase subunit IV protein levels only in skeletal muscle. No increase in mitochondrial DNA copy number was observed in liver and skeletal muscle despite an increase in mitochondrial citrate synthase activity. The results indicate that adiposity resistance in methionine-restricted rats is associated with mitochondrial biogenesis in inguinal adipose tissue and increased mitochondrial aerobic capacity in liver and skeletal muscle.


Comparing genomic and epigenomic features across species using the WashU Comparative Epigenome Browser.
Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over syntenic regions simultaneously. The browser also displays genetic differences between the genomes from single-nucleotide variants (SNVs) to structural variants (SVs) to visualize the association between epigenomic differences and genetic differences. Instead of anchoring all data sets to the reference genome coordinates, it creates independent coordinates of different genome assemblies to faithfully present features and data mapped to different genomes. It uses a simple, intuitive genome-align track to illustrate the syntenic relationship between different species. It extends the widely used WashU Epigenome Browser infrastructure and can be expanded to support multiple species. This new browser function will greatly facilitate comparative genomic/epigenomic research, as well as support the recent growing needs to directly compare and benchmark the T2T CHM13 assembly and other human genome assemblies.


Comparative study of inflorescence development in Oleaceae.
Investigations of inflorescence architecture offer insight into the evolution of an astounding array of reproductive shoot systems in the angiosperms, as well as the potential to genetically manipulate these branching patterns to improve crop yield and enhance the aesthetics of horticultural species. The diversity of inflorescences in the economically important family Oleaceae was studied from a comparative developmental point of view for the first time, based on species of seven genera (Chionanthus, Fontanesia, Fraxinus, Jasminum, Ligustrum, Olea, Syringa). Series of developmental stages of chemically fixed inflorescences were studied with epi-illumination light microscopy. All taxa studied have inflorescences with terminal flowers. The inflorescences are mostly panicles, but in some cases thyrsoids or compound botryoids. Phyllotaxis of the flower-subtending bracts is mostly decussate, rarely tricussate (Fraxinus) or spiral (Jasminum). Accessory flowers or accessory inflorescences, almost unknown in Oleaceae as yet, were found in two genera. In Syringa, common bract-flower primordia are formed by a delay in early bract development compared to flower development. Such a delay is also expressed by the loss of bracts in the distal part of inflorescence branches in Syringa and Chionanthus. Significant variation in branching pattern and phyllotaxy was observed among the studied species of Oleaceae. The suppression of bracts and formation of accessory flowers were found as special features of inflorescence ontogeny. The occurrence of accessory flowers and accessory partial inflorescences is interesting from the point of view of dense and flower-rich inflorescences in ornamental species.


Risk factors for airway remodeling in asthma manifested by a low postbronchodilator FEV1/vital capacity ratio: a longitudinal population study from childhood to adulthood.
Airway remodeling may lead to irreversible loss of lung function in asthma. The impact of childhood asthma, airway responsiveness, atopy, and smoking on airway remodeling was investigated in a birth cohort studied longitudinally to age 26. A low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to vital capacity (VC) at age 18 or 26 was used as a marker of airway remodeling. "Normal" study members with no history of asthma ever, no wheezing in the last year, and no smoking ever were used to determine sex- and age-specific reference values for this ratio. The lower limit of normal was defined as the mean ratio minus 1.96 standard deviation, delimiting the 2.5% of the normal population with the lowest FEV1/VC ratio. A low postbronchodilator FEV1/VC ratio was found in 7.4% and 6.4% of study members at ages 18 and age 26 and 4.6% at both assessments. Lung function was low throughout childhood in those with a consistently low postbronchodilator FEV1/VC ratio at both ages. Those with consistently low postbronchodilator ratios also showed a greater decline in the prebronchodilator FEV1/VC ratio from ages 9 to 26 compared with those with normal postbronchodilator ratios at both ages (males, -12% versus -6%, p < 0.0001; females, -10.5% versus -5.5%, p < 0.01). Asthma, male sex, airway hyperresponsiveness, and low lung function in childhood were each independently associated with a low postbronchodilator FEV1/VC ratio, which in turn was associated with an accelerated decline in lung function and decreased reversibility. These data suggest that airway remodeling in asthma, as manifested by impaired lung function, begins in childhood and continues into adult life.


SLC11A1 (NRAMP1) but not SLC11A2 (NRAMP2) polymorphisms are associated with susceptibility to tuberculosis in a high-incidence community in South Africa.
Stellenbosch University Faculty of Health Sciences, and metropolitan Cape Town, Western Cape, South Africa. To investigate whether the reported association between SLC11A1 (also NRAMP1) polymorphisms and susceptibility to tuberculosis (TB) can be confirmed in a different population, and whether polymorphisms in SLC11A2 (also NRAMP2, DCT1, DMT1) are associated with TB. A case-control study design was used to compare the frequencies of five polymorphisms in SLC11A1 and three in SLC11A2 between a group of bacteriologically confirmed TB patients and healthy community controls. The 5' (GT)9 allele in the promoter of SLC1A1 was found at significantly higher frequencies among 265 controls than in 224 pulmonary TB (PTB) patients (P = 0.002; OR 0.6; 95% CI 0.43-0.83). Homozygotes for the TGTG deletion (1729+55del4) in the 3'UTR of SLC11A1 were over-represented among PTB patients (P = 0.013; OR 5.19; 95% CI 1.42-18.94). Stepwise logistic regression analysis indicated that the 5' and 3' polymorphisms contribute separate main effects. Tuberculous meningitis patients (n = 22) showed the same allele and genotype frequency as PTB patients. No SLC11A2 polymorphisms tested were associated with TB. The 5' (GT)n allele driving the highest rate of transcription of SLC11A1 appears to be associated with protection against TB in the majority of the populations studied.


Symptoms Experienced and Information Needs of Women Receiving Chemotherapy.
This study is carried out to determine the symptoms and information necessity on chemotherapy (CT) treatment of the women with breast cancer. A total of 170 women older than 18 years old, who receive CT with breast cancer diagnosis, are volunteered to participate in the study. Mixed method was used in the study. Data are collected using Descriptive Data Form, Interview Form and Memorial Symptom Assessment Scale. As a result of the cluster analysis, four clusters and the symptoms within have been obtained. These are: pain, lack of energy, feeling drowsy, sweat, swelling of hands, and feet in the first cluster; feeling nervous, difficulty sleeping, feeling sad, worrying in the second cluster; nausea, feeling bloating, change in the way food tastes, hair loss, constipation in the third cluster; vomiting, diarrhea, problems with sexual interest, lack of appetite, dizziness, and weight loss in the forth cluster. Women's information necessity related to the CT are follows: the effects of CT, other treatment options beyond CT, complementary methods, the effect of the CT treatment on reproductive health and sexuality, nutrition, and symptom control. The results of this study will enable determination of symptom clusters, which health professionals are easier to focus on these symptoms. An understanding information need of patients can help to ensure that individual's coping strategies and self-management.


Notch and the survival of regulatory T cells: location is everything!
Signaling through the T cell receptor induces T lymphocytes to divide, differentiate, and perform numerous effector functions. Once activated, effector T cells are exquisitely sensitive to changes in available cytokines, particularly the survival cytokine interleukin-2 (IL-2). Removal of IL-2 rapidly initiates apoptosis in response to cytokine withdrawal. In contrast to effector T cells, regulatory T cells (T(regs)) are resistant to apoptosis induced by cytokine withdrawal. A study exploring the differences between these two T cell subsets reveals a role for Notch1 in protecting T(regs) from apoptosis. Protection from apoptosis induced by cytokine withdrawal correlated with Notch1 localization in the cytosol of T(regs) and its association with phosphatidylinositol 3-kinase and Rictor, a component of the mammalian target of rapamycin complex. Notch1 localization in the nucleus in effector T cells, on the other hand, was correlated with susceptibility to apoptosis induced by cytokine withdrawal. This study highlights how Notch1 can deliver opposing signals in different cellular contexts and suggests that localization of Notch1 can have a substantial influence on life-and-death decisions in T lymphocytes.


Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis.
The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacterium's total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori. World Health Organization.


A pilot study of mindfulness-based stress reduction for hot flashes.
A variety of results from both population and laboratory studies suggest that stress and hot flashes (HFs) are correlated and that HFs are more severe in women with lower coping abilities. The objective of this pilot study was to obtain information on the feasibility and effect of participation in a mindfulness-based stress reduction (MBSR) program on HF severity and menopause-related quality of life. Fifteen women volunteers reporting a minimum of seven moderate to severe HFs per day at study intake attended the eight weekly MBSR classes at the University of Massachusetts Medical School. Participants were assessed for menopause-related quality of life before beginning and at the conclusion of the MBSR program. Women also kept a daily log of their HFs through the course of the 7 weeks of the MBSR program and for 4 weeks after it. Women's scores on quality-of-life measures increased significantly, and the median reported HF severity, calculated as the weekly average of a daily HF severity score, decreased 40% over the course of the 11 weeks of the assessment period. The women were individually interviewed at the completion of their participation, and the results of the interviews were consistent with the results from daily diaries. These results provide preliminary positive evidence of the feasibility and efficacy of MBSR in supporting women who are experiencing severe HFs, and it warrants further investigation.


SCF(TIR1/AFB)-auxin signalling regulates PIN vacuolar trafficking and auxin fluxes during root gravitropism.
The distribution of the phytohormone auxin regulates many aspects of plant development including growth response to gravity. Gravitropic root curvature involves coordinated and asymmetric cell elongation between the lower and upper side of the root, mediated by differential cellular auxin levels. The asymmetry in the auxin distribution is established and maintained by a spatio-temporal regulation of the PIN-FORMED (PIN) auxin transporter activity. We provide novel insights into the complex regulation of PIN abundance and activity during root gravitropism. We show that PIN2 turnover is differentially regulated on the upper and lower side of gravistimulated roots by distinct but partially overlapping auxin feedback mechanisms. In addition to regulating transcription and clathrin-mediated internalization, auxin also controls PIN abundance at the plasma membrane by promoting their vacuolar targeting and degradation. This effect of elevated auxin levels requires the activity of SKP-Cullin-F-box(TIR1/AFB) (SCF(TIR1/AFB))-dependent pathway. Importantly, also suboptimal auxin levels mediate PIN degradation utilizing the same signalling pathway. These feedback mechanisms are functionally important during gravitropic response and ensure fine-tuning of auxin fluxes for maintaining as well as terminating asymmetric growth.


The costs of removing the unsanctioned import of marine plastic litter to small island states.
Small island states receive unprecedented amounts of the world's plastic waste. In March 2019, we removed as much plastic litter as possible from Aldabra Atoll, a remote UNESCO World Heritage Site, and estimated the money and effort required to remove the remaining debris. We removed 25 tonnes at a cost of $224,537, which equates to around $10,000 per day of clean-up operations or $8,900 per tonne of litter. We estimate that 513 tonnes (95% CI 212-814) remains on Aldabra, the largest accumulation reported for any single island. We calculate that removing it will cost approximately $4.68 million and require 18,000 person-hours of labour. By weight, the composition is dominated by litter from the regional fishing industry (83%) and flip-flops from further afield (7%). Given the serious detrimental effects of plastic litter on marine ecosystems, we conclude that clean-up efforts are a vital management action for islands like Aldabra, despite the high financial cost and should be integrated alongside policies directed at 'turning off the tap'. We recommend that international funding be made available for such efforts, especially considering the transboundary nature of both the marine plastic litter problem and the ecosystem services provided by biodiversity-rich islands.


Serological determination of hepatitis C virus genotype: comparison with a standardized genotyping assay.
In patients with chronic hepatitis C, determination of hepatitis C virus (HCV) genotype could be routinely run in the future to tailor treatment schedules. The suitabilities of two versions of a serological, so-called serotyping assay (Murex HCV Serotyping Assay version 1-3 [SA1-3] and Murex HCV Serotyping Assay version 1-6 [SA1-6]; Murex Diagnostics Ltd.), based on the detection of genotype-specific antibodies directed to epitopes encoded by the NS4 region of the genome, for the routine determination of HCV genotypes were studied. The results were compared with those of a molecular biology-based genotyping method (HCV Line Probe Assay [INNO-LiPA HCV]; Innogenetics S.A.), based on hybridization of PCR products onto genotype-specific probes designed in the 5' noncoding region of the genome, obtained with pretreatment serum samples from 88 patients with chronic hepatitis C eligible for interferon therapy. Definitive genotyping was performed by sequence analysis of three regions of the viral genome in all samples with discrepant typing results found among at least two of the three assays studied. In all instances, sequence analysis confirmed the result of the INNO-LiPA HCV test. The sensitivity of SA1-3 was 75% relative to the results obtained by the genotyping assay. The results were concordant with those of genotyping for 92% of the samples typeable by SA1-3. The sensitivity of SA1-6 was 89% relative to the results obtained by the genotyping assay. The results were concordant with those of genotyping for 94% of the samples typeable by SA1-6. Overall, SA1-6 had increased sensitivity relative to SA1-3 but remained less sensitive than the genotyping assay on the basis of PCR amplification of HCV RNA. Cross-reactivities between different HCV genotypes could be responsible for the mistyping of 8 (SA1-3) and 6% (SA1-6) of the samples. Subtyping of 1a and 1b is still not possible with the existing peptides, but discriminating between subtypes may not be necessary for routine use.


Guided parent-delivered cognitive behavioural therapy for Japanese children and parents: a single-arm uncontrolled study.
Guided parent-delivered cognitive behavioural therapy (GPD-CBT) is an effective low-intensity treatment for childhood anxiety disorder in Western countries and can increase access to evidence-based psychological therapies. This study aimed to examine its feasibility in a Japanese sample. Twelve children with anxiety disorders and their parents participated in the study, and ten children and parents completed the program. Participants were assessed at pre-, post- and one-month follow-up using a diagnostic interview for anxiety disorders, self- and parent-report measures for anxiety, depression, parental behaviour, and parental anxiety. Four children (40% of completers) were free from their primary diagnoses immediately following the brief treatment, and seven children (70%) at the one-month follow-up. Changes in disorder severity, child and parent reported anxiety symptoms, and child reported depression symptoms were consistent with those found in Western trials of GPD-CBT and of Japanese trials of more intensive CBT for child anxiety disorders that involves both the child and the parent. Moderate increases were also found in child reported parental autonomy behaviours; however, there were only small changes in parent self-reported anxiety. These results support the potential of GPD-CBT to increase access to evidence-based treatments for anxiety disorders in Japanese children.


What drives developmental change in adolescent disclosure and maternal knowledge? Heterogeneity in within-family processes.
This study aimed to gain a better understanding of the normative declines in adolescent disclosure and maternal knowledge over the course of adolescence, by assessing the underlying monitoring processes. Multilevel structural equation models were applied to 15 assessments among 479 families across 5 years (13 years at T1, 57% boys, 11% low socioeconomic status). Developmental declines in mother-perceived disclosure and knowledge were observed, which were partially explained by processes operating at the level of the family unit. On average, mothers were more knowledgeable in weeks with more disclosure and more solicitation, and adolescent disclosure was higher in weeks with more maternal solicitation and less control. The effect sizes and even the directions of these within-family correlations varied between families, however. This heterogeneity was partially explained by the level of maternal control and adolescent disclosure, and by the families' socioeconomic status. Within-family fluctuations in knowledge and disclosure were also correlated with fluctuations in relationship quality and adolescent and mother mood. Overall, these within-family processes explained up to 14% of the normative developmental decline in disclosure and 19% of the decline in knowledge. This study thus suggests that a wide variety in monitoring processes may drive normative declines in adolescent disclosure and maternal knowledge. (PsycINFO Database Record


Skeletal muscle beta-adrenergic receptors: variations due to fiber type and training.
To determine the relationship between oxidative capacity and characteristics of beta-adrenergic receptors (beta AR) in skeletal muscle, selected biochemical variables were quantitated in particulate preparations from soleus and gastrocnemius muscle from rats subjected to 10 wk of treadmill running and from three control groups: free-fed, sedentary controls; food-restricted, pair-weighted controls; and animals trained by swimming. Beta AR density and isoproterenol-stimulated adenylate cyclase activity were considerably greater in the slow-twitch oxidative soleus muscle than in the mixed fiber type gastrocnemius in animals from each group (P less than 0.005). Succinic dehydrogenase (SDH) activity of gastrocnemius was increased 23-42% (P less than 0.05) in runners over each of the control groups, concommitantly with a 15-27% increase (P less than 0.05) in beta AR density (Bmax for binding of 125I-cyanopindolol). In 24 animals from all four treatment groups, there was a significant correlation between SDH activity and beta AR density (r = 0.68; P less than 0.001). We conclude that BAR density correlates positively with oxidative capacity in skeletal muscle, but further studies are required to determine the physiological importance of these differences.


Association of soy and fiber consumption with the risk of endometrial cancer.
The authors conducted a case-control study among the multi-ethnic population of Hawaii to examine the role of dietary soy, fiber, and related foods and nutrients on the risk of endometrial cancer. Endometrial cancer cases (n = 332) diagnosed between 1985 and 1993 were identified from the five main ethnic groups in the state (Japanese, Caucasian, Native Hawaiian, Filipino, and Chinese) through the rapid-reporting system of the Hawaii Tumor Registry. Population controls (n = 511) were selected randomly from lists of female Oahu residents and matched to cases on age (+/-2.5 years) and ethnicity. All subjects were interviewed using a diet history questionnaire that included over 250 food items. Non-dietary risk factors for endometrial cancer included nulliparity, never using oral contraceptives, fertility drug use, use of unopposed estrogens, a history of diabetes mellitus or hypertension, and a high Quetelet's index (kg/cm2). Energy intake from fat, but not from other sources, was positively associated with the risk of endometrial cancer. The authors also found a positive, monotonic relation of fat intake with the odds ratios for endometrial cancer after adjustment for energy intake. The consumption of fiber, but not starch, was inversely related to risk after adjustment for energy intake and other confounders. Similar inverse gradients in the odds ratios were obtained for crude fiber, non-starch polysaccharide, and dietary fiber. Sources of fiber, including cereal and vegetable and fruit fiber, were associated with a 29-46% reduction in risk for women in the highest quartiles of consumption. Vitamin A and possibly vitamin C, but not vitamin E, were also inversely associated with endometrial cancer, although trends were not strong. High consumption of soy products and other legumes was associated with a decreased risk of endometrial cancer (p for trend = 0.01; odds ratio = 0.46, 95% confidence interval 0.26-0.83) for the highest compared with the lowest quartile of soy intake. Similar reductions in risk were found for increased consumption of other sources of phytoestrogens such as whole grains, vegetables, fruits, and seaweeds. Ethnic-specific analyses were generally consistent with these results. The observed dietary associations appeared to be largely independent of other risk factors, although the effects of soy and legumes on risk were limited to women who were never pregnant or who had never used unopposed estrogens. These data suggest that plant-based diets low in calories from fat, high in fiber, and rich in legumes (especially soybeans), whole grain foods, vegetables, and fruits reduce the risk of endometrial cancer. These dietary associations may explain in part the reduced rates of uterine cancer in Asian countries compared with those in the United States.


3D display based on parallax barrier with multiview zones.
A 3D display based on a parallax barrier with multiview zones is proposed. This display consists of a 2D display panel and a parallax barrier. The basic element of the parallax barrier has three narrow slits. They can show three columns of subpixels on the 2D display panel and form 3D pixels. The parallax barrier can provide multiview zones. In these multiview zones, the proposed 3D display can use a small number of views to achieve a high density of views. Therefore, the distance between views is the same as the conventional ones with more views. Considering the proposed display has fewer views, which bring more 3D pixels in the 3D images, the resolution and brightness will be higher than the conventional ones. A 12-view prototype of the proposed 3D display is developed, and it provides the same density of views as a conventional one with 28 views. Experimental results show the proposed display has higher resolution and brightness than the conventional one. The cross talk is also limited at a low level.


Novel method to process cystic fibrosis sputum for determination of oxidative state.
Induced sputum is the most commonly used method to analyze airway inflammation in cystic fibrosis (CF) patients ex vivo. Due to the complex matrix of the sample material, precise and reliable analysis of sputum constituents depends critically on preanalytical issues. Here we compared the commonly used method for sputum processing by dithiothreitol (DTT) with a novel mechanical method in regard to basal cellular parameters, neutrophil markers and glutathione (GSH) levels. Sputum samples from CF patients were processed in parallel with or without the use of DTT. The key improvement of the mechanical method was the processing in many very small aliquots. Cellular and humoral markers were assessed and compared according to Bland-Altman. Total cell count, cell viability, differential cell count, neutrophil elastase levels and flow cytometrically analyzed neutrophil markers (CD63, CD11b, DHR) did not differ between the two methods. Intracellular and extracellular GSH levels were significantly higher in DTT-treated samples (p = 0.002). The mechanical sputum-processing method presented had a similar yield of cells and fluids as the conventional DTT method and the advantage of omitting the introduction of reducing agents. This method allows a more reliable analysis of redox-dependent airway inflammation in sputum cells and fluid from CF patients than methods utilizing DTT.


Childhood-onset Leber hereditary optic neuropathy.
The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup. Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m.3460G>A, m.11778G>A or m.14484T>C. In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m.3460G>A and m.14484T>C mutations compared with the m.11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) ≥0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA <0.05 in their better seeing eye. Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.


Flux and composition of interstellar dust at Saturn from Cassini's Cosmic Dust Analyzer.
Interstellar dust (ISD) is the condensed phase of the interstellar medium. In situ data from the Cosmic Dust Analyzer on board the Cassini spacecraft reveal that the Saturnian system is passed by ISD grains from our immediate interstellar neighborhood, the local interstellar cloud. We determine the mass distribution of 36 interstellar grains, their elemental composition, and a lower limit for the ISD flux at Saturn. Mass spectra and grain dynamics suggest the presence of magnesium-rich grains of silicate and oxide composition, partly with iron inclusions. Major rock-forming elements (magnesium, silicon, iron, and calcium) are present in cosmic abundances, with only small grain-to-grain variations, but sulfur and carbon are depleted. The ISD grains in the solar neighborhood appear to be homogenized, likely by repeated processing in the interstellar medium.


Psychiatric disorders in Norwegian 8- to 10-year-olds: an epidemiological survey of prevalence, risk factors, and service use.
The Bergen Child Study is a longitudinal study of child mental health from the city of Bergen, Norway. We present methods and results from the first wave of the study, focusing on prevalence of disorders, associations with risk factors, and the use of services. The target population included all 9,430 children attending grades 2 to 4 in Bergen schools during the academic year 2002/2003. The main screening instrument was the Strengths and Difficulties Questionnaire, whereas diagnoses were based on the Development and Well-Being Assessment. Information about child and family risk factors and service use was also obtained in this second stage. In the first phase, the teacher Strengths and Difficulties Questionnaire was obtained for 9,155 (97%) of the target children and the matching parent Strengths and Difficulties Questionnaire for 6,297 (67%); 1,011 children (11%) were assessed with the Development and Well-Being Assessment in the second phase. The weighted prevalence for any DSM-IV psychiatric disorder was 7.0% (95% confidence interval 5.6%-8.5%). Disorders were associated with age, gender, learning difficulties, family type, and poverty. Although 75% of children with attention-deficit/hyperactivity disorder had been in contact with specialist mental health services, this was true for only 13% of those with pure emotional disorders. The overall prevalence of psychiatric disorders in children is relatively low in this Norwegian sample, when assessed with the Development and Well-Being Assessment. Children with emotional disorders have limited access to specialist services.


Cell adhesion to plasma electrolytic oxidation (PEO) titania coatings, assessed using a centrifuging technique.
The adhesion of bovine chondrocytes and human osteoblasts to three titania-based coatings, formed by plasma electrolytic oxidation (PEO), was compared to that on uncoated Ti-6Al-4V substrates, and some comparisons were also made with plasma sprayed hydroxyapatite (HA) coatings. This was done using a centrifuge, with accelerations of up to 160,000 g, so as to induce buoyancy forces that created normal or shear stresses at the interface. It is shown that, on all surfaces, it was easier to remove cells under normal loading than under shear loading. Cell adhesion to the PEO coatings was stronger than that on Ti-6Al-4V and similar to that on HA. Cell proliferation rates were relatively high on one of the PEO coatings, which was virtually free of aluminium, but low on the other two, which contained significant levels of aluminium. It is concluded that the Al-free PEO coating offers promise for application to prosthetic implants.


An Auto-luminescent Fluorescent BCG Whole Blood Assay to Enable Evaluation of Paediatric Mycobacterial Responses Using Minimal Blood Volumes.
Introduction: Understanding protective human immunity against mycobacteria is critical to developing and evaluating new vaccines against tuberculosis. Children are the most susceptible population to infection, disease, and death from tuberculosis, but also have the strongest evidence of BCG-inducible protection. Limited amounts of blood can be obtained for research purposes in paediatrics and therefore there is a need for high-yield, low-volume, human immunology assays. Methods: We transformed BCG Danish with plasmids encoding luciferase full operon derived from Photorhabdus luminescens together with Green Fluorescent Protein and antibiotic selection markers. We characterised the luminescent and fluorescent properties of this recombinant BCG strain (BCG-GFP-LuxFO) using a luminometer and flow cytometry and developed a paediatric whole blood in vitro infection model. Results: Luminescence of BCG-GFP-LuxFO correlated with optical density (Spearman Rank Correlation coefficient r = 0.985, p < 0.0001) and colony forming units (CFUs) in liquid culture medium (r = 0.971, p < 0.0001). Fluorescence of BCG-GFP-LuxFO in paediatric whole blood was confirmed by flow cytometry in granulocytes and monocytes 1 h following infection. Luminescence of BCG-GFP-LuxFO in whole blood corresponded with CFUs (r = 0.7123, p < 0.0001). Conclusion: The BCG-GFP-LuxFO assay requires 225 μL whole blood per sample, from which serial luminescence measurements can be obtained, together with biochemical analysis of supernatants and cellular assay applications using its fluorescent properties. This offers the opportunity to study human-mycobacterial interactions using multiple experimental modalities with only minimal blood volumes. It is therefore a valuable method for investigating paediatric immunity to tuberculosis.


The influence of deer browsing on the reproductive biology of Canada yew (Taxus canadensis marsh.) : II. Pollen limitation: an indirect effect.
Hand-pollination significantly increased seed production in a Canada yew (Taxus canadensis) population that had been browsed previously by white-tailed deer (Odocoileus virginianus) indicating that pollen availability limited seed production in this population. Handpollination did not significantly increase seed production in a population never browsed by deer. Deer-browsing significantly reduces yew density and pollen production, which in turn results in reduced pollination and seed production. Pollen limitation of yew seed production is an indirect effect of deer browsing on Canada yew and results from an interaction between the direct effect of deer browsing and the pollination syndrome of Canada yew. Artificially created female yews had lower seed set than monoecious yews when yew seed production was pollen-limited, but not when pollen did not limit seed production.


Enteroccocus pallens as a potential novel human pathogen: three cases of spontaneous bacterial peritonitis.
Enterococcus pallens is one of the four yellow-pigmented members of the genus Enterococcus. To date, a single report of E. pallens isolated from a human sample has been published. We report three cases of E. pallens spontaneous bacterial peritonitis in patients with liver cirrhosis that all occurred in Quebec, Canada. Ascitic fluid analysis revealed the presence of E. pallens in culture. Identification was made by classical biochemical testing and MALDI-TOF MS, as well as 16S rRNA and elongation factor (tuf) gene sequencing. Two of the three patients recovered after antimicrobial treatment. This report identifies E. pallens as a novel human pathogen that appears to possess particular but as-yet unidentified virulence factors that favour the development of peritoneal fluid infections, as previously reported for other Enterococcus species. Clinical microbiologist should be aware of this micro-organism which can be identified by phenotypic and molecular methods.


Optogenetic surface stimulation of the rat cervical spinal cord.
Electrical intraspinal microstimulation (ISMS) at various sites along the cervical spinal cord permits forelimb muscle activation, elicits complex limb movements and may enhance functional recovery after spinal cord injury. Here, we explore optogenetic spinal stimulation (OSS) as a less invasive and cell type-specific alternative to ISMS. To map forelimb muscle activation by OSS in rats, adeno-associated viruses (AAV) carrying the blue-light sensitive ion channels channelrhodopsin-2 (ChR2) and Chronos were injected into the cervical spinal cord at different depths and volumes. Following an AAV incubation period of several weeks, OSS-induced forelimb muscle activation and movements were assessed at 16 sites along the dorsal surface of the cervical spinal cord. Three distinct movement types were observed. We find that AAV injection volume and depth can be titrated to achieve OSS-based activation of several movements. Optical stimulation of the spinal cord is thus a promising method for dissecting the function of spinal circuitry and targeting therapies following injury. NEW & NOTEWORTHY Optogenetics in the spinal cord can be used both for therapeutic treatments and to uncover basic mechanisms of spinal cord physiology. For the first time, we describe the methodology and outcomes of optogenetic surface stimulation of the rat spinal cord. Specifically, we describe the evoked responses of forelimbs and address the effects of different adeno-associated virus injection paradigms. Additionally, we are the first to report on the limitations of light penetration through the rat spinal cord.


Maternal and newborn outcomes among women with schizophrenia: a retrospective population-based cohort study.
More women with schizophrenia are becoming pregnant, such that contemporary data are needed about maternal and newborn outcomes in this potentially vulnerable group. We aimed to quantify maternal and newborn health outcomes among women with schizophrenia. Retrospective cohort study. Population based in Ontario, Canada, from 2002 to 2011. Ontario women aged 15-49 years who gave birth to a liveborn or stillborn singleton infant. Women with schizophrenia (n = 1391) were identified based on either an inpatient diagnosis or two or more outpatient physician service claims for schizophrenia within 5 years prior to conception. The reference group comprised 432 358 women without diagnosed mental illness within the 5 years preceding conception in the index pregnancy. The primary maternal outcomes were gestational diabetes mellitus, gestational hypertension, pre-eclampsia/eclampsia, and venous thromboembolism. The primary neonatal outcomes were preterm birth, and small and large birthweight for gestational age (SGA and LGA). Secondary outcomes included additional key perinatal health indicators. Schizophrenia was associated with a higher risk of pre-eclampsia (adjusted odds ratio, aOR 1.84; 95% confidence interval, 95% CI 1.28-2.66), venous thromboembolism (aOR 1.72, 95% CI 1.04-2.85), preterm birth (aOR 1.75, 95% CI 1.46-2.08), SGA (aOR 1.49, 95% CI 1.19-1.86), and LGA (aOR 1.53, 95% CI 1.17-1.99). Women with schizophrenia also required more intensive hospital resources, including operative delivery and admission to a maternal intensive care unit, paralleled by higher neonatal morbidity. Women with schizophrenia are at higher risk of multiple adverse pregnancy outcomes, paralleled by higher neonatal morbidity. Attention should focus on interventions to reduce the identified health disparities.


Histomorphometric and fluorescence microscopic evaluation of interfacial bone healing around 3 different dental implants before and after radiation therapy.
Radiation therapy influence on bone healing around 3 types of endosseous dental implants in dogs was evaluated. Implants with 3 different surfaces (A = machined commercially pure titanium screws, B = commercially pure titanium plasma spray-coated cylinders, C = hydroxyapatite [HA] -ceramic coated cylinders) were first implanted unilaterally into the right posterior edentulous mandibles of 7 dogs as nonirradiated controls. After 12 weeks without functional loading and after sequential fluorochrome labeling these implants were retrieved by block dissection. In this same surgery, implants were placed on the contralateral side. Three weeks postimplantation the implant-containing hemimandibles were Cobalt 60 irradiated with the biologic equivalent of 5,000 cGy. Twelve weeks postimplantation and after labeling these irradiated implants were retrieved at sacrifice. On scanning electron, light, and fluorescence microscopic images of undecalcified longitudinal ground sections of the implants with surrounding tissues, percent bone-to-implant contact (% BIC), bone formation, and remodeling were histometrically and subjectively evaluated. Woven bone formation started 1 week after implantation at the implant interfaces on both the nonirradiated and the irradiated sides. Average BICs (total/cortical/spongious bone bed) of 26%/49%/36% for surface A, 46%/48%/64% for surface B, and 81%/83%/78% for surface C were observed. In the irradiated hemimandibles average BICs (total/cortical/spongious bone bed) were reduced to 11%/9%/4% for surface A, 43%/46%/43% for surface B, and 63%/85%/76% for surface C, with increased resorption of peri-implant bone and retarded bone formation after irradiation. Reductions of total % BIC in all irradiated implants, though not statistically significant, were significant (P < or = .05) on implant surfaces A and B in the spongious bone bed. Retarded bone formation on surfaces A and B in the spongious bone bed represented a more radiation-sensitive situation at the time of radiation onset compared to advanced bone formation and maturation at surface C.


Conventional CD11chigh Dendritic Cells Are Important for T Cell Priming during the Initial Phase of Plasmodium yoelii Infection, but Are Dispensable at Later Time Points.
Dendritic cells (DCs) are highly specialized antigen-presenting cells that orchestrate adaptive immune responses to pathogens. During malaria infection pro- and anti-inflammatory T cell responses have to be tightly balanced to ensure parasite clearance without induction of severe immune pathologies. However, the precise role of CD11chigh DCs in this process is still discussed controversially. Here, we demonstrate that long-term depletion of conventional CD11chigh DCs in Plasmodium yoelii (P. yoelii)-infected diphtheria toxin (DT)-treated RosaiDTR/CD11c-cre mice interferes with the activation of CD8+ and CD4+ T cells as well as CD4+Foxp3+ regulatory T cells at early time points during infection. Moreover, systemic levels of the pro-inflammatory cytokines IFN-γ and TNF-α were decreased in P. yoelii-infected mice deficient for CD11chigh DCs compared to infected RosaiDTR controls. To further elucidate the importance of CD11chigh DCs during the later phase of infection, we treated RosaiDTR/CD11c-cre and control mice with DT only from day 4 of P. yoelii infection onward. Strikingly, this approach had no impact on the activation and IFN-γ production of CD4+ and CD8+ effector T cells. These results indicate that CD11chigh DCs play a crucial role in eliciting effector T cell responses during the initial phase, but are dispensable during ongoing infection with P. yoelii.


Statistical significance approximation in local trend analysis of high-throughput time-series data using the theory of Markov chains.
Local trend (i.e. shape) analysis of time series data reveals co-changing patterns in dynamics of biological systems. However, slow permutation procedures to evaluate the statistical significance of local trend scores have limited its applications to high-throughput time series data analysis, e.g., data from the next generation sequencing technology based studies. By extending the theories for the tail probability of the range of sum of Markovian random variables, we propose formulae for approximating the statistical significance of local trend scores. Using simulations and real data, we show that the approximate p-value is close to that obtained using a large number of permutations (starting at time points >20 with no delay and >30 with delay of at most three time steps) in that the non-zero decimals of the p-values obtained by the approximation and the permutations are mostly the same when the approximate p-value is less than 0.05. In addition, the approximate p-value is slightly larger than that based on permutations making hypothesis testing based on the approximate p-value conservative. The approximation enables efficient calculation of p-values for pairwise local trend analysis, making large scale all-versus-all comparisons possible. We also propose a hybrid approach by integrating the approximation and permutations to obtain accurate p-values for significantly associated pairs. We further demonstrate its use with the analysis of the Polymouth Marine Laboratory (PML) microbial community time series from high-throughput sequencing data and found interesting organism co-occurrence dynamic patterns. The software tool is integrated into the eLSA software package that now provides accelerated local trend and similarity analysis pipelines for time series data. The package is freely available from the eLSA website: http://bitbucket.org/charade/elsa.


Effectiveness of Ginger on Pain and Function in Knee Osteoarthritis: A PRISMA Systematic Review and Meta-Analysis.
Ginger has been proposed as a complementary treatment for musculoskeletal pain. However, efficacy, type, and safety remains unclear. To determine the effectiveness of consumption or topical application of ginger for pain relief and knee function improvement in patients with knee osteoarthritis. Systematic review with meta-analysis of randomized clinical trials. An electronic search was performed on Medline, Central, CINAHL, PEDro, SPORTDiscus, and LILACS databases. The eligibility criteria for selecting studies included clinical trials that compared consumption and/or topical ginger with placebo or other interventions for the pain relief and knee function in patients with medical diagnosis of knee osteoarthritis. Seven clinical trials met the eligibility criteria, and for the quantitative synthesis, 4 studies were included. For the comparison capsules versus placebo, mean difference for pain was -7.88 mm; 95% confidence interval (CI), 11.92 to 3.85 (P = 0.00), and standard mean difference for knee function was -1.61 points; 95% CI, -4.30 to -1.09 (P = 0.24). For the comparison of topical ginger versus standard treatment, standard mean difference for pain was 0.79 mm; 95% CI, -1.97 to 0.39 (P = 0.19), and standard mean difference for knee function was -0.51 points; 95% CI, -1.15 to 0.13 (P = 0.12). The current evidence is heterogeneous and has a poor methodologic quality. There is insufficient evidence to support the use of oral ginger compared with placebo in the pain relief and function improvement in patients with knee osteoarthritis. For other comparisons, no statistically significant differences were found. Osteoarthritis, knee osteoarthritis, ginger, pain, randomized clinical trial, systematic review.


Suitability of cryopreservation for the long-term storage of rare and endangered plant species: a case history for Cosmos atrosanguineus.
The suitability of cryopreservation for the secure, long-term storage of the rare and endangered species Cosmos atrosanguineus was investigated. Using encapsulation/dehydration of shoot tips in alginate strips, survival rates of up to 100 % and shoot regeneration of up to 35 % were achieved. Light and electron microscopy studies indicated that cellular damage to some regions of the shoot tip during the freeze/thaw procedure was high, although cell survival in and around the meristematic region allowed shoot tip regeneration. The genetic fingerprinting technique, amplified fragment length polymorphisms (AFLPs), showed that no detectable genetic variation was present between material of C. atrosanguineus at the time of initiation into tissue culture and that which had been cryopreserved, stored in liquid nitrogen for 12 months and regenerated. Weaned plantlets that were grown under glasshouse conditions exhibited no morphological variation from non-frozen controls.


Improvement of Post-hypoxic Myoclonus with Bilateral Pallidal Deep Brain Stimulation: A Case Report and Review of the Literature.
Post-hypoxic myoclonus (PHM) is a syndrome that occurs when a patient has suffered hypoxic brain injury. The myoclonus is usually multifocal and generalized, often stemming from both cortical and subcortical origins. In severe cases, pharmacological treatments with antiepileptic medications may not satisfactorily control the myoclonus. We present a case of a 23-year-old male with chronic medication refractory PHM following a cardiopulmonary arrest related to an asthmatic attack who improved with bilateral globus pallidus internus (GPi) deep brain stimulation (DBS). We review the clinical features of PHM, as well as the preoperative and postoperative Unified Myoclonus Rating Scale scores and DBS programming parameters in this patient and compare them with the three other published PHM-DBS cases in the literature. This patient experienced an alleviation of myoclonic jerks at rest and a 39% reduction in action myoclonus with improvement in both positive and negative myoclonus with bilateral GPi-DBS. High frequency stimulation (130 Hz) with amplitudes >2.5 V were needed for the therapeutic response. We demonstrate a robust improvement in a medication refractory PHM patient with bilateral GPi-DBS, and suggest that it is a viable therapeutic option for debilitating post-hypoxic myoclonus.


Ipilimumab for advanced melanoma: a nursing perspective.
To discuss the response patterns and side effects related to ipilimumab, a new immunotherapeutic agent under investigation in the treatment of advanced melanoma and other malignancies. Published articles, abstracts, research data, and clinical experience. Ipilimumab is a fully human monoclonal antibody that inhibits the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a naturally immunosuppressive molecule. The most common side effects are immune mediated (e.g., inflammatory diarrhea, pruritus) and appear to occur as a direct result of CTLA-4 inhibition and enhanced immune system activation. Side effects generally are grade I or II and resolve with standard treatments. Most grade III or IV events are managed successfully after swift diagnosis and treatment with corticosteroids; steroid-refractory events resolve after treatment with infliximab or mycophenolate. The response patterns and side effects associated with ipilimumab therapy greatly differ from those common to other advanced melanoma therapies (e.g., chemotherapy, cytokines, vaccines). Nurses have an important role in educating patients about the differences between anti-CTLA-4 therapy and chemotherapy. In addition, teaching patients to recognize ipilimumab's side effects and report them early can result in fast treatment to prevent symptom progression from grade I or II to III or IV. Communication between nurses and patients throughout the treatment process will help patients benefit maximally from the new therapeutic strategy.


Differences in spinopelvic kinematics in sweep and scull ergometer rowing.
The spinopelvic kinematics of sweep and scull have yet to be investigated, despite evidence suggesting that sweep rowing may be provocative for low back pain (LBP). The aim of this study was to determine whether differences existed in spinopelvic kinematics in high-level rowers without LBP in sweep and scull ergometer rowing. Repeated measures study. Institute of Sport Laboratory. Ten high-level rowers. Kinematics of the pelvis, lower lumbar, upper lumbar, and lower thoracic regions during the drive phase of the rowing stroke were measured while rowing on an interchangeable sweep/scull ergometer. Total and segmental spinopelvic kinematics. Sweep rowing showed greater lateral bend (P < 0.05) throughout the stroke, which was predominately due to movement of the upper lumbar and lower thoracic regions. Furthermore, sweep rowing displayed a greater magnitude (P < 0.05) of axial rotation at the catch (created at the pelvis). Both sweep and scull rowing showed values close to end range flexion for the lower lumbar spine at the catch and early drive phases. No difference (P > 0.05) was evident in lateral bend or axial rotation values for the lower lumbar region. Some differences exist in spinopelvic kinematics between sweep and scull ergometer rowing. However, it may be speculated that the lack of differences in lateral bend and axial rotation at the lower lumbar spine in sweep rowing may represent an adaptive and protective approach of experienced rowers. This may be the focus of future research studies.


Genetic analysis of an ephemeral intraspecific hybrid zone in the hypervariable tree, Metrosideros polymorpha, on Hawai'i Island.
Intraspecific hybrid zones involving long-lived woody species are rare and can provide insights into the genetic basis of early-diverging traits in speciation. Within the landscape-dominant Hawaiian tree, Metrosideros polymorpha, are morphologically distinct successional varieties, incana and glaberrima, that dominate new and old lava flows, respectively, below 1200 me on volcanically active Hawai'i Island, with var. glaberrima also extending to higher elevations and bogs. Here, we use morphological measurements on 86 adult trees to document the presence of an incana-glaberrima hybrid zone on the 1855 Mauna Loa lava flow on east Hawai'i Island and parent-offspring analysis of 1311 greenhouse seedlings from 71 crosses involving 72 adults to estimate heritabilities and genetic correlations among vegetative traits. Both the variation in adult leaf pubescence at the site and the consistency between adult and offspring phenotypes suggest the presence of two hybrid classes, F1s and var. incana backcrosses, as would be expected on a relatively young lava flow. Nine nuclear microsatellite loci failed to distinguish parental and hybrid genotypes. All four leaf traits examined showed an additive genetic basis with moderate to strong heritabilities, and genetic correlations were stronger for the more range-restricted var. incana. The differences between varieties in trait values, heritabilities and genetic correlations, coupled with high genetic variation within but low genetic variation between varieties, are consistent with a multi-million-year history of alternating periods of disruptive selection in contrasting environments and admixture in ephemeral hybrid zones. Finally, the contrasting genetic architectures suggest different evolutionary trajectories of leaf traits in these forms.


Practices to Foster Physician Presence and Connection With Patients in the Clinical Encounter.
Time constraints, technology, and administrative demands of modern medicine often impede the human connection that is central to clinical care, contributing to physician and patient dissatisfaction. To identify evidence and narrative-based practices that promote clinician presence, a state of awareness, focus, and attention with the intent to understand patients. Preliminary practices were derived through a systematic literature review (from January 1997 to August 2017, with a subsequent bridge search to September 2019) of effective interpersonal interventions; observations of primary care encounters in 3 diverse clinics (n = 27 encounters); and qualitative interviews with physicians (n = 10), patients (n = 27), and nonmedical professionals whose occupations involve intense interpersonal interactions (eg, firefighter, chaplain, social worker; n = 30). After evidence synthesis, promising practices were reviewed in a 3-round modified Delphi process by a panel of 14 researchers, clinicians, patients, caregivers, and health system leaders. Panelists rated each practice using 9-point Likert scales (-4 to +4) that reflected the potential effect on patient and clinician experience and feasibility of implementation; after the third round, panelists selected their "top 5" practices from among those with median ratings of at least +2 for all 3 criteria. Final recommendations incorporate elements from all highly rated practices and emphasize the practices with the greatest number of panelist votes. The systematic literature review (n = 73 studies) and qualitative research activities yielded 31 preliminary practices. Following evidence synthesis, 13 distinct practices were reviewed by the Delphi panel, 8 of which met criteria for inclusion and were combined into a final set of 5 recommendations: (1) prepare with intention (take a moment to prepare and focus before greeting a patient); (2) listen intently and completely (sit down, lean forward, avoid interruptions); (3) agree on what matters most (find out what the patient cares about and incorporate these priorities into the visit agenda); (4) connect with the patient's story (consider life circumstances that influence the patient's health; acknowledge positive efforts; celebrate successes); and (5) explore emotional cues (notice, name, and validate the patient's emotions). This mixed-methods study identified 5 practices that have the potential to enhance physician presence and meaningful connection with patients in the clinical encounter. Evaluation and validation of the outcomes associated with implementing the 5 practices is needed, along with system-level interventions to create a supportive environment for implementation.


Delivery of definable number of drug or growth factor loaded poly(DL-lactic acid-co-glycolic acid) microparticles within human embryonic stem cell derived aggregates.
Embryoid bodies (EBs) generated from embryonic stem cells are used to study processes of differentiation within a three dimensional (3D) cell environment. In many instances however, EBs are dispersed to single cell suspensions with a subsequent monolayer culture. Moreover, where the 3D integrity of an EB is maintained, cytokines or drugs of interest to stimulate differentiation are often added directly to the culture medium at fixed concentrations and effects are usually limited to the outer layers of the EB. The aim of this study was to create an EB model with localised drug and or growth factor delivery directly within the EB. Using poly(DL-lactic acid-co-glycolic acid) microparticles (MPs) with an average diameter of 13μm, we have demonstrated controllable incorporation of defined numbers of MPs within human ES cell derived EBs, down to 1 MP per EB. This was achieved by coating MPs with human ES cell lysate and centrifugation of specific ratios of ES cells and MPs to form 3D aggregates. Using MPs loaded with simvastatin (pro or active drug) or BMP-2, we have demonstrated osteogenic differentiation within the 3D aggregates, maintained in culture for up to 21days, and quantified by real time QPCR for osteocalcin. Immunostaining for RUNX2 and osteocalcin, and also histochemical staining with picrosirius red to demonstrate collage type 1 and Alizarin red to demonstrate calcium/mineralisation further demonstrated osteogenic differentiation and revealed regional staining associated with the locations of MPs within the aggregates. We also demonstrated endothelial differentiation within human ES cell-derived aggregates using VEGF loaded MPs. In conclusion, we demonstrate an effective and reliable approach for engineering stem aggregates with definable number of MPs within the 3D cellular structure. We also achieved localised osteogenic and endothelial differentiation associated with MPs releasing encapsulated drug molecules or cytokines directly within the cell aggregate. This provides a powerful tool for controlling and investigating differentiation within 3D cell cultures and has applications to drug delivery, drug discovery, stem cell biology, tissue engineering and regenerative medicine.


Mediators and Moderators of the Effectiveness of a Community Health Worker Intervention That Improved Dietary Outcomes in Pregnant Latino Women.
Pregnancy is an opportune time to initiate diabetes prevention strategies for minority and underserved women, using culturally tailored interventions delivered by community health workers. A community-partnered randomized controlled trial (RCT) with pregnant Latino women resulted in significantly improved vegetable, fiber, added sugar, and total fat consumption compared to a minimal intervention group. However, studying RCT intervention effects alone does not explain the mechanisms by which the intervention was successful or help identify which participants may have benefitted most. To improve the development and targeting of future community health worker interventions for high-risk pregnant women, we examined baseline characteristics (moderators) and potential mechanisms (mediators) associated with these dietary changes. Secondary analysis of data for 220 Latina RCT participants was conducted. A linear regression with effects for intervention group, moderator, and interaction between intervention group and moderator was used to test each hypothesized moderator of dietary changes. Sobel-Goodman mediation test was used to assess mediating effects on dietary outcomes. Results varied by dietary outcome. Improvements in vegetable consumption were greatest for women who reported high spousal support at baseline. Women younger than age 30 were more likely to reduce added sugar consumption than older women. Participants who reported higher baseline perceived control were more likely to reduce fat consumption. No examined mediators were significantly associated with intervention effects. Future interventions with pregnant Latinas may benefit from tailoring dietary goals to consider age, level of spousal support, and perceived control to eat healthy.


Comparison of Syringe Compression Force Between ENFit and Legacy Feeding Tubes.
Since initial report in 1972, misconnections continue to be an issue, especially in hospitalized patients with multiple access devices. A new small-bore connector standard (ENFit) has been proposed in order to minimize misconnections. Commercially available finalized ENFit tubes of a variety of sizes (14 French [Fr] size, 18Fr, 20Fr, 24Fr, and low-profile) were obtained for current testing. Variety of commercially available formulas including blenderized tube feeding (BTF) products (Jevity 1 Cal, Abbott Nutrition, Abbott Park, IL; Nourish, Functional Formularies, Centerville, OH; Real Food Blends, Chesterton, IN) were tested. Data from individual measurements were aggregated for ENFit and legacy tubes and revealed higher syringe compression force in legacy tubes compared with ENFit tubes for 20Fr size with Jevity formula. Our institution's BTF formula revealed that legacy tubes had lower syringe compression force than ENFit tubes for 14Fr tube size. Remaining measurements revealed no significant difference. Model 1 of regression analysis revealed that only formula and tube size were significant with R2 of 0.63. Model 2 evaluating the impact of tube size, blender, time of blending, and legacy vs ENFit revealed that tube size, blender used, and blending time were significant with legacy vs ENFit being nonsignificant (R2 of 0.72). Overall, only a small number of tube sizes (14Fr and 20Fr) with selected formulas revealed a significant difference between ENFit and Legacy tubes, with remaining studies finding no significant difference. Regression analysis revealed that variables such as formula, size of tube, blender used, and time of blending may have more impact on compression force.


Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early Adversity and Psychopathology.
Telomere shortening and alterations of mitochondrial biogenesis are involved in cellular aging. Childhood adversity is associated with telomere shortening, and several investigations have shown short telomeres in psychiatric disorders. Recent studies have examined whether mitochondria might be involved in neuropsychiatric conditions; findings are limited and no prior work has examined this in relation to stress exposure. Two-hundred ninety healthy adults provided information on childhood parental loss and maltreatment and completed diagnostic interviews. Participants were categorized into four groups based upon the presence or absence of childhood adversity and the presence or absence of lifetime psychopathology (depressive, anxiety, and substance use disorders). Telomere length and mitochondrial DNA (mtDNA) copy number were measured from leukocyte DNA by quantitative polymerase chain reaction. Childhood adversity and lifetime psychopathology were each associated with shorter telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. A history of substance disorders was also associated with significantly higher mtDNA copy numbers. This study provides the first evidence of an alteration of mitochondrial biogenesis with early life stress and with anxiety and substance use disorders. We replicate prior work on telomere length and psychopathology and show that this effect is not secondary to medication use or comorbid medical illness. Finally, we show that early life stress and psychopathology are each associated with these markers of cellular aging.


From the guest editors.
Carlos Castilo-Chavez is a Regents Professor, a Joaquin Bustoz Jr. Professor of Mathematical Biology, and a Distinguished Sustainability Scientist at Arizona State University. His research program is at the interface of the mathematical and natural and social sciences with emphasis on (i) the role of dynamic social landscapes on disease dispersal; (ii) the role of environmental and social structures on the dynamics of addiction and disease evolution, and (iii) Dynamics of complex systems at the interphase of ecology, epidemiology and the social sciences. Castillo-Chavez has co-authored over two hundred publications (see goggle scholar citations) that include journal articles and edited research volumes. Specifically, he co-authored a textbook in Mathematical Biology in 2001 (second edition in 2012); a volume (with Harvey Thomas Banks) on the use of mathematical models in homeland security published in SIAM's Frontiers in Applied Mathematics Series (2003); and co-edited volumes in the Series Contemporary Mathematics entitled '' Mathematical Studies on Human Disease Dynamics: Emerging Paradigms and Challenges'' (American Mathematical Society, 2006) and Mathematical and Statistical Estimation Approaches in Epidemiology (Springer-Verlag, 2009) highlighting his interests in the applications of mathematics in emerging and re-emerging diseases. Castillo-Chavez is a member of the Santa Fe Institute's external faculty, adjunct professor at Cornell University, and contributor, as a member of the Steering Committee of the '' Committee for the Review of the Evaluation Data on the Effectiveness of NSF-Supported and Commercially Generated Mathematics Curriculum Materials,'' to a 2004 NRC report. The CBMS workshop '' Mathematical Epidemiology with Applications'' lectures delivered by C. Castillo-Chavez and F. Brauer in 2011 have been published by SIAM in 2013.


Genome analysis of three Pneumocystis species reveals adaptation mechanisms to life exclusively in mammalian hosts.
Pneumocystis jirovecii is a major cause of life-threatening pneumonia in immunosuppressed patients including transplant recipients and those with HIV/AIDS, yet surprisingly little is known about the biology of this fungal pathogen. Here we report near complete genome assemblies for three Pneumocystis species that infect humans, rats and mice. Pneumocystis genomes are highly compact relative to other fungi, with substantial reductions of ribosomal RNA genes, transporters, transcription factors and many metabolic pathways, but contain expansions of surface proteins, especially a unique and complex surface glycoprotein superfamily, as well as proteases and RNA processing proteins. Unexpectedly, the key fungal cell wall components chitin and outer chain N-mannans are absent, based on genome content and experimental validation. Our findings suggest that Pneumocystis has developed unique mechanisms of adaptation to life exclusively in mammalian hosts, including dependence on the lungs for gas and nutrients and highly efficient strategies to escape both host innate and acquired immune defenses.


Alveolar macrophages: reduced number in rats after prolonged inhalation of lead sesquioxide.
A decreased number of alveolar macrophages was found in washings from lungs of rats inhaling small particles of lead sesquioxide for 3 to 12 months, as compared with control animals exposed to filtered air. This result contrasts with that reported by others for animals given massive exposures to various dusts for short periods of time. Because the concentrations of lead were comparable to those observed in some industrial(150 microg/m(3)) or urban (10 microg/m(3)) environmental conditions, the results may be significant in terms of human lung clearance processes after such exposures.


SorCS2-mediated NR2A trafficking regulates motor deficits in Huntington's disease.
Motor dysfunction is a prominent and disabling feature of Huntington's disease (HD), but the molecular mechanisms that dictate its onset and progression are unknown. The N-methyl-D-aspartate receptor 2A (NR2A) subunit regulates motor skill development and synaptic plasticity in medium spiny neurons (MSNs) of the striatum, cells that are most severely impacted by HD. Here, we document reduced NR2A receptor subunits on the dendritic membranes and at the synapses of MSNs in zQ175 mice that model HD. We identify that SorCS2, a vacuolar protein sorting 10 protein-domain (VPS10P-domain) receptor, interacts with VPS35, a core component of retromer, thereby regulating surface trafficking of NR2A in MSNs. In the zQ175 striatum, SorCS2 is markedly decreased in an age- and allele-dependent manner. Notably, SorCS2 selectively interacts with mutant huntingtin (mtHTT), but not WT huntingtin (wtHTT), and is mislocalized to perinuclear clusters in striatal neurons of human HD patients and zQ175 mice. Genetic deficiency of SorCS2 accelerates the onset and exacerbates the motor coordination deficit of zQ175 mice. Together, our results identify SorCS2 as an interacting protein of mtHTT and demonstrate that impaired SorCS2-mediated NR2A subunit trafficking to dendritic surface of MSNs is, to our knowledge, a novel mechanism contributing to motor coordination deficits of HD.


Pneumonia, Intake Problems, and Survival Among Nursing Home Residents With Variable Stages of Dementia in the Netherlands: Results From a Prospective Observational Study.
We explored how pneumonia and intake problems affect survival in nursing home residents in variable stages of dementia. In a longitudinal observational study (372 residents) with up to 3.5 years of follow-up, we examined relationships between dementia severity, the development of pneumonia, intake problems, and mortality using joint modeling, Cox models, and mediation analyses. Dementia severity was measured semiannually with the Bedford Alzheimer Nursing Severity-Scale (BANS-S). The median BANS-S score at baseline was 13 (range, 7 to 28). Pneumonia occurred in 103 (28%) and intake problems in 126 (34%) of 367 residents with complete registration of pneumonia and intake problems. Compared with dementia severity, incident pneumonia and, even more so, incident intake problems were more strongly associated with mortality risk. Pneumonia and intake problems both mediated the relationship between more severe dementia and mortality. Developing pneumonia and intake problems affects survival, and this is not limited to advanced dementia. The occurrence of pneumonia and intake problems are important signals to consider a palliative care approach in nursing home residents with dementia, and an active focus on advance care planning is needed. Future studies should investigate whether this is also relevant for patients in primary care.


Analysis of mouse brain peptides using mass spectrometry-based peptidomics: implications for novel functions ranging from non-classical neuropeptides to microproteins.
Peptides are known to play many important physiological roles in signaling. A large number of peptides have been detected in mouse brain extracts using mass spectrometry-based peptidomics studies, and 850 peptides have been identified. Half of these peptides are derived from secretory pathway proteins and many are known bioactive neuropeptides which activate G protein-coupled receptors; these are termed "classical neuropeptides". In addition, 427 peptides were identified that are derived from non-secretory pathway proteins; the majority are cystosolic, and the remainder are mitochondrial, nuclear, lysosomal, or membrane proteins. Many of these peptides represent the N- or C-terminus of the protein, rather than internal fragments, raising the possibility that they are formed by selective processing rather than protein degradation. In addition to consideration of the cleavage site required to generate the intracellular peptides, their potential functions are discussed. Several of the cytosolic peptides were previously found to interact with receptors and/or otherwise influence cellular activity; examples include hemorphins, hemopressins, diazepam binding inhibitor, and hippocampal cholinergic neurostimulating peptide. The possibility that these peptides are secreted from cells and function in cell-cell signaling is discussed. If these intracellular peptides can be shown to be secreted in levels sufficient to produce a biological effect, they would appropriately be called "non-classical neuropeptides" by analogy with non-classical neurotransmitters such as nitric oxide and anandamide. It is also possible that intracellular peptides function as "microproteins" and modulate protein-protein interactions; evidence for this function is discussed, along with future directions that are needed to establish this and other possible functions for peptides.


Effectiveness of antioxidants (propolis, blueberry, vitamin E) associated with verapamil in the medical management of Peyronie's disease: a study of 151 cases.
A total of 151 patients (age: 24-74 years, mean: 55 ± 10.3) diagnosed with Peyronie's disease were enrolled in a non-surgical treatment. In addition to medical histories and physical examinations, all patients underwent the following tests: penile ultrasound, IIEF questionnaire and photographic documentation. The penile curvature was measured by taking a photograph during maximum erection. All 151 patients were treated at different times and with different combinations of drugs, and afterwards, they were clinically studied and divided into five different treatment groups: 1st = verapamil (injection + iontophoresis) + vitamin E + topical diclofenac + blueberries; 2nd = verapamil (injection + iontophoresis) + vitamin E + topical diclofenac + propolis; 3rd = verapamil (injection) + vitamin E + topical Diclofenac; 4th = verapamil (iontophoresis) + vitamin E + topical diclofenac; 5th = verapamil (injection + iontophoresis) + topical diclofenac + blueberries + propolis. All patients were treated for 6 months after which they underwent the same follow-up tests as performed prior to the treatment. The following was achieved: group 1 had the most reduction in plaque size (-66.4%; p = 0.000), group 2 obtained the highest rate where penile curvature disappeared (24.5%; p = 0.019); the best results with reference to decrease in curvature angle were reached by the 2nd group (-14°) and group 1 obtained -9.6° (p = 0.000).


Same-day discharge compared with overnight hospitalization after uncomplicated percutaneous coronary intervention: a systematic review and meta-analysis.
This study sought to evaluate outcomes of same-day discharge (SDD) following percutaneous coronary intervention (PCI) versus overnight hospitalization (ON). Although there are data on the safety and feasibility of SDD after PCI, ON continues to be prevalent. The Cochrane search strategy was used to search the PubMed database, EMBASE, and the Cochrane Library for relevant literature. Thirteen studies (5 randomized and 8 observational) of SDD after uncomplicated PCI versus ON met inclusion criteria. Data were pooled using a random effects model, and reported as odds ratios (OR) with their 95% confidence intervals (CI). The primary outcomes were incidence of total complications, major adverse cardiovascular events (MACE), and rehospitalization within 30 days after PCI. A total of 13 studies, involving 111,830 patients were pooled. There was significant variation in the definition of outcomes across studies. For total complications, the strategy of SDD compared with ON after PCI had an estimated OR of 1.20 (95% CI: 0.82 to 1.74) in randomized and 0.67 (95% CI: 0.27 to 1.66) in observational studies. Similar results were found for MACE (randomized, OR: 0.99, 95% CI: 0.45 to 2.18; observational, OR: 0.59, 95% CI: 0.06 to 5.57) and rehospitalizations (randomized, OR: 1.10, 95% CI: 0.70 to 1.74; observational, OR: 0.62, 95% CI: 0.10 to 3.98) at 30 days post PCI. There is considerable heterogeneity across published studies comparing SDD with ON. This, coupled with the low event rate and wide corresponding CIs, suggest that an adequately powered multicenter randomized trial comparing SDD with ON would require a very large sample size (>17,000). Until such a trial is completed, SDD after uncomplicated PCI seems a reasonable approach in selected patients.


The theory of speciation via the founder principle.
The founder principle has been used to explain many instances of rapid speciation. Advances from theoretical population genetics are incorporated into MAYR's original founder-effect genetic-revolution model to yield a newer model called the genetic transilience. The basic theoretical edifice lies upon the fact that founder event can sometimes lead to an accumulation of inbreeding and an induction of gametic disequilibrium. This, in turn, causes alleles to be selected more for their homozygous fitness effects and for their effects on a more stable genetic background. Selection occurring in multi-locus systems controlling integrated developmental, physiological, behavioral, etc, traits is particularly sensitive to these founder effects. If sufficient genetic variability exists in the founder population, such multilocus genetic systems can respond to drift and the altered selective forces by undergoing a rapid shift to a new adaptive peak known as the genetic transilience. A genetic transilience is, therefore, most likely to occur when the founder event causes a rapid accumulation of inbreeding without a severe reduction in genetic variability. The implications of this model are then examined for three aspects of the founder-effect genetic-transilience model: the attributes of the ancestral population, the nature of the sampling process used to generate the founders and the attributes of the founder population. The model is used to explain several features of the evolution of the Hawaiian Drosophila, and experimental designs are outlined to test the major predictions of the theory. Hence, this theory of speciation can be tested in the laboratory, using systems and techniques that already exist--a rare attribute of most models of speciation.


Temporal dynamics of verbal object comprehension.
Knowledge of the stage composition and the temporal dynamics of human cognitive operations is critical for building theories of higher mental activity. This information has been difficult to acquire, even with different combinations of techniques such as refined behavioral testing, electrical recording/interference, and metabolic imaging studies. Verbal object comprehension was studied herein in a single individual, by using three tasks (object naming, auditory word comprehension, and visual word comprehension), two languages (English and Farsi), and four techniques (stimulus manipulation, direct cortical electrical interference, electrocorticography, and a variation of the technique of direct cortical electrical interference to produce time-delimited effects, called timeslicing), in a subject in whom indwelling subdural electrode arrays had been placed for clinical purposes. Electrical interference at a pair of electrodes on the left lateral occipitotemporal gyrus interfered with naming in both languages and with comprehension in the language tested (English). The naming and comprehension deficit resulted from interference with processing of verbal object meaning. Electrocorticography indices of cortical activation at this site during naming started 250-300 msec after visual stimulus presentation. By using the timeslicing technique, which varies the onset of electrical interference relative to the behavioral task, we found that completion of processing for verbal object meaning varied from 450 to 750 msec after current onset. This variability was found to be a function of the subject's familiarity with the objects.


Serum androgens and sex hormone-binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada.
Differences in endogenous androgen levels have been hypothesized to explain ethnic differences in prostate cancer risk. To examine this hypothesis, we gathered data on serum concentrations of androgens and sex hormone-binding globulin (SHBG) in healthy older men from four ethnic groups at different levels of prostate cancer risk. As part of a population-based case-control study of prostate cancer we conducted in California, Hawaii, and Vancouver, Canada, 1127 African-American, white, Chinese-American, and Japanese-American control men, mostly ages 60 years or older (mean age, 69.9 years) provided information on various lifestyle factors and donated an early morning fasting blood sample between March 1990 and March 1992. We used these data to examine the distributions of serum androgens [testosterone (total, free, and bioavailable), dihydrotestosterone (DHT)], the ratio of DHT to total testosterone (DHT:testosterone ratio), and SHBG in these four ethnic groups. We also assessed correlations between concentrations of these measures with age, body size, physical activity, and other personal characteristics, and we evaluated ethnic differences in concentrations of androgens and SHBG after adjusting for these characteristics. In each of the four ethnic groups, concentrations of free and bioavailable testosterone declined with age, whereas SHBG concentrations increased with age. Age-adjusted concentrations of all androgen measures and SHBG decreased with increasing levels of Quetelet's index. After adjustment for age and Quetelet's index, androgens and SHBG showed no clear and consistent relationships to physical activity, alcohol consumption, or tobacco use. DHT:testosterone ratio was higher in men reporting a history of benign prostate disease than in men without such a history, and higher in vasectomized men than in nonvasectomized men. SHBG concentrations were higher in men reporting one or more first-degree relatives with prostate cancer than in men without such a family history. After adjustment for age and Quetelet's index, the levels of total and bioavailable testosterone were highest in Asian-Americans, intermediate in African-Americans, and lowest in whites. However, the DHT:testosterone ratio was highest in African-Americans, intermediate in whites, and lowest in Asian-Americans, corresponding to the respective incidence rates in these groups and providing indirect evidence for ethnic differences in 5alpha-reductase enzyme activity.


VO2max trainability and high intensity interval training in humans: a meta-analysis.
Endurance exercise training studies frequently show modest changes in VO2max with training and very limited responses in some subjects. By contrast, studies using interval training (IT) or combined IT and continuous training (CT) have reported mean increases in VO2max of up to ~1.0 L · min(-1). This raises questions about the role of exercise intensity and the trainability of VO2max. To address this topic we analyzed IT and IT/CT studies published in English from 1965-2012. Inclusion criteria were: 1)≥ 3 healthy sedentary/recreationally active humans <45 yrs old, 2) training duration 6-13 weeks, 3) ≥ 3 days/week, 4) ≥ 10 minutes of high intensity work, 5) ≥ 1:1 work/rest ratio, and 6) results reported as mean ± SD or SE, ranges of change, or individual data. Due to heterogeneity (I(2) value of 70), statistical synthesis of the data used a random effects model. The summary statistic of interest was the change in VO2max. A total of 334 subjects (120 women) from 37 studies were identified. Participants were grouped into 40 distinct training groups, so the unit of analysis was 40 rather than 37. An increase in VO2max of 0.51 L · min(-1) (95% CI: 0.43 to 0.60 L · min(-1)) was observed. A subset of 9 studies, with 72 subjects, that featured longer intervals showed even larger (~0.8-0.9 L · min(-1)) changes in VO2max with evidence of a marked response in all subjects. These results suggest that ideas about trainability and VO2max should be further evaluated with standardized IT or IT/CT training programs.